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Beauty Glossary: Magnesium

BellaSugarUK — Tue, 07 Oct 2008 23:00:00 -0700

I was recently lucky enough to attend an expert skincare lecture on anti-ageing. Internationally acclaimed dermatologist and skincare pioneer Dr. Zein Obagi talked about ways to help keep our skin looking young and healthy for as long as possible.

One of the ingredients in his new range of ZO Skin Health brand, which will be available from November in Harrods and Selfridges, particularly caught my eye. Magnesium is a wonder ingredient in skincare as it has many boosting properties. Alongside potassium, this mineral is a staple in many anti-ageing creams because of it's replenishing qualities.

According to Dr. Obagi, it is ideal for improving circulation and stimulating the skin. Medically, magnesium is a very important ingredient of the green coloring matter in plants (chlorophyll) and is needed for normal development of the body. Approximately 70 percent of the magnesium in the body is found in the skeletal system. At least half of the magnesium in the body is combined with calcium and phosphorus in the bones. The remainder is in the muscles, red blood cells and the other tissues of the body.

For the benefits of magnesium on your health and your skin, just read more.

Magnesium ensures the strength and firmness of the bones. In addition, it makes the teeth harder and stronger. A regular intake of magnesium counteracts acidity, poor circulation and glandular disorders.

Magnesium is also essential to slow down the ageing process in the skin and is present in hundreds of key biochemical processes in the human body. It also stimulates the skin to ensure that healthy elasticity is maintained and moisture levels remain normal. As well as being an ingredient in skincare, it is essential to ensure you get enough of this mineral in your diet, if you want to stay young and beautiful (not to mention healthy). Magnesium rich foods include brown rice, wheat germ, wheat bran, almonds, and peanuts.

Source

Magnesium

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Magnesium is a mineral that is involved in over 300 reactions in the body. It is important for every organ in the body, particularly the heart, muscles, and kidneys. It also contributes to the composition of teeth and bones. Most importantly, it activates enzymes, contributes to energy production, and helps regulate calcium levels as well as copper, zinc, potassium, vitamin D, and other important nutrients in the body.

Magnesium is available in many foods. However, most people in the United States probably do not get as much magnesium as they should from their diet. Magnesium is found in whole unprocessed foods in the diet. However, different methods for calculating amounts of magnesium in foods often lead to conflicting results. In addition, not all foods have been thoroughly analyzed.

Despite the fact that dietary levels of magnesium are often low, actual deficiency of this nutrient is rare. Certain medical conditions, however, can upset the body's magnesium balance. For example, intestinal flu with vomiting or diarrhea can cause temporary magnesium deficiencies. Certain stomach and bowel diseases (such as irritable bowel syndrome or IBS and ulcerative colitis), diabetes, pancreatitis, hyperthyroidism (high thyroid hormone levels), kidney malfunction, and use of diuretics can lead to deficiencies. Too much coffee, soda, salt, or alcohol intake as well as heavy menstrual periods, excessive sweating, and prolonged stress can also lower magnesium levels.

Symptoms of magnesium deficiency may include agitation and anxiety, restless leg syndrome (RLS), sleep disorders, irritability, nausea and vomiting, abnormal heart rhythms, low blood pressure, confusion, muscle spasm and weakness, hyperventilation, insomnia, poor nail growth, and even seizures.

Foods rich in magnesium include unrefined grains, nuts and green vegetables. Green leafy vegetables are particularly good sources of magnesium because of their chlorophyll content.

Uses

Getting enough magnesium may help facilitate the results of conventional treatment for the following conditions:

Asthma and emphysema

A population-based clinical study of over 2,500 children aged 11 - 19 years found that low dietary magnesium intake may be associated with a risk of developing asthma. The same was found in a group of over 2,600 adults aged 18 - 70. In addition, some clinical studies suggest that intravenous and inhaled magnesium can help treat acute attacks of asthma in children aged 6 - 18 as well as adults. However, evidence from other clinical studies report that long-term oral magnesium supplementation does not lead to improved control in adult asthma.

Attention deficit/hyperactivity disorder (ADHD)

Some experts believe that children with attention deficit/hyperactivity disorder (ADHD) may be exhibiting the effects of mild magnesium deficiency (such as irritability, decreased attention span, and mental confusion). In one clinical study of 116 children with ADHD, 95% were magnesium deficient. In a separate clinical study, 75 magnesium-deficient children with ADHD were randomly assigned to receive magnesium supplements in addition to standard treatment or standard treatment alone for 6 months. Those who received magnesium demonstrated a significant improvement in behavior, whereas those who received only standard therapy without magnesium exhibited worsening behavior.

These results suggest that magnesium supplementation, or at least high amounts of magnesium in the diet, may prove to be beneficial for children with ADHD.

Depression

Major depression is a mood disorder characterized by a sense of inadequacy, despondency, decreased activity, pessimism, and sadness where these symptoms severely disrupt and negatively affect the person's life. Clinical studies have found that dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms, including agitation, anxiety, irritability, confusion, sleeplessness, headache, confusion, and hyperexcitability.

Diabetes

Type 2 diabetes is associated with low levels of magnesium in the blood. A large clinical study of over 2000 people found that higher dietary intake of magnesium may protect against development of type 2 diabetes. Magnesium was found to improve insulin sensitivity in these people, reducing the risk of developing type 2 diabetes. Other clinical studies have found similar results, especially in the elderly. Magnesium deficiency in diabetic patients may decrease their immunity, making them more susceptible to infections and illnesses.

Fibromyalgia

Results of a preliminary clinical study including 24 people with fibromyalgia suggest that a proprietary tablet containing both malic acid and magnesium may improve pain and tenderness associated with this health condition when taken for at least 2 months. Others suggest that the combination of calcium and magnesium may be helpful for some people with fibromyalgia.

However, a review article evaluating many studies concluded that magnesium with malic acid offered no relief for those with this condition. Whether these supplements ease the discomfort of fibromyalgia may vary from one individual to the next. More studies are needed.

Heart disease

Magnesium is essential to heart health. This mineral is particularly important for maintaining a normal heart rhythm and is often used by physicians to treat irregular heartbeat (arrhythmia). People with congestive heart failure (CHF) are often at particular risk for developing an arrhythmia. For this reason, your doctor may determine that magnesium should be a part of the treatment of CHF.

Results of studies using magnesium to treat heart attack survivors, however, have been inconsistent. Some studies have reported reduced death rates as well as fewer arrhythmias and improved blood pressure when magnesium is used as part of the treatment following a heart attack. In a hospital setting, if you have had a heart attack, the doctor will determine if magnesium supplementation, either intravenously or orally, is necessary.

High blood pressure

Eating low-fat dairy products along with lots of fruits and vegetables on a regular basis is associated with lower blood pressure. All of these foods are rich in magnesium as well as calcium and potassium. Singling out which of these nutrients is responsible for lowering blood pressure is difficult. A large clinical study of over 8,500 women found that a higher intake of dietary magnesium may decrease the development of high blood pressure in women.

Human immunodeficiency virus (HIV)

Several clinical studies suggest that between 30 - 65% of people with human immunodeficiency virus (HIV) have low levels of magnesium. Those with low levels may be more likely to complain of fatigue (excessive tiredness), diminished energy, and confusion. Whether magnesium supplements would improve these symptoms in people with HIV, however, has not been evaluated.

Intravenous magnesium is sometimes used by doctors to lower high blood pressure in a hypertensive crisis. Using magnesium supplements (even oral ones) for high blood pressure should only be done under the supervision of a competent health care provider.

Inflammatory bowel disease (IBD)

People with inflammatory bowel disease (IBD, particularly ulcerative colitis) may have low magnesium levels. In addition, there is some early clinical evidence that dietary magnesium supplements may be of some value for preventing IBD flare-ups.

Infertility and miscarriage

A small clinical study of infertile women as well as women with a history of miscarriage found that low levels of magnesium may impair reproductive function and increase the risk for miscarriage. The authors of the study suggest that one aspect of the treatment of infertility (particularly in women with a history of miscarriage) should include magnesium along with selenium. More research in this area is needed.

Menopause

Because magnesium improves the absorption of calcium from the gastrointestinal tract, some practitioners suggest that women take calcium and magnesium together at a ratio of 2:1, particularly around the time of menopause. This helps prevent osteoporosis (loss of bone mass).

In addition, as estrogen levels drop during menopause, magnesium levels seem to diminish as well. For this reason, magnesium may also help to relieve some menopausal symptoms such as hot flashes, depression, and insomnia. More research is needed.

Migraine headache

Magnesium levels tend to be lower in those with migraine headaches, including children and teenagers, when compared to those with tension headaches or no headaches at all. In addition, a few clinical studies suggest that magnesium supplements may decrease the length of time that one suffers from a migraine and reduces the amount of medication needed.

Some experts suggest that oral magnesium may be an appropriate alternative to prescription medication for people who suffer from migraine headaches. Other experts suggest that combining magnesium with the herb feverfew along with vitamin B2 (riboflavin) may be particularly helpful when you have a headache.

On the other hand, magnesium sulfate seems to be less effective than prescription medications for preventing migraines in those who have 3 or more headaches per month. The only exception to this may be women who get migraine headaches around the time of their menstrual period. In addition, magnesium supplements may prove to be a welcome option for migraine sufferers who cannot tolerate medications due to side effects or who can't take migraine medications due to pregnancy or heart disease. These issues are under scientific investigation.

Osteoporosis

Calcium, vitamin D, magnesium, and other micronutrient deficiencies are believed to play a role in the development of osteoporosis. Adequate intake of calcium, magnesium, and vitamin D coupled with overall proper nutrition and weight-bearing exercise throughout childhood and adulthood are the primary preventive measures for this condition, in both men and women.

Preeclampsia and eclampsia

Intravenous magnesium sulfate is commonly used to prevent complications from preeclampsia and eclampsia. Preeclampsia is a condition characterized by a sharp rise in blood pressure during the third trimester of pregnancy. Women with preeclampsia may develop seizures, which is then called eclampsia. Magnesium, administered in the hospital intravenously (IV or into the veins), is the treatment of choice to prevent or treat seizures associated with eclampsia.

Premenstrual Syndrome (PMS)

Scientific evidence and clinical experience suggest that magnesium supplements may help relieve symptoms associated with PMS, particularly bloating, insomnia, leg swelling, weight gain, and breast tenderness. Preliminary information suggests that magnesium may be helpful for alleviating mood swings as well.

Stroke

Population-based information suggests that people with low magnesium in their diet may be at greater risk for stroke. Some preliminary clinical evidence suggests that magnesium sulfate may be helpful in the treatment of a stroke or transient ischemic attack (TIA, or a temporary disturbance of blood supply to an area of the brain). More research is needed to know for certain if use of this mineral following a stroke or TIA is helpful.

Other

A small clinical study including only 10 patients found that magnesium improved insomnia related to restless legs syndrome (a disorder characterized by uncomfortable sensations in the legs, which are worse during periods of inactivity or rest or while sitting or lying down). In another study including 42 patients undergoing abdominal hysterectomy, those who received intravenous magnesium sulfate before and after surgery required fewer pain-killers, experienced less discomfort, and slept better after surgery compared to those who received placebo.

Magnesium levels were also reported lower in alcoholics and those addicted to heroin. More studies are needed in using magnesium for addictive disorders.

Dietary Sources

Rich sources of magnesium include tofu, legumes, whole grains, green leafy vegetables, wheat bran, Brazil nuts, soybean flour, almonds, cashews, blackstrap molasses, pumpkin and squash seeds, pine nuts, and black walnuts. Other good dietary sources of this mineral include peanuts, whole wheat flour, oat flour, beet greens, spinach, pistachio nuts, shredded wheat, bran cereals, oatmeal, bananas, and baked potatoes (with skin), chocolate, and cocoa powder. Many herbs, spices, and seaweeds supply magnesium, such as agar seaweed, coriander, dill weed, celery seed, sage, dried mustard, basil, cocoa powder, fennel seed, savory, cumin seed, tarragon, marjoram, poppy seed.

Available Forms

Magnesium is available in many forms. Recommended types include magnesium citrate, magnesium gluconate, and magnesium lactate, all of which are more easily absorbed into the body than other forms such as magnesium oxide. Time-release preparations may improve magnesium absorption. Ask your health care provider.

Other familiar sources of magnesium are magnesium hydroxide (often used as a laxative or antacid) and magnesium sulfate (generally used orally as a laxative or in multivitamins, or added to a bath). Some magnesium can be absorbed through the skin.

How to Take It

Be sure to check with your health care provider before taking magnesium supplements and before considering them for a child. Under certain circumstances, such as certain heart arrhythmias and preeclampsia, a doctor will have magnesium administered intravenously (into the veins) in the hospital.

It is a good idea to take a B vitamin complex, or a multivitamin containing B vitamins, because the level of vitamin B6 in the body determines how much magnesium will be absorbed into the cells.

Dosages are based on the dietary reference intakes (DRIs) issued from the Food and Nutrition Board of the United States Government's Office of Dietary Supplements, part of the National Institutes of Health.

Pediatric

For infants and children up to 3 years of age: The recommended dietary intake is 40 - 80 mg daily.

For children 4 - 6 years of age: The recommended dietary intake is 120 mg daily.

For children 7 - 10 years of age: The recommended dietary intake is 170 mg daily.

For adolescent and adult males: The recommended dietary intake is 270 - 400 mg daily.

For adolescent and adult females: The recommended dietary intake is 280 - 300 mg daily.

For pregnant females: The recommended dietary intake is 320 mg daily.

For breast-feeding females: The recommended dietary intake is 340 - 335 mg daily.

Magnesium needs increase during times of protein synthesis, such as pregnancy, recovering from surgery and illnesses, and athletic training.

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable health care provider. Individuals with heart or kidney disease should not take magnesium supplements except under the guidance of a qualified health care provider.

It is extremely rare to overdose on magnesium from food alone. However, people who consume excessive amounts of milk of magnesia (as a laxative or antacid) or epsom salts (as a laxative or tonic) may overdose on this magnesium, especially if they have kidney problems. Too much magnesium can cause serious health problems, including nausea, vomiting, severely lowered blood pressure, slowed heart rate, deficiencies of other minerals, confusion, coma, and even death. More common side effects from magnesium include upset stomach and diarrhea.

Magnesium competes with calcium for absorption and can cause a calcium deficiency if calcium intake levels are already low. Magnesium may be depleted from the body due to certain medications. Medications that may decrease magnesium levels in the body include chemotherapy drugs, diuretics, digoxin (Lanoxin), hormonal supplementation, steroids, and certain antibiotics.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use magnesium without first talking to your health care provider.

Antibiotics --The absorption of quinolone antibiotics, such as ciprofloxacin (Cipro) and moxifloxacin (Avelox), tetracycline antibiotics, including tetracycline (Sumycin), doxycycline (Vibramycin), and minocycline (Minocin), and nitrofurantoin (Macrodandin), may be diminished when taking magnesium supplements. Therefore, magnesium should be taken 1 hour before or 2 hours after taking these medications to avoid interference with absorption.

Blood Pressure Medications, Calcium Channel Blockers --Magnesium may increase the likelihood of negative side effects (such as dizziness, nausea, and fluid retention) from calcium channel blockers (particularly nifedipine or Procardia) in pregnant women. Other calcium channel blockers include amlodipine (Norvasc), diltiazem (Cardizem), felodipine (Plendil), and verapamil (Calan).

Diabetic Medications -- Magnesium hydroxide, commonly found in antacids such as Alternagel, may increase the absorption of glipizide and glyburide, medications used to control blood sugar levels. Ultimately, this may prove to allow for reduction in the dosage of those medications.

Digoxin -- It is important that normal levels of magnesium be maintained while taking digoxin (Lanoxin) because low blood levels of magnesium can increase adverse effects from this drug, including heart palpitations and nausea. In addition, digoxin can lead to increased loss of magnesium in the urine. A health care provider will follow magnesium levels closely to determine whether magnesium supplementation is necessary in individuals taking digoxin.

Diuretics -- Two types of diuretics known as loop (such as furosemide or Lasix) and thiazide (including hydrochlorothiazide) can deplete magnesium levels. For this reason, doctors who prescribe diuretics may consider recommending magnesium supplements as well.

Hormone Replacement Therapy for menopause -- Magnesium levels tend to decrease during menopause. Clinical studies suggest, however, that hormone replacement therapy may help prevent the loss of this mineral. Postmenopausal women or those taking hormone replacement therapy should talk with a health care provider about the risks and benefits of magnesium supplementation.

Levothyroxine -- There have been case reports of magnesium containing antacids reducing the effectiveness of levothyroxine, which is taken for an under active thyroid. This is important because many people take laxatives containing magnesium without letting their doctor know.

Penicillamine -- Penicillamine, a medication used for the treatment of Wilson's disease (a condition characterized by high levels of copper in the body) and rheumatoid arthritis, can inactivate magnesium, particularly when high doses of the drug are used over a long period of time. Even with this relative inactivation, however, supplementation with magnesium and other nutrients by those taking penicillamine may reduce side effects associated with this medication. A health care provider can determine whether magnesium supplements are safe and appropriate if you are taking penicillamine.

Tiludronate and Alendronate -- Magnesium may interfere with absorption of medications used in osteoporosis, including alendronate (Fosamax). Magnesium supplements or magnesium-containing antacids should be taken at least 1 hour before or 2 hours after taking these medications to minimize potential interference with absorption.

Others -- Aminoglycoside antibiotics (such as gentamicin and tobramycin), thiazide diuretics (such as hydrochlorothiazide), loop diuretics (such as furosemide and bumetanide), amphotericin B, corticosteroids (prednisone or Deltasone), antacids, and insulin may lower magnesium levels. Please refer to the depletions monographs on some of these medications for more information.

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Review Date:
5/14/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

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Health Benefits of Pears

FitSugar — Thu, 22 Oct 2009 09:00:13 -0700

Apples are in season in the Autumn, but pears are too. The soft, sweet, buttery flesh of the pear makes this Fall fruit one of my favorites. Plus there are so many varieties to choose from - Bartlett, Bosc, and Anjou - that they each seem like a different fruit. These juicy gems are pretty healthy for you, too.

Pears are high in fiber. One medium-sized pear contains six grams, so snacking on a pear can help you meet your daily requirement of 25 to 30 grams. They're a delicious way to keep you regular too, which can help prevent colon cancer. A diet high in fiber can also keep your cholesterol levels down, which is good news for your ticker. Getting your fill of fiber from fruit is also linked to a lower risk for breast cancer.
Pears contain a fair amount of vitamins A, C, K, B2, B3, and B6. For expecting or nursing moms, they also contain folate. Pears aren't too shabby in the mineral department either, containing calcium, magnesium, potassium, copper, and manganese. Vitamin C and copper are antioxidant nutrients, so eating pears is good for your immune system, and may help prevent cancer.
Pears also contain boron, which our bodies need in order to retain calcium, so this fruit can also be linked to osteoporosis prevention.

For the other health benefits, read more.

The hydroxycinnamic acid found in pears is also associated with preventing stomach and lung cancer.
It's a hypo-allergenic fruit. That means those with food sensitivities can usually eat pears with no adverse effects.
Eating three or more servings of fruits a day, such as pears, may also lower your risk of age-related macular degeneration (ARMD), the primary cause of vision loss in older adults.
Quercetin is another antioxidant found in the skin of pears. It helps prevent cancer and artery damage that can lead to heart problems. A recent study at Cornell University found it may also protect against Alzheimer’s disease. So don't peel your pears!

Tell me, what's your favorite type of pear?

Psoriasis

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Types of Psoriasis
Causes
Risk Factors
Diagnosis
Treatment
Topical Medications
Systemic Medications
Phototherapy
Managing Psoriasis
Outlook
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

Psoriasis that develops on the hands or feet is often very difficult to treat. However, an advanced clinical trial showed that a medication called efalizumab (Raptiva) effectively cleared or nearly cleared moderate-to-severe symptoms in adults after 12 weeks.

Several studies have shown that most people with severe psoriasis who are treated with infliximab (Remicade) have significant improvement in symptoms by week 10. The findings were presented at the 2007 annual meeting of the American Academy of Dermatology.

Continuing etanercept (Enbrel) after 12 weeks improves disease severity without an increase in infections or side effects, according to a study published in the Archives of Dermatology.

Disease classification

The National Psoriasis Foundation has proposed a new way to classify psoriasis. Instead of being grouped as mild, moderate, or severe, the group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

Coexisting conditions

Studies from Newfoundland and Germany have revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Previous research has found an increased risk of heart disease in psoriasis patients. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Such patients should receive comprehensive health examinations to reduce the risk, the authors recommended. Study participants were considered to have severe psoriasis if they required systemic treatment.

Smoking and psoriasis

Introduction

Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches, covered by a silvery, flaky surface. The main disease activity leading to psoriasis occurs in the epidermis, the top five layers of the skin.

The process starts in the basal (bottom) layer of the epidermis, where keratinocytes are made. Keratinocytes are immature skin cells that produce keratin, a tough protein that helps form hair, nails, and skin. In normal cell growth, keratinocytes grow and move from the bottom layer to the skin's surface and shed unnoticed. This process takes about a month.

In persons with psoriasis, the keratinocytes multiply very rapidly and travel from the basal layer to the surface in about 4 days. The skin cannot shed these cells quickly enough, so they build up, leading to thick, dry patches, or plaques. Silvery, flaky areas of dead skin build up on the surface of the plaques before being shed. The underlying skin layer (dermis), which contains the nerves and blood and lymphatic vessels, becomes red and swollen.

Types of Psoriasis

Various forms of psoriasis exist. Some can occur alone or at the same time as other types, or one may follow another. The most common type is called plaque psoriasis, also known as psoriasis vulgaris.

Plaque psoriasis leads to skin patches that start off in small areas, about one-eighth of an inch wide. They usually appear in the same areas on opposite sides of the body.

The patches slowly grow larger and develop thick, dry plaque. If the plaque is scratched or scraped, bleeding spots the sizes of pinheads appear underneath. This is known as the Auspitz sign.

Some patches may become ring shaped (annular), with a clear center and scaly raised borders that may appear wavy and snake-like.

As the disease progresses, eventually separate patches may join together to form larger areas. In some cases, the patches can become very large and cover wide areas of the back or chest. This is known as geographic plaques because the skin lesions resemble maps.

Plaque psoriasis may persist for long periods. More often it flares up periodically, triggered by certain factors such as cold weather, infection, or stress.

Patches most often occur on the:

Elbows
Knees
Lower back

The may also be seen on the:

Upper pelvic bone area
Bottom of the feet
Calves and thighs
Genital areas
Palms of hands

Psoriasis of the scalp affects about 50% of patients. In some cases, the psoriasis may cover the scalp with thick plaques that extend down from the hairline to the forehead.

Psoriasis patches rarely affects the face in adulthood. In children, psoriasis is most likely to start in the scalp and spread to other parts of the body. Unlike in adults, it also may occur on the face and ears.

Psoriatic arthritis (PsA) is an inflammatory condition characterized by stiff, tender, and inflamed joints. Estimates on its prevalence among those with psoriasis range from 2 - 42%. AIDS patients and those with severe psoriasis are at higher risk for developing PsA.

About 80% of PsA patients have psoriasis in the nails. Arthritic and skin flare-ups tend to occur at the same time. It is not clear whether psoriatic arthritis is a unique disease or a genuine variation of psoriasis, although evidence suggests they are both caused by the same immune system problem.

Although patients with psoriatic arthritis tend to have mild skin symptoms, the disease affects the entire body. PsA, therefore, is more serious than the more common plaque psoriasis. Infrequently, the course of PsA has been associated with a syndrome known by the acronym SAPHO, which stands for:

Synovitis (inflammation in the joints)
Acne
Pustule eruptions
Hyperostosis (abnormal bony growths)
Osteolysis (bone destruction)

Some experts group PsA into five forms. The forms differ according to the location and severity of the affected joint:

Symmetric PsA: Symptoms occur in the same location on both sides of the body. It usually affects multiple joints. In about half of the cases, the condition will get worse. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe.
Asymmetric PsA: This form involves periodic joint pain and redness, usually in only one to three joints, which can be the knee, hip, ankle, wrist, or one or more fingers. The pain does not occur in the same location on both sides of the body.
Distal interphalangeal predominant (DIP): DIP involves the joints of the fingers and toes closest to the nail. It occurs in about 5% of PsA cases.
PsA in the spine: Inflammation in the spinal column (spondylitis) is the primary symptom in about 5% of PsA cases. Such patients may have stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in many patients with PsA, even though stiffness and burning sensations in these areas are not the primary symptoms. When it affects the spine, psoriatic arthritis most frequently targets the sacrum (the lowest part of the spine). Movement is difficult.
Arthritis mutilans: This is a severe, deforming, and progressive form of arthritis. It affects less than 5% of PsA cases. It mainly affects the small joints of the hands and feet, but it can also be found in the neck and lower back. Arthritic and skin flares and remissions tend to coincide.

People who start to smoke after developing psoriasis may delay the onset of psoriatic arthritis, according to research presented at the 2007 annual meeting of the Society for Investigational Dermatology. Researchers found that in nonsmokers, the time between psoriasis diagnosis and psoriatic arthritis development was 13 years, compared to 23 among those who started smoking after the onset of psoriasis. Study participants who smoked before developing psoriasis had psoriatic arthritis occur in about 8 years. However, smoking causes serious health problems and should not be considered as a way to delay this type of psoriasis.


Psoriasis Form	Description of Skin Patches	Comments
Guttate Psoriasis	The patches are teardrop-shaped and appear suddenly, usually over the trunk and often on the arms, legs, or scalp. They often disappear without treatment.	Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults 1 - 3 weeks after a viral or bacterial (usually streptococcal) respiratory or throat infection. A family history of psoriasis and stressful life events are also highly linked with the start of guttate psoriasis. Guttate psoriasis can also develop in patients who have already had other forms of psoriasis, most often in people treated with widely-applied topical (rub-on) products containing corticosteroids.
Inverse Psoriasis	Patches usually appear as smooth inflamed patches without a scaly surface. They occur in the folds of the skin, such as under the armpits or breast, or in the groin.	Inverse psoriasis may be especially difficult to treat.
Seborrheic Psoriasis	Patches appear as red scaly areas on the scalp, behind the ears, above the shoulder blades, in the armpits or groin, or in the center of the face.	Seborrheic psoriasis may be especially difficult to treat.
Nail Psoriasis	Tiny white pits are scattered in groups across the nail. Toenails and sometimes fingernails may have yellowish spots. Long ridges may also develop across and down the nail. The nail bed often separates from the skin of the finger and collections of dead skin can build up underneath the nail.	Over half of patients with psoriasis have abnormal changes in their nails, which may appear before other skin symptoms. In some cases, nail psoriasis is the only symptom.
Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)	This is a rare and severe form of psoriasis, in which the skin surface becomes scaly and red. The disease covers all or nearly all of the body.	About 20% of such cases evolve from psoriasis itself. The condition may also be triggered by certain psoriasis treatments, and other medications such as corticosteroids or synthetic antimalarial drugs.
Pustular Psoriasis	Patches become pus-filled and blister-like. The blisters eventually turn brown and form a scaly crust or peel off. Pustules usually appear on the hands and feet. When they form on the palms and soles, the condition is called palmar-plantar pustulosis.	Pustular psoriasis may erupt as the first occurrence of psoriasis, or it may evolve from plaque psoriasis. A number of conditions may trigger pustular psoriasis, including infection, pregnancy, certain drugs, and metal allergies. It can also accompany other forms of psoriasis and be very severe.

Causes

The precise causes of psoriasis are unknown. It is generally believed to be due to damage in factors in the immune system, enzymes, and other materials that control skin cell division. This prompts an abnormal immune response, which causes rapid production of immature skin cells and inflammation.

The Normal Immune System Response. The inflammatory process is the result of the body's immune response, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign invaders, such as bacteria or viruses.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight infections.
In the process, the surrounding area becomes inflamed (red and swollen), and some healthy tissue is injured.

The Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign substances (antigens) and launch an offensive or defensive action against them:

B cells produce antibodies, which are designed to attack the antigens. Antibodies can either ride along with a B cell or travel on their own.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells (TH cells).

Killer T cells directly attack antigens found on bacteria or other cells.
Helper T stimulate B cells and other white cells to attack the antigen.

The actions of the helper T cells are of special interest. Researchers have found high numbers of helper T cells in psoriatic plaques. Helper T cells normally stimulate B cells to produce antibodies. In psoriasis, however, they appear to direct the B cells to produce autoantibodies ("self" antibodies), which attack skin cells. In psoriatic arthritis, cells in the joints also come under attack.

Helper T cells also release or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are very important for healing. If overproduced, however, they can cause serious damage, including inflammation and injury during the psoriasis disease process. In psoriasis, researchers are particularly interested in cytokines known as GRO-alpha, tumor necrosis factor, and certain interleukins.

Cytokines attract large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, producing two key players in the inflammatory process:

Leukotrienes: These chemicals attract even more white blood cells to the inflamed area.
Prostaglandins: These chemicals widen blood vessels and increase blood flow.

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system. HLA molecules pick off parts of antigens and present them on the surface of a cell so that the various infection-fighting factors in the immune system can recognize and destroy them. Most immune disorders, including psoriatic arthritis, are due to problems with this system. For example, psoriasis patients with an HLA genetic factor called HLA-CW6 tend to develop psoriasis at an earlier than average age. However, only 10% of people who have this gene develop psoriasis. Other genetic and environmental factors are required to actually trigger the disease.

PSORs. Researchers have now identified four key genes (named PSOR 1 - 4) that are involved with psoriasis. Of particular interest are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis factor, another immune factor strongly associated with psoriasis.

Weather, stress, injury, infection, and medications, while not direct causes, are often important in triggering the disease process leading to the start and worsening of psoriasis.

Weather. Cold, dry weather is a common trigger of psoriasis flare-ups. Hot, damp, sunny weather helps relieve the problem in most patients. However, some people have photosensitive psoriasis, which actually improves in winter and worsens in summer when skin is exposed to sunlight.

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. Other research has suggested that stress can trigger specific immune factors associated with psoriasis flares.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. For example:

Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and strep throat, are known to trigger guttate psoriasis in children and young adults. The infections may make ordinary plaque psoriasis worse.
Human immunodeficiency virus (HIV) is also associated with psoriasis.
An uncommon form of human papillomaviruses (HPV) called EV-HPV has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play a role in the continuation of psoriasis. This HPV form is not the virus associated with cervical cancer and genital warts.

Skin Injuries and the Köbner Response. The Köbner response is a delayed response to skin injuries, in which psoriasis develops later on at the site of the injury. In some cases, even mild abrasions can cause an eruption, which may be a factor in the frequency of psoriasis on the elbows or knees. It should be noted that psoriasis can develop in areas with no history of skin injury.

Medications. Drugs that can trigger the onset of the disease, worsen symptoms, or cause a flare-up include:

Angiotensin-converting enzyme (ACE) inhibitors, drugs used to treat high blood pressure and heart problems
Beta-blockers, drugs used to treat high blood pressure and heart problems
Chloroquine, a medicine used to treat malaria
Lithium for bipolar disorder treatment
Indomethacin, a nonsteroidal anti-inflammatory drug (NSAIDs) -- Note: Other NSAIDs, such as meclofenamate, may actually improve the condition.
Progesterone, used in female hormone therapies

Flare-ups of severe psoriasis may occur in persons who stop taking steroids taken by mouth, or who discontinue use of very strong steroid ointments that cover wide skin areas. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.

Medications that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Köbner response.

Risk Factors

Between 5.8 and 7.5 million Americans have psoriasis. Risk factors for psoriasis include:

Age under 20. About 40% develop the condition before age 20. Psoriasis (most often plaque psoriasis) can even occur in infants.
Climate. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more frequently in African-Americans and in Caucasians who live in colder climates than in people of any ethnicity who live in Africa.
Ethnicity. Psoriasis is uncommon in Native Americans of either North or South American descent.
Family history of the disease. About 35% of those with psoriasis have one or more family members with the disorder.
Male gender. Some studies have indicated that more men than women have psoriasis.

Diagnosis

A microscopic examination of tissue taken from the affected skin patch is needed to make a definitive diagnosis of psoriasis and to distinguish it from other skin disorders. Usually in psoriasis, the examination will show a large number of dry skin cells, but without many signs of inflammation or infection. Specific changes in the nails are often strong signs of psoriasis.

Several conditions produce symptoms that resemble those of psoriasis. For example:

Seborrheic psoriasis is hard to distinguish from seborrheic dermatitis (dandruff is one form of this condition). Seborrheic dermatitis patches are usually greasy, yellowish, and crusty. Nail involvement may also help differentiate psoriasis.
Generalized erythrodermic psoriasis may be confused with drug allergic reactions, atopic eczema, and symptoms of lymphomas.
Fungal infections, other skin conditions, or circulation problems may also cause nail changes typical of psoriasis.

Symptoms of psoriatic arthritis may also resemble the following:

Rheumatoid arthritis (RA). As in rheumatoid arthritis, psoriatic arthritis can cause pain or tenderness in one or more joints, and morning stiffness is common. People with psoriatic arthritis, however, lack a particular antibody, called rheumatoid factor, which is found in the blood of many people with rheumatoid arthritis.
Systemic lupus erythematosus (SLE). Symptoms of SLE may include both a psoriasis-like rash and arthritis, which could make the diagnosis difficult.
Reiter's disease. Reiter's disease is a syndrome that includes arthritis and inflammation in the eyes and urinary tract. It also causes skin lesions that are very similar to psoriasis, which are usually raised patches on the lips, penis, palms, and soles.
Gout. Gout causes pain, often in the fingers and toes.

Some evidence now indicates that inflammation in psoriatic arthritis may be distinguished from other arthritic conditions by its occurrence in sites where muscle tissue inserts into the bone (called enthesitis) rather than in the joint, which is a common site in other inflammatory arthritic conditions.

Severity of psoriasis itself ranges from one or two flaky inflamed patches to widespread pustular psoriasis that, in rare cases, can be life threatening. To help determine the best treatment for a patient, doctors usually classify the disease as mild to severe. The classification depends on how much of the skin is affected:

Mild psoriasis affects less than 3% of the body surface. Most cases of psoriasis are limited to less than 2% of the skin.
Moderate psoriasis covers 3 - 10% of the skin.
If more than 10% of the body is affected, the disease is considered severe.

The palm of the hand equals 1% of the body. The severity of the disease is also measured by its effect on a person’s quality of life.

However, the National Psoriasis Foundation has proposed a new classification method. The group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

While disease severity impacts treatment success, some forms of psoriasis can be very resistant to treatment even though they are not categorized as severe. They include:

Any psoriasis on the palms and soles (hand and foot psoriasis)
Inverse psoriasis (which occurs in the folds of the skin)
Scalp psoriasis
Psoriatic arthritis

Treatment

Many creams, ointments, lotions, and pills are available for the treatment of psoriasis. Many patients require only over-the-counter treatment, or even none at all during relapses.

About a third of patients with psoriasis, however, do not respond to over-the-counter remedies and lifestyle changes, and require aggressive treatments. In some cases, such treatments need to be lifelong.

In general, there are three treatment options for patients with psoriasis.

Topical medications such as lotions, ointments, creams, and shampoos
Body-wide (systemic) medications, which involve pills or injections that affect the whole body, not just the skin
Phototherapy, which uses light to treat psoriasis lesions

Individual requirements vary widely, and treatment selection must be carefully discussed with the doctor.

Giving treatment in a particular order is a strategy for providing both quick relief of symptoms and long-term maintenance. It involves three main steps:

The quick fix, to clear the psoriatic lesions during an acute outbreak (for example, a high-strength topical steroid in mild-to-moderate psoriasis, or an oral immunosuppressant in more severe cases)
The transitional phase, intended to gradually introduce the maintenance drug
Ongoing maintenance therapy

Choices for transitional or maintenance treatments depend on the severity of the condition. Some examples are described in the following sections.

In severe chronic cases, a doctor may recommend rotational therapy. This approach alternates treatments. The goal is to prevent severe side effects or build-up of resistance from long-term use of a single medicine. An example of a rotational schedule may be the following:

The patient gets phototherapy for about 2 years.
The patient then takes one or two powerful body-wide drugs for 1 - 2 years and stops.
Phototherapy starts again, and the cycle repeats.

Some doctors use the Koo-Menter Psoriasis Instrument (KMPI) to decide which patients should receive a pill or an injection. The KMPI’s questions include:

Does psoriasis cover at least 5% of the patient’s body?
Is the patient disabled by psoriasis?
Does psoriasis affect the patient’s quality of life?

If the answer to these questions is "yes," three additional questions are considered:

Is light therapy inappropriate for the patient?
Is the patient’s psoriasis resistant to light therapy?
Does the patient have psoriatic arthritis?

If the answer to these questions is “yes,” a doctor may decide to prescribe a pill or injected drugs.

Doctors increasingly use combinations of pills, creams, ointments, and phototherapy instead of single medications. Combinations of oral treatments are particularly useful, since the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and the patient and doctor should discuss the best treatment for individual needs.

Topical Medications

Topical medications are those applied only to the surface of the body. They come in the following forms:

Creams
Foams
Gels
Lotions
Occlusive tapes
Ointments
Shampoos
Solutions
Sprays

In general, topical treatments are the first line for mild-to-moderate psoriasis, but they may also be used, alone or in combination, with more powerful treatments for moderate-to-severe cases. Topical medicines rarely produce complete clearance, however.

Corticosteroid topical treatments are the mainstay of psoriasis treatments in the United States. They work for most patients. Such treatments:

Decrease inflammation
Block cell production
Relieve itching

Corticosteroids are available in a wide range of strengths, and are generally given as follows:

Less potent drugs are used for mild-to-moderate psoriasis.
Stronger drugs are reserved for more severe disease.

In the past, topical steroids have been used twice a day. Studies are reporting, however, that certain drugs may work just as well if taken once a day. Most studies have evaluated high-potency steroids, but one study suggested that those of medium strength, such as triamcinolone (Aureocort, Tri-Adcortyl), may be equally beneficial as a once-daily treatment. However, corticosteroids used alone clear psoriasis in only 4 - 36% of patients.

Combination therapy. Combinations with other drugs are often needed. For example, an effective, topical regimen uses the following combination for maintenance therapy:

A high-potency steroid (such as halobetasol) on the weekend
A vitamin D3 topical medication called calcipotriene, twice daily on weekdays

In one study, more than 75% of patients with mild-to-moderate psoriasis remained in remission for at least 6 months with this regimen.

Side Effects. The more powerful the corticosteroid, the more effective it is. But it also has a higher risk for severe side effects. Side effects may include:

Burning
Irritation
Dryness
Acne
Thinning of the skin; skin may become shiny, fragile, and easily cut
Dilated (widened) blood vessels
Loss of skin color

Loss of Effectiveness. In most cases, the patients become tolerant to the effects of the drugs, and the drugs no longer work as they should. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical medication for 3 full days each week.

Note: This list is not all inclusive.
Low potency (some are available over the counter)	Desonide (Tridesilon, DesOwen) Flumethasone pivalate (Locorten) Fluocinolone acetonide (Synalar, Derma-Smoothe) Hydrocortisone (Hytone, Penecort, Synacort, Cort-Dome, Nutracort, Westcort) Triamcinolone acetonide (Aristocort)
Low to medium potency	Alclometasone dipropionate (Aclovate) Hydrocortisone (Locoid, Pandel) Hydrocortisone valerate (Westcort) Prednicarbate (Dermatop)
Medium to upper-mid potency	Clocortolone pivalate (Cloderm) Fluticasone propionate (Cutivate) Mometasone furoate (Elocon) Triamcinolone acetonide (Aureocort, Tri-Adcortyl, Kenalog)
High potency	Betamethasone (Diprosone) Amcinonide (Cyclocort) Desoximetasone (Topicort) Diflorasone diacetate (Florone, Maxiflor) Fluocinonide (Lidex) Halcinonide (Halog)
Very high potency	Halobetasol propionate (Ultravate) Betamethasone (Diprolene, Luxiq) Clobetasol propionate (Temovate, Olux) Diflorasone diacetate (Florone, Maxiflor, Psorcon)

Coal tar preparations have been used to treat psoriasis for about 100 years, although their use has declined with the introduction of topical vitamin D3-related medicines. Crude coal tar stops the action of enzymes that contribute to psoriasis, and helps prevent new cell production. Tar is often used in combination with other drugs and with ultraviolet B (UVB) phototherapy.

Side Effects. Preparations have the following drawbacks:

Stains on clothing
Skin irritation
Sun sensitivity and increased risk of sunburn for up to 24 hours after use

Anthralin (Dritho-Scalp, Drithocreme, Micanol) is related to a medication called chrysarobin, in use since the early 1900s. Anthralin slows skin cell reproduction and can produce remissions that last for months. It is recommended only for chronic or inactive psoriasis, not for acute or inflamed eruptions. Persons with kidney problems should use anthralin with caution.

As with tar, its use has also declined with introduction of the topical vitamin D-related medicines, but newer formulations, such as Micanol, have made its use more tolerable. Micanol (Psoriatec) is an anthralin formulated in microcapsules, which dissolve and allow the drug to be delivered directly to the target skin areas. It is particularly useful for scalp psoriasis, and it is less likely to stain.

Side Effects. Anthralin may cause the following side effects:

Skin irritation and burning
Staining of clothes, hair, fabrics, plastics, and other household products

Patients should not use anthralin on their faces. Fair skinned people should generally avoid it. Triethanolamine (CuraStain) is a chemical that can neutralize anthralin and help reduce irritation from short-contact anthralin treatment. It should be applied 1 or 2 minutes before washing off the anthralin. It is then reapplied after drying the skin.

Washing stained items with hypochlorite (Clorox) detergents can help remove stains. Many people use disposable gloves while applying the treatment to avoid staining hands.

Application. Apply anthralin only to the psoriasis plaques. Rub the cream in well, and wipe off any excess. Wash off only with lukewarm water, not soap. Using hot water will trigger the staining action. A technique called short-contact anthralin therapy (SCAT), also called minute therapy, is useful for local areas of psoriasis. In such cases, anthralin is applied for only 10 minutes to an hour.

A topical form of vitamin D3, calcipotriene (Dovonex) is proving to be both safe and effective. It is now available in a foam preparation, which makes compliance even easier. Several other topical vitamin D3 related drugs showing promise include maxacalcitol (Oxarol), tacalcitol, and calcitriol (Silkis).

Calcipotriene appears to:

Block skin cell reproduction
Enhance the maturity of keratinocytes (the impaired skin cells in psoriasis)
Acts as an anti-inflammatory

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Using the drug in combination with other topical and systemic treatments may improve effectiveness. Calcipotriene doesn't work as well as the highest potency corticosteroids, but products or regimens that combine both medications are proving to be more effective than either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, was approved by the U.S. Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. Studies show the combination works better than either drug alone.

Combining vitamin D ointments with systemic medicines, notably methotrexate, acitretin, or cyclosporine, increases effectiveness and allows lower doses or either medication, thereby reducing side effects.

Studies also report success in some patients who use vitamin D ointments in combination with phototherapy treatment.

Side Effects. Calcipotriene may cause the following side effects:

A possible lowering of vitamin D levels, which may affect bone growth in some children
A possible increase in blood calcium levels (seen in some people who apply calcipotriene to large areas)
Skin irritation in about 20% of patients, particularly on the face and in skin folds

Calcipotriene appears to cause greater skin irritation than potent corticosteroids. Diluting the drug with petrolatum or applying topical corticosteroids to sensitive areas may prevent this problem.

Retinoids are related to vitamin A. They are used for various skin disorders. Tazarotene (Tazorac) is the first topical retinoid found to be effective for mild-to-moderate psoriasis. It is available in cream or gel form.

Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. It can be used on the scalp and nails, but it is not recommended for the genital areas or around the eyes. The gel should be used on only 20% of the body at anytime; the cream on up to 35%. (Note: The palm of the hand is about 1% of the body surface.)

Combining topical retinoids with other psoriasis treatments, such as with topical steroids, works better than using the drug by itself.

Side Effects. Tazarotene may cause dryness and irritation of healthy skin. Applying zinc oxide and moisturizer around the treated area can protect the healthy skin.

