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Link Time!

BellaSugar — Thu, 12 Nov 2009 13:00:44 -0800

Pupa cosmetics makes palettes that look like geisha - FabSugar UK
Bobbi Brown's new mascara promises an extreme party - Temptalia
Nice eye shadows, shame about the lip gloss - Makeup and Beauty Blog
Victoria's Secret hires its first Asian model for its show - The Cut
Hand creams for big and small budgets - Beauty Snob
This scale tweets your weight to the world. - Lemondrop
Don't call the return of Scott Barnes a comeback. He's been here for years. - Stylelist
Kellie Pickler has drastically changed her hair color - People Style Watch
Bobby pins can be very fashionable - Fashionista

Racial Preferences in Dating: Fetishism or Not a Big Deal?

TresSugar — Fri, 10 Jul 2009 12:00:00 -0700

We all have our physical preferences when it comes to finding a romantic partner. Some women want men to be tall, broad shouldered, and dark haired. Men may want a big-breasted blonde. We objectify those we find attractive to some extent, but what are the implications of preferring someone of a different race?

After reading an article a friend sent me, A White Woman Explains Why She Prefers Black Men, I realized that there's a big implication: the desire could be based on racial assumptions and stereotypes that, just because they're "positive," don't make them any less pernicious, objectifying, or, to put it bluntly, racist. Want to find out about racial fetishism? Then read more.

Whether you have "jungle fever" or "yellow fever" (you date blacks or Asians exclusively), you would be described, in the parlance of the day, as having a "fetish." One thoughtful person has explained a fetish this way:

Sexual fetishism in general is the sexual attraction to something which is not in itself a sexual object, such as feet or leather. Sexually fetishizing a person or group of people however means reducing them to objects, important only in their sexual function or interest to the fetishizer. Race fetishization means effectively reducing all members of a racial group to a monolithic whole, only valued in terms of their racial stereotypes. You are hearing racial fetishization when people talk about how black men have big penises, Asian women are exotic and submissive . . . just because a stereotyped characteristic is a "good" characteristic, that doesn't mean it's not racist.

So how does our White Woman (who is also a sex columnist) Who Prefers Black Men rate on the racial fetishizer scale? She's off the charts, a textbook case. Here are some salient bits from her essay.

That phrase, "Once you go black, you never go back'" is all about the feeling of the skin . . . Black men have more energy, style and edge than white men . . . something white guys don't have anymore: confidence in their masculinity, their sexuality . . . I am sure there must be some black men who aren't good in bed. Personally, I have not experienced one who isn't . . . They look better than white men, they touch and kiss and make love better than white men. Statistically, their penises are only a fraction of an inch bigger on average, but they seem bigger and harder . . .

Obviously, this white woman likes black men - a lot. It's all about sexualizing them, though, reducing all of them to their skin, to their presumed sexual prowess, their instinctual energy and innate masculinity. If racism is about assuming things about people based on their physical traits, how is this not racism? More disturbingly, her desire, conscious or not, participates in the kind of sexualization of black men that once justified their persecution and even murder.

So what to do about these nonpolitically correct desires? Censor them? Pretend they don't exist? One of my favorite sex columnists, Dan Savage from Savage Love, provides some intelligent advice. He never argues that we should police our desires, just that we be aware of where they're coming from and what they could mean in how we treat our partners. "There's nothing wrong," he tells one person seeking advice who has a fantasy of having a black man have sex with his wife, "with treating someone like a piece of meat during sex . . . some people enjoy being treated like pieces of meat . . . Consent is . . . always and everywhere the magic ingredient . . . As long as you understand the cultural forces that shaped your fantasy . . . there's nothing unethical about realizing your fantasy."

One wonders if these black men who Susan Bakos hooks up with know that she views them all the same way. (One wonders if she thinks viewing them this way is problematic at all.) The heart may want what it wants, Woody Allen said euphemistically about hooking up with his adopted daughter, but that desire can have ripple effects far beyond the couple in question, particularly when one woman's desire is presented, without any qualms or self-questioning, in an essay many people will read.

Healthy Eating Tip: Make Nori Wraps Like Alicia Silverstone

FitSugar — Fri, 08 May 2009 09:00:00 -0700

The Kind Diet book by Alicia Silverstone doesn't hit stores until Fall, but you don't have to wait until then to get a taste of her vegan tips. A common qualm about veganism is that meals are time-consuming, but this famous vegan implied that doesn't have to be true and said, "One of the recipes in my book is leftover nori (a type of seaweed) wraps. Anything in the fridge I want to use up, I shove into nori. It's delicious."

Alicia sells the perks of seaweed by saying, "It makes your skin look amazing and your hair really strong," but the benefits of including seaweed in your diet are more than skin-deep. The sea vegetable is an excellent source of essential minerals like iodine, vitamin K, B-vitamins, magnesium, iron, and calcium.

You can usually find packages of nori in the Asian food section of your supermarket. It comes in thin sheets, making it ideal for wrapping, and Alicia has shown us that it's not just for wrapping raw fish.

Source

Systemic lupus erythematosus

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Systematic Lupus Erythematosus (SLE)

SLE is an autoimmune disease that causes a chronic inflammatory condition. The inflammation triggered by SLE affects many organs in the body, including skin, joints, kidneys, lung, and nervous system. Women, especially African-American and Asian women, are at highest risk for developing SLE.

Symptoms and Diagnosis

Not all patients with SLE experience the same symptoms. The most common symptoms are joint pain, skin rash, and fever. Symptoms can develop slowly or appear suddenly. Many patients with SLE have “flares,” in which symptoms suddenly worsen and then disappear for long periods of time. Diagnosing SLE is complicated because symptoms vary widely and can resemble other conditions. A doctor will base an SLE diagnosis on certain specific criteria including symptom history and the results of blood tests for antinuclear antibodies.

Treatment

No drug can cure SLE, but many different drugs can help control symptoms and relieve discomfort. The choice of drugs depends on the severity of the condition as well as other factors. Patients with mild SLE may be helped by nonsteroidal anti-inflammatory drugs (NSAIDs) while patients with more severe SLE may require corticosteroids or immunosuppressants. Researchers are working to develop new drugs and treatments for SLE.

Living with SLE

Patients can make lifestyle changes to help cope with SLE. These include:

Avoid excessive sunlight exposure, and wear sunscreen (ultraviolet light is the one of the main triggers of flares).
Get plenty of rest (fatigue is another common SLE symptom).
Engage in regular light-to-moderate exercise to help fight fatigue and heart disease, and to keep joints flexible.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, often life-long, autoimmune disease. It can be mild to severe, and affects mostly women. SLE may affect various parts of the body, but it most often manifests in the skin, joints, blood, and kidneys. SLE was first described in 1828. Its very name helps define the disease:

Systemic is used because the disease can affect organs and tissue throughout the body.
Lupus is Latin for wolf. It refers to the rash that extends across the bridge of the nose and upper cheekbones and was thought to resemble a wolf bite.
Erythematosus is from the Greek word for red and refers to the color of the rash.

Lupus has many different symptoms. Common ones include:

Fatigue
Joint pain or swelling
Skin rashes

Causes

Systemic lupus erythematosus is a complex disorder that occurs as a consequence of a number of independent processes and factors.

Environmental factors, such as viruses, exposure to chemicals, or sunlight trigger inflammatory or immune activity. This immune activation may begin as an appropriate response to an unwanted "invader." But, because of a combination of genetic factors, an individual with lupus develops an ongoing immune response that does not shut itself off appropriately. This leads to waxing and waning flares of inflammation that can involve various organs of the body, depending on specific features of this self-perpetuating immune response in individual patients.

The exact combination of genes that predispose individuals to SLE may differ somewhat from patient to patient, but probably share certain common features which tend to impair the ability of the body to get rid of immune-triggering particles and which tend to prolong or increase the degree of immune responsiveness to these triggers.

A major characteristic of lupus is that it is an autoimmune response in which immune factors, called autoantibodies, attack the person's own cells. Some autoantibodies are normal in a well-balanced immune system, and serve various roles to help the body dispose of wastes, protect from infectious invaders, and to keep blood vessels clear. In healthy people, autoantibodies tend to be well-regulated and well "masked," or covered up, until needed. Therefore, it is probably the high activity and high detectability of autoantibodies that makes lupus unique, not the fact that they exist.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, 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 proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to fight any infections.
In the process, the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting any bleeding blood vessels and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has special factors that control and limit this inflammatory process.

The Infection Fighters. B cells and T cells are two important components of the immune system that play a role in the inflammation associated with lupus. Both B cells and T cells belong to a family of immune cells called lymphocytes. Lymphocytes help fight infection.

B cells and T cells are involved in the immune system's response to infection. Antigens are foreign bodies (such as bacteria and viruses) that stimulate the immune system to produce autoantibodies. When a T cell recognizes an antigen it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

For reasons that are still not completely understood, both the T cells and B cells become overactive in lupus patients. In lupus, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal range of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

Autoantibodies. In the majority of patients with SLE, antinuclear antibodies (ANA) are detectable. Such autoantibodies may be present in individuals up to 7 years prior to their developing symptoms of lupus. Some subtypes of ANA are found in lupus patients and only rarely in people without lupus. These include:

Anti-ds DNA. An autoantibody called anti-double stranded DNA (anti-ds DNA) may play an important role in some lupus patients.
Anti-Sm antibodies. This antibody is found most often in lupus patients of African descent and is almost never detected in people without lupus.
Anti-Ro (SSA) and Anti-La (SSB)
Antiphospholipid antibodies

Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, including:

Infections
Injuries
Tissue repair
Blood clotting
Clearing of debris from inflamed blood vessels
Other aspects of healing.

If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells.

Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE.

Researchers estimated that 20 - 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors identify patients at particular risk for severe disease before they develop symptoms.
A genetic risk factor for lupus in African-American women has been identified.
Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
An abnormal gene identified in some patients with SLE promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African-Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk).

The researchers also observed that a genetic variation in CTLA-4, a protein that helps regulate T cell immune system response, appeared to modify the risk of lupus associated with EBV-IgA antibodies. Therefore, an individual’s CTLA-4 genotype could determine the immune system’s responsiveness in fighting repeat episodes of EBV infection.

Click the icon to see an image of mononucleosis.

Some research suggests that different viruses may imprint specific types of SLE. For instance cytomegalovirus may affect blood vessels and cause problems such as Raynaud's phenomenon or blood abnormalities, but may not affect the kidney as much. These are speculations, however, and not a proven association.

Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. When they bombard the skin, they can alter the structure of DNA in cells below the surface. The immune system may perceive these altered skin cells as foreign and trigger an autoimmune response against them. UV light is categorized as UVB or UVA depending on the length of the wave.

UVB are short waves (280 - 320 nm). The shorter the wavelengths, the more damage they do.
UVA are longer waves (320 - 400 nm). Some research suggests that UVA wavelengths in the longest range, known as UVA1 (340 - 400 nm), may actually repair DNA and normalize immune responses.

Chemicals. Clusters of SLE cases have occurred in populations with high exposure to certain chemicals. Chlorinated pesticides and crystalline silica are two suspects. A number of other chemicals are under investigation. However, it is very difficult to determine a causal role for any specific chemicals. (Silicone breast implants have been under intense scrutiny as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some drugs have been associated with a temporary lupus syndrome (drug-induced lupus), which resolves when these drugs are stopped.

Hormones. Cytokines, major immune factors that are active in SLE, are directly affected by sex hormones. In general, estrogen enhances antibody production, and testosterone reduces antibody production, although their exact role in SLE may be more complicated than that since there are various ways in which each hormone might influence various immune cells. Women with SLE may have lower levels of several active male hormones (androgens), and some men who are affected by SLE may also have abnormal androgen levels.

Premature menopause, and its accompanying symptoms (such as hot flashes), is common in women with SLE. Hormone replacement therapy (HRT), which is used to relieve these symptoms, increases the risk for blood clots and heart problems. It is not clear whether HRT triggers SLE flares. Women should discuss with their doctors whether HRT is an appropriate and safe choice. Guidelines recommend that women who take HRT use the lowest possible dose for the shortest possible time. Women with SLE who have active disease, antiphospholipid antibodies, or a history of blood clots or heart disease should not use HRT.

Oral Contraceptives. Female patients with lupus used to be cautioned against taking oral contraceptives (OCs) due to the possibility that estrogen could trigger lupus flare-ups. However, recent evidence indicates that OCs are safe, at least for women with inactive or stable lupus. Women who have been newly diagnosed with lupus should avoid OCs. Lupus can cause complications in its early stages. For this reason, women should wait until the disease reaches a stable state before taking OCs. In addition, women who have a history of, or who are at high risk for, blood clots (particularly women with antiphospholipid syndrome) should not use OCs. The estrogen in OCs increases the risk for blood clots.

Risk Factors

The number of people diagnosed with lupus has more than tripled over the past four decades. Some experts believe this may simply indicate a greater degree of doctor training in recognizing the syndrome.

About 90% of lupus patients are women, most diagnosed when they are in their childbearing ages. Hormones may be an explanation. After menopause, women are only 2.5 times as likely as men to contract SLE. Flares also become somewhat less common after menopause in women who have chronic SLE.

African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics and Asians are also more susceptible to the disease.

A family history plays a strong role in SLE. A brother or sister of a patient with the disorder has 20 times the risk as someone without an immediate family member with SLE.

The disease is rare in childhood. When it does occur, it is often associated with thrombotic thrombocytopenia purpura, a condition resulting from abnormally low levels of blood platelets. SLE in children may also be caused by certain medications, including minocycline and zafirlukast.

Rheumatoid Arthritis. Studies have investigated the relationship among hormones, SLE, and rheumatoid arthritis, another autoimmune disease. Higher levels of estrogen are associated with SLE, while lower levels are associated with rheumatoid arthritis. Some research suggests that some patients, in fact, progress from one disease to the other, and that such transitions occur during major hormonal shifts, such as the onset of menopause or pregnancy.

Rheumatoid arthritis is a systemic autoimmune disease that initially attacks the lining, or synovium, of the joints.

Many prescription drugs can cause lupus-like skin symptoms. In one study, the most common drugs causing these symptoms were high blood pressure (hypertension) medications, including hydrochlorothiazide, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. About 40 different drugs have been linked to lupus onset. Anyone diagnosed with cutaneous lupus erythematosus should be sure to tell their doctors all the medications (including herbs and supplements) that they are taking.

Smoking. Smoking may be a risk factor for triggering SLE and can increase the risk for skin and kidney problems in women who have the disease.

Symptoms

SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to be worse during winter months, perhaps because prolonged exposure to sunlight in the summer causes a gradual build-up of factors that trigger symptoms months later.

The most common symptom is joint pain, which occurs in about 90% of patients with SLE. Characteristics of this symptom vary widely:

It is often accompanied by swelling and redness.
It can last from hours to months.
It may be mild or severe.
It can occur in one joint, move from one to another, or flare erratically.
Pain often occurs in the morning and improves during the day, only to return later when the patient tires.
The joints most affected are fingers, wrists, elbows, knees, and ankles. (Joints in the spine and neck are not affected.)

Children may experience these symptoms as growing pains, and, in all patients, they may be the only symptoms for many years.

Fever occurs in 90% of patients with SLE and is usually caused by the inflammatory process of the disease, not by infection. It is low-grade except during an acute lupus crisis.

Three-quarters of patients with SLE have skin inflammation and skin lesions (ulcers, rashes, or other injured areas). About half of these lesions are photosensitive; that is, they are aggravated by ultraviolet (UV) radiation from sunlight, even from light coming through a window. (UV radiation may even trigger systemic flares in patients with SLE.)

A number of different skin conditions have been described in patients with SLE.

Discoid Lupus Erythematosus. About 20% of patients have discoid lesions. In such cases, the condition is often known as discoid lupus erythematosus (DLE). Patients with this condition may have the following skin abnormalities:

Discoid means coin-shaped, so these lesions are round and raised. They are also scaly. Untreated, the margins gradually extend outward as the center dries out and shrivels, causing severe scarring. If discoid lesions appear on the scalp, they can plug hair follicles and cause irreversible hair loss. Discoid lesions can also appear on the upper body.

Lupus, discoid -- view of lesions on the chest: This close-up picture of the neck clearly shows the typical rounded appearance of discoid lupus. The whitish appearance is caused by scaling. The two dark spots are biopsy sites and are not part of the disease.

A butterfly-shaped rash across the face may accompany this condition. This rash causes little scarring, although spidery, branching lines of swollen capillaries (the tiniest blood vessels) may appear.

Click the icon to see an image of systemic lupus erythematosus.

Most patients with this condition have only a limited skin disorder. In only about 10% of cases does discoid lupus develop into full-blown SLE.

Subacute Cutaneous Lupus Erythematosus. Subacute cutaneous lupus erythematosus (SCLE) can cause skin lesions on parts of the body that are exposed to sunlight. These lesions do not cause scarring.

Vasculitis. Patients with SLE sometimes develop inflammation in the blood vessels (vasculitis) that may have the following effects on the skin:

Red welts may form across large areas of the body.
Sometimes deep red bumps may appear, particularly on the leg, where they may ulcerate.
In some people, reddish-purple lesions appear on the pads of fingers and toes or near the nails of fingers and toes.
Lesions caused by vasculitis may ulcerate or blister if they erupt on mucous membranes in the mouth, nose, or vagina and can be painful if they occur on the throat.
Vasulitis can attack blood vessels in almost any other organ, including the brain, the heart, and the gastrointestinal tract.

Click the icon to see an image of vasculitis.

Other symptoms include:

Fatigue
Loss of appetite, nausea, and weight loss
Chest pain
Bruising
Menstrual irregularities
Thought and concentration disturbances
Personality changes
Sleep disorders, such as restless legs syndrome and sleep apnea
Dryness of the eyes and mouth
Brittle hair or hair loss

Hair loss or breakage may also occur in about half of patients with SLE during severe flares or after pregnancy or severe illness. In such cases, hair grows back.

Raynaud's phenomenon is a condition in which cold or stress can cause spasms in impaired blood vessels, resulting in pain in fingers and toes. It occurs as part of the inflammatory response in blood vessels, which can narrow them and reduce circulation. In extreme cases, gangrene can result.

Click the icon to see an image of Raynaud's phenomenon.

A number of conditions may resemble SLE:

Scleroderma: Hardening of the skin caused by overproduction of collagen
Multiple sclerosis: Fatigue, heaviness or clumsiness in the arms and legs
Rheumatoid arthritis: Inflammation of the lining of the joints
Sjögren syndrome: Characterized by dry eyes and dry mouth
Mixed connective tissue disorder: Similar to SLE, but milder
Myositis: Inflammation and degeneration of muscle tissues
Rosacea: Flushed face with pus-filled blisters
Seborrheic dermatitis: Sores on lips and nose
Lichen planus: Swollen rash that itches, typically on scalp, arms, legs, or in the mouth
Dermatomyositis: Bluish-red skin eruptions on face and upper body
Lyme disease: Bulls-eye rash, joint inflammation, and flu-like symptoms

Complications

Systemic lupus erythematosus (SLE) is one of the most serious rheumatic diseases. According to a 2002 government study, the annual number of deaths has risen from 879 - 1,406 since 1979. About a third of these deaths occur in people aged 15 - 44 years, mostly women. Such numbers may be underestimates, since SLE can affect so many organs that a cause of death in some people with SLE may not be directly attributed to the condition. A primary cause of death among patients with lupus is atherosclerosis, a disease of the coronary blood vessels resulting from accelerated buildup of plaque.

SLE is unpredictable and varies greatly form one individual to the next. Severity also appears to differ among ethnic groups and countries. In European and North American patients with SLE for example, overall 5-year survival rates are 93 - 95%, while in Asia or Africa they are considerable lower (60 - 70%). Other research indicates that African-American and Hispanic American patients suffer greater organ damage than Caucasian patients. Genetic factors appear to have some influence on specific effects of SLE on organ damage among ethnic groups. However, the poorer outlook among minority groups and in underdeveloped nations is probably due to less access to good health care.

Mild SLE. About 20 - 30% of cases are mild. For many of these patients, the only symptoms may be the skin rashes of discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) with or without joint aches. The number and intensity of symptoms in mild cases often decrease over time, as does the likelihood of major organ involvement. These skin conditions, however, are not absolute insurance against more severe disease, and patients with mild SLE should be tested for organ involvement.

Widespread SLE. Most commonly, SLE is a chronic, life-long disease, alternating between periods of symptom relapse, (called flares), and remission. The disease may begin in any of the various systems of the body and progress unpredictably to others. The following are typical patterns:

Symptom relapses, or flares, occur on the average of two or three times a year.
Between flares, most patients with SLE function at about 90% of normal capacity.

The degree of severity depends on different factors:

Severity of the inflammatory response
Frequency of episodes
The degree of organ or system involvement

Vital organs or systems, such as lungs, kidneys, nervous system, joints skin, and others are affected in 50 - 75% of patients with SLE. Infections followed by kidney failure are the chief causes of death in patients with SLE.

Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Long-term progress of the disease is affected greatly by treatment in the initial acute phase of the disease, so a speedy and accurate diagnosis is all-important. The 10-year survival rate with treatment is now 85 - 95%, and many people have a normal life span. SLE that develops later in life is generally less serious than SLE that strikes in childhood.

Almost 85% of patients with SLE experience problems associated with abnormalities in the blood.

Anemia. About half of patients with SLE are anemic. Causes include:

Iron deficiencies resulting from excessive menstruation
Iron deficiencies from gastro-intestinal bleeding caused by some of the treatments
A specific anemia called hemolytic anemia, which destroys red blood cells
Anemia of chronic disease

Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and be severely (acute).

Antiphospholipid Syndrome. Between 34 - 42% of patients with SLE have antiphospholipid syndrome (APS). This is a specific set of conditions related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. These autoantibodies react against fat molecules called phospholipids, and so are called antiphospholipids. Their actions have complex effects that include causing narrowing and abnormalities of blood vessels.

Patients who have APS have a very incidence of blood clots, which most often occur in the deep veins in the legs (32%). Blood clotting, in turn, puts patients at higher risk for stroke (13%) and pulmonary embolism (clots in the lungs) (9%).

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins). Such a clot prevents normal return of blood from the leg to the heart.

About 22% of patients have thrombocytopenia -- a reduction in blood platelets that can cause bleeding.
The effects on blood vessels have also been associated with confusion, headaches, and seizures. Leg ulcers can also develop.
Patients with APS who become pregnant have a high incidence of pregnancy loss, especially in the late term.

Not all patients with APS carry both of the autoantibodies, and they can also wax and wane and so have varying effects. APS also occurs without lupus in about half of patients with the syndrome.

Thrombocytopenia. In thrombocytopenia, antibodies attack blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines. (This condition can also occur in APS, but it is not considered to be one of the standard features of the syndrome.)

Neutropenia. Neutropenia is a drop in the number of white blood cells. Patients with SLE often neutropenia, but the condition is usually harmless unless the reductions are so severe that they leave the patient vulnerable to infections.

Acute Lupus Hemophagocyte Syndrome. A rare blood complication of SLE that occurs primarily in Asians is called acute lupus hemophagocytic syndrome. It is generally of short duration and characterized by fever and a sudden drop in blood cells and platelets.

Lymphomas. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). A 2005 study reported that patients with SLE were over seven times more likely to develop NHL than healthy patients.

Heart disease is a primary cause of death in lupus patients. The immune response in SLE can cause inflammation and other damaging effects that can cause significant injury to the arteries and tissues associated with the circulation and the heart. In addition, SLE treatments (particularly corticosteroids) affect cholesterol, weight, and other factors that can also affect the heart. For decades, experts questioned the extent to which the drugs used to treat SLE contributed to the high rate of atherosclerosis in such patients. Numerous studies now suggest that something about the disease process itself, possibly the chronic inflammation of the blood vessels, probably lies at the root of this dangerous problem. In any event, patients with SLE, have a higher chance for the following conditions, which put them at risk for heart attack or stroke:

Atherosclerosis, or plaque buildup in the arteries
Increased stiffness in the arteries
Unhealthy cholesterol and lipid (fatty molecules) levels
High blood pressure, most likely because of kidney injury and corticosteroid treatments
Congestive heart failure
Pericarditis, an inflammation of the tissue surrounding the heart (occurs in about 30% of patients)
Myocarditis, an inflammation of the heart muscle itself (rare)

Click the icon to see an image of pericarditis.

Abnormalities in the valves of the heart (rare)
Blood clots

The risk for cardiovascular disease, heart attack, and stroke is much higher than average in younger women with SLE. The risks decline as such women age.

SLE affects the lungs in about 60% of patients:

Recurrent inflammation of the membrane lining the lung (pleurisy) is the most common problem.
In some cases, fluid accumulates, a condition called pleural effusion, and can cause stabbing localized pain that worsens when coughing, sneezing, laughing, or taking a deep breath.
Inflammation of the lung itself in SLE is called lupus pneumonitis. It can be caused by infections or by the SLE inflammatory process. Symptoms are the same in both cases: fever, chest pain, labored breathing, and coughing. Rarely, lupus pneumonitis becomes chronic and causes scarring in the lungs, which reduces their ability to deliver oxygen to the blood.
A very serious and also rare condition called pulmonary hypertension occurs when high pressure develops in the vessels supplying blood to the lungs.

Click the icon to see an image of primary pulmonary hypertension.

The kidneys are a crucial battleground in SLE because it is here that the debris left over from the immune attacks is most likely to be deposited. About 50% of patients with SLE exhibit inflammation of the kidneys (called lupus nephritis).This condition occurs in different forms and can vary widely in severity.

Click the icon to see an image of the kidney.

Proliferative nephritis is a serious variant of lupus nephritis. It occurs when the inflammatory process causes widespread damage and scarring in the blood vessels of the kidneys, which filters waste products, water, and salts out of the blood. The condition is associated with high blood pressure and kidney deterioration.
Membranous lupus nephritis is another variant that is often associated with a good outlook. In some cases, however, if the kidney is persistently exposed to high protein levels, the disorder can progress to fatal end-stage kidney (renal) disease.

Serious complications occur eventually in about 30% of patients. If kidney injury develops, it almost always occurs within 10 years of the onset of SLE, rarely after that.

Nearly all patients with SLE report some symptoms relating to problems that occur in the central nervous system (CNS), which includes the spinal cord and the brain. Most of these symptoms are minor and some, such as headache, may be related to depression rather than the disease itself. CNS involvement is more likely to occur in the first year, usually during flare-ups in other organs. Symptoms vary widely and may be indistinguishable from psychiatric or neurologic disorders or from the side effects of some medications used for SLE. Central nervous system symptoms are usually mild, but there is little effective treatment available for them. CNS symptoms get worse as the disease progresses.

The most serious CNS disorder is inflammation of the blood vessels in the brain, which occurs in 10% of patients with SLE. Fever, seizures, psychosis, and even coma can occur. Other CNS side effects include:

Irritability
Emotional disorders (anxiety, depression)
Mild impairment of concentration and memory
Migraine and tension headaches
Problems with the reflex systems, sensation, vision, hearing, and motor control

Infections are a common complication and a major cause of death in all stages of SLE. The immune system is indeed overactive in SLE, but it is also abnormal and reduces the ability to fight infections. Patients are not only prone to the ordinary streptococcal and staphylococcal infections, but they are also susceptible to fungal and parasitic infections (called opportunistic infections), which are common in people with weakened immune systems. They also face an increased risk for herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressants, treatments used for SLE, also increase the risk for infections, thereby compounding the problem.

About 45% of patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, and diarrhea. Severe inflammation of the intestinal tract occurs in less than 5% of patients and causes acute cramping, vomiting, diarrhea, and, rarely, intestinal perforation, which can be life-threatening. Fluid retention and swelling can cause intestinal obstruction, which is much less serious but causes the same type of severe pain. Inflammation of the pancreas can be caused by the disease and by corticosteroid therapy.

Arthritis caused by SLE almost never leads to destruction or deformity of joints. The inflammatory process can, however, damage muscles and cause weakness. Patients with SLE also commonly experience reductions in bone mass density (osteoporosis) and have a higher risk for fractures, whether or not they are taking corticosteroids (which can increase the risk for osteoporosis). Women who have SLE should have regular bone mineral density scans to monitor bone health.

Click the icon to see an image of osteoporosis.

Inflamed blood vessels in the eye can reduce blood supply to the retina, resulting in degeneration of nerve cells and a risk of hemorrhage in the retina. The most common symptoms are cotton-wool-like spots on the retina. In about 5% of patients sudden temporary blindness may occur.

In one study, 40% of patients with SLE quit work within 4 years of diagnosis, and many had to modify their work conditions. Significant factors that predicted job loss included high physical demands from the work itself, a more severe condition at the time of diagnosis, and lower educational levels. People with lower income jobs were at particular risk for leaving them.

Women with lupus who conceive face high-risk pregnancies. It is important for women to understand the potential complications and plan accordingly. The most important advice is to avoid becoming pregnant when lupus is active.

Research suggests that the following factors predict a successful pregnancy:

Disease state at time of conception. Experts strongly recommend that women wait to conceive until their disease state has been inactive for at least 6 months.
Kidney (renal) function. Women should make sure that their kidney function is evaluated prior to conception. Poor kidney function can worsen high blood pressure and cause excess protein in the urine. These complications increase the risk for preeclampsia and miscarriage.
Lupus-related antibodies. Antiphospholipid and anticardiolipin antibodies can increase the risks for preeclampsia, miscarriage, and stillbirths. Anti-SSA and anti-SSB antibodies can increase the risk for neonatal lupus erythematosus, a condition that can cause skin rash and liver and heart damage to the newborn baby. Levels of these antibodies should be tested at the start of pregnancy. Certain medications (aspirin, heparin) and tests (fetal heart monitoring) may be needed to ensure a safe pregnancy.
Medication use during pregnancy. Women with active disease may need to take low-dose corticosteroids, but women with inactive disease should avoid these drugs. Steroids appear to pose a low risk for birth defects, but can increase a pregnant woman’s risks for gestational diabetes, high blood pressure, infection, and osteoporosis. For patients who need immunosuppressive therapy, azathioprine (Imuran) is an option. Methotrexate (Rheumatrex) and cyclophosphamide (Cytoxan) should not be taken during pregnancy.

Pregnancy Risks

Women with lupus are 20 times more likely to die during pregnancy than women without the disease. The risk for maternal death is due to the following serious conditions that can develop during pregnancy:

Miscarriages. About 25% of lupus pregnancies result in miscarriage. The risk is highest for patients with antiphospholipid antibodies, active kidney disease, or high blood pressure.
Blood clots. Women with lupus have a 6 times greater risk for developing deep vein thrombosis (blood clots) than women without the disease.
Clotting complications. Low blood platelet count and anemia are also risks. Women with lupus are 3 times more likely to need a transfusion during pregnancy than women without lupus.
Infections. Blood infections (sepsis), pneumonia, and urinary tract infections are more common in pregnant women with lupus.
Preeclampsia. Women with lupus are three times more likely than healthy women to develop preeclampsia (pregnancy-related high blood pressure), which can be potentially life threatening.

Birth Complications

Pre-term birth. Women with lupus are 2.5 times more likely to have pre-term labor than women without lupus. Pre-term labor increases the risk for giving birth to low-weight babies.
Stillbirths. A 2005 study reported that the risk of still births was 10 times greater for women who had not yet been diagnosed with lupus, and 4 times greater for women with diagnosed lupus, compared with healthy women. This suggests that lupus may have a pre-disease state.
Caesarean section. Thirty-seven percent of women with lupus require a C-section compared with 22% of women without the disease.

Despite these obstacles, many women with lupus have healthy pregnancies and deliver healthy babies. To increase the odds of a successful pregnancy, it is important for women to plan carefully before becoming pregnant. Be sure to find knowledgeable doctors with whom you can communicate and trust. Experts recommend that pregnant women with lupus assemble an interdisciplinary health care team that includes a rheumatologist, high-risk obstetrician, and (for patients with kidney disease) a nephrologist.

Diagnosis

No single test can confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjögren syndrome or scleroderma, may even be present at the same time as SLE.

1. Characteristic rash across the cheek

2. Discoid lesion rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Inflammation of membranes in the lungs, the heart, or the abdomen

7. Evidence of kidney disease

8. Evidence of severe neurologic disease

9. Blood disorders, including low red and white blood cell and platelet counts

10. Immunologic abnormalities

11. Positive antinuclear antibody (ANA)

Note: A patient must experienced four of the criteria before a doctor can classify the condition as SLE. These criteria, proposed by the American College of Rheumatology, are not to be relied upon solely for diagnosis, however.