At levels high enough to be effective for psoriasis, tazarotene can cause severe skin irritation on treated areas. This medicine, then, is usually used in combination with other treatments, therefore allowing a lower dose. Mixing the drug in equal amounts with petroleum jelly (Vaseline) initially and then gradually increasing the amount of tazarotene may help the skin areas become less sensitive. It should be noted that the skin can become very red while it is actually improving.

Vitamin A derivatives (drugs related to vitamin A) have been associated with birth defects and should not be used by women who are pregnant, who wish to conceive, or who are nursing.

Salicylic acid applied to the skin helps remove scaly plaque and enhance the actions of other medications. It should not be used to cover wide areas of the body, since it can cause nausea and ringing in the ears. Combinations with high potency steroids, such as mometasone furoate (Combisor), clobetasol propionate, and betamethasone, are proving to be very helpful. Only Combisor is available in the United States.

Watertight (occlusive) tapes or wrappings may help heal psoriasis. Occlusive tapes are particularly useful for psoriatic cuts on the palms and soles. In such cases, the tape should be applied across the cuts until they heal.

Occlusive tapes retain sweat, which helps restore moisture to the outer skin layer and prevent scaling. They also protect against abrasion and irritation.

High-Potency Corticosteroid Tapes. Applying a corticosteroid beneath an occlusive tape, or using a tape that already has a potent corticosteroid (Cordran Tape) such as flurandrenolide may be especially beneficial. Studies are showing that high-potency corticosteroid-containing tapes are more effective than using high-potency corticosteroid ointments alone.

However, the tapes are expensive and are associated with a high rate of skin irritation, increased secondary infections, and a greater chance of symptoms relapse after treatment is stopped. Infection risk may be reduced by changing tapes every 12 hours.

The use of corticosteroids under occlusive tapes on large areas of psoriasis also increases the risk for adrenal insufficiency, a sometimes dangerous condition that occurs because the body loses its ability to produce natural steroids. Children are especially vulnerable to this effect.

Other Medications with Occlusive Tapes or Wrappings. The tapes may be used in combination with other medications, such as fluorouracil. Occlusive wrappings are not usually used with tazarotene (Tazorac) and should never be used without a doctor's recommendation.

Numerous topical medications are under investigation. One such medication, tacrolimus (Protopic), is an immunosuppressant that is proving to be useful in allergic skin disorders and is being studied for psoriasis. Studies have been mixed on its benefits, although new delivery methods may make it more effective. It may prove to be safe for sensitive areas, such as the face. Pimecrolimus (Elidel), a similar medication, is also being studied.

Systemic Medications

Systemic treatment uses various medications that affect the whole body, not just the skin. Many systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer.

Systemic treatments for psoriasis may be taken by mouth or injection. The medicines can have significant side effects and are generally reserved for severe psoriasis.

At this time, the only systemic medications specifically approved for psoriasis are:

Cyclosporine
Methotrexate
Retinoids

As with all medications for psoriasis, the patient should use the lowest strength medication first. The primary treatment is called a first-line treatment, the next is known as a second-line treatment, and so on. Combinations of medications are often used.

Methotrexate (Rheumatrex) is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first line, or primary, systemic drug used to treat adults with severe psoriasis. The medicine is one of the few systemic drugs proven to help patients with psoriatic arthritis.

The drug is taken weekly, not daily. (Deadly reactions have been reported in people who mistakenly took it once a day.)

Side Effects. Common side effects of methotrexate include:

Anemia
Headache
Mild hair loss
Mouth sores
Nausea
Possible muscle aches
Rash
Vomiting

Many of these side effects are due to folic acid deficiency. Patients should ask their doctor if folic acid supplements (generally recommended at 1 - 5 mg daily) are necessary.

More serious side effects include:

Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. Patients with active infections should avoid this drug.
Infertility, miscarriage, and birth defects. If used during pregnancy, the drug can cause miscarriages or birth defects in the baby. It may harm fertility in men.
Kidney complications.
Liver damage. In one study, 25% of patients taking methotrexate for 5 years developed scarring of the liver. Those with existing liver problems should not take this medicine, if possible. Regular monitoring for liver toxicity, including blood tests and liver biopsies, is important in patients who take the drug.
Lung disease. This side effect can be sudden and severe, and occurs in up to 5% of people who take methotrexate. Risk factors include diabetes, existing lung inflammation, protein in urine, and use of rheumatoid arthritis drugs called DMARDs.
Lymphomas. A few cases have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease has gone into remission when the drug was stopped. Most studies have found no significant risk for cancers in patients taking methotrexate.
Osteoporosis. Low doses of methotrexate do not appear to have any significant effect on bone loss, but long-term studies are needed to confirm this.
Radiation recall: An uncommon side effect in patients who have previously been burned by radiation cancer treatments or sunburns. In such cases, a flare-up of symptoms occurs in the previously affected skin areas.
Severe anemia. Folic acid supplements can offset this effect.
Toxic effects on bone marrow. This can cause reduced blood cell production.

Despite its side effects, some experts view methotrexate as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with other severe forms of the disease, including psoriatic arthritis, generalized erythrodermic, and pustular psoriasis.

Methotrexate appears to be effective in children, but more safety research is needed.

Drug Interactions. Many drugs interact with methotrexate, occasionally with harmful results. For example, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.

A serious, harmful reaction can occur if methotrexate is taken with common, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen. Other NSAIDs, namely ketoprofen, flurbiprofen, and piroxicam, appear to be safe when given with methotrexate and may be used in patients with psoriatic arthritis. Rheumatoid arthritis (RA) patients who take methotrexate often take NSAIDs as well, but methotrexate doses in psoriasis patients are usually much higher than those in RA.

People Who Should Avoid Methotrexate. Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before planning a pregnancy. It may also cause temporary impairment of fertility in men.

Persons with the following conditions should also avoid taking methotrexate:

Alcoholism
Anemia or other blood abnormalities
Immunosuppression
Kidney problems
Liver problems (including hepatitis)
Rheumatoid arthritis
Peptic ulcers

Patients at risk for liver complications include those with diabetes and obesity. Anyone with a history of hepatitis should have a liver biopsy before taking methotrexate.

Oral retinoids are vitamin A-related medications taken by mouth. This group of medicines is also a first-line treatment for adults with severe psoriasis. Oral retinoids used for psoriasis include acitretin (Soriatane) and isotretinoin (Accutane).

Acitretin is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic variants. When used alone, it is much less effective against more common forms, such as plaque or guttate psoriasis. However, combinations with PUVA phototherapy can markedly improve the response even in these patients.

Accutane, more commonly used to treat acne, is far less potent than acitretin, but may still be effective against pustular psoriasis and also be effective with phototherapy.

Oral retinoids help control cell reproduction and have anti-inflammatory properties. They may even improve arthritis that accompanies psoriasis.

Combination therapy. Acitretin may work the best when combined with other treatments, usually topical drugs and especially phototherapy. Combination therapy allows lower doses of oral retinoids to be used, which diminishes many skin and mucous membrane side effects. Acitretin combined with phototherapy has some of the highest clearance rates of any treatment.

Side Effects. All retinoids have the same potentially serious toxicities as do high doses of vitamin A. Side effects include:

Bone and joint pain
Bruising
Depression and possible suicide risk (with isotretinoin)
Eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision
Fatigue
Headache
Increased bone growth, particularly in the ankles, pelvic area, and knees
Increased triglyceride levels
Liver damage
Nail problems
Skin and mucous membrane problems, including dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles

In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. Patients experiencing these symptoms should call a doctor immediately and stop taking the drug.

Oral retinoids should not be taken during pregnancy.

Despite these side effects, oral retinoids remain among the safest systemic therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects. Certain cholesterol-lowering drugs, including gemfibrozil (Lopid) or certain statins, such as atorvastatin (Lipitor), may help control triglyceride levels.

Maintenance doses should be as low as possible and should be taken every second or third day.

Taking retinoids during pregnancy significantly increases the risk for severe birth defects in the unborn child. Pregnant or nursing women or those planning to become pregnant should not use these drugs. Women of childbearing age who take retinoids should have regular pregnancy tests.

Doctors recommend that acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential for causing birth defects during that time. It's important to note that cooking products and over-the-counter preparations, such as cough syrup, may contain alcohol and be inadvertently consumed.
Women who are pregnant or plan to become pregnant should not use isotretinoin. As of December 31, 2005, everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE.

Cyclosporine (Neoral, Sandimmune, SangCya) blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first line, or primary, systemic drug used to treat adults with severe psoriasis. Neoral is the preparation used most often for psoriasis and clears psoriasis in many patients within 8 - 12 weeks.

Side Effects. Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for patients who do not respond to phototherapy or less potent systemic medications (for example, methotrexate or acitretin).

Common and temporary side effects include:

Fatigue
Gingivitis
Gout
Hair growth
Headaches
Joint pain
Tremor

More serious complications may include:

Kidney damage
High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, since other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
High cholesterol and lipid levels
High levels of calcium and low levels of magnesium
Increased risk for infections
Liver problems
Lymphomas
Skin cancers (Patients who have taken cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. According to a 2003 study, the risk is six times that of the general population. The risks are highest with long use and previous use of PUVA, methotrexate, or other immunosuppressants.)

To reduce complications of cyclosporine, the dosage is decreased after improvement occurs. Maintenance therapy is usually limited to a year, although some experts believe that a microemulsion form of Neoral (Neoral-Neo) may be safe for up to 2 years. Patients should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.

Patients Who Should not Use Cyclosporine. Because the drug suppresses the immune system, people with active infections or cancer should avoid it. Patients with uncontrolled high blood pressure and impaired kidney function should also not use this medication. Cyclosporine therapy for children with psoriasis has not been well studied.

Drug and Food Interactions. Cyclosporine interacts with numerous drugs -- both prescription and over-the-counter preparations -- and also grapefruit and grapefruit juice.

Biological response modifiers, sometimes called "biologics," belong to a new class of drugs that are considered the most exciting development in psoriasis treatment. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not damage the entire immune system the way that general immunosuppressants do.

Biologics are considered second- or third-line treatments, and may be used alone or sometimes in combination with first-line systemic drugs.

There are different types of biologics used to treat psoriasis:

T cell blockers block immune cells linked to inflammation.
Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.

Types of T-cell blockers:

Alefacept (Amevive). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Studies suggest that the drug produces 50 - 75% improvement in symptoms. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. Patients need weekly blood tests to make sure T cell levels do not drop too low. Side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
Efalizumab (Raptiva). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 - 75% improvement in symptoms within 4 - 6 weeks of starting the drug. Patients give themselves shots of this drug for 12 weeks. Some clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients have flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia and antibiotic-resistant infections.

Types of TNF blockers:

Etanercept (Enbrel) is approved for the treatment of psoriatic arthritis and moderate-to-severe plaque psoriasis. The drug is given either alone or in combination with methotrexate. Side effects include infections and lymphoma, a type of cancer. Patients inject themselves under the skin, once or twice a week for 12 weeks. However, a 2007 study published in the Archives of Dermatology found that continuing etanercept after 12 weeks lowers the severity of disease without increasing infections or side effects. Study participants randomly received 50 milligrams of the drug or a placebo biweekly up to 84 weeks. Strongest improvements were noted at 48 weeks among those who received the drug.
Infliximab (Remicade) is approved for the treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first 6 weeks of treatment. After the initial treatment period, patients receive an infusion every 8 weeks. Therapy takes 2 hours and is given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug. Several studies have shown that symptoms improve significiantly by week 10 in the majority of patients with severe psoriasis who are treated with infliximab.
Adalimumab (Humira) is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis. Results from a Phase III (late-stage) study show that the drug works better than methotrexate in the treatment of moderate-to-severe psoriasis.
Efalizumab (Raptiva) appears to effectively clear or nearly clear moderate-to-severe hand and foot psoriasis after 12 weeks. This type of psoriasis is often very difficult to control and treat.

Interleukins (IL) being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. For example, in a 2003 study, 75% of patients with severe psoriasis who were treated with interleukin-4 (rhuIL-4) experienced improvement rates of more than 68%.

A study of 180 patients with moderate-to-severe plaque psoriasis has shown that an investigational medicine called ABT-874 greatly reduced symptoms in most patients. ABT-874 targets proteins that are responsible for psoriasis-related inflammation.

Leflunomide. Leflunomide (Arava) is a disease-modifying antirheumatic drug (DMARD), which blocks autoimmune antibodies and is a powerful anti-inflammatory medication. It is proving to be active against psoriatic arthritis. Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury.

Sulfasalazine. Sulfasalazine (Azulfidine) is sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only medications proven to help patients with psoriatic arthritis. Many people, however, stop taking the drug because of common side effects that include headaches, gastrointestinal complaints, and rash. Benefits, if any, should be apparent in 4 - 6 weeks.

Immunosuppressants. Some immunosuppressants being studied for psoriasis include tacrolimus (Prograf), pimecrolium, and sirolimus. In one study, for example, tacrolimus showed an 83% reduction in symptoms in patients with psoriasis who used the drug. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and so have fewer side effects. (Some are also being studied as topical treatments.)

Phototherapy

Phototherapy means to treat with light.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the DNA inside skin cells and injures it. This can cause wrinkles, aging skin, and skin cancers. However, these same damaging effects can destroy the skin cells that form psoriasis patches.

Phototherapy for psoriasis can be given as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Ultraviolet A (UVA) is a main part of sunlight. UVA phototherapy uses a photosensitizing medication (usually psoralen) in combination with UVA radiation to be effective. A photosensitizing medication makes a person more sensitive to light. Treatment with psoralen and UVA is referred to as PUVA. This approach is very powerful and effective in more than 85% of patients who use it. However, it poses a higher risk for skin cancers than UVB.

PUVA treatments cause inflammation and redness in the skin to develop within 2 - 3 days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation.

Forms of psoralen include methoxsalen, 8-methoxypsoralen (8-MOP), or bergapten (5-MOP). The effectiveness of the treatment is based on a chemical reaction in the skin between the psoralen and light, which creates redness and inflammation that prevents the psoriasis disease process.

People should avoid this treatment if they are taking drugs or have conditions that cause them to be light sensitive. They should also take protective measures before, during, and after each treatment.

Initial PUVA Treatment Phase. The initial phase typically follows these steps:

Psoralen is typically taken by mouth in the form of 8-methoxypsoralen (for example, Oxsoralen) 75 minutes to 2 hours before the treatment starts. Psoralen reaches the skin through the bloodstream, where it increases the skin's sensitivity to UVA radiation.
Topical preparations of psoralen are alternatives to pills. They can be "painted on" or applied to the affected areas by soaking or bathing in a psoralen solution. PUVA-bath therapy may be especially useful for persistent psoriasis on the palms and soles or for patients with liver disease or who get severe nausea from taking the pill form. UVA should be given within 15 minutes of using topical psoralen.
The patient enters and stands in a light box, a unit lined with ultraviolet lamps. The initial UVA exposure time is very short (seconds to several minutes), and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for full effect, but during that period, treatment intensity may vary.

If there is no response after 10 treatments, the doctor may increase the UVA energy.
If there is still no response after 15 treatments, the psoralen dosage may be increased.
If a patient's skin does not improve at all or worsens after these changes, the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following 2 weeks.
If the skin does not improve over the following 2 weeks, PUVA treatment has failed. If skin improves during this resting period, treatment resumes.

Maintenance Phase. Once the psoriasis has improved by about 95%, the patient may be put on a maintenance schedule. Often only one or two treatments a month are needed, but some people may need more frequent treatments. As maintenance continues and the interval between treatments lengthens, the patients may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates. Nearly 90% of patients achieve marked improvement or clearing within 20 - 30 treatment sessions.

Combinations. Combining acitretin, calcipotriene, methotrexate, or tazarotene gel with PUVA may enhance effectiveness or increase response. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers, while methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA.

The psoralen methoxsalen causes a general ill-feeling and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food, or taking ginger 20 minutes before taking the drug, may be helpful.
Skin reactions, including itching, sunburn, and blistering, are common. These can generally be avoided with careful administration of PUVA therapy and protective measures. Antihistamines, baths with special oatmeal preparations (Aveeno), and capsaicin ointment (Zostrix) may be helpful.
After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not get this treatment.
The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can change DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increase the risk for basal cell skin cancer, both of which are nearly always curable. One study reported an increased risk of melanoma. The risk for skin cancers is higher in persons who have:

A family or personal history of skin cancer
Light skin and fair or red hair
Received radiation or x-ray treatments or taken immunosuppressant drugs
Received over 200 PUVA treatments

Discussions are under way about discontinuing PUVA for psoriasis. The arguments generally are as follows:

Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments. In one long-term study, only 9 out of 1,380 patients developed melanoma. However, 7 of these cases occurred in the last 5 years of the study, indicating that the danger persists and more patients in this study are likely to develop this serious skin cancer as time goes on.
Supporters of PUVA argue that it is not yet known if the people who developed melanoma experienced sunburn during the procedures or if they already had risk factors for skin cancers. If so, then properly given treatments could still be considered safe for patients without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, the addition of retinoids may protect against skin cancers while proving to be a very effective combination.

Side effects of UVA radiation can be severe. Protective measures are needed during, before, and after treatment. Patients should avoid prolonged exposure to the sun for 24 hours before the oral treatment starts.

Protective Measures During Treatment:

Patients should wear specially designed goggles to protect the eyes from UVA radiation.
Sensitive areas, such as genitals, abdominal skin, and breasts, should be covered until tanning occurs in the exposed areas, after about a third of the treatment period. Note that PUVA is associated with a high risk for genital skin cancers, so male genitals must be covered throughout the process.

The following safety features should be available in the PUVA chamber:

Lamps with protective shields
A viewing window for a health professional to check the patient periodically
A door that can be opened by the patient easily and with little pressure
A timer that terminates the session automatically
An accessible alarm device

Protective Measures After Treatment. The drugs used in PUVA increase susceptibility for a natural sunburn for hours after treatment. The patient should take the following precautions:

Patients should wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. They should begin wearing them as soon as they take the drug, and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes that can cause cataracts. There is no need to wear these glasses after sundown.
For about 8 hours after taking the drug, patients must also avoid exposure to daylight, even if the day is cloudy or exposure occurs through windows.
Patients who must go out should wear heavy opaque clothing (clothes that do not let light through), including hats and gloves.
Patients should apply sunblock over all exposed areas, including the lips. The sunblock should have an SPF (sun protection factor) of more than 15 and include ingredients that block both UVB and UVA radiation.
No patient should spend a long time in sunlight for at least 2 days after the combined treatment.

Ultraviolet B is another main part of sunlight, and is the main cause of sunburn. It generally affects the outer skin layers. UVB radiation reduces the abnormally rapid skin cell growth that occurs with psoriasis.

Types of UVB therapy:

Broadband UVB
Narrowband UVB (NB-UVB)
Laser treatments

Broad spectrum or broad band UVB is radiation in the wavelength of 290 - 350 nanometers, and is the standard UVB phototherapy treatment in the United States. It is not as potent as the treatments that use narrow-band UVB or PUVA, and is not useful for chronic psoriasis.

Broadband UVB may be given with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is given as follows:

Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the patient can obtain a prescription for equipment that can be used at home. Even at home, treatment must always be supervised.
In preparation, the patient fully undresses, although unaffected areas may be covered to avoid overexposure.
The initial session may last as little as a few seconds, depending on whether the patient has a lighter or darker skin, with the lightest skin exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. It should be noted that the condition may worsen initially.
UVB therapy usually requires about 20 - 40 treatments (about three per week). Full results take about 3 weeks.

Use of Medication. UVB was commonly used with coal tar (the Goeckerman regimen) in past decades, and then with anthralin (the Ingram regimen). Other medications are being studied with some success, and may prove to be tolerated better.

The Goeckerman regimen requires daily treatments for up to 4 weeks. The coal tar or anthralin are applied once or twice each day and then washed off before the procedure. Studies indicate that a low-dose (1%) coal tar preparation is as effective as high dose (6%). Such regimens are unpleasant, but still useful for some patients with severe psoriasis, since they can achieve long-term remission (up to 6 - 12 months).

Some evidence suggests that using a simple emollient (such as Vaseline or mineral oil) that enhances UVB light penetration can be effective. This addition to the treatment increases the risk for sunburns, however, and patients must be careful to avoid sun exposure. Researchers are tring combinations of other topical and oral medications. For example, combining UVB with methotrexate, or retinoids such as a tazarotene gel or oral acitretin, is producing positive results. Combinations with any of these drugs, however, must be supervised carefully to avoid serious reactions.

Side Effects of UVB. The treatment can cause itching and redness. UVB radiation from sunlight is known to increase the risk for skin cancers. There is no strong evidence, however, that UVB treatments pose any risk for skin cancers except on male genitalia. This risk, however, can be significant (4.5%) at high doses.

Narrow band radiation may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis.

NB-UVB is used without medications and is very strong. Whether it has any affect, however, on the disease process itself is unclear. The light wavelength is between 310 - 312 nanometers, which, theoretically, is the most beneficial part of sunlight.

Exposure times are shorter but of higher intensity than with broadband UVB. This therapy is probably less likely than PUVA to cause skin cancers.

Clearance of 75% typically occurs after 10 - 12 treatments. NB-UVB treatments performed three times a week achieve results that are equal to twice-weekly PUVA treatments. Weekly NB-UVB treatments are not effective. Studies so far are mixed on whether NB-UVB remission rates are equal to those of PUVA.

Patients prefer NB-UVB over other PUVA treatments because they do not have to wear protective eyewear, take medications, or experience unpleasant side effects, notably nausea. It is also safe for pregnant women and children.

Combinations with topical medications, such as tazarotene or psoralens, may help NB-UVB therapy work better.

Laser UVB Treatment. A recent variation of a device called an excimer laser (Xtrac) delivers a precise UVB wavelength of 308 nanometers. The laser is more effective than narrow-band UVB for localized psoriasis, since it allows very specific areas of skin to be targeted. (Note: The therapy is not suitable for the scalp.) Generally, 8 - 10 treatments given twice a week will clear psoriasis. Remission rates are similar to NB-UVB, but the excimer laser can clear the psoriasis faster and at lower doses. It also spares the healthy skin around it. Blistering is a common side effect. More comparison studies are needed to determine risk and benefits compared to NB-UVB, particularly any long-term risk for skin cancer.

Pulsed-Dye Lasers. Pulsed-dye lasers give off high-intensity yellow light, which destroys the tiny blood vessels that make up psoriatic plaques. This treatment has been used for years to remove birthmarks, such as port wine stains and unsightly blood vessels on the skin. Some studies have reported significant (but not complete) improvement, and remissions that have lasted up to 13 months. Treatment sessions last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms when taking acitretin and exposed to a UVB commercial tanning unit (specifically, a Wolff tanning bed).

However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer.

Managing Psoriasis

Although sunburn carries a risk for skin cancer and can make psoriasis worse, regular exposure to the sun helps clear psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sun bath only until the skin starts to tan.

Vacations in sunny areas, such as Hawaii or the Caribbean, can offer relief. For those who can afford it, a prolonged stay of several weeks at the Dead Sea in Israel has proven to significantly improve or clear 88% of those with psoriasis who go there. The region offers a unique combination of intense but naturally filtered UVA radiation combined with minerals and salts from the sea.

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. A small 1999 study found that hypnosis aimed at reducing stress may relieve symptoms.

Another study found that some patients with psoriasis had a traumatic or stressful event coincide with the appearance of psoriasis. Talking to a psychiatrist about the issue resulted in significant symptom improvement in 62% of study patients who recalled such an event.

If skin becomes dry and itchy, the patient may try the following:

Soak in a warm bath for about 15 minutes.
Afterward, apply salicylic acid first, which removes scaly skin and may promote the penetration of both moisturizers and topical prescription medications.
Then, apply a thick moisturizer or emollient, such as Vaseline, Cetaphil cream, or Eucerin cream. Lotions are not good enough moisturizers.
Special gloves made of Gore-Tex (DermaPore) may be worn at night over a thick moisturizer cream. These gloves are protective but also allow moisture to escape.

Some experts suggest that many common moisturizers may actually increase water loss in psoriasis, but studies still have to confirm this. In the meantime, if moisturizers help relieve the condition, patients should use them.

Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. It is used to relieve arthritic pain and may help relieve psoriatic itching. Capsaicin should be handled using a glove and applied to affected areas three or four times daily. The patient will usually have a burning sensation when the drug is first applied, but this sensation lessens with use.

Folic Acid. Patients should be sure they get enough of the B vitamin folate (folic acid). Folate-rich foods include liver, asparagus, fruits, green leafy vegetables, dried beans and peas, orange juice, and yeast. Many types of bread and other commercial grain products now have added folic acid.

Omega-3 Fatty Acids. Omega-3 fatty acids, particularly those found in some fish oil, have anti-inflammatory properties that may benefit some patients with psoriasis and other autoimmune conditions.

Patients with persistent psoriasis may be tempted to try alternative or untested treatments, including herbs and other nontraditional therapies. Researchers at the Medical College of Georgia say green tea slowed the growth of skin cells in animal studies and may one day prove to be useful in treating psoriasis. More research is needed.

Several traditional remedies for psoriasis include various other herbal supplements, but to date no clinical studies have been reported on these substances. No one should use any unproven therapy without consulting a doctor to be sure such treatment is not harmful, and does not interfere with any standard medications they take.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been many reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for psoriasis:

Zinc pyrithione is sometimes used, but its effectiveness is doubtful. A number of so-called natural psoriasis products (Skin-Cap, Blue Cap, Miralex) that contain this compound also contain prescription-strength corticosteroids. Such steroids have the same side effects as those in standard psoriasis agents. These products have been banned in the U.S. and Canada, but similar untested medications are available over the Internet.
Gotu Kola (Centella asiatica) is sometimes applied in a cream for psoriasis. The oral form of the herb has serious side effects, however, including increasing the risk for miscarriage in pregnant women.

Outlook

Psoriasis is lifelong and not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious.

In general, studies report the following features of its course:

The condition almost always relapses. In a few cases, large areas of plaque can persist for years.
Psoriasis nearly always goes into remission, however, often clearing on its own. In one study, 30% of patients reported untreated psoriasis going into remissions that lasted 1 - 54 years.
Psoriasis can improve during pregnancy, especially during the second and third months. Increased levels of estrogen may be responsible for this improvement. Relapse may occur after giving birth.

The emotional and social consequences of psoriasis should not be underestimated.

Many patients suffer severe humiliation and depression if plaques are visible. Some even withdraw from society and become isolated.
Some patients are forced to leave their jobs and go on disability if the condition becomes incapacitating.

Researchers have reported the following:

Surveys of patients with psoriasis report a negative mental and physical impact that is nearly equivalent to that of other major chronic conditions, including cancer, high blood pressure, diabetes, heart disease, and depression.
In one study, 75% of patients reported that psoriasis hurt their confidence.
Another study reported that 8% of people with psoriasis felt their life was not worth living.

Some patients, particularly men, use alcohol and smoking as self-medication to reduce the emotional consequences of psoriasis. In fact, studies have found that people with psoriasis have higher mortality rates, mostly from heavy drinking. Smoking has also been cited as a major risk, particularly for pustular psoriasis. Some experts believe that drinking and smoking may actually cause biological damage that contributes to psoriasis itself.

However, smoking may delay the onset of psoriatic arthritis in some patients, depending on when they started the habit. Psoriatic arthritis tends to occur about a decade after psoriasis develops. The review of 281 psoriasis patients showed that the condition appeared after about 13 years in nonsmokers, compared to 23 years in those who began smoking after the first onset of psoriasis. Psoriatic arthritis appeared after 8 years in people who smoked before developing psoriasis.

Folate Deficiency in Severe Psoriasis. Severe psoriasis can also cause folate deficiency. Folate is a B vitamin that is important for nerve function, preventing birth defects. It also prevents elevations of homocysteine, a factor that may play a critical role in heart disease.

Skin Cancers. In one study, patients with severe psoriasis (who receive medications that affect the whole body) were at higher than normal risk for developing cancers, primarily skin cancers and lymphomas. The risk was not any higher for patients with milder psoriasis. There is some indication, however, that patients with psoriasis have a higher risk for non-melanoma skin cancers regardless of treatments.

Heart Attacks. A study released in October 2006 shows an increased risk of heart attacks in people with psoriasis. The risk was highest in young patients with severe psoriasis.

Other Coexisting Conditions: Studies done in Newfoundland and Germany have also revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Increased Risk of Death. Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Study authors encourage patients to receive comprehensive health examinations to reduce the risk. Study participants were considered to have severe psoriasis if they required systemic treatment.

Impaired Temperature Regulation. Erythrodermic psoriasis, in which psoriasis covers the entire skin, can cause abnormalities in the body's ability to regulate temperature.

Zumbusch Psoriasis. A combination of erythrodermic and pustular psoriasis causes a serious condition called Zumbusch psoriasis:

The condition can develop abruptly.
Symptoms may include fever, chills, weight loss, and muscle weakness.
Patients may develop excessive fluid build-up, protein loss, and electrolyte imbalances. In such cases, hospitalization is required. Fluid and chemical balances must be restored and temperature stabilized as soon as possible.

Zumbusch psoriasis can be life threatening, particularly in the elderly. The condition is very rare in children and, if it occurs, tends to improve more quickly than in adults, possibly even without medication.

Most cases of psoriatic arthritis (PsA) are mild, but complications can occur:

Severe joint deformity and destruction (called arthritis mutilans) may develop, generally in the small joints of the hands and feet. Studies report this happens in about 5 - 16% of patients. Psoriasis patients with other arthritic conditions (osteoarthritis or rheumatoid arthritis) in the joints of the fingers tend to have a higher risk.
People with PsA may have a higher risk for respiratory illnesses.

Some earlier studies indicated that patients with psoriatic arthritis had a shorter lifespan than the general population, but more recent studies found no significant difference.

Resources

www.psoriasis.org -- National Psoriasis Foundation
www.aad.org -- American Academy of Dermatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.clinicaltrials.gov -- Find clinical trials

References

Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006 Oct 11;296(14):1735-41.

U.S. Food and Drug Administration. CDER Drug and Biologic Approvals for Calendar Year 2006 -- Updated through August 31, 2006. Last accessed on 15 October, 2006.

FDA Announces Strengthened Risk Management Program to Enhance Safe Use of Isotretinoin (Accutane) for Treating Severe Acne. US Food and Drug Administration. Rockville, MD: National Press Office; August 12, 2005.

Anstey AV and Kragballe K. Retrospective assessment of PASI 50 and PASI 75 attainment with a calcipotriol/betamethasone dipropionate ointment. Int J Dermatol. 2006 Aug;45(:970-5.

National Psoriasis Foundation. About Psoriasis: Statistics. Last Accessed 9 October, 2006.

Antoni CE, Kavanaugh A, Kirkham B, Tutuncu Z, Burmester GR, Schneider U. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227-1236.

Bowcock AM, Cookson WO. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Human Mol Genet. 2004;13 Spec No 1:R43-55.

Feldman SR, Koo JY, Menter A, Bagel J. Decision points for the initiation of systemic treatment for psoriasis. J Am Acad Dermatol. 2005;53(1):101-107.

Murase JE, Chan KK, Garite TJ, Cooper DM, Weinstein GD. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;141(5):601-6.

Review Date:
9/19/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Kidney stones

FitSugar — Wed, 08 Oct 2008 17:35:35 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Diagnosis
Treatment
Medications
Other Treatments
Complications
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research:

Patients who have the most common type of gastric bypass surgery, the Roux-en-Y, are at increased risk for kidney stones, beginning 6 months after surgery, according to a study published in 2006.

Causes of Kidney Stones:

Calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of this imbalance is unknown.
Having acidic urine or too much uric acid in the body leads to the formation of uric acid stones.
Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes.
Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Treatments:

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 - 3 days.
Certain medications can prevent recurrence of stones in people who are at high risk.
Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. The shock waves are delivered from outside the body.
Surgery may be necessary if the stone or stones are too big to pass, and cannot be broken down through ESWL.
A change of diet and increased drinking of fluids, especially water, will help prevent a recurrence.

Introduction

Kidney stones are hard, solid rocks that form in the urinary tract. In many cases, the stones are very small and can pass out of the body without any problems. However, if a stone (even a small one) blocks the flow of urine, excruciating pain may result, and prompt medical treatment may be needed.

The process of urination begins in the kidneys. The kidneys filter out fluids and waste from the body, producing urine. The two kidneys are located deep behind the abdominal organs, below the ribs and toward the middle of the back.

Each kidney contains over a million nephrons. These are the tiny filtration units of the kidney.
Each nephron is composed of a tiny group of blood vessels (a glomerulus) enclosed in a funnel-like structure called Bowman's capsule.
Each glomerulus filters waste products, water, and salts out of the liquid part of the blood (plasma) that has entered the kidney.
About 1% of the plasma is converted into urine. The rest returns into the blood to prevent dehydration. Urine is primarily made of acids, urea, and creatinine (nitrogen compounds).
Urine passes from Bowman's capsule into tiny tubules, which lead to large collecting tubes in the center of the kidney. As the urine passes through this network, it becomes more concentrated.
Urine then flows from the kidney through thin tubes called ureters into the bladder.
The bladder's stretchy walls expand to store the incoming urine until it leaves the body through a tube called the urethra.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Click the icon to see an image of the urinary tract.

Occasionally, various salts build up on the inside surfaces of the kidney and form crystals. Eventually these crystals become large enough to form stones in the kidney, a condition called nephrolithiasis. Kidney stones (renal calculi) may also form in the ureter or the bladder. Combinations of minerals and other chemicals, some derived from a person's diet, make up the salts in these stones.

Click the icon to see an image of the kidney stones.

Calcium Stones. About 70 - 90% of all kidney stones are made of calcium, usually combined with oxalate, or oxalic acid. A number of common vegetables, fruits, and grains contain oxalate.

About 6% of calcium stones are made of calcium phosphate (called brushite).

Uric Acid Stones. Uric acid is responsible for close to 10% of kidney stones. It is the breakdown product of purines, nitrogen compounds found in our bodies and in certain foods. The breakdown of purines to uric acid occurs in the liver, and from there uric acid enters the bloodstream, most of it passing into the kidneys. From the kidneys, uric acid leaves the body in the urine. Often, uric acid stones occur with calcium stones.

Struvite Stones. Struvite stones are made of magnesium ammonium phosphate. They are almost always associated with certain urinary tract infections. Worldwide, they make up to 30% of all kidney stones. In the United States, however, less than 15% of all stones are struvite. Most struvite stones occur in women. The rate of these stones may be declining in America, perhaps because of better control of urinary tract infections.

Cystine Stones. A build-up of the amino acid cystine, a building block of protein, causes 1% of kidney stones in adults and up to 8% of stones in children. The tendency to form these stones is inherited. Cystine stones are marked by rapid growth and recurrence, which, if not treated promptly, can eventually lead to kidney failure.

Xanthine Stones. Other kidney stones are composed of xanthine, a nitrogen compound. These stones are extremely uncommon and usually occur as a result of a rare genetic disorder.

Click the icon to see an animation about kidney stones.

Causes

The key process in the development of kidney stones is supersaturation.

The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

Magnesium
Citrate
Pyrophosphate
Enzymes

These substances:

Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
Prevent crystal formation
Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

Uric acid and cystine stones mainly form in acidic urine.
Calcium phosphate and struvite stones increase in alkaline urine.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known, and the condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones:

Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
Renal calcium leak: In this condition, the filtering processes in the kidney fail, causing an increase of calcium in the urine.
Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

Severe vitamin B6 deficiencies (usually due to genetic disorders)
Deficiencies in Oxalobacter formigene, an intestinal bacteria that breaks down oxalate
Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes a buildup of oxalate
Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

A study published in 2006 found that patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, were at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. The study found that patients who underwent the procedure developed hyperoxaluria, and the condition was common 12 months after surgery. The authors also noted an increased number of kidney stone incidents in this patient group.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
Immobilization: Lack of movement can lead to kidney stones.
Renal tubular acidosis: This disorder causes acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream but also reduces protective citrate levels.

Hyperuricosuria is a condition of high levels of uric acid in urine. It occurs in between 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine (hypocitraturia) is a significant risk factor for calcium stones. In addition, hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

Renal tubular acidosis
Potassium or magnesium deficiency
Urinary tract infection
Kidney failure
Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Human body tissues, certain foods, and certain alcoholic drinks contain substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal.

The following conditions are usually seen in patients with uric acid stones:

Too much acid in the urine for a long period (the most important cause of uric acid stones)
Lower than normal amounts of urine produced.
Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
Diabetes: New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings were published in the May 2006 Journal of the American Society of Nephrology.
Insulin resistance: People with insulin resistance are at an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
Genetic factors: Genetic factors can increase a person's risk for uric acid stones.
Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

Certain medications (chemotherapy drugs, diuretics, and salicylates)
Binge drinking
Not eating for long periods of time (fasting)
Lead poisoning
Blood cancers (leukemia, multiple myeloma, and lymphomas)
Some rare types of anemia (low levels of red blood cells in the blood)
Chronic diarrhea

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.

Risk Factors

Kidney stones are one of the most common disorders of the urinary tract. They are an ancient health problem. Evidence of kidney stones has been found in an Egyptian mummy estimated to be more than 7,000 years old.

An estimated 1.3 million Americans seek medical help for kidney stones each year. At this time, studies suggest kidney stones affect over 5% of Americans and that the rate has increased since the 1970s, perhaps because of increases in animal and dietary protein intake.

Men. The risk of kidney stones increases in a man's 40s and continues to rise until age 70. Caucasian men are at higher risk than other groups.

Women. The risk of kidney stones peaks in a woman's 50s. In younger women, stones are more likely to develop during the late stages of pregnancy. Pregnant women tend to have a higher calcium intake, but their kidneys do no handle the calcium as well as they did prior to pregnancy. Kidney stones are still a rare occurrence during pregnancy, however, affecting only 1 in 1,500 pregnancies.

Risk Factors in Children. Stones in the urinary tract in children are usually due to genetic factors. Most of the time, the cause is too much calcium in the urine (hypercalciuria). Deformities in the urinary tract pose a significant risk for kidney stones in children. Children with low birth weight who need to be fed intravenously are also at risk for stones.

Obesity and weight gain are both associated with an increased risk of kidney stones.

Men who weigh more than 220 lbs are 44% more likely to develop kidney stones than men who weigh less than 150 lbs.
Women who are obese are 90% more likely to develop kidney stones than women with a lower body mass index (BMI).

Higher BMIs and larger waist circumferences are both risk factors for kidney stones. Researchers think that there may be a link between fat tissue, insulin resistance, and urine composition. People with larger body sizes may excrete more calcium and uric acid, which increase the risk of kidney stone formation.

A family history of kidney stones increases one's risk for the condition. Researchers are looking into markers or other factors that might predict kidney stones in relatives, although none has yet been clearly identified. One report found that among the siblings of patients with calcium stones, sisters with higher urinary calcium levels and more acidic urine were more likely to develop stones. Brothers with high urinary calcium, low urinary potassium, and older age were more likely to have the problem. A family history of gout may also make a person vulnerable to stones.

According to a 2003 study of American ethnic groups, Caucasians have the highest incidence of kidney stones (5.9%) followed by Mexican Americans (2.6%). African-Americans have the lowest risk (1.7%).

Dietary factors, minerals in local water, or both may contribute to geographic differences that have been observed in the occurrence of kidney stones. Studies have reported the highest occurrence of kidney stones in the southern region of the United States and the lowest in the west. One study suggested that the higher risk may be due to a higher rate of high blood pressure in the southern states and certain dietary habits, particularly lower intake of magnesium and low use of calcium supplements.

Specific Foods. In general, certain foods increase the risk for stones only in people who have genetic or medical vulnerability. People whose diets are high in animal protein and low in fiber and fluids may be at higher risk for stones. A number of foods contain oxalic acid, but there is no proof that such foods make any major contribution to calcium oxalate stones in people without other risk factors. However, several studies have shown that increasing dietary calcium and restricting salt, animal protein, and foods rich in oxalate can help prevent calcium oxalate stones from returning.

Stress. One study reported that people who had a major, stressful life experience were more likely to develop stones than those who had not. Some experts speculate that this increased risk may be due to a hormone called vasopressin, which is released in response to stress. Vasopressin also increases the concentration of urine.

Sleep Position. Sleeping in the same position consistently may influence risk. A 2001 study reported that in people who had a history of kidney stones, recurrences tended to occur on the same side that people slept on. An earlier study suggested that people who had kidney stones were more apt to sleep on their stomachs. Movement during sleep did not appear to affect the risk.

Being Bedridden. Any medical or physical condition that keeps a person in bed or immobile increases blood levels of calcium from bone breakdown, thereby posing a risk for stone formation.

Gout. Patients with gout are at a high risk of uric acid stones. These patients have very acidic urine, and a 2002 study suggested that the two disorders may have a common source.

High Blood Pressure. Persons with high blood pressure are up to three times more likely to develop kidney stones. It is not entirely clear whether having high blood pressure increases the risk for a stone, whether stones lead to high blood pressure, or if there is an action linking both.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis cause problems in absorption of substances in the intestines. These problems significantly increase the risk for kidney stones, particularly in men.

Urinary Tract Infections (UTIs): Urinary tract infections are almost always the cause of struvite stones.

Hyperparathyroidism: The parathyroid glands regulate calcium levels in the body through the parathyroid hormone. In hyperparathyroidism, one or more of these glands makes too much parathyroid hormone. Some people with hyperparathyroidism develop kidney stones. Surgery to remove the hyperactive parathyroid gland in such patients reduces the risk for stone formation, but the risk still remains high for some time after surgery.

Other Medical Conditions. Kidney disease, chronic diarrhea, certain cancers (such as leukemia and lymphoma), and sarcoidosis put people at higher risk for stones.

AIDS medications. Over 10% of persons with AIDS who take the medicine indinavir develop stones. The risk is even higher in patients with AIDS who also have hepatitis B, hepatitis C, or hemophilia, as well as those who are very thin or who take the antibiotic combination TMP-SMX. In one study of persons with AIDS who took a combination of indinavir, zidovudine, and lamivudine, 36% developed kidney stones.

Other Drugs. Kidney stones are a rare side effect of thyroid hormones and loop diuretics (drugs that increase urination). In fact, diuretics are also used to prevent calcium stones. Certain cancer chemotherapies can also cause kidney stones. Long-term use of medications, such as antacids, which change the acidic content of urine, may increase the risk for kidney stones.

Symptoms

In many cases, kidney stones do not produce symptoms. However, if a stone becomes stuck in the ureter (the thin tube between the bladder and the kidney), symptoms can be very severe. Often, they vary depending on the stone's location and its progress.

Kidney stone attacks tend to be most common late at night or in the early morning, possibly because of minimal urine output or constriction of the ureters during the early morning hours. Kidney stone attacks are least common during the late afternoon

Pain usually begins abruptly on one side and then usually continues as intense, constant pain. (In some cases it persists for a few minutes, disappears, and then returns after about 10 minutes.)
The patient cannot become comfortable and usually stands, sits, paces, or reclines in a vain search for a position that will bring relief.
If the stone is in the kidney or upper urinary tract, the pain usually starts in one flank area (to the side of the back near the waist). It typically moves to the groin as the stone passes down.
If the stone is too large to pass easily, the pain follows the muscle contractions in the wall of the ureter as they try to squeeze the stone along into the bladder.
Nausea and vomiting may occur.
Blood in the urine may be present.
As the stone passes down the ureter closer to the bladder, a person may feel the need to urinate more often or a burning sensation during urination.
If fever and chills accompany any of these symptoms, an infection may be present.

The size of the stone does not necessarily predict the severity of the pain; a very tiny crystal with sharp edges can cause intense pain while a larger round stone may not be as distressing. Struvite stones can often occur without symptoms.

Diagnosis

The doctor will perform a physical exam. This includes pressing against abdominal areas for tender locations that might indicate the presence of the stone.

The patient's age is a significant factor. Kidney stones that occur in children and young patients are more apt to result from inherited problems that cause cystine, xanthine, or, in some cases, calcium oxalate stones. In adult patients, calcium stones are most common.