Methods for measuring the antibodies involved with SLE vary, and the range of results can be bewildering. Repeat tests may be needed.

Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.

High levels of ANA are found in more than 98% of patients with SLE. A number of other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
They also may be weakly present in about 20 - 40% of healthy women.
Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.

In general, the ANA test is considered a screening test:

If SLE symptoms are present and the ANA test is positive, other tests for SLE will be administered.
If SLE symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE, and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients. Although the antibody is not usually seen in lupus patients, its confirmed presence almost always indicates SLE.
When the ANA is negative but the diagnosis is still strongly suspected, a test for anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB) antibodies may identify patients with a rare condition called ANA negative, Ro lupus. These autoantibodies may be involved in the sun-sensitive rashes experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mother's antibodies cross the placenta and cause inflammation in the developing child's skin or heart.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests may be able to detect the presence of the two major antiphospholipid antibodies:

A quarter to a half of patients with SLE may have these antibodies. They attack blood-clotting regulator proteins that stick to phospholipids, fatty compounds found in cell membranes throughout the body. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of (and irregularities in) blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.
The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. There is some evidence that complete deficiencies of C1q may be a key factor in the inability of the immune system to contain the autoimmunity process. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.

Click the icon to see an image of the formed elements of blood.

If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are present in about 80% of patients with active SLE and in 30 - 40% of those with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although it can also be present with normal creative levels.
Tests for detecting anti-ds DNA antibodies and complement. High levels of anti-ds DNA and low levels of complement C3 suggest kidney damage. (It should be noted, however, that some patients with severe kidney damage show low levels of anti-ds DNA.) Testing for anti-C1q antibodies now appears to be an even more reliable indicator of lupus nephritis.
Urine analysis. Urine analyses should be performed at 4- to 6-month intervals to check for signs of kidney involvement.
A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.

Click the icon to see an image of an electrocardiogram.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, experts recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.

Treatment

No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. Treatment of SLE varies depending on the extent and severity of the disease.

Only three drugs are FDA-approved for the treatment of lupus:

Prednisone
Aspirin
Hydroxychloroquine

However, none of these drugs are the current standard of care. In everyday practice, numerous other drugs are commonly used. Researchers are conducting numerous clinical studies and drug investigations. Genetic research in lupus is progressing very rapidly, and hopefully new drugs will be approved in the future. There are also different drugs available to treat some of the conditions associated with lupus.

Less intensive treatments may be effective for symptoms of mild lupus. They include:

Creams and sunblocks for rashes
Nonsteroidal anti-inflammatory drugs for fever, arthritis, and headache
Antimalarial drugs for pleurisy, mild kidney involvement, and inflammation of the tissue surrounding the heart

More aggressive treatment is needed if there is serious disease progression, as evidenced by:

Hemolytic anemia
Low platelet count with an accompanying rash (thrombocytopenia purpura)
Major involvement in the lungs or heart
Significant kidney damage
Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract
Severe central nervous system symptoms

The primary approach to treating severe SLE is to suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs. Investigational drugs and procedures are also showing promise.

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspects of SLE. They are discussed elsewhere in this report.

Treatment for Cutaneous and Mild SLE

Creams. Steroid creams are often used for skin lesions. However, many patients with discoid lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) may help some lesions that do not clear up with steroid creams.

Sun Protection. Sun protection is essential. Patients should always use sunblock creams (not just sunscreens) and always wear hats and clothing made of tightly woven fabrics.

Common NSAIDs. NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil).

For people with lupus, NSAIDs may help relieve:

Joint pain and swelling
Muscle pain

Side Effects. Regular, long-term use of NSAIDs can cause ulcers and gastrointestinal bleeding, which can lead to anemia. To avoid these problems, it’s best to take NSAIDs with food or immediately after a meal. Long-term use of NSAIDs (with the exception of aspirin) can also increase the risk for heart attack and stroke.

Other NSAID side effects may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Patients who have kidney problems associated with lupus (lupus nephritis) should be especially cautious about using NSAIDs. Experts recommend that patients with lupus who take NSAIDs on a regular basis should have their liver and kidney function tested every 3 - 4 months.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are more likely to bleed than those caused by the bacteria Helicobacter pylori.

Those at high risk for bleeding include people over age 60, anyone with a history of ulcers or gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

A doctor may prescribe antimalarial drugs for discoid lupus (skin sores) or mild lupus when skin problems and joint pains are the predominant symptoms:

Hydroxychloroquine (Plaquenil) is the most common antimalarial drug used for lupus. This drug is effective as maintenance therapy to reduce flares in patients with mild or inactive disease. Hydroxychloroquine may help protect against blood clots in people with antiphospholipid syndrome, high cholesterol levels, and bone loss.
Other antimalarial drugs include chloroquine (Aralen) or quinacrine (Atabrine).

Treatment may start initially with high doses in order to accumulate high levels of the drug in the bloodstream. It is not known exactly why antimalarials work. Some researchers believe they inhibit the immune response, and others think they interfere specifically with inflammation.

A 2006 study suggested that anti-malarial drugs work best in patients who have genetic predispositions to certain types of immune-fighting proteins. The study found that patients who had genetic variations causing abnormally high levels of tumor necrosis alpha (TNF-alpha) and abnormally low levels of interleukin-10 (IL-10) responded best to these drugs.

Side Effects. Side effects of antimalarials may include:

Skin rash
Change in skin color (yellow in the case of quinacrine)
Gastrointestinal problems
Headache
Hair loss
Muscle aches
Eye damage

The most serious is damage to the retina, although this is very uncommon at low doses. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated, but it is not reversible if the damage develops after taking chloroquine. An eye exam is advisable about every 6 months.

Antimalarials may also be used in combination with other anti-SLE drugs, including immunosuppressants and corticosteroids. It should be noted that smoking significantly reduces the effectiveness of antimalarial drugs.

Treatment for Severe SLE

Severe SLE is treated with corticosteroids, also called steroids, which suppress the inflammatory process. Steroids can help relieve many of the complications and symptoms, including anemia and kidney involvement.

Oral prednisone (Deltasone, Orasone) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solumedrol), hydrocortisone, and dexamethasone (Decadron).

Some people need to take oral prednisone for only a short time; others may require it for a long duration. An intravenous administration of methylprednisolone using "pulse" therapy for 3 days is proving useful for flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants, may be beneficial.

Regimens vary widely, depending on the severity and location of the disease. Most patients with SLE can eventually function without prednisone, although some may have to choose between the long-term toxicity of corticosteroids and the complications of active disease.

Side Effects of Long-Term Oral Corticosteroids. Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. The bone-thinning condition osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, alendronate etidronate, risedronate, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Other side effects associated with prolonged use of oral steroids include:

Cataracts
Glaucoma
Diabetes
Fluid retention
Susceptibility to infections
Weight gain
High blood pressure
Acne
Excess hair growth
Wasting of the muscles
Menstrual irregularities
Irritability
Insomnia
Psychosis

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. A few cases of severe adrenal insufficiency have occurred when patients switched from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctors measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Drugs known as immunosuppressants are often used, either alone or with corticosteroids for very active SLE, particularly when kidney or neurologic involvement or acute blood vessel inflammation is present. These drugs suppress the immune system by damaging cells that grow rapidly, including those that produce antibodies. About a third of patients take immunosuppressants at some point in the course of the disease.

Specific Immunosuppressants. The most common immunosuppressants are:

Cyclophosphamide (Cytoxan) used to be considered the gold standard of treatment for lupus kidney disease (lupus nephritis). Cyclophosphamide is given intravenously and is sometimes used in combination with corticosteroids or other drugs. It has been used for lupus since the 1970s. Side effects are very severe and include nausea, vomiting, hair loss, infertility, and infections.
Mycophenolate mofetil (CellCept) is now becoming the new standard. Many recent studies have shown that CellCept works better than cyclophosphamide and causes far fewer severe side effects (diarrhea is the main side effect). Unlike cyclophosphamide, it is taken by mouth. Most doctors now recommend CellCept as a first-line treatment for newly diagnosed patients with mild or moderate lupus kidney disease. It may not be appropriate for patients with kidney failure or rapidly progressing kidney disease.
Azathioprine (Imuran) has the lowest toxicity, but is less effective than other immunosuppressants.
Cyclosporine (Sandimmune) has been used for years, mostly for SLE associated with kidney involvement. High blood pressure is common, however, with this drug.

The most frequent side effects of immunosuppressants include:

Stomach and intestinal problems
Skin rash
Mouth sores
Hair loss

Serious side effects of immunosuppressants include:

Low blood cell counts
Anemia
Menstrual irregularity
Early menopause
Ovarian failure
Infertility
Herpes zoster (shingles)
Liver and bladder toxicity
Increased risk of cancer

In general, immunosuppressants should not be used alone unless corticosteroids are ineffective or inappropriate. Grapefruit juice has an enzyme that may enhance the effects of some immunosuppressants.

Monoclonal Antibodies (MAbs). A MAb is a laboratory-made protein that targets specific immune cells, such as B cells. B cell over-activation has been identified as a key component of the lupus disease process. Promising MAbs in development for SLE treatment include:

Epratuzumab is being investigated for treatment of moderate-to-severe lupus. It is currently in Phase III trials.
Belimumab (Lymphostat-B) is also in Phase III trials.
Rituximab (Rituxan), a lymphoma cancer and rheumatoid arthritis drug, has shown good results in early trials in improving lupus symptoms. Researchers think it may affect how T cells and B cells interact. However, in December 2006 the FDA warned of several cases of progressive multifocal leukoencephalopathy (PML) in patients with lupus who took this drug. PML is a life-threatening brain infection. Some patients developed PML as late as 12 months after their last dose of rituximab. Two patients with lupus died from PML.

Intravenous Immunoglobulins. Intravenous immunoglobulins (IVIG) are sometimes used for patients who have not responded to other SLE treatments. Immunoglobulins are antibodies produced by immune system B-lymphocyte cells. IVIG is a blood product that contains these antibodies.

Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a natural steroid hormone that is produced by the adrenal glands and converted into estrogen and androgen. The synthetic equivalent of DHEA, prasterone (Prestara), is being investigated as a potential treatment for SLE. Several clinical trials have indicated promising, although mixed, results for prasterone’s effect on preventing bone mineral density loss in women who take prednisone. Prasterone is still in the drug development stage and it is not clear when, or if, it will be commercially available.

Autologous Stem Cell Transplantation. Some patients with severe lupus have achieved at least short-term remission after undergoing autologous transplantation of stem cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. A 2006 study in the Journal of the American Medical Association indicated that autologous stem cell transplantation can help boost the immune system and lead to remission. Patients in the study had severe lupus that was resistant to standard treatments. Results were long-lasting. Researchers calculated that patients had a 50% chance of remaining disease-free after 5 years.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

Plasmapheresis. Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves first taking blood from the patient. The plasma, which contains the inflammatory antibodies and other immunologically active substances, is discarded and replaced with other fluids. The blood is then returned. Plasmapheresis is not useful for routine management of patients but may have some benefits for patients who do not respond to standard treatments or in specific cases, such as lupus patients with hemolytic anemia.


Infections, Inflammation, or Hypertension in the Lungs	Preventive Measures. Immunizations with inactive viruses and preventive antibiotics should be considered for patients with SLE who are at high risk for infection. Treating Infections. Lung infections need to be treated aggressively with antibiotics. However, antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash. Treating Lung Inflammation. While inflammation of the lung (pneumonitis) resembles pneumonia, it is not an infection but is a result of the autoimmune process. This condition needs to be treated with corticosteroids or immunosuppressants, but only if the doctor is sure infection is not present. Treating Pulmonary Hypertension. Pulmonary hypertension is very serious. Drugs known as prostacylins -- which include epoprostenol, iloprost, and treprostinil -- are standard drugs. Bosentan (Tracleer) is the first oral drug approved for pulmonary hypertension. An inhaled iloprost formulation (Ventavis) was approved in 2004. Sildenafil (Viagra, Revatio) may also be used for this condition. Lung transplantation may be required.
Bleeding and Clotting Disorders	Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS). (Aspirin does not appear to be protective in men who carry the autoantibodies responsible for APS.) In patients who have experienced blood clots, treatment with the anticoagulant warfarin (Coumadin) is advisable. This blood-thinning drug may be needed lifelong. Scientists are investigating other treatment options, including autologous stem cell transplantation. The procedure has shown promise in studies for treating lupus-associated APS, but it is still experimental. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). Treatments that may be effective for thrombocytopenia include combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG may be helpful in some patients. Surgical removal of the spleen may be advisable if bleeding disorders are a serious problem, but this option should be considered carefully, because the spleen provides one line of defense against infection. (Abnormal spleen function, in any case, appears to be fairly common in SLE.)
Kidney Disease	Drugs. Mycophenolate mofetil (CellCept), a newer drug, can help treat kidney disease associated with SLE and has fewer side effects than other immunosuppressants. It is taken by mouth. Recent studies suggest that it works better than cyclophosphamide. CellCept may be best for patients with mild-to-moderate lupus kidney disease and may not be appropriate for patients with advanced kidney disease. Intravenous cyclophosphamide is the most effective drug at this time for proliferative lupus nephritis, and, in combination with a steroid, has been shown to control advanced kidney disease in 60 - 90% of patients. It has severe side effects, including nausea, vomiting, hair loss, and infertility. Steroids are also useful for treating active kidney disease and for managing milder forms of nephritis. Procedures. Kidney transplant or dialysis should be considered for patients with SLE with severe kidney damage. For unknown reasons, SLE does not generally recur in the transplanted kidneys. Studies are conflicting, however, over whether SLE transplant patients have higher organ-rejection rates than other kidney-transplant recipients. Both transplantation and dialysis have potentially serious complications. Plasmapheresis. It is not clear if plasmapheresis is beneficial for SLE kidney disease.
Osteoporosis	Treatments for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERMs). [For more information, see In-Depth Report #18: Osteoporosis.]
Heart Disease	The need for aggressive treatment of high blood pressure often accompanies kidney disease. SLE is also accompanied by high cholesterol levels, which requires diet changes and drug therapies. [For more information, see In-Depth Reports #3: Coronary artery disease; #14: High blood pressure; #23: Cholesterol; and #43: Heart healthy diet.]

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Click the icon to see an illustrated series detailing kidney transplant.

Lifestyle Changes

People with SLE should try to maintain a healthy and active lifestyle. Light-to-moderate exercise, interspersed with rest periods, is good for the heart, helps fight depression and fatigue, and can help keep joints flexible.

Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important.

It is very important that patients with SLE avoid excessive exposure to sunlight. Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing and sunblocks. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.

Chronic stress has profound physical effects and influences the progression of SLE. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy activities may also help prevent the depression and anxiety associated with the disease.

Resources

www.lupus.org -- Lupus Foundation of America
www.lupusny.org -- SLE Foundation of America
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.lupusresearchinstitute.org -- Lupus Research Institute

References

Bernatsky S, Ramsey-Goldman R, Isenberg D, Rahman A, Dooley MA, Sibley J, et al. Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 2007 May;46(5):830-2. Epub 2007 Jan 25.

Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96.

Dörner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther. 2006;8(3):R74. Epub 2006 Apr 21.

Gompel A, Piette JC. Systemic lupus erythematosus and hormone replacement therapy. Menopause Int. 2007 Jun;13(2):65-70.

Harel-Meir M, Sherer Y, Shoenfeld Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Clin Pract Rheumatol. 2007 Dec;3(12):707-15.

Khamashta MA. Systemic lupus erythematosus and pregnancy. Best Pract Res Clin Rheumatol. 2006 Aug;20(4):685-94.

Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol. 2007 Jan;19(1):49-54.

Kocis P. Prasterone. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10. Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Oct;2(10):562-9.

Mackillop LH, Germain SJ, Nelson-Piercy C. Systemic lupus erythematosus. BMJ. 2007 Nov 3;335(7626):933-6.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005 Apr;32(4):616-21.

Sabahi R, Anolik JH. B-cell-targeted therapy for systemic lupus erythematosus. Drugs. 2006;66(15):1933-48.

Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum. 2007 Sep;56(9):3070-9.

Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, Portales-Pérez D, Baranda L, Abud-Mendoza C, et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther. 2006;8(3):R83. Epub 2006 May 5.

Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):968-75. Epub 2007 Aug 8.

Walsh M, Jayne D. Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int. 2007 Sep;72(6):676-82. Epub 2007 Jul 4.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Aging changes in hair and nails

admin — Thu, 04 Sep 2008 19:18:29 -0700

Overview

Information

Illustrations

Hair follicle of young person

Aged hair follicle

Aging changes in nails

HEALTH GUIDE REFERENCE FROM A.D.A.M

Information

Hair color change is probably one of the most obvious signs of aging. Hair color is caused by a pigment (melanin) produced by hair follicles. With aging, the follicle produces less melanin.

Graying often begins in the 30s, although this varies widely. Graying usually begins at the temples and extends to the top of the scalp. Hair becomes progressively lighter, eventually turning white.

Many people have some gray scalp hair by the time they are in their 40s. Body and facial hair also turn gray, but usually later than scalp hair. The hair in the armpit, chest, and pubic area may gray less or not at all.

Graying is genetically determined. Gray hair tends to occur earlier in Caucasians and later in Asian races. Nutritional supplements, vitamins, and other products will not stop or decrease the rate of graying.

HAIR THICKNESS CHANGES

Hair is a protein strand that grows through an opening (follicle) in the skin. A single hair has a normal life of about 4 or 5 years. That hair then falls out and is replaced with a new hair.

How much hair you have on your body and head is determined by your genes. However, almost everyone experiences some hair loss with aging. The rate of hair growth slows.

The hair strands become smaller and have less pigment, so the thick, coarse hair of a young adult eventually becomes thin, fine, light-colored hair. Many hair follicles stop producing new hairs altogether.

About a quarter of men begin to show signs of baldness by the time they are 30 years old, and about two-thirds of men have significant baldness by age 60. Men develop a typical pattern of baldness associated with the male hormone testosterone (male-pattern baldness). Hair may be lost at the temples or at the top of the head.

Women may also develop a typical pattern of hair loss as they age (female-pattern baldness). The hair becomes less dense all over and the scalp may become visible.

Body and facial hair are also lost, but the hairs that remain may become coarser. Some women may notice a loss of body hair, but may find that they have coarse facial hair, especially on the chin and around the lips.

Men may find the hair of their eyebrows, ears, and nose becoming longer and coarser.

NAIL CHANGES

The nails also change with aging. They grow slower and may become dull and brittle. They may become yellowed and opaque.

Nails, especially toenails, may become hard and thick. Ingrown toenails may be more common. The tips of the fingernails may fragment.

Sometimes, lengthwise ridges will develop in the fingernails and toenails. This can be a normal aging change. However, some nail changes can be caused by infections, nutritional deficiencies, trauma, and other problems.

Check with your health care provider if your nails develop pits, ridges, lines, changed shape, or other changes. These can be related to iron deficiency, kidney disease, and nutritional deficiencies.

Epilepsy

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Causes
Outlook and Effects
Diagnosis
Treatment
Treatment After The First S...
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved levetiracetam (Keppra) for treatment of primary generalized tonic-clonic seizures in adults, and children ages 6 years and older, who have idiopathic generalized epilepsy. Levetiracetam was previously approved for partial-onset seizures and myoclonic seizures.

Carbamazepine and Genetic Testing

In 2007, the FDA recommended that patients of Asian ancestry get a genetic test prior to taking carbamazepine (Tegetrol, Equetro, Carbatrol). Rare, but serious, side effects of carbamazepine include life-threatening skin reactions such as Stevens-Johnson syndrome. The risk for these skin reactions is significantly higher for patients of Asian ancestry. A simple blood test can check for the presence of a genetic mutation that increases this risk. Patients who test positive for this gene should not take carbamazepine unless the benefits clearly outweigh the risks.

Epilepsy and Suicide Risk

People with epilepsy have a high risk for suicide, especially within 6 months of diagnosis, suggests a 2007 study in Lancet Neurology. The researchers found that suicide risk was especially high for people who have both epilepsy and another psychiatric condition (such as depression, anxiety, schizophrenia, or alcoholism). The researchers recommend that doctors carefully monitor newly diagnosed patients.

Ketogenic Diet

The ketogenic diet, which is characterized by high fat and low carbohydrate intake, is resurging in popularity for the treatment of children with difficult-to-control seizures, according to a 2007 review in Pediatrics. The ketogenic diet helps stop or reduce seizures in about a third of children. The diet is complex. Parents should seek supervision and guidance from a doctor or trained health professional.

Introduction

Epilepsy is characterized by unprovoked, recurring seizures that disrupt the nervous system and can cause mental and physical dysfunction. In the U.S., about 2.5 million people are affected by epilepsy and seizures. About 10% of the American population will experience at least one seizure during their lifetime.

The structures of the brain include: the brainstem, consisting of the spinal cord, the medulla oblongata, the pons and the midbrain; the cerebellum; the cerebrum (one half, or hemisphere shown); and the diencephalon.

Epilepsy affects all age groups. Males have a slightly higher risk than females. The incidence is highest in children, with another, but lesser, peak occurring after age 60. According to one estimate, 14% of epilepsy patients are under 15 years old, and about 25% are over age 64.

Every year, 25,000 - 40,000 American children have a first seizure that is unrelated to a fever. Epilepsy is decreasing in childhood but increasing in the elderly, probably because of mild strokes and cardiac arrest.

Epilepsy is not a single disorder but rather a wide spectrum of problems. What all types of epilepsy share are recurrent, unprovoked seizures caused by an uncontrolled electrical discharge from nerve cells in the cerebral cortex. This part of the brain controls higher mental functions, general movement, and the functions of the internal organs in the abdominal cavity, perception, and behavioral reactions.

Seizures are a symptom of epilepsy. Epilepsy types are generally put into two categories, which are based on the specific biologic mechanisms involved in the seizure and the anatomical location of the seizure. The two types are:

Partial (also called focal or localized) seizures. These seizures are more common than generalized seizures and occur in one or more specific locations in the brain. In some cases, partial seizures can spread to wide regions of the brain. They are likely to develop from specific injuries, but in most cases the exact origins are unknown.
Generalized seizures. These seizures typically occur in both sides of the brain. Many forms of these seizures are genetically based. There is usually normal neurologic function.

Experts are finding, however, that these categories do not actually reflect what is now known about the brain's anatomy. For example, the words "partial" and "generalized" suggest that seizures either involve only part of the brain or are widespread. However, a number of events in the brain occur with either type, muddying these distinctions. Researchers are now in the process of making clearer definitions and terms that reflect what actually is happening in the brain.

New classification systems better define specific epilepsies. Some professional groups now suggest that epilepsies be classified in the following five ways:

Type of seizure (partial or generalized)
Description of the seizure onset and evolution
Specific syndromes that are associated with one or more seizure types (however, not all seizures will be part of a syndrome)
Specific causes of the seizures, if known
Degree of impairment

These seizures are subcategorized as "simple" or "complex partial."

Simple Partial Seizures. A person with a simple partial seizure (sometimes known as Jacksonian epilepsy) does not lose consciousness, but may experience confusion, jerking movements, tingling, or odd mental and emotional events. Such events may include deja vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles.
Complex Partial Seizures. Slightly over half of seizures in adults are complex partial type. About 80% of these seizures originate in the temporal lobe, the part of the brain located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. They may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated; some sufferers even appear to be drunk. After a few seconds, a patient may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than 2 minutes. They may occur infrequently, or as often as every day. A throbbing headache may follow a complex partial seizure.

In some cases, simple or complex partial seizures evolve into what are known as secondarily generalized seizures. The progress may be so rapid that the partial stage is not even noticed.

While the term "partial" implies the seizures affect only small or specific brain locations, in reality, they almost always involve diffuse and even widespread areas. In the future, the term "focal seizures" will most likely replace the term "partial seizures," and its subcategories. Until new classifications are more widely in use, this report will continue to use the term "partial seizures" and its subcategories.

Generalized seizures are caused by nerve cell disturbances that occur in more widespread areas of the brain than do partial seizures. Therefore, they have a more serious effect on the patient. They are further subcategorized as tonic-clonic (or grand mal) or absence (petit mal) seizures.

Tonic-Clonic (Grand Mal) Seizures. The first stage of a grand mal seizure is called the tonic phase, in which the muscles suddenly contract, causing the patient to fall and lie stiffly for about 10 - 30 seconds. Some people experience a premonition or aura before a grand mal seizure. Most, however, lose consciousness without warning. If the throat or larynx is affected, there may be a high-pitched musical sound (stridor) when the patient inhales. Spasms occur for about 30 seconds to 1 minute. Then the seizure enters the second phase, called the clonic phase. The muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control. The seizure usually lasts a total of 2 - 3 minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue. A severe throbbing headache similar to migraine may also follow the tonic-clonic phases.
Absence (Petit Mal) Seizures. Absence or petit mal seizures are brief losses of consciousness that occur for 3 - 30 seconds. Physical movement and loss of attention may stop for only a moment. Such seizures may pass unnoticed by others. Small children may simply appear to be staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures, or even with attention deficit disorder. [See In-Depth Report #30: Attention deficit hyperactivity disorder.] In petit mal, however, a person may experience attacks as often as 50 - 100 times a day. About 25% of patients with petit mal develop grand mal seizures. An electroencephalogram (EEG) test that shows a specific brain wave pattern can usually identify these patients.

Click the icon to see a depiction of a tonic-clonic seizure.

Atonic (Akinetic) Seizures. A person who has an atonic (or akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall. A brief atonic episode is known as a drop attack.

Simply Tonic or Clonic Seizures. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not tonic rigidity.

Myoclonic. Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk.

Epilepsy is also grouped according to a set of common characteristics, including:

Patient age
Type of seizure or seizures
Whether a cause is known or not (idiopathic)

A few syndromes and inherited epilepsies are listed as follows. They do not represent all epilepsies.

West Syndrome (Infantile Spasms). West syndrome, also called infantile spasms, is a disorder that involves spasms and developmental delay in children within the first year, usually in infants ages 4 - 8 months.

Benign Familial Neonatal Convulsions. Benign familial neonatal convulsions (BFNC) are a rare, inherited form of generalized seizures that occur in infancy. BFNC appears to be caused by genetic defects that affect ion channels in nerve cells that carry potassium.

Juvenile Myoclonic Epilepsy (Impulsive Petit Mal). Juvenile myoclonic epilepsy, also called impulsive petit mal epilepsy, is characterized by generalized seizures, usually tonic-clonic marked by jerky movements (called myoclonic jerks), and sometimes absence seizures. This accounts for 7% of epilepsies, and usually occurs in individuals ages 8 - 20.

Adult Myoclonic Epilepsy. Some research suggests that adult myoclonic epilepsy may be a previously un-described and distinct syndrome. It involves the development of generalized epilepsy of unknown causes in middle-aged adults.

Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome is a severe form of epilepsy in young children that causes multiple seizures and some developmental retardation. It usually involves absence, tonic, and partial seizures.

Myoclonic-Astatic Epilepsy. Myoclonic-astatic epilepsy (MAE) is a combination of myoclonic seizures and astasia (a decrease or loss of muscular coordination), often resulting in the inability to sit or stand without aid.

Progressive Myoclonic Epilepsy. Progressive myoclonic epilepsy is an inherited disorder occurring in children ages 6 - 15. It usually involves tonic-clonic seizures and marked sensitivity to light flashes. Although the disease was previously considered to be progressive throughout life, current therapies have significantly improved its outlook.

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare, inherited syndrome that usually occurs during childhood, typically around age 11. However, onset varies widely within families. Seizures can be dystonic (twisting contractions) or tonic (muscle contractions), or involve thrashing. They are brief, frequent, and occur in clusters during the night. The seizures often subside with age. ADNFLE appears to be caused by an alteration in the brain receptor neuronal nicotinic acetylcholine,

Landau-Kleffner Syndrome. Landau-Kleffner syndrome is an epileptic condition that results in the inability to communicate either with speech or by writing (aphasia).

Contactin-Associated Protein-Like 2 (CASPR2) Epilepsy. CASPR2 is associated with a childhood epilepsy and autism disorder found in closely related relatives in Amish communities.

Status epilepticus (SE) is a serious, potentially life-threatening, condition that can lead to chronic epilepsy. It occurs in 100,000 - 150,000 people in the U.S. each year, over half of whom are children. Permanent brain damage or death can result if the seizure is not treated effectively.

The condition is defined as recurrent convulsions that last for more than 20 minutes and are interrupted by only brief periods of partial relief. Although any type of seizure can be sustained or recurrent, the most serious form of status epilepticus is the generalized convulsive or tonic-clonic type. In more than a third of cases, status epilepticus occurs with the first seizure. The trigger is often unknown, but can include the following:

Failure to take anti-epileptic medications (accounts for about a third of status epilepticus events)
Abrupt withdrawal of certain anti-epileptic drugs, particularly barbiturates and benzodiazepines
High fever
Poisoning
Electrolyte imbalances (imbalance in calcium, sodium, and potassium)
Cardiac arrest
Stroke. In one study, about 9% of stroke patients with seizures had status epilepticus, which resulted in higher disability after the stroke, particularly if these severe seizures occurred within a week of the stroke
Low blood sugar in people with diabetes
Central nervous system infection
Brain tumor
Alcohol withdrawal

Causes

The cause of a seizure is determined in about 28% of partial epilepsy patients. In the rest, however, epilepsy is deemed idiopathic, which means that the cause is unknown. The age of seizure onset can sometimes offer a clue. Idiopathic epilepsy is rare in children and young adults.

Epileptic seizures are triggered by abnormalities in the brain that cause a group of nerve cells in the cerebral cortex to become activated simultaneously, emitting sudden and excessive bursts of electrical energy. A seizure's effect depends on the location in the brain where this electrical hyperactivity occurs. Effects range from brief moments of confusion to minor spasms to loss of consciousness.

Click the icon to see an animation about the nervous system.

Ion Channels. Sodium, potassium, and calcium act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures.

Neurotransmitters. Abnormalities may occur in neurotransmitters, the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest:

Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.
Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated behaviors (eating, relaxation, sleep). Imbalances in serotonin are also associated with depression.
Acetylcholine is a neurotransmitter that is important for learning and memory.

Dozens of genetic syndromes representing a variety of seizure patterns may account for the different forms epilepsy.

A genetic cause has been identified for at least some cases of juvenile myoclonic epilepsy, which represents 10% of all epilepsy cases. (Such research and other studies have pointed to the GABA signaling system as an important player in many cases of epilepsy.)

Febrile seizures are caused by high fever. They usually occur in children ages 3 months to 5 years. Between 10 - 15% of children with epilepsy have a history of febrile seizures before they develop epilepsy. However, febrile seizures are quite common and occur in about 3% of all children under 5 years old. Nearly all are brief and have no long-lasting effect.

In young children, high fever from a vaccination can, in rare instances, trigger seizures. These seizures are almost always temporary and have no serious consequences.

Some controversy arose a few years ago over the possibility that the DTP (diphtheria-tetanus-pertussis) vaccine might trigger epilepsy or other neurologic diseases. Some experts suggest that children who have neurologic events following their DTP shot already have a preexisting impairment such as epilepsy, which is revealed, but not caused by, the vaccine. Children with existing epilepsy may be at risk for seizures 2 or 3 days after the vaccination. Infants with suspected neurologic problems may have their vaccinations delayed until their neurologic situation is clarified, but not beyond their first birthday. Also, a newer version of the DTP vaccine does not contain a live virus and so reduces the risk of any seizure.

Brain Tumors. Both cancerous and noncancerous brain tumors can cause seizures in all patients.

Hydrocephalus and Shunts. Hydrocephalus occurs when cerebrospinal fluid (CSF) accumulates in the brain, leading to excessive swelling of the brain ventricles. The resulting pressure can damage the brain's tissue. Hydrocephalus itself is not commonly known to cause seizures, but its treatment, which involves insertion of a shunt, may cause them. The shunt is a device that drains the excess fluid from the brain. Up to half of children who receive shunts may experience epileptic seizures, particularly if the shunt is placed before 2 years of age. More research on its relationship to epileptic seizures is needed.

Focal Cortical Dysplasia. This is an abnormality in fetal development in which the normal migration of nerve cells is altered. It can cause very severe epilepsy that is difficult to treat.