A medical history may help predict which crystal has formed the stone. The doctor will need to know the following:

Any previous kidney stone attacks
Histories of cancer, sarcoidosis, or small bowel disease
Any medications being taken, including non-prescription substances, particularly high doses of vitamins D or C and calcium-containing antacids

Many conditions can cause symptoms similar to kidney stones. Usually the diagnosis is easily made because of the specific nature of the symptoms, but it is not always clear. Urinary tract infections can cause similar, but usually less intense, pain. In fact, infection may be present with a kidney stone. Other causes of pain that may mimic kidney stones include:

Gallstones
Diverticulitis (infection or irritation of abnormal pockets in the intestines)
Intestinal blockage
Blood clots
Irritable bowel syndrome
Appendicitis
Stomach ulcers
Hiatal hernia (when the upper part of the stomach bulges into the chest, through an opening in the diaphragm)
Pancreatitis (inflammation of the pancreas)
Hepatitis
Pelvic inflammatory disease
Inflammatory bowel disease (Crohn's and colitis)
Heart attack

Various imaging techniques are helpful in determining the presence of kidney stones. The best approach uses spiral (or helical) computed tomography scans. If it is not available, the patient will need ultrasound or standard x-rays. If no stones show up, but the patient has severe pain that suggests the presence of kidney stones, the next step is an intravenous pyelogram.

X-Rays. A standard x-ray of the kidneys, ureters, and bladder may be a good first step for identifying many stones, since many are visible on x-rays. Calcium stones can be identified on x-rays by their white color. Cystine crystals can also show up on x-rays.

Spiral (or Helical) Computed Tomography. A type of computed tomography (CT) scan, called a spiral or helical CT scan, is currently the best method for diagnosing stones in either the kidneys or the ureters. This test is fast, does not require instruments or foreign chemicals to enter the body, and provides detailed accurate images of even very small stones. If stones are not present, a spiral CT scan can often identify other causes of pain in the kidney area. It is better than x-rays, ultrasound, and intravenous pyelogram -- the previous standard test for detecting kidney stones. Experts hope spiral CT will eventually be able to identify the chemicals present in a stone.

Ultrasound. Ultrasound can detect clear uric acid stones and obstruction in the urinary tract. It is not useful for finding very small stones, but some research indicates that it may be a useful first diagnostic step in the emergency room to help predict the likelihood of a stone, including suspected stones in children.

Intravenous Pyelogram. With intravenous pyelogram (IVP), the doctor injects a special dye into the patient. A technician will then take x-rays as the dye enters the kidneys and travels down the urinary tract. IVP is invasive but, until recently, was the most cost-effective method for detecting stones. Where it is available, spiral CT is now preferred, since it gives a faster diagnosis, is more accurate, is safer, and is similar in cost.

In any case, IVP should not be used on patients with kidney failure. There is also a risk for an allergic reaction to standard dyes, although newer less allergenic ones are becoming available.

In the procedure intravenous pyelogram (IVP), the patient is injected with dye. X-rays are taken as the dye travels through the urinary tract. This procedure is done to confirm the presence of kidney stones, although some stones may be too small to see.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) techniques are showing promise for diagnosing urinary tract obstruction but do not yet accurately reveal small stones, or ones that do not cause a blockage. Because no radiation is involved with MRI, however, it may prove to be a good option for pregnant women.

Urine samples are required to evaluate features of the urine, including its acidity and the presence of:

Red or white blood cells
Infection
Crystals
High or low levels of chemicals that inhibit or promote stone formation

Clean-Catch Urine Sample for Culturing. After determining that a kidney stone is present, the health care provider usually gives the patient a collection kit, including filters, to try to catch the stone or gravel as it passes out. The urine may also be tested (cultured) for the presence of infection-causing organisms. A clean-catch urine sample is almost always required for culturing. To provide a clean catch, do the following:

First, wash your hands thoroughly, then wash the penis or vulva and surrounding area four times with downward strokes, using a new soapy sponge each time.
Begin urinating into the toilet and stop after a few drops.
Position the container to catch the middle portion of the urine stream. Ideally, this urine will contain only the bacteria and other evidence of the stone.
Urinate the remainder into the toilet.
Tighten the cap on the container securely, being careful not to touch the inside of the rim.

Click the icon to see an image of a calcium urine test.

Twenty-Four Hour Urine Collection. A 24-hour urine collection may be needed to measure urine volume and levels of acidity, calcium, sodium, uric acid, oxalate, citrate, and creatinine.

You should not change any of your usual eating or drinking patterns when performing this test.
Discard the first urination on the day of the test.
Afterward all urine passed over the next 24 hours is collected, including the first urination on the morning of day two.
A second 24-hour urine collection may be needed to determine if treatment is working or if the first analysis was not conclusive and the doctor suspects a less common stone, such as a cystine or xanthine stone.

Click the icon to see an image of a uric acid urine test.

Urine tests that are used to determine the specific chemical and biological factors causing the stone should be performed about 6 weeks after the attack, since the attack itself may change the levels of such substances, including calcium, phosphate, and citrate. It should be noted that calcium levels in the urine may be abnormal even in many people without stones. In addition, high urinary concentrations of calcium may pose a greater or lesser risk depending on age. (In one 2001 study, middle-aged adults with high urinary calcium concentrations had a much greater risk than older adults with high levels.)

The kidney stones obtained from the urine sample are examined under a microscope. The crystal formations are often specific enough so that the doctor is able to identify the substance causing the stone.

Calcium oxalate crystals are eight-sided, while calcium phosphate crystals tend to have irregular shapes.
Uric acid stones are sometimes described as pear-shaped or diamond-shaped.
Some struvite stones have very specific shapes commonly described as "coffin lids." Struvite crystals may also occur in a formation known as a staghorn, which can be large and damaging to the kidney.

Testing whether urine is acidic or alkaline helps to identify the specific type of stone. The levels of acidity or alkalinity in any solution, including urine, are indicated by the pH scale:

A pH value of 7.0 is neutral.
A solution with a low pH (below 7.0) is acidic. (A low pH favors uric acid and cystine stones.)
A solution with a high pH is alkaline. (A high pH favors calcium phosphate and struvite stones.)

A dipstick test for blood in the urine (called hematuria) is typically performed when patients appear in the emergency room with flank pain (the primary symptom of kidney stones). About a third of kidney stone patients, however, do not show blood in the urine, so other tests may be needed.

Blood Tests for Stone Factors. Blood and urine tests help determine what substances form the crystals. This allows the doctor to determine the appropriate treatment and preventive measures.

Blood tests may help determine blood levels of urea nitrogen, creatinine, calcium, phosphate, and uric acid for patients with known or suspected calcium oxalate stones. Doctors will usually schedule these tests about 6 weeks after the attack, in order to measure these substances when the stone has been passed, and the patient has been stabilized. This is particularly true in patients with recurrent stones.

Parathyroid Tests. Tests to detect parathyroid hormone levels are given if the doctor suspects hyperparathyroidism, based on other signs and symptoms.

Tests for Infection. A test result that shows a high white blood cell count might indicate infection. Such results, however, could be misleading, since the number of white blood cells could also increase in response to the extreme physical stress of a kidney stone attack.

Tests for Metabolic Problems. About half of children with stones have an identifiable metabolic disorder, which increases their risk of stone recurrence five-fold. Experts argue whether tests for metabolic disorders are routinely needed once the stone composition has been determined. Studies suggest the following:

People with recurrent calcium stones have a wide range of irregular blood or urine test results, indicating a variety of possible metabolic disorders. For example, calcium stones in middle-aged women may be due to parathyroid abnormalities.
Calcium phosphate stones most likely result from renal tubular acidosis.
People with non-calcium stones generally have identifiable metabolic disorders.
Determining the stone composition may be sufficient for treatment, and may help avoid unnecessary metabolic tests.

Treatment

When tests show there is a kidney stone, the next step is to determine treatment. The patient should be admitted to the emergency room if they have severe vomiting, fever, or symptoms of infection.

Strong opioid painkillers, such as meperidine (Demerol), are often required for a severe kidney stone attack. However, doctors will usually not give such drugs until they confirm the presence of a kidney stone on an x-ray. In some cases, powerful nonsteroidal anti-inflammatory drugs (NSAIDs) may work just as well as opioids, and they have fewer side effects. However, they do take longer to work.

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 to 3 days. In some cases, a stone may take weeks to months to pass, although pain usually goes away before that.

The patient should drink plenty of water (two to three quarts a day) to help move the stone along, and take painkillers as needed. The doctor usually provides a collection kit with a filter and asks the patient to save any passed stones for testing.

If the stone has not passed in 2 - 3 days, the patient will need additional treatments. In some severe cases, hospitalization may be necessary.

Specific procedures vary depending on the size of the stone or complexity of the situation. Noninvasive procedures are proving to be very beneficial in eliminating stones, and have largely replaced invasive surgeries.

For small stones that are lodged in the lower part of the ureter, ureteroscopy or shock wave lithotripsy are the procedures of choice.
For larger stones, ureteroscopy, percutaneous nephrolithotomy, and shock wave lithotripsy are all potentially useful. The choice of any of these procedures depends on a number of factors, including location of the stone and the presence of any problems that caused the stone in the first place.
In some complicated cases, standard open surgical procedures (called nephrolithotomy) may be required.

See "Other Treatments" section for more information on kidney stone surgery.


Stone Type	Diet and Lifestyle	Medications	Procedures
Calcium Oxalate	Plenty of fluids. (Choose water, lemon juice. Avoid grapefruit, apple, and cranberry juice.) Limit the amount of protein and salt in the diet. Increase fiber. Limit the amount of fats in the diet, particularly in people who have short bowel syndrome. Balance normal calcium intake with potassium- and phosphate-rich foods. Limit the amount of calcium in the diet (only in people who have genetic abnormalities that cause high intestinal absorption of calcium). Limit the amount of foods high in oxalates (only in patients with rare intestinal conditions that cause hyperoxaluria).	Diuretics ("water pills"), Citrate salts, phosphates, cholestyramine.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Uric Acid	Plenty of fluids. (Choose water, blackcurrant juice. Avoid cranberry juice.) Increase calcium intake (be sure well-balanced with potassium and phosphates). Reduce protein and other foods with high-purine content.	Potassium citrate, sodium bicarbonate, allopurinol.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Struvite stones	Plenty of fluids (water, cranberry juice). Reduce proteins.	Antibiotics to eliminate any infection. Acetohydroxamic acid (AHA) may be helpful in combination with antibiotics. In some cases, organic acids given through urinary tract.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.
Cystine stones	Very high fluid intake (four quarts a day). Limit the amount of protein in the diet.	Alkalizing agents (such as bicarbonate). Sometimes d-penicillamine, tiopronine, or captopril useful for lowering cystine levels.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.

Medications

Diuretics. Diuretics are medicines commonly used to treat high blood pressure and other disorders. They remove fluid and sodium from the body. Low doses of a class of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. Thiazides include:

Hydrochlorothiazide (Esidrix, HydroDiuril)
Chlorothiazide (Diuril)
Trichlormethiazide (Metahydrin, Naqua)
Chlorthalidone (Hygroton)

However, thiazides also cause potassium loss, which reduces citrate levels and can increase the risk for stones. Patients taking thiazide pills should also take potassium citrate, to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide does not work.

Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:

Potassium magnesium citrate is available over the counter. It is proving to be very beneficial in preventing kidney stones. In one study, potassium magnesium citrate reduced the risk for kidney stone recurrence by 85%.
Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) is given as the only treatment to people with normal urine calcium levels. Between 70 - 75% of patients with recurrent stones have ongoing remission (no stone recurrence) with potassium citrate treatment. However, some people cannot tolerate potassium citrate because of side effects (stomach problems).
Magnesium citrate (Citroma, Citro-Nesia) may help people who develop calcium stones from impaired intestinal absorption due to short bowel disease.

None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain this mineral or prevent its loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid citrate supplements, or discuss using non-tablet forms with their doctor.

Phosphates. Phosphates help reduce the breakdown of bone that releases calcium into the bloodstream. They are also involved in the kidney's reabsorption of calcium from the urine.

Phosphate compounds:

Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the doctor. Diarrhea is a possible side effect.
Cellulose phosphate (Calcibind) is recommended only for severe hypercalciuria that is associated with recurrent calcium stones and is caused by excessive absorption of calcium from the intestines. However, this drug may increase oxalate levels and decrease magnesium levels, which can lead to different stones. Taking magnesium supplements and reducing dietary oxalates, calcium, and ascorbic acid may help offset these risks. Cellulose phosphate may also cause bloating.

Avoid acidic forms of phosphate, since they increase the risks for both hypocitraturia and hypercalciuria.

Cholestyramine (Questran, Questran Light) is a drug used to reduce cholesterol levels. However, it also binds with oxalate in the intestine, so it is also used to reduce high oxalate levels in urine (hyperoxaluria). The drug usually comes in a powder that is dissolved in liquid.

Bloating and constipation are common side effects of this drug. Cholestyramine also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, take other drugs 1 hour before, or 4 - 6 hours after, taking cholestyramine.

Long-term use of cholestyramine may cause deficiencies of vitamins A, D, E, and K. Vitamin supplements may be necessary.

Sodium Bicarbonate. Patients whose persistently acidic urine causes uric acid stones may take sodium bicarbonate to reduce urine acidity. Patients taking sodium bicarbonate must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become too alkaline. This increases the risk for calcium phosphate stones. Patients who need to reduce the amount of sodium they take in (as a result of other medical conditions) should not use sodium bicarbonate.

Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.

Allopurinol. Allopurinol (Lupurin, Zyloprim) is very effective in reducing high levels of uric acid, and may be helpful for patients with uric acid stones. Allopurinol will not prevent calcium stones from forming. There is also a slight risk for the formation of xanthine stones with this drug. Side effects include diarrhea, headache, and fever. More severe complications include blood disorders that may produce fatigue, bleeding, or bruising. The drug may also increase the risk for cataracts.

About 2% of patients experience an allergic reaction to allopurinol that causes a rash. In rare cases, the rash can become severe and widespread enough to be life threatening. Allergic individuals who have experienced only a mild rash to sodium bicarbonate may be able to build up their tolerance for allopurinol by undergoing a desensitization process. In this process, patients start with small doses of allopurinol and gradually increase them, if no reaction develops.

Allopurinol reduces uric acid levels rapidly, so it may trigger an attack of gout in vulnerable people. To prevent this problem, patients taking allopurinol should also take a nonsteroidal anti-inflammatory drug (NSAID) for 2 or 3 months. Aspirin should not be taken, since it increases uric acid levels. Patients should discuss the appropriate NSAID choice with their doctor.

Before patients can receive any medical treatment for struvite stones, they must have surgery to completely remove the stones.

Antibiotics for Eliminating Infection. Persons with struvite stones receive ongoing treatment with antibiotics to keep the urine free of the bacteria that cause urinary tract infections. Careful follow-up and urine testing is extremely important. A high-pH urine indicates low acidity and an increased risk of infection.

Acetohydroxamic Acid (AHA). Acetohydroxamic acid (AHA or Lithostat) is beneficial when used with long-term antibiotics. AHA blocks enzymes that bacteria release, and has been effective in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron levels in the body, so anemia is a common problem. Patients may need to take iron supplements. Other side effects include nausea, vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs.

Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by specific struvite-causing organisms.

Patients taking this medicine should avoid alcohol. Pregnant women should not take acetohydroxamic acid.

Organic Acids. Medical treatments to dissolve stones may be useful in patients who do not respond to other medications, or in combination with surgeries. Acidic urine dissolves struvite stones, so the doctor may wash the urinary tract with a solution of organic acids (such as Renacidin). Candidates for such washes must have sterile urine (no bacteria or other organisms in the urine) and healthy kidney function. In surgical patients, the wash is performed 4 or 5 days after the operation. The wash starts with saline (salt solution) for 1 - 2 days and, if there are no problems, the organic acid solution follows for another 1 or 2 days, until all stones dissolve. Regular urine tests are necessary to ensure that the bacteria do not return.

Aluminum Hydroxide Gel. An aluminum hydroxide anti-acid gel may reduce phosphate levels that are important in struvite stone formation, but it has a long-term risk of causing aluminum toxicity. Long-term reduction of phosphorus can also increase the risk for calcium oxalate stones. Experts recommend limiting phosphorus through a low-protein diet, rather than through the use of this gel.

The first-line treatment for cystine stones is increasing the alkalization of urine so the stones can dissolve. If alkalization fails, drug treatments may include d-penicillamine, alpha-mercaptopropionylglycine (tiopronine), or captopril. These medications lower cystine concentration.

Patients with cystine stones must drink plenty of fluids, much more than patients with other stones. The patients should drink at least four quarts of water over a 24-hour period.

Other Treatments

Surgery is usually needed if the stone is too large to pass on its own, if there are signs that the stone is growing, or if the stone is blocking the urine flow and causing a urinary tract infection or kidney damage.

Until recently, the procedure to remove a stone was a very painful, major surgery, requiring 4-6 weeks of recovery. Today, treatments for stones are much less invasive. Major surgery is performed in less than 2% of patients.

Stone removal procedures:

Extracorporeal shock wave lithotripsy (ESWL) is used for small stones (less than one centimeter, or slightly less than half an inch) that occur in the upper part of the ureter and do not pass on their own. One study indicated lithotripsy might even be safe and effective for patients whose stones are associated with malformed kidneys, although such patients are at higher risk for stone recurrence and should be carefully monitored.
Percutaneous nephrolithotomy (PNL). PNL can be used for very large stones in the upper urinary tract, when ESWL fails, for kidney transplant patients, or when the kidneys or surrounding areas are malformed. PNL is the preferred procedure for drug-resistant cystine stones, which are usually also resistant to shock wave therapy.
Ureteroscopy. For stones in the lower tract, ureteroscopy is generally the best procedure, although lithotripsy is also usually feasible and patients ordinarily prefer it.
Standard open surgery (nephrolithotomy) may be required if any of these procedures fail or are not appropriate, or in special cases, such as when the patient is very obese.

Most procedures are more effective for calcium and uric acid stones and less effective for struvite and cystine stones, although new techniques may be improving their effects on all stones.

Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. ("Extracorporeal" means "outside the body," and "lithotripsy" means stone-breaking.) ESWL is not used for cystine stones. The procedure generally does not work for stones larger than three centimeters in diameter (which is slightly over an inch). There are several variations of ESWL. The following is a typical procedure:

Most ESWL procedures use some anesthesia, although they are often done on an outpatient basis.
The patient is positioned in a water bath. (In some procedures the patient lies on a soft cushion.)
The procedure uses ultrasound to generate shock waves that travel through the skin and body tissues until they hit the dense stones. (The doctor pinpoints the stone during treatment by using x-rays or ultrasound.)
The shock waves crush the stones into tiny sand-like pieces that usually pass easily through the urinary tract.
The shattered stone fragments may cause discomfort as they pass through the urinary tract. In such cases, the doctor may insert a small tube called a stent through the bladder into the ureter to help the fragments pass. This practice, however, has not proved to speed up passage of the stones in most cases and is not used routinely.

Extracorporeal shock wave lithotripsy (ESWL) is a procedure used to shatter simple stones in the kidney or upper urinary tract. Ultrasonic waves are passed through the body until they strike the dense stones. Pulses of sonic waves pulverize the stones, which are then more easily passed through the ureter and out of the body in the urine.

Success rates of ESWL range from 50 - 90%, depending on the location of the stone and the surgeon's technique and level of experience. Recovery time is short, and most people can resume normal activities in a few days.

Complications. Complications may include the following:

The most common complication is blood in the urine, which lasts for a few days after treatment. To reduce the chances of bleeding, doctors usually tell patients to avoid taking aspirin and other NSAIDs, which can promote bleeding, for 7 - 10 days before the treatment.
Bruising and minor discomfort due to the shock waves are common in the back or abdomen.
Sometimes the stone does not completely break up with one treatment, and additional treatments may be required. Inability to pass stone fragments may also be a particular problem in patients who have cysts or other kidney problems.
Higher risk for diabetes later. A 2006 study published in the journal Urology found that 17% of patients who received shock-wave lithotripsy developed diabetes later in life. The diabetes risk was related to the number and intensity of shocks.
Higher risk for hypertension (high blood pressure). The same study that linked ESWL to diabetes also showed that people who received shock-wave lithotripsy treatment were 47% more likely to develop high blood pressure than those who had their stones treated without surgery.

ESWL appears to be safe for children, although a 2001 study reported temporary damage in the kidney tubules after treatment. It is unclear if this complication has any long-term consequences. Experts recommend using the least amount of shocks and impact possible in young people. If more than one treatment is needed, there should be a waiting period of at least 15 days between treatments.

Percutaneous nephrolithotomy may be used when ESWL is not available or effective (such as if the stone is very large, in an inaccessible location, or is a cystine stone). It is also preferred over ESWL for stones that have remained in the ureter for more than 4 weeks.

It is more effective than ESWL for patients with severe obesity, and appears to be safe for the very elderly and the very young. Success rates are nearly 98% for kidney stones and 88% for ureteral stones. They may vary by the technique used and the specific patients. For example, success rates are slightly lower in children, although the procedure can be done safely in young patients. Long-term effects are unknown.

A typical procedure is as follows:

The surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney.
The surgeon then inserts an instrument called a nephroscope through the tunnel.
The stone is located and removed. If it is large, it is destroyed using ultrasound, lasers, or other devices. The surgeon then removes the fragments. An advantage of percutaneous nephrolithotomy over ESWL is that the surgeon is able to remove the stone fragments directly, instead of relying on their natural passage from the kidney.
Generally, patients stay in the hospital for 5 or 6 days and may need a small device called a nephrostomy tube left in the kidney during the healing process.

Devices Used to Destroy Stones. For large stones, some type of energy-delivering device may be needed to break the stone into small pieces. They are referred to as intracorporeal lithotripsy devices (meaning stone breakers within the body). The device may be one of the following:

Ultrasound is currently the preferred method. It results in a stone-free rate of 94%. A rigid nephroscope delivers the ultrasound waves.
Pneumatic (compressed air) lithotripsy uses a probe that comes in direct contract with a stone. Compressed air causes a piston to collide rapidly with the probe, and the result is a "jackhammer" action against the stone, causing the stone to break up. This method, however, can send stone fragments into other parts of the urinary tract.
A more recent device uses a combination pneumatic probe and ultrasound, with stone-free rates of 80 - 89%. It may prove to be superior to ultrasound alone and be effective against stones of all types.
The holmium laser literally melts the stones and destroys up to 100% of stones of any composition. It uses a flexible nephroscope and has an excellent safety record. It should be used sparingly, however, with particular caution against large uric acid stones until more is understood about its effect. Another device, the erbium: YAG laser, although showing promise in lithotripsy, is not currently practical.

Complications. Complication rates are about 3%. Major complications occur in about 1% of cases. These complications may include scarring of the tissue, but studies indicate that it does not impair kidney function, even if the patient requires repeat surgery. There is also a risk for blood loss during and after the procedure, which, in some cases, can be significant.

Because the procedure requires large volumes of fluid, fluid overload is a potential problem, particularly in children or patients with heart disease.

In some cases, infection may result. Other complications may include a collapsed lung and injuries to areas outside the kidney (but within the operative area), such as the abdomen or chest.

Ureteroscopy may be used for stones in the middle and lower ureter. With the arrival of smaller instruments, this procedure can be done successfully in children as well. The procedure involves the following:

The patient receives a general anesthetic, though no incision is required for the procedure.
The surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter.
The surgeon locates the stone or stones.
The surgeon can remove smaller stones by grasping them with small forceps. A laser or pneumatic device breaks up large stones.
The surgeon may decide to leave a small tube, or stent, in the ureter for a few days after treatment, to help the lining of the ureter heal.

Complication rates range from 10 - 20%, with major problems occurring in up to 6% of patients. In some cases, large stones are not broken up into small enough pieces. This can result in blockage of the urinary tract and possible kidney damage.

Imaging tests, such as ultrasound or spiral CT, are useful within 3 months to check for residual stones, and a second procedure may be required. The risk of complications is highest when the procedure is performed by less experienced surgeons, or if stones are found in the kidney. The risk for perforation of the ureter increases the longer the procedure takes.

Open surgery involves incisions through the patient's flank and into the kidney. The surgeon will cool the kidneys using ice. X-rays during the procedure help locate the stone. At the beginning of the surgery, the surgeon will isolate the arteries supplying the kidneys, ensuring they are not harmed during the surgery. The surgeon will then locate and remove the stone. The surgeon will also correct any blockage in the affected area. The surgery, called nephrolithotomy, is very invasive and is restricted to the following:

Patients with very large or complex stones that cannot be removed using less invasive measures
Very obese patients

Some centers report success with extracorporeal shock wave lithotripsy, however, in patients who would normally be nephrolithotomy candidates. Therefore, even these patients should discuss other options with their surgeon.

The procedure is not appropriate for patients with:

Bleeding or clotting disorders
Untreated widespread infection
Severe and chronic kidney insufficiency (unless removing the stone will improve kidney function)

Complications

Between 70 - 90% of crystals remain tiny enough so that they can travel through the urinary tract and leave the body in the urine without being noticed. When they do cause symptoms, however, kidney stones have been described as one of the most painful disorders to afflict humans. The pain they cause is sometimes called renal colic. ("Renal" means "kidney.")

Obstruction and Infection. Although kidney stones often lead to obstruction (blockage) of the urinary tract, the blockage is usually temporary and causes no lasting damage. In some cases, however, particularly if the obstruction progresses with no symptoms, infection may occur, which can be serious and need immediate attention.

Kidney Failure. It is very rare for kidney stones to cause kidney failure, although some people have risk factors that make them more vulnerable to this serious complication. Risk factors include the following:

Very frequent recurrences (such as in people with cystine stones or other inherited forms of kidney stone disorders)
Accompanying episodes of urinary tract infections with obstruction, a particular risk with struvite stones
A history of multiple urologic procedures for kidney stones
Greater size of the kidney stone gravel

Without preventive treatment, calcium stones recur in 10% of patients within a year of the first attack, and in half of patients within 5 - 7 years. Individual risk for recurrence, however, varies depending on the stone and the underlying condition. For example, a 15-year-old with inherited cystine stones has a very high risk for recurrence, while a middle-aged man with a first calcium oxalate stone has a good chance of never passing another.

Prevention

All individuals who have experienced kidney stones should take some specific preventive measures to prevent recurrence. The following are some general observations:

The most important dietary recommendations for reducing the risk for calcium stones are increasing fluid intake, restricting sodium, and reducing protein intake.
A lower risk for calcium stones is also associated with higher potassium intake.
A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. (Increasing calcium alone may pose a modest risk for stones.)
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine, which promote stone formation.

Because different kidney stone types may require specific dietary changes, patients should work with their doctors to develop an individualized plan. It is important to note that nutritional considerations are very important in preventing recurrence, and patients should be vigilant in complying with the proper diet.

Good voiding habits, particularly frequent urination, are important. Therefore, of all the preventive recommendations, drinking enough fluids is the most important guideline for people with any type of kidney stones.

In general, patients with calcium or uric acid stones should drink at least 10 full glasses of fluid each day (at least half should be water). This includes one with each meal and drinking fluids at night, even if it means getting up from sleep. Fluid intake should produce at least two and a half quarts of urine each day.
To prevent cystine stones, patients should drink even more water -- over a gallon, or 16 8-ounce cups, every day. Patients should drink this amount at regular intervals throughout the night and day.

In all cases, patients need more fluid after exertion and during times of stress. If they drink enough, the urine should be pale and almost watery, not dark and yellow.

Water. Although water is best, it may vary depending on its source. Variations in water itself may have different impacts. One study reported that drinking hard tap water increased urinary calcium concentration by 50% compared to soft bottled water. On the other hand, mineral water containing both calcium and magnesium may reduce several risk factors for both calcium and uric acid stone formation.

Juices and Specific Effects. Other beverages have various positive or negative effects, depending on the type of stone:

Lemon Juice: Drinking one-half cup of pure lemon juice (enough to make eight glasses of lemonade) every day raises citrate levels in the urine, which might protect against calcium stones. (While orange juice also increases citrate levels, it does not lower calcium and it raises oxalate levels. Therefore, it is not recommended.)
Cranberry and Apple Juice: Apple and cranberry juice contain oxalates, and both have been associated with a higher risk for calcium oxalate stones. Cranberry juice has properties that may increase the risk for both calcium oxalate and uric acid stones. On the other hand, cranberry juice helps prevent urinary tract infections and so may be helpful for reducing the risk for struvite and brushite stones. (These stones are far less common, however.)
Black Currant Juice: In one study, black currant juice reduced urine acidity and was associated with protection against uric acid stones.
Grapefruit Juice: A number of studies have found a risk for stones from drinking grapefruit juice. In one study, just one 8-ounce cup of grapefruit juice per day increased the risk for forming stones by 44%.

Other Beverages and Their Effects on Stone Formation.

Soft Drinks. Patients with stones should avoid cola drinks, since they can severely reduce citrate levels in the urine. Many soft drinks contain phosphoric acid, which increases the risk for stones. Some research shows that drinking one quart (less than three 12-ounce cans) of soda per week may increase a person's risk of developing stones by 15%.
Alcohol. Wine may be protective against kidney stones. A study conducted in Finland, suggests that the risk of developing stones also decreases with beer consumption. However, it is important to remember that beer is high in oxalates. Beer and other alcoholic beverages also contain purines, which may increase the specific risk for the less common uric acid stones in susceptible people. Binge drinking, in any case, increases uric acid and the risk for stones.
Coffee and Tea. Some research reported a lower risk for stones in people who drink tea and both regular and decaffeinated coffee.

A long-term 2002 study followed men with calcium oxalate stones and high levels of urinary calcium. The study found that a low-sodium, low-protein diet, containing normal levels of calcium, dramatically reduced the recurrence of stones compared to a diet that was simply low in calcium.

Salt Restriction. Because salt intake increases the amount of calcium in urine, patients with calcium stones should limit their sodium intake. Sodium may also increase levels of urate, the crystalline substance that can trigger formation of recurrent calcium oxalate stones. Although the relative contribution of limiting sodium intake has not been confirmed, some researchers believe that restricting sodium along with increasing fluid intake is the most important dietary measure for preventing stones.

Protein Restriction. Protein increases uric acid, calcium, and oxalate levels in the urine, and reduces citrate levels. Diets high in protein, particularly meat protein, have been consistently connected with kidney stones. (Meat protein has a higher sulfur content and produces more acid than vegetable protein.) A 2002 study of those following a high-protein, low-carbohydrate diet (such as the Atkins diet, for example), found dramatically increased levels of urinary uric acid and calcium after just several weeks. These effects put patients at higher risk for not just kidney stones, but possibly osteoporosis as well. According to Swiss studies, about a third of people at risk for calcium stones may have a sensitivity to meat proteins that causes mild hyperoxaluria.

Whether restricting meat protein alone has any protective value without restricting sodium as well is unknown. Most studies to date have found no difference in stone development between people with low and normal meat protein diets over four years. A 2000 study reported that only dramatic reductions in meat protein had any preventive effect against stone recurrence.

Although the precise role of dietary protein in kidney stones needs further clarification, it is reasonable for everyone to consume meat protein in moderation. People with struvite stones, who need to reduce phosphates in their diets, should also cut down on proteins.

Calcium from Foods. Dietary calcium recommendations for kidney stone prevention need to be determined on an individual basis. A doctor will suggest calcium guidelines based on a patient's age, gender, body size, and type of stone. Most studies indicate that dietary calcium (found in milk, yogurt, and cheese) protects against many types of calcium oxalate stones. Large studies of both men and women found that those with the highest intake of calcium from foods had a much lower risk for stones than those who had little calcium in their diets. A diet containing a normal amount of calcium, but reduced amounts of animal protein and salt, may protect against stones better than a low-calcium regimen. However, calcium metabolism changes as people age. Some studies suggest that a high calcium intake protects against kidney stones in men younger than age 60, but not in older men.

Dietary calcium may actually bind the oxalate in foods, preventing it from being absorbed into the blood and excreted into the urine. In a normal healthy diet, dairy products supply almost 80% of the daily calcium requirement. For people who have calcium stones associated with resorption (the breakdown of bone that releases calcium into the bloodstream), limiting calcium intake could cause further bone loss.

Calcium Supplements. Evidence on calcium supplements is mixed, although in general many studies suggest that they reduce oxalate levels and so help prevent calcium oxalate stones. One study suggested that taking 500 mg of calcium supplements a day regularly may "reprogram" the intestines to absorb less calcium and may therefore be protective. Experts generally agree that calcium supplementation within dosage recommendations (about 1,200 mg per day) remains safe. In one study, however, women who took calcium supplements had a 20% higher risk for stones. Research indicates that dosages of calcium above 2,000 mg per day are clearly associated with the formation of stones. Some experts speculate that this higher risk may occur because supplements are often taken in the morning, either without food or with breakfast, which is typically low in oxalates. Taking supplements with later meals may not produce the same risk.

Calcium Restriction in Certain Cases. Some patients, such as those whose stones are caused by genetic defects in which the intestine absorbs too much calcium, may need to limit calcium intake. More studies are needed to define this group precisely.

Fiber may be beneficial for people with kidney stones. In addition, some fiber-rich foods may contain compounds that help protect against kidney stones. A wide variety of high-fiber plant foods contain a compound called phytate (also called inositol hexaphosphate, InsP6, or IP6), which appears to help prevent crystallization of calcium salts, both oxalate and phosphate. Phytate is found in legumes and wheat and rice bran. (Soybeans are also rich in phytate but they are also very high in oxalates, so the overall effects of soy on kidney stones are not clear.)

A high intake of purines can increase the amount of uric acid in the urine. Those at risk for uric acid stones should reduce their intake of foods and beverages that contain purines. These include beer and other alcoholic beverages, anchovies, sardines, yeast, organ meats (such as liver and kidneys), legumes (including dried beans, peas, and soybeans), mushrooms, spinach, asparagus, cauliflower, and poultry.

Most people with calcium oxalate stones should not avoid oxalate-rich foods unless the doctor specifically recommends a restrictive diet. Oxalate binds with calcium in the intestine, which may actually reduce calcium absorption. Some studies, in fact, indicate that eating foods containing oxalates and calcium together may reduce the risk of stones. Most of the foods that contain oxalates are very important for good health. Limiting oxalates may be particularly harmful in people with bowel disorders marked by malabsorption.

Foods high in oxalic acid include beets, soy, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard.
Foods containing moderate amounts of oxalates include beans (green and wax), blackberries, blueberries, carrots, celery, coffee (roasted), concord grapes, currants, dandelion greens, endive, gooseberries, lemon peel, okra, green onions, oranges, green peppers, black raspberries, strawberries, and sweet potatoes.

Certain fats may play a beneficial or harmful role in specific cases of kidney stones.

Restricted Fats in Patients with Stones Associated with Bowel Disease. Patients who have stones associated with short-bowel syndrome should eat foods with lower amounts of fats and oxalates. If patients with short-bowel syndrome eat too much fat, calcium may bind to unabsorbed fat instead of to oxalates. This increased oxalate levels, resulting in increased risk of stone formation.

Fish Oil. Omega-3 fatty acids, found in oily fish like mackerel, salmon, and albacore tuna, have many health benefits, but the most current evidence suggests they do not help prevent kidney stones. A 2005 study of over 200,000 adults found that increased omega-3 fatty acid intake did not reduce kidney stone risk.

Vitamin B6. Vitamin B6, or pyridoxine, is used to treat people with primary hyperoxaluria, a severe inherited disorder. Patients should not try to treat themselves with vitamin B6. Very high doses (500 to 2,000 mg daily over long periods) can cause nerve damage, with loss of balance and numbness in the feet and hands. Food sources of vitamin B6 include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.

Vitamin C. Ascorbic acid (vitamin C) may change in the body to tiny crystals, called oxalates. These crystals do not dissolve. People with hyperoxaluria (too much oxalate in the urine) should avoid vitamin C supplements. Even for men with normal oxalate levels, higher consumption of vitamin C (more than 1,000 mg a day) may increase kidney stone risk.

Magnesium and potassium may help reduce the risk for kidney stones in men.

Because of an association between stress and kidney stones, relaxation and stress management techniques may also be beneficial.

Dietary Considerations. People with kidney stones appear to be more sensitive to certain foods than people who do not form kidney stones. Therefore, vulnerable people should make specific changes in their diet. They should work with their doctors to develop a dietary plan that fits their individual situation. Drinking plenty of fluids is important for preventing recurrence of any kidney stone.

Indications for Drug Treatments. If dietary treatments fail, drug therapy may be helpful. A number of drugs are available to prevent recurrences of calcium oxalate and other stones. Medications that inhibit the formation of stones include allopurinol, thiazide, potassium citrate, and potassium-magnesium citrate. In addition, drug treatments can sometimes also help prevent other complications related to stones, such as osteoporosis.

Correcting Underlying Conditions Known to Cause Kidney Stones. It is also important to treat and correct, if possible, any underlying disorder that may be causing stones to form. Such disorders include distal renal tubular acidosis, hyperthyroidism, sarcoidosis, and certain cancers. To prevent calcium stones that form in hyperparathyroid patients, a surgeon may remove the affected parathyroid gland (located in the neck). In most cases, only one of the glands is enlarged. Removing it ends the patient's problem with kidney stones.

Resources

www.kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Information Clearinghouse
www.urologyhealth.org -- American Urological Association
www.kidney.org -- National Kidney Foundation
www.ohf.org -- Oxalosis and Hyperoxaluria Foundation

References

Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric Acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422-8. Epub 2006 Apr 5.

Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(:885-891.

Finkielstein VA. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10); 1407-1409.

Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol. 2006;175(5):1742-7.

Sinha MK, Collazo-Clavell ML, Rule A, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney International. 2007;72:100-107.

Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005;15(2):119-126.

Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232.

Taylor EN, Stampfer MJ, Curhan GC. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005;45(2):267-274.

Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462.

Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005 Sep;68(3):1230-5.

Wasserstein AG. Nephrolithiasis. American Journal of Kidney Diseases. 45(2);2005:422-28.

Review Date:
7/24/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Osteoporosis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Fractures
Risk Factors
Diagnosis
Lifestyle Changes
Medications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration (FDA) approved zoledronic acid (Reclast) for postmenopausal osteoporosis treatment. Zoledronic acid is given as an injection once a year. A 2007 study in the New England Journal of Medicine indicated that zoledronic acid can significantly reduce the risk of spine, hip, and other fractures.
In 2007, the FDA approved raloxifene (Evista) for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis.

Calcium and Vitamin D for Osteoporosis Prevention

In 2007, the Food and Drug Administration proposed allowing manufacturers of food and supplements to put a health claim on their products stating that the combination of calcium and vitamin D can reduce the risk of osteoporosis.
In 2007, the National Osteoporosis Foundation updated its daily intake guidelines to recommend 1,200 mg of calcium, and 800 - 1,000 IU of vitamin D3, for adults age 50 and older.
Calcium plus vitamin D is effective in preventing osteoporosis in people age 50 years and older, according to a 2007 review in the Lancet. The researchers found that a minimum of 1,200 mg of calcium and at least 800 IU of vitamin D per day gave the most protection.

Fosamax: Taking a Break (Without Breaking a Bone)

Women at low risk for fracture may be able to temporarily stop taking alendronate (Fosamax) after 5 years, suggests a 2006 study in the Journal of the American Medical Association.

Antidepressants and Osteoporosis Risk

Selective serotonin reuptake inhibitors (SSRIs), the most commonly used class of antidepressants, may increase the risk for bone loss in both older men and women, according to several studies published in 2007 in the Archives of Internal Medicine. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). The researchers did not find that other types of antidepressants are associated with reduced bone mineral density.

Introduction

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur with mild stress.

The skeleton consists of groups of bones which protect and move the body.

Until a healthy person is around age 40, the process of breaking down and building up bone by cells called osteoclasts and osteoblasts is a nearly perfectly coupled system, with one phase stimulating the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. The reasons why this occurs during aging are not clear. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.

The Function of Bones. The skeleton has a dual function:

It provides structural support for muscles and organs.
It also serves as a depot for the body’s calcium and other essential minerals, such as phosphorus and magnesium.

The skeleton holds 99% of the body’s calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.

Bone Turnover: the Breakdown and Growth of Bones. Like other organs in the body, bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:

Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.

Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The bone build up (formation)-break down (resorption) balance is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.

In women, estrogen loss after menopause is associated with rapid resorption and loss of bone density. This group, then, is at highest risk for osteoporosis and therefore for fracture.

There are two primary kinds of osteoporosis: type I and type II:

Type I. Type I, or high turnover, osteoporosis occurs in 5 - 20% of women, most often between the ages of 50 and 75. This is because of the sudden postmenopausal decrease in estrogen levels, which results in a rapid depletion of calcium from the skeleton. This is associated with fractures that occur when the vertebrae compress together, causing a collapse of the spine. It is also associated with fractures of the hip, wrist, or forearm caused by falls or minor accidents. Women have a higher risk for type 1 osteoporosis than men.
Type II. Type II, or low turnover, osteoporosis (also known as age-related or senile osteoporosis) results when the process of resorption and formation of bone are no longer coordinated, and bone breakdown overcomes bone building. (This occurs with age in everyone to some degree.) Type II osteoporosis affects both men and women and is primarily associated with leg and spinal fractures. Older women can have both type I and type II osteoporosis.

Click the icon to see an image of a compression fracture.

What determines the existence of osteoporosis, whether type I or type II, is the amount of calcium left in the skeleton and whether it places a person at risk for fracture. Someone who has exceptionally dense bones to begin with will probably never lose enough calcium to reach the point where osteoporosis occurs, whereas a person who has low bone density could easily develop osteoporosis despite losing only a relatively small amount of calcium.

Secondary osteoporosis is caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).

Click the icon to see an image of osteoporosis.

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe several different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a woman’s ovaries stop producing estrogen. Estrogen comes in several forms:

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
The other important but less powerful estrogens are estrone and estriol.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. Even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

Estrogen’s most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
One study reported that part of estrogen’s beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.

Click the icon to see an image of the adrenal glands.

Studies have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with hip fracture in women after menopause:

Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.
Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the parathyroid glands.

Several studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

Of particular interest are genetic factors that affect vitamin D, a critical nutrient for calcium absorption in the body.
Many studies are looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroid drugs (also called glucocorticoids or steroids). Oral corticosteroids can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) -- a class of antidepressants that includes fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- may be associated with bone loss in both older men and women, according to two 2007 studies in the Archives of Internal Medicine. The researchers did not find an increased risk for bone loss with other types of antidepressants.

Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.

Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years. Some, but not all, studies suggest that combination estrogen-progestin oral contraceptives increase the risk for osteoporosis later in life. Women who take birth control pills should be sure to get adequate calcium and vitamin D from diet or supplements.

Other Medications. Anti-epileptic (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists). A 2006 study in the Journal of the American Medical Association suggested that long-term (greater than 1 year) use of proton-pump inhibitors (PPIs) may increase the risk for hip fractures. PPIs are used to treat gastroesophageal reflux disease (heartburn) and include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).

Predisposing Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.

Symptoms

Many people confuse osteoporosis with arthritis and believe they can wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, the mechanisms that cause arthritis are entirely different from those in osteoporosis. Osteoporosis usually becomes quite advanced before symptoms appear.

All too often, osteoporosis becomes apparent in dramatic fashion: a fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.

Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.

Click the icon to see an image of osteoporosis.

Fractures

Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and that for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly nonviolent fractures.

Click the icon to see an animation about osteoporosis.

Each year, there are an estimated 500,000 spinal fractures, 300,000 hip fractures, 200,000 broken wrists and 300,000 fractures of other bones. About 80% of these fractures occur after relatively minor falls or accidents.

Between 25 - 60% of women older than age 60 develop spinal compression fractures. Studies on men with osteoporosis report that they have a 6% risk for hip fracture and between 16 - 25% risk for any fractures related to osteoporosis.

Click the icon to see an image of a compression fracture.

Click the icon to see an image of a hip fracture.

Unfortunately, studies continue to report inadequate treatment after a fracture. In a major 2003 study, for example, only 8.4% of women who had sustained fractures were tested for osteoporosis. Worse, less than half of these women received any treatment for osteoporosis. Overall, in the study fewer than 4% of men and half of women who had sustained fractures were evaluated and treated according to recommended guidelines. The older a woman was, the less likely she was to have adequate treatment.

Risk Factors for Fracture and Falling. The risk for fracture itself in people with low bone density is compounded by certain features. Having multiple risk factors for osteoporosis itself poses a higher risk for fractures. However, not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture.