Hippocampal Sclerosis. Hardened tissue (sclerosis) in the brain's hippocampus is the most commonly identified abnormality in patients with partial epilepsy. Such abnormal brain tissue leads to structural reorganization, and both the loss and regeneration of nerve cells.

Cavernous Angiomas. Cavernous angiomas are blood vessels that grow abnormally and, like a tumor, can put pressure on nerve tissue.

Other Causes of Seizures in Children. Seizures in infants and children may be due to birth defects, difficulties during delivery, or poisoning.

Alcohol Abuse. Alcohol abuse is one of the most common causes of adolescent- and adult-onset seizures. Seizures, nearly always generalized tonic-clonic, occur in about 10% of adults during withdrawal. Multiple seizures happen in about 60% of these patients. The first seizure occurs 7 hours to 2 days after the last drink, and the time between the first and last seizure is usually 6 hours or less. [For more information, see In-Depth Report #56: Alcoholism.]

Sudden withdrawal from certain antianxiety or antidepressant drugs such as benzodiazepines, barbiturates, and tricyclic antidepressants can also contribute to seizures.

Head Injuries in Adults. Head injuries to adults can cause seizures, with the risk highest in severe head trauma. A first seizure related to the injury can occur years later, but only very rarely. People with mild head injuries, which involve loss of consciousness for fewer than 30 minutes, have only a slight risk that lasts up to 5 years after the injury.

Head Injuries in Infants and Children. Infants are at high risk for head trauma, and the severity of injury may be difficult to determine. The risk of even one seizure is generally only a concern after severe head trauma. Most children who have had a minor or not very serious head injury do not need to have medications to prevent seizures, especially when an evaluation in the emergency department was unnecessary.

Stroke. Seizure is a symptom of a major stroke. Even injury to the brain from small strokes may cause seizures. Patients who have had a severe stroke are 5 times more likely to develop epilepsy than patients who have had a mild stroke.

Seizures in adults can also be caused by:

Low blood sugar (hypoglycemia), a complication of diabetes in both children and adults.
Medications such as theophylline, meperidine, tricyclic antidepressants, phenothiazines, lidocaine, quinolones, penicillins, selective serotonin re-uptake inhibitors, isoniazid, antihistamines, cyclosporine, interferons, cocaine, lithium, amphetamines, and alcohol (withdrawal).
Occupational exposure to environmental triggers. High exposure to certain chemicals has been linked with seizures.
Alzheimer's or other degenerative brain diseases in the elderly.
Infections of the brain and central nervous system such encephalitis and meningitis.

The organs of the central nervous system (brain and spinal cord) are covered by three connective tissue layers called the meninges. They consist of the pia mater (closest to the CNS structures), the arachnoid, and the dura mater (farthest from the CNS). The meninges help support blood vessels and contain cerebrospinal fluid. The structures are involved in meningitis, an inflammation of the meninges, which, if severe, may become encephalitis, an inflammation of the brain.

Between 20 - 45% of cases of untreatable seizures have a psychologic rather than physical origin. In this form of epilepsy, known as pseudoepilepsy or psychogenic epilepsy, the patient has no conscious intent of forcing a seizure and does not show unusual emotional behavior or signs of hysteria. It is very difficult to treat and can be very disabling. Pseudoepilepsy can usually be distinguished from true epilepsy using an electroencephalogram (EEG), which measures brain waves. The cause of pseudoepilepsy is unknown.

Outlook and Effects

Most patients can control their seizures with a single drug and stop drug treatment completely after 2 years without seizures. In fact, patients who respond well to an anti-epileptic drug (AED), have a better chance for remaining seizure-free in the future. In general, patients who do not have good control with medications are more likely to have difficulty with epilepsy treatment.

Injuries from Falls. Because many people with seizures fall, injuries are common. Although such injuries are usually minor, people with epilepsy have a higher incidence of fractures than those without the disorder. Epilepsy patients who take the drug phenytoin have an even higher risk, since the drug can cause osteoporosis.

Household Accidents. According to a 2006 study, the kitchen and bathroom are two of the most dangerous places for children with epilepsy. Parents should take precautions to prevent burning accidents from stoves and other heat sources. Children with epilepsy should never be left alone when bathing.

Driving and the Risk for Accidents. Being unable to drive is an extremely distressing and severe component of epilepsy. Drivers with well-controlled epilepsy are not at a high or unacceptable risk for automobile accidents. Uncontrolled epilepsy, however, poses a high risk. Needless to say, seizures can be very dangerous if they occur while a person is driving. Studies have reported that more than a fourth of drivers with uncontrolled epilepsy had a seizure-related accident at some time. Many of these accidents resulted in injuries to the patient or others.

Certain factors can help predict who may safely drive:

A long duration between seizures. In one study, being seizure-free for 6 months reduced the risk for accidents by 85%, and being seizure-free for 1 year lowered the risk by 93%. State laws restricting driving in people with seizures vary from requiring seizure-free periods of 3 months (which is too short for protection) to 18 months.
Having few seizure-related accidents.
Having a reliable pre-seizure warning sign, such as an aura.

Accidents while Swimming. Swimming poses another danger for people with epilepsy, particularly those with tonic seizures, which can cause the diaphragm to expel air quite suddenly. People with epilepsy who swim should avoid deep and cloudy water (a clear swimming pool is best), and always swim with a knowledgeable, competent, and experienced companion or have a supervisor on site.

Epileptic patients who are cured have a normal lifespan. Their long-term survival rates are lower than average if medications or surgery fail to stop the seizures. The lower survival rate is partly due to a higher-than-average risk for death due to accidents and suicide. The specific cause of the seizure may also contribute to fatalities.

There is a very low risk for sudden death in patients with epilepsy. Although the causes of such events are not fully known, experts suspect heart arrhythmias in many cases.

Long-Term General Effects. In general, the long-term effects of seizures vary widely depending on the seizure's cause. The long-term outlook for children with idiopathic epilepsy (epilepsy of unknown causes) is very favorable. One study reported that 68 - 92% of these patients were seizure-free after 20 years. Another study reported that they had a survival rate no different from children without these seizures.

Children whose epilepsy is a result of a specific condition (for example, a head injury or neurologic disorder) have higher mortality rates than the normal population, but their lower survival rates are most often due to the underlying condition, not the epilepsy itself.

Effect on Memory and Learning. The studies on the effects of seizures on memory and learning vary widely and depend on many factors. In general, the earlier a child has seizures and the more extensive the area of the brain affected, the poorer the outcome. Children with seizures that are not well-controlled are at higher risk for intellectual decline.

Social and Behavioral Consequences. Learning and language problems, and emotional and behavioral disorders, occur in a significant number of children with several of the partial epilepsy syndromes. These children perform worse on behavioral tests than do other children. Whether these problems are caused by the seizure disorder and anti-seizure medications or are simply part of the seizure disorder remains unclear.

Effect on Mental Functioning in Adults. The effects of adult epilepsy on mental functioning are not clear. More research is needed in this area, as results have been contradictory.

Psychological Health. About 25 - 75% of adults with epilepsy show signs of depression. People with epilepsy have a high risk for suicide, particularly in the first 6 months following diagnosis. The risk for suicide is highest among people who have epilepsy and an accompanying psychiatric condition such as depression, anxiety disorder, schizophrenia, or chronic alcohol use.

Overall Health. Many patients with epilepsy describe their overall health as "fair" or "poor," compared to those who do not have epilepsy. People with epilepsy also report a higher frequency of pain, depression, anxiety, and sleep problems. In fact, their overall health state is comparable to people with other chronic diseases, including arthritis, heart problems, diabetes, and cancer. Treatments can cause considerable physical effects, such as osteoporosis and weight changes.

Effects on Sexual Function. There have been studies suggesting that up to two-thirds of patients with epilepsy experience sexual disturbances, including impotence in men. Causes of these problems may be emotional, medication induced, or a result of changes in hormone levels:

Epilepsy in childhood may cause disturbances in hormones regulating puberty.
Persistent seizures in adults may be associated with other hormonal and neurologic changes that contribute to sexual dysfunction.
Negative emotions due to epilepsy can reduce sexual drive.
Medications may be responsible for many of these cases, although newer drugs may reduce this problem.

Studies have been conflicting on the effects of fertility from epilepsy, but most suggest that fertility rates among women with epilepsy are lower than among women in the general population. A number of factors, including anti-epileptic drugs (AEDs) or social factors such as marriage at an older age, may contribute to this lower rate. Certain AEDs, particularly valproate, disrupt ovulation and menstruation by increasing male hormone levels and weight and causing polycystic ovaries.

Preparing to Become Pregnant. A woman should visit her doctor at least 3 months before becoming pregnant to talk about risks of medications and the possibility of making any changes.

A woman who has been seizure-free for 2 or more years may attempt to discontinue drugs under her doctor’s supervision.
If she has not been seizure-free, she should continue medications but try to reduce them to a single drug, if possible. (Again, under a doctor’s supervision.)
If a woman taking antiseizure medications has an unplanned pregnancy, there may be no point in switching medications right away, since the effects of the drugs last for 10 weeks. However, she should notify her doctor immediately.
Folic acid is recommended for all pregnant women, and women with epilepsy should talk with their doctor about taking a supplement of folic acid (5 mg) at least 3 months before conception as well as during the first trimester.

Effect of Pregnancy on Seizure Frequency. The frequency and intensity of seizures vary widely in women with epilepsy. About 25% of pregnant women with epilepsy face an increase in events, and the risk is highest in those who have more than one seizure per month prior to becoming pregnant. In most cases, however, there is no change at all. Some pregnant women even have a decrease in seizures. The risk is lower in women who experience less than one seizure in the 9 months prior to becoming pregnant.

The following conditions may contribute to an increase in seizures during pregnancy:

Nausea and vomiting (vitamin B6 and antihistamines may help with nausea)
Fluid retention
Higher estrogen levels
Psychological and emotional stress
Medication noncompliance from fear of side effects
Problems with sleeping
Changes in absorption of anticonvulsants

Anti-epileptic drug levels are monitored at least three times during the pregnancy, more often if seizures are occurring or levels are not normal. Dosage levels should be adjusted accordingly.

Effects of Epilepsy on the Pregnant Patient and the Fetus. Women who become pregnant have a risk for uncontrolled seizures and birth defects from antiseizure medications. In studies of women who were carefully monitored, however, 95% of pregnancies (which is close to normal) had favorable outcomes.

Isolated seizures do not appear to pose any adverse effects to the mother or the unborn child, but repeated seizures and status epilepticus can lead to great dangers. In one study, the effect of epilepsy on complications during pregnancy was the same as in non-epileptic women except for a higher rate of premature deliveries (8.2% in the women with epilepsy).

Drugs Used During Pregnancy. Some types of anti-epileptic drugs (AEDs) can increase the risks for birth defects, especially when taken during the first trimester of pregnancy. Expert guidelines advise that pregnant women use the most effective medication for their type of epilepsy at the lowest dose possible to control seizures. They should also have their doctors take blood tests during pregnancy to monitor their drug levels.

The fetus should be carefully monitored with ultrasonic evaluation and sometimes amniocentesis (visual tests and examination of the fluid in the womb for birth defects and other fetal problems).

In general, research indicates that 90% of women who take AEDs will give birth to healthy children. Still, doctors recommend that women of child-bearing age use a drug other than valproate if possible.

The risk for malformation is higher when more medications are used. For example, there is a 3% risk of birth defects with women who use one anticonvulsant. The risk increases to 20% when four drugs are used.

Birth Defects Associated with Medication. The most common birth defects related to anti-epileptic drugs are:

Cleft lip or palate (risks from lamotrigine, phenobarbital, phenytoin, valproate especially when taken during the first trimester).
Genital or urinary abnormalities (risk from most standard drugs).
Neural tube defects (NTD) in the skull or spinal column (risk of 2% with valproate and 1% with carbamazepine). These complications are most often due to lower folic acid levels caused by both pregnancy itself and antiseizure drugs. Folic acid supplements can help prevent this problem.
Mental impairment (known risk with phenytoin and valproate; inconclusive in carbamazepine and phenobarbital).
Heart defects (risk from phenobarbital, phenytoin, valproate).

Many antiseizure drugs also cause a deficiency in vitamin K clotting factors that increases the risk for hemorrhage in the newborn. Treatment with vitamin K during the last month of pregnancy and a single dose given to the newborn is recommended.

Labor and Delivery. Seizures occur during labor and after delivery in a small percentage of women with epilepsy. The following labor complications are more common among pregnant women with epilepsy: Vaginal bleeding, anemia, and preeclampsia (extremely high blood pressure in the third trimester). If seizures occur during labor, they are generally treated intravenously with benzodiazepines or phenytoin. If tonic-clonic seizures, absence seizures, or status epilepticus occur, a cesarean section may be appropriate.

Postnatal Care

Monitoring the Infant. The infant should be thoroughly examined for any birth defects. Also, if the mother was given phenobarbital or primidone while pregnant, the infant should be monitored for up to 8 months to see if withdrawal symptoms develop. Drug dosages will also need to be adjusted for the mother after delivery.

Breast-feeding. Women on most AEDs typically can nurse their babies, since usually only a small amount of the drug enters the breast milk. The lowest levels are with phenytoin and valproate. (Ethosuximide and possibly levetiracetam are exceptions and should be avoided when a woman is breast-feeding. Women taking phenobarbital are also usually advised not to nurse.) A mother should watch for signs of lethargy or extreme sleepiness in her infant, which could be caused by her medication.

Diagnosis

An epilepsy diagnosis is often made during an emergency visit for a seizure. If a person seeks medical help for a previous or suspected seizure, the doctor will ask about the patient's medical history, including seizure events.

Conditions that cause similar symptoms to epilepsy include:

Syncope. Syncope, a brief lapse of consciousness in which blood flow is reduced to the brain, can mimic epilepsy. It often misdiagnosed as epilepsy. Patients with syncope do not have the rhythmic contracting and then relaxing of the body's muscles.
Migraines. Migraine headaches, particularly migraine with auras, may sometimes be confused with epilepsy. With epileptic seizure, the preceding aura is often seen as multiple, brightly colored, circular spots, while migraine sufferers tend to see black, white, or colorless lined or zigzag flickering patterns. Typically the migraine pain expands gradually over minutes toward one side.
Panic Attacks. In some patients, partial seizures may resemble a panic disorder. Symptoms of panic disorder include palpitations, sweating, trembling, sensation of breathlessness, chest pain, feeling of choking, nausea, faintness, chills or flushes, fear of losing control, and fear of dying.
Narcolepsy. Narcolepsy, a sleep disorder that causes a sudden loss of muscle tone and excessive daytime sleepiness, can be confused with epilepsy.

Electroencephalogram (EEG). The most important diagnostic tool for epilepsy is an EEG, which measures brain waves. Ideally, it should be performed within 24 hours of a seizure. An EEG recording session may last for less than an hour, but in some cases the doctor will want a day-long recording. Long-term monitoring may be necessary in some cases when patients do not respond to medications. Portable EEG units are available in some places, which can be used to monitor patients throughout normal activities. EEGs are not foolproof. Repeated EEGs are often needed to confirm a diagnosis, particularly for certain partial seizures that often produce an initially normal EEG reading.

Video Electroencephalography (Video EEG). For this task, patients are admitted to a special part of the hospital where they are monitored both by EEG and are also watched by a video camera. Patients may need this for a variety of reasons including withdrawal or addition of medications in a patient with difficult-to treat-epilepsy, before epilepsy surgery for some patients, and also when psychogenic nonepileptic seizures are suspected.

Computerized Tomography (CT) Scans. Usually, the first brain imaging test ordered for most adults and children with first-time seizures is a CT scan. This imaging technique is sensitive enough for most purposes. In children, even if the scan is normal, the doctor will follow up to be sure other problems are not present.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of both the bony structures and the soft tissues. Clear images of organs such as the brain, muscles, joint structures, veins and arteries, as well as anomalies like tumors and hemorrhages may be obtained with or without the injection of contrasting dye.

Magnetic Resonance Imaging (MRI). Experts strongly recommend MRIs for children with first seizures in certain cases, such as children under 1 year old and those with seizures that are associated with any unexplained significant mental or motor problems. These images may help to determine if the disorder can be treated with surgery, and may be used as a guide for surgeons.

Other Advanced Imaging Techniques. More advanced scanning techniques are emerging as important tools for epilepsy researchers. By detecting abnormalities, such as changes in brain activity, positron emission tomography (PET) may help locate damaged or scarred locations in the brain where partial seizures are triggered. These findings may help determine which patients with severe epilepsy are good candidates for surgery. Single-photon emission computer tomography (SPECT) may also be used to decide if the surgery should be performed and what part of the brain needs to be removed. Both of these imaging techniques are generally only needed when an MRI of the brain has not been helpful.

Treatment

You cannot stop a seizure, but you can help the patient prevent serious injury.

Remain calm, and do not panic, then take the following actions:

Wipe away any excess saliva to prevent obstruction of the airway. Do not put anything in the patient's mouth. It is an old wives' tale that people having seizures will swallow their tongues.
Turn the victim gently on the side. Do not try to hold the patient down to prevent shaking.
Rest the patient's head on something flat and soft to protect it from banging on the floor and to support the neck.
Move sharp objects out of the way to prevent injury.

Do not leave the seizure victim alone. Anyone nearby should call 911. Patients should be taken to an emergency room when:

A first-time seizure occurs
Any seizure lasts beyond 2 - 3 minutes
The patient has been injured
The patient is pregnant
The patient is diabetic
Parents, caregivers, or bystanders are at all uncertain

Not all patients with chronic epilepsy need to go to the hospital after a seizure. Hospitalization may not be necessary in many patients whose seizure is not severe or repetitive, and who have no risk factors for complications. All patients or caregivers, however, should contact their doctor after a seizure occurs.

Initial Management. The earlier a patient is treated, the better the results. Initial management of status epilepticus consists of:

Administer any seizure medications
Support systems to maintain or attain normal breathing, blood pressure, electrolyte balances, body temperature, and heart functions
Oxygen for patients who may need it
Attention by medical personnel trained to determine any treatable cause of status epilepticus, such as drug withdrawal, low blood sugar, infection, substance abuse (particularly cocaine), or eclampsia (elevated blood pressure induced by pregnancy)

Medications for Status Epilepticus. Doctors will try one or more of the following medications initially:

Benzodiazepine. An intravenously (IV), intramuscularly, or rectally administered benzodiazepine such as lorazepam (Ativan), diazepam (Valium), clonazepam, or midazolam (Versed) is usually used.
Phenytoin or Fosphenytoin. Many doctors use phenytoin or fosphenytoin if seizures are not controlled by a benzodiazepine.
Phenobarbital. Although effective, barbiturates, such as phenobarbital (Barbita, Luminal), are generally used only when other drugs have failed.

All of these medications carry a risk for hypotension, an abrupt and possibly dangerous drop in blood pressure, which may require treatment.

Treatment After The First Seizure

Children with febrile seizures rarely have any long-term effects and generally do not require drug treatment. In very rare cases, children experience severe fever-related seizures known as complex febrile convulsions. In such cases, there is a risk for brain injury that may lead to temporal lobe epilepsy, but this is very small. Such seizures last over 15 minutes, occur more than once within 24 hours, and may affect only one side of the body.

Treatment with anti-epileptic drugs (AEDs) is usually initiated or strongly considered for the following patients:

Children and adults who have had two or three seizures, unless there is either a long separation between seizures or the seizure is provoked by an injury or other specific causes. (In children, risk for recurrence after a single unprovoked seizure is rare. The risk even after a second seizure is low, even when the seizure is prolonged.)
Children and adults after a single seizure if tests reveal any brain injury, or if specific syndromes put a person at special risk for recurrence, for instance, in cases of myoclonic epilepsy.

There is some debate about whether to treat every adult patient with an AED after a single initial seizure. Some experts do not recommend treating adult patients after a single seizure if they have a normal neurologic examination, EEG, and imaging studies. A 2005 study of patients with single or infrequent seizures found that while early AED treatment reduced the risk of seizure for a few years, it had no effect on long-term outcomes. This study also suggested that delaying AED treatment does not increase the risk of developing lifelong epilepsy.

Some doctors believe, however, that any adult who has a first seizure should begin on-going AED treatment, since 30 - 70% of these patients are likely to experience a subsequent event. According to one study, when young adults were given a single drug (usually carbamazepine) after a first generalized seizure, only 22% had a subsequent seizure compared to about 70% of those who were not given treatment.

Most epileptic seizures can be controlled using a single-drug regimen. First-line AED drugs include phenytoin (Dilantin), carbamazepine (Tegretol, Carbatrol), and divalproex sodium (Depakote). Patients generally begin with low doses and build up until the seizures are controlled or a toxic reaction occurs. If a single drug fails to control seizures, other drugs are added on. The specific drugs and whether more than one should be used are determined by various factors, including the patient's age and the seizure's type, frequency, and cause.

Drugs fail to control epilepsy in about 30% of patients. For patients who have little or no benefit from their initial drug regimen the likelihood of good or complete control from different medications or multidrug regimens is not very high.

Reasons for Failure. An AED may fail to reduce seizures due to such factors as:

The wrong dose level.
Improper timing.
Introducing the medication too rapidly.
Not managing conditions that triggered the seizure.
Instability of the drugs. Many of the tablet forms disintegrate easily with moisture, so pills should be stored in a dry place, not in the bathroom, and kept away from heat.
Patients not taking medication as prescribed. Over 40% of patients experience toxic or bothersome effects from older AEDs, which often causes them to withdraw. Among the most distressing are sleepiness, problems in coordination, and weight gain.
Some evidence suggests that about a quarter of patients who do not respond to AEDs actually have nonepileptic seizures that in many cases are caused by psychiatric conditions (such as panic attack or personality disorders).

The doctor should first address these issues. If the patient still does not respond, the doctor will usually try a different drug. If this fails, one or even two additional drugs at a time may be used. When seizures do not respond to the first two or three drugs, the odds of a fourth or fifth working diminish greatly, despite a number of new medications on the market. In such cases, the patient should ask about surgical alternatives.

Healthy Behaviors. In young people, a positive attitude, continued support from family and health care providers, emotional well-being, and good treatment results can increase patient compliance. Unhealthful behaviors, such as smoking and alcohol use, can have a negative effect.

During the first few months of therapy, the doctor will probably order blood tests once or twice to monitor drug levels and, if necessary, adjust dosages. Monitoring is used to check for AED complications, and to be sure the patient is complying with the regimen. Many experts feel, however, that these blood tests are a less reliable indicator of problems than the patient's own self-observations of his or her responses to the drug. For instance, blood tests may suggest that the dosage levels are insufficient according to general standards, yet the individual patient may be seizure-free and leading a normal life. It is very important that women have AED levels monitored during pregnancy.

An estimated 60% of all patients treated effectively can stop taking AEDs within 5 - 10 years. Evidence suggests that medications in children should not be halted for at least 2 years after the last seizure, particularly if they have partial seizures and abnormal EEGs. It is not clear whether children who have been free of generalized seizures need to wait more than 2 years or if they can withdraw earlier.

Children who tend to relapse after withdrawal from treatment usually have the following conditions or situations:

A family history of epilepsy
Require multiple medications to control seizures
Abnormal EEG readings after treatment has started
Partial seizures

There is also no clear evidence on whether adults who are free of any seizure type can safely withdraw from their medications within 2 years of their last seizure of if they should wait.

In any case, attempts to halt drugs should be done during periods when seizures will cause the least harm. For instance, the best time to test the effects of drug withdrawal in teenagers might be about a year before they are eligible to drive.

Anti-epileptic drugs interact with many other drugs, and may cause special problems in older patients who use multiple medications for other health problems. Elderly patients should have liver and kidney function tests performed before starting antiseizure medication. Standard drugs are usually effective, while safe, newer ones (including gabapentin, lamotrigine, oxcarbazepine, and gamma-vinyl-GABA) may sometimes prove to be useful as a sole therapy. These newer drugs also increase patient compliance because they tend to have fewer side effects than the older ones.

Hormonal fluctuations affect epilepsy in about a third to a half of female patients. Estrogen appears to increase activity, and progesterone reduces it. The effect of pregnancy on women with epilepsy is complex. The following treatments may help or affect women with epilepsy:

Hormonal Drugs that Suppress Ovulation. When seizures in women are worsened by hormonal changes, such as during the menstrual cycle, suppressing ovulation may be recommended using drugs called gonadotropin-releasing hormone agonists.
Oral contraceptives. Antiseizure medications affect many oral contraceptives (OCs). Carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and topiramate reduce the effects of OCs. Valproate does not, and may even increase hormonal levels. Gabapentin, lamotrigine, tiagabine, and vigabatrin may also prove to be safe with OCs, but more research is needed. Progestins may be the best contraceptive drugs for women with epilepsy at this time. Injected progestins may actually help prevent seizures in some cases.

More information on epilepsy and pregnancy can be found in this report under Outlook and Effects.

Medications

Many newer anti-epilepsy drugs (AEDs) are now available and are usually better tolerated than the older, standard AEDs. They often cause less sedation and require less monitoring. Although they are generally approved for use as add-ons to standard drugs that fail to control seizures, many doctors are now prescribing them as single drugs. Specific choices usually depend on the individual's particular condition and the specific side effects of the AED. None has emerged as being superior to either standard or newer drugs. All appear to offer some benefits, but, as with standard antiseizure drugs, they also have troublesome side effects.

Valproate (Depakene, valproic acid) and its delayed release form, divalproex sodium (Depakote), are anticonvulsants. Valproate is the most widely prescribed anti-epileptic drug worldwide.

Uses. Valproate is the first choice for patients with generalized seizures and is used to prevent nearly all other major seizures as well.

General Side Effects. These drugs have a number of side effects that vary depending on dosage and duration. Most side effects occur early in therapy and then subside. General side effects include:

Stomach and intestinal problems, which are experienced by nearly half of patients after starting the drugs and may still occur after several years of use. Divalproex sodium (Depakote) has a lower risk for these side effects than valproate (Depakene).
Increased appetite with significant weight gain often becomes a problem and can be a major reason for noncompliance, particularly in young people.
Hand tremors, irritability, and hyperactivity in children are fairly common.
Temporary hair thinning and hair loss have occurred. Taking zinc and selenium supplements may help reduce the effect.
Young girls may develop secondary male characteristics, and premenopausal women are at increased risk for menstrual irregularities and polycystic ovaries, due to elevated male hormones. The effects are reversible. (These side effects also appear in women using other anti-epileptic drugs, but the risk from valproate appears to be higher.)
Studies have reported symptoms of Parkinson's disease preceded by hearing loss in people who have taken it for more than a year, but they were reversible when the drug was withdrawn.
Valproate poses a higher risk for serious birth defects than many other AEDs. These birth defects include skull and limb deformities, and brain, heart, and lung problems. Experts recommend that women of child-bearing age use a different type of anti-epilepsy drug than valproate. If valproate is used, it should be prescribed at the lowest possible dose.
Cases of pancreatitis, a serious and even life-threatening inflammation in the pancreas, have been reported in children and adults taking valproate. (It is still very rare, however.)
Valproate and divalproex sodium are not usually recommended for young children because of an unusual, but potentially fatal, toxic effect on the liver. This very rare effect is most likely to affect children under 2 years of age who have birth defects and are taking more than one antiseizure drug. Some doctors recommend monitoring blood levels for liver function once prior to administering valproate or divalproex sodium, monthly during the first 6 months, and then periodically after that.
Children with epilepsy who take valproic acid may eventually develop some problems in the kidney, although they are generally not significant.

Symptoms of Toxic Side Effects in Liver or Pancreas.

Abdominal pain
Nausea or vomiting
Loss of appetite
Lethargy
Acute confusion
Water retention
Easy bruising
Yellowish skin coloring

Carbamazepine (Tegretol, Equetro, Carbatrol) is an effective anticonvulsant and specific analgesic when used alone or with other drugs. Carbamazepine also has the added benefit of relieving depression and improving alertness. An extended release form is available that allows twice-daily dosing rather than 3 times a day. A chewable form makes it easier for children to take.

Uses. This drug is used to prevent the following seizures or epilepsy syndromes:

Partial seizures. Patients tend to tolerate this drug better than others, although responses differ among individuals
Grand mal seizures
Combinations of grand mal and partial seizures
Autosomal dominant nocturnal frontal lobe epilepsy (an inherited disorder).

Side Effects. Different side effects may develop or resolve at different points in the treatment duration. Initial side effects may include:

Double vision, headache, sleepiness, dizziness, and stomach upset. These usually subside after a week and can be greatly reduced by starting with a small dose and building up gradually.
Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. The extended-release form of carbamazepine (Carbatrol) may help reduce these symptoms.

Serious side effects are less common but can include:

Carbamazepine may increase the risk for birth defects, especially if it is taken during the first trimester of pregnancy.
Skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, so severe the drug has to be discontinued develop in about 6% of patients. These skin reactions cause skin lesions, blisters, fever, itching, and other symptoms. People of Asian ancestry have a 10 times greater risk for skin reactions than other ethnicities. The FDA recommends that patients of Asian ancestry get a blood test prior to starting the drug to determine if they have the gene variant that increases this risk.
Water retention can be a problem in older people.
Hormonal changes, particularly higher levels of male hormones in both men and women, pose some risk for sexual dysfunction over time.
A decrease in white blood cells occurs in about 10% of those taking the drug. This is generally not serious unless infection accompanies it.
Other blood conditions can arise that are also potentially serious. Patients should be sure to inform the doctor if they have any sign of irregular heartbeats, sore throat, fever, easy bruising, or unusual bleeding.
Long-term therapy can cause bone loss (osteoporosis) in women, who should take preventive calcium and vitamin D supplements.
Children are at higher risk for behavioral problems.

Note: Citrus fruit, especially grapefruit, can increase carbamazepine's adverse effects and should be avoided by those taking this drug.

Uses. Phenytoin (Dilantin) is effective for adults who have the following seizures or conditions:

Grand mal seizures
Partial seizures
Status epilepticus
Can be effective for people with head injuries who are at high risk for seizures

This drug is not useful for the following seizures:

Petit mal seizures
Myoclonic seizures
Atonic seizures

Side Effects. Side effects are sometimes difficult to control. Some people may develop a toxic response to normal doses, while others, such as those with alcoholism, may require higher doses to achieve benefits. As with any drug, side effects generally rely on dosage and duration. Using phenytoin in combination with newer add-on drugs can allow lower doses and may reduce some of the risks. Side effects may include:

Excess body hair, eruptions and coarsening of the skin, and weight loss
Gum disease
Staggering, lethargy, nausea, depression, eye-muscle problems, anemia, and an increase in seizures can occur as a result of high doses.
Liver damage may develop in rare cases.
Bone loss from long-term therapy. Patients should take preventive calcium and vitamin D supplements and exercise regularly to improve bone mass.
Severe and even rare life-threatening skin reactions (Stevens-Johnson syndrome)
An increased risk for birth defects

Phenobarbital (Luminal), also called phenobaritone, is a barbiturate anticonvulsant and is often the initial drug prescribed for newborns and young children. It is a relatively inexpensive drug. Primidone (Mysoline) is converted in the body to phenobarbital, and has the same benefits and adverse effects. It is reported that primidone is not as well-tolerated as phenobarbital. Some experts believe that primidone has no advantage over the other drug.

Uses. Barbiturates are used to also prevent grand mal (tonic-clonic) seizures or partial seizures. They are no longer typically used as a first-line drug.

Side Effects. Phenobarbital has fewer toxic effects on other parts of the body than most anti-epileptic drugs, and drug dependence is unusual, given the low doses used for patients with epilepsy. Nevertheless, withdrawal is common because of side effects, and therefore it is less likely to be used over time than other drugs, including phenytoin, another relatively inexpensive but effective drug.

Patients sometimes describe their state as "zombie-like." The most common and troublesome side effects are:

Drowsiness
Memory problems
Problems with tasks requiring sustained performance
Problems with motor skills
Hyperactivity in some patients, particularly in children and the elderly
Depression in some adults

Some controversy has arisen over studies indicating that children taking phenobarbital score lower on intelligence tests, even for some months after going off the drug.

Uses. Ethosuximide (Zarontin) is used for petit mal (absence) in children and adults when the patient has experienced no other type of seizures. Ethosuximide succeeds in abolishing petit mal seizures in 60% of patients and controls them in up to 90%. Methsuximide (Celontin), a drug similar to ethosuximide, may be suitable as an add-on treatment for intractable epilepsy in children without causing serious or permanent side effects.

Side Effects. Use of this drug can cause stomach problems, dizziness, loss of coordination, and lethargy. In rare cases, it has caused severe and even fatal blood abnormalities. Periodic blood counts are recommended for patients taking this drug.

Uses. Clonazepam (Klonopin) is recommended for myoclonic and atonic seizures that cannot be controlled by other drugs and for Lennox-Gastaut (absence variant). It may be useful in newborns when other drugs are ineffective. Although clonazepam can prevent generalized or partial seizures, patients generally develop tolerance to the drug, and then seizures recur.

Side Effects. People who have had liver disease or acute angle glaucoma should not take clonazepam, and people with lung problems should approach the drug with caution. Clonazepam can be addictive, and abrupt withdrawal has been known to trigger status epilepticus. Side effects include the following: drowsiness, imbalance and staggering, irritability, aggression, hyperactivity in children, weight gain, eye muscle problems, slurred speech, tremors, skin problems, and stomach problems.

Uses. Lamotrigine (Lamictal) is approved as add-on (adjunctive) therapy for partial seizures, and generalized seizures associated with Lennox-Gastaut syndrome, in children aged 2 years and older and in adults. Lamotrigine is also approved as add-on therapy for treatment of primary generalized tonic-clonic (PGTC) seizures, also known as “grand mal” seizures, in children aged 2 years and older and adults. Lamotrigine can be used as a single drug treatment (monotherapy) for adults with partial seizures who have not responded to monotherapy with carbamazepine, phenytoin, phenobarbital, primidone, or valproate. Birth control pills lower blood levels of lamotrigine.

Side Effects. Common side effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. Although most cases of rash are mild, in rare cases the rash can become very severe. The risk of rash increases if the drug is started at too high a dose or if the patient is also taking valproate. (Serious rash is more common in young children who take the drug than it is in adults.) Rash is most likely to develop within the first 8 weeks of treatment. Be sure to immediately notify your doctor if you develop a rash, even if it is mild.

Studies suggest that lamotrigine may cause fewer problems with sexual function in men than other antiseizure drugs. A 2006 study indicated that lamotrigine may cause fewer cognitive problems (such as confusion and difficulty concentrating) than topiramate.

Gabapentin (Neurontin) is an effective add-on drug for controlling complex partial seizures and secondarily generalized partial seizures and is approved for adults and children with these seizures. It has achieved response rates in patients with resistant partial epilepsy. It is not at all useful for generalized petit mal seizures.

Side Effects. Its toxicity is low, and side effects include sleepiness, headache, fatigue, and dizziness. Some weight gain has been reported. Gabapentin has no significant interactive effects when taken with other drugs. Children may experience hyperactivity or aggressive behavior. Long-term adverse effects are still unknown.

Pregabalin (Lyrica) is similar to gabapentin.

Uses. Approved as add-on therapy to treat partial-onset seizures in adults with epilepsy. In clinical trials, half of the patients who received pregabalin experienced a 50% reduction in seizure frequency.

Side Effects. These may include dizziness, sleepiness, dry mouth, swelling in hands and feet, blurred vision, weight gain, and trouble concentrating

Uses. Topiramate (Topamax, generic) is similar to phenytoin and carbamazepine and is effective and safe for a wide variety of seizures in adults and children. It is approved as add-on therapy for patients 2 years and older with generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome. It is also approved as single therapy for patients 10 years and older with tonic-clonic seizures or partial-onset seizures. Studies have shown a 34 - 87% reduction in seizure frequency with some patients becoming seizure-free.

Side Effects. Most side effects are mild to moderate and can be reduced or even prevented by beginning at low doses and increasing dosage gradually. Serious side effects may include glaucoma, decreased sweating, increased body temperature, kidney stones, sleepiness, dizziness, confusion, and trouble concentrating. Patients should immediately tell their doctor if they have blurred vision or eye pain. Topiramate may have fewer interactions with oral contraceptives than other AEDs.

Oxcarbazepine (Trileptal, generic) is similar to phenytoin and carbamazepine but generally has fewer side effects.

Uses. Approved as single therapy or add-on therapy for partial seizures in adults and for children ages 4 years and older.

Side Effects. Serious side effects, while rare, include Stevens-Johnson syndrome and toxic epidermal necrolysis. These skin reactions cause a severe rash that can be life threatening. Rash and fever may also be a sign of multi-organ hypersensitivity, another serious side effect associated with this drug. Oxcarbazepine can also reduce sodium levels (hyponatremia). Your doctor may want to monitor the sodium level in your blood. This drug can also reduce the effectiveness of birth control pills. Women who take oxcarbazepine may need to use a different type of contraceptive.

Zonisamide (Zonegran) is a unique drug that blocks sodium and calcium channels and may have nerve-protecting properties.

Uses. It is approved as add-on therapy for adults with partial seizures, and studies indicate it is often effective against infantile spasms (West syndrome) and myoclonic seizures.

Side Effects. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Children are especially at risk for this side effect, which can be serious. (The drug has not been approved for children.) Other side effects tend to decrease over time and include dizziness, forgetfulness, headache, weight loss, and nausea.

Levetiracetam (Keppra) is known as a nootropic drug.

Uses. This drug is approved both in oral and intravenous forms as add-on therapy for:

Partial onset seizures in adults and children ages 4 years and older
Myoclonic seizures in adults and adolescents ages 12 years and older who have juvenile myoclonic epilepsy
Primary generalized tonic-clonic seizures in adults and children ages 6 years and older who have idiopathic generalized epilepsy

Some experts believe that levetiracetam represents a significant advance and will prove to be an important first-line drug. Levetiracetam appears to have fewer drug interactions than other anti-epileptic drugs and may be particularly useful for older patients.

Side Effects. These tend to occur mostly in the first month. They include sleepiness and fatigue, muscle weakness and coordination difficulties, headache, flu symptoms, dizziness, behavioral abnormalities, possible risk of a reduced white blood cell count, and a higher rate of infections. Caution is advised for patients with kidney dysfunction. There have been some reports of adverse effects on mood (irritability, depression, and anxiety), but recent studies have found fewer such effects than with other AEDs. Epilepsy, rather than the drug, is likely to be the cause of these mood changes. About 1% of patients report considerable weight loss.

Tiagabine (Gabitril) has properties similar to phenytoin and carbamazepine, and is also showing promise.

Side Effects. Evidence has reported some significant side effects with its use, including dizziness, fatigue, agitation, and tremor. At least one study suggested that it has more adverse effects than lamotrigine and is not as well tolerated. In February 2005, the FDA issued a warning advising that tiagabine may cause seizures in patients without epilepsy. Tiagabine is only approved for use with other anti-epilepsy medicines to treat partial seizures in adults and children 12 years and older.

Felbamate. Felbamate (Felbatol) is an effective antiseizure drug. However, after reports of deaths from a serious blood condition known as aplastic anemia or from liver failure, felbamate is recommended only under certain circumstances. They include severe epilepsy, such as Lennox-Gastaut syndrome or as monotherapy for partial seizures in adults when other drugs fail.

Vigabatrin. Vigabatrin (Sabril) is a chemical called gamma-vinyl GABA. It was designed to increase the brain levels of gamma aminobutyric acid (GABA), the enzyme that inhibits seizure activity. It has serious side effects, however, and is generally prescribed in the U.S. only in certain cases, such as in low doses for patients with Lennox-Gastaut syndrome. Overseas it is also used for partial seizures and as first-line therapy in children with infantile spasms (West syndrome). Between 10 - 30% of people on long-term treatment have developed irreversible visual disturbances, including reductions in acuity and color vision. Men are at higher risk for this side effect than are women. Further studies are needed to determine the extent and severity of this complication, particularly in children. There is a slight risk for depression or psychosis when vigabatrin is used as add-on therapy, and particularly if the drug is administered too quickly. These risks are far lower if the drug is used as sole therapy.

Older Drugs. Some older but less effective drugs may still play a role against epilepsy:

Acetazolamide (Diamox) is sometimes used against common types of seizures, but patients quickly develop a tolerance for it. Some experts suggest it still may be useful when drug interactions are a problem, when a rapid effect is required, or when an additional drug is needed for a short time.
Trimethadione (Tridione) is effective for petit mal seizures, but has very serious side effects, and its use is severely limited.

Infantile spasms are treated with vigabatrin, adrenocorticotropic hormone (ACTH), or valproate. Some experts recommend that vigabatrin be given first and ACTH administered 10 - 14 days later. In one small study, no infants who were given this combination relapsed after 4 months. Newer drugs may also be effective for this problem, but their effects on small children are not yet wholly known.

New AEDs. Retigabine is an investigational GABA enhancer that works in a different way from existing AEDs. It is currently in phase III trials for treatment of partial-onset seizures in patients who are receiving other AEDs. Talampanel is another new type of drug, known as an AMAP receptor antagonist, that is currently in early trials. Other drugs under investigation are related to existing AEDs. For example, brivaracetam and seletracetam are similar to levetiraceptam, fluorofelbamate is similar to felbamate, and eslicarbazepine is similar to oxcarbazepine.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis) that may have properties that protect nerve cells. Some patients claim a reduction in seizures while other active users of marijuana report no effect on seizures. No one has reported worse seizures from the drug. Animal studies further support some protection from cannabinoids against seizures. Clinical studies using humans have not been conducted.

Melatonin. Melatonin is a hormone found in the brain that is best known for its role in sleep. Some researchers believe that it might have properties that could benefit patients with epilepsy. Melatonin is a powerful hormone that can have major effects on all parts of the body. No one with epilepsy should experiment with this supplement except as part of a clinical trial. In some studies, melatonin has been found to cause seizures in children who have existing neurologic problems.

Surgery

Surgical techniques to remove injured brain tissue may be appropriate for many patients with epilepsy. The surgeon's goal is to remove only the damaged tissue in order to prevent seizures and to avoid healthy brain tissue. Surgical techniques for reaching these goals have improved significantly over the past decades due to advances in imaging and monitoring, new surgical techniques, and a better understanding of the brain and epilepsy.

A number of tests using imaging and electroencephalography (EEG) can determine if surgery is an option:

The general approach is to first use long-term EEG monitoring to locate the brain tissue that triggers the epileptic event.
Advanced imaging techniques can provide valuable additional information. They include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), or single-photon emission computer tomography (SPECT) scans.

If the imaging tests indicate that more than one site is involved or their results conflict, then more invasive monitoring of the brain may be required, although the newer imaging tests are proving to be very accurate tools. If such tests pinpoint a specific area in the brain as the location for seizures, surgery is possible. MEG, for example, is now approved for imaging parts of the brain involved with motor control, sensation, and language function, and may become important in evaluating patients who are likely candidates for surgery. The doctor will also examine the test results to determine if the offending nerve cells perform vital functions and try to predict surgical outcome in certain cases.

The major areas of the brain have one or more specific functions.

The most common surgical procedure for epilepsy is temporal lobectomy, which is performed when epilepsy occurs in the temporal lobe. (Surgery is not as successful in epilepsies that occur in the frontal lobe.) It involves removing small portions from the hippocampus. The hippocampus is a part of the brain that is involved in memory processing. It is part of the limbic system, which controls emotions.

Click the icon to see an image of the limbic system of the brain.

Candidates. Candidates for this surgery usually have a history of seizures. Anti-epileptic drugs have not helped them. Young children may be more difficult candidates because they often have injured areas outside the temporal lobes. Nevertheless, surgery can be very successful in many children, even if more than one area is involved.

Success Rates. New imaging techniques are dramatically improving the success rates of temporal lobe surgery. Studies have shown that many patients remain seizure-free after temporal lobectomy. In a randomized controlled trial, around 60% of patients became free of disabling seizures after surgery versus only 8% of patients treated with medications. In general, around 60 - 80% of patients are seizure free 1 - 2 years after surgery.

Patients may still need to take medications after surgery, even if seizures are very infrequent. Cure is not always possible, and some patients may still experience some seizures. Double vision is very common after the operation, but it is typically temporary and resolves within a few months.

Studies also suggest that temporal lobe surgery improves quality of life and can help relieve depression and anxiety. Other studies indicate that surgery may even prolong survival. Some experts theorize that surgery stabilizes parts of the brain that influence heart rate and may reduce the risk of sudden death, a rare complication of epilepsy.

Effects on Mental Functioning. Although surgery on the left temporal lobe does not impair intelligence to any significant degree, some studies suggest negative effects of mental functioning and behavior. A risk of impairment of verbal memory is also present.

In general, surgical effects on mental functioning and behavior depend on the extent and location of the surgical area.

Lesionectomy is a procedure that removes abnormal tissues in certain conditions, such as:

Cavernous angiomas (abnormal clusters of blood vessels)
Low-grade brain tumors
Cortical dysplasias (these are abnormalities in fetal development in which the normal migration of nerve cells is altered for some reason)

This local surgery, which can cure the patient's epilepsy, has become possible with the advent of advanced imaging techniques such as MRI.

Other surgical procedures called hemispherectomy and corpus callosotomy offer hope for specific patients. They include infants and young children with catastrophic seizures that occur in one, or part of, a hemisphere and for patients whose seizures are due to specific structural brain abnormalities or tumors.

Hemispherectomy. Hemispherectomy is the removal of half the brain, leaving the deep structures intact. Surgery can take 12 hours and there is always some paralysis on one side of the body. There is also a small risk for hydrocephalus, coma, or even death. Quality of life is almost always improved, however, and the surgery does not reduce intelligence.

Corpus Callosotomy. Corpus callosotomy involves cutting the nerve fibers that connect one side of the brain to another. It does not remove brain tissue. It may be done in two stages. In the first, there is a partial separation. If seizures continue, the surgeon may perform a complete separation. This surgery can reduce (although not entirely stop) uncontrolled tonic clonic seizures. It has been used in patients with specific syndromes, such as Lennox-Gastaut syndrome. The procedure can have very severe complications, however.

Electrical stimulation of areas in the brain that affect epilepsy is helping many patients with refractory epilepsy. Vagus nerve stimulation (VNS), an electrical stimulation of the vagus nerve, is now an accepted therapy for severe epilepsy that does not respond to AEDs. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. They affect swallowing, speech, and many other functions. They also appear to connect to parts of the brain that are involved with seizures. The procedure is as follows:

Click the icon to see a depiction of epilepsy treatment.

A battery-powered device similar to a pacemaker is implanted under the skin in the upper left of the chest.
A lead is then attached to the left vagus nerve in the lower part of the neck.
The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. (Patients may also pass a magnet over the device to give it an extra dose if they sense a seizure coming on. This appears to help about 25 - 30% of patients.)
The batteries wear out after 3 - 5 years and need to be removed and replaced by a simple surgical procedure.

An investigational approach called deep brain stimulation (DBS) targets the thalamus, the part of the brain that produces most epileptic seizures. Early results have been promising. Researchers are also studying other implanted brain and nerve stimulation devices such as the responsive neurostimulator system (RNS), which detects seizures and stops them by sending electrical stimulation to the brain. A third investigational approach, trigeminal nerve stimulation (TNS), stimulates a nerve involved in inhibiting seizures.

Candidates. The American Academy of Neurology recommends VNS for:

Patients who are over 12 years old, and
Have partial seizures that do not respond to medication, and
Are not appropriate candidates for surgery

Evidence is accumulating, however, to indicate that VNS is effective and safe for many patients of all ages and for refractory epilepsy of many types.

Success Rates. Studies are reporting that the procedure reduces seizures within 4 months by up to 50% and even more in many patients. Studies report that it has been effective for longer than 7 years. In one study that followed patients for a year, the benefits of VNS appeared to increase over time.

Complications. Vagus nerve stimulation does not eliminate seizures in most patients and is still somewhat invasive. VNS can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Some studies suggest that the treatment causes adverse changes in breathing during sleep and may cause lung function deterioration in people with existing lung disease. People who have obstructive sleep apnea also should be cautious about this procedure. Turning off the VNS (for example before an MRI or surgery) may increase the risk for status epilepticus. (However, VNS may also be helpful for treating status epilepticus in some patients.)

Stereotactic Radio Surgery. Focused beams of radiation are able to destroy lesions deep in the brain without the need for open surgery. Typically used for brain tumors, stereotactic radio surgery is also under investigation for temporal lobe epilepsy and for seizures due to cavernous malformations. It may be used for patients when an open surgical approach is not possible.

Lifestyle Changes

The best preventive measure is to comply strictly with the drug regimen as prescribed. Seizures cannot be prevented by lifestyle changes alone, but people can make behavioral changes that improve their lives and give them a sense of control.

In most cases, there is no known cause for epileptic seizures, but specific events or conditions may trigger them and should be avoided.

Inadequate or Fragmented Sleep. Inadequate or fragmented sleep can set off seizures in many people. In one study, the lowest risk for seizures was during REM sleep (when dreams occur). The highest risk was during light non-REM stages of sleep. Using sleep hygiene or other methods to improve sleep may be helpful.

Food Allergies. Food allergies may provoke seizures in children who also have migraine headaches, hyperactive behavior, and abdominal pains. Parents should consult an allergist if they suspect foods or additives might be playing a role in such cases.

Alcohol and Smoking. Alcohol and smoking should be avoided, although light alcohol consumption does not appear to increase seizure activity in people who are not alcoholics or sensitive to alcohol.

Flashing Lights. Patients should avoid exposure to flashing or strobe lights. Video games have been known to trigger seizures in people with existing epilepsy, but apparently only if they are already sensitive to flashing lights. Seizures have been reported in Japan among people who watched cartoons with rapidly fluctuating colors and quick flashes. The frequency of flashes per second is measured in hertz (Hz). Screens that emit a lower hertz (such as 50 Hz screens sold in Europe) are more likely to cause seizures in people with epilepsy than a higher-hertz screen (such as 100 Hz screens sold in the U.S.).

Relaxation methods include diaphragmatic rhythmic breathing, biofeedback, and meditation techniques. No strong evidence supports their value on reducing actual attacks (although some people have reported that they have), but they may be helpful in reducing anxiety in people who have positive experiences with them. There have been some reports that deep breathing (a common relaxation technique) triggers seizures in certain people.

Exercise is important for many aspects of epilepsy, although it can be problematic. Weight-bearing exercise helps maintain bone density, which can be reduced by many of the medications, particularly the older ones. Exercise can also help to prevent weight gain, which is a problem with some drugs. There have been some reports that exercise may trigger seizures in some patients, but this is uncommon. A number of studies have found no significant association between physical activity and a higher incidence of seizures in patients with epilepsy. Nevertheless, if patients are concerned they should discuss this issue with their doctors.

Some small studies have reported significant benefits from the practice of yoga, which employs weight bearing and balancing postures. In one study, a system of meditation called Sahaja yoga changed EEG readings of brain waves and reduced seizures. Other studies report a 50% reduction in seizures and an overall decline in the number of attacks per month. Still, well-controlled studies are needed to confirm these benefits.

All patients should maintain a healthy diet, including plenty of whole grains, fresh vegetables, and fruits. In addition, dairy foods may be important to maintain calcium levels. Fasting has been used to prevent seizures since ancient times. In the 1920s, a high-fat, no-sugar, low protein diet, known as a ketogenic diet, was used to prevent seizures. It lost popularity after the introduction of anti-epileptic drugs but is now proving to be effective with many children. Researchers are investigating whether the Atkins diet (high protein, low carbohydrate) may help people with epilepsy. Both the ketogenic diet and the Atkins diet can interfere with some anti-epileptic medications such as topiramate. Talk to your doctor before beginning any special diet or a weight loss program.

The ketogenic diet, which is very high in fat (90%), very low in carbohydrates, and low in protein, has been studied and debated for decades. It has proven to be helpful for many children with severe epilepsy that does not respond to AEDs. It is not clear why it works. The standard theory is that burning fat instead of carbohydrates causes an increase in ketones. Excess ketones (called ketosis) appears to alter certain amino acids in the brain and to increase levels of the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Benefits of the Ketogenic Diet. Studies report that about 10 - 15% of children who use the diet are seizure free after 1 year, while 30% are nearly seizure free. Some parents report that the diet helps improve their children’s alertness, even if seizures continue. Many children who try the ketogenic diet are able to stop or at least reduce their medications.

Candidates of the Ketogenic Diet. The Ketogenic Diet seems to be most helpful for children who have difficult-to-control seizures, in particular:

Generalized and partial seizures (the diet does not appear to be as helpful for children with partial-onset seizures)
Myoclonic-atastic epilepsy
Infantile spasm

Typical Ketogenic Diet. (This diet must be professionally monitored! Parents can endanger their children if they try the program on their own without consulting a doctor or trained health expert.) The child fasts for the first 1 - 2 days, then the diet is gradually introduced. The regimen uses small amounts of carbohydrates and large amounts of fats (up to 90%), with very few proteins and no sugar. Children generally consume 75% of their usual daily calorie requirements.

A typical dinner may include a chicken cutlet or piece of fish, broccoli with cheese, lettuce with mayonnaise, and a whipped cream sundae. Vegetables may include celery, cucumbers, or asparagus, cauliflower, and spinach. Breakfast might consist of an omelet, bacon, and cocoa with cream. (Artificial sweeteners are used for any desserts.)

The diet is difficult, as a slight deviation from the diet can provoke a seizure. Children cannot take medications that contain sugar (which is common in many drugs produced for children). Some sunscreens and lotions contain sorbitol, a carbohydrate that can be absorbed through skin. About 40 - 50% of patients find the diet too difficult or ineffective and stop it after 6 months.

Researchers are also investigating the Atkins diet, a popular weight-loss diet that has similar effects but is less restrictive than the ketogenic diet. Early results indicate that it might be helpful for some young people. Another alternative is a low glycemic index diet, which contains even fewer carbohydrates than the Atkins diet. Still, parents should not put their children on these diets without support from a doctor.

Side Effects and Complications. To prevent serious side effects, children need regular monitoring by a doctor, especially when the diet is first initiated.

Side effects or complications that may occur at the start of the diet include:

Acidosis, a build-up of acid in the blood and body
Low blood sugar (hypoglycemia)
Stomach upset
Dehydration
Lethargy

Side effects that may occur later on include:

Unhealthy cholesterol and lipid levels
Kidney stones, which may be a complication of acidosis, occur in about 5% of children on the diet. Patients should drink plenty of fluids. Oral potassium citrate (Polycitra K) may be protective.
Slowing of growth (tends to occur more in younger children than older children
Decreased bone density

Because most patients remain on the diet for only 2 years, the risks for potential long-term damage appear minimal.

Many patients with epilepsy and parents whose children have epilepsy can benefit from support associations. These services are usually free and available in most cities.

Tips for Helping Children. Some of the following tips may help the child with epilepsy:

Children should be treated as normally as possible by parents and siblings.
Children should be assured that they will not die from epilepsy.
Often children can be given the hope that they will outgrow the disorder.
Most children will not have seizures triggered by sports or by any other ordinary activities that are enjoyable and healthy.
As soon as they are old enough, children should be active participants in maintaining their drug regimens, which should be presented in as positive a light as possible.

Therapies for Children and Adults. Because of the risks for serious emotional consequences, psychological therapy may be beneficial and even necessary for some adults and children. In one study, cognitive behavioral therapy was helpful in lowering seizure rates in young people with juvenile myoclonic epilepsy. This approach offers a structured counseling program that helps people change behaviors that can reduce seizure risk factors such as anxiety and insomnia.

Resources

www.epilepsyfoundation.org -- Epilepsy Foundation
www.aesnet.org -- American Epilepsy Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

References

Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007 Aug;6(:693-8.

Foldvary-Schaefer N, Wyllie E. Epilepsy. In: Goetz C, ed. Textbook of Clinical Neurology. 3rd edition. Saunders. 2007.

Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar;119(3):535-43.

Johnson MV. Seizures in childhood. In: Behrman RE, ed. Nelson Textbook of Pediatrics. 17th edition. Saunders. 2004.

Krebs PP. Psychogenic nonepileptic seizures. Am J Electroneurodiagnostic Technol. 2007 Mar;47(1):20-8.

Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007 Nov 20;69(21):1996-2007.

Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.

Leone MA, Solari A, Beghi E; FIRST Group. Treatment of the first tonic-clonic seizure does not affect long-term remission of epilepsy. Neurology. 2006 Dec 26;67(12):2227-9.

Salanova V, Worth R. Neurostimulators in epilepsy. Curr Neurol Neurosci Rep. 2007 Jul;7(4):315-9.

Spencer SS. Seizures and epilepsy. In: Goldman L, ed. Cecil Medicine. 23rd edition. Saunders. 2007.

Tomson T, Hiilesmaa V. Epilepsy in pregnancy. BMJ. 2007 Oct 13;335(7623):769-73.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Hirsutism

FitSugar — Wed, 08 Oct 2008 17:34:54 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Hirsutism is excessive growth of dark, coarse body and facial hair in women. The abnormal hair growth typically occurs in a pattern seen in adult males. While some body and facial hair growth is normal, women with hirsutism tend to produce elevated levels of male sex hormones called androgens from their ovaries and adrenal glands. Most cases of hirsutism are not excessive and have no underlying cause, but some may indicate the presence of a more serious underlying condition, such as Cushing's syndrome. An estimated 8% of adult women in the United States have hirsutism.

Signs and Symptoms

The primary signs and symptoms of hirsutism include:

Hair growth on the abdomen, breasts, and upper lip (male-pattern hair growth in women)
Irregular menstrual periods
Acne
Abnormally strong smelling perspiration
Loss of feminine body shape
Signs of masculinity -- deepening voice, frontal balding, enlarged clitoris, enlarged shoulder muscles
Cushing's syndrome -- a condition marked by obesity (especially around the abdomen), high blood pressure, diabetes, and thinning of the skin

Causes

Identifiable causes of hirsutism are generally related to increased secretion of androgens from the ovaries or adrenal glands. This can result from a variety of conditions, including:

Polycystic ovarian syndrome (PCOS) -- often associated with infertility
Tumors on the adrenal glands or ovaries
Cushing's syndrome
Severe insulin resistance
Obesity

Hirsutism may also be caused by:

Medications that can cause hair growth -- phenytoin, minoxidil, diazoxide, cyclosporine, and hexachlorobenzene
Anorexia nervosa
Anabolic steroids
Danazol -- a substance used to treat endometriosis
Hormone replacement therapy (HRT) containing androgens
Birth control pills containing high levels of androgen hormones

Risk Factors

The following factors may increase an individual's risk of hirsutism:

Genetics -- hair patterns are inherited
Anorexia nervosa
Race and ethnicity -- the condition is more common in women predominantly of European ancestry than it is in those of Asian, Native American, or African ancestry. It is also more common in dark-skinned women.
Menopause
Obesity

Diagnosis

The first step is to conduct a physical examination. During the physical exam, the doctor will inspect the body for all sites of abnormal hair growth and ask questions about the onset and progression of the condition. A doctor may also perform a pelvic examination to determine whether tumors or cysts are present on the ovaries. After performing the physical examination, one of the following may be necessary to identify the cause of hirsutism:

Laboratory tests -- may detect elevated androgen levels
CT scan, MRI, pelvic ultrasound -- used to identify cysts or tumors on the ovaries or adrenal glands
Laparoscopy -- an instrument is inserted into the abdominal wall to detect cysts or tumors on the ovaries.

Preventive Care

Even if an individual is at risk for hirsutism, there are steps she can take to prevent it. For example, studies suggest that obese women with PCOS may be less likely to develop hirsutism if they consume a low-calorie diet.

Treatment

The specific treatment for hirsutism depends on the extent of the problem, whether or not an underlying cause can be identified, and, if so, what the root of that cause is. For example, an individual with hirsutism will usually be advised to discontinue medications that may be contributing to the condition. If a tumor is located on the ovaries or adrenal glands, the doctor will likely recommend that it be surgically removed. Overweight individuals with hirsutism may be urged to participate in a weight loss program since calorie restriction may lower androgen production in the body. Although no medications for hirsutism have been approved by the U.S. Food and Drug Administration (FDA), some drugs may suppress androgen secretion and reduce hair growth. If no underlying cause that can be treated by conventional medication is identified, it may be possible to control the symptoms of hirsutism with acupuncture, and cosmetic therapies that conceal or remove excess hair (such as bleaching and waxing). Psychological support may also be helpful since hirsutism is often a frustrating and embarrassing condition.

Lifestyle

Eating a balanced diet and getting adequate exercise can help control weight, which may diminish or prevent hirsutism related to obesity.

Medications

While there are currently no medications approved by the FDA specifically for the treatment of hirsutism, certain medications may be used to suppress the production and secretion of androgens in the body. Up to 70% of individuals with hirsutism may respond to these medications, but it can take 6 months or longer for the medications to effectively reduce hair growth and they must be taken indefinitely to keep the symptoms under control. These medications include:

Glucocorticoids (such as Dexamethasone)
Certain birth control pills with low levels of androgen hormones, such as desogestrel or norgestimate
Spironolactone

Surgery and Other Procedures

A doctor may recommend the following surgical procedures in severe cases of hirsutism:

Tumor removal -- if a tumor on the ovaries or adrenal glands is the cause
Ovary removal after childbearing years -- if ovaries are producing elevated levels of androgens

Nutrition and Dietary Supplements

A comprehensive treatment plan for hirsutism may include a range of complementary and alternative therapies. Preliminary studies suggest that nutritional supplements may reduce the symptoms of some hirsutism. Ask your team of health care providers about the best ways to incorporate these therapies into your overall treatment plan. Always tell your health care provider about the herbs and supplements you are using or considering using.

Following these nutritional tips may help reduce symptoms:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes) and vegetables (such as squash and bell peppers).
Avoid refined foods, such as white breads, pastas, and especially sugar.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
Use healthy oils in foods, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Drink soy milk, for bone health and hormonal balance.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise at least 30 minutes daily, five days a week.

You may address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc and selenium.
Calcium-D-Glucarate, 200 mg two times daily, may help the body detoxify hormones and decrease symptoms of hirsutism.
Diindolylmethane, a natural supplement commonly sold under the trade name Indolplex, 120 mg daily, can help the body process hormones in the most beneficial way, creating helping balance the underlying hormonal balances which may be causing hirsutism.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 - 3 tablespoonfuls oil daily, to help decrease inflammation and help with immunity.
Vitamin C, 500 - 1,000 mg, one to three times daily, as an antioxidant and for immune support.
Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, when needed for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
Astaxanthin, 2 - 6 mg daily, for immune and antioxidant support.
Alpha-lipoic acid, 25 - 50 mg twice daily, for antioxidant support.
Ipriflavone (soy isoflavones) standardized extract, 200 mg three times a day, for breast cancer support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant and immune activity.
Melatonin, 2 - 6 mg at bedtime as needed, for immune support and sleep. Consult your health care provider if you are taking prescription medications, as melatonin.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted. Talk with your health care provider about which herb may be best for you.

Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant, anticancer, and immune effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
Saw palmetto (Serenoa repens) standardized extract, 160 mg two times daily, for hormonal support.
Chaste tree (Vitex agnus castus) standardized extract, 20 - 40 mg daily before breakfast, for hormonal balance.
Black cohosh (Actaea racemosa) standardized extract, 20 - 40 mg two times a day, for hormonal balance.
Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support.
Rhodiola (Rhodiola rosea) standardized extract, 100 - 600 mg daily, for antioxidant and anti-stress activity.

Acupuncture

One small study of women with hirsutism found that acupuncture markedly reduced both hair density and hair length and significantly reduced their levels of the male sex hormone testosterone (a type of androgen). This study is promising, but further research will be required to determine whether greater numbers of women with hirsutism would benefit from acupuncture and what causes of hirsutism respond best to acupuncture.

Other Considerations

Pregnancy

Medications that alter androgen levels should generally not be taken during pregnancy. A doctor can provide guidance and appropriate medical care.

Hair growth may increase during the third trimester, especially on the face, extremities, and breasts. This hair growth is considered normal and is not a sign of hirsutism.

Prognosis and Complications

If the underlying cause of hirsutism can be identified and treated, the symptoms of hirsutism may be effectively controlled. Long-term medication, when appropriate, will slow hair growth, but it generally won't eliminate existing hair patterns on the face and body. There are some cosmetic therapies that can reduce the appearance of excessive hair growth. Counseling with a trained professional may also be helpful for women who experience psychological stress as a result of their hair growth.

Supporting Research

Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int 199:61:S23–7.