Falling, of course, is the primary risk factor for fracture. So, additional risk factors for fracture are those that increase the risk for falling. They include:

Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), with the risk increasing with multiple health problems. Such problems may account for 30% of falls in older women.
Taking multiple medications (especially tranquilizers and antidepressants).
Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
Poor concentration or mental impairment.
Impaired vision.
Hazardous environment (such as the presence of throw rugs in the house).

Between 25 - 36% of women who experience a hip fracture die within a year afterward, and about a quarter of the patients require nursing home treatment. The mortality rates after major fractures may be even higher in older men than in older women. Mortality rates after hip fractures declined from the 1960s through the early 1980s, but they have since leveled off. Whether or not medical advances can improve mortality rates in the future, prevention of osteoporosis is extremely important.

Risk Factors

Gender. An estimated 10 million adults in the United States have osteoporosis and another 34 million have low bone mass that places them at risk for developing osteoporosis. A 2004 report from the Surgeon General's office estimates that by 2020, half of all Americans over age 50 could be at risk for this condition. Eighty percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is far lower. Nevertheless, after age 50, bone loss increases and, according to recent studies, more rapidly than previously thought.

Ethnicity. Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk. About 20% of non-Hispanic white and Asian women older than age 50 have osteoporosis, and over 50% are at risk due to low bone mass. Osteoporosis affects 10% of Hispanic women (49% at risk) and 5% of non-Hispanic black women (35% at risk). Body type can also be a factor. Osteoporosis is more common in women who have a small, thin body frame and bone structure.

Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women.

Natural and Surgical Causes of Estrogen Deficiency.

Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
Surgical removal of ovaries.
Missing periods for 3 months or longer.
Never giving birth.
Pregnancy and nursing do not increase the risk for osteoporosis even though during those times calcium is diverted from the mother to the baby. A factor believed to be associated with reduced bone density is elevated at a constant level during nursing, but as the baby is weaned, levels of the factor decline and bone formation is restored.

Female Athlete Triad. In athletes, excessive exercise plays a major role in many cases of anorexia (and, to a lesser degree, bulimia), which in turn increases the risk for low estrogen levels and bone loss. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Osteoporosis
Amenorrhea (absence or irregular menstruation)
Eating disorders

Some specific risk factors in men include:

Hormonal deficiencies, including both testosterone and estrogen, which occur in older men (although much more slowly than in women). Estrogen deficiencies may also play a major role in osteoporosis in older men. It is unknown yet what normal estrogen levels are in men.
Medical conditions that can reduce testosterone levels, such as prostate cancer treatments, testicular surgery, and mumps.
Hypogonadism, which is a severe deficiency in the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones.

Of concern, are studies suggesting that men who have osteoporosis and suffer hip fractures are far less likely to be tested and treated for low bone density than are women. In one study, only 27% of men were treated for osteoporosis compared to 71% of women.

Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies, of course, are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.

Calcium requires adequate vitamin D in order to be absorbed by the body. In the United States, many food sources of calcium such as milk are fortified with vitamin D.

Click the icon to see an image of the sources of calcium.

Lack of Exercise. Lack of exercise can put thinner people at risk for osteoporosis.

Being Underweight. Being underweight is a risk factor for osteoporosis in men as well as women. (Shortness, thinness, and narrow hips all increase the risk for fracture in people with low bone density.)

Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly it they are elderly.

Click the icon to see an image of the sources of vitamin D.

Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don’t smoke. Men who smoke also have lower bone density.

Diabetes. Diabetes changes bone quality and density and increases the risk for osteoporosis, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture.
Type 2 diabetes, on the other hand, is associated with an increased bone density. In such cases, the bone quality itself may be impaired, since people with type 2 diabetes are still at higher risk for fractures.

Older patients with any diabetes type are at high risk for falling, which compounds the risk for fracture.

The maximum density that bones achieved during the growing years is a major factor in whether a person goes on to develop osteoporosis. Persons, usually women, who never develop peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include children who are:

Born prematurely
Have anorexia nervosa (more common in girls)
Young, highly competitive athletes
Take oral corticosteroid drugs (inhaled steroids, which are common in asthma treatments, appear to pose a very low risk or none at all)
Have certain medical conditions (cystic fibrosis, epilepsy, inflammatory bowel disease, and celiac disease)
Have delayed puberty

Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).

Diagnosis

About 20 - 30% of Caucasian women in the U.S. can expect to be affected by osteoporosis, including having a spinal fracture, after age 60. Hispanic, Asian, and Native American women have an even higher risk. Nearly all of them are unaware of the condition and so fail to seek a diagnosis. Even worse, studies continue to report inadequate evaluation for osteoporosis even after a fracture.

Evidence suggests that screening for osteoporosis can help prevent fractures. Expert groups now recommend bone density screening for the following people:

All women over age 65.
Any postmenopausal women under 65 years with risk factors for osteoporosis (being thin, being a smoker, having a family history of osteoporosis, corticosteroids use, or any serious high-risk condition, such as hyperthyroidism or early menopause).
Any older men or women who suffer a fracture. (Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis. Men are especially less likely to be tested.)

Whether perimenopausal women should be screened is unclear. (Perimenopause is the period that extends a few years before and after menopause, usually ages 50 - 59.) Some experts believe that women as young as 21 who have strong risk factors for osteoporosis (such as anorexia or absence of menstruation due to over-exercising) should consider being tested. It is also important that older women continue to get bone density tests. A 2006 study found that only 10% of women over age 75 receive bone density screenings, even though they are the age group most likely to have hip fractures.

Bone Densitometry. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DEXA). DEXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Bone mineral density is usually measured at the hip rather than the spine or wrist, which appears to be the most predictive of hip fracture. (Hip fractures are the most dangerous fractures, particularly in women older than sixty.) The bone density in the spine may also be measured. (Spinal bone density in older people however may be misleading. Bone density in this group may increase because of compression on the spinal bones from arthritic changes in the spine. Therefore, bone density measurements may be normal or even high, but the patient may actually be at risk for fracture.)

Click the icon to see an image of a hip fracture.

Ultrasound. Ultrasound techniques measure bone density in the heels, fingers, and leg bones. In early studies, advanced ultrasound techniques, such as quantitative ultrasound (QUS), are promising for improving accuracy in predicting fractures when used with DEXA. Ultrasound itself is less expensive than DEXA and uses no radiation. Ultrasound bone tests are sometimes given at health fairs or other non-medical settings. It should be noted that these results typically vary widely from measurements of the hipbone and are not reliable when used alone.

Quantitative Computed Tomography. Quantitative computed tomography (QCT) scans, a form of CT scans, can provide highly detailed information about spinal density. Radiation doses from this technique are higher than the others. Whether QCT predicts fracture risk accurately is, however, unknown.

Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm. However, low scores on bone density are not very accurate in determining fracture risk without consideration of other risk factors for fracture.

In general, doctors take the following steps to determine osteoporosis:

Bone mineral density ) is measured, typically in the hipbone, using bone densitometry.
Measurements of bone mineral density are given as mg/cm.² This is the average concentration of bone mineral in the areas that are being scanned. In general, bone is normal if results are greater than 833 mg/cm.² Low bone density (osteopenia) is between 833 and 648 mg/cm.² Osteoporosis is diagnosed with results below 648 mg/cm.²

These measurements still do not always indicate the true risk for fracture. The doctor also assesses risk factors and other considerations. The next step is to compare the patient's bone mineral density to normal bone density, which is defined as the average bone mineral density in the hipbones of premenopausal Caucasian women. (This group is used as the basis for the norm because of their high risk and greater proportion in the American population.)

The health professional then uses this comparison to determine her standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:

A T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
A Z score gives the standard deviation of the patient in relationship to the norm in her own age group. Z scores may be used to monitor the effects of treatments in women who have been diagnosed with osteoporosis.

For example, the lifetime risks for a younger woman with a specific T-score would be higher than the same scores in an older woman because the younger woman would have a longer time to lose bone density. In general, the T scores in a 55-year-old woman suggest the following degrees of risk for hip fracture.

One standard deviation or less below the norm indicates normal bone mineral density. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
Between 1 and 2.5 standard deviation s below normal defines osteopenia, which is low bone density. This carries between a 20 - 50% lifetime risk for fracture.
More than 2.5 standard deviation s predicts osteoporosis and over a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, risks for falling, and especially a history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in 1 year and 28.6% over 5 years. In similar women with a previous fracture, the probability of fracture at 1 year is 11% and at 5 years is 71.8%.

Not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture. Techniques to measure bone strength may better identify women at higher or lower risk.

Note: Because the standards are based on Caucasian women, they do not necessarily apply to men, children, or to non-Caucasian women. For example, men have a lower risk for fracture at the same standard deviations as women. Researchers are attempting to establish risk guidelines for these groups as well.

Laboratory blood or urine tests for identifying certain markers of bone loss may prove to be useful in certain cases:

High levels of the chemicals deoxypyridinoline and C-telopeptide in the blood may indicate increased risk for hip fracture. These substances are produced when bone is broken down.
A urine test detecting a substance called N-telopeptide may indicate bone loss (although it is not associated with any risk for fracture).

Lifestyle Changes

Because osteoporosis affects such a considerable portion of the female population, total prevention may not be possible, particularly for high-risk groups. Once a woman goes through menopause and more rapid bone depletion occurs, the line between prevention and treatment blurs. Despite their lower risk for osteoporosis, men should also protect their bones with the same healthy lifestyle habits.

Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Everyone who is in good health should aim for more. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients, those at risk or those who have serious medical conditions, should talk to their doctors.

Specific exercises may be better than others, depending on the age group:

Children should begin exercising before adolescence, since bone mass increases during puberty and reaches its peak between ages 20 and 30. Some evidence suggests that exercise may help develop bone mass in teenagers more effectively than high calcium intake. High-intensity exercises may be particularly bone-strengthening in young people. (Such regimes should not be confused with the athlete-triad -- intense competitive exercise, eating disorders, and menstrual irregularities -- that causes osteoporosis in young athletes.)
Weight-bearing exercise applies tension to muscle and bone and, in young people, encourages the body to compensate for the added stress, increasing bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. (Young men need high-intensity exercises to increase bone mass.) Careful weight training is also very beneficial for elderly people, especially women.
Regular brisk long walks improve bone density and mobility and may relieve osteoarthritic pain. High-impact exercises can be very bone-protective in young and middle-aged adults who have no precluding medical or physical conditions. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. (Older people, particularly women who engage in jumping exercises should do so under supervision.) Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
Exercises specifically targeted to strengthen the back help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, have been found to decrease the risk of falling. In one study, tai chi reduced the risk of falling by almost half.

Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.

Click the icon to see an image of osteoporosis.

In 2007, the Food and Drug Administration (FDA) proposed a new health claim for foods and dietary supplements that contain calcium and vitamin D. The FDA’s recommendation will allow manufacturers of these products to state that the combination of calcium and vitamin D can reduce the risk of osteoporosis. Also in 2007, the National Osteoporosis Foundation (NOF) updated its recommendations for getting enough calcium and vitamin D3. The NOF now recommends 1,200 mg of calcium/day and 800 - 1,200 I.U. of vitamin D3/day for adults age 50 and older. (For strong bones, people need enough of both calcium and vitamin D.)

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. Many studies, including a 2007 review in the Lancet, show that a combination of calcium and vitamin D can help prevent osteoporosis. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve slightly (by 1%) hip bone density
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether or not you should take calcium supplements.

Appropriate Daily Doses. Recommended daily amounts of calcium depend on age and risk factors:

In young people, children ages 3 - 8 should take 800 mg of calcium per day, while children and adolescents ages 9 - 17 need 1,300 mg per day. Teenage girls who do not have enough calcium in their diets should consider taking supplements, which can help build bone density during these critical years.
The standard recommended dose for people over age 50 is about 1,200 mg per day, but actual dosage may be higher or lower depending on risk factors. Even doses of 1,000 mg may help preserve bone in many postmenopausal women without osteoporosis, including during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1,000 mg daily may not add any protective benefits without bone-building medication.
Some experts suggest that all pregnant women, adolescents, and those on corticosteroids take 1,000 - 1,300 mg of calcium every day.
Breast-feeding women should have 2,000 mg per day.

Forms of Calcium Supplements. There are several different kinds of calcium supplements, such as calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions. Their value in preserving bones depends on many different factors:

Calcium Concentrations. Forty percent of calcium carbonate is actually calcium, whereas calcium citrate is 24% calcium, and calcium gluconate is only 9% calcium.
Calcium Absorption Capabilities. The calcium must also be absorbed from the stomach into the bloodstream. Calcium citrate is better absorbed than many other calcium compounds. It was reported to be the first calcium supplement to preserve bone density after menopause. (Calcium citrate also increases iron absorption. Milk and other calcium compounds tend to reduce iron absorption.) One simple method for testing the absorbency of a particular brand of calcium tablet is to place it in a glass of white vinegar at full strength and check to be sure that it breaks up within 30 minutes. Taking large amounts of antacids can impair calcium absorption. People should take calcium supplements after meals.

Side Effects. Calcium supplements, even at normal doses of about 1,000 mg a day, can increase the risk for kidney stones. People should be careful not to exceed the upper limit of 2,500 mg per day. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Calcium may boost the effects of drugs used to treat osteoporosis.

Click the icon to see an image of kidney stones.

Although not a specific side effect of calcium, there has been much public concern about reports of a small amount of lead in calcium supplements. Although exposure to high levels of lead can cause health problems, the amount in such supplements is very small and may pose little or no hazard.

Vitamin D. Vitamin D helps the stomach and the gastrointestinal tract absorb calcium. It also is the essential companion to calcium in maintaining strong bones. Moreover, vitamin D protects against osteoporosis only in combination with calcium.

Click the icon to see an image of the benefits of vitamin D.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. People also can get it from dietary supplements.

As a person ages, vitamin D levels decline. They also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of the sources of vitamin D.

Most current adult guidelines recommend:

400 IU (10 mcg) for people aged 50 - 60.
600 IU (15 mcg) for those over age 70 who do not have sufficient exposure to sunlight. (Evidence suggests that higher doses of vitamin D -- up to 1,000 IU per day -- may help prevent fractures in people with osteoporosis.)

There are various recommendations for daily vitamin D intake. In 2007, the National Osteoporosis Foundation updated its guidelines to recommend 400 - 800 IU of vitamin D3 for adults younger than age 50, and 800 - 1,000 IU of vitamin D3 for adults age 50 and older. Vitamin D3, also called cholecalciferol, is the form of vitamin D that is best for bone health. In addition to supplements, food sources for vitamin D3 include fortified milk, egg yolks, saltwater fish, and liver.

In 2007, the U.S. National Institute of Health’s Office of Dietary Supplements released a report regarding vitamin D and bone health. Researchers were not able to definitely separate the effect of vitamin D from that of calcium, as most clinical trials evaluate the combination of these supplements. The report did indicate that a combination of daily vitamin D3 (700 - 800 IU) and calcium (500 - 1,200 mg) decreases the risks of falls, fractures, and bone loss in elderly people (ages 62 - 85 years).

Sufficient sunlight exposure and drinking milk fortified with vitamin D supply most people’s normal needs for vitamin D. One cup of whole milk provides about 100 IU of vitamin D.

Vitamin D is toxic in doses above 2,000 IU a day. No one should exceed the recommended daily intake of vitamin D except under the direction of a doctor.

Many people could become deficient in vitamin D as they avoid sunlight to prevent skin cancers and instead increase their intake of milk products, such as yogurt and skim milk, which may have little vitamin D. Such individuals may need to take supplements. People with darker skin have a higher risk for vitamin D deficiency than those with lighter skin.

Vitamin D derivatives are being investigated for treating osteoporosis. Calcitriol (Calcijex, Rocaltrol), for example, is a prescription-form of vitamin D that can increase bone mass and decrease the rate of spinal fractures. However, calcitriol increases the risk for high blood calcium levels (hypercalcemia) and requires frequent monitoring.

Vitamin K. Vitamin K has properties that protect bone and prevent fracture. Because intestinal bacteria produce vitamin K, and the vitamin is found in leafy vegetables, deficiencies are rare. Some evidence suggests, however, that people may not be consuming enough of this nutrient. Vitamin K affects blood clotting, and taking supplements is not recommended without first talking to a doctor. Vitamin K2 (menatetrenone), a form of vitamin K, may help prevent fractures in people with osteoporosis.

Click the icon to see an image of the benefits of vitamin K.

Click the icon to see an image of the sources of vitamin K.

Vitamin B12. Studies suggest that people need the right amounts of vitamin B12 and folic acid to maintain their bone mineral density.

Vitamin A. High amounts of dietary vitamin A reduce bone density and may even increase the risk for fracture in postmenopausal women. (A form of vitamin A, retinoic acid, has been found to stimulate bone breakdown.)

The DASH Diet and Low Sodium. Perhaps a good general approach for people at risk for osteoporosis (or almost any adult) is the DASH diet plus sodium (salt) restriction. The DASH (Dietary Approaches to Stop Hypertension) diet is used to help people with hypertension maintain healthy blood pressures. A 2003 study also reported that it might help protect bones and improve cholesterol levels. This diet not only is rich in important nutrients and fiber but also includes foods that contain far more potassium, calcium, and magnesium, than are found in the average American diet. All of these minerals are important for bone protection. The dietary recommendations are as follows:

Avoid saturated fat (although include calcium-rich dairy products that are no- or low-fat). When choosing fats, select monounsaturated oils, such as olive or canola oils. These fats are also found in some fish. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In one study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet.
Choose whole grains over white flour or pasta products. Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, magnesium, and other minerals that are important for bone (as well as heart) protection.
Choose protein preferably from fish, poultry, or soy products. Soy in combination with fiber-rich foods or supplements may have specific benefits. Oily fish may also be particularly beneficial. They contain omega-3 fatty acids, which have been associated with heart and nerve protection.

Salt Restriction. Reducing salt may protect both the heart and the bones. High sodium intake interferes with calcium retention. Note: Fast foods and commercial snacks are usually high in sodium and have been linked with weak bones.

Dairy Products and Calcium-Rich Foods. Although some studies have reported that dairy products benefit the bones, it is not entirely clear if high-calcium diets reduce the risk for fractures compared to adequate intake of vitamin D. Until more is known, people should be sure their diets have sufficient calcium. Dietary calcium is available from many good sources.

Milk and Dairy Products. The best source of calcium in the diet is from milk fortified with vitamin D. Four glasses of milk provide about 1,200 mg of calcium. (Skim milk and yogurt products, unfortunately, are often low in vitamin D, which is important for calcium absorption.) According to a 2003 study, girls who have low milk intake increase their risk for fracture in adulthood. One report even suggests that milk proteins actually slow bone break down. It is not clear, however, if drinking milk after menopause offers any significant bone protection.
Other Calcium-Rich Foods. Other calcium-rich foods include shrimp, canned salmon or sardines, black strap molasses, calcium-fortified tofu, and almonds. A number of commercial foods, including orange juice and some cereals, are now calcium fortified. Dark green vegetables (broccoli, kale, turnip greens) are rich in calcium but little of it is absorbed (kale is best).

Click the icon to see an image of milk and the facial bones.

Mineral-Rich Fruits and Vegetables.

Potassium. Potassium may be very important for strong bones and may help counteract negative effects of high-protein diets. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli.
Magnesium. Some studies have observed that low levels of magnesium may contribute to thinning bones. Some studies suggest that magnesium supplements help suppress the cycle that leads to bone loss. Experts recommend 350 mg a day for supplements. However, excessive magnesium may be harmful in people with diabetes or kidney disease. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut.
Other Minerals. Phosphorous, boron, and zinc have also been associated with bone protection.

Protein. Protein may be important for frail older people for improving muscle strength. Researchers, meanwhile, have associated both low and high protein intake with bone loss. Protein deficiencies appear to trigger hormonal changes that increase bone breakdown. On the other hand, high protein intake increases urinary calcium loss, which can impair bone density in people with low-calcium diets. High-protein diets, however, do not appear to cause bone loss if calcium intake is also high. The bottom line is to eat enough protein but to balance it with plenty of calcium-rich, and other mineral-rich, foods.

The protein source (meat, soy, or fish) may have some effect on bone density, although the effects are not clear. Studies are mixed on whether protein from meat has a positive or negative effect on bone loss. In any case, the best sources of protein for bone protection may be from oily fish or soy.

Choosing protein from fish (especially oily fish such as sardines, salmon, mackerel, fresh tuna, and herring) is a good option. Oily fish are high in vitamin D, which is bone protective. Such fish are also heart protective. Wild salmon has a much higher vitamin D content than farmed salmon. American brands of canned tuna, meanwhile, generally do not contain significant amounts of vitamin D.
Soy may have some modest protection against bone loss. Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. In particular, the isoflavone genistein is being studied for its effects on bone health. A small 2007 study indicated that genistein supplements, when taken with vitamin D and calcium, may help improve bone density in postmenopausal women with thinning bones. (However, other studies indicate that soy has no effect on bone density in healthy premenopausal women.) Soy food products that also contain calcium, such as tofu, may be particularly beneficial. In such cases, 3 ounces of tofu supply 60% of daily calcium requirements.

Alcohol. Alcohol has different effects on bones depending on how much is consumed. One study found that women older than age 65 who drank one to two drinks (1 - 2 oz) of alcohol weekly had higher bone density than non-drinkers. Alcohol in moderate amounts may reduce parathyroid hormone and increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Cola, Coffee, Tea and Caffeine. One study suggested that drinking tea regularly may help protect bones. Nevertheless, there has been some concern that caffeine consumption, particularly from coffee, may increase calcium levels in urine and reduce levels in the body. In one trial, consumption of lots of coffee (9 or more cups per day) was associated with an increased risk of hip fractures in women, but not in men. However, not all studies support a risk. Some evidence suggests that caffeine may pose a danger for bone loss only in elderly thin women -- but not in those who have normal or high weight. Drinking carbonated beverages, particularly cola, may increase the risk for bone fractures in people with low bone density.

Everyone who smokes should quit. The risk for osteoporosis from smoking appears to diminish after quitting.

An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:

Slow walking
Inability to walk in a straight line
Certain medications (such as tranquilizers and sleeping pills)
Low blood pressure when rising in the morning
Poor vision

Recommendations for preventing falls or fractures from falls in elderly people include:

Exercise to maintain strength and balance if there are no conflicting medical conditions. In one study of older people, this was the single best intervention for preventing falls.
Do not use loose rugs on the floors.
Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
Rooms should be well lit.
Have regular eye checkups.
Try wearing hip pads. Hip pads are specially designed to protect hipbones against falls and are worn under clothing. Evidence on their protection against fractures is weak, however, particularly since compliance is poor. Nevertheless, newer hip pads that are thinner and made with newer materials may be helpful and more appealing.
Wear thinner, hard-soled shoes. Studies indicate these shoes are just as comfortable as the popular resilient-soled footwear, but they may be difficult to find. Soft-soled high-resilient so-called athletic footwear may contribute to impaired balance and dangerous falls, in part, because these cushioned shoes offer less stability.

Medications

Many drugs are available to treat osteoporosis. Unfortunately, studies continue to report that doctors fail to evaluate and adequately treat both men and women for this condition, even after a fracture. According to one study of women over age 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their doctors. Among those who were diagnosed, only 36% received appropriate medication. Among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines, indicated two other studies. In one of the studies, only 24% of women received treatment for osteoporosis after a fracture. In both studies, the older a woman was, the less likely she was to have adequate evaluation or treatment.

Drugs Used to Treat Osteoporosis. Two types of drugs are used to treat osteoporosis:

Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
Anabolic, or Bone-Forming, Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This medicine is proving to be very effective in restoring bone and preventing fractions. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

Bisphosphonates are antiresorptive drugs. They are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, just blocking resorption will interrupt this process and impair the second half of the process -- bone formation. Some researchers think that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PTH), then following this treatment with bisphosphonates to prevent the breakdown of bone. (Administering the two drugs simultaneously is not effective because bisphosphonates interfere with the way PTH works.)

A 2006 study of the bisphosphonate alendronate (Fosamax), the most widely used osteoporosis drug, indicated that women at low risk for fracture may be able to stop using the drug after 5 years without increasing their fracture risk for another 5 years. However, the Journal of the American Medical Association study also suggested that it is safer for women at high risk for spine fractures to keep taking alendronate on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

Oral bisphosphonates. These pills include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium. Risedronate and alendronate are approved for both men and women.
Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for osteoporosis. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may experience muscle and joint pain. To avoid stomach problems, doctors recommend:

Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. In clinical studies, teriparatide (Forteo), a drug made from selected amino acids found in parathyroid hormone, reduced the risk for spinal and non-spinal fractures by 50 - 65%. It may prove to be a very useful drug for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, researchers are investigating a nasal spray version of PTH. In addition to easing patient discomfort, there is some preliminary evidence that nasal-administered PTH may be better absorbed than injections. Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone replacement therapy (HRT) is sometimes used to prevent osteoporosis. A Women’s Health Initiative (WHI) study found that women who received estrogen, or estrogen plus progestin, therapy had fewer fractures than women who received placebo.

However, WHI studies have also shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The Food and Drug Administration recommends that women first try other medications for prevention of osteoporosis.

HRT is available in many different forms, including pills and skin patches. [See In-Depth Report #40: Menopause.]

New SERMs. Bazedoxifene (Viviant) is a new selective estrogen receptor modulator (SERM) that is in phase III clinical trials. In research presented at the 2007 annual meeting of the American Society for Bone and Mineral Research (ASBMR), bazedoxifene reduced new cases of non-spine fracture by 52% compared to placebo.
Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Results presented at the 2007 ASBMR meeting indicated that denosumab may help increase bone mineral density by as much as 10.6%. Odanacatib is another biologic drug showing promise in phase IIB trials. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.
Strontium. Strontium, a chemical element found in bone, may help increase bone formation and decrease bone resorption. NB S101 is a strontium drug currently in phase II trials.

Treatment

Nonsurgical treatments for fractures include braces, plaster cases, and manipulation of the fracture. Such approaches have not been well studied to determine an optimal method, and patients should discuss all options with their doctors.

Reconstructive surgery is usually used for hip fractures and should be performed within 48 hours, assuming the patient has no other complicating medical conditions. After surgery, the patient should be mobilized within the first day. In one study, protein supplements helped people with hip fractures recover more quickly and reduced bone loss.

Percutaneous vertebroplasty and kyphoplasty are surgical procedures used to lessen pain. Research to date suggests that they are safe and provide pain relief for many patients. In some cases they may increase height. There have been few controlled trials, however, and more research is needed to determine long-term effects.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into damaged vertebrae. It is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. Success rates of over 90% have been reported. Serious complications occur in fewer than 1% of cases.

Kyphoplasty. Kyphoplasty is a variant of percutaneous vertebroplasty that may help prevent kyphosis (hunchback) in patients whose spines have collapsed. The procedure inserts a balloon into the fractured vertebrae. As the balloon inflates, the spine is moved upward, to its original location. The balloon is then removed, and the bone and the core of the newly-erect vertebrae are filled with cement. In one 2003 study, short-term symptom relief improved by 70% and was immediate. Long-term effectiveness is not yet known.

Resources

www.nof.org -- National Osteoporosis Foundation
www.niams.nih.gov/Health_Info/Bone -- National Institutes of Health, Osteoporosis and Related Bone Diseases
www.menopause.org -- North American Menopause Society
www.asbmr.org -- American Society for Bone and Mineral Research
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases

References

Agency for Healthcare Research and Quality. Effectiveness and Safety of Vitamin D in Relation to Bone Health, Structured Abstract. August 2007. Rockville, MD.

Bilezikian JP. Osteonecrosis of the jaw -- do bisphosphonates pose a risk? N Engl J Med. 2006 Nov 30;355(22):2278-81.

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007 Jun 25;167(12):1246-51.

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Migraine headaches

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Treatment Approaches
Medications Used for Treatm...
Prevention
Medications Used for Preven...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Migraine Surveys

About 17.1% of women and 5.6% of men suffer migraines, according to the 2007 American Migraine Prevalence and Prevention survey. Nearly a third of respondents reported 3 or more migraine attacks per month. Over half were severely impaired or needed bed rest during attacks. Although many patients met the criteria for preventive medication, only a small percentage actually received it.
About 20% of patients with migraine take potentially addictive opioid and barbiturate drugs, even though these drugs have not been approved by the Food and Drug Administration (FDA) for migraine treatment, according to a 2007 survey commissioned by the U.S. National Headache Foundation.

FDA Actions

The opioid drug fentanyl (Fentora) should not be prescribed "off-label" to patients with migraine or other severe headaches, warns the FDA, following several reports of drug-related deaths. Fentanyl is approved only for treating cancer pain.
In 2007, the FDA pulled 15 unapproved ergotamine preparations off the market because they lacked a warning label describing the risks for serious drug interactions.

Migraines in Adolescents

Many adolescents may stop having migraines, or transition to less severe types of headaches, when they reach adulthood, suggests a small 2006 study in Neurology.
Zolmitriptan (Zomig) nasal spray appears to be safe and effective for adolescent migraine, indicates a 2007 study in Pediatrics. Zolmitriptan, like all migraine drugs, is currently approved only for adults.

Sumatriptan-Naproxen Combination

A combination of the triptan drug sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug naproxen (Aleve) works better for migraine pain relief than either drug alone, according to a 2007 study in the Journal of the American Medical Association.

Introduction

The pain from a headache does not start from inside the brain. (The brain itself can not feel pain.) Instead, headache pain begins in one or more of the following locations:

The tissues covering the brain
The structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Headache is generally categorized as primary or secondary.

Primary Headache. A headache is considered primary when a disease or other medical condition does not cause it.

Tension headache is the most common primary headache and accounts for 90% of all headaches. [See In-Depth Report # 11: Tension headaches.]
Neurovascular headaches are the second most common primary headaches. This type includes migraines and cluster headaches. [See In-Depth Report # 99: Cluster headaches.] Such headaches are caused by an interaction between blood vessel and nerve abnormalities.

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Over-the-counter pain medications can relieve most headaches.

Click the icon to see a depiction of migraine cause.

Secondary Headache. Secondary headaches are caused by other medical conditions, such as sinusitis, neck injuries or abnormalities, and stroke. About 2% of headaches are secondary headaches caused by abnormalities or infections in the nasal or sinus passages. [See "Causes of Secondary Headaches," in this report.]

It is not uncommon for someone to experience a combination of headache types.

Click the icon to see a comparison of headache symptoms.

Migraine is now recognized as a chronic illness, not simply as a headache. About 28 million people suffer from migraines annually. They are often classified by whether or not auras (seeing bright "spots" or "stars") accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four phases to a migraine (although they may not all occur in every patient): The prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 1 in 5 patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

In some cases, patients eventually experience on-going and chronic headaches. In fact, in an analysis using two different diagnostic methods, between 87 - 90% of daily chronic headaches were actually migraines. Some doctors believe that, unless otherwise demonstrated, any chronic headache consisting of episodes of disabling pain that recur regularly over years should be considered as a migraine.

Chronic migraines may occur from overuse of migraine medications (called a rebound headache) or may develop over time (called transformed migraine).

Rebound Headache. The most common cause of chronic migraine is the rebound effect, which is a cycle caused by overuse of migraine medications. The process involves the following:

Patients typically have taken pain medication for more than 3 days a week on an ongoing basis.
When the patients stop taking medication, they experience a rebound headache.
They start taking the drugs again.
Eventually the headache simply persists, and medications are no longer effective.

Medications implicated in rebound migraines include nonprescription painkillers (acetaminophen, aspirin, ibuprofen), barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.)

Transformed Migraines. In some cases, migraines themselves evolve into chronic, daily headaches called transformed migraines. Such headaches resemble tension headaches but are more likely to be accompanied by gastrointestinal distress and mental or visual disturbances and, in women, to be affected by menstrual cycles. In one study, the risk for transformed migraines were associated with other factors, including allergies, asthma, hypothyroidism, hypertension, and a daily intake of caffeine.

Migraines are defined by the number and length of attacks and whether an aura is present.

Definition of Migraines without Auras (Common Migraine). To be defined as a migraine without aura, a patient should have at least five attacks that have the following characteristics:

A. Each untreated, or unsuccessfully treated, attack must last 4 - 72 hours.

B. It must have at least two of the following four characteristics:

Pain on one side of the head
Pulsing or throbbing pain
Pain severe enough to impair or prevent daily activities
Pain must be intensified by exertion, such as walking up stairs

C. During a headache at least one of the following symptoms must also be present:

Nausea, vomiting or both
Sensitivity to light and noise

In addition, other neurologic or medical conditions that might be causing this pain must be ruled out, or, if they do occur, they are not related in time to the suspected migraine.

Definition of Migraines with Auras (Classic Migraine). To be defined as a migraine with aura, the patients must have at least two attacks that have three out of four of the following events.

At least one fully reversible aura symptom suggesting the headache starts in the cerebral cortex or brain stem.
At least one aura symptom that develops gradually over more than 4 minutes ,or two or more aura symptoms that occur in succession.
No single aura symptom that lasts more than 1 hour. (There may be successive aura symptoms that extend that time, but each one should not last more than 60 minutes.)
The headache itself may begin before, at the same time, or at an interval of no more than an hour after the aura.

As with common migraines, other neurologic or medical conditions that might be causing this pain must be ruled out or if they occur, they are not related in time to the suspected migraine.

Click the icon to see a definition of a migraine.

Although migraine is considered to be a specific chronic illness, it has various presentations that occur in different individuals.

Menstrual Migraines. Migraines are often tied to a woman’s menstrual cycle. Researchers think that estrogen plays a role. About half of women with migraines report an association with menstruation. Compared to migraines that occur at other times of the month, menstrual migraines tend to be more severe, last longer, and not have auras. Triptan drugs can provide relief and may also help prevent these types of migraines.

The highest incidence of migraines typically occurs during the early follicular phase, (beginning of menstruation). A 2005 study found that women are 1.7 times more likely to have a migraine during the 2 days before menstruation begins. But, women are 2.5 times more likely to have a migraine during the first 3 days of menstruation. During this time, migraines are more likely to be severe, with symptoms that include vomiting.

Ophthalmoplegic Migraine. This very rare headache tends to occur in younger adults. The pain centers around one eye and is usually less intense than in a standard migraine. It may be accompanied by vomiting, double vision, a droopy eyelid, and paralysis of eye muscles. Attacks can last from hours to months. A computed tomography (CT) or magnetic resonance imaging (MRI) scan may be needed to rule out an aneurysm (a rupture blood vessel) in the brain.

Retinal Migraine. Symptoms of retinal migraine are short-term blind spots or total blindness in one eye that lasts less than an hour. A headache may precede or occur with the eye symptoms. Sometimes retinal migraines develop without headache. Other eye and neurologic disorders must be ruled out.

Basilar Migraine. Considered a subtype of migraine with aura, this migraine starts in the basilar artery, which forms at the base of the skull. It occurs mainly in young people. Symptoms may include vertigo (the room spins), ringing in the ears, slurred speech, unsteadiness, possibly loss of consciousness, and severe headaches.

Familial Hemiplegic Migraine. This is a very rare inherited genetic migraine disease. It can cause temporary paralysis on one side of the body, vision problems, and vertigo. These symptoms occur about 10 - 90 minutes before the headache.

Status Migrainosus. This is a serious and rare migraine. It is so severe and lasts so long that it requires hospitalization.

About 90% of people seeking help for headaches have a primary headache disorder. The balance of secondary headaches is caused by an underlying disorder that produces the headache as a symptom. Many conditions cause headaches as a symptom. Some of the most common are listed below.

Sinus Headache. Many primary headaches, including migraine, are misdiagnosed as sinus headaches. Nearly 9 in 10 patients who think they have sinus headaches actually have or probably have had a migraine. Sinus headaches occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but telling the difference between these two kinds of headache is difficult, particularly if a headache is the only symptom of sinusitis. The two may even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (Rarely, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headache Due to Neck Problems. Some headaches may be caused by abnormalities of the neck muscles resulting from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Nerves in the neck converge in the trigeminal nerve in the face and can generate pain signals that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head, it is usually more severe on one side. The quality of the headache may be similar to an aching tension headache or a mild migraine without aura.

Temporomandibular Joint Dysfunction. Temporomandibular joint dysfunction (TMJ) is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of having a brain tumor is common among people with headaches, but a headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraine or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the two are rarely associated. An exception is malignant hypertension, an uncommon medical emergency, in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention. It is important to determine if a clot or bleeding is causing the stroke, since treatments are very different.

Head Injuries. It is obvious that a significant blow to the head will cause pain. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. In very rare instances, ordinary physical strain may injure or weaken the meninges, causing a leakage of cerebrovascular fluid (the fluid that bathes the brain). This can cause severe headache and nausea, which are relieved by lying flat. The condition is very treatable. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain. (It may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing.) Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Click the icon to see an image of the sinuses.

Prognosis

For many people, migraines eventually go into remission and sometimes disappear completely, particularly as they age. Estrogen decline after menopause may be responsible for remission in some older women. One study reported that the following people with migraines (called migraineurs) have a better chance of remission if they have:

A family history of migraine with aura
Migraines that are not triggered by light
No other primary headaches

According to another study, a history of head trauma or oral contraceptive use predicted a poorer long-term outlook.

Migraine or severe headache is a risk factor for stroke in both men and women, especially before age 50. About 19% of all strokes occur in people with a history of migraine. Research indicates that migraine also increases the risk for other types of heart problems.

Migraine with aura carries a higher risk for stroke than without auras. A 2005 analysis of over 12,000 participants from an atherosclerosis risk study found that migraine with aura was significantly associated with higher risk for stroke and transient ischemic attacks. Another 2005 study suggested that people who experience migraine with aura tend to have more cardiovascular risk factors than people without migraine. These risk factors included worse cholesterol profile, higher blood pressure, early history of heart disease and stroke, and greater likelihood of using oral contraceptives.

Results from a 2005 study showed that women who have migraine with aura are at increased risk of ischemic stroke compared with those who do not have auras and those who have non-migraine headaches. Women under age 55 had the highest risk, with more than double the risk. A 2006 Women’s Health Study of women ages 45 and older found that migraine with aura also increases women’s risk for heart attack, angina, and death due to ischemic heart disease (in which blood flow is decreased due to narrowing of coronary arteries). Migraine without aura did not increase heart disease and stroke risks.

Studies suggest specific stroke risk factors for younger women with migraines, particularly those with auras. Smoking, high blood pressure, and birth control pills considerably raise one's risk 10 - 20 times.

Researchers are also studying the relationship between patent foramen ovale (PFO) and migraine. A PFO is a hole in the wall dividing the upper left and right heart chambers. About half of patients with PFO have severe migraines with aura. Researchers are investigating whether surgical repair of the PFO may help control migraines in patients with this heart condition.

Migraine and other headaches associated with aura may increase the risk for retina damage (retinopathy) among middle-aged people, suggests a 2007 study.

The negative impact of migraines on quality of life, families, and even work productivity is significant and often underrated as a serious complication. Studies indicate that people with migraines have poorer social interactions and emotional health than patients with chronic medical illnesses, including asthma, diabetes, and arthritis. Anxiety (particularly panic disorders) and major depression are also strongly associated with migraines.

A 2005 National Headache Foundation-sponsored survey of migraine sufferers reported that:

90% of people with migraines could not function normally on the day of a migraine attack
80% experienced abnormal sensitivity to light and noise
75% experienced nausea and vomiting
30% required bed rest
25% missed at least 1 day of work due to migraine in past 3 months

Effect of Pregnancy on Migraines. In one study, pregnant women with tension or migraine headaches experienced 80% fewer headaches, usually after the end of the first trimester.

Effect of Migraine on the Pregnant Woman or Fetus. Migraine headaches do not pose any added risks during pregnancy to the mother or the fetus, although women with migraines may be at higher risk for having smaller (but not premature) babies.

Causes

Until recently, the general theory on the migraine process rested solely on the idea that abnormalities of blood vessel (vascular) systems in the head were responsible for migraines. Now, however, doctors tend to believe that migraine starts with an underlying central nervous system disorder. When triggered by various stimuli, this disorder sets off a chain of neurologic and biochemical events, some of which subsequently affect the brain's vascular system. No experimental model fully explains the migraine process.

There is certainly a strong genetic component in migraine with or without auras. Researchers have located a single genetic mutation responsible for the very rare familial hemiplegic migraine, but several genes are likely to be involved in the great majority of migraine cases. Numerous chemicals, structures, nerve pathways, and other players involved in the process are under investigation.

Central Nervous Disorder. One theory that attempts to integrate many of the known events in the migraine process is as follows:

Stress or some unknown factor triggers the release of certain protein fragments called peptides (Substance P, calcitonin gene-related peptide, and others).
These peptides dilate blood vessels and produce an inflammatory response that triggers over-excitation of the nerve cells in the trigeminal pathway. [This nerve pathway runs from the brain stem to the head and face. These nerves spread to the meninges (the membrane covering of the brain).]
While the brain itself is insensitive to pain, the meninges and blood vessels around the brain are sensitive to pain. Some doctors suggest that pain occurs when blood drains from the center of the head to the blood vessels around the brain.
Auras are believed to be a response to blood flow changes that cause a rapid reduction in brain activity that reaches the cerebral cortex (the outer layer of the brain), referred to as spreading depression. This effect may be visualized as an electrical wave spreading through the brain just as a wave of water is caused by the dropping of a pebble. Some research suggests that in people with auras, the cortical spreading depression itself activates the inflammation in the trigeminal nerves that triggers pain in the meninges.

One theory of the cause of migraine is a central nervous system (CNS) disorder. The CNS consists of the brain and spinal cord. In migraine, various stimuli may cause a series of neurologic and biochemical events that affect the brain's vascular system.

Abnormal Calcium Channels. Some migraines may be due to abnormalities in the channels within cells that transport the electrical ions calcium, magnesium, sodium, and potassium. Calcium channels appear to play a particularly critical role in migraine:

Calcium channels regulate the release of serotonin, an important neurotransmitter in the migraine process. (A neurotransmitter is a chemical messenger that allows communication between nerves in the brain.)
Magnesium interacts with calcium channels, and magnesium deficiencies have been detected in the brains of patients with migraine.
Calcium channels also play a major role in cortical spreading depression, the brain event that appears to be important in migraine symptoms.

Some patients with migraines may inherit one or more factors that impair calcium channels, making them susceptible to headaches. For example, mutations in a gene that encodes calcium channels appears to be responsible for familial hemiplegic migraine.

Researchers are also investigating factors that are common to both migraines and tension-type headaches. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Serotonin and Other Neurotransmitter Levels. Neurotransmitters are chemical messengers in the brain. Serotonin is a neurotransmitter (chemical messenger in the brain) that is important for sleep, well-being, and other factors that affect quality of life. Abnormalities in serotonin levels have been observed in both tension-type and migraine headache sufferers. Altered levels of other neurotransmitters, importantly dopamine and stress hormones, also occur with migraine and tension-type headaches.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people over-sensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Reduced Magnesium Levels. Magnesium deficiencies have been observed in people with both tension-type and migraine headaches. Researchers have noted a drop in magnesium levels before or during a migraine attack. Magnesium plays a role in nerve cell function. Reduced levels could be a destabilizing factor, causing the nerves in the brain to misfire, possibly even accounting for the auras that many sufferers experience.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger that may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are slightly more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Inflammation in the Maxillary Nerve. Early studies suggest that some chronic tension-type and migraine headaches may be caused by inflammation in the nerve that runs behind the cheekbone (the maxillary nerve) -- not around the covering of the brain. In fact, some work using ice water for reducing swelling in areas of the gums above the last upper molars has relieved some severe migraine and tension-type headaches.

A wide range of events and conditions can alter conditions in the brain that bring on nerve excitation and trigger migraines. They include, but are not limited to:

Emotional stress
Intense physical exertion (exercise, lifting, and even bowel movements or sexual activity)
Abrupt weather changes
Bright or flickering lights
High altitude
Travel motion
Lack of sleep
Low blood sugar and fasting
Chemicals found in certain foods. More than 100 foods may potentially trigger migraine headache. Caffeine is one such trigger. Caffeine withdrawal can also trigger migraines in people who are accustomed to caffeine. Experts recommend that patients keep a headache diary to track which foods trigger migraine.