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Review Date:
10/21/2006
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. Copyright

adam.com

Melanoma and other skin cancers

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Melanoma
Nonmelanoma Skin Cancer
Precancerous Skin Condition...
Causes
Risk Factors
Prevention
Screening
Diagnosis
Staging
Treatment for Melanoma
Treatment for Nonmelanoma S...
Prognosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk factors

According to a report in the Archives of Dermatology, marathon runners are more likely than the general population to develop skin changes that increase the risk for melanoma.

Prevention

A study published in The Lancet indicates that the best ways to avoid sun damage are to reduce the time you spend in the sun and to wear a hat and clothing to protect as much of your skin as possible. Fabrics that are thick and tightly woven offer the best protection.

The U.S. Food and Drug Administration has approved a new type of sunscreen that may more effectively block UVA than products currently available in the United States. UVA light penetrates the skin deeper than other forms of sunlight. Exposure to UVA is believed to contribute to skin cancers. The new sunscreen, called Anthelios SX, is available over the counter.

Screening

A study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they understand their personal risk factors for melanoma and know where to go to have such an exam. The study emphasizes the importance of skin cancer awareness and education.

One-time melanoma screening for adults over age 50 seems to be as cost-effective as other nationally recommended cancer screening programs, according to a report in the Archives of Dermatology. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology. The earlier melanoma is diagnosed and treated, the greater your chances of survival.

Introduction

Skin cancer is cancer that starts in the skin. Skin cancers are divided into two major groups:

Nonmelanoma, which includes basal cell cancer and squamous cell cancer
Melanoma, the deadliest form of skin cancer

Different skin cancers start in different layers or cells of the skin. To understand how skin cancer develops, it is useful to know something about the skin.

The Skin. The skin is the largest organ in the body and consists of layers.

The outermost layer of the skin is called the epidermis. It is only about 20 cells deep, roughly as thick as a sheet of paper.
The dermis ranges in thickness from 1 - 4 millimeters (about 1/32 - 1/8 inch). The dermis contains tiny blood and lymph vessels, which increase in number deeper in the skin.

The skin is the largest organ of the body. The skin and its derivatives (hair, nails, sweat, and oil glands) make up the integumentary system. One of the main functions of the skin is protection. It protects the body from external factors, such as bacteria, chemicals, and temperature. The skin contains secretions that can kill bacteria, and the pigment melanin provides a chemical pigment defense against ultraviolet light that can damage skin cells. The skin also helps control body temperature.

Melanocytes. A layer of cells between the epidermis and the dermis, called melanocytes, produces a brown-black skin pigment ( melanin) that determines skin and hair color. Melanin also helps protect against the damaging rays of the sun.

As a person ages, melanocytes often proliferate, forming concentrated clusters that appear on the surface as small, dark, flat, or dome-shaped spots, which are usually harmless moles or liver spots.

When cell proliferation occurs in a controlled and contained manner, the resulting lesion is benign and is commonly referred to as a mole or nevus.
Sometimes, however, pigment cells grow out of control and become a cancerous and life-threatening melanoma.

Click the icon to see an image of melanin.

Melanoma

At first, melanoma cells are found in the epidermis and top layers of the dermis. However, once they grow downward into the dermis, the cancer can come into contact with lymph and blood vessels. The thicker the melanoma, the greater the likelihood that it could spread to distant sites.

Removal of the lesion before it reaches the deeper layers of the skin is important for achieving a cure.

Superficial Spreading Melanoma. Superficial spreading melanoma is the most common and most curable. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.

Nodular Melanoma. Nodular melanoma appears as a fast-growing brown or black lump, and its characteristics do not always fit the definitions described above. It is important to check for this type of melanoma because it is associated with an outbreak of other tumors.

Lentigo Maligna. Lentigo maligna (sometimes called Hutchinson's freckle) usually occurs in elderly people and is marked by flat, mottled, tan-to-brown freckle-like spots with irregular borders. These lesions often appear on the face or other sun-exposed areas and typically enlarge slowly for 5 - 15 years before cancer appears.

Acral Lentiginous Melanoma. Although rare, acral lentiginous melanoma is the most common melanoma among African and Asian populations. It commonly appears as a dark patch on the palms, soles, fingers, toes, under fingernails or toenails, or in mucous membranes.

Melanoma cells usually spread first through the lymph vessels or glands. Melanoma cells can also spread by way of blood vessels to various organs, spreading cancer to the liver, lungs, brain, or other sites.

Melanomas tend to grow in stages:

Most melanomas tend to be flat initially and spread laterally across the skin surface as they grow. At this early stage, which can last 1 - 5 years or longer, removal of the growth has an excellent chance of curing the melanoma. Still, there is a chance that some of these melanomas are invasive, and they should be treated aggressively.
Lesions that become raised or dome-shaped over at least part of their surface indicate that downward growth has occurred. In some cases, this growth is very rapid, occurring over a period of weeks to months.

Any suspicious lesion should be checked immediately, particularly if it has grown quickly or is partially flat and partially raised.

Common sites of melanoma in men include:

Head
Middle of the body (trunk)
Neck

Common sites of melanoma in women include:

Arms
Legs

However, any area of the skin may be affected. You may not notice melanomas if they appear on areas that are difficult to examine, such as the scalp or the back.

Less common sites for melanoma include:

Fingers
Palms
Soles of the feet
Genitals
Lips
Under the fingernails or toenails

The presence of a dark lesion under the nail that runs into the adjoining skin and doesn't heal may signal melanoma.

Rarely, melanomas appear in the mouth, in the iris of the eye, or in the retina at the back of the eye, where they may be detected during dental or eye examinations.

Click the icon to see an image of melanoma.

Nonmelanoma Skin Cancer

The two other types of skin cancers are called basal cell cancer and squamous cell cancer. These are nonmelanoma skin cancers.

Basal cell cancer starts in the lowest part of the epidermis in round cells called basal cells. Basal cell is the most common form of skin cancer. It occurs in about 800,000 - 900,000 people every year.

Basal cell cancer usually develops later in life in areas that have received the most sun exposure, such as the head, neck, back, and especially the nose. However, some basal cell cancers appear in areas not exposed to the sun.

Basal cell cancers have many different appearances:

They usually appear as a round area of thickened skin that does not change color or cause pain or itching.
Very slowly, the lesion spreads out and develops a slightly raised edge, which may be translucent and smooth. Infrequently, basal cell cancers resemble malignant melanomas in color.
Eventually, the center becomes hollowed and covered with a thin skin, which can become sore and open.
A form known as aggressive-growth basal cell cancer resembles a scar with a hard base. This type is more likely to spread and must be treated very aggressively.

Basal cell cancer is a cancerous (malignant) skin tumor involving basal skin cells. Basal cell skin cancers usually occur on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation. Once a suspicious lesion is found, a biopsy is needed to prove the diagnosis of basal cell cancer. Treatment varies depending on the size, depth, and location of the cancer.

Basal cell cancers are sometimes hard to tell from benign skin conditions. For instance, occasionally they arise in unexposed skin, where they may mimic an ordinary mole, cyst, or pimple. They may be particularly difficult to distinguish from benign cysts when they occur near the eyes.

Usually, basal cells grow slowly. They are rarely deadly. Most basal cell cancers need not be treated as an emergency, although late treatment can cause disfigurement, so they should be removed as early as possible.

Basal cell cancers that are most likely to spread include those that are larger than 1 centimeter, scar-like, and those located on the cheek, nose, neck, earlobe, eyelid, or temple.

Some studies have shown that people with basal cell cancer may be at higher risk for second cancers, including melanoma, cancer of the lip, salivary glands, larynx, lung, breast, and kidney, and non-Hodgkin's lymphoma. Those at higher risk for such cancers appear to be men and anyone diagnosed before 60 with basal cell cancer.

Squamous cell cancer develops from flat, scale-like skin cells called keratinocytes, which lie under the top layer of the epidermis. Most squamous cell cancers occur on sun-exposed areas, especially the forehead, temple, ears, neck, and back of the hands. People who have spent considerable time sunbathing may develop them on their lower legs.

Types of squamous cell cancer:

Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of this type of cancer. The cancer has not spread. Cancer areas appear as large reddish patches (often over 1 inch) that are scaly and crusted.
Invasive squamous cell carcinoma is highly likely to spread (metastasize). The skin cancer lesions can grown rapidly (over months) or slowly (over years). Eventually they become ulcerated.

Click the icon to see an image of squamous cell cancer.

Prompt treatment is desirable because squamous cell cancers are more likely to spread to local lymph nodes than basal cell cancer. Squamous cell cancers most likely to spread include:

Deep lesions, those larger than 2 cm in diameter, or patches with poorly defined margins
Recurrent lesions
Squamous cell cancer on neck, earlobe, eyelid, lips, or temple
Squamous cell cancer that develops in ulcers
Squamous cell cancer that develops on skin areas that have been previously treated with radiation or exposed to cancer-killing chemicals

People with squamous cell cancers seem to be at higher risk for other cancers, including melanoma, lung cancer, non-Hodgkin's lymphoma, bladder cancer, leukemia, testicular and prostate cancer in men, and breast cancer in women.

Precancerous Skin Conditions

Actinic (Solar) Keratosis. Actinic keratosis (also called solar keratosis) is a precancerous skin lesion caused by too much sun exposure. Such lesions can turn into cancer, but not always.

Actinic keratoses occur after years of sun exposure. They appear predominantly on sun-exposed skin, such as the face, neck, back of the hands and forearms, upper chest, and upper back. Men may develop keratoses along the rim of the ear.

Actinic keratoses have the following characteristics:

Lesions typically occur on the surface of the skin and have a sandpaper-like feel. In fact, they are sometimes more easily felt than seen.
Most lesions are pink and even flesh-colored. Some are red or brown, scaly, and tender. At times, they can resemble melanomas; even dermatologists may have trouble telling the two apart.
They can range in size from microscopic to several inches in diameter.

Keratoacanthomas. Keratoacanthomas closely resemble squamous cell cancers, but they are not malignant. The majority occur in sun-exposed skin, usually on the hands or face. They are typically skin colored or slightly red when they first develop, but their appearance typically changes:

In the early stages, keratoacanthomas are smooth, red, and dome shaped.
Within a few weeks, they can grow rapidly, usually to 1 or 2 centimeters. Some reach the size of a quarter in less than a month and can be rather disfiguring.
They eventually stop growing and become crater-like with a surrounding outer rim of tissue and sometimes have a crusty interior.

Most will spontaneously get better within 1 year, but they almost always scar after healing. Also about 25% develop into squamous cell cancers, most frequently in older people and in sun-exposed areas. Removal by surgery (sometimes by radiation) is recommended. They may also be treated with 5-fluorouracil, either as a cream or injections.

Causes

You cannot overestimate the role of the sun as the most important cause of prematurely aging skin (called photoaging ) and skin cancers.

Long-term repetitive and cumulative exposure to sunlight appears to be responsible for the vast majority of undesirable consequences of aging skin, including basal cell and squamous cell cancers.

Melanoma is more likely to be caused by intense exposure to sunlight in early life.

UVA and UVB Radiation. When sunlight penetrates the top layers of the skin, ultraviolet (UVA or UVB) radiation strikes the DNA inside the skin cells and damages it.

UVB is the main type of radiation responsible for sunburns. It primarily affects the outer skin layers. This type of ultraviolet light is most intense at midday when sunlight is brightest.
UVA penetrates more deeply and efficiently. Unlike UVB, window glass does not filter out UVA rays.

Damaging Effects of UV Radiation. Both UVA and UVB rays cause damage, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders, and cancer, although the mechanisms are not yet fully clear. The following are some ways in which cancer may develop and some defensive actions that the skin uses to defend itself against DNA damage.

Oxidation and Antioxidants. The effects of UV radiation are implicated in the production of oxidants, also called free radicals. Free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter the DNA. This contributes to the aging process and sometimes to cancer.
Defective DNA Repair and Protective Enzymes. Some skin cancers are caused by a breakdown in the body's mechanisms that help repair DNA damage. For example, xeroderma pigmentosum (XP) is a rare genetic disease in which the body cannot repair damage caused by ultraviolet light. Normally, a number of enzymes in the skin help protect against this damage.
Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune system cells attack developing cancer cells at the very earliest stages. However, certain substances in the skin, particularly a chemical called urocanic acid, can suppress such immune factors when exposed to sunlight.

Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are very severely damaged. Apoptosis in the skin kills off cells harmed by UVA so that they do not turn cancerous. The peeling after sunburn is the result of these dead skin cells. However, some gene defects or other factors interfere with apoptosis. If this occurs, damaged cells can continue to spread, resulting in skin cancer.

A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental assaults (particularly sunlight).

Mutations in Genes that Regulate Cell Growth. Noninherited mutations in a number of genes that block tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.

Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may be a viable treatment path.
P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.
Genetic mutations that regulate Ku70 and Ku80 proteins may disrupt processes that repair strands of DNA.
Researchers are also studying mutations in a gene that encodes for a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and may account for many sporadic (non-inherited) cases of melanoma.
Of further interest are mutations in genes that regulate Fas proteins, which are involved in apoptosis, a natural process of cell self-destruction. When apoptosis goes awry in melanoma cells, proliferation can become rampant.

CDKN2A Mutations. Mutations in a gene regulator called CDKN2A are the most common causes of inherited melanoma, which is still very uncommon. Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A, although it is not clear if knowing the results of the test would benefit people carrying the gene.

Variations in the Melanocortin-1 Receptor Gene. One study found that the greater the number of variations from normal in a gene called the melanocortin-1 receptor gene, the greater the risk for melanoma. The gene plays an important role in determining if a person has red hair, fair skin, and sensitivity to UV radiation. Interestingly, people who had olive and darker skin and who carried one or more variations of the gene had a higher than average risk for melanoma.

Aging may weaken the body's ability to fend off impending cancers, including melanomas. As a person ages, they lose Langerhans cells that help fight off early skin cancers. The number of these immune cells decreases with age, possibly setting the stage for skin cancers in later life.

Risk Factors

In the United States, the rate of melanoma is rising more rapidly than any other cancer. According to the American Cancer Society, about 59,940 persons will be diagnosed with melanoma in 2007. More than 8,000 people will die from the cancer.

Survival rates have been improving, however, and the increase in melanomas has occurred principally with thin, less aggressive forms of the disease. Some experts believe this is due to the increased awareness from effective public programs and earlier diagnosis.

A risk factor is anything that increases your chance of getting a disease. The following factors increase your risk for skin cancer:

Age over 40
Being male
Fair skin
Too much exposure to sunlight and ultraviolet radiation
Personal history of skin cancer
Family history of skin cancer
Smoking
Certain chronic or severe skin problems
Certain medical conditions or treatments that affect your immune system
Exposure to chemicals or radiation

Melanoma in Adults. Melanoma is most common in people over 40, and the incidence increases significantly as people get older. Before age 40, melanomas are slightly more common in women than men, but after age 40 men are more often affected. Men are also more likely to have invasive and fatal melanoma than are women, although some research suggests that the higher rates are only because men fail to seek a diagnosis of suspicious skin changes before they become dangerous. The rate in women levels off somewhat between age 45 and 60; researchers speculate that menopause could have some sort of protective effect during those years.

Melanoma in Children. Melanoma is rare in children under age 10. Among children ages 10 - 14 the incidence is only 0.3 per 100,000. Between ages 14 - 19, it is still very rare, 1.3 per 100,000. Parents, then, should not be unduly alarmed by every minor skin imperfection in their children. Nevertheless, melanoma is as serious in children as in adults, and early detection is still critical.

Skin cancer is associated with both duration and intensity of sun exposure. Risk of melanoma increases with excessive sun exposure during the first 10 - 18 years of life. Sunburns are also dangerous, with five or more sunburns doubling the risk of developing cancer. Cancer typically arises many years later.

Marathon runners are more likely than the general population to develop skin changes that increase your risk for melanoma. That's because marathon runners spend a lot of time outdoors. The study findings are published in the Archives of Dermatology.

Tanning Devices. Tanning beds and sunlamps increase the risk for developing melanoma, according to a 2005 review of epidemiologic studies. Previous findings have suggested that women who use tanning devices more than once a month significantly increase their melanoma risk. Women in their 20s, as well as blondes and redheads, are especially at risk.

Ethnic Groups and Complexion. People with light skin, blue, gray, or green eyes, red or blond hair, and lots of freckles are at highest risk for developing melanoma. The risk increases for those who are easily sunburned and rarely tan, particularly if they live close to the equator where sunlight is most intense. Darker ethnic groups or those with swarthy complexions are not immune, however.

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). Tanning and Sunburn Risk People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning Risk
I	Always burns, never tans, sensitive to sun exposure.
II	Burns easily, tans minimally.
III	Burns moderately, tans gradually to light brown.
IV	Burns minimally, always tans well to moderately brown.
V	Rarely burns, tans profusely to dark.
VI	Never burns, deeply pigmented, least sensitive.

Australia has the highest melanoma rate in the world. In the United States the rate is highest in California, Florida, and Texas. The disease is by no means limited to such sunny states and countries, however. In general, the risks are highest in regions where the population tends to be blonde and fair-skinned. Norway, for example, has had the highest rate of melanoma in Europe, and rates are soaring in the UK, particularly among men, perhaps because Britons are increasingly vacationing in sunny climates.

Melanoma. Individuals who have been diagnosed with melanoma are at increased risk for a second primary melanoma. According to one 2003 study, the risk over time for developing a second melanoma is 1% in the first year after diagnosis, 2.1% at 5 years, 3.2% at 10 years, and 5.3% at 20 years. The risk is especially higher in older men and in those with first melanomas on the upper body and face.

People with family members who have or had melanoma should also be considered at high risk and examined on a regular basis.

Nonmelanoma Skin Cancers. Nonmelanoma skin cancers, including basal and squamous cell carcinomas, increase the risk of dying from other cancers, including melanoma itself, lung cancer, non-Hodgkin's lymphoma, bladder cancer, and leukemia as well as testicular and prostate cancers (in men) and breast cancer (in women).

Psoriasis. Psoriasis increases the risk for squamous cell carcinoma, but studies conflict on whether it has any effect on melanoma. One study, in fact, reported a lower risk. Nevertheless, there is some evidence that long-term treatment for psoriasis using UVA radiation (PUVA) may increase the risk for melanoma. In one study, there was a significantly higher risk even with relatively few treatments. In one study, invasive melanoma had occurred in 2.8% of patients 15 or more years after the initial treatment.

Moles (Nevi) and Other Dark Blemishes. Certain moles and dark blemishes increase the risk for skin cancer. Any mole ( nevus) or other blemish that seems new, changing, or unusual in any way should be evaluated by a health care professional.

Some specific moles or dark blemishes that are risk factors for melanoma include:

Freckles. Freckles typically appear in children on sun-exposed areas and are usually evenly brown or tan. The more freckles a person develops as a child, the greater the risk for melanoma in adulthood.
Dysplastic (or Atypical) Nevi. About 30% of the population has moles called dysplastic nevi, or atypical moles. They are larger than ordinary moles (most are 5 mm across, about the size of a pencil eraser, or larger), have irregular borders, and are various shades or colors. Individuals who have dysplastic nevi plus a family history of melanoma (a syndrome known as FAMM) are at a high risk for developing melanoma at an early age (younger than 40). The risk for those with atypical moles and no family history of melanoma is less clear.
Large birthmarks (giant congenital nevi). Very large birthmarks more than 8 inches across are major risk factors for melanoma. In such cases, cancer usually appears by age 10. Medium-sized congenital nevi do not appear to increase the risk for melanoma. Whenever possible, very large birthmarks should be removed during infancy. Experts disagree, however, about whether small birthmarks need to be removed. Parents should watch any birthmark for changes.

The more moles one has the higher the risk that one of them will become cancerous, although the danger is still very small. A 2003 study estimated that the risk for a single mole to develop into melanoma by age 80 is 1 in 3,164 in men and 1 in 10,800 for women.

The risk is higher, however, with atypical moles. One study of people with melanoma indicated that the presence of even one atypical mole doubled the normal risk.

Some skin blemishes can look like -- but are not -- melanoma. Noncancerous moles typically have the following characteristics:

They generally remain small with clearly defined, regular borders, and uniform coloration. Some have a regular stippled or net-like pattern of pigmentation, however, and may even resemble early melanoma.
They typically first appear during childhood, puberty, or young adulthood. They may naturally grow, darken, or increase in number at certain times of life, such as adolescence or pregnancy.

Examples of moles or blemishes that may resemble skin cancer include:

Blue nevus. A benign mole that may easily be mistaken for melanoma. It is a blue-black, smooth, raised nodule and commonly occurs on the buttocks, hands, or feet.

Liver Spots. Liver spots are usually evenly brown or tan sun-induced lesions that are universal signs of aging. Occurring most noticeably on the hands and face, these harmless blemishes tend to enlarge and darken over time.

Spindle Cell (Spitz) Nevus. Children may develop a benign lesion called a spindle cell (or Spitz) nevus. The mole is firm, raised, and pink or reddish-brown. It may be smooth or scaly and usually appears on the face, particularly the cheeks. It is not harmful, but it may be difficult to differentiate from a melanoma, even for experts.

Non-Hodgkin's Lymphoma. Survivors of either non-Hodgkin's lymphoma or melanoma face a higher risk for the other malignancy. These may have common causes, such as exposure to UV radiation or shared genetic factors.

Human papillomavirus (HPV). Genital warts (human papillomavirus, or HPV) may also increase the risk of squamous cell cancer in the genital and anal areas and around fingernails.

Immunosuppression. Skin cancer risk is increased in persons whose immune systems are suppressed because of certain medications, organ transplantation, or medical conditions such as AIDS. Melanoma has also developed in patients who received heart transplants from donors who had the disease. Immune-suppressing drugs used to treat autoimmune disorders may also increase the risk of skin cancer. Potential skin cancer risks have been associated with the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic).

Rheumatoid arthritis. Despite previous concerns, the rheumatoid arthritis drug etanercept (Enbrel) does not raise the risk for developing squamous cell skin cancer. The findings are reported in the Archives of Dermatology. Etanercept works by blocking tumor necrosis factor (TNF), an immune system chemical messenger that is involved in inflammatory processes and diseases.

Occupational exposure to radiation, such as in health care or industrial settings, may increase the risk for melanoma. Airline pilots, too, are at increased risk for melanoma. It is uncertain, however, whether this higher risk is from excessive exposure to ionizing radiation at high altitudes or because they have more opportunity to spend time in sunny regions. Experts disagree over whether frequent flyers are also at increased jeopardy.

Prevention

The best way to lower the risk your risk of skin cancer is to protect your skin from the sun and UV light.

Wear sunscreen. The use of sunscreens is complex, and everyone should understand how and when to use them. Follow instructions closely and reapply as directed after swimming or sweating. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Many parents are now taking effective steps to protect their children, although experts worry that they are relying too much on sunscreen and less on other protective measures. Adolescents are at special risk for sun-related cancers because, according to a 2002 study, most of them do not take protective measures when out in the sun. According to the study, boys are less likely to use sunscreen than girls, but girls are more likely to get sunburn and use tanning salons more often.

The best way to prevent skin damage in any case is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. Do not rely on sunscreen alone for sun protection. Also wear protective clothing and sunglasses.
Avoid exposure particularly during the hours of 10 a.m. to 4 p.m., when UV rays are the strongest.
Clouds and haze do not protect you from the sun and in some cases may intensify UVB rays.
Avoid reflective surfaces such as water, sand, concrete, and white-painted areas.
UV intensity depends on the angle of the sun, not heat or brightness. The dangers are greater the closer to the start of summer.
Skin burns faster at higher altitudes. One study suggested that an average complexioned person burns in 6 minutes at 11,000 feet at noon compared to 25 minutes at sea level.
Avoid sun lamps, tanning beds, and tanning salons. The machines use mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon are as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning.

Wear protective clothing, sunglasses, and a hat to shield your face from the sun's rays. Special clothing can block out UV rays and is rated using sun protection factor (SPF) ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however.

Everyone, including children, should wear hats with wide brims. (Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.)
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays when in the sun.

Click the icon to see a depiction of sun protection.

When choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, and benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. And many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little.

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis.

Calculating the SPF. SPF is a ratio based on the amount of UVB radiation needed to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11
Moderate: SPF 12 through 29
High: 30+

Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.

SPF Levels by Age Group. Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. All young children should be well-covered with clothing, sunglasses, and hats. Children should be kept out of the sun during peak sunlight periods. Do not use sunscreens on babies younger than 6 months without consulting a doctor.

Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.

Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. Apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen every day, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however. Sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include:

Until recently, many sunscreens blocked only or predominantly blocked UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Studies then may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may stay out too long during peak sunlight hours. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. A 2002 study found that people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. A later study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure.

Underexposure to sunlight. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems such as:

Vitamin D deficiency. The body makes vitamin D through a chemical reaction to UVB sunlight. Too many sun-protection measures may increase the risk for developing vitamin D deficiency. Vitamin D helps prevent rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. (Warning: Vitamin D is poisonous when taken in high doses.) People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin.
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from seasonal affective disorder (SAD), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary.

A study published in 1994 in the New England Journal of Medicine found that persons with a history of nonmelanoma skin cancer who ate a low-fat diet were much less likely to develop actinic keratosis, a precancerous skin condition.

However, the low-fat diet did not appear to have any effect on the development of basal cell cancer.

Chemoprevention is the use of a substance to prevent or reduce your risk of cancer. Certain drugs have been used to help block the development of skin cancers, including melanoma. For example, a medicine called imiquimod is approved to prevent skin cancer in certain individuals. This medicine prompts the immune system to fight off foreign substances, including cancer cells. Chemopreventive agents under investigation and showing promise for skin cancer include:

Nonsteroidal anti-inflammatory drugs
Difluoromethylornithine (DFMO)
Catechins (phytochemicals found in certain foods)
Anti-aging drugs called retinoids (vitamin A derivatives)

Retinoids have been shown to prevent nonmelanoma skin cancer in patients with basal cell nevus syndrome, xeroderma pigmentosum, and transplanted organs. Oral retinoids include isotretinoin and acitretin. They may also prevent the development of squamous cell carcinoma in patients who are taking such medicines to treat psoriasis.

Early animal studies had suggested that cholesterol-lowering statins or fibrates may reduce the risk of skin cancer, but human studies have produced inconsistent results. A review of several studies has concluded that such drugs do not decrease your risk of melanoma. The findings are published in the Journal of the National Cancer Institute.

Researchers are also studying chemopreventative compounds that target genetic mechanisms in the skin. They may prove to be beneficial ingredients in creams or lotions used to prevent skin cancers on a molecular level. They include cytokine interleukin-12 and T4 endonuclease 5 (T4N5).

Studies have shown that mice with round-the-clock access to an exercise wheel developed skin cancer more slowly when exposed to UVB. Their tumors were also fewer in number and smaller. Analysis of the data suggested that exercise might trigger the death of the developing cancer cells faster than they can grow. Exercise also made the mice lose weight, and the number of tumors decreased as fat disappeared.

Antioxidants are chemicals or drugs that help prevent cell damage from unstable molecules called free radicals. Antioxidants promote to protect the skin include vitamins C and E, and coenzyme Q10 (CoQ10).

Studies suggest that vitamin E creams, particularly those made from a type of Vitamin E called alpha tocopherol, decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also shown that such creams reduce UV-related skin cancer.

Vitamin C is a very potent antioxidant. It is also called ascorbic acid. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts reduced skin swelling and protected immune factors from sunlight.

Selenium in the form of L-selenomethionine has protected against sun damage and even delayed skin cancer in animal studies. It is not known if such benefits apply to people.

Click the icon to read about the antioxidant selenium.

Antioxidant Skin Creams. There are wide claims about the benefits of antioxidants for wrinkles when used in skin creams. However, to date, only vitamin E, C, and selenium-based skin products have been shown to help reduce sun damage to the skin. However, most available brands contain very low concentrations of these antioxidants. In addition, the antioxidants are also not well absorbed by the skin, so the effect may be short-term.

Antioxidant Pills. One small study found that taking a combination of vitamins C and E supplements by mouth may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins alone does not appear to have the same effect.

Other Natural Substances. The following natural substances have antioxidant properties and are being tried for sun-protection:

Both green and black tea appear to have properties that may provide some protection against skin cancers and photoaging. A 2001 study using extracts of topical green tea suggested that it might protect against ultraviolet damage. Green tea skin care products are now available, but their quality is unregulated.
Ginger also appears to have some sun protective qualities.
Silymarin, a substance found in the milk thistle family (which includes artichokes), may prevent UVB-promoted cancers in animals.
Garlic has been shown to protect animals against UVB damage. Whether these results may be applied to humans, and what quantities of garlic might be beneficial, is still unknown.

Warning Note: A wide range of herbal products may contribute to dermatological problems. Some Chinese herbal creams have been found to contain corticosteroids. Mercury or arsenic contaminants have been found in some Ayurvedic therapies. In addition, several oral herbal remedies used for medical or emotional conditions may produce irritation in reaction to sunlight (photosensitivity). They include, but are not limited to, St. John's wort, kava, and yohimbe.

Screening

Education and prevention programs have led to improved screening for skin cancer, which in turn has improved diagnosis and survival rates for melanoma. For example, a study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they were aware of personal risk factors and where they could go to have an exam performed.

Skin cancers may have many different appearances. They can be small, shiny, or waxy, scaly and rough, firm and red, crusty or bleeding, or have other features. Itching, tenderness, scaling, bleeding, crusting, or sores can signal potentially cancerous changes in any mole.

A mnemonic device, ABCDE, is used to describe several features that help to distinguish skin cancer from noncancerous growths.

Asymmetry (A). Skin cancers usually grow in an irregular, asymmetric fashion. That means one half of the abnormal skin area is different than the other half.
Border Irregularity (B). Noncancerous lesions generally have clearly defined borders. Melanoma lesions often have notched or indistinct borders that may signal ongoing growth and spread of the cancer.
Color Variation (C). One of the earliest signs of melanoma may be the appearance of various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. Occasionally, lesions are flesh colored or surrounded by redness or lighter areas of depigmentation.
- Pink or red areas may result from inflammation of blood vessels within the skin.
- Blue areas reflect pigment in the deeper layers of the skin.
- White areas can arise from dead cancerous tissue.
Diameter (D). A diameter of 6 millimeters or larger (about the size of a pencil eraser) is worrisome. Melanomas start out small; by the time a lesion has grown this large, other abnormalities will most likely be present. A doctor should examine any suspicious lesion, no matter what size it is.
Evolution (E). A lesion that is growing or changing deserves evaluation.

The ABCDE plan is a general guide. It will not help detect the early stages of nodular melanoma and may also miss amelanotic melanoma, which is not pigmented.

You should keep in mind that the most important warning sign of melanoma is a new or changing skin lesion, regardless of size or color. Changes that occur over a short period of time (particularly over a few weeks) are most worrisome.

Anyone with risk factors for skin cancer should check the entire body about once a month. People who regularly check moles on their skin may have a lower risk of developing advanced melanoma.

Experts suggest drawing a map of the body, indicating locations of moles, areas of discoloration, lumps, or other blemishes. Whenever a person conducts a self-examination, they should compare their body to the map to check for new lesions, lumps, or moles and for changes in shape, color, and size.

Some experts have defined three specific body areas to look for skin cancers, including melanomas:

Areas visible to anyone, such as the arms or face -- about 60% of melanomas are found on such areas.
Areas usually covered with clothing and visible only to the patients or their partners -- about 34% of melanomas are detected in these areas.
Hidden areas such as the scalp, buttock folds, and mouth -- about 6% of melanomas, usually more advanced, are found here.

Ask a partner to help you check these areas. Turn on a hair dryer to separate hair and examine the scalp.

Some experts recommend that everyone, especially those with a high risk of developing melanoma, have a dermatologist perform a whole body skin exam. Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology.

High-risk people include those with a personal or family history of melanoma and individuals with atypical nevi (irregular moles that are also larger than normal).

Such people should protect themselves from overexposure to sunlight and have a medical examination of the entire skin surface every 3 - 12 months, with the frequency depending on risk factors. Doctors may take photographs of any moles at each visit and compare them with previous photos for any changes.

Examinations for Patients Previously Treated for Melanoma. People who have had melanoma and have been treated successfully are at risk for recurrence or a second primary melanoma. Based on recurrence rates by cancer stage, a team of researchers suggested the following guidelines for being reexamined by the doctor after treatment:

Stage I patients: Yearly exam
Stage II patients: Every 6 months for years 1 and 2 and annually thereafter
Stage III patients: Every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 to 5

All patients should be checked annually after year 5. These are guidelines only and may be changed, depending on individual patient characteristics.