Risk Factors

About 30 million Americans suffer from migraine headaches. They affect about 17% of all women and 6% of men. In fact, 70% of all migraine sufferers are women. Migraine is more prevalent among women throughout the world and in every culture. Although the incidence of migraine is similar for boys and girls during childhood, it increases in girls after puberty. Most people with migraine have 1 - 4 attacks per month.

Hormone Fluctuations in Women. Most migraines in women develop during the hormonally active years between adolescence and menopause. Fluctuations of estrogen and progesterone, rather than their presence, appear to increase the risk for migraines and their severity in some women.

About half of women with migraines report headaches associated with their menstrual cycle, although true menstrual migraines may actually be less common. True menstrual migraines tend not to have auras and to increase in prevalence between 2 days before and 5 days after the onset of period.
The first 3 months of pregnancy can worsen migraines in some women, although one study reported that pregnancy had little effect one way or the other on severity in most women with chronic headaches.
Women whose migraines are affected by pregnancy or menstruation are also likely to have worse migraines if they take oral contraceptives or hormone replacement therapies.

General Age of Onset. More than 20% of adults with migraines report that their headaches started before age 10, and over 45% say they started before age 20. The incidence of migraine declines in both men and women after age 40.

Migraine in Children. Migraine headaches occur in all ages and can appear in children as young as 4 years of age. Migraines in children are equally prevalent in boys and girls. Studies estimate that about 4 – 10% of all children suffer from migraine. Research indicates that overweight children may be especially susceptible to headaches, although this association is most likely due to poor nutrition and lack of exercise rather than excess weight. Children who have sleep problems, especially difficulty falling asleep, may also be more prone to migraines.

A small 2006 study indicated that some adolescents with migraine may eventually grow out of their condition. By the end of the 10-year study, 38% of patients had stopped having migraines, and 20% had transitioned into less severe tension-type headache. Children with a family history of migraine were more likely to continue having migraines.

Migraine Onset in Older Adults. Although uncommon, late-life migraine occurs in about 1% of the population, usually in men. In such cases, it often occurs as migraine with visual disturbances but without headache.

Migraine headaches can be inherited. If both parents suffer from migraines, their children have a 75% chance of getting them. When only one parent gets migraines, there is a 50% chance that children will be afflicted.

Caucasians have a higher risk than either African-Americans or Asians. Worldwide, one study reported that migraines are most common in North America. They are slightly less prevalent in South America and Europe and far less common in Asia and Africa. Investigators believe that the differences are due to genetic variations, not lifestyle factors.

People with migraine have a higher incidence of other medical conditions, including:

Asthma and allergies. These conditions have also been associated with a higher risk for conversion from having periodic migraines attacks to a chronic form (transformed migraines).
H. pylori infection. People who are infected with the bacteria H. pylori, the major cause of peptic ulcers, are at higher risk for migraines.
Epilepsy. Patients with epilepsy are twice as likely to have migraines as the general population.
Fibromyalgia
Systemic lupus erythematosus
Raynaud syndrome
Mitral valve prolapse
Narcolepsy

One study suggested that women with migraines tend to over-respond to stressful situations. In the study, they were more likely than other women to be diligent, conscientious, and overly sensitive to pressure from others. More likely, however, a person's family history of migraine, rather than any personality trait, is the important risk factor.

Diagnosis

Anyone, including children, who has recurring or persistent headaches should consult a doctor. There are no blood tests or imaging techniques that can be used to diagnose migraine headaches. A diagnosis will be made on the basis of history and physical exam, and, if necessary, tests may be necessary to rule out other diseases or conditions that may be causing the headaches. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting
Behaviors during a headache. This may help distinguish between migraine and tension headaches. The predominant behavior with tension headaches is massaging the scalp, temples, or the nape of the neck. A person with migraines is more apt to use compression (such as tying a scarf around the forehead and temples) or to apply cold. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The presence of auras or other visual disturbances do not always identify migraine:

Patients with severe sinus infections may experience double vision or visual loss. (This is an emergency condition, since it indicates the infection has spread to areas around the eyes.)
Many migraine sufferers have no auras.
Many elderly people with late-onset migraine have auras but no pain.

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Some tips include:

Note all conditions, including any foods eaten, preceding an attack. Often two or more triggers interact to produce a headache. For example, a combination of weather changes and fatigue can make headaches more likely than the presence of just one of these events.
Keep a migraine record for at least three menstrual cycles. For women, this can help to confirm or refute a diagnosis of menstrual migraine.
Track medications. This is important for identifying possible rebound headache or transformed migraine.
Attempt to define the intensity of the headache using a number system, such as:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
Any uncharacteristic dietary changes
Any current medications or recent withdrawals from any drugs, including over-the-counter or natural remedies.
Any history of caffeine, alcohol, or drug abuse.
Any serious stress, depression, and anxiety.

The doctor will also need a general medical and family history of headaches or diseases, such as epilepsy, that may increase their risk. Migraine tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor may ask questions to test short-term memory and related aspects of mental function.

Diagnosing the cause of persistent daily headache is difficult, even for expert doctors. Studies report that people who visit the emergency room with disabling headache are often misdiagnosed as tension-type headaches instead of migraines. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

Differentiating Rebound Headaches from Transformed Migraines. Migraines that evolve to chronic headaches must be first differentiated between natural transformed migraines and rebound headaches (the most common cause of persistent migraines):

A transformed migraine is usually more consistent in its severity and its location than a rebound headache.
Transformed migraines are less sensitive to triggers than rebound headaches.

Differentiating Transformed from Tension Headaches. Once rebound headache is ruled out, the doctor must then differentiate natural transformed migraines from tension headaches:

In most cases of transformed migraine (but not tension headache), gastrointestinal or neurologic symptoms are present.
Transformed migraine is also frequently associated with menstrual fluctuations in women.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headaches that wake them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headaches.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other imaging tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT). These tests are only performed if there is reason to suspect an underlying disease or as part of clinical studies.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of not only the bony structures but also the soft tissues. Clear images of organs and structures, such as the brain, muscles, joints, veins and arteries, as well as of tumors and hemorrhages, may be obtained with or without the injection of contrasting dye.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition by believing it to be one of their usual headaches. Such patients should call a doctor promptly if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Treatment Approaches

Many effective headache remedies are available for treating a migraine attack. Still, a study that analyzed over 800,000 cases of migraine reported that most migraines are not treated according to any recommended guidelines. In the study, 30% of patients were treated with potentially addictive opioids -- most often merepidine (Demerol). Furthermore, 70% of these patients were not offered effective and available anti-migraine drugs. Anti-nausea drugs that have no effect on headaches were used six times more often than drugs that reduce headaches.

A 2007 survey of migraine sufferers, commissioned by the U.S. National Headache Foundation, reported that 20% of patients are prescribed non-approved medications containing opioids or barbiturates. The survey also indicated that patients who take non-approved drugs are more likely to experience drug-related side effects. For mild migraines, non-prescription treatments (Excedrin Migraine, Advil Migraine, Motrin Migraine Pain) are the best first choice. For severe migraines, doctors recommend starting with a triptan drug.

Preventive treatment, used to stop migraine attacks before they happen, may help many patients. According to another 2007 survey, more than 1 in 4 patients with migraine are candidates for preventive therapy but most do not receive it.

As many as 30% of patients with migraine also have accompanying headaches resulting from tension, drugs, infections, or other causes. It is important to distinguish between headache types in order to determine appropriate treatment.

General Guidelines. The general goals of treatment are:

Choose drugs with as few side effects as possible. Patients should talk to their doctors about various methods for administering the medication (pills, injections, nasal spray, or rectal suppositories) and begin with the one they believe will be the least distressing.
Treat the attack rapidly, within an hour of symptom onset if possible. Start with low doses, and build up dosage slowly.
Try to minimize the use of back-up or "rescue medications." (A rescue medication is typically a narcotic opiate drug, which is used for pain relief when other medications fail.)
Try to guard against rebound effect. Nearly all drugs used for migraine can cause rebound headache, and patients should not take any the drugs for longer than 2 days per week.
It may take 2 - 4 months for any drug to be effective.

Stepped-Up Treatment Approach. Some doctors recommend a stepped-up treatment course for an acute migraine attack. This involves starting with the least potent treatments and taking increasingly more powerful drugs until the pain stops. In this approach, patients may need up to five different medications to achieve pain relief. A typical stepped-up approach is the following:

The patient should first use nonprescription pain relievers (NSAIDs, Excedrin Migraine) and stress-reduction techniques.
If these are not effective within 2 hours, the patient should take migraine-specific drugs. Triptans are the first choice, then ergot derivatives.
Patients with migraines associated with severe nausea or vomiting may use injected or rectally administered drugs. Nausea itself should be treated with specific anti-nausea drugs, such as metoclopramide (Reglan).
If migraine medications fail to relieve symptoms within 4 hours, rescue drugs (opioids, corticosteroids) may be used.

Stratified Approach. Many doctors and patients now prefer the stratified approach. The doctor first estimates the severity of the patient's condition based on his or her history. Then, depending on the severity of a typical attack, the doctor decides whether the patient should start with more or less powerful drugs at the first signs of the migraine:

Patients with less disabling migraines start with general pain relievers.
Patients with a history of moderate-to-severe migraines start with migraine-specific prescription medicine, such as a triptan, at the onset of mild pain.

Some studies report dramatic relief with the stratified approach. In one study, zolmitriptan, a newer triptan, reduced the intensity of headaches within 2 hours in 70% of patients with moderate pain but only in 44% of those with severe headaches.

Side effects can be severe with many migraine drugs, although newer drugs, such as the recent generation triptans, may provide effective early relief without significant side effects.

Studies estimate that between 5 - 10% of children have migraines but that the disorder is underdiagnosed in children. An interesting study reported that when children drew pictures in response to their doctors' questions about their migraines, the doctors were able to tell the difference between migraine and non-migraine headaches in the majority of cases.

Symptoms in Children. The standard diagnostic criteria for migraine in adults may apply to only about two-thirds of migraines in children and adolescents. For example, doctors have seen the following differences:

Headaches tend to last for a shorter time (as little as an hour) in children.
Migraine pain tends to occur in the face and on both sides of the head in two-thirds of child patients.
Children often have a form of migraine known as a migraine equivalent or abdominal migraine, which does not cause a headache at all. Instead, children experience periodic bouts of nausea and vomiting (called cyclic vomiting syndrome) or other secondary symptoms found in adult migraine, such as a reaction against light or sound. Cyclic vomiting may occur in nearly 2% of school-aged children with or without a migraine association.
Migraine triggers in children are similar to those in adults, but common ones in children are anxiety and fear, and eating ice cream.

Outlook in Children. Migraine in children is disabling, as it is in adults, and they tend to lose more school days than other children. Children with frequent headaches may also be at higher risk for headaches in adulthood and also for other physical and psychiatric problems. However, some children who have migraine eventually stop having attacks when they reach adulthood, or have less severe types of headaches.

Treatments in Children. Most children with migraines may need only mild pain relievers and home remedies (such as ginger tea) to treat their headaches. The American Academy of Neurology’s 2004 practice guidelines for children and adolescents recommend the following drug treatments:

For children age 6 years and older, ibuprofen (Advil) is recommended. Acetaminophen (Tylenol) may also be effective. Acetaminophen works faster than ibuprofen, but the effects of ibuprofen last longer.
For adolescents age 12 years and older, sumaptriptan (Imitrex) nasal spray is recommended.

Preventive Measures in Children. Non-medication methods, including biofeedback and muscle relaxation techniques may be helpful. In one study of children with migraines and poor sleep habits, who were taught how to sleep better instructions without using medications had significantly fewer migraine attacks.

If these methods fail, then preventive drugs may be used, although evidence is weak on the effectiveness of standard migraine preventive drugs in children.

If medication overuse causes rebound migraines develop, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may need only to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient can usually stop abruptly or gradually. The patient should expect the following:

Most headache drugs can be stopped abruptly, but the patient should talk to their doctor first. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days.
The patient may take other pain medicines during the first days. Examples of drugs that may be used include dihydroergotamine (with or without metoclopramide), NSAIDs (in mild cases), corticosteroids, or valproate.
The patient must expect their headache to get worse after they stop taking their medications, no matter which method they use. Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).
If the symptoms do not respond to treatment and cause severe nausea and vomiting, the patient may need to be hospitalized.

On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward, and one study reported that 82% of patients significantly improved 4 months after medication withdrawal.

Medications Used for Treatment

Many different medications are used to treat migraines. However, the Food and Drug Administration (FDA) has specifically approved only the following types of drugs for migraine treatment:

Non-prescription drugs: Excedrin Migraine, Advil Migraine, Motrin Migraine Pain
Prescription drugs: Triptans and ergotamine

Other types of drugs, including opioids and barbiturates, are sometimes prescribed off-label for migraine treatment. Opioids and barbiturates have not been approved by the FDA for migraine relief, and they can be addictive.

All FDA-approved migraine treatments are approved only for adults. No migraine products have officially been approved for use in children.

Some patients with mild migraines respond well to over-the-counter (OTC) painkillers, particularly if they take the medicine at the very first sign of an attack.

The Food and Drug Administration has approved three OTC (nonprescription) products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relieve of migraine and its symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) use a pad containing a gel that cools the skin for up to 4 hours and can be placed on the forehead, temple, or back of the neck.

Non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen, and naproxen. They were among the first types of drugs tried to treat mild-to-moderate migraines. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Anaprox, Aleve) are all available without prescription. Naproxen may have specific benefits for migraine. A 2007 study indicated that a combination of naproxen and sumatriptan provides better migraine pain relief than either drug alone.

Other types of NSAIDs are available only by prescription. Some studies indicate that the NSAID combination diclofenac-potassium (Cataflam) may work faster than the migraine drug sumatriptan (Imitrex) and help reduce nausea. The combination is not appropriate for people allergic to aspirin or at risk for bleeding.

Injectable NSAIDs, particularly ketorolac (Toradol), may be very effective for severe and persistent migraines. A 2003 study found that intravenous ketorolac provided greater pain relief than nasal sumatriptan (Imitrex). A 2005 study presented at the annual meeting of the American Headache Society reported that intravenous ketorolac was more effective than opioid drugs for late-stage treatment of severe migraine attacks.

COX-2s are a class of prescription drugs that have the anti-inflammatory effects of NSAIDs, but do not upset most people's stomachs. However, most of these drugs have been withdrawn from the U.S. market due to increased risk for heart attack and stroke. Celecoxib (Celebrex) is the only available COX-2, and it has a strong warning label alerting users of the potential for heart attack, stroke, and serious gastrointestinal problems. (The warning is the same one the Food and Drug Administration recommended for the labels of prescription NSAIDs in 2005.)

NSAID Side Effects. High dosages and long-term use of NSAIDs can increase the risk for heart problems, kidney problems, and stomach bleeding. In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process.

Triptans are recommended as first-line drugs for adult patients with moderate-to-severe migraines when NSAIDs are not effective. Triptans have the following benefits:

They are effective for most patients with migraine, as well as patients with combination tension and migraine headaches.
They do not have the sedative effect of other migraine drugs.
Withdrawal after overuse appears to be shorter and less severe than with other migraine medications

Sumatriptan. Sumatriptan (Imitrex) has the longest track record and is the most studied of all triptans. It is available as a fast-dissolving pill, nasal spray, or injection. Injected sumatriptan works the fastest of all the triptans and is the most effective, but it can cause pain at the injection site. The nasal spray form bypasses the stomach and is absorbed more quickly than the oral form. Some patients report relief as soon as 15 minutes after administration. The spray tends to work less well when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Sumatriptan is effective for many patients, but headache recurs in 20 - 40% of people within 24 hours after taking the drug.

A 2007 study in the Journal of the American Medical Association suggested that a combination of sumatriptan and naproxen works better than either drug alone.

Other Triptans. Newer triptans include almotriptan (Axert), zolmitriptan (Zomig), naratriptan (Amerge), rizatriptan (Maxalt), frovatriptan (Frova), and eletriptan (Relpax). Comparison studies with sumatriptan suggest that some of the newer drugs have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. They are also being investigated for prevention under certain circumstances, such as menstrual migraines, but benefits appear limited.

Studies on newer triptans indicate:

Almotriptan is as effective as oral sumatriptan and may have fewer side effects, particularly chest pain, than most other triptans.
Rizatriptan may have the most rapid effects of all oral triptans. Zolmitriptan also has a more rapid effect than sumatriptan (although there appears to be no significant difference in adverse effects). Both rizatriptan and zolmitriptan are also available as rapidly dissolving wafers.
Eleptriptan is also very rapidly effective at high doses, but at those levels may have significant adverse effects. (To date, it does not seem to have any advantages over other triptans in head-to-head comparisons.)
Naratriptan and frovatriptan have a delayed response but long duration, few side effects, and lower risk for recurrence than with sumatriptan. Some evidence suggests that they may have specific benefits for stopping prolonged migraines and may even play a role in prevention.
Frovatriptan: A large study of more than 500 women with an average 12-year history of menstrual migraines examined the use of frovatriptan for the short-term prevention of such headaches. Researchers found that the migraines disappeared in over half of the women on the higher dose (5 mg) of frovatriptan.
Zolmitriptan (Zomig): Several studies indicate that zomitriptan nasal spray may be safe and effective for adolescents. In one study, zolmitriptan relieved pain within 2 hours for nearly half of the children (aged 12 - 17 years) enrolled in the trial. Zolmitriptan nasal spray is approved only for adults.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include:

Tingling and numbness in the toes
Sensations of warmth
Discomfort in the ear, nose, and throat
Nausea
Drowsiness
Dizziness
Muscle weakness
Heaviness, pain, or both in the chest. (About 40% of patients taking sumatriptan experience these symptoms, and they are major factors in discontinuing the drug. Newer drugs, such as almotriptan, produce fewer chest symptoms.)
Rapid heart rate

Complications of Triptans. The following are potentially serious problems.

Complications of heart and circulation. Triptans narrow (constrict) blood vessels. Because of this effect, spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
Serotonin syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptan drugs used to treat migraine, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) -- such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with a SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following people should avoid triptans or take them with caution and only with the advisement of a doctor:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Children and adolescents. They may be safe, but controlled studies are needed to confirm this. (Triptans should not, in any case, be the first-line treatment for children.)
People with basilar or hemiplegic migraines. (Triptans are not indicated for these migraineurs.)
There is no evidence to date of any higher risk for birth defects in pregnant women who take triptans. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their doctors.

Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first anti-migraine drugs available. Ergotamine is available by prescription in the following preparations:

Dihydroergotamine (DHE) is an ergot derivative. It is administered as a nasal spray form (Migranal) or by injection, which can be performed at home.
Ergotamine is available tablets taken by mouth, tablets taken under the tongue (sublingual), and rectal suppositories. Some of the tablet forms of ergotamine contain caffeine.

Ergotamine’s role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Injected, oral, and nasal-spray forms are all inferior to the triptans. Ergotamine may still be helpful for patients with status migrainous or those with frequent recurring headaches.

Side Effects. Side effects of ergotamine include:

Nausea
Dizziness
Tingling sensations
Muscle cramps
Chest or abdominal pain

The following are potentially serious problems:

Toxicity. Ergotamine is toxic at high levels.
Adverse effects on blood vessels. Ergot can cause persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke.

Internal scarring (fibrosis). Scarring can occur in the areas around the lungs, heart, or kidneys. It is often reversible if the drug is stopped.

The following patients should avoid ergots:

Pregnant women. Ergots can cause miscarriage.
People over age 60.
Patients with serious, chronic health problems, particularly those of the heart and circulation.

Ergotamine can interact with other medications, such as antifungal drugs and some antibiotics. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label. The five FDA-approved ergotamine products that remain on the market are:

Migergot suppository (marketed by G and W Labs)
Ergotamine Tartrate and Caffeine tablets (marketed by Mikart and West Ward)
Cafergot tablets (marketed by Sandoz)
Ergomar sublingual tablets (marketed by Rosedale Therapeutics)

Nasal drops containing lidocaine, a local anesthetic, can provide effective and quick pain relief within 15 minutes for many migraine sufferers. However, lidocaine has certain downsides:

It is rather difficult to administer. Patients must be lying down with their head dangling.
The headache often relapses in an hour, and other drugs must then be used.
Side effects include unpleasant taste, burning sensation, and facial numbness.

However, the drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. It should not be used for any other form of headache.

If the pain is very severe and does respond to other drugs, doctors may try painkillers containing opioids. Opioid drugs include morphine, codeine, meperidine (Demerol), and oxycodone (Oxycontin)]. Butorphanol is an opioid in nasal spray form that may be useful as a rescue treatment when others fail.

Opioids are not approved for migraine treatment and should not be used as first-line therapy. Nevertheless, many opioid products are prescribed to patients with migraine, sometimes with dangerous results. In 2007, following reports of several drug-related deaths, the Food and Drug Administration warned that the cancer pain pill fentanyl (Fentora) should not be used to treat patients with migraine or others conditions for which the drug is not specifically approved.

Side Effects. Side effects for all opioids include drowsiness, impaired judgment, nausea, and constipation. There is a risk for addiction, and these drugs can become ineffective with long-term use for chronic migraines. Doctors should not prescribe opioids to patients at risk for drug abuse, including those with personality or psychiatric disorders.

Metoclopramide (Reglan) is used in combinations with other drugs to treat the nausea and vomiting that occurs with other drugs and with migraine itself. Metoclopramide and other anti-nausea drugs, such as domperidone (Motilium), may help the intestine better absorb migraine medications.

New drugs in clinical trials include tonabersat (a gap junction blocker), trexima (a combination triptan and non-steroidal anti-inflammatory drug), GW274150 (a nitric oxide synthase inhibitor), and MK-0974 (a calcitonin gene-related peptide antagonist). Researchers are also investigating a nasal spray containing capsaicin, the chemical found in cayenne peppers.

Prevention

There are several ways to prevent migraine attacks. You should try a healthy diet, the right amount of sleep, and non-drug approaches, such as biofeedback, first for prevention.

Behavioral techniques that reduce stress and empower the patient may help some people with migraines. Studies report between 35 - 50% reduction in migraine and tension-type headaches with these approaches. They generally include:

Biofeedback therapy
Cognitive-behavioral therapy
Relaxation techniques

Behavioral methods may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. They may be particularly beneficial for children, adolescents, and pregnant and nursing women, and anyone who cannot take most migraine medications.

Biofeedback. Studies have demonstrated some effectiveness from biofeedback for migraine headaches. Biofeedback training teaches the patient to monitor and modify physical responses, such as muscle tension, using special instruments for feedback.

Cognitive Behavioral Therapy. Behavioral therapy may be useful alone but is particularly beneficial for patients who are on preventive drug treatments. It typically uses the headache diary to track activities and headaches. The patient then works with the therapist to change or add behaviors or medications that will reduce the frequency and severity of attacks.

Alternative non-drug therapies used for headache management and prevention include hypnosis, meditation, visualization and guided imagery, acupuncture, acupressure, yoga, and other relaxation exercises. There is no clear evidence that any of these techniques have specific value for migraines.

Some studies report the following:

Acupuncture. Acupuncture is a Chinese medicine technique that uses thin needles to stimulate specific points aligned with energy pathways in the body. Studies have showed mixed results on the benefits of acupuncture for migraine. A 2005 study published in the Journal of the American Medical Association reported that acupuncture was no more effective than sham acupuncture (needles placed at non-acupuncture points) in preventing migraines. More than 300 people were enrolled in this randomized trial. A 2006 study of 960 people, published in Lancet Neurology, found that real acupuncture, sham acupuncture, and standard drug treatment were all equally effective in preventing migraine attacks.
Relaxation Techniques. Muscle relaxation techniques may be helpful. One study reported that relaxation treatments appeared to help adolescents with migraine but not tension headaches.

Hormonal drugs, such as oral contraceptives or hormone replacement therapy, have a mixed effect on women with migraines. Oral contraceptives have been associated with worse headaches in 18 - 50% of women and have also been linked to a higher risk for stroke in women with classic migraines (with auras). Young women should avoid or stop oral contraception if they have classic migraines, migraines that worsen or change character after oral contraceptives , if they have close relatives with stroke or heart disease, or if they smoke.

Some evidence suggests, however, that oral contraceptives may help prevent true menstrual migraines (which do not have auras). In such cases, their benefits may outweigh the low risk of a serious adverse event. Keeping a migraine record for at least three menstrual cycles can help confirm whether a woman actually has a true menstrual migraine.

Making a few minor changes in your lifestyle can make your migraines more bearable. Improving sleep habits is important for everyone, and especially those with headaches. What you eat also has a huge impact on migraines, so dietary changes can be extremely beneficial, too.

Avoiding Food Triggers. Avoiding foods that trigger migraine is an important preventive measure. Common food triggers include monosodium glutamate (MSG), processed lunch meats that contain nitrates, dried fruits that contain sulfites, aged cheese, alcohol and red wine, chocolate, and caffeine. However, people’s responses to triggers differ. Keeping a headache diary that tracks diet and headache onset can help identify individual food triggers.

Healthy Diet. One study indicated that a diet low in fat and high in complex carbohydrates may significantly reduce the frequency, severity, and duration of migraine headaches. Such a diet is healthy in general, in any case.

Eating Regularly. Eating regularly is important to prevent low blood sugar. People with migraines who fast periodically for religious reasons might consider taking preventive medications.

Fish Oil. Some studies suggest that omega-3 fatty acids, which are found in fish oil, have anti-inflammatory and nerve protecting actions. These fatty acids can be found in oily fish, such as salmon, mackerel, or sardines. They can also be obtained in supplements of specific omega-3 compounds (DHA-EPA).

Exercise is certainly helpful for relieving stress. An analysis of several studies reported that aerobic exercise in particular might help prevent migraines. It is important, however, to warm up gradually before beginning a session, since sudden, vigorous exercise might actually precipitate or aggravate a migraine attack.

Manufacturers of herbal remedies and dietary supplements do not need Food and Drug Administration approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Riboflavin (Vitamin B2). There is reasonable evidence on the benefits of vitamin B2 for migraine sufferers. In one study, patients who took 400 mg of vitamin B2 (riboflavin) reduced their migraine attacks by half, although the vitamin had no effect on the severity or duration of migraines that did occur. In another study, it helped increase the effectiveness of beta-blockers, drugs used to prevent migraines in some people. Vitamin B2 is generally safe, although some people taking high doses develop diarrhea.

Magnesium Supplements. Studies have reported a higher rate of magnesium deficiencies in some patients with migraine, such as those with menstrual migraines. Magnesium helps relax blood vessels. Some patients report relief from supplements.

Feverfew. Feverfew is the most studied herbal remedy for headaches and is effective in some cases. However, like all effective headache remedies, overuse can cause a rebound effect.

Ginger. In general, herbal medicines should never be used by children or pregnant or nursing women without medical counsel. One exception may be ginger, which has no side effects and can be eaten in powder or fresh form, as long as quantities are not excessive. Some people have reported less pain and frequency of migraines while taking ginger, and children can take it without danger.

Medications Used for Prevention

The Food and Drug Administration has approved four drugs for prevention of migraine:

Propanolol (Inderal)
Timolol (Blacadrene)
Divalproex sodium (Depakote)
Topiramate (Topamax)

Propanolol and timolol are beta-blocker drugs. Divalproex and topiramate are anti-seizure drugs. Many other drugs are also being used or investigated for preventing migraines.

Beta-blockers are usually prescribed to reduce high blood pressure. Some beta-blockers, however, are also useful in reducing the frequency of migraine attacks and their severity when they occur. Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. Metoprolol (Toprol), atenolol (Tenormin), and nadolol (Corgard) are also being studied for migraine prevention.

Side Effects. Side effects may include:

Fatigue and lethargy are common.
Some people experience vivid dreams and nightmares, depression, and memory loss.
Dizziness and lightheadedness may occur upon standing.
Exercise capacity may be reduced.
Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems, and sexual dysfunction.

If side effects occur, the patient should call a doctor, but it is extremely important not to stop the drug abruptly. Some evidence suggests that people with migraines who have had a stroke should avoid beta-blockers.

Anti-seizure drugs, also called anti-epileptic drugs or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA may also have a role in migraines. These drugs are commonly used for epilepsy and bipolar disease. Anti-seizure drugs are more expensive than other drugs. They also have significant side effects. Divalproex sodium (Depakote) and topiramate (Topamax) are the only anti-seizure drugs that are approved for migraine prevention. However, if patients do not respond to either of these drugs, doctors may try other types of anti-seizure medications.

Divalproex Sodium (Depakote). Divalproex sodium (Depakote) was first approved in 1996 for migraine prevention. A once-a-day formulation of divalproex (Depakote ER) was approved in 2000. Doctors sometimes prescribe a similar drug, valproate (Depakene). Pregnant patients should not use these drugs, as they may cause birth defects.

Topiramate (Topamax). In 2004, the Food and Drug Administration approved topiramate for prevention of migraines in adults. Studies from 2006 indicated that the drug works well when used on a long-term basis. Patients in these studies experienced significantly fewer migraines for up to 14 months. Topiramate’s most common side effect is a tingling sensation in the arms and legs. Weight loss is also a side effect. In clinical trials, patients lost an average of 3.8% of their body weight.

Other Anti-Seizure Drugs Under Investigation. Researchers are studying other types of anti-seizure drugs for migraine prevention. These include levetiracetam (Keppra), gabapentin (Neurontin), pregabalin (Lyrica), zonisamide (Zonegran), tiagabine (Gabitril), and the investigational drug lacosamide (LCM).

Side Effects. Anti-seizure medication's side effects vary by drug but may include:

Nausea and vomiting
Diarrhea
Cramps
Hair loss
Dizziness
Sleepiness
Blurred vision
Weight gain
Valproate and divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver

Amitriptyline (Elavil, Endep), a tricyclic antidepressant drug, has been used for many years as a first-line treatment for migraine prevention. It may work best for patients who also have depression or insomnia. Tricyclics can have significant side effects, including disturbances in heart rhythms, and can be fatal in overdose. Although other tricyclic antidepressants may have fewer side effects than amitritpyline, they do not appear to be particularly effective for migraine prevention.

Researchers have investigated newer types of antidepressants, including serotonin-reuptake inhibitors(SSRIs), such as fluoxetine (Prozac). However, studies to date do not indicate that SSRIs are helpful for migraine prevention.

Muscle Relaxants. Botulinum toxin A (Botox) injection, a common wrinkle treatment, causes small muscles to relax. This approach is now being used with some success for treating disorders that involve over-excited muscle activity, including myofascial pain syndrome and migraine. One study reported complete migraine relief in more than half of patients being tested and improvement of more than 50% in another 35% of patients. Relief lasted 3 - 4 months with no adverse effects. A study presented at the 2005 meeting of the American Headache Society reported that patients who regularly received Botox injections every 3 months reduced both the frequency of migraine attacks and their reliance on pain medications

Angiotensin Converting Enzyme Inhibitors. Commonly used for treating high blood pressure, angiotensin converting enzyme (ACE) inhibitors block the production of the protein angiotensin, which constricts blood vessels and may be involved in migraine. Studies using the ACE inhibitor lisinopril (Prinivil, Zestril) are reporting significant reduction in migraine attacks.

Angiotensin-Receptor Blockers. Angiotensin-receptor blockers (ARBs) have actions similar to ACE inhibitors, but may have fewer side effects. In one study, patients who took the ARB candesartan (Atacand) had significantly fewer headaches compared to patients who received placebo.

Neurostimulation Devices. Researchers are investigating a transcranial magnetic stimulation (TMS) device to help stop migraines before they occur. The hair dryer-size device is held to the back of the head and delivers quick magnetic pulses. The device is used when a patient experiences the first signs of a migraine. Other types of nerve stimulation devices are also under investigation.

Inhalation Devices. These devices use heat to vaporize a drug so that it can be inhaled into the lungs. Clinical trials are currently testing this device with procholorperazine (Compazine), a tranquilizer drug that is used to treat nausea and vomiting.

Nasal Devices. New types of nasal sprays and powders are being researched. Some of them use capsaicin, the chemical found in cayenne peppers, to help relieve pain.

Skin Patches. The Actyve transdermal patch uses a small battery-powered system to deliver a triptan drug through the skin.

Drugs. New drugs in development include tonabersat (gap junction blocker), trexima (combination triptan and non-steroidal anti-inflammatory drug), and GW274150 (nitric oxide synthase inhibitor).

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.clinicaltrials.gov -- Find clinical trials
www.migraineinfo.org -- National Migraine Association

References

Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54.

Lewis DW, Winner P, Hershey AD, Wasiewski WW; Adolescent Migraine Steering Committee. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007 Aug;120(2):390-6.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9.

Monastero R, Camarda C, Pipia C, Camarda R. Prognosis of migraine headaches in adolescents: a 10-year follow-up study. Neurology. 2006 Oct 24;67(:1353-6.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Diabetes is a chronic (long-term) condition marked by abnormally high levels of sugar (glucose) in the blood. People with diabetes either do not produce enough insulin -- a hormone that is needed to convert sugar, starches and other food into energy needed for daily life -- or cannot use the insulin that their bodies produce. As a result, glucose builds up in the bloodstream. If left untreated, diabetes can lead to blindness, kidney disease, nerve disease, heart disease, and stroke.

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 20.8 million Americans have diabetes.

While an estimated 14.6 million have been diagnosed with diabetes (both type 1 and type 2), unfortunately, 6.2 million people (or nearly one-third) are unaware that they have type 2 diabetes.

Diabetes is widely recognized as one of the leading causes of death and disability in the United States. The Centers for Disease Control and Prevention (CDC) recognize diabetes as the 6th leading cause of death in the U.S.

There are two major types of diabetes:

Type 1 -- Also known as juvenile or insulin-dependent diabetes, type 1 diabetes occurs when the pancreas produces too little insulin to regulate blood sugar levels appropriately. It is usually diagnosed in childhood.
Type 2 -- This form of the disease is far more common than type 1 and makes up 90% or more of all cases of diabetes. It usually occurs in adulthood. It occurs when the pancreas does not make enough insulin to keep blood glucose levels normal. Many people with type 2 diabetes do not know they have it, although it is a serious condition. Type 2 diabetes is becoming more common due to the growing number of older Americans, increasing obesity, and failure to exercise.

Pre-diabetes occurs in those individuals with blood glucose levels that are higher than normal but not high enough for a diagnosis of diabetes. This condition raises the risk of developing type 2 diabetes, heart disease, and stroke. Pre-diabetes is also called impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), depending on the test used to diagnose it. Some individuals have both IFG and IGT. In IFG, glucose levels are a little high when it has been several hours after eating. In IGT, glucose levels are a little higher than normal right after eating. Pre-diabetes is becoming more common in the U.S., according to estimates provided by the U.S. Department of Health and Human Services (DHHS). Many individuals with pre-diabetes go on to develop type 2 diabetes within 10 years.

Gestational diabetes is high blood glucose that develops at any time during pregnancy in a person who does not have diabetes. Four percent of all pregnant women develop gestational diabetes. Although it usually disappears after delivery, the mother is at increased risk of developing type 2 diabetes later in life.

Diabetes may also be associated with genetic syndromes, surgery, drugs, malnutrition, infections, and other illnesses.

Signs and Symptoms

Type 1: Type 1 diabetes can occur at any age, but it usually starts in people younger than 30. Symptoms are usually severe and occur rapidly. They include:

Increased thirst
Increased urination
Weight loss despite increased appetite
Nausea
Vomiting
Abdominal pain
Fatigue
Absence of menstruation

Type 2: People with type 2 diabetes often have no symptoms, and their condition is detected only when a routine exam reveals high levels of glucose in their blood. Occasionally, however, a person with type 2 diabetes may experience symptoms listed below, which tend to appear slowly over time:

Numbness or burning sensation of the feet, ankles, and legs
Blurred or poor vision
Impotence
Fatigue
Poor wound healing

In some cases, symptoms may mimic type 1 diabetes and appear more abruptly:

Excessive urination and thirst
Yeast infections
Whole body itching
Coma -- in severe cases, high blood glucose may affect water distribution in brain cells, causing a state of deep unconsciousness, or coma.

Causes

Both type 1 and type 2 diabetes are caused by the absence, insufficient production, or lack of response by cells in the body to the hormone insulin. Insulin is a key regulator of the body's metabolism. After meals, food is digested in the stomach and intestines. Sugar (glucose) molecules are absorbed directly into the bloodstream, and blood glucose levels rise. Under normal circumstances, the rise in blood glucose levels signals specific cells in the pancreas -- called beta cells -- to secrete insulin into the bloodstream. Insulin, in turn, enables glucose to enter cells in the body that may be burned for energy or stored for future use.

In type 1 diabetes, the beta cells of the pancreas produce little or no insulin, the hormone that allows glucose to enter body cells. Once glucose enters a cell, it is used as fuel. Without adequate insulin, glucose builds up in the bloodstream instead of going into the cells. The body is unable to use this glucose for energy despite high levels in the bloodstream, leading to increased hunger.

In addition, the high levels of glucose in the blood cause the patient to urinate more, which leads to excessive thirst. Within 5 - 10 years after diagnosis, the insulin-producing beta cells of the pancreas are completely destroyed, and no more insulin is produced.

The exact cause of type 1 diabetes is not known. Type 1 diabetes accounts for 3% of all new cases of diabetes each year. There is 1 new case per every 7,000 children per year. New cases are less common among adults older than 20.

Type 2 diabetes usually develops in older, overweight individuals who become resistant to the effects of insulin over time. When type 2 diabetes is diagnosed, the pancreas is usually producing enough insulin but, for unknown reasons, the body cannot use the insulin effectively. This is called insulin resistance. This means that the insulin produced by your pancreas cannot connect with fat and muscle cells to let glucose inside and produce energy. This causes hyperglycemia (high blood glucose). To compensate, the pancreas produces more insulin. The cells sense this flood of insulin and become even more resistant, resulting in a vicious cycle of high glucose levels and often high insulin levels.

Inflammation has also been found to be common among those with type 2 diabetes. Inflammatory markers (chemicals in the body that lead to inflammation), such as interleukin-6 (Il-6) and C-reactive protein, have been found to be increased in those with type 2 diabetes.

Type 2 diabetes usually occurs gradually. Most people with type 2 diabetes are overweight at the time of diagnosis. However, the disease can also develop in lean people, especially the elderly.

Risk Factors

Type 1 diabetes

Family history of type 1 diabetes
Mother who had pre-eclampsia (a condition characterized by a sharp increase in
Blood pressure during the third trimester of pregnancy)
Family history of autoimmune diseases, including Hashimoto's thyroiditis, Graves disease, myasthenia gravis, Addison's disease, or pernicious anemia
Viral infections during infancy, including mumps, rubella, and coxsackie
Child of an older mother
Northern European or Mediterranean descent
Lack of breast-feeding and consumption of cow's milk during infancy (still controversial)

Type 2 diabetes

Family history of type 2 diabetes (one-quarter to one-third of all individuals with type 2 diabetes have a family history of the condition)
Age older than 45 years
Excess body fat, particularly around the waist
Sedentary lifestyle and high-fat, high-calorie diet
Abnormal levels of cholesterol or triglycerides in the blood
High blood pressure
History of gestational diabetes or polycystic ovary syndrome (a hormonal disorder that causes women to have irregular or no menstruation)
African-American, Hispanic American or Native American (particularly Pima tribe in Arizona) descent
Low birth weight or a mother's malnutrition in pregnancy (this may cause metabolic disturbances in a fetus that lead to diabetes later in the child's life)

Diagnosis

According to the American Diabetes Association, all pregnant women should be screened for gestational diabetes during their third trimester, People who are 45 years or older should have their blood glucose levels checked every 3 years. Those who have a high risk of developing diabetes (such as people with a family history of the disease) should be tested more often.

Different types of tests are used to diagnose diabetes: Random plasma glucose level, fasting plasma glucose level, and oral glucose tolerance test.

If the fasting glucose level is 100 - 125 mg/dL, the individual has a form of pre-diabetes called impaired fasting glucose (IFG), meaning that the individual is more likely to develop type 2 diabetes but does not have the condition yet. A level of 126 mg/dL or above, confirmed by repeating the test on another day, means that the individual has diabetes.

Other diagnostic tests for diabetes includes fructosamine testing and hemoglobin A1c. The American Diabetes Association (ADA) recommends A1c as the best test to find out if an individual's blood sugar is under control over time. The test should be performed every 3 months for insulin-treated patients, during treatment changes, or when blood glucose is elevated. For stable patients on oral agents, health care professionals recommended testing A1c at least twice per year. The ADA currently recommends an A1c goal of less than 7.0%. Studies have reported that there is a 10% decrease in relative risk of microvascular complications, such as diabetic nephropathy or diabetic neuropathy, for every 1% reduction in hemoglobin A1c.

People with diabetes must closely monitor their blood sugar and see their doctor regularly. Self-monitoring of blood glucose is done by checking the glucose content of a drop of blood. Regular testing tells you how well diet, medication, and exercise are working together to control your diabetes. Dieticians can also be an integral part of care.

Preventive Care

Type 1 diabetes

There is currently no proven way to prevent type 1 diabetes. However, research conducted in Finland suggests that adequate amounts of vitamin D, particularly in the first year of life, may decrease one's chances of developing type 1 diabetes within the first 30 years of life. In northern Finland (where the annual exposure to sunlight is very limited) researchers followed 10,000 infants for up to 30 years. Those given at least 2,000 IU of vitamin D per day (generally from cod liver oil) for the first year of life were significantly less likely to develop type 1 diabetes over a 30 years than infants who were given less than that. Other studies have confirmed that doses of 2,000 IU or higher of vitamin D may have a strong protective effect against type 1 diabetes. For this reason, caretakers of infants and children at increased risk for type 1 diabetes might wish to consider supplementation. Experts suggest supplementing these individuals at the high end of current U.S. recommendations for vitamin D, which is 200 - 1,000 IU.

Type 2 diabetes

Considerable evidence from population-based studies suggests that type 2 diabetes is highly preventable -- particularly through exercise and weight management. Individuals who are physically inactive or overweight are much more likely to develop type 2 diabetes. Similarly, people who move from a non-Westernized country to a Westernized country (such as the United States where more people are overweight and live sedentary lives), increase their risk for type 2 diabetes. Studies suggest that you do not need vigorous physical activity to lower your risk of diabetes; moderate, regular exercise such as walking for 30 minutes most days of the week, is enough. In general, lifestyle changes recommended to treat diabetes may help prevent the condition as well.

Treatment Approach

The goal of diabetes treatment is to achieve and maintain a healthy blood glucose levels. A major study called the Diabetes Control and Complications Trial (DCCT) found that people with diabetes who kept their blood glucose levels close to normal reduced their risk of developing major complications from the condition.

People with diabetes can use the following therapies to help manage their blood glucose levels and to prevent complications:

Lifestyle changes, such as a well-balanced diet and regular exercise
Medications, particularly insulin for individuals with type 1 diabetes and some people with type 2 diabetes
Supplements, including fiber and chromium
Relaxation techniques
Acupuncture for pain from nerve damage

Lifestyle

People with diabetes can improve significantly from lifestyle changes -- particularly diet and exercise. People with type 2 diabetes may even eliminate the need for medications when they make appropriate lifestyle changes.

Diet

The American Diabetes Association (ADA) recommends that people with diabetes consume a healthy, low-fat diet, rich in grains, fruits, and vegetables. A healthy diet typically includes 10 - 20% of daily calories from protein such as poultry, fish, dairy, and vegetable sources. People with diabetes who also have kidney disease should work with their health care providers to limit protein intake to 10% of daily calories. A low-fat diet typically includes 30% or less of daily calories from fat -- less than 10% from saturated fats and up to 10% from polyunsaturated fats (such as fats from fish).

Carbohydrates tend to have the greatest effect on blood glucose. The balance between the amount of carbohydrate eaten and the available insulin determines how much the blood glucose level goes up after meals or snacks. To help control blood glucose, people should watch how many carbohydrate servings they eat each day. Foods that contain a high amount of carbohydrates include grains, pasta, and rice; breads, crackers, and cereals; starchy vegetables, including potatoes, corn, peas, and winter squash; legumes such as beans, peas, and lentils; fruits and fruit juices; milk and yogurt; and sweets and desserts. Non-starchy vegetables, such as spinach, kale, broccoli, salad greens, and green beans, are very low in carbohydrates. Carbohydrate counting can ensure that the right amount of carbohydrate is eaten at each meal and snack. A dietician can help each person work out a dietary plan that is right for them.

In addition, weight loss should be part of the plan for those with type 2 diabetes. Moderate weight loss (achieved by reducing calories by 250 - 500 per day and exercising regularly) not only controls blood sugars but blood pressure and cholesterol as well. People with diabetes who eat healthy, well-balanced diets will not need to take extra vitamins or minerals to treat their condition.

Exercise

Exercise plays an important role in controlling diabetes because it lowers blood sugar and helps insulin work more efficiently in the body. Exercise also enhances cardiovascular fitness by improving blood flow and increasing the heart's pumping power, promoting weight loss, and lowering blood pressure. However, exercise has the most value when it’s done regularly -- at least three to four sessions per week for 30 - 60 minutes per session. As little as 20 minutes of walking, three times a week, has a proven beneficial effect. People with type 2 diabetes who exercise regularly have been shown to lose weight and gain better control over their blood pressure, thereby reducing their risk for cardiovascular disease (a major complication of diabetes). Studies have also shown that people with type 1 diabetes who regularly exercise reduce their need for insulin injections.

Despite the benefits of exercise, many people have difficulty sticking with an exercise program for a long period of time. Health care providers can help develop suitable routines as well as strategies that may improve adherence to such routines. Anyone with long-standing diabetes should have a thorough screening before starting an exercise program and receive careful monitoring from a physician.

Medications

Medications for diabetes must always be used in combination with lifestyle changes, particularly diet and exercise, to improve the symptoms of diabetes. Medications include insulin, oral sulfonylureas (like glimepiride, glyburide, and tolazamide), biguanides (Metformin), alpha-glucosidase inhibitors (such as acarbose), thiazolidinediones (such as rosiglitazone) and meglitinides (including repaglinide and nateglinide). A new agent in the fight against diabetes, exenatide (Byetta), is an injectable drug that reduces the level of sugar (glucose) in the blood. In clinical studies, exenatide-treated patients achieved lower blood glucose levels and experienced weight loss. Exenatide was approved by the U.S. Food and Drug Administration in May 2005.

Nutrition and Dietary Supplements

Considerable research has been conducted on the relationship between diabetes and specific nutrients and dietary supplements. Dietary supplements may increase the effects of blood sugar lowering medications, including insulin. Whenever considering the use of supplements or making dietary changes, be sure to discuss these changes with your health care provider to ensure safety and appropriateness.

Supplements with Blood Sugar Lowering Effects

Chromium -- Found in a variety of foods and supplements, including liver, brewer's yeast, cheese, meats, fish, fruits, vegetables, and whole grains, chromium appears to enhance the body's sensitivity to insulin. Researchers believe that chromium helps insulin pull glucose from the bloodstream into the cells for energy. The benefit of chromium supplements for diabetes has been studied and debated for a number of years. While some studies show no beneficial effects of chromium use for people with diabetes, other studies have shown that chromium supplements may reduce blood glucose levels in individuals with type 2 diabetes and reduce the need for insulin in those with type 1 diabetes. Most Americans get at least 50 mcg of chromium in their diets each day. The National Research Council estimates that intakes of 50 - 200 mcg per day are safe and effective. Clinical studies showing improved blood sugar control for those with diabetes have used doses of chromium picolinate ranging from 200 - 1,000 mcg per day. However, until human studies of long-term safety are conducted with higher doses, it is best to use 200 mcg or less per day.

Magnesium -- Several clinical studies have demonstrated a strong association between low levels of magnesium in the blood and type 2 diabetes. However, researchers are still unclear about the cause and effect in that association. They are investigating whether low magnesium levels worsen blood sugar control in people with type 2 diabetes or whether diabetes causes magnesium deficiencies. Some experts believe that low magnesium levels worsen blood sugar control and that foods rich in magnesium (such as whole grains, green leafy vegetables, bananas, legumes, nuts, and seeds) or magnesium supplements may promote healthy blood glucose levels. At least one small study suggests that taking magnesium supplements may improve the action of insulin and decrease blood sugar levels, particularly in the elderly. People with severe heart disease or kidney disease should not take magnesium supplements. People with diabetes should discuss whether it’s safe and appropriate to take magnesium supplements with a health care provider.

Fiber -- Studies suggest that a high-fiber diet may help:

Prevent development of type 2 diabetes
Lower average glucose and insulin levels in people who already have type 2 diabetes
Improve cholesterol and triglyceride levels in those with diabetes

In a large-scale study of nurses in the United States, women who consumed the most whole grain foods in their diets were nearly 40% less likely to develop diabetes than women who consumed the least.

Studies have also shown that cholesterol levels improved in people with type 2 diabetes after they took supplements of a soluble fiber known as psyllium (Plantago psyllium).

Beta-glucan is a soluble fiber derived from the cell walls of algae, bacteria, fungi, yeast, and plants. It is commonly used for its cholesterol-lowering effects. There are several human trials supporting the use of beta-glucan for glycemic (blood sugar) control.

Vanadium -- Vanadium is an essential trace mineral present in the soil and in many foods. It appears to mimic the action of insulin and, in a number of human studies, vanadyl sulfate (a form of vanadium) has increased insulin sensitivity in those with type 2 diabetes. Animal studies and some small human studies also suggest that vanadium may lower blood glucose to normal levels (reducing the need for insulin) in people with diabetes. One preliminary clinical study found that people with diabetes using insulin who were given vanadium were able to lower their dose of insulin.

Antioxidants

Antioxidants such as beta-carotene and vitamin C are scavengers of free radicals -- unstable and potentially damaging molecules generated by normal chemical reactions in the body. Free radicals are unstable because they lack one electron. In an attempt to replace this missing electron, the free radical molecules react with neighboring molecules in a process called oxidation. Some clinical studies suggest that people with diabetes have elevated levels of free radicals and lower levels of antioxidants. Preliminary clinical studies show that the following antioxidants may improve symptoms of diabetes (by returning blood glucose levels to the normal range) and reduce the risk of associated complications:

Vitamin E
Selenium
Zinc

Two additional substances that show preliminary evidence to possibly help control blood sugar include:

Biotin (a B-complex vitamin) -- helpful for type 2 diabetes; brewer's yeast is a good source of biotin
Vitamin B6 -- helpful for both type 1 and type 2 diabetes

Supplements with Cardiovascular Effects

Because insulin resistance is often associated with cardiovascular disease, people with diabetes may benefit from nutrients that help manage elevated blood lipid levels, high blood pressure, or heart failure. Although the following supplements have been shown to improve cardiovascular health, there is some concern that they may raise blood glucose levels. People with diabetes interested in trying the following supplements should first consult with their health care providers:

Coenzyme Q10 (CoQ10)
Niacin
Omega-3 Fatty acids

Although clinical studies have not shown that either CoQ10 or omega-3 fatty acid supplements raise blood sugar levels, people with diabetes should discuss the safety and appropriateness of using these, or any supplements, with their doctor or pharmacist.

In addition, the following antioxidants have been shown to improve cholesterol levels in people with type 2 diabetes:

Beta-carotene
Vitamin C (1000 mg per day)
Vitamin E (800 IU per day)

Several clinical studies have also found that elevated manganese levels may help protect against LDL oxidation (a process that contributes to the development of plaque in the arteries).

Supplements that May Reduce Complications of Diabetes

More than one-third of all people with diabetes develop a painful condition known as diabetic neuropathy (nerve damage). Some researchers speculate that elevated levels of free radicals, which can cause damage to nerves and blood vessels, may cause this condition. Clinical studies suggest that the following antioxidant supplements may improve nerve communication in damaged areas and reduce the symptoms of diabetic neuropathy:

Alpha-lipoic acid
Gamma-linolenic acid [evening primrose oil (Oenothera biennis ) is a rich source]

Herbs

People have long used plant-based medicines in the treatment of diabetes. For instance, the plant extract guanidine, which lowers blood glucose, prompted the development and use of biguanides, a commonly used oral medication for diabetes. Other herbs may have a role in the management or prevention of diabetes. These include:

Bitter melon (Momordica charantia). Bitter melon has traditionally been used as a remedy for lowering blood glucose in patients with diabetes mellitus. Preliminary clinical studies have indicated that bitter melon may decrease serum glucose levels.
Fenugreek seeds (Trigonella foenum graecum). Fenugreek seeds, a spice found in many curry preparations, are high in fiber and have been shown to regulate glucose and improve lipid levels in both animals and humans. In two small studies of people with either type 1 or type 2 diabetes, fenugreek seed powder lowered blood glucose and improved levels of blood cholesterol and trigylcerides, among other beneficial effects.
Gymnema (Gymnema sylvestre). Preliminary human research reports that gymnema may be beneficial in patients with type 1 or type 2 diabetes when it is added to diabetes drugs being taken by mouth or to insulin. Gymnema may alter the ability to detect sweet tastes.
Cinnamon (Cinnamomum zeylanicum). In a clinical study of 60 people with type 2 diabetes, intake of 1, 3, or 6 grams of cinnamon per day reduced glucose, triglyceride, LDL cholesterol, and total cholesterol. Other clinical studies have found similar results. As a result, experts claim that cinnamon may play an important role in regulating blood sugar in people with diabetes.
American ginseng (Panax quinquefolium). Although both Asian (Panax ginseng) and American (Panax quinquefolium) appear to lower blood glucose levels, only American ginseng has been studied scientifically. Several clinical studies report a blood sugar lowering effect of American ginseng (Panax quinquefolium) in individuals with type 2 diabetes, both on fasting blood glucose and on postprandial glucose levels. One clinical study found that people with type 2 diabetes who take American ginseng before or together with a glucose meal experience a reduction in glucose levels after they consume the meal.

Acupuncture

Some researchers speculate that acupuncture may trigger the release of natural painkillers and reduce the debilitating symptoms of a complication of diabetes known as neuropathy (nerve damage). In one clinical study of people with diabetes suffering from chronic, painful neuropathy, acupuncture reduced pain and improved sleep in 77% of the participants and eliminated the need for pain medications in 32% of the participants. Given these findings, acupuncture may be a reasonable option for people with diabetes who have neuropathy and either find no symptom relief or develop side effects from conventional drug treatment.

Mind-Body Medicine

Stressful life events can worsen diabetes in several ways. For example, stress stimulates the nervous and endocrine systems in ways that increase blood glucose levels and disrupts healthful behaviors (increasing the chances that an individual may consume a high level of calories and limit his or her physical activity -- a pattern that leads to elevated blood glucose).

It makes sense, then, to consider stress management as part of the treatment and prevention of diabetes. Clinical studies have reported that people with diabetes who participate in biofeedback sessions (a technique that increases awareness and control of the body's response to stress) are more likely to reach target blood glucose levels than those who do not receive biofeedback. Although other studies have produced results that contradict this, researchers and clinicians agree that long-term stress is likely to worsen diabetes and that biofeedback, tai chi, yoga, and other forms of relaxation may help motivate people with diabetes to change their habits in order to manage their condition.

Other Considerations

Pregnancy

Women of child-bearing age who have diabetes should consult an endocrine specialist about the benefits of managing glucose levels before trying to conceive.

About 4% of all pregnant women in the United States are diagnosed with gestational diabetes. Risk factors for developing diabetes while pregnant include:

Modest weight gain prior to pregnancy (11 - 22 pounds or more)
Family history of diabetes
Tobacco use
African-American, Hispanic American, or Asian ancestry
Age older than 50 at conception

Normalizing glucose levels in women with gestational diabetes reduces their risk of complications, such as having an overweight baby, birth trauma, or the need for cesarean section. If the mother's glucose levels are uncontrolled, an infant can be stillborn or suffer from any number of complications, including defects of the brain or central nervous system, an abnormally large body or organs, heart or kidney abnormalities, asphyxia, respiratory distress, and congestive heart failure.

If dietary restrictions fail to improve glucose levels, a woman with gestational diabetes may need insulin. Women should not take oral diabetes medications during pregnancy. Women who develop gestational diabetes may experience the condition again in subsequent pregnancies. Gestational diabetes also increases the risk for developing type 2 diabetes.

Prognosis and Complications

People who maintain tight control over their blood glucose levels can prevent or delay the development of long-term complications from diabetes. Type 1 diabetes generally has more complications than type 2 diabetes.

Long-term complications of diabetes may include:

Heart disease and stroke
Vision loss and blindness
Kidney disease
Neuropathy (nerve damage)
Foot ulcers and infections
Skin problems, including bruising, dryness, itching, hair loss, warts, gangrene (tissue death), and skin ulcers

Supporting Research

Baker H. Nutrition in the elderly: nutritional aspects of chronic diseases. Geriatrics. 2007;62(9):21-5.

Batty GD, Kivimaki M, Smith GD, Marmot MG, Shipley MJ. Obesity and overweight in relation to mortality in men with and without type 2 diabetes/impaired glucose tolerance: the original Whitehall Study. Diabetes Care. 2007;30(9):2388-91.

Bo S, Ciccone G, Baldi C, et al., Effectiveness of a Lifestyle Intervention on Metabolic Syndrome. A Randomized Controlled Trial. J Gen Intern Med. 2007; [Epub ahead of print].

Bozkurt O, de Boer A, Grobbee DE, et al. Pharmacogenetics of glucose-lowering drug treatment: a systematic review. Mol Diagn Ther. 2007;11(5):291-302.

Casellini CM, Vinik AI. Clinical manifestations and current treatment options for diabetic neuropathies. Endocr Pract. 2007;13(5):550-66.

Diabetes Research in Children Network (DirecNet) Study Group, Buckingham B, Beck RW, Tamborlane WV, et al. Continuous glucose monitoring in children with type 1 diabetes. J Pediatr. 2007;151(4):388-93, 393.e1-2.

Herder C, Schneitler S, Rathmann W, et al. Low-Grade Inflammation, Obesity and Insulin Resistance in Adolescents. J Clin Endocrinol Metab. 2007; [Epub ahead of print].

Howes JB, Sullivan D, Lai N. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of postmenopausal women with mild to moderate hypercholesterolemia. Atherosclerosis. 2000;152(1):143-147.

Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500-1503.

Kapoor R, Huang YS. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol. 2006;7(6):531-4.

Khan A, Khattak K, Sadfar M, Anderson R, Khan M. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215-3218.

Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Scientific Statement: AHA Dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation. 2000;102(18):2284-2299.

Kris-Etherton P, Eckel RH, Howard BV, St. Jeor S, Bazzare TL. AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Circulation. 2001;103:1823.

Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr. 2000;72(5):1095-1100.

Malnick SD, Somin M. The VALIDD study. Lancet. 2007;370(9591):931; author reply 931-2.

Marz W, Wieland H. HMG-CoA reducatse inhibition: anti-inflammatory effects beyond lipid lowering. Herz. 2000;25(6):117-25.

Mosdol A, Witte DR, Frost G, Marmot MG, Brunner EJ. Dietary glycemic index and glycemic load are associated with high-density-lipoprotein cholesterol at baseline but not with increased risk of diabetes in the Whitehall II study. Am J Clin Nutr. 2007;86(4):988-94.

National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.

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Pedersen BK. IL-6 signalling in exercise and disease. Biochem Soc Trans. 2007;35(Pt 5):1295-7.

Peek ME, Cargill A, Huang ES. Diabetes health disparities: a systematic review of health care interventions. Med Care Res Rev. 2007;64(5 Suppl):101S-56S.

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Sirtori CR, Pazzucconi F, Colombo L, Battistin P, Bondioli A, Descheemaeker K. Double-blind study of high-protein soya milk v. cow's milk to the diet of patients with severe hypercholesterolaemia and resistance to or intolerance of statins. Brit J Nutr. 1999;82:91-96.

Srivastava AK. Anti-diabetic and toxic effects of vanadium compounds. Mol Cell Biochem. 2000;206(1-2):177-182.

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Review Date:
12/7/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Peptic ulcers

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Treatment
Treatment for NSAID-Induced...
Medications
Treatment for Bleeding Ulce...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk with cardiovascular medications

While nonsteroidal anti-inflammatory drugs are the major medications responsible for causing peptic ulcers, drugs taken for cardiovascular disease and its risk factors may also cause ulcers. Recent studies have found an association between increased risk of ulcer and the following drugs:

Spironolactone, a common diuretic used in heart failure
Niacin, a drug used to lower "bad" cholesterol and raise "good" cholesterol
Vitamin K antagonists, commonly prescribed anticoagulants
Dipyridamole, a drug for secondary stroke prevention
Low-dose aspirin, prescribed for both heart attack and stroke prevention

Risk of peptic ulcer increases dramatically when these drugs are used in combination. Considering the millions of people who take these medications to prevent a life-threatening cardiovascular event, their impact on peptic ulcer development could be monumental.

Atypical symptoms of GERD

The burning pain of gastroesophageal reflux disease (GERD) can be confused with that of an ulcer. However, GERD pain typically develops after meals and is relieved by antacids. Elderly patients may have different symptoms that can include loss of appetite, weight loss, anemia, vomiting, or difficulty swallowing. A careful examination may be necessary to diagnose the underlying cause, since GERD and peptic ulcer may coexist.

Adjustments in triple therapy

Peptic ulcers are commonly treated with the triple combination of two antibiotics (amoxicillin and clarithromycin) and a proton-pump inhibitor. Therapy usually lasts for 2 weeks. Recent studies indicate that 1 week may be just as effective. In addition, taking the antibiotics in sequence, rather than at the same time, may work better to eliminate H. pylori, the bacteria responsible for most ulcers.

Healing foods

Milk may not be the ideal food for people with peptic ulcers because it encourages the production of stomach acid. However, certain qualities found in fermented milks and yogurts may actually offer protection against gastric ulcers. Likewise, the phenolic compounds found in virgin olive oil appear to kill many strains of H. pylori, including some that have become resistant to antibiotics. Vegetables contain dietary nitrate, which increases nitric oxide in the gut, causing the mucus layer to thicken. This increases protection against H. pylori invasion.

Protection when taking NSAIDs

People who take NSAIDs for pain control have an immediate increased risk of ulcers. Chronic use increases risk dramatically. Taking a proton-pump inhibitor (PPI) or H2 blocker is necessary to reduce this risk. A review of clinical trials found three PPIs [omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)] to be more effective than the H2 blocker ranitidine (Zantac). When NSAIDs were discontinued, however, healing rates with ranitidine reached nearly 100%.

Introduction

A peptic ulcer is an open sore or raw area that tends to develop in one of two places:

The lining of the stomach ( gastric ulcer), or
The upper part of the small intestine -- the duodenum ( duodenal ulcers). In the U.S., duodenal ulcers are 3 times more common than gastric ulcers.

A peptic ulcer is an open sore or raw area in the lining of the stomach (gastric) or the upper part of the small intestine (duodenal).

Ulcers average between one-quarter and one-half inch in diameter. They develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.

The two important digestive juices are hydrochloric acid and the enzyme pepsin. Both substances are critical in the breakdown and digestion of starches, fats, and proteins in food. They play different roles in ulcers:

Click the icon to see an image of the stomach.

Hydrochloric acid. A common misbelief is that excess hydrochloric acid, which is secreted in the stomach, is solely responsible for producing ulcers. Patients with duodenal ulcers do tend to have higher-than-normal levels of hydrochloric acid, but most patients with gastric ulcers have normal or lower-than-normal acid levels. Some stomach acid is important for protecting against H. pylori, the bacteria that causes most peptic ulcers. [Note: An exception is ulcers that occur in Zollinger-Ellison syndrome. This is a rare genetic condition in which very high levels of gastrin, a potent acid, are secreted by tumors in the pancreas or duodenum.]
Pepsin. Pepsin is an enzyme that breaks down proteins in food. Since the stomach and duodenum are also composed of protein, they are also susceptible to the actions of pepsin. Pepsin is, then, also important in the formation of ulcers.

Fortunately, the body has a defense system to protect the stomach and intestine against these powerful substances:

The mucous layer, which coats the stomach and duodenum, forms the first line of defense.
Bicarbonate, which the mucous layer secretes, neutralizes the digestive acids.
Hormone-like substances called prostaglandins help dilate the blood vessels in the stomach to ensure good blood flow and protect against injury. Prostaglandins are also believed to stimulate bicarbonate and mucus production.

Disrupting any of these defense mechanisms makes the stomach and intestine lining susceptible to the actions of acid and pepsin, increasing the risk for ulcers.

Causes

Before the discovery of the bacterium Helicobacter (H.) pylori, the stomach was believed to be a sterile environment. However, in 1982 two Australian scientists identified H. pylori as the main cause of stomach ulcers. They showed that inflammation of the stomach and stomach ulcers result from an infection of the stomach caused by the H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Price in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:

H. pylori's corkscrew shape enables it to penetrate the mucous layer of the stomach or duodenum so it can attach itself to the lining.
It survives in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.
H. pylori then produces a number of toxins and factors that can cause inflammation and damage to the lining, leading to ulcers in certain individuals.
It also alters certain immune factors that allow it to evade detection and cause persistent inflammation for a life -- even without invading the mucous membrane.

Even if ulcers do not develop, the bacterium is now considered to be a major cause of active chronic inflammation in the stomach (gastritis) and in the upper part of the small intestine (duodenitis).

It is also strongly linked to stomach (gastric) cancer and possibly other non-intestinal problems.

Factors that Trigger Ulcers in H. pylori Carriers.H. pylori is found in about 25% of people who do not have peptic ulcers. The magnitude of H. pylori infection, particularly in older people, may not always predict the presence or absence of peptic ulcers. Other variables must to be present to actually trigger ulcers. These may include:

Genetic Factors. Some people harbor genetic strains of H. pylori that may make the bacteria more dangerous and increase the risk for ulcers. The most intensively investigated genetic factor is cytotoxin-associated gene A (CagA), which has been associated with both gastric and duodenal ulcers, as well as with stomach cancer. Other genetic types that may also increase bacterial severity are called vacuolating cytotoxin (vacA) and antigen-binding adhesin (BabA) genotypes. Some of these genetic factors may be more or less important for development of ulcers, depending on ethnicity.
Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in the immune response of the intestine, which allow the bacteria to injure the lining.
Lifestyle Factors. Although lifestyle factors such as chronic stress, drinking coffee, and smoking were long believed to be primary causes of ulcers, it is now thought they only increase susceptibility to ulcers in some H. pylori carriers.
Shift Work and Other Causes of Interrupted Sleep. People who work the night shift have a significantly higher incidence of ulcers than day workers. Researchers suspect that frequent interruptions of sleep may weaken the ability of the immune system to protect against endotoxins.

When H. pylori was first identified as the major cause of peptic ulcers, it was found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori- associated ulcers has declined. For example, a 2001 study suggested that about half of ulcers are not caused by H. pylori. Instead, they tend to be caused by regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and other common pain relievers. Genetic factors or, rarely, Crohn's disease or Zollinger-Ellison syndrome, also cause ulcers.

Some researchers now believe that duodenal ulcers are not caused by H. pylori, but that the presence of the bacteria simply delays healing. This fact, they say, may explain why up to half of cases of acute duodenal perforation show no evidence of H. pylori, and why duodenal ulcers can recur even after H. pylori has been eradicated.

A 2006 study published in the Journal of Biological Chemistry indicates that a protein called decay-accelerating factor (DAF) acts as receptor for H. pylori. Animal studies show that blocking this interaction renders H. pylori harmless to the stomach. Researchers hope the discovery leads to new drugs that can reduce the risk of peptic ulcer.

Long-term use of NSAIDs is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. About 20 million people take prescription NSAIDs regularly, and more than 25 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn), although many others are available. Patients with NSAID-caused ulcers should stop taking these drugs.

There is no doubt NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding is continuous for as long as a patient takes these drugs and may persist for about one year after stopping. Short courses of NSAIDs for temporary pain relief should not cause major problems, because the stomach has time to recover and repair any damage that has occurred.

Specific NSAIDs pose greater or lesser risks for ulcers and bleeding. No NSAIDs, however, even over-the-counter brands, should be used long-term except under a doctor's direction.

Lowest Risk

Medium Risk

Highest Risk

Nabumetone (Relafen)

Etodolac (Lodine)

Salsalate

Sulindac (Clinoril)

Aspirin. Even low-dose ("baby") aspirin (81 mg) may pose some risk

Ibuprofen (Motrin, Advil, Nuprin, Rufen)

Naproxen (Aleve, Naprosyn, Naprelan, Anaprox)

Diclofenac (Voltaren), Tolmetin (Tolectin)

NOTE: Drugs in the medium risk group vary in risk. For example, studies show that naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding.

Flurbiprofen (Ansaid), Piroxicam (Feldene), Fenoprofen Indomethacin (Indocin), Meclofenamate (Meclomen)

Ketoprofen (Actron, Orudis KT). Note: Ketoprofen is often considered a medium-risk drug, but one study reported that taking the drug in low doses for as little as 1 week causes significant GI injury.

Certain drugs other than NSAIDs may cause or aggravate ulcers, particularly those taken for cardiovascular disease and its risk factors. A review of more than 306,000 primary care patients found that spironolactone, a common diuretic prescribed in heart failure, was associated with a 2.7% increased risk of ulcer or upper GI bleeding. Exacerbation of peptic ulcers is a rare but noted side effect of niacin, a drug that can reduce LDL cholesterol and raise HDL cholesterol. Low-dose aspirin, dipyridamole, and vitamin K antagonists such as Coumadin nearly double the risk of upper GI bleeding. When these drugs are used in combination, the risk soars.

Risk of GI perforation was seen in phase 3 clinical trials of bevacizumab, the first vascular endothelial growth factor agent (VEGF) approved by the FDA. This drug has been shown to increase survival and stop the progression of metastatic colorectal cancer when used in combination with chemotherapy. While the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, the drug must be discontinued.

The least common major cause of peptic ulcer disease is Zollinger-Ellison syndrome (ZES).

Rarely, certain conditions may cause ulceration in the stomach or intestine, including:

Radiation treatments
Bacterial or viral infections
Alcohol abuse
Physical injury
Burns

What is ZES? Zollinger-Ellison syndrome (ZES) is the least common major cause of peptic ulcer disease. In this condition, tumors in the pancreas and duodenum (gastrinomas) produce excessive amounts of gastrin, a hormone that stimulates gastric acid formation. These tumors are usually malignant, so proper and prompt management of the disease is essential.

Another cause of peptic ulcer, although far less common than H. pylori or NSAIDs, is Zollinger-Ellison syndrome. A large amount of excess acid is produced in response to the overproduction of the hormone gastrin, which in turn is caused by tumors on the pancreas or duodenum. These tumors are usually malignant, must be removed and acid production suppressed to relieve the recurrence of the ulcers.

Who Gets ZES? The incidence of ZES in the United States is estimated at 1 case per million people per year, and at 0.1 - 1% among patients with peptic ulcers. The mean age at onset is 45 - 50, and men are affected more often than women.

How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and have no history of NSAID use. Diarrhea may precede ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or the jejunum (the middle section of the small intestine) are signs of ZES. GERD is more prevalent and often more severe in patients with ZES, and can be complicated by ulcerations and strictures of the esophagus.

How Is ZES Treated? Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with an intravenous proton-pump inhibitor (Protonix). Previously, removing the stomach was the only option.

Symptoms

Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. Peptic ulcers can occur without dyspepsia or any other gastrointestinal symptom, especially when caused by NSAIDs. Dyspepsia may be persistent or recurrent and can encompass a variety of symptoms in the upper abdomen, including:

Pain or discomfort
Bloating
A feeling of fullness. People with severe dyspepsia are unable to drink as much fluid as people with mild or no dyspepsia.
Hunger and an empty feeling in the stomach, often 1 - 3 hours after a meal
Mild nausea (Vomiting, in fact, may relieve symptoms.)
Regurgitation (sensation of acid backing up into the throat.)
Belching

Ulcer Pain. The pain of ulcers can be either localized in one place or diffuse. The pain is described as a burning, gnawing, or aching in the upper abdomen, or as a stabbing pain penetrating through the gut. The symptoms may vary depending on the location of the ulcer:

Duodenal ulcers often cause a gnawing pain in the upper stomach area several hours after a meal, and the pain is often relieved by eating a meal.
Gastric ulcers may cause a dull, aching pain, often right after a meal; eating does not relieve the pain and may even worsen it. Pain may also occur at night.

Ulcer pain may be particularly confusing or disconcerting when it radiates to the back or to the chest behind the breastbone. In such cases it can be confused with other conditions such as heart attack.

Because ulcers can cause hidden bleeding, patients may experience the symptoms of anemia, including fatigue and shortness of breath.

A sudden onset of severe symptoms may indicate intestinal obstruction, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:

Tarry, black, or bloody stools
Severe vomiting, which may include blood or a substance with the appearance of coffee grounds (a sign of a serious hemorrhage) or entire stomach contents (sign of intestinal obstruction)
Severe abdominal pain with or without vomiting or evidence of blood

Anyone who experiences any of these symptoms should go to the emergency room immediately.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds or the presence of black tarry stools may indicate serious bleeding.

Complications

Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life.

Peptic ulcers caused by H. pylori or NSAIDs can be very serious if they hemorrhage or perforate the stomach or duodenum. Up to 15% of people with ulcers experience some degree of bleeding, which can be life-threatening. Ulcers that form where the small intestine joins the stomach can swell and scar, resulting in a narrowing or closing of the intestinal opening. In such cases, the patient will vomit the entire contents of the stomach, and emergency treatment is necessary.

Complications of peptic ulcers cause an estimated 6,500 deaths each year. These figures, however, do not reflect the high number of deaths associated with NSAID use. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori. NSAID-related bleeding and stomach problems may be responsible for as many as 107,000 hospital admissions and 16,500 deaths each year.

Because there are usually no GI symptoms from NSAID ulcers until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding. The risk for a poor outcome is highest in people who have had long-term bleeding from NSAIDs, blood clotting disorders, low systolic blood pressure, mental instability, or the presence of another serious, unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.

H. pylori is strongly associated with certain cancers. Some studies have also linked it to a number of non-gastrointestinal illnesses as well, although the evidence is inconsistent.

Stomach Cancers. Stomach cancer, also called gastric cancer, is the second most common cause of cancer worldwide. In developing countries where the rate of H. pylori is very high, the risk of stomach cancer is 6 times higher than in the U.S. An important 2001 study strongly supported previous work that found a causal link between H. pylori infection and stomach cancer. In this study, uninfected people did not develop stomach cancer. However, the stomach cancer rates for H. pylori-associated conditions were 4.7% for nonulcer dyspepsia, 3.4% for gastric ulcers, and 2.2% of stomach polyps. Experts now suggest that H. pylori may be as carcinogenic to the stomach as cigarette smoke is to the lungs.

Eradication of H. pylori may reduce the risk of stomach cancer, but not eliminate it. A Japanese study found that continued risk is associated with degree of mucosal atrophy before H. pylori eradication therapy is started. This is something than can be measured during an endoscopy.

The process most likely starts in childhood. Infection with H. pylori promotes a precancerous condition called atrophic gastritis. This may lead to cancer through the following steps:

The stomach becomes chronically inflamed and loses patches of glands that secrete protein and acid.
Acid protects against carcinogens, substances that cause cancerous changes in cells.
New cells replace destroyed cells, but the new cells do not produce enough acid to protect against carcinogens.
Over time, cancer cells may develop and proliferate in the stomach.

Onset of H. pylori infection in adulthood poses a lower risk, since the development of atrophic gastritis takes years, and an adult is likely to die of other causes first. Other factors, such as specific genetic strains and diets, might also influence a higher risk for stomach cancer. For example, a diet high in salt and low in fresh fruits and vegetables has been associated with a greater risk. Some evidence suggests that the virulent H. pylori strain called cytotoxin-associated gene A (CagA) may also be a particular risk factor for precancerous changes.

Interestingly, people with duodenal ulcers caused by H. pylori appear to have a lower risk of stomach cancer, although scientists do not know why. It may be that different H. pylori strains affect the duodenum and the stomach. Or, the high levels of acid found in the duodenum may help prevent the spread of the bacteria to critical areas of the stomach.

Pancreatic Cancer. H. pylori has recently been linked to pancreatic cancer. The excess risk is high in patients with unoperated gastric ulcers -- 20% after 15 years and 50% after the first hospitalization. Surgery decreased the risk dramatically. Unoperated duodenal ulcers, on the other hand, were not associated with increased risk of pancreatic cancer.

Heart Disease. Some research has reported a very high rate of H. pylori infection in men with coronary artery disease, but more recent work has found no relationship between the bacteria and heart disease. A 2001 study suggested that the only relationship between H. pylori and heart disease may be that people with both tend to be in lower socioeconomic groups. Further studies are needed.

Other Diseases. H. pylori has also been weakly associated with other nonintestinal disorders, including migraine, Raynaud's disease (marked by cold extremities), and some skin disorders, such as chronic hives.

Risk Factors

About 25 million people in the U.S. are expected to develop peptic ulcers at some point in their lives. Peptic ulcer disease affects all age groups, but is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise beginning around age 25 and continues until age 75; gastric ulcers peak at age 55 - 65.

Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas with widespread H. pylori infection. The increased use of proton-pump inhibitor drugs may be responsible for this trend.

H. pylori grows and colonizes only in the intestinal tracts of primates. The bacteria are most likely transmitted directly from person to person. Still, little is yet known about its transmission.

Who Is Infected with H. pylori? About half the world's adults are infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life, if not treated. The prevalence in children ranges from less than 10% to more than 80%, with the highest infection rates (3 - 10%) in developing countries and the lowest (0.5%) in industrialized nations, where rates continue to decline. Even in industrialized countries, however, infection rates in regions with crowded, unsanitary conditions are equal to those in developing countries.

How Does the Bacteria Pass from Person to Person? It is not entirely clear how the bacteria are transmitted. One study did not find that infected students posed any risk for their classmates. Transmission within families may be the most important route for H. pylori. A 2002 study reported that spouses of people with peptic ulcers are at significantly higher risk for ulcers, suggesting that the bacteria may be transmitted during intimate contact. Some evidence suggests that bacteria may spread during GI tract illness, particularly when vomiting occurs. The bacteria also may be passed in stools. Since H. pylori can live in water, but not apparently in food, the bacteria may also be transmitting through sewage-contaminated water.

Who Is at Risk for Ulcers from H. pylori? Although H. pylori infection is common, ulcers in children are very rare, and only a minority of infected adults develops ulcers. Some known risk factors include smoking, alcohol use, having a relative with peptic ulcers, being male, and the presence of the cytotoxin-associated gene A (CagA). Experts are unable to determine, however, any single factor or group of factors that can determine which infected patients are most likely to develop ulcers.

Between 15 - 25% of patients who have taken NSAIDs regularly will have evidence of one or more ulcers, but in most cases these ulcers are very small. Given the widespread use of NSAIDs, however, the potential total number of people who can develop serious problems may be very large. Long-term NSAID use can damage the stomach and, possibly, the small intestine.

In April 2005, the FDA asked manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes the increased risk for cardiovascular events and GI bleeding in people taking these drugs. (Pharmaceutical companies are trying to develop new COX-2 inhibitors without these dangerous side effects. Early safety studies of the novel COX-2 inhibitor known as CS-706 showed its effect on gastric mucosa to be the same as placebo.)

The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and GI risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Frequent Users of NSAIDs. Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems. Even low-dose aspirin (81 mg) may pose some risk, although the risk is lower than with standard doses. In one 4-year study, 4.5% of regular NSAID users were hospitalized for GI bleeding. The highest risk, however, was found in people who require long-term use of very high-dose NSAIDs, notably patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic stress.

Contributing Factors. Certain factors add to the risk for ulcers in NSAID-users:

Age 65 and older
History of peptic ulcers or upper gastrointestinal bleeding
Other serious ailments, such as congestive heart failure
Use of other medications, such as the anticoagulant warfarin (Coumadin), corticosteroids, or the osteoporosis drug alendronate (Fosamax)
Alcohol abuse
Those infected with H. pylori. A 2002 study reported that the combination of NSAID use and H. pylori posed a 3.5-fold greater risk of ulcers than either factor alone. However, not all studies have reported the higher risk in infected patients.

Stress and Psychological Factors. Although stress is no longer considered a cause of ulcers, studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing. Some experts estimate that social and psychological factors play a contributory role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. Some experts even believe that the anecdotal relationship between stress and ulcers is so strong that treatment of psychological factors is warranted.

Smoking. Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases mucosal blood flow. Results of studies on the actual effect of smoking on ulcers, however, are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of nonsmokers experienced a relapse of their ulcer disease after 1 year, but that all heavy smokers relapsed after 3 months. Other studies have found no increased risk for ulcers in smokers. In any case, any impact of smoking on ulcers does not seem to be affected by the presence of H. pylori.

Tobacco use and exposure may cause an acceleration of coronary artery disease and peptic ulcer disease. It is also linked to reproductive disturbances, esophageal reflux, hypertension, fetal illness and death, and delayed wound healing.

Diagnosis

Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Dyspepsia, however, occurs in 20 - 40% of people who live in industrialized nations, and only about 15 - 25% of these people actually have ulcers. A number of steps are needed to make an accurate diagnosis of ulcers.

The doctor will ask for a thorough report of a patient's dyspepsia and other important symptoms, such as weight loss or fatigue, present and past medication use (especially chronic use of NSAIDs), family members with ulcers, and drinking and smoking habits.

In addition to peptic ulcers, a number of conditions, notably gastroesophageal reflux disease (GERD) and irritable bowel syndrome, cause dyspepsia. Often, however, no cause can be determined. In such cases, the symptoms are referred to collectively as functional dyspepsia.

Peptic ulcer symptoms, particularly abdominal pain and chest pain, may resemble those of other conditions, such as gallstones or heart attack. Certain features may help to distinguish these different conditions. However, symptoms often overlap, and it is impossible to make a diagnosis based on symptoms alone. A number of tests are needed.

The following disorders may be confused with peptic ulcers:

GERD. About half of patients with GERD also have dyspepsia. With GERD or other problems in the esophagus, the main symptom is usually heartburn, a burning pain that radiates up to the throat. It typically develops after meals and is relieved by antacids. The patient may have difficulty swallowing and may experience regurgitation or acid reflux. Elderly patients with GERD are less likely to have these symptoms, but instead may experience loss of appetite, weight loss, anemia, vomiting, or dysphagia (difficulty or painful swallowing). [See In-Depth Report #85: Gastroesophageal Reflux Disease.]
Heart Events. Cardiac pain, such as angina or a heart attack, is more likely to occur with exercise and may radiate to the neck, jaw, or arms. In addition, patients typically have distinct risk factors for heart disease, such as a family history, smoking, high blood pressure, obesity, or high cholesterol. [See In-Depth Report #12: Heart Attack.]
Gallstones. The primary symptom in gallstones is typically a steady gripping or gnawing pain on the right side under the rib cage, which can be quite severe and can radiate to the upper back. Some patients experience pain behind the breastbone. The pain is often precipitated by a fatty or heavy meal, but gallstones almost never cause dyspepsia. [See In-Depth Report #10: Gallstones and Gallbladder Disease.]
Irritable Bowel Syndrome. Irritable bowel syndrome can cause dyspepsia, nausea and vomiting, bloating, and abdominal pain. It occurs more often in women than in men.

Dyspepsia may also occur with gastritis, stomach cancer, or as a side effect of certain drugs, including NSAIDs, antibiotics, iron, corticosteroids, theophylline, and calcium blockers.

When ulcers are suspected, the doctor will prescribe tests to detect bleeding. These may include a rectal exam, a complete blood count, and a fecal occult blood test (FOBT). The FOBT tests for hidden (occult) blood in stools. Typically, the patient is asked to supply up to 6 stool specimens in a specially prepared package. A small quantity of feces is smeared on treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Traditional radiology tests have not yet proven valuable for diagnosing ulcers. However, radiologists in France who performed multidetector computed tomography (MDCT) scans on preoperative patients with proven GI perforations found the technology to be highly accurate in pinpointing the location of the perforations.

Simple blood, breath, and stool tests can now detect H. pylori with a fairly high degree of accuracy. It is not entirely clear, however, which individuals should be screened for H. pylori.

Candidates for Screening. Some doctors currently test for H. pylori only in individuals with dyspepsia who also have high-risk conditions, such as:

Strong indication for ulcers, such as weight loss, anemia, or indications of bleeding
History of active ulcers
Risk factors for stomach cancer or other complications from ulcers

Smokers and those who experience regular and persistent pain on an empty stomach may also be good candidates for screening tests. Some doctors argue that testing for H. pylori may be beneficial for patients with dyspepsia who are regular NSAID users. In fact, given the possible risk for stomach cancer in H. pylori- infected people with dyspepsia, some experts now recommend that any patient with dyspepsia lasting longer than 4 weeks should have a blood test for H. pylori. This is a subject of considerable debate, however.

Specific Screening Tests for H. pylori. The following screening tests used or under investigation for H. pylori:

Breath Test. A simple test called the carbon isotope-urea breath test (UBT) can identify up to 99% of people who harbor H. pylori. Up to 2 weeks before the test, the patient must discontinue taking any antibiotics, bismuth-containing agents such as Pepto-Bismol, and proton-pump inhibitors (PPIs). As part of the test, the patient swallows a special substance containing urea (a compound in mammals metabolized from nitrogen) that has been treated with carbon atoms. If H. pylori is present, the bacteria convert the urea into carbon dioxide, which is detected and recorded in the patient's exhaled breath after 10 minutes.
Blood Tests. Blood tests are used to measure antibodies to H. pylori, with results available in minutes. Diagnostic accuracy is reported at 80 - 90%. One such important test is called enzyme-linked immunosorbent assay (ELISA). An ELISA test of the urine is also showing promise in children.
Stool Test. A test to detect genetic fingerprints of H. pylori in the feces appears to be as accurate as the breath test for initial detection of the bacteria and for detecting recurrences after antibiotic therapy.

It should be noted that such tests are not as accurate as endoscopy, an invasive procedure, which is needed to confirm a diagnosis of H. pylori. The breath and stool tests, however, can be particularly useful after treatment to determine if a patient has been cured.

Test and Treat. Depending on the results of the screening tests, some doctors take the following steps:

Approach for Noninfected Individuals. People who do not have evidence of H. pylori on a blood or breath test are typically given a 4-week course of acid-suppressing medication, usually a PPI such as omeprazole (Prilosec).
Approach for H. pylori-Infected Individuals. Patients with evidence of bacterial infection are given antibiotics. If this does not relieve symptoms, they are given a 6-week course of the PPI omeprazole (Prilosec). (Whether to give antibiotics to infected patients with non-ulcer dyspepsia is controversial and is discussed in the section, What Are the Guidelines for Treating Peptic Ulcers Caused by H. pylori?)

If symptoms persist, endoscopy is usually performed. Endoscopy is an invasive procedure, but is the only procedure in which a biopsy of stomach tissue can be taken, making it the most accurate test.

Experts debate whether endoscopy should be performed on all patients who do not respond to initial medication, since it does not appear to add any useful information on treatment choices, unless there is evidence or suspicion of bleeding or serious complications.

While endoscopy is the gold standard for diagnosing upper GI disorders, because it allows doctors to biopsy the stomach, 3-dimensional CT imaging may also be valuable. Researchers in China compared the results of endoscopy to the results of noninvasive CT imaging performed to diagnose GI disease. They found that the CT imaging correctly diagnosed 50 of 52 cases, including 5 cases of peptic ulcer disease. Three-dimensional CT imaging clearly showed the GI tract lesions. It is currently considered a valuable complement to endoscopy.

Endoscopy is a procedure used to evaluate the esophagus, stomach, and duodenum using a long, thin tube tipped with a tiny video camera (endoscope). When combined with biopsy, endoscopy is the most accurate procedure for detecting the presence of peptic ulcers, bleeding, and stomach cancer, or for confirming the presence of H. pylori.

Appropriate Candidates for Endoscopy. Because endoscopy is invasive and expensive, it is unsuitable for screening everyone with dyspepsia. Most individuals with these symptoms are managed effectively without endoscopy. Endoscopy is usually reserved for patients with dyspepsia who also have risk factors for ulcers, stomach cancer, or both. Such factors include the following:

Having so-called "alarm" symptoms (unexplained weight loss, gastrointestinal bleeding, vomiting, difficulty swallowing, or anemia).
Being over 45 (when the risk for stomach cancer increases).

There is some debate whether patients under 45 with persistent dyspepsia and no alarm symptoms should have endoscopy.