Some studies also suggest that regular screening of family members of people with melanoma could prevent a number of serious cases. A 2007 report in the Archives of Dermatology has called for expanded melanoma screening programs. The study found that one-time melanoma screening for adults over age 50 seems to be as cost-effective as other recommended cancer screenings. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

An experienced doctor should first rule out benign conditions that resemble melanoma, such as a noncancerous mole called a melanocytic nevi.

In rare instances, a melanoma will be difficult to detect. For example, an uncommon form, called a myxoid melanoma, may be mistaken for a benign skin disorder known as a myxoid fibrohistiocytic lesion. Other opinions from a second pathologist, computerized image processing or advanced staining techniques, may help to confirm the diagnosis.

A study published in the Archives of Internal Medicine has found that melanoma tends to be diagnosed at a later stage in persons who are not light-skinned. The study involved nearly 50,000 patients with melanoma, and included Caucasians, Hispanics, Asian/Pacific Islanders, African-Americans, and American Indians.

Some doctors now use dermoscopy (also called dermatoscopy or epiluminescence microscopy). This technique uses a handheld scope-like device that enhances the suspected lesion. It is still not clear if such devices are any better than the naked eye of a trained professional. Of interest, however, was a 2002 study suggesting that it was very useful in identifying possible melanomas in suspicious nail abnormalities and therefore avoiding many painful biopsies in this area. A 2004 study confirmed that adding dermoscopy to conventional naked-eye examination leads to fewer biopsies than using naked-eye examination alone.

A recently developed Australian device (the Solarscan) may improve detection. It is shaped like a hair dryer and takes an image of the suspicious lesion; it then reads the image and compares it with a databank of melanoma images to help determine if it is cancerous. It can also store the image of the lesion and compare it for changes with later images taken at subsequent check ups. The device is not yet used in the United States. It still requires FDA approval. Testing is under way to confirm its accuracy.

A skin biopsy is the removal of skin tissue for examination under a microscope. The exact type of biopsy depends on how deep the lesion has penetrated the skin.

Shave biopsy uses a thin surgical blade to shave off the top layers of skin. The doctor may use this type of biopsy to diagnose basal cell cancer.
Punch biopsy uses a round, cookie-cutter-like tool. It is used to take a deeper sample skin.
Incisional and excisional biopsies remove tumors that have grown deep into the skin. An incisional biopsy cuts out part of the tumor. An excisional biopsy removes the entire tumor. These biopsies are used to diagnose melanoma.

All of the above-mentioned biopsies can be done using local anesthesia.

A lymph node biopsy helps the doctor determine whether cancer has spread to one or more lymph nodes.

A procedure called sentinel lymph node (SLN) biopsy is now recommended for cancers that are thicker than 1 millimeter and generally unnecessary for those thinner than 0.75 millimeter, unless they are ulcerated. Although some evidence suggests this procedure may improve survival, no clinical trials have proven to date that this procedure improves the outlook in persons with melanoma.

Sentinel node biopsy is a technique that helps determine if a cancer has spread. When a cancer has been detected, often the next step is to find the lymph node closest to the tumor site and retrieve it for analysis. The concept of the "sentinel" node, or the first node to drain the area of the cancer, allows a more accurate staging of the cancer, and leaves unaffected nodes behind to continue the important job of draining fluids. The procedure involves the injection of a dye (sometimes mildly radioactive) to pinpoint the lymph node which is closest to the cancer site. Sentinel node biopsy is used to stage many kinds of cancer, including melanoma.

This procedure involves the following:

A tiny amount of a tracer, either a radioactively labeled substance (radioisotope) or a blue dye, is injected into the tumor site.
These substances then flow through the lymph system into the sentinel node, the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed and biopsied.

The results of the biopsy can help doctors decide whether or not to remove other lymph nodes:

If the sentinel node and others shows signs of cancer then the nearby lymph nodes are removed.
If they do not, then the remainder of the lymph nodes will likely be cancer-free, and further surgery is not needed.

If melanoma has been diagnosed, the doctor will perform other tests to see if the cancer has spread, such as a chest x-ray.

Blood tests that show high levels of lactate dehydrogenase suggest that the cancer has spread. Blood tests to assess liver function and other factors to help determine specific sites where the cancer may appear.

Advanced imaging techniques, such as computed tomography (CT) or positron emission tomography (PET), may also be used. PET is particularly accurate. One study reported that PET was able to diagnose melanoma that had spread even when other tests, including CT, did not. PET can also be very accurate for identifying recurrent melanomas.

Biomarkers are specific substances that are linked to cancer. Blood tests to detect biomarkers may be used to identify microscopic cancers if sentinel node biopsy results are uncertain. Researchers are continually investigating other biomarkers that may indicate whether the cancer had spread or how severe it is, which would help determine whether treatments should be more or less aggressive.

A number of proteins and other factors detected in blood tests are showing promise as markers for microscopic metastasis. Examples include antibodies to MART-1, Melan-A, tyrosinase, and microphthalmia transcription factor (Mitf). Combinations of some of these factors may improve detection rates.

Staging

Staging is the process used to determine the size of the tumor and where and how far it has spread. When a cancer spreads, it’s said to have metastasized. Staging helps the health care team plan for appropriate treatment.

Basal cell cancer is rarely staged, because it doesn't usually spread to other organs. However, it may be staged if it's very, very large.
Squamous cell cancer may be staged in persons who have a high risk of the cancer spreading.
Melanoma is always staged.

Health professionals have come up with various methods for staging the cancer. This report uses the TNM staging system recommended by American Joint Committee on Cancer.

T = tumor. T is followed by a number to indicate thickness.
N = node. N is followed by numbers to indicate the number of lymph nodes involved.
M = metastasis. Metastasis is the spread of cancer to far away sites.

In addition a stage will include whether the melanoma is ulcerated or not, an indication of severity. Ulceration is determined if skin layers over the tumor appear indistinct under the microscope.

In general, the thicker the lesion and the farther the cancer has spread, the higher the assigned stage. The higher the stage, the worse the long-term outlook.

The earliest melanomas, which do not penetrate beneath the surface of the skin and are known as melanoma in situ, are highly curable and are called stage 0 or not given a stage.
Melanomas less than 4 mm thick suggest Stage I or II cancers, and the next step is to attempt to determine if they have spread or are likely to spread to the lymph nodes.
Melanomas that are over 4 mm thick indicated later stages. In such cases, the lymph nodes are sometimes removed to attempt to prevent the cancer from spreading, although about 70% of these melanomas have already spread.

Specific stages are as follows:

Stage I. Cure rates are excellent with surgical removal, since they are least likely to have spread.

Stage 1A. Tumor has not spread to the nodes. It is less than 1 mm and is not ulcerated.
Stage IB. Tumor has not spread to the nodes. It is less than 1 mm, but is ulcerated, or the tumor is between 1.01 and 2 mm but is not ulcerated.

Stage II. Melanomas can be cured, but the success rate lags behind that of Stage I because a small number of cancer cells may have spread to distant sites. In addition to surgery, other forms of therapy may be recommended.

Stage IIA. Tumor has not spread to the nodes. It is between 1.01 and 2 mm and is ulcerated, or it is 2.01 to 4 mm without ulceration.
Stage IIB. Tumor has not spread to the nodes. It is between 2.01 and 4 mm and is ulcerated or greater than 4 mm without ulceration.

Stage III. Survival rate is lower than earlier stages.

Stage IIIA. Tumor has spread to 1 node and it is up to 4 mm without ulceration. Sentinel biopsy has detected microscopic evidence of tumor cells in the node (micrometastasis).
Stage IIIB. Tumor is up to 4 mm without ulceration and has spread to one node or there is evidence of micrometastasis in two nodes.
Stage IIIC. Tumor is any thickness and ulceration may or may not be present. It has spread to 2 or 3 nodes. Additional "satellite" melanomas on the skin more than 2 cm (about an inch) from the original lesion may be present; these are sometimes called "metastases in transit."

Treatment for Melanoma

Treatment for melanoma depends on various factors, including:

The site of the original lesion
The stage of the cancer
The patient's age and general health

Treatment options include:

Surgery to remove the melanoma cancer cells
Chemotherapy
Immunotherapy
Radiation therapy
Palliative therapy

Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the diagnosis biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.

Mohs micrographic surgery is a technique used to remove very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.

The amount of tissue removed depends on the size, depth, and degree of invasion:

Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk of recurrence.
Thicker lesions require wider surgical cuts.

It used to be customary to remove a large area, regardless of the stage of cancer. This potentially disfiguring approach has been abandoned because studies have shown that excising wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.

Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond, removing them may reduce the chance of recurrence and help patients live longer.

Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible and prolong survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.

Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate residual cancer cells after standard surgery for lentigo maligna melanomas, an atypical form of melanoma that has a wide surface and is difficult to treat.

Recurrence rates are very high with lentigo maligna after conservative surgery. Although this is a very slowly progressive condition, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should discuss with their doctor carefully staged surgery to remove all diseased tissue with as little cosmetic harm as possible.

Chemotherapy is often used to treat recurrent or metastatic melanomas. This type of therapy is not intended as a cure but can prolong life and improve its quality.

Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.

Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones most often used.
Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some low-level activity against melanoma.

Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which works best.

Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction.
Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy may preserve fertility in some women.
Rarely, secondary cancers such as leukemia.
Problems in concentration, motor function, and memory, which may be long-term.

Treating Side Effects

Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs and most patients who take more powerful drugs.

Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and so requires fewer injections.

Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.

Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for metastasized or recurrent melanoma that occurs on the arm or leg. It does not appear to be useful for preventing metastasis after a first occurrence of melanoma in one of these locations.

This technique involves the following:

The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
Anticancer drugs are added to the blood in doses up to 10 times the standard doses.
The blood is then heated to enhance the drug's potency.
The chemo-infused blood is then sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
Adverse effects occur in less than 1% of cases and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.

In addition to arms and legs, perfusion techniques have been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.

Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain persons with melanoma.

Cytokines. Cytokines are small proteins that play an important role in the body's immune response. Certain cytokines called interferons are used as a therapy for metastatic melanoma. These medicines are usually given along with chemotherapy or other immunotherapies, or both.

A number of cytokines and combinations are being investigated. They include:

Interferon alpha-2b (Intron) is the only FDA approved immunotherapy for late stage melanoma. The most common side effects are fatigue, depression, and flu-like symptoms, which can be severe. Starting an antidepressant, such as paroxetine (Paxil), several weeks before interferon therapy may help prevent depression.
Pegylated interferon and natural human interferon are long-acting forms are under investigation. One study showed that low-dose natural interferon after chemotherapy increased the 5-year relapse-free survival rate.
Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with metastatic melanoma. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable and nearly always reversible.
Granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine, Sargramostim) is an injectable cytokine under study. The drug boosts production of immune cells in the blood and bone marrow. An inhaled form of the drug is being tested for melanoma that has spread to the lungs.
T-cell therapy uses white blood cells, called tumor-infiltrating lymphocytes (TIL), that taken from the patient. The cells are modified so they better fight cancer and are then reinjected back into the patient. T-cell therapy is showing promising results, especially for patients with advanced melanoma who have failed to respond to other treatments.

A chemical called histamine is a powerful inhibitor of reactive oxygen species, ROS, which may inactivate immune cells that fight cancer. Researchers are investigating to see if it can be used along with interleukin-2 cytokine therapy. In one study, the added benefits of histamine were modest except in patients with liver metastatic; in these patients, survival improved by 129 days, which was significant.

Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are uniquely expressed by melanoma cells.

Many therapeutic melanoma vaccines are in advanced stages of development, but none is approved for use in the United States.

There are two basic types of therapeutic vaccines:

Autologous vaccines
Allogenic vaccines

Sometimes a combination of the two are used. In this case, it's called a hybrid.

Autologous vaccines are made from the patient's own cancer cells. This produces a very specific immune response that can target the patient's cancer precisely. Oncophage (HSPPC-96) and M-Vax are autologous vaccines for melanoma that have shown promise in early clinical trials. One problem with the autologous approach is that there is no way to scientifically assess outcome or even guarantee repeated success since each vaccine is unique to the individual patient. This approach is also appropriate only for select patients.

Allogenic vaccines are made in a laboratory using cells from someone other than the patient. They may be made from proteins from tumor cells, genetic material, or even bacteria. One such vaccine is Canvaxin. Early studies showed this vaccine increased survival rates in some patients with Stage 3 melanoma. However, a later trial was halted because the vaccine did not appear to improve make such patients live any longer.

Vaccine immunotherapy requires the body to build up its own defenses. It can take months before beneficial effects occur, but when they do, tumor reduction is much more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.

Antisense Compounds. Antisense compounds can prevent defective cancer genes from being translated into proteins that cause abnormal cell proliferation.

Monoclonal Antibodies (MAb). Antibodies are natural substances produced by immune cells that home in and destroy cancer cells. Scientists are identifying specific antibodies that may attack melanoma cells and cloning them to create monoclonal antibodies. MAbs have shown promise for other cancers and are now being tested for melanoma, often in combination with vaccines and other forms of immunotherapy.

In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in some cases, however.

In some patients with tumors less than 3 cm deep, however, radiation may help slow down metastasis when combined with a super-heating process using microwaves.
Brachytherapy, in which radioactive seeds are implanted close to the tumor, has also been used with success for melanoma of the eye.
Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
Radiotherapy using a so-called gamma knife (very focused gamma radiation) is also effective for cancer that has metastasized to the brain, in some cases halting the growth and, in rare situations, even eliminating it.

The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgical removal of metastatic tumors may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.

Patients should ask their doctor's about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.

Tetracyclines. Chemically modified tetracyclines, a common antibiotic, have been shown to modify metalloproteinase, an enzyme in the skin that promotes skin cancers, including melanoma.

Anti-Angiogenesis Agents. An anti-angiogenesis drug is one that blocks the formation of new blood vessels. The growth of new blood vessels helps cancer cells grow and spread. The anti-angiogenesis drug thalidomide (Thalomid) is approved for treatment of melanoma but requires special prescribing precautions. This drug had gained notoriety in the 1960s because of devastating birth defects in the children of women who took it during pregnancy. Scientists are investigating drugs that are chemically similar to thalidomide but have fewer side effects.

Curcumin. The yellow spice found in turmeric and curry powders may contain cancer-fighting properties. In a preliminary laboratory study, curcumin stopped the growth of melanoma cells. It is far too early, however, to recommend curcumin for clinical use.

Treatment for Nonmelanoma Skin Cancer

A number of options are available for treating nonmelanoma skin cancer, including surgery, cryosurgery, phototherapy, radiation, and topical 5-fluorouracil.

For any skin cancer and for some keratoses that require removal, surgery is the first treatment. It is usually one of the following:

Excisional Surgery. This is the surgical removal of the cancerous lesion.

Curettage and Electrodesiccation. This procedure involves scraping away of the cancerous tissue followed by electric cauterization to stop the bleeding.

Mohs Micrographic Surgery. Mohs surgery is a meticulous procedure used for skin cancers at high risk for recurrence or becoming invasive. The technique removes very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete. A human skin substitute (Apligraf) is applied to the surgical area. It helps speed up wound healing to achieve a better cosmetic effect.

Good candidates for Mohs surgery include:

Persons with squamous cell cancer
Persons with basal cell cancer greater than 1 cm (about half an inch)
Persons with basal cell cancer on the face, ear, or neck
Young people with skin cancer

Mohs surgery saves more healthy tissue than other procedures and is highly effective. It results in a 99% cure rate for primary tumors and a 95% cure rate for recurrent ones. It can be safely performed in the doctor's office. Complications are uncommon but can include bleeding and infection.

Lasers. Laser surgery may be useful for certain basal cells and for keratoses that appear on the lips, although it is not clear whether lasers offer any advantages over other surgical treatments. Lasers do not appear to be very effective for thick or tough squamous cell cancers.

Cryosurgery removes skin cancer cells or actinic keratoses by freezing the affected tissue with liquid nitrogen. Studies have shown that cyrosurgery can be used to remove even wide areas of actinic keratoses and that it may be more successful over the long term than treatment with 5-fluorouracil, the standard drug. Cryosurgery also appears to reduce the risk for squamous cell cancer in these patients.

A head-to-head comparison of a freezing technique with Mohs micrographic surgery in patients with basal cell cancer reported similar recurrence rates with each approach. Over 85% of the patients with the freezing technique were satisfied with the appearance of the area afterwards. Five-year recurrence rates were only 2.1%.

Cryotherapy achieves good cosmetic results for many patients. However, it may cause blistering and ulceration, leading to pain and infection, as well as harmless, but undesirable, skin-color changes.

In unusual cases where the skin cancer may be in an inoperable position (such as the eyelid or the tip of the nose) or if cancer has recurred multiple times, radiation therapy may be indicated. Radiation is directed at the tumor. It may take 1 - 4 weeks with treatments performed several times a week. One technique being investigated for basal and squamous cell cancer uses radiation implants (brachytherapy) and custom-made molds to specifically target the radiation to the cancer site. Studies suggest that this treatment is very effective with few complications.

Topical phototherapy with the drug aminolevulinic acid (ALA) is a nonsurgical method that is proving to be a good choice for treating actinic keratoses and nonmelanoma skin cancers. The technique involves shining blue light onto the cancer area after that patient has taken ALA. ALA accumulates in the skin cells. When the cells are exposed to intense light, the chemical causes them to die. This approach allows precise targeting of one or more lesions, leaving healthy skin unaffected.

It does not penetrate deeper than the epidermis (the top layer of the skin), so it does not produce scarring or changes in skin color, as cryotherapy or other more invasive treatments do.

It can cause pain and irritation, including stinging, itching, and burning, but in one study only 3% of patients stopped using it for these reasons. In a 2002 study, the procedure was more painful for patients with actinic keratoses than for those with nonmelanoma skin cancers. It was also painful when large areas were affected, and men experienced more pain than women.

ALA Phototherapy for Actinic Keratoses. Phototherapy works best on flat lesions performed in two treatments, and is more effective for clearing lesions on the face than those on the scalp. Phototherapy can also treat multiple lesions at the same time instead of sequentially, as in cryotherapy. Studies suggest that it may work as well as cryotherapy and achieve better cosmetic results. (More patients report burning and itching with phototherapy, however.) Phototherapy is also equal to topical 5-fluorouracil in effectiveness and achieving a satisfactory appearance.

ALA Phototherapy for Nonmelanoma Skin Cancers. In patients with squamous cell cancer-in-situ and basal cell cancer, phototherapy has been equal to cryotherapy, with superior healing and appearance afterward. A 2003 study reported that it was more effective than topical 5-fluorouracil for patients with Bowen's disease, and there were fewer side effects.

Some studies have shown that about 10% of patients using phototherapy have a recurrence within 1 year. These recurrence rates are higher than with surgery and other standard treatments. Longer-term studies are required before ALA phototherapy can be recommended for most patients with nonmelanoma skin cancers.

Chemical peeling, or exfoliation, is useful for solar keratoses on the face, especially in people with fair, dry skin. Alpha-hydroxy acids, for example, are being investigated for keratoses. Dermabrasion, which "sands" the skin, may also be effective, although scarring is possible. A 2002 study found laser resurfacing to treat severe sun damage on the face; however, it may not prevent nonmelanoma skin cancers.

A number of medications are being used for keratoses and some may be helpful for skin cancers as well. Besides cryotherapy, 5-fluorouracil is the other most commonly used treatment for actinic keratoses. Other medications are also available.


Medication	Skin Conditions Affected	Oral or Topical		Comments
5-Fluorouracil	Actinic keratoses, Bowen's disease and small nonmelanoma skin cancers.		Topical cream (Efudex, Fluoroplex) or injected gel containing 5-FU and epinephrine (AccuSite).	5-Fluorouracil (5-FU) removes actinic keratoses and is useful for some patients with a large number of lesions. It requires twice daily application for 3 - 4 weeks. It can cause significant redness, irritation, swelling, and crusting, which takes 2 - 4 weeks to heal. Newer preparations are reducing these side effects. It is still unclear if this medication protects against recurrent keratoses or future skin cancer. Of concern is the possibility that (5-FU) will clear the top of a skin cancer and obscure the rest of the cancer that lies beneath the surface of the skin. A 10-year 2003 study of patients with Bowen's disease reported that 5-FU was safe and effective, with only 2 out of 26 cancers recurring.
Diclofenac and hyaluronan (Solaraze)	Actinic keratoses (approved). Investigated for basal cell.		Topical gel applied twice a day.	Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). When used to treat actinic keratoses, it is delivered to the skin with hyaluronan, a water-seeking molecule that helps maintain skin tension. It has modest effects and when healing occurs, it may not be evident for at least a month after treatment ends. However, it causes less irritation than 5-FU and may be useful for some people.
Imiquimod (Aldara)	FDA approved for the treatment of superficial basal cell cancer. Previously approved for treating actinic keratoses. Investigated for Bowen's disease and squamous cell cancer.		Imiquimod is a topical cream.	Imiquimod triggers the production of immune factors that help fight cell proliferation. Aldara should be used only when surgery for basal cell cancer is inappropriate. It is not approved for use on the face.
Alpha-Interferons	Basal cell cancer, squamous cell cancer.		Require injections administered three times a week.	Interferons are immune factors that are being used to treat a number of serious conditions. Alpha-interferon injections may be effective against skin cancers that are hard to treat using conventional surgical measures. Cosmetic results reported to be good or very good by 83% of patients.

Prognosis

Virtually all basal and squamous type skin cancers can be cured if treated early.

The outlook for melanoma depends on when it is diagnosed.

If melanoma is detected in its earliest form, the 5-year survival rate is 99%. Other localized forms of melanoma have very favorable outlooks.

If the cancer is found after the melanoma has spread, the 5-year survival rate drops.

If melanoma spreads to nearby areas (regional metastatic), the rate is 65%.
If melanoma has spread to distant areas of the body, the survival rate is 15%.

In general, after patients are treated for melanoma, the longer they remain free of cancer recurrence following treatment the better the chance of remaining disease-free. However, relapses are not uncommon in those whose initial melanoma was large.

Anyone who has recovered from melanoma should be especially strict about adhering to preventive guidelines and remain vigilant for suspicious lesions, since the risk for developing a new melanoma is increased even if the first one was successfully cured. Such relapses may occur years after the original diagnosis.

Resources

www.aad.org -- American Academy of Dermatology
www.cancer.org -- American Cancer Society
www.asds.net -- American Society for Dermatologic Surgery
www.mpip.org -- Melanoma Patients' Information Page
www.cancer.gov -- National Cancer Institute
www.nccn.org -- National Comprehensive Cancer Network
www.skincancer.org -- The Skin Cancer Foundation
www.epa.gov/sunwise/uvindex.html -- UV index information

References

Ambros-Rudolph CM, Hofmann-Wellenhof R, Richtig E, et al. Malignant melanoma in marathon runners. Arch Dermatol. 2006;142:1471-1474.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, GA: American Cancer Society; 2007.

Chemotherapy for Inoperable Liver Metastases from Ocular Melanoma. NCI Cancer Bulletin. November 30, 2004;1(46):7.

Dale KM, Coleman CI, Henyan NN et al. Statins and Cancer Risk: A Meta-Analysis. JAMA. 2006;295:74-80.

Delavalle RP. Melanoma chemoprevention. Program presented at: Annual meeting of the American Academy of Dermatology. March 3, 2006; San Diego, CA.

Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346-2357.

Early Detection and Surgery for Melanoma in Lymph Nodes May Increase Survival. NCI Cancer Bulletin. May 17, 2005;2(20):2.

Freeman SR, Drake AL, Heilig LF, et al. Statins, Fibrates, and Melanoma Risk: a Systematic Review and Meta-analysis. J Natl Cancer Inst. 2006;98:1538-46.

Gallagher RP, Spinelli JJ, Lee TK. Tanning beds, sunlamps, and risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2005;14(3):562-566.

Lautenschlager S, Wulf HC, Pittelkow MR. Photoprotection. The Lancet [early online publication]. May 3, 2007.

Lebwohl M. Cutaneous oncology. Program presented at: Annual meeting of the American Academy of Dermatology; March 7, 2006; San Diego, CA.

Michna L, Wagner GC, Lou YR, XE JG, Peng QY, Lin Y, Carlson K, Shih WJ, Conney AH, Lu XP. Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis. May 2006.

Pennie M, Soon S, Risser J, et al. Melanoma outcomes for medicare patients. Arch Dermatol. 2007; 143:488-494.

Response to Immunotherapy for Melanoma Tied to Autoimmunity. NCI Cancer Bulletin. February 21, 2006;3(: 4.

Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. 2005;104(4):879-890.

Treatment for Metastatic Ocular Melanoma. NCI Cancer Bulletin. March 7, 2006;3(10):8.

Veierod MB, Weiderpass E, Thorn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 2003;95(20):1530-1538.

Weinstock MA. Cutaneous melanoma: public health approach to early detection. Dermatologic Therapy. 2006;19(1):26-31.

Review Date:
6/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Hepatitis

FitSugar — Wed, 08 Oct 2008 17:35:31 -0700

In This Report

Highlights
Introduction
Diagnosis
Hepatitis A
Hepatitis B and D
Hepatitis C
Autoimmune Hepatitis
Symptom Management
Outlook
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2006, the FDA approved telbivudine (Tyzeka), a new type of nucleoside analog drug, for treatment of chronic hepatitis B. There are now six drugs approved for hepatitis B treatment.
In 2007, the FDA approved HepaGam B, an intravenous immune globulin drug, for preventing hepatitis B recurrence following liver transplantation.

Drug Warning

In 2007, the FDA revised the prescribing label for entecavir (Baraclude), a drug used to treat hepatitis B. The new label advises against using entacavir in patients infected with both hepatitis B and HIV who are not receiving antiretroviral (anti-HIV) therapy.

Hepatitis C May Increase Lymphoma Risk

Hepatitis C infection increases the risk for developing non-Hodgkin’s lymphoma (NHL) by 20 - 30%, according to a 2007 study of male war veterans published in the Journal of the American Medical Association.

Causes of Death in Hepatitis B and C

Liver disease in general, and liver cancer in particular, is the leading cause of death in patients infected with hepatitis B, according to a 2006 study in the Lancet. Hepatitis B is the leading cause of liver cancer.
Patients with hepatitis C are also at high risk for death from liver disease. However, the Lancet study indicated that young women with hepatitis C face an even higher risk of dying from illegal intravenous drug use.

Drug Research

Adefovir (Hepsera) is commonly used to treat hepatitis B, but many patients eventually develop drug resistance. A 2006 study suggested that adefovir works well for about 5 years, with resistance occurring in about 20% of patients.
Combination treatment with pegylated interferon and ribavirin is an effective treatment for hepatitis C, but causes many side effects. Researchers are studying whether some patients may be able to succeed with a shorter course of treatment. Unfortunately, a 2007 New England Journal of Medicine study suggested that 16 weeks of treatment does not work as well as the standard 24-week course.

Introduction

Hepatitis is a disorder in which viruses or other mechanisms produce inflammation in liver cells, resulting in their injury or destruction. The liver is the largest organ in the body, occupying the entire upper right quadrant of the abdomen. It performs over 500 vital functions including:

The liver processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.
The liver manufactures bile, the greenish fluid stored in the gallbladder that helps digest fats.
One of the liver's major contributions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.
Old red blood cells are removed from the blood by the liver and spleen, and the iron contained in them is recycled to the bone marrow to make new red blood cells.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

Damage to the liver can impair these and many other processes. Hepatitis varies in severity from a self-limited condition with total recovery to a life-threatening or life-long disease. It can occur from many different causes:

In the most common hepatitis cases (viral hepatitis), specific viruses incite the immune system to fight off infections. Specific immune factors become over-produced that cause injury.
Hepatitis can also result from an autoimmune condition, in which abnormal immune factors attack the body's own liver cells.
Inflammation of the liver can also occur from medical problems, drugs, alcoholism, chemicals, and environmental toxins.

No matter what the cause of hepatitis, it can take either an acute (short term) or chronic (long term) form. In some cases, acute hepatitis develops into a chronic condition, but chronic hepatitis can also occur on its own. Although chronic hepatitis is generally the more serious condition, patients having either condition can experience varying degrees of severity.

Acute Hepatitis. Acute hepatitis can begin suddenly or gradually, but it has a limited course and rarely lasts beyond 1 or 2 months. Usually, there is only spotty liver cell damage and evidence of immune system activity. Rarely, acute hepatitis can cause severe, even life-threatening, liver damage.

Chronic Hepatitis. The chronic forms of hepatitis last for prolonged periods. Doctors usually categorize chronic hepatitis by indications of severity:

Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver.
Chronic active hepatitis involves extensive liver damage and cell injury beyond the portal tract.

Click the icon to see an image of aggressive hepatitis.

Most cases of hepatitis are caused by viruses that infect liver cells and begin replicating. They are defined by the letters A through G:

Hepatitis A, B, and C are the most common viral forms of hepatitis. Investigators are still looking for additional viruses that may be implicated in hepatitis unexplained by the current known viruses.
Other hepatitis viruses include hepatitis E and hepatitis G. Like hepatitis A, hepatitis E is caused by contact with contaminated food or water. It is not serious except in pregnant women, when it can be life threatening. Hepatitis G is always chronic and most likely has the same modes of transmission as hepatitis C. It does not appear to have serious effects.

Scientists do not know exactly how these viruses actually cause hepatitis (inflammation in the liver). As the virus reproduces in the liver, several proteins and enzymes, including many that attach to the surface of the viral protein, are also produced. Some of these may be directly responsible for liver damage. Researchers are investigating elevated levels of specific immune factors, including T cell sub-types in the liver of hepatitis C and B patients. T cells are important infection fighters in the immune system that in some cases release powerful inflammatory substances (tumor necrosis factor and interferon gamma) that can cause considerable damage leading to hepatitis B or C.

Autoimmune chronic hepatitis accounts for about 20% of all chronic hepatitis cases. Like other autoimmune disorders, this condition develops because a genetically defective immune system attacks the body's own cells and organs (in this case the liver). The attack is triggered by an environmental factor, probably a virus. Suspects include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in susceptible individuals. In about 30% of cases, autoimmune hepatitis is associated with other disorders that involve autoimmune attacks on other parts of the body.

Alcohol. About 10 - 35% of heavy drinkers develop alcoholic hepatitis. In the body, alcohol breaks down into various chemicals, some of which are very toxic to the liver. After years of drinking, liver damage can be very severe, leading to cirrhosis in about 10 - 20% of cases. Although heavy drinking itself is the major risk factor for alcoholic hepatitis, genetic factors may play a role in increasing a person's risk for alcoholic hepatitis. Women who abuse alcohol are at higher risk for alcoholic hepatitis and cirrhosis than are men who drink heavily. High-fat diets may also increase the risk in heavy drinkers.

Drugs. Because the liver plays such a major role in metabolizing drugs, hundreds of medications can cause reactions that are similar to those of acute viral hepatitis. Symptoms can appear anywhere from 2 weeks to 6 months after starting drug treatment. In most cases, they disappear when the drug is withdrawn, but in rare circumstances they may progress to serious liver disease. Drugs most noted for liver interactions include halothane, isoniazid, methyldopa, phenytoin, valproic acid, and the sulfonamide drugs. Very high doses of acetaminophen (Tylenol) have been known to cause severe liver damage and even death, particularly when used with alcohol.

Nonalcoholic fatty liver disease (NAFLD) affects between 10 - 24% of the population. It covers several conditions, including nonalcoholic steatohepatitis (NASH). NAFLD has features similar to alcoholic hepatitis, particularly a fatty liver, but it occurs in individuals who drink little or no alcohol. Severe obesity and diabetes are the major risk factors for NAFLD as well as complications from NAFLD. NAFLD is usually benign and very slowly progressive. In certain patients, however, it can lead to cirrhosis, liver failure, or liver cancer. [For more information, see In-Depth Report #75: Cirrhosis.]

Diagnosis

In people suspected of having or carrying viral hepatitis, doctors will measure certain substances in the blood.

Bilirubin. Bilirubin is one of the most important factors indicative of hepatitis. It is a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise. (High levels of bilirubin cause the yellowish skin tone, known as jaundice.)
Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Blood is drawn from a vein (venipuncture), usually from the inside of the elbow or the back of the hand. A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. Preparation may vary depending on the specific test.