The Procedure. Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center, and typically involves the following:

The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and relax the patient.
The doctor then places the thin, flexible plastic tube into the patient's mouth and down the esophagus into the stomach.
A tiny camera in the endoscope allows the doctor to see the surface of the esophagus, stomach, and duodenum, and to search for abnormalities.
The doctor will remove about 10 small tissue samples (biopsies), which will be tested for H. pylori.

In endoscopy, the doctor places a long, thin, flexible tube (called an endoscope) down the patient's throat and into the stomach and duodenum. A camera and light on the tip of the endoscope enables the doctor to check for abnormalities. Tiny samples may be taken to check for H. pylori bacteria, a cause of many peptic ulcers. If a bleeding ulcer is found, it may be sealed with a burning tool (cauterized) during the procedure.

Note: Some evidence suggests that patients who take PPIs should stop taking the medication 2 weeks before an endoscopy, since it may mask ulcers.

Capsule Endoscopy.Capsule endoscopy involves swallowing a capsule the size of a large vitamin, which contains tiny camera, light source, and radio transmitter. The device takes pictures as it passes through the intestinal tract. At this point, its benefits are limited to the small intestine, so it is unlikely to play a role in the diagnosis of peptic or gastric ulcers. However, capsule endoscopy has the potential to be an important tool for the diagnosis of obscure upper GI bleeding. Patients who have used it have usually found it painless and preferable to conventional endoscopy.

An upper GI (gastrointestinal) series was the standard diagnostic method for peptic ulcers until the introduction of adequate tests for detecting H. pylori. In an upper GI series, the patient drinks a solution containing barium. X-rays are then taken, which may reveal inflammation, active ulcer craters, or deformities and scarring due to previous ulcers. Endoscopy is more accurate, although it is more invasive and expensive.

Click the icon to see an illustrated series detailing treatment of GI bleeding.

Stool tests may show traces of blood that are not visible to the naked eye, and blood tests may reveal anemia in those who have bleeding ulcers. If Zollinger-Ellison syndrome is suspected, blood levels of gastrin should be measured.

Treatment

Antibiotic regimens that eradicate H. pylori can cure peptic ulcers and are now the standard medications used for ulcers in infected individuals who are not taking NSAIDs. Eliminating H. pylori can also cure the rare MALT lymphomas caused by this bacterium. Other drugs, such as proton-pump inhibitors or H2 blockers, are useful for relieving ulcer symptoms.

Patients with Clear Evidence of Ulcers. Antibiotics are clearly indicated for patients who have both ulcers and H. pylori infection. Despite such clear indications, however, European and American studies continue to suggest that many doctors only treat symptoms and not the ulcers themselves. Studies also suggest that most doctors do not counsel patients on the potential dangers of NSAIDs and other drugs that can cause ulcers.

There is considerable debate about whether to test for H. pylori and treat infected patients who have dyspepsia, but no evidence of ulcers.

The best approach for treating dyspepsia is highly controversial. Options include the following:

Test and Treat. This approach involves testing for H. pylori and eradicating the bacteria in infected patients.
Prescribing potent acid-suppressing agents. This approach generally employs a trial of potent acid-suppressing drugs called proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) or esomeprazole (Nexium).

In either case, endoscopy is usually performed if symptoms persist after 4 weeks. Some evidence suggests that PPIs may mask ulcers, so patients taking these drugs may need to discontinue them for 2 weeks before endoscopy.

Arguments for Testing and Treating Patients with Dyspepsia. The argument supporting testing and treating patients with nonulcer dyspepsia is as follows:

Protection against ulcers. Some evidence suggests that antibiotic treatments for infected patients with dyspepsia may prevent ulcers from developing. A 2002 study found that antibiotic regimens to eradicate H. pylori greatly decreased the likelihood of ulcers in infected patients with nonulcer dyspepsia who were chronic NSAID users.
Protection against gastric cancer. Some evidence suggests that eradicating H. pylori may prevent or delay the onset of stomach cancer in people with long-term dyspepsia who are infected with the bacteria. A large 2001 study conducted in Japan, where gastric cancer is especially common, found that such cancers developed in about 3% of infected patients with nonulcer dyspepsia. However, none occurred in dyspeptic patients who were treated with antibiotics for H. pylori.

Arguments against Testing and Treating Patients with Dyspepsia. The arguments against testing and treating are as follows:

Lack of significant effect on symptoms. Studies are mixed on whether antibiotics have much effect on dyspepsia symptoms. In a 2003 study, overall symptom scores after 1 year were not significantly different between dyspeptic patients who were treated for H. pylori and patients who were maintained on PPIs.
Lower rates of H. pylori in the U.S. The number of people with H. pylori infection is declining in the U.S., possibly making the test-and-treat approach too expensive for the number of people it helps.
Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating H. pylori may also have other adverse effects.
Overuse of antibiotics. Concern that such treatments without clear evidence of ulcers will lead to unnecessary antibiotic prescriptions, increasing the risk for side effects. Overuse may also contribute to a growing public health problem -- the emergence of bacteria that are resistant to antibiotics.

The standard treatment regimen for H. pylori uses 2 antibiotics and a PPI. Cure rates after antibiotic treatment range from 70 - 90%. A typical regimen contains three drugs:

A PPI. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). PPIs are important for all types of peptic ulcers, and are a critical partner in antibiotic regimens. They reduce acidity in the intestinal tract, and increase the ability of antibiotics to destroy H. pylori.
Two antibiotics. The standard antibiotics are clarithromycin (Biaxin) and amoxicillin. Some doctors substitute the antibiotic metronidazole (Flagyl) for either clarithromycin or amoxicillin.

This combination treatment is typically taken for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well. A report published in 2006 evaluated a shorter course of treatment using the PPI rabeprazole and 2 antibiotics. They found that a 4-day treatment eliminated H. pylori and was associated with fewer side effects. A study published in 2007 comparing 1- and 2-week treatments with amoxicillin, clarithromycin, and omeprazole for H. pylori eradication found both regimens to be similar in efficacy, safety, and compliance.

Interestingly, an Italian study indicated that giving antibiotics sequentially instead of at the same time may be even more effective. The researchers found that patients who took amoxicillin for 5 days, followed by clarithromycin for 5 days, had higher H. pylori eradication rates (89%) than those who took both antibiotics for 10 days (77%).

A 2007 study showed that eradication rates with this 3-drug regimen could be improved, and side effects reduced, by adding probiotics ("good" bacteria) and the milk protein bovine lactoferrin. These products are often found in yogurts and other forms of fermented milk.

Follow-Up. Follow-up testing for the bacteria should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.

In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate success, nor does persistence of dyspepsia necessarily mean that treatment has failed. Heartburn and other symptoms from GERD, for example, can worsen and require acid-suppressing medication.

Failure. Treatment fails in about 15% of patients, mostly when they fail to adhere to the regimen. Compliance with standard antibiotic regimens may be poor for the following reasons:

The triple-drug regimens are complicated and require many pills. Helicide or two-drug combinations may help offset this problem.
About 30% of patients suffer side effects from the H. pylori regimen. Gastrointestinal problems are very common, and severe diarrhea can occur.

Treatment may also fail if the patients harbor strains of H. pylori that are resistant to the antibiotics. When this happens, different drugs are tried.

Reinfection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Reinfection with the bacteria is possible, however, in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%.

Weight Gain. Some patients may gain weight.

Gastroesophageal Reflux Disease. Of ongoing interest are reports of a lower incidence of H. pylori in patients with GERD. There are some important unanswered questions associated with this issue:

Is the lower incidence of H. pylori in GERD patients significant, and does the bacteria actually protect against GERD? Studies have not conclusively found any significant risk for GERD in people who are not infected with H. pylori, except possibly in certain regions. In a 2003 study, the absence of H. pylori infection in people with GERD was more pronounced in Asian patients than in those from Europe and North America. That being said, guidelines for eradication of H. pylori infection published in 2007 by the European Helicobacter Study Group state that "Eradication of H. pylori infection does not cause gastroesophageal reflux disease (GERD) or exacerbate GERD, and may prevent peptic ulcer in patients who are naive users of NSAIDs."
Does eliminating the bacteria with antibiotic therapy actually produce GERD in some people? One study observed that patients cured of H. pylori infection were twice as likely to develop GERD as those who remained infected. However, a 2003 analysis of 8 studies reported no higher risk for GERD after antibiotic treatments. In addition, GERD patients did not experience worsening of symptoms. Longer follow-up studies are needed however to determine the long-term consequences, if any.
What is the proper management of people who have GERD and H. pylori infection? Patients with severe GERD usually require on-going therapy with PPIs, which are powerful acid-suppressors. Some evidence suggests that in such patients, the combination of H. pylori and chronic acid suppression may lead to atrophic gastritis, a precancerous condition in the stomach. Guidelines then advocate eliminating the bacteria with antibiotics. There is some concern that once the bacteria are eliminated, however, GERD may worsen, which can pose a risk for Barrett's esophagus, which is also a precancerous condition. On the encouraging side, however, evidence to date does not suggest any higher risk for more serious GERD complications after H. pylori is eliminated.

Effects on Other Gastrointestinal Infections. In children, there is some evidence that H. pylori protects against E. coli and other GI infections, particularly those that cause diarrhea. If this is true, treating infected children for H. pylori should be done only if the bacteria are causing harm.

Click the icon to see an animation on ulcer treatment.

Treatment for NSAID-Induced Ulcers

Preventing Ulcers or Rebleeding Caused by NSAIDs. If NSAID-caused ulcers or bleeding are identified, patients should:

Get tested for H. pylori and, if they are infected, take antibiotics.
Possibly use a PPI. Studies suggest these medications lower the risk for NSAID-caused ulcers, although they do not completely prevent them.

People who still need to take NSAIDs should:

Use the lowest NSAID dose possible.
Try the prescription drugs misoprostol (Cytotec) or Arthrotec. Misoprostol works as well as a PPI, however, it has many side effects. Arthrotec is a combination of misoprostol and the NSAID diclofenac.

A warning to women: misoprostol can induce labor at any stage of pregnancy. Pregnant women should not use the drug.

Healing Existing Ulcers. A number of drugs are used to treat NSAID-caused ulcers. PPIs -- omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium) -- are used most often. Other drugs that may be useful include H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), and ranitidine (Zantac). Sucralfate is another drug used to heal ulcers and reduce the stomach upset caused by NSAIDs.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs, while causing less gastrointestinal distress. However, following numerous reports of cardiovascular events, the FDA banned rofecoxib (Vioxx) and valdecoxib (Bextra) from use in the U.S. Celecoxib (Celebrex) is still available, but patients should discuss with their doctor whether this drug is appropriate and safe for them.

Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac. It may reduce the risk for gastrointestinal bleeding. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Acetaminophen. Acetaminophen (Tylenol, Anacin-3) is the most common alternative to NSAIDs. Acetaminophen is inexpensive and generally safe. It poses far less of a risk of gastrointestinal problems than NSAIDs. It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg); some studies suggest that ulcer risk is increased even in doses exceeding 2 grams (2,000 mg) a day, if the drug is used on a long-term basis. Patients who take high doses of acetaminophen for long periods are also at risk for liver damage, particularly if they drink alcohol. It may pose a small risk for serious kidney complications in people with preexisting kidney disease, although acetaminophen remains the drug of choice for patients with impaired kidney function.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, dependence and abuse have been reported. It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these agents.

Medications

The following drugs are sometimes used in the treatments of peptic ulcers caused by either NSAIDs or H. pylori. They are described in alphabetical order.

Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild dyspepsia. They play no major role in either the prevention or healing of ulcers, but help in the following ways:

All rely on various combinations of three basic compounds -- magnesium, calcium, or aluminum -- to neutralize stomach acid.
They may defend the stomach by increasing acid-buffering bicarbonate and mucus secretion.

It is generally believed that liquid antacids work faster and are more potent than tablets, although some evidence suggests that both forms work equally well.

Basic Salts Used in Antacids. There are three basic salts used in antacids:

Magnesium. Magnesium compounds are available in the form of magnesium carbonate, magnesium trisilicate, and, most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of these magnesium compounds is diarrhea.
Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid-acting antacid, but it can cause constipation. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. Hypercalcemia can lead to kidney failure.
Aluminum. The most common side effect of antacids containing aluminum compounds (Amphogel, Alternagel) is constipation. Maalox and Mylanta are combinations of aluminum and magnesium, which balance the side effects of diarrhea and constipation. People who take large amounts of antacids containing aluminum may be at risk for calcium loss and osteoporosis. Long-term use also increases the risk of kidney stones. People who have recently experienced GI bleeding should not use aluminum compounds.

Interactions with Other Drugs. Antacids can reduce the absorption of a number of drugs. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking these other drugs 1 hour before or 3 hours after taking the antacid.

Drugs that are absorbed less well if taken with antacids

Drugs that are made more potent by antacids

Tetracycline

Ciprofloxacin (Cipro)

Propranolol (Inderal)

Captopril (Capoten)

Ranitidine (Zantac)

Famotidine (Pepcid AC)

Valproic acid

Sulfonylureas

Quinidine

Levodopa

H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin, and to antibiotics in the macrolide class, such as clarithromycin. Either type of agent serves effectively as a second antibiotic in a three-drug regimen. Other antibiotics that are sometimes used include tetracycline, metronidazole, and ciprofloxacin.

Amoxicillin is the most common form of penicillin. It is inexpensive, but many people are allergic to it.
Clarithromycin (Biaxin) is a macrolide and is the most expensive antibiotic used against H. pylori. It is very effective, but there is growing bacterial resistance to this drug. Resistance rates tend to be higher in women and increase with age. Researchers fear that resistance will increase as more people use the drug.
Tetracycline is effective, but this medicine has unique side effects, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration. Pregnant women cannot take tetracycline.
Ciprofloxacin (Cipro), a fluoroquinolone, is also sometimes used in ulcer regimens.
Metronidazole (Flagyl) was the mainstay in initial combination regimens for H. pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug. Today, about 25 - 35% of H. pylori bacteria are metronidazole-resistant.

Side Effects of Antibiotics.

The most common side effects of nearly all antibiotics are gastrointestinal problems such as cramps, nausea, vomiting, and diarrhea.
Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare, but severe -- even life-threatening -- anaphylactic shock.
Some drugs, including certain over-the-counter medications, interact with antibiotics; patients should report to all medications they are taking to their doctor.
Antibiotics double the risk of vaginal infections in women.

Compounds that contain bismuth are often used in the three-drug antibiotic regimens. They destroy the cell walls of H. pylori bacteria. The only bismuth compound available in the U.S. has been bismuth subsalicylate (Pepto-Bismol), although a drug combination of the H2 blocker ranitidine and bismuth citrate (Tritec) has been released. High doses can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.

H2 blockers interfere with acid production by blocking histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.

Four H2 blockers are currently available over-the-counter in the U.S.: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. There are some differences between these drugs:

Famotidine (Pepcid AC). Famotidine is the most potent H2 blocker. The most common side effect is headache, which occurs in 4. 7% of people who take it. Famotidine is virtually free of drug interactions, but it may have significant adverse effects in patients with kidney problems.
Cimetidine (Tagamet). Cimetidine has few side effects; about 1% of people taking cimetidine experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, including phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.
Ranitidine (Zantac). Ranitidine interacts with very few drugs. In one study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people younger than age 60, but there was no difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of people who take it.

That being said, a literature review of clinical trials showed that the PPIs are more effective than the H2 blockers in healing ulcers in people who take NSAIDs. After 8 weeks of treatment, healing rates of both gastric and duodenal ulcers were:

92% and 88% with esomeprazole 40 mg and 20 mg (vs 74% with ranitidine).
87% and 84% with omeprazole 40 mg and 20 mg (vs 64% with ranitidine).
And 73 - 74% and 66 - 69% with lansoprazole 30 mg and 15 mg (vs 50 - 53% with ranitidine).
However, healing rates with ranitidine reached nearly 100% when NSAIDs were discontinued.

Nizatidine (Axid). Nizatidine is nearly free of side effects and drug interactions.

Long-Term Concerns. In most cases, these H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs, be sure to tell your doctor about any other drugs you are taking. There are also some concerns about possible long-term effects -- for example, that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infection. More research is needed. However, the following concerns are real:

Liver damage. This is more likely with ranitidine than other H2 blockers, but is rare in any event.
Kidney-related complications. With famotidine, adverse effects on the central nervous system in patients with even moderate kidney insufficiency have been reported, resulting in anxiety, depression, and mental disturbances.
Increased risk for pneumonia in hospitalized patients.
Ulcer perforation and bleeding. Some experts are concerned that the use of acid-blocking drugs may actually increase the risk for serious complications by masking the ulcer's symptoms.

Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major intestinal toxicity of NSAIDs.

Actions against Ulcers. Misoprostol can reduce formation of ulcers in the upper small intestine by two-thirds and in the stomach by three-fourths. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful in healing existing ulcers.

Side Effects.

Diarrhea and other gastrointestinal problems are severe enough to cause 20% of patients to stop taking the drug. Taking misoprostol after meals should minimize these effects. One study indicated that taking the drug 2 - 3 times a day, instead of the standard regimen of 4 times, may prove to be just as effective and cause fewer side effects.
Misoprostol can induce abortion or cause birth defects and should not be taken by pregnant women. If pregnancy occurs during treatment, the drug should be discontinued at once and the doctor contacted immediately.

Actions against Ulcers. PPIs are the drugs of choice for managing patients with peptic ulcers from any cause. They suppress the production of stomach acid by blocking the gastric acid pump -- the molecule in the stomach glands that is responsible for acid secretion.

PPIs can be used either as part of a multidrug regimen for H. pylori or alone for preventing and healing NSAID-caused ulcers. One retrospective study found that adding a PPI to diclofenac therapy reduced hospitalization for ulcers by 60%. They are also useful in treating ulcers caused by Zollinger-Ellison syndrome. Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18 - 20% of people of Asian descent.

Standard Brands. Most PPIs are available by prescription as oral drugs. There is no evidence that one brand of PPI works better than another. Brands approved for ulcer prevention and treatment include:

Omeprazole (generic, Prilosec OTC)
Esomeprazole (Nexium)
Lansoprazole (Prevacid)
Rabeprazole (Aciphex)

Possible Adverse Effects.

Side effects are uncommon, but may include headache, diarrhea, constipation, nausea, and itching.
Pregnant women and nursing mothers should avoid taking PPIs, although recent studies suggest that these drugs do not increase the risk of birth defects.
PPIs may interact with certain drugs, such as antiseizure agents (such as phenytoin), antianxiety drugs (such as diazepam), and blood thinners (such as warfarin).
Long-term use of high-dose PPIs may produce vitamin B12 deficiency, but studies are needed to confirm this risk.
In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in stomach cancer with long-term use of these drugs.

Sucralfate (Carafate) seems to work by adhering to the ulcer crater and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. Sucralfate has an ulcer-healing rate similar to that of H2 blockers. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate does interact with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Treatment for Bleeding Ulcers

When a patient comes to the hospital with bleeding ulcers, endoscopy is usually performed. This procedure is critical for the diagnosis, determination of treatment options, and treatment of bleeding ulcers.

In high-risk patients or those with evidence of bleeding, options include watchful waiting with medical treatments or surgery. The first critical steps for massive bleeding are to stabilize the patient and support vital functions with fluid replacement and possibly blood transfusions. People on NSAIDs should discontinue them, if possible.

Depending on the intensity of the bleeding, patients can be released from the hospital within a day or kept up to 3 days after endoscopy. Bleeding stops spontaneously in about 70 - 80% of patients, but about 30% of patients who come to the hospital for bleeding ulcers need surgery. Endoscopy is the surgical procedure most often used for treating bleeding ulcers and patients at high-risk for rebleeding. It is usually combined with medications, such as epinephrine and intravenous proton-pump inhibitors.

Between 10 - 20% of patients require more invasive procedures for bleeding, usually major abdominal surgery.

Endoscopy is important for both diagnosing and treating bleeding ulcers. The doctor first places a thin, flexible plastic tube called an endoscope into the patient's mouth and down the esophagus into the stomach.

Endoscopy for Diagnosing Bleeding Ulcers and Determining Risk of Rebleeding. With endoscopy, doctors are able to detect the signs of bleeding, such as active spurting or oozing of blood from arteries. Endoscopy can also detect specific features in the ulcers referred to as stigmata, which indicate a higher or lower risk of rebleeding.

Such features include the following:

Low risk (5 -15%) for bleeding: flat dot; a clean or white base.
High risk (30 - 50%) for bleeding: swollen but nonbleeding blood vessels; blood clots that adhere to ulcers.
According to one study, if patients with these high-risk features are untreated, their risk for rebleeding after endoscopy ranges from about 10% on the first day after endoscopy to about 3% by the third day. Identifying and treating patients with stigmata can reduce these risks. Other factors that increase the risk for rebleeding include bleeding disorders, very low blood pressure, other serious medical conditions, and bleeding that started after hospitalization.
After endoscopy, high-dose PPI therapy has been shown to significantly reduce the rate of rebleeding, need for surgery, and death from hemorrhage. The medication may be given intravenously, but studies show that oral PPI therapy is probably just as effective.

Endoscopy as Treatment. Endoscopy is usually used to treat bleeding from visible vessels that are less than 2 mm in diameter. This approach also appears to be very effective in preventing rebleeding in patients whose ulcers are not bleeding, but who have high-risk features (swollen blood vessels or clots adhering to ulcers).

The following is a typical endoscopy procedure:

The surgeon passes a probe through an endoscopic tube and applies electricity, heat, or small clips to coagulate the blood and stop the bleeding. This procedure also causes fluid buildup, which helps to compress the blood vessels.
In high-risk cases, the doctor may inject epinephrine (commonly known as adrenaline) directly into the ulcer to enhance the effects of the heating process. Epinephrine activates the process leading to blood coagulation, narrows the arteries, and enhances blood clotting.
Intravenous (IV) administration of a PPI (usually omeprazole or pantoprazole) significantly prevents rebleeding and appears to be cost-effective. In one study, the use of IV PPIs reduced the risk of bleeding from 23% to 7%. (Oral PPIs are also effective, but studies are needed to compare their effectiveness versus IV PPIs.) A PPI may also be useful for initial bleeding episodes when endoscopy is unsuccessful, inappropriate, or unavailable.

Intravenous H2 blockers are often used, but a major analysis reported no benefit in bleeding duodenal ulcers, although they may be effective in gastric ulcers.

Endoscopy is effective in controlling bleeding in more than 85% of appropriate candidates. If rebleeding occurs, a repeat endoscopy is effective in about 75% of patients. Those who fail to respond require major abdominal surgery. The most serious complication from endoscopy is perforation of the stomach or intestinal wall, which occurred in about 1.4% of patients in a large 2002 study.

While endoscopy and clipping are routine treatment for bleeding ulcers in the U.S., a Korean study found little difference in outcomes between clipping (plus H2 therapy) and oral PPI therapy alone. In a randomized test of 129 patients, hemostasis (end of bleeding) was achieved in 93.5% of patients after clipping and 92.5% of patients on oral PPIs at 24 hours. The rate of rebleeding was 6.9% with clipping and 7.5% with PPIs.

Other Medical Considerations. Certain agents may be warranted after endoscopy:

Patients who harbor the H. pylori bacteria, even when the bleeding has been caused by NSAID use, should be treated with antibiotic therapy to eliminate the bacteria. Triple therapy, including antibiotics, to eliminate H. pylori immediately after endoscopy is warranted in most patients infected with the bacteria.
Somatostatin (a hormone used to prevent bleeding in cirrhosis) is also useful for reducing persistent peptic ulcer bleeding or the risk of recurrence. Researchers are investigating adding other therapies, such as fibrin glue, a blood clotting factor. To date, no therapy has proven to be more effective than current treatments.

Major abdominal surgery for bleeding ulcers is now generally performed only when endoscopy fails or is not appropriate. Certain emergencies may require surgical repair, such as when an ulcer perforates the wall of the stomach or intestine, causing sudden intense pain and life-threatening infection.

Surgical Approaches. The standard major surgical approach uses a wide abdominal incision and standard surgical instruments (called open surgery). Laparoscopic techniques employ small abdominal incisions and the insertion of tubes that contain miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers. Surgery is not effective for upper GI ulceration caused by chronic NSAID use.

Major Surgical Procedures. There are a number of surgical procedures aimed at long-term relief of ulcer complications. These include:

Click the icon to see an illustrated series detailing a gastrectomy procedure.

Vagotomy, in which the vagus nerve is cut to interrupt messages from the brain that stimulate acid secretion in the stomach. This surgery may impair stomach emptying. A recent variation that cuts only parts of the nerve may reduce this complication.
Antrectomy, in which the lower part of the stomach is removed. This part manufactures the hormone responsible for stimulation of digestive juices.
Pyloroplasty, which enlarges the opening into the small intestine so that stomach contents can pass into it more easily.

Antrectomy and pyloroplasty are usually performed with vagotomy.

Lifestyle Changes

In the past, it was common practice to tell people suffering from peptic ulcers to consume small, frequent amounts of bland foods. Exhaustive research conducted since that time has shown that a bland diet is not effective in reducing the incidence or recurrence of ulcers, and that eating numerous small meals throughout the day is no more effective than eating three meals a day. Large amounts of food should still be avoided, because stretching the stomach can result in painful symptoms.

Fruits and Vegetables. The good news is that a diet rich in fiber may cut the risk of developing ulcers in half and speed healing of existing ulcers. Fiber found in fruits and vegetables is particularly protective; vitamin A contained in many of these foods may increase the benefit. Some studies on associations between specific food chemicals and ulcers are as follows:

In one study, apples and yams appeared to be especially helpful.
Apples, celery, cranberries, onions, red wine, and green and black tea are also high in natural chemicals known as flavonoids, which appear to inhibit H. pylori growth and have many other health benefits. Cranberry juice specifically may have properties that help prevent H. pylori from infecting the intestinal lining.
Grapefruit has antioxidant properties that may help heal ulcers.
Studies on rats have found that dietary nitrate increases nitric oxide in the gut and causes the mucus layer to thicken. Pretreatment with nitrate provided dramatic protection against diclofenac-induced ulcers. High levels of dietary nitrate are found in many vegetables.
Laboratory experiments suggest that sulforaphone, a compound found in broccoli and broccoli sprouts, may be lethal to even drug-resistant strains of H. pylori.
Tea has chemicals that may help protect against cancers in the stomach and esophagus.

Milk. Milk actually encourages the production of acid in the stomach, although moderate amounts (2 - 3 cups a day) appear to do no harm. Animal studies show that a milk protein called bovine alpha-lactalbumin protects against gastric ulcers caused by stress. Certain probiotics, which are "good" bacteria added to yogurt and other fermented milk drinks, may also have gastric protective qualities.

Coffee and Carbonated Beverages. Coffee (both caffeinated and decaffeinated), soft drinks, and fruit juices with citric acid increase stomach acid production. Although no studies have proven that any of these drinks contribute to ulcers, consuming more than 3 cups of coffee per day may increase susceptibility to H. pylori infection.

Spices and Peppers. Studies conducted on spices and peppers have yielded conflicting results. The rule of thumb is to use these substances moderately, and to avoid them if they irritate the stomach.

Garlic. Some studies suggest that high amounts of garlic may have some protective properties against stomach cancer, although a recent study concluded that it offered no benefits against H. pylori and, in high amounts, can cause considerable GI distress.

Olive Oil. Studies from Spain have shown that phenolic compounds in virgin olive oil may have strong bactericidal activity against 8 strains of H. pylori, 3 of which are resistant to antibiotics.

Vitamins. Although no vitamins have been shown to protect against ulcers, H. pylori appears to impair absorption of vitamin C, which may play a role in the higher risk of stomach cancer.

Some evidence exists that exercise may help reduce the risk for ulcers in some people. In one study, exercise was associated with a lower risk for duodenal, but not gastric, ulcers in men. In this study, exercise appeared to have no effect on ulcer development in women.

Stress relief programs have not been shown to promote ulcer healing, but they may have other health benefits.

Melatonin is a hormone found in the brain that is normally associated with sleep. Researchers have observed that the GI tract is rich in melatonin, and that the hormone may have properties that help prevent ulcers, reduce acid secretion, and improve blood flow. It is not known whether this would benefit people with peptic ulcers, but it appears to warrant some research. In the U.S., melatonin is classified as a dietary supplement and not a drug, so its quality and effectiveness are uncontrolled. The U.S. is the only developed nation that does not regulate this agent.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology

References

deBortoli M, Leonardi G, Ciancia E, et al. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J. Gastroenterol. 2007;102(5):951-956.

Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007;99(6A):22C-31C.

Hainaux B, Agneessens E, Bertinotti R, et al. Accuracy of MDCT in predicting site of gastrointestinal tract perforation. Am J Roentgenol. 2006;187(5):1179-1183.

Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMS. 2006;333(7571):726. Epub 2006 Sept 19.

Hobsley M, Tovey F, Horton J. Precise role of H. pylori in duodenal ulceration. World J Gastroenterol. 2006;12(40):6413-6419.

Goer A, Gothe H, Schiffhorst G, Sterzel A, Grass U, Haussler B. Comparison of the effects of diclofenac or other non-steroidal anti-inflammatory drugs (NSAIDs) and dicolfenac or other NSAIDs in combination with proton pump inhibitors (PPI) on hospitalization due to peptic ulcer disease. Pharmacoepidemiol Drug Saf. 2007 Feb 26 [Epub ahead of print].

Jansson EA, Petersson J, Reinders C, et al. Protection from nonsteroidal anti-inflammatory (NSAID)-induced gastric ulcers by dietary nitrate. Free Radic Biol Med. 2007;41(4):510-518.

Keefer L, Stepanski EJ, Ranjbaran Z, Benson LM, Keshavarzian A. An initial report of sleep disturbance in inactive inflammatory bowel disease. J Clin Sleep Med. 2006;2(4):409-416.

Kim JI, Cheung DY, Cho SH, et al. Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding peptic ulcer: a prospective, randomized, controlled trial. Dig Dis Sci. 2007 May 19 [Epub ahead of print].

Luo J, Nordenvall C, Nyren O, Adami HO, Permert J, Ye W. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007;120(2):368-372.

Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastrict III Consensus Report. Gut. 2007;56(6):772-781.

Miki K, Urita Y, Ishikawa F, et al. Effect of Bifidobacterium bifidum fermented milk on Helicobacter pylori and serum pepsinogen levels in humans. J Dairy Sci. 2007;90(6):2630-2640.

Moberly JB, Harris SI, Diff DS, et al. A randomized, double-blind, one-week study comparing the effects of a novel COX-2 inhibitor and naproxen on the gastric mucosa. Dig Dis Sci. 2007;52(2):442-450.

Moore ML. Misoprostol-is more research needed? J Perinat Educ. 2002;11(3):43-47.

Murthy S, Keyvani L, Leeson S, Targownik LE. Intravenous versus high-dose oral proton pump inhibitor therapy after endoscopic hemostasis of high-risk lesions in patients with acute nonvariceal upper gastrointestinal bleeding. Dig Dis Sci. 2007;63(11):773-775.

Pietroiusti A, Forlini A, Magrini A, et al. Shift work increases the frequency of duodenal ulcer in H. pylori infected workers. Occup Environ Med. 2006;63(11):773-775.

Pilotto A, Franceschi M, Leandro G, et al. Clinical features of reflux esophagitis in older people: a study of 840 consecutive patients. J Am Geriatr Soc. 2006;54(10):1537-1542.

Romero C, Medina E, Vargas J, Brenes M, De Castro A. In vitro activity of olive oil polyphenols against Helicobacter pylori. J Agric Food Chem. 2007;55(3):680-688.

Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol. 2007;14(6):1860-1869.

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Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F. Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER study. Gut. 2007;56(4):475-479.

Review Date:
6/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Gastroesophageal reflux disease and heartburn

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Barrett's Esophagus
Diagnosis
Treatment
Prevention
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research

Obesity and GERD. Increased weight in women is linked to more frequent GERD symptoms, according to the Nurses' Health Study, which included 10,545 female participants. Overweight and obese women were two to three times more likely to have frequent symptoms than women of normal weight. GERD symptoms decreased nearly 40% in women whose body mass index (BMI) dropped by more than 3.5, compared to women whose BMI remained the same.
Proton-Pump Inhibitors and Bone Fracture. Long-term use of PPIs may increase the risk of hip fractures in older adults, according to a study in the Journal of the American Medical Association. People taking high doses of PPIs for more than a year were 2.6 times as likely to fracture a hip as those who were not taking the drug. The authors suggested that the stomach acids blocked by PPIs may be needed to absorb calcium, or the drugs may interfere with the body's natural process of breaking down and rebuilding bones.
PPIs and H2 Blockers in Children. Otherwise healthy children who take PPI inhibitors or H2 blockers may be at increased risk for intestinal and respiratory infections, according to a study of 186 children with GERD. The rate of gastroenteritis and community-acquired pneumonia significantly increased in children who were taking these medications when researchers compared the 4 months before and after enrollment in the study.

New Approval

Proton-Pump Inhibitor Approved for Adolescents. Esomeprazole (Nexium) delayed-release capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. Research shows that this medication reduces heartburn symptoms in adolescents.

Introduction

Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move backward into the esophagus (an action called reflux). Reflux occurs if the muscular actions in the esophagus or other protective mechanisms fail.

Click the icon to see an animation about heartburn.

The hallmark symptoms of GERD are:

Heartburn: a burning sensation in the chest and throat.
Regurgitation: a sensation of acid backed up in the esophagus.

Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful.

Heartburn is a condition in which the acidic stomach contents back up into the esophagus, causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

The esophagus, commonly called the food pipe, is a narrow muscular tube about nine-and-a-half inches long. It begins below the tongue and ends at the stomach. The esophagus is narrowest at the top and bottom; it also narrows slightly in the middle. The esophagus consists of three basic layers:

An outer layer of fibrous tissue.
A middle layer containing smoother muscle.
An inner membrane, which contains numerous tiny glands.

Click the icon to see an image of the esophagus.

When a person swallows food, the esophagus moves it into the stomach through the action of peristalsis, wave-like muscle contractions. In the stomach, the starch, fat, and protein in food are broken down by acid and various enzymes, notably hydrochloric acid and pepsin. The lining of the stomach has a thin layer of mucous that protects it from these fluids.

If acid and enzymes back up into the esophagus, however, its lining offers only a weak defense. The esophagus is protected using specific muscles and other factors.

The most important structure protecting the esophagus may be the lower esophageal sphincter (LES). The LES is a band of muscle around the bottom of the esophagus where it meets the stomach.

The LES opens after a person swallows to let food enter the stomach and then immediately closes to prevent regurgitation of the stomach contents, including gastric acid.
The LES maintains this pressure barrier until food is swallowed again.

Click the icon to see an image of the stomach.

If the pressure barrier is not sufficient to prevent regurgitation and acid backs-up (reflux), then peristaltic action of the esophagus serves as an additional defense mechanism and pushes the contents back down into the stomach.

Esophagitis. In most people, GERD symptoms are short-lived and occur infrequently. In about 20% of cases, however, the condition becomes chronic. When the acid causes irritation or inflammation, the condition is called esophagitis. If the damage becomes extensive and injures the esophagus, the disorder is known as erosive esophagitis.

Non-Erosive Esophageal Reflux Disease. Symptoms of gastroesophageal reflux disease can occur without any signs of inflammation or injury to the esophagus. This condition is also referred to as non-erosive esophageal reflux disease (NERD). NERD rarely progresses to full-blown GERD. Patients with NERD have no signs of inflammation or erosion in the esophagus, but they experience certain symptoms of GERD, such as burning sensations behind the breastbone for at least 3 months. Researchers suggest that nerves lying near the surface of the lining become exposed to acid that has penetrated the layers. The nerves then trigger prolonged and painful symptoms in response.

Barrett's Esophagus. A small percentage of patients with GERD may eventually develop Barrett's esophagus, a serious complication of GERD that results in precancerous changes in the tissue lining the esophagus.

Eosinophilic Esophagitis. This is a distinct disorder characterized by difficult or painful swallowing. It can occur along with GERD. The lining of the esophagus develops furrows and rings. This condition can be treated with swallowed fluticasone propionate, the active ingredient in some asthma medications.

Causes

Anyone who eats a large amount of acidic foods can have mild and temporary heartburn. This is especially true when lifting, bending over, or taking a nap after eating a large meal high in fatty, acidic foods. Persistent GERD, however, may be due to various conditions, including abnormal biologic or structural factors.

The band of muscle tissue called the LES is responsible for closing and opening the lower end of the esophagus and is essential for maintaining a pressure barrier against contents from the stomach. It is a complex area of smooth muscles and various hormones. If it weakens and loses tone, the LES cannot close up completely after food empties into the stomach. In such cases, acid from the stomach backs up into the esophagus. Dietary substances, drugs, and nervous system factors can weaken the LES and impair its function.

A study showed that more than half of GERD patients had abnormal nerve or muscle function in the stomach. These abnormalities cause impaired motility, which is the inability of muscles to act spontaneously. The stomach muscles do not contract normally, which causes delays in stomach emptying, increasing the risk for acid back-up.

Some studies suggest that most people with atypical GERD symptoms (such as hoarseness, chronic cough, or the feeling of having a lump in the throat) may have specific abnormalities in the esophagus. (In one study, such abnormalities appeared in 73% of patients who had atypical symptoms.)

Motility Abnormalities. Problems in spontaneous muscle action (peristalsis) in the esophagus commonly occur in GERD, although it is not clear if such occurrences are a cause or result of long-term effects of GERD.

Adult-Ringed Esophagus. This condition is characterized by an esophagus with multiple rings and persistent trouble with swallowing (including getting food stuck in the esophagus). It occurs mostly in men.

The hiatus is a small hole in the diaphragm through which the esophagus passes into the stomach. It normally fits very snugly, but it may weaken and enlarge. When this happens, part of the stomach muscles may protrude into it, producing a condition called hiatal hernia. It is very common, occurring in over half of people over 60 years old, and is rarely serious. Until recent years, it was believed that most cases of persistent heartburn were caused by a hiatal hernia. Hiatal hernia may impair LES muscle function. Studies have failed to confirm evidence, however, that it is a common cause of GERD, although its presence may increase GERD symptoms in patients with both conditions.

A hiatal hernia occurs when part of the stomach protrudes up into the chest through the sheet of muscle called the diaphragm. This may result from a weakening of the surrounding tissues and may be aggravated by obesity or smoking.

Studies indicate that 31 - 43% of reflux may be hereditary. An inherited risk exists in many cases of GERD, possibly because of inherited muscular or structural problems in the stomach or esophagus. Genetic factors may play an especially strong role in susceptibility to Barrett's esophagus, a precancerous condition caused by very severe GERD.

At least half of people with asthma also have GERD. Some experts speculate that the coughing and sneezing accompanying asthmatic attacks cause changes in pressure in the chest that can trigger reflux. Certain asthma drugs that dilate the airways may relax the LES and contribute to GERD. On the other hand, GERD has been associated with a number of other upper respiratory problems and may be a cause of asthma, rather than a result.

Crohn's disease is a chronic ailment that causes inflammation and injury in the colon and other parts of the gastrointestinal tract, including the esophagus. Other disorders that may affect areas that can contribute to GERD include diabetes, any gastrointestinal disorder, peptic ulcers, lymphomas, and cancer.

Click the icon to see an image of inflammatory bowel disease.

Helicobacter Pylori, also called H. pylori, is a bacterium found in the mucous membranes and is now known to be a major cause of peptic ulcers. Antibiotics used to eradicate H. pylori are now accepted treatment for curing ulcers. Of some concern, however, are studies indicating that H. Pylori may actually protect against GERD by reducing stomach acid. Furthermore, curing ulcers by eliminating the bacteria might actually trigger GERD in some people. Studies are mixed, however, on whether patients with cured H. Pylori infections are at risk for GERD. An analysis of 8 studies reported no higher risk for GERD after antibiotic treatments, nor was GERD any worse in patients who already had it. Seven of the 8 studies, however, were conducted only 2 months after antibiotic treatment. Longer follow-up studies are needed to determine long-term consequences, if any.

In any case, the bacteria should be eradicated in infected patients with existing GERD who are taking ongoing acid suppressing agents. There is some evidence that the combination of H. pylori and chronic acid suppression in these patients can lead to atrophic gastritis, a precancerous condition in the stomach.

In some cases, the esophagus appears normal, but GERD symptoms are present. This may indicate an over-reaction of the immune system to irritants that are introduced into the esophagus. In such cases, the immune system reacts with an exaggerated (or hyper-reactive) response, triggering the release of certain factors that end up causing inflammation and possibly injury. (This event is similar to the asthmatic response in the airways.)

NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs), common causes of peptic ulcers, may also cause GERD and increase severity in people who already have GERD. In a 3-year study of 25,000 people, NSAID users were twice as likely to have GERD symptoms as non-users. Symptoms did not become evident until after about 6 months of regular use. There are dozens of NSAIDs, including over-the-counter aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve), as well as prescription anti-inflammatory medicines. A person with GERD who takes the occasional aspirin or other NSAID will not necessarily experience adverse effects. This is especially true if there are no risk factors or indications of ulcers. Acetaminophen (Tylenol), which is NOT an NSAID, is a good alternative for those who want to relieve mild pain. It does not, however, relieve inflammation.

Other Drugs. Many other drugs can cause GERD, including but not limited to the following: calcium channel blockers (used to treat high blood pressure and angina), anticholinergics (used in drugs that treat urinary tract disorders, allergies, and glaucoma), beta adrenergic agonists (used for asthma and obstructive lung diseases), dopamine (used in Parkinson's disease), bisphosphonates (used to treat osteoporosis), sedatives, antibiotics, potassium, or iron pills.

Weakened peristaltic movement in the esophagus may contribute to GERD. If the mucous membrane is impaired, even a normal amount of acid can harm the esophagus. Pressure on the abdomen caused by obesity and also wearing tight clothing can contribute to acid backing up into the esophagus.

Click the icon to see an image of peristalsis.

Risk Factors

GERD occurs monthly in about half of American adults. People of all ages are susceptible to GERD. Elderly people with GERD tend to have a more serious condition than younger people.

Eating Pattern. Anyone who eats a heavy meal and subsequently lies on the back or bends over from the waist is at risk for an attack of heartburn. Anyone who snacks at bedtime is at high risk for heartburn.

Pregnancy. Pregnant women are particularly vulnerable to heartburn in their third trimester as the growing uterus puts increasing pressure on the stomach. Heartburn in such cases is often resistant to dietary interventions and even antacids.

Obesity. A number of studies suggest that obesity contributes to GERD and may increase the risk for erosive esophagitis in GERD patients. The Nurses' Health Study found that being overweight or obese significantly increased GERD symptoms in women. The higher a woman's body mass index (BMI), the study found, the more frequent were her symptoms. Women who lost weight in the study saw a decrease in their symptoms. Research suggests that the prevalence of GERD symptoms among obese patients has been underreported. Other researchers have reported that increased BMI is associated with a higher risk for cancer of the esophagus (esophageal adenocarcinoma).

Respiratory Diseases. People with asthma are at very high risk for GERD. One study indicated that patients with chronic obstructive pulmonary diseases (e.g., emphysema or chronic bronchitis) were more likely to have GERD.

Chronic obstructive pulmonary disease (COPD) refers to chronic lung disorders that result in blocked air flow in the lungs. The two main COPD disorders are emphysema and chronic bronchitis, the most common causes of respiratory failure. Emphysema occurs when the walls between the lung's air sacs become weakened and the sacs get enlarged and filled with too much air. Damage from COPD is usually permanent and irreversible.

Smoking. Increasing evidence indicates that smoking raises the risk for GERD. Studies suggest that smoking reduces LES muscle function, increases acid secretion, impairs muscle reflexes in the throat, and damages protective mucous membranes. Smoking reduces salivation, which helps neutralize acid. Whether it is the smoke, nicotine, or both that triggers GERD is unknown. Some people who use nicotine patches to quit smoking, for example, experience heartburn, but it is not clear if it's the nicotine or stress that produces acid back-up.

Alcohol Use. Alcohol has mixed effects on GERD. It relaxes the LES muscles and, in high amounts, may irritate the mucous membrane of the esophagus. All alcoholic beverages increase stomach acid levels. A combination of heavy alcohol use and smoking increases the risk for esophageal cancer. (Small amounts of alcohol, however, may actually protect the mucosal layer.)

In general, overweight Caucasian males over 40 are at highest risk for complications, notably Barrett's esophagus. Others at high risk for severe symptoms, inflammation, or both include:

People who use nonsteroidal anti-inflammatory drugs (NSAIDs). Studies suggest that certain NSAID users are at higher risk for GERD, including older adults, women, alcohol and tobacco users, and patients with asthma, hiatal hernia, or obesity. One study reported that NSAIDs put people at risk for ulcers but not for erosive esophagitis or strictures. Interestingly, NSAIDs are being studied for protection against Barrett's esophagus.
People with hiatal hernia

GERD is very common in children of all ages, but it is usually mild. Heartburn has been reported in 1.8% of 3-year-olds and in 5.2% of young people 10 - 17 years old. Children with the following conditions are at higher risk for severe GERD:

Neurologic impairments
Food allergies
Scoliosis
Cyclic vomiting
Cystic fibrosis
Problems in the lungs, ear, nose, or throat
Any medical condition affecting the digestive tract

Symptoms in Children. A physician should examine any child who has the following symptoms as soon as possible, because they may indicate complications such as anemia, failure to gain weight, or respiratory problems. Symptoms of severe GERD in infants and small children may include:

Chronic coughing
Frequent infections
Wheezing
Gasping or frequent cessation in breathing while asleep (called sleep apnea). However, one study found no association between GERD and apneas in premature infants.
Frequent vomiting in infants. About half of all infants up to 3 months old regurgitate milk at least once a day. Some simply spit up; others vomit large amounts after feedings. Vomiting in infants and older children is rarely a sign of GERD. In infants it usually resolves by age one. Severe vomiting -- particularly if it is bilious (green colored) -- always requires a doctor's visit, since it could be a symptom of severe obstruction.
Having to burp babies very frequently during and after feeding.

Babies and children may experience these symptoms without having GERD. An Australian study suggested that many infants who have normal irritability may be treated inappropriately for reflux disorders.

Feeding Problems. Feeding problems may be more severe than previously thought in children with GERD. In one study, children who had GERD and problems swallowing tended to refuse food and were late in eating solids. They also cried more and reacted more negatively in general than non-GERD babies. Such behaviors negatively affected the mothers as well. These findings were supported in an earlier study which reported that children at 1 year who had GERD in infancy were no longer spitting up, but still tended to have negative dining experiences ("too slow," "upsetting"). However, these children were at no greater risk for respiratory illnesses than other 1-year-old children.

Associations with Asthma and Infections in the Upper Airways. In addition to asthma, GERD is associated with other upper airway problems, including ear infections and sinusitis. Some experts argue that the association with common childhood infections and asthma is unfounded, since GERD is normal in most children.

Dental Erosion. GERD can cause irreversible loss of tooth enamel. Based on a 2002 study, some experts suggest checking for GERD in children with dental erosions. In the study, no child without GERD experienced loss of tooth enamel.

Rare Complications in Infants. Although GERD is very common, the following complications are very rare and only occur in certain cases:

Failure to thrive
Feeding problems and severe vomiting may cause anemia
Acid back-up may be inhaled into the airways and cause pneumonia

The infant's life may be in danger if acid reflux causes spasms in the larynx severe enough to block the airways. In fact, some experts believe this action may contribute to sudden infant death syndrome (SIDS). More research is needed to determine whether this association is valid.

Managing GERD in Infancy. Here are some hints on managing GERD in infants:

During and after feeding, infants should be positioned vertically and burped frequently.
If a baby with GERD is fed formula, the mother should ask the doctor how to thicken it in order to prevent splashing up from the stomach.
Parents of infants with GERD should discuss the baby's sleeping position with their pediatrician. Experts strongly recommend that all healthy infants sleep on their backs to help prevent sudden infant death syndrome (SIDS). For babies with GERD, however, lying on the back may obstruct the airways. In one study, infants with gastroesophageal reflux who spent prolonged periods of time in infant seats, including car seats, had more reflux than those who spent waking time on their stomachs. If the physician recommends that babies with GERD sleep on their stomachs, parents should be sure that their infant's mattress is very firm, possibly tilted up at the head, and that there are no pillows. The baby's head should be turned so that the mouth and nose are completely unobstructed.
Because food allergies may trigger GERD in children, parents may want to discuss a dietary plan with their physician that starts the child on formulas using non-allergenic proteins, and then incrementally adds other foods until symptoms are triggered.

Managing GERD in Children. The same drugs used in adults may be tried in children with chronic GERD. While some drugs are available over the counter, they should not be given to children without physician supervision.

Milder medications, such as antacids, are used first.
H2 blockers may be tried next. They are available over the counter and include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). The FDA has issued a warning on Pepcid AC for adults with kidney problems.
Proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) and lansoprazole (Prevacid), are even more powerful agents that suppress the production of stomach acid. Delayed-release esomeprazole (Nexium) capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. One study found that esomeprazole (Nexium) in either a 20 or 40 mg dose once a day significantly reduced heartburn symptoms in adolescents. PPIs appear to be safe and effective even for children as young as 1 year old who fail the less intensive therapies. However, a 2006 study found that otherwise healthy children who were treated with H2 blockers and PPIs had an increased risk of developing respiratory and intestinal infections.

Surgical fundoplication involves wrapping the upper curve of the stomach (fundus) around the esophagus. The goal of this surgical technique is to strengthen the LES. Until recently, surgery was the primary treatment for children with severe complications from GERD because older drug therapies had severe side effects, were ineffective, or had not been designed for children. However, with the introduction of proton-pump inhibitor drugs, some children may be able to avoid surgery. Surgical fundoplication can be performed laparoscopically through small incisions. In one study, of 238 children from 5 months to 16 years of age who underwent laparoscopic fundoplication, all but 9 were symptom free at least 5 years after the surgery. A 2006 study found that children who underwent antireflux surgery before age 4 were less likely to be hospitalized again, or to have reflux-related events such as pneumonia and esophagitis after the surgery.

Symptoms

Heartburn. Heartburn is the primary symptom of GERD. It is a burning sensation that radiates up from the stomach to the chest and throat. Heartburn is most likely to occur in connection with the following activities:

After a heavy meal
Bending over
Lifting
Lying down, particularly on the back

According to one study, nearly three-quarters of patients with frequent GERD symptoms experience them at night. Patients with nighttime GERD also tend to experience more severe pain than those whose symptoms occur at other times. One study found that patients with nighttime pain reported levels of severity that were similar to those reported in angina and heart failure.

The severity of heartburn does not necessarily indicate actual injury in the esophagus. For example, Barrett's esophagus, which causes precancerous changes in the esophagus, may trigger few symptoms, especially in elderly people. On the other hand, people can suffer severe heartburn without the presence of damage to the esophagus.

Dyspepsia. Up to half of GERD patients have dyspepsia, a syndrome consisting of the following:

Pain and discomfort in the upper abdomen
Fullness in the stomach
Nausea after eating

People can have dyspepsia without having GERD.

Regurgitation. Regurgitation is the feeling of acid backing up in the throat. Sometimes acid regurgitates as far as the mouth and can be experienced as a "wet burp." Uncommonly, it may come out forcefully as vomit.

Many patients with GERD do not experience heartburn or regurgitation. Elderly patients with GERD often have less typical symptoms than do younger people. Instead symptoms may appear in other locations.

Chest Sensations or Pain. Patients may have the sensation that food is trapped behind the breastbone. Chest pain is a common symptom of GERD. It is very important to differentiate it from chest pain caused by heart conditions, such as angina and heart attack.

Symptoms in the Throat. Less commonly, GERD may produce symptoms that occur in the throat:

Acid laryngitis. A condition that includes hoarseness, dry cough, the sensation of having a lump in the throat, and the need to repeatedly clear the throat.
Trouble swallowing (dysphagia). In severe cases, patients may even choke or food may become trapped in the esophagus, causing severe chest pain. This may indicate a temporary spasm that narrows the tube, or it could also be an indication of serious esophageal damage or abnormalities.
Chronic sore throat
Persistent hiccups

Coughing and Respiratory Symptoms. Asthmatic symptoms, such as coughing and wheezing, may occur. In fact, in one study, GERD alone accounted for 41.1% of cases of chronic cough in nonsmoking patients. The incidence was even higher when GERD and asthma were combined.

Chronic Nausea and Vomiting. Nausea that persists for weeks or even months and is not attributable to a common cause of stomach upset may be a symptom of acid reflux. In rare cases, vomiting can occur as often as once a day. All other causes of chronic nausea and vomiting should be ruled out, including ulcers, stomach cancer, obstruction, and pancreas or gallbladder disorders.

Complications

Nearly everyone has an attack of heartburn at some point in their lives. In the vast majority of cases the condition is temporary and mild, causing only transient discomfort. If patients develop persistent gastroesophageal reflux disease with frequent relapses, however, and it remains untreated, serious complications may develop over time. They can include the following:

Erosive esophagitis (severe inflammation in the esophagus)
Severe narrowing (stricture) of the esophagus
Barrett's esophagus
Problems in other areas, including the teeth, throat, and airways leading to the lungs

Older people are at higher risk for complications from persistent GERD. The following conditions also put individuals at risk for recurrent and serious GERD:

The esophagus is very inflamed.
Initial symptoms are severe.
Symptoms persist in spite of treatments that successfully heal the esophagus.
There are severe underlying muscular abnormalities.

Erosive esophagitis develops in chronic GERD patients when acid causes enough irritation and inflammation to produce extensive injuries in the esophagus. Some studies have suggested that overweight Caucasian males with GERD are at highest risk for this condition. In anyone, however, the longer and more severe the GERD condition, the higher the risk for erosive esophagitis.

Bleeding. In one study, bleeding occurred in more than 8% of patients with erosive esophagitis (severe inflammation of the esophagus), which is associated with GERD. In very severe cases, the patient may detect dark-colored, tarry stools (indicating the presence of blood) or may vomit blood, particularly if ulcers have developed in the esophagus. This is a sign of severe damage and requires immediate attention.

Sometimes long-term bleeding can result in iron-deficiency anemia and may even require emergency transfusions. This condition can occur without heartburn or other warning symptoms, or even obvious blood in the stools.

Barrett's Esophagus (BE) and Esophageal Cancer. In some cases, BE develops as an advanced stage of erosive esophagitis. BE results in abnormal cellular changes in the esophagus that, in turn, put a patient at risk for esophageal cancer. There are many issues involved with BE, however, including its prevalence and true severity, that are unresolved.

Of note, GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.

If the esophagus becomes severely injured over time, narrowed regions called strictures can develop, which may impair swallowing (dysphagia). Food may even become blocked in some cases. Stretching procedures or surgery may be required to restore normal swallowing. Paradoxically, strictures may actually prevent other GERD symptoms by helping to keep acid from traveling up the esophagus.

Asthma. Asthma and GERD often occur together. Studies report that reflux disorder coincides with 32 - 80% of asthma cases. Some theories for the causal connection between GERD and asthma are as follows:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerves, which run through the gastrointestinal tract. These stimulated nerves trigger the nearby airways in the lung to constrict, which causes asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that causes asthma symptoms.

There is some evidence that asthma causes GERD. In contrast, some evidence suggests that GERD causes asthma. Some clinical trials report that treating GERD in patients who also have asthma reduces symptoms of both conditions. Not all such patients report improved asthma symptoms with GERD treatments, and these treatments do not appear to have much effect on actual lung function. One study suggested that this approach works in asthmatic individuals who tended to be overweight and to have severe GERD in the lower part of the esophagus.

Other Respiratory and Airway Conditions. Current studies indicate an association between GERD and various upper respiratory problems that occur in the sinuses, ear and nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid from the esophagus (aspirates) into the lungs, serious pneumonia can occur. It is not yet known whether treatment of GERD would also reduce the risk for these respiratory conditions.

Dental erosion (the loss of the tooth's enamel coating) is a very common problem among GERD patients, including children. It results from the acid backing up into the mouth and eroding the enamel.

An estimated 20 - 60% of patients with GERD have atypical symptoms in the throat (hoarseness, sore throat) without any significant heartburn. A failure to diagnose and treat GERD may lead to persistent throat conditions such as chronic laryngitis, hoarseness, difficulty in speaking, sore throat, cough, constant throat clearing, and granulomas (soft, pink bumps) on the vocal cords.

GERD commonly occurs with obstructive sleep apnea, a condition in which breathing stops temporarily but repeatedly during sleep. It is not clear which condition is responsible for the other, but GERD is particularly severe when both conditions occur together. One study reported that spasms in the vocal cords caused by acid reflux may block the flow of air and cause sleep apnea in adults. On the other hand, other research suggests that the disordered breathing in sleep apnea alters pressure in the chest area and causes GERD. Both conditions may also have risk factors in common, such as sleeping on the back. Studies suggest that in such patients GERD can be markedly improved with a continuous positive airway pressure (CPAP) device, which opens the airways and is the standard treatment for severe sleep apnea.

Barrett's Esophagus

Barrett's esophagus (BE) is a serious condition in which changes occur in the cells that line the lower esophagus and cause the cells to become abnormal and precancerous. Barrett's esophagus is categorized as either long-segment or short-segment disease:

Long-segment BE occurs when abnormal cells affect 3 cm or more of the esophagus. This condition occurs in about 3 - 7% of GERD patients. It is associated with a more severe condition.
Short-segment BE affects less than 3 cm of the esophagus and is found in about 10 - 17% of GERD patients.

About 10% of patients with symptomatic GERD have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. Some studies suggest that individuals at highest risk for BE are obese white males over the age of 50 with persistent GERD who drink alcohol. However, a number of studies have reported no relationship between alcohol use or being male and overweight with BE. Such studies have also reported no higher risk in smokers or relatives of BE patients. Only the persistence of symptoms suggested a higher risk. Nevertheless, not all patients with BE have either esophagitis or symptoms of GERD.

The true prevalence of BE, in fact, is not entirely clear, since studies suggest that significantly more than half of people with BE have no GERD symptoms at all. BE, then, is likely to be much more prevalent and probably less harmful than is currently believed. (BE that occurs without symptoms can only be identified in clinical trials or in autopsies, so it is difficult to determine the true extent.) Some evidence suggests that the presence of specific immune factors may be involved in determining the development of BE.

The rate of esophageal cancer has been rising steadily at about 2% a year in white men. The American Cancer Society estimates that there will be 15,560 new cases of esophageal cancer and 13,940 deaths from the disease in 2007. Esophageal cancer is also very difficult to cure. The 5-year survival rate for all stages of esophageal cancer is 17% in white patients, and 12% in African-American patients. Most cases of esophageal cancer start with BE, with less than half of the cases developing with any symptoms. Of note, only a minority of BE patients develop cancer. Some evidence suggests that acid reflux may contribute to the development of cancer in BE. Researchers have speculated that exposure to extra acid in people with Barrett's esophagus produces more of an enzyme called NOX5-S, which may put stress on cells, leading to DNA damage.

Evidence suggests that asymptomatic BE is quite common in the general population, and if true, BE would pose far less of a threat than is now believed. (GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.)

Barrett's esophagus is diagnosed using endoscopy, a procedure that involves inserting a tube down the throat so that the physician can view the esophagus.

Monitoring High-Risk GERD Patients. Some experts recommend a one-time screening test for BE using endoscopy in high-risk patients (such as Caucasian overweight men) with chronic GERD.

Monitoring Patients with Barrett's Esophagus for Cancer. Periodic endoscopy is recommended for detecting early cancer in patients who have been diagnosed with Barrett's esophagus. In an important 2002 study, 5-year survival was 73% in BE patients whose cancer was detected with endoscopy screening and was 0% in patients who were not regularly screened.

To date, no treatments can reverse the cellular damage done after Barrett's esophagus has developed, although some procedures are showing promise.

Medications. Some evidence suggests that a combination of proton-pump inhibitors to suppress acid, coupled with anti-inflammatory COX-2 inhibitors, might be a promising approach.

Proton-Pump Inhibitors. Some experts recommend very aggressive treatments to reduce acid reflux using high-dose proton-pump inhibitors. The standard agent has been omeprazole (Prilosec). Newer oral PPIs include lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). Even when drugs relieve symptoms completely, the condition usually recurs within months after the drugs are discontinued. In chronic cases, drugs may need to be taken throughout a patient's life. These agents provide no protection against Barrett's esophagus. Still, there is some evidence that acid reflux may contribute to the development of cancer in BE, although it is not yet known if acid blockers have any protective effects against cancer in these patients.
COX-2 (cyclooxygenase-2) inhibitors reduce inflammation and pain, as do well-known agents such as aspirin and ibuprofen, but COX-2 inhibitors may pose less of a risk for peptic ulcers and bleeding. Some early evidence suggests they may be protective against cancerous changes in patients with Barrett's esophagus. However, Vioxx and Bextra have been withdrawn from the market due to their association with an increased risk of heart attack. Celebrex remains available, but must be used with caution, especially by patients with cardiovascular risk factors. Also, research is mixed on the benefits of NSAIDs for esophageal cancer. Some studies have found that they may decrease the risk of developing or dying from esophageal cancer. However, a 2007 study indicated that a small dose of Celebrex did not prevent the progression of cancer in Barrett's esophagus patients.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds, or the presence of black tarry stools, may indicate serious bleeding.

Procedures to Remove the Mucous Lining. Various techniques or devices have been developed to remove (ablate) the mucous lining of the esophagus. The intention is to remove early cancerous or precancerous tissue and allow regrowth of new and hopefully healthy tissue in the esophagus. Such techniques include photodynamic therapy (PDT) or laser, electrical, or heat probes.

Studies on the use of these ablation techniques combined with aggressive use of proton-pump inhibitors or surgical treatments are very encouraging. Some of these techniques may eventually even offer potential cures. At this time, they can be very effective in removing harmful tissue, although the benefits do not last in all patients. In one study, an average of 5.6 years after anti-GERD surgery and laser treatment, only a third of patients showed no evidence of renewed precancerous cell growth. These procedures also have complications, such as possible problems swallowing, that patients should discuss with their physician.

Esophagectomy. Esophagectomy is the surgical removal of all or part of the esophagus. Patients with Barrett's esophagus, who are otherwise healthy, are candidates for this procedure if endoscopy shows developing cancer. After esophageal removal, in total or in part, a new conduit for foods and fluids must be established to replace the absent esophagus. Alternatives include the stomach, colon, and part of the small intestine called the jejunum. The stomach is the optimal choice.

Diagnosis

If a patient suffers from chronic heartburn, chances are good the patient also has GERD. (Occasional heartburn does not necessarily indicate the presence of GERD.) The following is the general diagnostic approach:

A physician can usually make an easy diagnosis of GERD if the patient finds relief from persistent heartburn and acid regurgitation after taking antacids for short periods.
If the diagnosis is uncertain but the physician still suspects GERD, a drug trial using a proton-pump inhibitor medication, such as omeprazole (Prilosec) identifies 80 - 90% of people with the conditions. This class of medication blocks stomach acid secretion.

Laboratory or more invasive tests, including endoscopy, may be required if the diagnosis is still uncertain, if atypical symptoms are present, if Barrett's esophagus is suspected, or if complications, such as signs of bleeding or difficulty in swallowing, are present. Some of these tests are described below.

A barium swallow radiograph (x-ray) is useful for identifying structural abnormalities and erosive esophagitis (severe inflammation). When taking this test, the patient drinks a solution containing barium, then x-rays are taken. This test can show stricture, active ulcer craters, hiatal hernia, erosion, or other abnormalities. The test cannot reveal mild irritation.

Upper endoscopy, also called esophagogastroduodenoscopy or panendoscopy, is more accurate than a barium-swallow radiograph. It is also more invasive and expensive. It is widely used in GERD, including for identifying and grading severe esophagitis, for periodic monitoring of patients with Barrett's esophagus or for screening people at high risk, or when other complications are suspected. It is also now employed as part of various surgical techniques.

Endoscopy to Diagnose GERD. Endoscopy may be performed either in a hospital or in a doctor's office:

First, the patient should eat nothing for at least 6 hours before the procedure.
The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and to relax the patient.
Next, the physician places an endoscope (a thin flexible plastic tube containing a tiny camera) into the patient's mouth and down the esophagus. The procedure does not interfere with breathing. It may be slightly uncomfortable for some patients; others are able to sleep through it.
Once the endoscope is in place, the tiny camera allows the physician to see the surface of the esophagus and to search for abnormalities, including hiatal hernia and damage to the mucous lining.
The physician performs a biopsy (the removal and microscopic examination of small tissue sections). The biopsy may detect tissue injury indicative of GERD. It may also be used to detect cancer or other conditions, such as yeast (Candida albicans) or viral infections (e.g., herpes simplex and cytomegalovirus). Such infections are more likely to occur in people with impaired immune systems.
Complications from the procedure are uncommon. If they occur, complications are almost always mild and typically include minor bleeding from the biopsy site or irritation where medications were injected.

If a patient has moderate-to-severe GERD symptoms and the procedure reveals injury in the esophagus, usually no further tests are needed to confirm a diagnosis. The test is not foolproof, however. A visual view misses about half of esophageal abnormalities.

Capsule Endoscopy. Capsule endoscopy was first approved for use in 2001. A new version of this pill-sized camera, renamed PillCam, was approved by the FDA in 2004. PillCam reduces the imaging time previously required by the original capsule endoscopy technique. The PillCam capsule contains tiny video cameras on both ends. After the patient swallows the capsule, a series of 2600 color pictures are transmitted to a recording device where they can be downloaded and interpreted by a doctor. A newer version of the PillCam takes 14 frames per second as opposed to the 4 frames per second of the original device. The newer PillCam is superior in visualizing the entire esophagus and in identifying GERD. The entire procedure takes 20 minutes. The capsule is naturally passed through the digestive system within 24 hours. Capsule endoscopy may provide a more attractive and less invasive alternative for patients than traditional endoscopy. However, while capsule endoscopy is useful as a screening device for diagnosing esophageal conditions such as GERD and Barrett's esophagus, traditional endoscopy is still required for gathering tissue samples or removing polyps.

The (ambulatory) pH monitor examination may be employed to determine acid back-up. It is useful when endoscopy has not detected damage to the mucous lining in the esophagus, but GERD symptoms are present. pH monitoring may be used when patients have not found relief from medicine or surgery. The traditional trans-nasal catheter diagnostic procedure involved inserting a tubular probe through the nose and down to the esophagus. The tube was left in place for 24 hours. This test was irritating to the throat, and uncomfortable and awkward for most patients.

A new method, known as the Bravo pH test, uses a small capsule-sized data transmitter that is temporarily attached to the wall of the esophagus during endoscopy. The capsule records pH levels and transmits these data to a pager-sized receiver worn by the patient. Patients can continue their usual diet and activity schedule during the 24 - 48-hour monitoring period. After a few days, the capsule detaches from the esophagus, passes through the digestive tract, and is eliminated through a bowel movement.

Manometry is a technique that measures muscular pressure. It employs a tube containing various openings, which is placed through the esophagus. As the muscular action of the esophagus exerts pressure on the tube in various locations, a computer connected to the tube measures it. It is useful for the following situations:

To determine if a GERD patient would benefit from surgery by measuring pressure exerted by the lower esophageal sphincter muscles (LES).
To detect impaired stomach motility (an inability of the muscles to contract normally), which cannot be surgically corrected with standard procedures.
To determine if impaired peristalsis or other motor abnormalities are causing chest pain in people with GERD who have these symptoms.

Blood and Stool Tests. Stool tests may show traces of blood that are not visible. Blood tests for anemia should be performed if bleeding is suspected.

Bernstein Test. For patients with chest pain in which the diagnosis is uncertain, a procedure called the Bernstein test may be useful, although it is rarely used. A tube is inserted through the patient's nasal passage. Then solutions of hydrochloric acid and saline are administered separately into the esophagus. If the acid infusion causes symptoms and the saline solution does not, then a diagnosis of GERD is established.

Because many illnesses share similar symptoms, careful analysis and consideration of the patient's history is key to an accurate diagnosis. The following are only a few of the conditions that could accompany or resemble GERD.

Dyspepsia. The most common disorder confused with GERD is dyspepsia, which is defined as pain or discomfort in the upper abdomen without heartburn. Specific symptoms may include a feeling of fullness (particularly early in the meal), bloating, and nausea. Dyspepsia can be a symptom of GERD, but does not always occur with GERD. The drug metoclopramide (Reglan) helps stomach emptying and may be helpful for this condition.

Angina and Chest Pain. About 600,000 people come to emergency rooms each year with chest pains. More than 100,000 of these people are believed to actually have GERD. Chest pain from both GERD and from severe angina can occur after a heavy meal. In general, a heart problem is probably not responsible for the pain if it is worse at night and does not occur after exercise. It should be noted that the two conditions often coexist. In fact, there is some theory that in patients with coronary artery disease, acid reflux may actually trigger angina. In such cases, experts believe that acid in the esophagus may activate nerves that temporarily impair blood flow to the heart.

Asthma. Because asthma and GERD commonly occur together, physicians must be sure that each disorder is diagnosed accurately.

Other Diseases. Many gastrointestinal diseases (e.g., inflammatory bowel disease, ulcers, intestinal cancers) can cause GERD, but they are often easily identified, since they have other symptoms and affect other areas of the intestinal tract.

Treatment

Acid suppression continues to be the mainstay for treating GERD. The aim of drug therapy is to reduce the amount of acid present and improve any abnormalities in muscle function of the lower esophageal sphincter (LES), the esophagus, or the stomach.

Most cases of gastroesophageal reflux are mild and can be managed with lifestyle changes and over-the-counter medications and antacids.

Patients with moderate-to-severe symptoms that do not respond to lifestyle measures, or who are diagnosed at a late stage may be started on more or less potent agents depending on their complications at diagnosis. Experts argue, however, about the best way to initiate drug treatment for GERD in most of these patients. The two major treatment options are known as the step-up and step-down approaches:

Step-up. With a step-up drug approach the patient first tries an H2 blocker drug, which is available over the counter. These drugs include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). If the condition fails to improve, therapy is "stepped up" to the more powerful proton-pump inhibitors, usually omeprazole (Prilosec).
Step-down. A step-down approach first uses a more potent agent, most often a proton-pump inhibitor (PPI), such as omeprazole (Prilosec). When patients have been symptom-free for 2 months or longer, they are then "stepped down" to a half-dose. If symptoms do not recur, the drug is withdrawn. If symptoms recur, the patient is put on high-dose H2 blockers. In one study using this step-down approach, 58% of patients remained symptom-free after a year, with 27% not using any medications at all. Some physicians argue that the step-down approach should be used for most patients with moderate-to-severe GERD.

Recent guidelines indicate that PPIs should be the first drug treatment, and that these drugs should be given once a day for approximately 8 weeks. Even when symptoms are completely relieved by medication, they usually return within a few months after drug treatment has stopped. Long-term maintenance may be necessary.

If neither approach relieves symptoms, the physician should look for other conditions. Endoscopy and other tests might be used to confirm GERD and rule out other disorders. In some cases, bile, not acid, may be responsible for symptoms, so that acid-reducing or blocking agents would not be helpful. (Bile is a fluid that is present in the small intestine and gallbladder.)

Surgery may be indicated under certain circumstances:

If lifestyle changes and drug treatments have failed
In patients with other medical complications
In younger people with chronic GERD, who face a lifetime of expense and inconvenience with maintenance drug treatment

Some physicians are recommending surgery as the treatment of choice for many more patients with chronic GERD, particularly since minimally invasive surgical procedures are becoming more widely available, and since only surgery improves regurgitation. Furthermore, persistent GERD appears to be much more serious than was previously believed, and the long-term safety of acid suppression using medication is still uncertain.

Nevertheless, anti-GERD procedures have many complications and high failure rates (ranging from 30% at 5 years to 63% at 10 years) and, as with medications, current surgical procedures cannot cure GERD. About 15% of patients still require anti-GERD medications after surgery. Furthermore, about 40% of surgical patients are at risk for new symptoms after surgery (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Finally, evidence -- notably an important 2002 Swedish study -- now strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus. New procedures may improve current results, but at this time patients should consider surgical options very carefully with both a surgeon and their primary doctor.

Prevention

People with heartburn should first try lifestyle and dietary changes. In one study, 44% of patients who experienced symptoms of gastroesophageal reflux disease (GERD) reported improvement after changing their diet. Some suggestions are the following:

Avoid or reduce consumption of foods and beverages that contain caffeine, chocolate, peppermint, spearmint, and alcohol. Both caffeinated and decaffeinated coffees increase acid secretion.
Avoid all carbonated drinks, because they increase the risk for GERD.
Although physicians often advise patients with GERD to cut down on fatty foods, many studies have found no evidence that a low-fat or high-fat meal makes any difference in symptom exacerbation. One small study, however, found that the frequency of GERD symptoms increased with a high-fat compared to a low-fat diet. Better studies are needed to confirm this. In any case, as a rule, it is always wise to avoid saturated fats (which are from animal products), and cut down on all fats if one is overweight.
Choose low-fat or skim dairy products, poultry, or fish. Increasing protein may help strengthen muscles in the muscle valve.
Consume whole-grain products rich in selenium, which may have some protective role against dangerous cell changes in Barrett's esophagus.
Eat a diet rich in fruits and vegetables, although it's best to avoid acidic vegetables and fruits (e.g., oranges, lemons, grapefruit, pineapple, tomatoes).

Patients who have trouble swallowing should avoid tough meats, vegetables with skins, doughy bread, and pasta.

Nearly three-quarters of patients with frequent GERD symptoms have them at night. Patients with nighttime GERD also tend to experience severe pain. It is very important to take preventive measures before going to sleep. Some suggestions for preventing acid reflux at night are as follows:

After meals, take a walk or, at the very least, remain upright.
Avoid bedtime snacks. In general, avoid eating for at least 2 hours prior to bedtime.
When going to bed, try lying on the left side rather than on the right. The stomach is located higher than the esophagus when a person sleeps on the right side, which can put pressure on the lower esophageal sphincter (LES), increasing the risk for fluid back-up.
Sleep in a tilted position to help keep acid in the stomach at night. To do this, raise the bed at an angle using 4- to 6-inch blocks at the head of the bed and use a wedge-support to elevate the top half of the body. (Extra pillows that only raise the head actually increase the risk for reflux.)

A reflux board is prescribed for use in children who have gastroesophageal reflux. A board tilts the child upward while he is lying in bed to prevent the stomach contents from going back into the esophagus and mouth, and possibly into the lungs.

Quitting smoking is essential.
People who are overweight should try to reduce food intake and exercise to lose weight.
People with GERD should avoid tight clothing, particularly around the abdomen.
If possible, GERD patients should avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Aleve), among others. Tylenol (acetaminophen) is a good alternative pain reliever.

Although gum chewing is commonly believed to increase the risk for GERD symptoms, one study reported it might be helpful. Because saliva helps neutralize acid and contains a number of other factors that protect the esophagus, chewing gum 30 minutes after a meal has been found to help relieve heartburn and even protect against damage caused by GERD. Chewing on anything at all can help since it stimulates saliva production.

Medications

Antacids neutralize digestive acids and are the primary drugs for mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. They all work by neutralizing the acid in the stomach. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucous secretion. Many antacids are available without a prescription and are the first drugs recommended to relieve heartburn and mild symptoms. Despite the many brands, they all rely on various combinations of three basic ingredients: magnesium, calcium, or aluminum.

Magnesium. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate, and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Magnesium salts offered in combination products with aluminum (Mylanta and Maalox) balance the side effects of diarrhea and constipation.

Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. These antacids are actually sources of calcium. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. This can lead to kidney failure and is very dangerous. None of the other antacids has this side effect.

Aluminum. Aluminum salts (Amphogel, Alternagel) are also available. The most common side effect of antacids containing aluminum salts is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they all work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten), and H2 blockers. Interactions can be avoided by taking the drugs 1 hour before or 3 hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones.

H2 blockers impede acid production by blocking or antagonizing the actions of histamine, a chemical found in the body that encourages acid secretion in the stomach. They are available over the counter and provide symptom relief in about half of GERD patients. It takes 30 - 90 minutes for them to work, but the benefits last for hours. The drugs are usually taken at bedtime. Some people may need to take them twice a day.

H2 blockers inhibit acid secretion for 6 - 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. In some studies, H2 blockers improved asthmatic symptoms in people who have both conditions. A 2001 study suggested, however, that they rarely provide complete symptom relief for chronic heartburn and dyspepsia and they have done little to reduce office visits to physicians for GERD.

Brands. Four H2 blockers are currently available in the U.S.:

Famotidine (Pepcid AC). Famotidine (Pepcid AC, Pepcid Oral) is the most potent H2 blocker. The most common side effect of famotidine is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free of drug interactions, but the FDA has issued a warning on its use in patients with kidney problems.
Cimetidine (Tagamet, Tagamet HB). Cimetidine (Tagamet) is the oldest H2 blocker. It has few side effects; approximately 1% of people taking it will experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, such as phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.
Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, Zantac Syrup). Ranitidine (Zantac) interacts with very few drugs. In a recent study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people less than 60 years old, but there was no difference in older patients. A common side effect associated with ranitidine is headache, which occurs in about 3% of the people who take it.
Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules). Nizatidine (Axid) is nearly free of side effects and drug interactions. A controlled-release form is proving to help alleviate nighttime GERD symptoms.

Famotidine is excreted primarily by the kidney. This can pose a danger to people with kidney problems. Physicians are now being advised by the U.S. Food and Drug Administration (FDA) and Health Canada to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.

Drug Combinations.

Over-the-counter antacids and H2 blockers: This combination may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD, but have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but have long-lasting benefits. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is now available as Pepcid Complete.
Proton-pump inhibitors and H2 blockers: Physicians sometimes recommend a nighttime dose of an H2 blocker for people who are taking proton-pump inhibitors twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. An important 2002 study, however, reported no additional benefits from the nighttime H2 blocker. Some experts recommended an H2 blocker in patients who are on proton-pump inhibitors only to prevent breakthrough symptoms, such as before a heavy meal.

Long Term Complications. In most cases, these agents have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than others. In all cases, however, the physician should be made aware of any other drugs a patient is taking. More research is needed. Anyone with kidney problems should use famotidine only under the direction of a physician.

Concerns and Limitations. Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms and increase the risk for serious complications.

These agents provide no protection against Barrett's esophagus. In fact, of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who are infected with H. pylori. Research on this question is still ongoing.

Proton-pump inhibitors (PPIs) suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the gastric acid pump. According to recent guidelines, initial drug treatment should be with PPIs once daily for about 8 weeks.

The standard agent has been omeprazole (Prilosec), which is now available over the counter without a prescription. Newer prescription oral PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).

Studies report significant relief from PPIs in most patients with heartburn. PPIs are effective for healing erosive esophagitis and may also be helpful in patients with chronic laryngitis that is suspected to be caused by GERD. The newer agents provide quicker symptom relief compared to omeprazole. However, a comparison study suggested that, to date, esomeprazole (Nexium) is the only newer oral PPI to show any significant advantage over omeprazole (Prilosec). All PPIs are more effective than the H2 blockers.

In addition to relieving most common symptoms, including heartburn, proton-pump inhibitors also have the following advantages:

They are effective in relieving chest pain and laryngitis caused by GERD.
They may also reduce acid reflux that typically occurs during strenuous exercise.

Patients with impaired esophageal muscular action are still likely to experience acid breakthrough and reflux at night. Proton-pump inhibitors also may have little or no effect on regurgitation or asthmatic symptoms. Some experts believe, however, that they should be the first drugs of choice, even for patients with milder symptoms. At this time, these drugs are recommended for the following patients:

Those with moderate symptoms that do not respond to H2 blockers
Those with severe symptoms
Those who have respiratory complications
Those who have persistent nausea
Those who have esophageal injury

These agents have no affect against non-acid reflux, such as bile back-up.

Adverse Effects. Proton-pump inhibitors may pose the following concerns:

Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.
Proton-pump inhibitors should be avoided by pregnant women and nursing mothers, although recent studies suggest that they do not pose an increased risk of birth defects.
They may interact with certain drugs, such as anti-seizure agents (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin).
Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but studies are needed to confirm whether there is any significant risk. High-dose PPIs used over the long-term also may increase the risk of hip fracture in older adults, according to one study.

There is some evidence that acid reflux may contribute to the higher risk of cancer in BE, but it is not yet confirmed whether acid-blockers have any protective effects against cancer in these patients. In fact, the long-term use of proton-pump inhibitors by people with H. pylori may, in theory at least, reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and so delay a diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with the long-term use of these drugs.

Sucralfate (Carafate) protects the mucous lining in the gastrointestinal tract. It seems to work by sticking to an ulcer crater and protecting it from damage due to stomach acid and pepsin. It may be helpful for maintenance therapy in people with mild-to-moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Most drugs used for GERD have no effect on non-acid reflux, such as back-up of bile. Baclofen, known as a gamma-amino butyric acid agonist, is commonly used to reduce muscle spasms. Investigators are now showing that it can reduce both acid and non-acid reflux episodes (as much as 70% in one study) and increase LES pressure, an important factor for preventing back-up.

Surgery

The standard surgical treatment for GERD is fundoplication. The goal of this procedure is twofold:

To increase LES pressure and, therefore, prevent acid back-up (reflux)
To repair any present hiatal hernia

There are two primary approaches:

Open Nissen fundoplication (the more invasive technique)
Laparoscopic fundoplication

In general, the overall long-term benefits of these procedures are similar. Some studies report that more than 90% of patients are free of heartburn after the operation and satisfied with their choice, even after 5 years. Fundoplication relieves GERD-induced coughs and some other respiratory symptoms in up to 85% of patients. (Its effect on asthma associated with GERD, however, is unclear.) It may enhance stomach emptying and improve peristalsis in about half of patients. (It may actually cause abnormal peristalsis in about 14% of patients, although in such cases the problem does not appear to be very significant.)

Still, it has other significant limitations and postoperative problems. For example, the results of one 2003 survey suggested that 18% of surgical patients still required anti-GERD medications and 38% had new symptoms (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Other studies have reported similar results. Also, fundoplication does not cure GERD. Finally, evidence from a 2002 Swedish study strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus.

Candidates. Fundoplication is recommended for patients whose condition includes one or more of the following:

Esophagitis (inflamed esophagus)
Symptoms that persist or are recurrent in spite of anti-reflux drug treatment
Strictures
Failure to gain or maintain weight (children)

Fundoplication has little benefit for patients with impaired stomach motility (an inability of the muscles to move spontaneously).

The Open Nissen Fundoplication Procedure. Until recently, most fundoplication procedures for GERD have been the 360° Nissen fundoplication. This is called an open procedure because it requires wide surgical incisions.

With this procedure, the physician wraps the upper part of the stomach (fundus) completely around the esophagus to form a collar-like structure.
The collar places pressure on the LES and prevents stomach fluids from backing up into the esophagus.
Open fundoplication requires a 6- to 10-day hospital stay.

Click the icon to see an illustrated series detailing gastroesophageal reflux surgery.

Laparoscopic Fundoplication. The standard invasive fundoplication procedure has been replaced in many cases by a less invasive fundoplication procedure that uses laparoscopy. In the operation:

Tiny incisions are made in the abdomen.
Small instruments and a tiny camera are inserted into tubes, through which the surgeon can view the region.
The surgeon creates a collar using the fundus, although the area is smaller to work with.

When performed by experienced surgeons, the procedure shows results that are equal to those of standard open fundoplication, but with faster recovery time.

Overall, laparoscopic fundoplication appears to be safe and effective in people of all ages, even babies. Laparoscopy is more difficult to perform in certain patients, including those who are obese, who have a short esophagus, or who have a history of previous surgery in the upper abdominal area. It may also be less successful in relieving atypical symptoms of GERD, including cough, abnormal chest pain, and choking. In about 8% of laparoscopies, it is necessary to convert to open surgery during the procedure because of unforeseen complications.

Other Variations. There are now a number of variants of fundoplication procedures. Examples include the following:

Toupet fundoplication employs only a partial wrap, as does a Thal fundoplication. Partial fundoplication procedures may be more effective in patients with poor or no esophageal motility (spontaneous muscle contraction). Those with normal motility may do better with the full-circle wrap.
Others use a very short and "floppy" Nissen full wrap.

Many surgeons report that such limited fundoplications result in earlier feeding and discharge from the hospital and a lower incidence of complications (trouble swallowing, gas bloating, gagging) than the full Nissan fundoplication. A British study, however, reported no significant differences in swallowing problems.

Postoperative Problems and Complications after Fundoplication. Postoperative problems can include a delay in intestinal functioning causing bloating, gagging, and vomiting. These side effects usually resolve in a few weeks. A 2003 study suggested, however, that 38% of patients develop such symptoms, and most occur more than a year after the procedures. If symptoms persist or if they start weeks or months after surgery, particularly if vomiting is present, then surgical complications are likely. Complications include the following:

An excessively wrapped fundus. This is fairly common and can cause difficulty swallowing (dysphagia), as well as gagging, gas, bloating, or an inability to burp. (A follow-up procedure that dilates the esophagus using an inflated balloon may help correct dysphagia, although it cannot treat other symptoms.)
Bowel obstruction
Wound infection
Injury to nearby organs
Respiratory complications, such as a collapsed lung. These are uncommon, particularly with laparoscopic fundoplication.
Muscle spasms after swallowing food. This can cause intense pain, and patients may require a liquid diet, sometimes for weeks. This is a rare complication in most patients, but it can be very high in children with neurologic abnormalities. Such children are already at very high risk for GERD.

Reasons for Treatment Failure. Long-term failure rates after fundoplication are 30% after 5 years and 63% after 10 years. Hiatal herniation is the most common reason for surgical failure and the need for a repeat fundoplication. Other common reasons for reoperation include breakdown, slippage, and excessive tightness of the wrap. Surgeon experience can lessen complication risks. Some studies have reported that repeat operations after open procedures occur in 9 - 30% of cases and 13% after laparoscopy. (Repeat surgery usually has good results.)

A number of treatments that make use of endoscopy are being used or investigated for increasing LES pressure and preventing reflux, as well as for treating severe GERD and its complications.

Transoral Flexible Endoscopic Suturing. Transoral flexible endoscopic suturing (sometimes referred to as Bard's procedure) uses a tiny device at the end of the endoscope that acts like a miniature sewing machine. It places stitches in two locations near the LES, which are then tied to tighten the valve and increase pressure. There is no incision and no need for general anesthesia.

Radiofrequency. Radiofrequency energy generated from the tip of a needle (sometimes called the Stretta procedure) heats and destroys tissue in the problem spots in the LES. Either the resulting scar tissue strengthens the muscle, or the heat kills the nerves that caused the malfunction. Patients may experience some chest or stomach pain afterwards. Few serious side effects have been reported, although there have been reports of perforation, hemorrhage, and even death. A recent study reported that 81% of patients remained symptom-free for up to 3 years following the Stretta procedure.

Implants. In 2003, the FDA approved the Enteryx procedure as a treatment option for people who have persistent symptoms of GERD and who regularly take and respond to PPIs. In 2005, however, the manufacturer of Enteryx (Boston Scientific), voluntarily removed Enteryx from clinical use due to problems related to the difficult injection technique.

Techniques to Stop Bleeding. Endoscopic ablation treatment of bleeding involves using a probe passed through the endoscopic tube, which applies electricity or heat to coagulate blood and stop the bleeding.

Dilation Procedures. Strictures (abnormally narrowed regions) may need to be dilated (opened) with endoscopy. Dilation may be performed by inflating a balloon in the passageway. About 30% of patients who need this procedure require a series of dilation treatments over a long duration in order to fully open the passageway. Long-term use of proton-pump inhibitors may reduce the duration of treatments.

One study also suggested that dilation may help correct swallowing problems that can occur after fundoplication. In the study dilation improved dysphagia in 67% of the surgical patients who had experienced it.

A recent advance is the development of small-caliber upper endoscopy, which does not require sedation and can be performed in the physician's office.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www.asge.org -- American Society for Gastrointestinal Endoscopy
www.ssat.com -- Society for Surgery of the Alimentary Tract
www.naspgn.org -- North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
www.reflux.org -- Pediatric/Adolescent Gastroesophageal Reflux Association
www.iffgd.org -- International Foundation for Functional Gastrointestinal Disorders

References

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Review Date:
5/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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