Radioimmunoassays. To identify the particular virus causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous and which can be targeted by antibodies.) Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be sufficient numbers of antibodies to be detectable by blood tests for up to weeks or months after hepatitis develops. Blood tests that are taken too early may miss these signs of infection.
Antibodies also linger after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. PCR is able to make multiple copies of the virus’ genetic material to the point where it is detectable.

A liver biopsy may be performed for acute viral hepatitis caught in a late stage or for severe cases of chronic hepatitis. No laboratory tests for enzyme or viral levels can truly determine the actual damage to the liver. A biopsy helps determine treatment possibilities, the extent of damage, and the long-term outlook.

The biopsy requires abdominal surgery, most often laparoscopy. This procedure takes about an hour. It requires general anesthesia and involves the following steps:

The surgeon makes one or more small incisions (about 0.5 - 1.0 inch) in the abdomen.
Carbon dioxide or nitrous oxide is delivered through the incision to inflate the abdomen so that the involved area is visible.
The surgeon inserts a thin tube, called a laparoscope, which contains a tiny camera. Surgical instruments are also inserted through the incision to remove the liver tissue for biopsy.

Click the icon to see an explanation of liver biopsy.

A less invasive procedure, called a minilaparoscopy, uses a smaller scope and may prove to reduce the time of the procedure.

Patients with cirrhosis are usually screened for liver cancer using tests for a substance called alpha-fetoprotein (AFP) and ultrasound. It is not known, however, if such screening has much impact on survival, since it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Hepatitis A

About a third of the U.S. population has antibodies to hepatitis A, indicating previous infection by the virus. The hepatitis A virus infects up to 200,000 Americans every year and causes symptoms in about 134,000 of them. Almost 30% are children under age 15.

Hepatitis A (formerly called infectious hepatitis) is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. Infected people can transmit it to others if they do not take strict sanitary precautions. Hepatitis A is infectious for 2 - 4 weeks before symptoms develop and for a few days afterward.

People at risk for passing the infection along or being infected include:

International travelers. Hepatitis A is the hepatitis strain people are most likely to encounter in the course of international travel. In fact, in spite of the availability of a vaccine, the increase in travel to underdeveloped countries has kept the incidence of hepatitis A steady in Western nations. The incidence may even be increasing.
Day care employees and children. It is estimated that between 11 - 16% of hepatitis A cases occur among day care employees and children who attend day care. The risk for children attending day care is very low, however, if hygienic precautions are used, particularly when changing babies and handling diapers.
Sexually active homosexual men.
Intravenous drug users.
Health care, food industry, and sewage workers.

A fly may act as a mechanical vector of diseases such as hepatitis A, which means the fly carries the infective organism on its feet or mouth parts and contaminates food or water which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

Symptoms of acute viral hepatitis may begin suddenly or develop gradually. They may be so mild that patients mistake the disease for the flu. They include:

Nearly all patients experience some fatigue and often have mild fever.
Gastrointestinal problems are very common, including nausea, vomiting, a general feeling of discomfort in the abdomen, or a sharper pain that may occur in the upper right area of the abdomen. This pain tends to increase during jerking movements, such as climbing stairs or riding on a bumpy road.
Gastrointestinal problems can also lead to loss of appetite, weight loss, and dehydration.
After about 2 weeks, dark urine and jaundice (a yellowish color in the skin and whites of the eyes) develops in some, but not all, patients. (Children tend not to develop jaundice.)
About half of all patients have light colored stools, muscle pain, drowsiness, irritability, and itching, usually mild.
Diarrhea and joint aches occur in about a quarter of patients.
The liver may be tender and enlarged, and most people have mild anemia.
In about 10% of patients, the spleen is enlarged.

Travelers should take the following precautions:

Get vaccinated against hepatitis A and possibly B if traveling for long periods of time to countries where epidemics occur.
Use only carbonated bottled water for brushing teeth and drinking. (Remember that ice cubes can carry infection.) Boiling water is the best method for eliminating infectious organisms. Bringing the water to a good boil for at least a minute generally renders it safe to drink.
Heated food should be hot to the touch and eaten promptly.
Don’t buy food from street vendors.
Beware of sliced fruit that may have been washed in contaminated water. Travelers themselves should peel all fresh fruits and vegetables.
Avoid dairy products.
Avoid raw or undercooked meat and fish.

Two vaccines (Havrix, Vaqta) are now available, both very safe and effective for preventing hepatitis A (HAV). They can be given along with immune globulin and other vaccines. A combination Hep A - Hep B vaccine (Twinrix) that contains both Havrix and Engerix-B (a hepatitis B vaccine) is also available.

Click the icon to see a discussion of hepatitis A vaccine.

Candidates for HAV Vaccinations. Vaccinations for hepatitis A are recommended for:

Children age 12 - 23 months (the U.S. Centers for Disease Control and Prevention recommends that children receive the first dose of the hepatitis A vaccine when they are 12 months old, and a second dose 6 months later). Hepatitis A used to affect mostly children, but now occurs mostly in adults.
Travelers to developing countries. (Travelers should also receive immune globulin if they are visiting high-risk areas within 4 weeks of the vaccination.)
Sexually active homosexual men
Illegal drug users, especially those who inject drugs
Health care workers
People with chronic liver disease
People with hemophilia or other blood-clotting disorders

Side Effects. Although there are few side effects, allergic responses from the vaccination can occur. Hair loss has been reported in very few people after a second administration. There may be pain at the injection site. (Havrix causes more pain at the injection site than Vaqta.)

Symptoms are usually mild, especially in children, and generally appear between 2 - 6 weeks after exposure to the virus. Adult patients are more likely to have fever, jaundice, and itching that can last up to several months.

Hepatitis A is the least serious of the common hepatitis viruses. It does not directly kill liver cells, and there is no risk for a chronic form. Severe (fulminant) hepatitis is the only major concern, but even if it develops, it is almost always less dangerous than with other viral types. Only 1 in a 1,000 patients is at risk for death from this complication. If hepatitis A infection occurs in patients with hepatitis C, however, superinfections can occur, even without cirrhosis, leading to a life-threatening form of fulminant hepatitis. (Infection of patients with hepatitis B who do not have cirrhosis does not appear to be as dangerous.)

Radioimmunoassays are generally used to identify IgM antibodies, first produced to fight hepatitis A. They appear early in the course of the disease and usually can be identified as soon as symptoms appear. IgM antibodies disappear during recovery, but those known as IgG antibodies persist, and their presence can be used to indicate a previous infection.

The primary goals for managing acute viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others.

Precautions for Preventing Transmission of Hepatitis A. Because hepatitis A and hepatitis E are usually passed through contaminated food, people with these viruses should not prepare food for others. Unfortunately, these viruses are most contagious before symptoms appear.

Using hot water when cleaning utensils or clothing is essential. Heating a contaminated article for 1 minute kills the virus. Simple household bleach is effective for disinfecting hard surfaces. Sterilizing is not necessary. Still, even with strong precautions, utensils used by the patient for eating and cooking should be kept separate from those used by others.
Abstain from sexual activity or take strict precautions.
Abstain from alcohol. Moderate drinking after recovery is not harmful for most people.

Hepatitis B and D

Hepatitis B and D were formerly called serum hepatitis. Hepatitis B is mainly transmitted through blood transfusions, contaminated needles, and sexual contact. Blood screening has reduced the risk from transfusions. It can also be passed from cuts, scrapes, and other breaks in the skin. Hepatitis D virus can replicate only by attaching to hepatitis B and therefore cannot exist without the B virus being present.

Risk Factors for Hepatitis B. About 1.2 million Americans are chronically infected with hepatitits B and between 20 - 30% acquired the infection when they were children. Men are at higher risk than women. Among ethnic groups living in the United States, Asians are at highest risk, due to the high rate of hepatitits B in Asian countries. Fortunately, in the US the number of new infections has declined dramatically -- by 67% between 1990 and 2002. In 2003, 7,526 cases were reported compared to over 20,000 in 1990. The greatest decrease has occurred in children. Among young adults and people living in the Northeast, however, the incidence has increased since 1999. This may indicate that sexual activity is an important route for viral transmission and that the protective effect of the vaccine has not yet reached older, high-risk groups. Also, as with hepatitis A, the increase in travelers to underdeveloped nations may be responsible for the steady rate.

Hepatitits B is far more common overseas and about 600,000 people die each year from conditions, such as liver cancer or cirrhosis, that are related to chronic hepatitis B. Nearly 70% of these infections were acquired during infancy or early childhood.

People at risk include:

Drug users who share needles.
Children of infected mothers. Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitits B before age 5. Children are more likely than adults to become chronic carriers, although between 6 - 12% of children spontaneously recover each year.
People with multiple sex partners or other high-risk sexual behavior.
Hospital workers and others exposed to blood products. Contaminated medical instruments, including fingerstick devices used for more than one individual, have been known to transmit the virus.
Staff members and clients of institutions for the developmentally disabled.
Prisoners.
Immigrants from areas where the disease rate is high. (International travelers who spend long periods in such areas may also be at risk.)

People at highest risk for becoming chronic carriers of the virus include:

Children infected before age 5, including newborns, most of whom become carriers.
Infected people with damaged immune systems, such as AIDS patients.

Risk Factors for Hepatitis D. Hepatitis D occurs only in people with hepatitis B. It is not common in the U.S. and the incidence of this hepatitis is declining rapidly overseas. Experts anticipate that it will be extremely rare in the near future. Those who recover from hepatitis B are immune to further infection from both hepatitis B and D viruses.

The following are some precautions for preventing the transmission of hepatitits B or hepatitits C:

All objects contaminated by blood from patients with hepatitis B or C must be handled with special care. (Restrictions on food preparation are not necessary for these hepatitis viruses.)
Patients with viral hepatitis should abstain from sexual activity or take strict precautions. Infected patients should use condoms and contraceptives that prevent passage of the virus, possibly even in relationships that last for years. Women partners or infected women should abstain from sexual activity during menstruation. Either partner with infections that cause bleeding in the genital or urinary areas should avoid sexual activity until the infection is no longer active.
Couples with an infected partner or people sharing household with an infected person should avoid sharing personal items, such as razors or toothbrushes.

Note: There is no evidence that the viruses can be passed through casual contact, or other contact without exposure to blood, including kissing, hugging, sneezing, or coughing or by sharing eating utensils or drinking glasses. People infected with chronic hepatitis B or C should not be excluded from work, school, play, childcare or any social or work settings on the basis of their infection.

Symptoms appear long after the initial infection, usually 4 - 24 weeks. Many patients may not even experience them or they may be mild and flu-like. About 10 - 20% of patients have a fever and rash. Nausea is not common. Sometimes there is general aching in the joints. The pain can resemble arthritis, affecting specific joints and accompanied by redness and swelling.

Most people with hepatitis B recover from the virus. The risk of progressing to the chronic form of hepatitis B is age dependent. Only 2 - 6% of people who are older than 5 years old when they acquire the virus will develop chronic hepatitis B. The risk for chronic hepatitis in children age 1 - 5 years is 30%, and the risk for infants under the age of 1 is up to 90%. In the U.S., about 1.25 million people are chronically infected with hepatitis B. Worldwide, about 400 million people are chronically infected.

Chronic hepatitis B infection significantly increases the risk for liver damage, including cirrhosis and liver cancer. In fact, hepatitis B is the leading cause of liver cancer worldwide. According to a 2006 Lancet study, liver disease, especially liver cancer, is the main cause of death in people with chronic hepatitis B. Because of these high risks, it is very important that patients with chronic hepatitis B receive regular screenings for liver cancer.

Patients with hepatitis B who are co-infected with hepatitis D may develop a more severe form of acute infection than those who have only hepatitis B. Co-infection with hepatitis B and D increases the risk of developing acute liver failure. Patients with chronic hepatitis B who develop chronic hepatitis D also face high risk for cirrhosis. Hepatitis D occurs only in people who are already infected with hepatitis B.

A diagnosis of hepatitis B relies on measuring the liver enzymes aspartate (AST) and alanine (ALT) -- released when the liver is damaged -- assays to identify the viral DNA, and a liver biopsy.

Doctors must then determine if the condition is chronic but inactive or whether it is more aggressive. This is done by identifying a specific antigen called HBsAg, which is a protein that is found in the blood in early stages of hepatitis B and suggests the presence of a viral replication. Most people develop antibodies to this antigen during convalescence. Their condition is referred to as HBeAG negative, or anti-HBe, and suggests that infection is on the wane. About 5 - 10% of people do not clear the infection but become carriers of the antigen (called HBsAG-positive). Evidence of its persistence for more than 6 months suggests that the condition is chronic.

Tests can identify specific genetic types of hepatitis B virus (designated A to G). It is not clear how significant they are in treating patients with hepatitits B.

It is important to remember, however, that viral levels are not an accurate measure of actual liver damage. Only a biopsy can determine this.

To diagnose hepatitis D using an antibody test, hepatitis B must already have been identified.

General precautions for preventing hepatitis B when traveling are the same as those for hepatitis A. In infected people, precautions for preventing transmission are similar to those for hepatitis C.

Vaccinations for Prevention of Hepatitis B. Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B and are safe even for infants and children. A triple-antigen hepatitis B vaccine (Hepacare) is proving to be effective for people who do not respond to the standard vaccines. Vaccination programs are also helping to reduce the risk for liver cancer. A combination vaccine (Twinrix) that contains Engerix-B and Havrix, a hepatitis A vaccine, is now approved for people with risk factors for both hepatitis A and B.

Click the icon to see an image discussing hepatitis B vaccine.

Until recently, the vaccine contained a mercury-based preservative called thimerosal. In response to concerns, professional organizations recommended suspending vaccinations in infants with noninfected mothers. In 1999, a thimerosal-free vaccine became available, and medical centers are now urged to continue vaccinations. Unfortunately, even after the thimerosal-free vaccine became available, a number of hospitals still have not restored vaccination of all infants. This is a safe vaccine. Parents should be sure their children are immunized.

Candidates for Hepatitits B Vaccinations. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade.

Typical schedules for hepatitis B vaccinations in childhood are as follows:

All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be given by age 2 months if the mother has no evidence of infection. Infants of mothers infected with hepatitits B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. Vaccinating the newborn prevents infection from being transmitted from mother to child.)
The second dose should be given at least 4 - 6 weeks after the first dose. The third dose is given at least 8 weeks after the second dose (typically when the baby is 6 - 23 months old).
Children who are 11 - 12 years old and who have not been immunized should receive two or three doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection lasts at least 10 years. Booster shots after that may be recommended, depending on continuing risk such as sexual exposure.

The following adults are at very high risk and should be vaccinated:

Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B virus that ranges from 15 - 30%.
People in the same household as hepatitits B infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitits B may be protected with immune globulin, which is sometimes administered with the vaccine.)
Travelers to developing countries.
Patients who require transfusions and have not been infected with hepatitits B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)
Sexually active homosexual or heterosexual individuals with multiple partners or who engage in high-risk sexual behavior.
People with any sexually transmitted diseases.

Other people at risk who may benefit from vaccinations include:

Patients and workers in mental institutions and morticians.
Patients on hemodialysis. (People on hemodialysis may need larger doses or boosters. They also may need to be re-vaccinated if blood tests indicate they are losing immunity.)
People who use injected drugs.
Pregnant women at risk for the virus should be vaccinated. There is no evidence that the vaccine is dangerous to the fetus.
People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

The regimen in adults is typically three doses given over 6 months. People with alcoholism may need high doses.

Soreness at the injection site is the most common side effect. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and there has been some concern about three small studies associating the vaccine with an insignificant increase in multiple sclerosis. Recent studies, however, have found no evidence to support these concerns. Nonetheless, some groups oppose the vaccination in children who are not in high-risk groups. It should be strongly stressed that worldwide 65 million people with chronic hepatitis are expected to die from liver disease. Vaccinations save lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitits B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine,Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the FDA approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitits B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitits B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitits B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitits B as the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitits B. Patients with lymphoma should be screened for hepatitits B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitits B and HIV should take entecavir only if they are also taking antiretroviral HIV drugs.

Investigational Drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitits B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitits B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Liver Transplantation. If the disease progresses to liver failure, liver transplantation may be an option. It is not foolproof, however. Viral recurrence is high in patients with hepatitis B. However, regular, lifelong injections of hepatitis B immune globulin (HepaGam B) can reduce the risk for re-infection following liver transplantation.

Hepatitis C

Hepatitis C is spread by contact with infected human blood. It is the most common blood-borne infection in the country. Until blood screening began in 1990, the hepatitis C virus was primarily transmitted through blood transfusions. Now, hepatitis C is transmitted mainly through intravenous drug use and sharing needles. Nearly half of people infected with hepatitis C have a history of injecting drugs. People who received a blood transfusion before 1992 are also at high risk, as are people who have had 20 or more sexual partners. Hepatitis C can also be passed from an infected mother to her baby during birth. (Breast-feeding does not increase the risk of transmission.)

Click the icon to see an image discussing hepatitis C.

About 4 million Americans have had an initial hepatitis C infection and an estimated 3.2 million have chronic hepatitis C. Hepatitis C affects about 170 million people worldwide. Most people with chronic hepatitis C are unaware that they have it. It is not possible to predict which patients will develop the chronic form of hepatitis C.

Ethnic Groups. In general, hepatitis C occurs most commonly in non-Caucasian men ages 30 - 49 years. Over 6% of African-Americans are infected with hepatitis C, about two to three times the risk for Caucasians.

Most patients with hepatitis C do not experience symptoms. If they appear at all, symptoms develop about 1 – 2 months after a person is infected. Symptoms of progressive chronic viral hepatitis may be very subtle. In some patients, itchy skin is the first symptom. Overall, fatigue is the most common symptom. Many patients do not experience any symptoms at all. Chronic hepatitis C can be present for 10 - 30 years, and cirrhosis or liver failure can sometimes develop before patients experience any clear symptom.

Some evidence suggests, however, that patients with chronic hepatitis C often experience an impaired quality of life, mostly from fatigue. Fatigue can impair daily function, vitality, and mood in ways that are similar to other chronic diseases. The severity of the fatigue is not necessarily related to the degree of liver injury. Some patients develop pain in small joints in the body (such as the hand) that may be nearly indistinguishable from symptoms of rheumatoid arthritis, fibromyalgia, or carpal tunnel syndrome. Recent research suggests that sexual dysfunction may be common among men with chronic hepatitis C. Other nonspecific symptoms include abdominal discomfort, loss of appetite, depression, and difficulty concentrating.

Acute Form. Acute hepatitis C is rarely recognized, since there are no symptoms in up to 80% of patients. About 15 - 45% of acute cases clear up on their own without becoming chronic. Early treatment with interferon drugs can significantly reduce the risk for progression to chronic hepatitis.

Chronic Form. About 55 - 85% of infected people develop chronic hepatitis. Chronic hepatitis C poses a risk for cirrhosis, liver cancer, or both.

Five - 20% of patients with chronic hepatitis C develop cirrhosis over a period of 20 – 30 years. The longer the patient has had the infection, the greater the risk. Patients who have had hepatitis C for more than 60 years have a 70% chance of developing cirrhosis.
Seventy percent of patients with chronic hepatitis C eventually develop chronic liver disease.
Of these patients, 4% eventually develop liver cancer. (Liver cancer rarely develops without cirrhosis first being present.)

About 1 - 5% of people with chronic hepatitis C eventually die from liver diseases (cirrhosis or liver cancer). However, according to a 2006 Lancet study, intravenous drug-related deaths are more common than liver-related deaths among younger female patients (ages 15 - 24) infected with hepatitis C or hepatitis C and B.

Patients with chronic hepatitis C may also be at higher risk for non-liver disorders, including the following:

Cryoglobulinemia (a disorder in which protein clumps form in the blood). This can cause skin rash and ulcers, kidney problems, arthritis, and sensations (such as tingling or pain) in the hands and feet. People with such symptoms may have particular difficulties with interferon, which can have similar side effects.
Porphyria cutanea tarda (a disorder that causes skin color and texture changes and sensitivity to light).
Certain autoimmune disorders, particularly hypothyroidism and rheumatoid arthritis.
Type 2 diabetes, particularly among younger people with hepatitis C who are overweight.
Some experts believe that hepatitis C may infect the central nervous system in certain patients, possibly accounting for the fatigue, depression, or both experienced by patients who have even relatively mild cases.
Certain types of lymphomas (cancers of the lymphatic system). According to a 2007 study in the Journal of the American Medical Association, hepatitis C infection increases the risk of developing non-Hodgkin’s lymphoma by 20 - 30%. The risk for a particular type of non-Hodgkin’s lymphoma, Waldenstrom’s macroglobulinemia, increases by 300%. However, this study only evaluated male Vietnam War veterans, so these risks may not apply to the general public.

Tests for Liver Enzymes. Blood tests showing elevated liver enzymes, particularly alanine aminotransferase (ALT), plus symptoms of hepatitis (jaundice, fatigue) are often first signs of acute hepatitis. In chronic hepatitis, however, liver enzymes may be normal or fluctuate. They also can be elevated even after the virus has cleared.

Tests to Identify the Virus. The standard first test for diagnosing hepatitis C is known as enzyme-linked immunosorbent assay (ELISA or EIA). The antibody for hepatitis C is used to identify the virus. The antibody may not show up for 6 weeks to 1 year after the onset of the disease, however, so its absence is not necessarily an indication of a healthy liver. A test called an immunoblot assay (called RIBA) may also be used to confirm the presence of the virus. An accurate home test (Hepatitis C Check) is now available. It supplies a lancet for obtaining a drop of blood, which is sent to the laboratory for EIA and possibly RIBA analysis. Results take about a week.

Tests to Identify Genetic Types and Viral Load. Additional tests called hepatitis C RNA assays may be used to confirm the diagnosis. They use a polymerase chain reaction (PCR) to detect the RNA (the genetic material) of the virus. Such tests may be performed if there is some doubt about a diagnosis but the doctor still firmly believes the virus is present.

hepatitis C RNA assays also determine virus levels (called viral load). Such levels do not reflect the severity of the condition or speed of progression, as they do for other viruses, such as HIV. However, high viral loads suggest a poorer response to treatment with interferons.

Such techniques may also help determine the genotype of the virus, which can be helpful in determining a treatment approach. There are six main genetic types of hepatitis C and more than 50 subtypes. They do not appear to affect the rate of progression of the disease itself, but they can differ significantly in their effects on response to treatment. Genotype 1 is the most difficult to treat and is the cause of up to 75% of the cases in the U.S. The other common genetic types are types 2 (15%) and 3 (7%), which are more responsive to treatment. People with hepatitis C need to have their genotype tested so that doctors can make appropriate treatment recommendations.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Liver Biopsy. Only a biopsy can determine the extent of injury in the liver. Some doctors now recommend biopsies for all patients with chronic hepatitis C, regardless of severity, because of the risk for liver damage even in patients without symptoms. If a biopsy does not show any scarring and liver enzymes are normal, patients can be assured that the outlook is very favorable.

No vaccines are available, but immune globulin helps protect against developing hepatitis C after transfusions. Periodic doses of immune globulin in sexual partners of infected people also appear to be protective. In infected people, preventing transmission is similar to those for hepatitis B.

Interferons. Interferons are natural proteins that activate certain immune functions in the body and have anti-viral properties. The natural interferons used for chronic hepatitis B and C are called type I interferons. They are given by injection, need to be taken three times a week, and include the following:

Interferon alfa 2b (Intron A). Used for both hepatitis B and C.
Interferon alfa 2a (Roferon-A). Mostly used for hepatitis C.
Interferon alfa-n1 (Wellferon). Approved but mostly used in Canada for hepatitis C.

Newer synthetic interferons have been developed that are showing some advantages over the natural forms:

Pegylated interferon (PegINF). Pegylated interferons use a small molecule called polythelene glycol (PEG), which attaches to a protein and extends the activity of the interferon. This action allows the drug to be taken only once a week. Drugs available include pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys).
Interferon alfacon-1 (Infergen). This drug is called a consensus interferon (CIFN) because it was genetically developed using the most commonly occurring amino acid sequences from each of the natural type 1 alpha interferons. It is 5 - 10 times more biologically active than natural type 1 interferons. CIFN is usually given three times a week when used as initial treatment for hepatitis C.

Interferon Candidates. The best candidates for interferon treatments are patients who are at greatest risk for cirrhosis. Factors suggesting a higher risk for cirrhosis include:

Detectable virus levels as determined by an assay test.
High levels of aminotransferase enzyme for more than 6 months.
Indication of liver scarring on biopsy.

Patients who are not good candidates for interferon and are usually ineligible include:

Women who are pregnant or planning to become pregnant soon.
Patients with advanced cirrhosis. (It is unclear if the drug improves survival in patients with advanced cirrhosis and, in any case, it may be dangerous for them.)
Patients with fluid in the abdomen (ascites).
Patients with anemia or risk factors for anemia should not take the combination treatments, although they may be candidates for interferon alone.

Several kinds of patients are ineligible for treatment because of the high risk for noncompliance and the severe psychiatric effects of the drugs. They include patients with psychiatric and medical problems and substance abusers. Some doctors believe that these patients could benefit from treatment.

Side Effects and Complications of Treatment with Interferon. Common side effects of any interferon are flu-like symptoms (fever, chills, muscle aches) that usually occur within 6 hours and gradually decline over 1 - 2 weeks. (Pegylated interferon may pose a higher risk for these symptoms than the natural interferons.)

Chronic or more serious effects include:

Emotional and mental changes. Depression can be very severe, and cases of suicidal thoughts have been reported. Other mental and emotional symptoms include anxiety, amnesia, confusion, irritability, impaired concentration, decreased alertness, memory problems, and mental slowing.
Changes in sensation.
Weight loss.
Skin rashes.
Hair loss.
Gastrointestinal problems, including nausea, vomiting, and diarrhea, and, in severe cases intestinal bleeding and ulcers.
Fatigue and general weakness.
Back pain.
Complications in the lungs, including worsening of asthma. In severe cases, interferon can cause shortness of breath, inflammation in the lungs, and pneumonia.
Possible negative effects on cholesterol and lipid levels.
Heart rhythm disturbances, which, in rare cases, can be serious.
Mild anemia.
Drop in platelet and white blood cell counts, increasing susceptibility to bacterial infections.
May trigger an autoimmune response, possibly causing anemia, diabetes, lupus-like symptoms, hypothyroidism, or even autoimmune hepatitis.
Complications in the eye, including bleeding that, in some cases, may lead to loss of vision if not detected promptly.
Rare reports of acute pancreatitis.
In children, interferon therapy temporarily disrupts growth.

Patients have a difficult time with prolonged therapy. Over 20% drop out if treatment lasts longer than 2 years. Depression is the most common reason for stopping the treatment.

Several different methods of administering interferons are under investigation to help reduce some of the problems associated with injections. These methods include pills, pumps, and controlled release implants.

Interferons in Combination with Ribavirin. Ribavirin, a nucleoside analog drug, does not work alone, but it can double sustained response rates when combined with an interferon.

Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with hepatitis C genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavirin.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavirin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations may help slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms such as fever, headaches, and muscle aches are the most common side effect.
Reduced white blood cell count.
Skin disorders such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

Determining Treatment Success. Doctors measure treatment success and approaches based on the patient’s response to the treatments:

Early Response. These are patients who respond to the drug right away. This means that their viral count drops very rapidly within the first few weeks of treatment and is still undetectable at 12 weeks. (One difficulty in deciding when to stop treatment, even in responders, is the inability to predict at 12 weeks which of these patients will relapse and which ones will have a sustained response.)
Sustained Response. Patients who are free of the virus longer than 6 months are considered to be sustained responders. The overall sustained response rates with the current standard combination of pegylated interferon and ribavirin is over 50%, with certain factors predicting higher or lower response rates.
Relapse. In relapse, the virus comes back again and requires retreatment. This is usually due to the development of mutant strains that are resistant to the drugs or because the original dose was too low.
Nonresponse. Patients are considered to be nonresponders if the virus is still detectable 12 weeks after interferon alone or after 24 weeks of combination therapy. Treating these patients again has achieved only a 15% response.

People at Risk for Poor Response to Combination Treatment. The following patients have a greater risk for not responding to combination treatment with interferon and ribavirin:

People at high risk for aggressive hepatitis C.
Having a high viral count.
Having a specific genetic type of the virus. Patients with genotype 1 do not respond as well to combination treatment as patients with genotypes 2 or 3.
Older age (especially older than 60 years).
African-Americans are less responsive to treatment than Caucasians or Asians. The reasons for this are unclear.

Failure can be due to other, modifiable factors, which should be assessed before stopping treatment, particularly in patients who had interferon alone. They include:

Interferon dose was too low.
Patient did not comply fully with the treatment.
Patient was consuming alcohol.
Treatment time was too short. Some evidence suggests that response can significantly improve for many patients with genotype 1 if treatment time is extended to 48 weeks.

Even if viral levels linger, interferon treatment may still have benefits. For example, patients with normal liver enzyme levels appear to have almost no risk for liver damage, even if viral levels persist after treatment. Evidence also suggests that interferon reduces liver scarring and may reduce the risk for liver cancer in some patients, even if the treatment does not eliminate the virus. More research is needed, however, to confirm these findings.

Investigational Drugs for Hepatitis C. The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs that may show promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavirin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T cells). It is being used for hepatitis B and is under investigation for hepatitis C in combinations interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Other drugs under investigation include vaccines, genetic therapies known as antisense oligonucleotides or monoclonal antibodies, and drugs that will help prevent or reduce progression of liver scarring or progression to liver cancer. Even if successful, none of these drugs will be available for many years.

Liver Transplantation for Hepatitis C. If the disease progresses to the point where it becomes life-threatening, liver transplantation may be an option. Nearly 40% of liver transplant patients are infected with hepatitis C. However, liver transplantation is not a cure for hepatitis C. The virus nearly always returns. One study of patients with hepatitis C reported 5-year risks for viral recurrence of 80% and for cirrhosis of 10%. A 2004 study found that the hepatitis C virus comes back with more severity in livers from living donors than livers taken from cadavers. Researchers are investigating retreatment with antiviral drugs.

In both hepatitis B and C, the disease often persists or returns despite treatment. The virus continually generates many “mutant viruses” that differ just slightly from the parent virus. These mutated viruses may be resistant to interferons and so, over time, the drugs become ineffective.

Autoimmune Hepatitis

Autoimmune chronic hepatitis typically occurs in women ages 20 - 40 who have other autoimmune diseases, including:

Systemic lupus erythematosus
Rheumatoid arthritis
Sjögren's syndrome
Inflammatory bowel disease
Glomerulonephritis
Hemolytic anemia

Some research indicates that the postmenopausal period may be another peak in incidence of autoimmune hepatitis among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, researches have not discovered major risk factors for this condition.

About 85% of people with chronic active autoimmune hepatitis do not have severe symptoms. When symptoms occur, they range from minimal to severe, and include fatigue, jaundice, fever, and weight loss. The liver and spleen are often enlarged. In addition, patients with this condition may experience skin disorders, including palmar erythema (red palms) and spider angioma (a blood-red spot, the size of a pinhead, from which tiny blood vessels radiate like spider legs). Itching is not common, however. The abdomen or legs may be swollen due to the accumulation of fluid.

If a patient has symptoms of chronic active hepatitis for 6 months or more and a virus cannot be identified, doctors usually suspect autoimmune hepatitis. Other autoimmune liver diseases, however, can confuse a diagnosis. To help confirm this condition, test results may show high levels of immune factors called serum globulins or certain antibodies to liver proteins. In some cases, a successful trial of steroid drugs may be the only way to diagnose autoimmune hepatitis.

Autoimmune hepatitis is usually benign and causes little trouble. There is a very small risk that it can evolve into the active form. One study reported a 10-year survival rate of 95%, which was similar to the same age group in the general population. However, it the condition evolves into the chronic active form, 5-year survival may be only 50% if the disease is not treated. (The survival rate can be higher in people with milder symptoms and less liver damage.)

Although very uncommon, severe autoimmune hepatitis can be life-threatening and require intensive therapy, possibly including liver transplantation. The risk for liver failure and bleeding in the stomach and esophagus is highest in the early years after disease onset. This risk diminishes over time but is replaced by an increase in liver cancer rates and bleeding in the stomach and intestines. The risk for liver cancer is not as high, however, as with chronic viral hepatitis.

Patients with autoimmune hepatitis who have mild symptoms and slight inflammation of the liver do not require any treatment except to relieve symptoms. They should be monitored, however, for any signs of disease progression. Severe autoimmune hepatitis is a life-threatening condition and requires intensive therapy.

Because of effective treatment options and in spite of a high rate of relapse, long-term survival rates in patients with autoimmune hepatitis are excellent. Drugs that block factors in the immune system and help reduce inflammation and symptoms of autoimmune hepatitis are most often used.

Corticosteroids. The corticosteroid prednisone (Deltasone, Orasone, Sterapred, generic) is the standard drug for treating autoimmune hepatitis. It produces remission of symptoms in about 80% of patients with autoimmune hepatitis. For most patients, steroids also reduce symptoms within 3 months, improve liver function within 6 months, and restore liver health within 2 years. Between 10 - 20% of patients continue to deteriorate despite steroid treatment, although higher doses may help some of these people. (Steroids are generally not useful for chronic hepatitis B or C. Suppressing the immune system in these patients can actually encourage the viruses to multipy more quickly.)

Treatment usually needs to continue for about 2 years before the disease is in complete remission. Usually, steroids are stopped when disease symptoms have disappeared, when blood tests show that aminotransferase (AST) levels are less than two times normal, and liver biopsies reveal no active cell damage. Steroid medications must be withdrawn very slowly. Patients who are very elderly or who have advanced (decompensated) cirrhosis are not good candidates for this treatment.

Unfortunately, remission rarely lasts more than 3 years. About half of patients relapse within 6 months, and only about 20% of patientsare disease-free for more than 5 years. A 2007 study indicated that AST, gamma-globulin, and immunoglobulin-G (IgG) levels are helpful in predicting which patients may relapse and which patients have the best chance for maintaining remission. Still, most patients with autoimmune hepatitis will eventually have a relapse. Re-administering prednisone therapy after relapse achieves another remission in about 80% of patients.

Corticosteroid side effects can be very distressing and sometimes serious. They include weight gain, skin problems, moon-shaped face, high blood pressure, diabetes, cataracts, mental disturbances, infections, and osteoporosis.

Azathioprine. Doctors often prescribe the drug azathioprine (Imuran) along with steroids to help reduce severe side effects caused by using steroids alone. When azathioprine is given in combination with prednisone, the prednisone dose can be reduced, thereby lowering the corticosteroid’s side effects. Azathioprine also suppresses the immune system and helps prevent relapse, but the drug will not induce remission by itself.

Other Drugs. Other immunosuppressant drugs, such as mycophenylate mofetil (MMF), cyclosporine (Neoral), or tacrolimus (Prograf) are sometimes prescribed for patients who are not helped by standard treatment.

Liver Transplantation and Autoimmune Hepatitis. If all therapies fail and the disease becomes life threatening, liver transplantation may be performed. Liver transplantation can be a successful option for many people. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years.

Symptom Management

The primary goals for managing viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others. For mild cases of acute viral hepatitis, no drug therapy or other treatment is either available or necessary. Hospitalization is needed only for people at high risk for complications such as pregnant women, elderly people, patients with other serious conditions, or those who have severe nausea and vomiting and need to have fluids administered intravenously.

The following tips may be useful:

All patients should abstain from alcohol and sexual contact during the acute phase.
Although most patients with hepatitis experience fatigue and require more rest than usual, they can be as physically active as they want without affecting recovery. In fact, patients should be encouraged to be as active as they can.
Depression is common, particularly in people used to an active life. Patients should be reassured that in the majority of hepatitis cases, recovery is complete.
The liver processes many types of medications. As soon as hepatitis is diagnosed, patients should stop taking all drugs (including over-the-counter-medication) except those prescribed or recommended by their doctors. Specific nonsteroidal anti-inflammatory drugs (NSAIDs) that should be avoided include ibuprofen (Advil, Motrin) and acetaminophen (Tylenol). Ibuprofen (Advil, Motrin) may increase liver enzymes and cause liver damage in patients with hepatitis C. Acetaminophen (Tylenol) may cause sudden liver failure in patients with hepatitis A or B. Acetaminophen can also damage the liver if taken in combination with alcohol.

After the onset of acute hepatitis, periodic visits to the doctor for repeat blood tests are necessary, the frequency of which depends on how well the patient feels. If symptoms still occur after 3 months and laboratory tests still indicate active presence of the virus, the patient should be evaluated every month. If symptoms persist beyond 6 months, a liver biopsy may be required to determine any liver damage.

Dietary Factors to Protect the Liver. In general, no vitamins or special diets have been proven to be particularly beneficial. The following may be helpful, however:

Eating many small snacks during the day, with larger ones in the morning, may help prevent weight loss while reducing the severity of nausea. Patients might be able to tolerate high-caloric drinks to supplement their regular diet.
One small Japanese study suggested that vitamin E might help protect against liver damage in patients with hepatitis C.
Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. Pork is high in the vitamin, but more healthy sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.
Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.
Higher coffee intake has been shown to reduce the risk for cirrhosis.

Manufacturers of herbal remedies and dietary supplements do not need FDA 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.

Popular herbal remedies for hepatitis include ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), and silymarin (found in milk thistle). Aside from milk thistle, there has been no evidence that these herbs are helpful for hepatitis. Studies on milk thistle’s benefit have been mixed. Some studies have indicated that milk thistle may help improve liver enzyme levels. However, a 2005 review found that the herb did not reduce deaths from liver disease caused by hepatitis B or C.

Patients with hepatitis should be aware that some herbal remedies may cause liver damage. In particular, kava (an herb used to relieve anxiety and tension) may be dangerous for people with chronic liver disease.

Outlook

In most cases of acute viral hepatitis, recovery is complete and the liver returns to normal within 2 - 8 weeks. In a small number of cases of hepatitis B or C, the condition can be prolonged and recovery may not occur for a year. About 5 - 10% of these patients will have a flare-up of milder symptoms before full recovery. A few of these patients may go on to develop chronic hepatitis. People who have been infected with a hepatitis virus continue to produce antibodies to that specific virus. This means that they cannot be reinfected with the same hepatitis virus again. Unfortunately, they are not protected from other types.

Serious consequences of acute viral hepatitis are rare, but can be life threatening if they occur. Pregnant women with acute hepatitis B, C, or E are at higher risk for complications of acute hepatitis.

In very rare cases, within 2 months of onset of acute hepatitis, a very serious condition known as fulminant hepatitis can develop. In this event, the liver fails with catastrophic consequences. The following events may develop:

A large swollen abdomen (known as ascites) and a peculiar hand-flapping tremor (called asterixis).
These symptoms may be followed by stomach and intestinal bleeding and mental confusion, stupor, or coma caused by brain injury (encephalopathy).

No medications, including corticosteroids, have any effect against the condition itself. Liver transplantation is currently the only life-saving treatment for fulminant acute hepatitis and has survival rates of up to 60%. Without liver transplantation, the chance of survival is only 20%.

Other serious and rare consequences of acute viral hepatitis are aplastic anemia (which can be fatal), pancreatitis, hypoglycemia, and polyarteritis, a serious inflammation of blood vessels.

Chronic Persistent Hepatitis. Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver. Cell injury in such cases is usually limited to the region of portal tracts, which contains vessels that carry blood to the liver from the digestive tract. In some cases, however, more extensive liver damage can occur over long periods of time and progress to chronic active hepatitis.

Chronic Active Hepatitis. If damage to the liver is extensive and cell injury occurs beyond the portal tract, chronic active hepatitis can develop. Significant liver damage has usually occurred by this time. Nearly every bodily process is affected by a damaged liver, including digestive, hormonal, and circulatory systems. Symptoms can significantly impair daily life.

Cirrhosis. If liver cells are destroyed between the portal tract and the central veins in the liver, progressive cell damage can build a layer of scar tissue over the liver, resulting in the condition known as cirrhosis. In such cases, the entire liver is threatened with malfunction and failure. If cirrhosis develops, the average survival time is about 10 years. The risk for cirrhosis is much higher in patients with hepatitis C than in those with hepatitis B. [For more information, see In-Depth Report #75: Cirrhosis.]
Liver Cancer. The risk for liver cancer in patients with cirrhosis is about 14% but varies widely depending on the cause of hepatitis. (Liver cancer is rare in patients who do not develop cirrhosis.)

Click the icon to see an image of cirrhosis of the liver.

Liver transplantation may be indicated for the following patients:

Those who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Current 5-year survival rates after liver transplantation are 55 - 80%, depending on different factors. Patients report improved quality of life and mental functioning after liver transplantation. Unfortunately, in about half of all patients with chronic hepatitis, the disease recurs after transplantation.

Patients should consider medical centers that have performed more than 50 transplants per year and produced better-than-average results. Unfortunately, there are far more people waiting for liver donors than there are available organs. [For more information on liver transplantation, see In-Depth Report #75: Cirrhosis.]

Resources

www.cdc.gov/hepatitis -- Centers for Disease Control and Prevention
www.hepfi.org -- Hepatitis Foundation International
www.hepb.org -- Hepatitis B Foundation
www.liverfoundation.org -- American Liver Foundation
www.aasld.org -- American Association for the Study of Liver Diseases
www.gastro.org -- American Gastrointestinal Association
www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.immunize.org -- Immunization Action Coalition
www.hivandhepatitis.com -- Hepatitis and HIV
www.unos.org -- United Network for Organ Sharing

References

Amin J, Law MG, Bartlett M, Kaldor JM, Dore GJ. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study. Lancet. 2006 Sep 9;368(9539):938-45.

Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA. 2007 May 9;297(18):2010-7.

Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. Epub 2006 Sep 20.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Montano-Loza AJ, Carpenter HA, Czaja AJ. Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse. Am J Gastroenterol. 2007 May;102(5):1005-12. Epub 2007 Feb 23.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34.

Wang CS, Wang ST, Yao WJ, Chang TT, Chou P. Hepatitis C virus infection and the development of type 2 diabetes in a community-based longitudinal study. Am J Epidemiol. 2007 Jul 15;166(2):196-203. Epub 2007 May 11.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, In-Depth Reports; Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Bipolar disorder

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

In This Report

Highlights
Introduction
Risk Factors
Causes
Prognosis
Diagnosis
Treatment
Medications
Other Treatments
Therapy and Lifestyle Chang...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17. Risperidone (an atypical antipsychotic) and lithium (a mood stabilizer) are the two drugs currently approved for treating pediatric patients with bipolar disorder.

Drug Warnings

Olanzapine (Zyprexa, Symbex) causes a greater risk for high blood sugar than other atypical antipsychotics, according to updated information added to the drug’s warning label. Olanzapine also causes weight gain and can increase the risk for unhealthy cholesterol levels.
All atypical antipsychotics increase the risk for diabetes. Patients who take these drugs should receive regular screenings for changes in blood sugar levels. Patients should also have their cholesterol levels monitored.

Bipolar Disorder in Children and Adolescents

Diagnoses of bipolar disorder in children have increased 40-fold in the past decade, according to an analysis in the Archives of General Psychiatry. There is debate whether bipolar disorder in children was under-diagnosed in the past or is being over-diagnosed now.
Bipolar symptoms in children differ from those of adults, with some symptoms overlapping with behavioral and conduct disorders. New guidelines from the American Academy of Child and Adolescent Psychiatry (AACP) caution that a diagnosis of bipolar disorder must be carefully made, especially considering the risks associated with drug therapy. The AACP also advises that there are currently no established criteria for diagnosing bipolar disorder in preschoolers.

Bipolar Depression

The antidepressants bupropion (Wellbutin) and paroxetine (Paxil) do not increase the risk for mania, but neither do they help ease depression any more than mood stabilizers, suggests a 2007 study in the New England Journal of Medicine.
Intensive psychotherapy in combination with medication can help improve depression outcomes, indicates a 2007 study in the Archives of General Psychiatry.

Introduction

Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:

Periods of mania with exaggerated euphoria, irritability, or both
Episodes of depression

Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.

Bipolar disorder is classified according to the pattern and severity of the symptoms as bipolar disorder I, bipolar disorder II, or cyclothymic disorder. Patients with one type may develop another. Nevertheless, they are distinct enough to merit separate classifications, and some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.

Bipolar Disorder I. Bipolar disorder I is characterized by at least one manic episode, with or without major depression, that lasts for at least 7 days. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.

Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.

Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by episodes of predominantly depressive symptoms, with occasional episodes of hypomania, which last for at least 4 days. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.

Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.

Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures, while bipolar II patients were "sunnier.")

The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.

Symptoms of the Depression Phase. The symptoms of depression experienced in bipolar disorder are almost identical to those of major depression, the primary form of unipolar depressive disorder. They include:

Sad mood
Fatigue or loss of energy
Sleep problems such as insomnia, excessive sleeping, or shallow sleep with frequent awakenings
Appetite changes
Diminished ability to concentrate or to make decisions
Agitation or markedly sedentary behavior
Feelings of guilt, pessimism, helplessness, or low self-esteem
Loss of interest or pleasure in life
Thoughts of, or attempts at, suicide

Distinguishing Between Unipolar and Bipolar Depression. It is often difficult to differentiate between unipolar and bipolar depression, particularly in patients with bipolar II disorder. They may differ in the following ways:

Bipolar depression typically lasts 2 - 3 months -- not as long as in major depression (although left untreated some bipolar disorder episodes can last 6 - 12 months or longer).
People with unipolar depression can still experience a variety of other moods, but none meet the criteria for a manic state.
Depressive symptoms in those with bipolar disorder tend to vary. For example, some patients experience increased sleep, gain weight, and feel a heaviness and slowness in their bodies. Other patients with bipolar depression experience impaired sleep, but unlike patients with unipolar depression, they do not feel sleepy the next day.
Bipolar depressive episodes tend to develop more gradually than do those caused by major depression.

Symptoms of the Acute Manic Phase. The acute pure manic phase is always characterized by mood elevation, presented in the following ways:

Exaggerated euphoria (a feeling of great happiness or well-being)
Irritability
Both euphoria and irritability

The episode lasts for at least few days but, in some cases, the episode may last weeks or even months and may be severe enough to require hospitalization.

Other symptoms must also be present to make a diagnosis. Some mental health professionals use the mnemonic device DIGFAST to identify them. In general, for a diagnosis of mania, a patient must have experienced either euphoria with three DIGFAST symptoms or irritability with four of these symptoms:

D. Distractibility. This is the most common symptom, and it is usually characterized by the inability to pay attention to any activity for very long.
I. Insomnia in mania typically means having high energy and requiring less sleep. (This differs from insomnia in depression, in which the patient has low energy plus an inability to sleep.)
G. Grandiosity. Patients with this symptom have an inflated sense of themselves, which, in severe cases, can be delusional. Close to 60% of all manic patients experience feelings of being all-powerful. Sometimes they feel that they are godlike or have celebrity status.
F. Flight of ideas. Thoughts literally race.
A. Activity. The patient may show an increase in intensity in goal-directed activities, which are related to social behavior, sexual activity, work or school.
S. Speech. The patient may talk excessively.
T. Thoughtlessness. Excessive involvement in high-risk activities is present (such as unrestrained shopping, promiscuity). Mood disturbance may be severe enough to damage one's job or social functioning or one's relationships with others. Some patients require hospitalization to prevent harm to others or to themselves.

Some patients with bipolar I may experience psychotic symptoms, including thought disorders, hallucinations, and catatonia (a state in which the patient goes into a stupor for long periods, which may give way to short periods of extreme excitement).

Hypomania. With hypomania the symptoms of mania are milder and of shorter duration (but they last at least 4 days). They do not affect social or work life as dramatically.

Mixed Mania State Symptoms. Mixed mania (also called mixed episodes or dysphoric mania) are manic episodes that also have a depressive component. In such a state, mania is present to a significant degree, but depression is present most of the day and nearly every day. Such mixed symptoms occur for at least a week.

Depressive Mixed State Symptoms. Depressive mixed state is characterized by major depression as the primary emotional state with manic features (such as irritability, distractibility, and racing thoughts). Such patients may receive an inaccurate diagnosis of unipolar depression.

Risk Factors

Between 1 - 2 million Americans may suffer from bipolar disorder. Researchers estimate that about 1% of Americans experience bipolar disorder during the course of their lifetime, but some studies indicate that prevalence may be as high as 4%. There is differing opinion on how to diagnose and categorize bipolar symptoms, which affects these estimates. The majority of people with bipolar disorder also have other psychiatric disorders, particularly anxiety and substance abuse.

Bipolar disorder affects both sexes equally, but there is a higher incidence of rapid cycling, mixed states, and cyclothymia in women. Early-onset bipolar disorder tends to occur more frequently in men and it is associated with a more severe condition. Men with bipolar disorder also tend to have higher rates of substance abuse (drugs, alcohol) than women.

Bipolar disorder frequently occurs within families, although genetic factors account for only about 60% of cases. Family members of patients with bipolar disorder also have a higher than average incidence of other psychiatric problems. They include schizophrenia, schizoaffective disorder, anxiety disorders, ADHD, and major depression.

Causes

No single cause may ever be found for bipolar disorder. Instead, a combination of biologic, genetic, and environmental factors appears to trigger and perpetuate the chemical imbalances in the brain that shape this complex disorder. Biologic factors observed or considered in bipolar disorder, as detected by use of imaging scans and other tests, include:

Oversecretion of cortisol, a stress hormone
Excessive influx of calcium into brain cells
Abnormal hyperactivity in parts of the brain associated with emotion and movement coordination
Low activity in parts of the brain associated with concentration, attention, inhibition, and judgment
A superfast "biologic clock"

The so-called biologic clock is a tiny cluster of nerves called the supra chiasmatic nucleus, or SCN. The SCN is located in the center of the brain in the hypothalamus region. It regulates a person's circadian rhythm, the daily cycle of life, which influences sleeping and waking.

The genetics of bipolar disorder are the most intensively studied of all psychiatric diseases. Multiple genes, involving several chromosomes, have been linked to its development. Bipolar disorder also may share these genetic factors with other disorders, including schizophrenia, epilepsy, and panic disorder. It is not clear if some of these disorders are variations of a single disease or separate disorders.

Bipolar Disorder and Schizophrenia. Researchers have been investigating whether common biologic factors are involved with schizophrenia, severe bipolar disorder, and other psychoses. Schizophrenia and bipolar disorder often show up in the same family. Researchers are identifying a number of common genetic and biologic pathways that they both share. Bipolar Disorder and Epilepsy. Neurotransmitters called gamma aminobutyric acid (GABA) and norepinephrine have been implicated in mania:

GABA helps prevent nerve cells from over-firing
Norepinephrine is a hormone that involves stress

Some research has associated similar biologic mechanisms in patients with epilepsy and bipolar disorder. As in epilepsy, the more episodes a bipolar disorder patient experiences early in the course of the disease, the more frequent and severe later episodes will be. Antiseizure drugs, in fact, can play an important role in the treatment of bipolar disorder.

Panic Disorder and Bipolar Disorder. Researchers are also studying the common biologic and genetic factors between panic disorder and bipolar disorder. While specific genes have not yet been identified, some researchers studying these illnesses now believe that they may represent different forms of a shared, complex condition.

Prognosis

Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes. Patients with the disease may experience symptoms in very different ways. A typical bipolar disorder patient averages 8 - 10 manic or depressive episodes over a lifetime. However, some people experience more and some fewer episodes.

Typical Bipolar Cycles. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression are neither regular nor predictable. Many patients experience mixed mania, or a mixed state, in which both mania and depression coexist for at least 7 days.

Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.

Differences Between Children and Adults. Research suggests that symptoms of bipolar disorder in children and adolescents differ from those of adults. While adults with bipolar disorder usually have distinct and persistent periods of mania and depression, children with bipolar disorder fluctuate rapidly in their mood and behavior. Mania in children is characterized by irritability and belligerence whereas adults tend to experience euphoria. Children with bipolar depression are frequently angry and restless, and may have additional mood and behavioral disorders such as anxiety, attention deficit hyperactivity disorder, conduct disorder, and substance abuse problems.

Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.

Bipolar disorder usually first occurs between the ages of 15 - 30 years, with an average age of onset at 25 years. However, bipolar disorder can affect people of all ages, including children. Bipolar disorder that occurs late in life often accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.

Patients with bipolar disorder, especially type II or cyclothymic disorder, have frequent episodes of major depression. Anxiety disorders also commonly coexist in these patients. For example, the occurrence of panic disorder in patients with bipolar disorder is 26 times that of the general population. Patients with bipolar disorder, particularly those with type II, are also subject to phobias. In one study, the presence of anxiety disorders was also associated with longer and more severe bipolar depressive episodes and with a higher risk for suicide.

Symptoms of bipolar disorder in children are often confused with attention-deficit hyperactivity disorder (ADHD). Furthermore, the two conditions can coincide. In one study, 65% of adolescents with bipolar disorder met criteria for ADHD. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some researchers believe that many of these disorders may actually be variations of a single disease.

The risk for suicide is very high in patients who suffer from bipolar disorder and who do not receive medical attention. Between 10 - 15% of patients with bipolar disorder I commit suicide, with the risks being highest during episodes of depression or mixed mania (simultaneous depression and mania). Some studies suggest that the risk for suicide in patients with bipolar disorder II is even higher than it is for those with bipolar disorder I or major depressive disorder. Patients who also suffer from an anxiety disorder are also at greater risk for suicide. (Rapid cycling, although a more severe variation of bipolar disorder, does not appear to increase the suicide risk in patients with bipolar disorder.)

Many pre- and early adolescent children with bipolar disorder are more severely ill than are adults with the disease, and the risk for suicide is high. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.

Studies suggest that patients with bipolar disorder may have varying degrees of problems with short- and long-term memory, speed of information processing, and mental flexibility. Such problems persist even between episodes. They tend to be more severe when a person has more manic episodes. Medications used for bipolar disorder could be responsible for some of these abnormalities, although some evidence suggests that such traits may have a biologic basis. These mental difficulties may make it harder for these patients to comply with medications or to participate in complex psychotherapies.

A small percentage of bipolar disorder patients demonstrate heightened productivity or creativity during manic phases. More often, however, the distorted thinking and impaired judgment that are characteristic of manic episodes can lead to dangerous behavior, including:

Spending money with reckless abandon, causing financial ruin in some cases
Angry, paranoid, and even violent behaviors
Openly promiscuous behavior

Such behaviors are often followed by low self-esteem and guilt, which are experienced during the depressed phases. During all stages of the illness, patients need to be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.

Cigarette smoking is prevalent among patients with bipolar disorder, particularly those who have frequent or severe psychotic symptoms. Some experts speculate that, as in schizophrenia, nicotine use may be a form of self-medication because of its specific effects on the brain.

Up to 60% of patients with bipolar disorder abuse other substances (most commonly alcohol, followed by marijuana or cocaine) at some point in the course of their illness.

The following are risk factors for alcoholism and substance abuse in patients with bipolar disorder:

Having mixed-state episodes rather than ones of pure mania
Being a man with bipolar disorder

Patients do not manifest their negative behaviors (such as spending sprees or even becoming verbally or physically aggressive) in a vacuum. They have a direct effect on others around them. It is very difficult for even the most loving of families or caregivers to be objective and consistently sympathetic with an individual who periodically and unexpectedly creates chaos around them.

Many patients and their families find it difficult to accept that these episodes are part of an illness and not simply extreme, but normal, characteristics. Such denial is often strengthened by patients who are highly articulate and deliberate, and who can intelligently justify their destructive behavior, not only to others, but also to themselves.

Family members may also feel socially alienated by the fact of having a relative with mental illness, and feel forced to conceal this information from acquaintances.

The economic burden of bipolar disorder is significant. It is estimated that the disorder costs the U.S. workplace about $14.1 billion annually in lost productivity, mostly due to poor functioning on the job. According to a 2006 study sponsored by the U.S. National Institute of Mental Health, bipolar disorder accounts for twice as much lost productivity as major depressive disorder (MDD), despite the fact that MDD is more prevalent. Each worker with bipolar disorder loses about 66 workdays a year compared with 27 workdays a year for workers with MDD. Research suggests that bipolar disorder’s depressive episodes impair productivity more than its manic episodes.

People with mental illness have a higher incidence of many medical conditions, including heart disease, asthma and other lung problems, gastrointestinal disorders, skin infections, diabetes, hypertension, migraine headaches, hypothyroidism, and cancer. Patients with bipolar disorder are also less likely to receive medical care than people without mental disorders. Substance abuse, including smoking, alcoholism, and drug abuse, also contributes to many of these problems as well as reduced access to care. Medications used for bipolar disorder can also increase the risk for medical problems.

However, people with bipolar disorder and other mental illness have a higher risk for a number of these conditions independent of these factors.

Diabetes. Diabetes is diagnosed almost three times more often in people with bipolar disorder than it is in the general population. Many patients with bipolar disorder are overweight, with about 25% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.

High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.

Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. Patients with bipolar II suffer from migraine more frequently than patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.

Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.

Diagnosis

Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.

When making a diagnosis of bipolar disorder, it is important that the doctor rule out other conditions that may be causing symptoms of bipolar disorder.

Distinguishing Mania from Normal Euphoria or Joy. A major difficulty with a diagnosis of bipolar disorder is the tendency for a patient to be unable to recognize his or her own condition, particularly when in the manic state. The patient often denies their symptoms, which may be perceived as positive feelings. The doctor should take a careful and complete history of any and all episodes of depression, mania, or both. Hypomania, the less severe variant of mania, may be particularly difficult to distinguish from normal joy or euphoria. It can often be distinguished by the following characteristics:

Hypomania persists for at least 4 days
Patients with hypomania are easily distracted and overly talkative
Patients with hypomania have difficulty functioning

Distinguishing Unipolar from Bipolar Depression. People with bipolar disorder are more likely to seek help because of a depressive episode and may not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.

Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.

A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.

Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.

Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:

The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
A flat emotional expression, with no variability in the voice among people with schizophrenia
People with bipolar disorder are typically very expressive

Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.

Other Causes of Mood Swings. Other conditions that can cause mood swings include:

Thyroid disorders
Adrenal disorders (Addison's disease or Cushing syndrome)
Vitamin B12 deficiency
Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease

Patients should be tested for drugs or alcohol if the doctor suspects that they have been using these substances. Blood tests for thyroid function should also be performed.

Noninvasive imaging tests of the brain using magnetic resonance imaging (MRI) and positron-emission tomographic (PET) scans are being evaluated in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments. However, imaging tests do not currently play a role in diagnosing bipolar disorder.

The number of children diagnosed with bipolar disorder has increased dramatically during the past decade. Psychiatrists debate whether bipolar disorder was formerly under-diagnosed in children or whether it is being over-diagnosed now. Part of the controversy concerns the diagnostic criteria used for children and adolescents. Some bipolar symptoms, such as irritable mania, share characteristics with common childhood anger outbursts or behavioral disorders such as conduct disorder and attention deficit hyperactivity disorder. In addition, many children with bipolar disorder also have behavioral and developmental disorders. These overlapping conditions can complicate diagnosis.

The American Academy of Child and Adolescent Psychiatry (AACP) recommends that doctors use specific screening questions to diagnose bipolar disorder. These questions are designed to evaluate periods of mood changes associated with sleep disorders and restlessness. Doctors should also ask about family histories of mood disorders. The AACP cautions that the validity of diagnosing bipolar disorder in children younger than 6 years old has not been established.

Bipolar disorder is treated with powerful psychiatric drugs that can cause serious side effects. It is very important to make sure that a child’s symptoms are due to bipolar disorder, rather than emotional or behavioral issues, before prescribing these medications.

Treatment

Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:

Treat and reduce the severity of acute episodes of mania or depression when they occur
Reduce the frequency of episodes
Avoid cycling from one phase to another
Help the patient function as best as possible between episodes

The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.

Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this “collaborative care” model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.

The treatments for bipolar disorder, while very effective, pose some specific challenges for the patient:

Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a patient is responding to treatment or naturally emerging from a bipolar phase.
A patient with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
The patient is likely to need more than one medication during the course of the disease. This increases the risk for distressing side effects. Noncompliance is common.
Patients often have more than one medical problem and need different drugs to treat each condition. Such medications may interact with drugs used to treat bipolar disorder or increase side effects. For example, children with bipolar disorder have a higher risk for attention deficit-hyperactivity disorder, which is treated with stimulants that can complicate bipolar treatment.
Family members who have not been educated about the disorder may interfere with the treatment.
Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
Treatments may be costly.

The following are the treatment options for most patients with bipolar disorder, depending on the bipolar disorder phase or episode. Patients should understand that, even with aggressive therapy, either mania or depression recurs in almost three-quarters of patients.

Drugs Used in Bipolar Disorder. Mood stabilizing drugs are the mainstay for patients with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used.

Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many patients with other bipolar subtypes.
Antiseizure Drugs. Valproate (valproic acid) carbamazepine (Tegretol, Carbatrol, Equetro), oxcarbazepine (Trileptal), and lamotrigine (Lamictal) are the most established antiseizure drugs. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify).

Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.

Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.

Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.

Step 1. Determine the Need for Hospitalization and Eliminate Triggers. The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods.

Patients often require hospitalization at the onset of acute mania. The need for hospitalization depends on a number of factors:

Whether the patient is at risk for suicide or for harming others
The availability of social and emotional support at home

Step 2. Control Symptoms of Acute Manic with a Mood Stabilizer. Doctors often try different drugs to control a manic episode. If a current drug does not work well, another type of drug may be added or substituted. It may take several weeks for a mood stabilizer to take effect, and other drugs may be needed.

The following is an example of a stepped approach recommended by some experts:

Initiating a mood-stabilizing drug is the critical first step. Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective in 60 - 80% of all hypomanic and manic episodes. Carbamazepine is usually used in place of valproate to treat patients with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the patient does not respond to a single drug.
If the patient does not respond fully within a week, atypical antipsychotics may be added to one or more mood stabilizers. Atypicals include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), apriprazole (Abilify), and ziprasidone (Geodon). Clozapine (Clozaril), the oldest atypical drug, also works well but it is not generally used because of its potential for severe side effects and the need for weekly monitoring of white blood cell counts.

Step 3. Addition of Other Treatments. Other treatments may be added to speed recovery, treat any psychosis, and achieve remission. They include:

Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol), may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.

Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:

When side effects are intolerable
When the patient does not respond to the maximum dose
When the patient improves and recovery is sustained

In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.

Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.

Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are very difficult and patients who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 - 3 months.

Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.

If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).

Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.

An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the Food and Drug Administration (FDA) approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax was the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.

Other Treatments. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches.

The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling:

Antidepressants, particularly SSRIs, may prompt rapid cycling and should be tapered off.
Lithium or valproate is a first-line treatment for rapid cycling.
Lamotrigine is an alternative treatment for rapid cycling.
Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
Electroconvulsive therapy can be useful in emergency situations.

In addition, other measures should be taken:

Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
Patients should avoid exposure to bright light.
All efforts should be made to help the patient sleep normally.

Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long maintenance therapy. This usually involves mood-stabilizing drugs:

Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also used as a first-line drug for treating depressive episodes.
Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.

The general recommendations for maintenance therapy with lithium are as follows:

The earlier lithium is started in the disease process, the better. Studies suggest that patients on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates due to an increased suicide risk.
Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.

Information on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy.

Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:

In women who discontinue lithium during pregnancy, the chance for recurrence of bipolar disorder is the same as in non-pregnant women, which is over 50%.
Pregnant women with bipolar disorder are at particularly high-risk for recurrence in the period after childbirth. In one study, symptoms recurred in 74% of women after delivery, and another 20% were hospitalized within 90 days after giving birth. The risk for depressive or mixed states is particularly high.

Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:

Lithium can pass through the placenta and affect the fetus. When possible, patients should avoid taking lithium during pregnancy, especially during the first 3 months. Studies report that lithium use during the first trimester may cause heart defects and thyroid problems in the baby. If taken immediately before childbirth, lithium can also cause muscle weakness and drowsiness in newborn infants. Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 - 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
The antiseizure drugs valproate and carbamazepine both greatly increase the risk for physical malformations, developmental delay, and spina bifida in babies. They appear to have minimal effect on breastfeeding, however. Lamotrigine can cause cleft lip and palate birth defects if taken during the first trimester.
Small studies have suggested that the atypical antipsychotic olanzapine does not increase the risk for birth defects. However, it does pose a great risk for excess weight gain that could be unhealthy during pregnancy. Less is known about the effects of other atypical antipsychotics during pregnancy.

Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor.

Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.

Until recently, lithium was the only drug approved for treating bipolar disorder in children (age 12 years and older). In 2007, the FDA approved the atypical antipsychotic risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17.

Lithium is generally used as the first-line treatment, with valproate and risperidone (or other atypical antipsychotics) as alternatives. If treatment with a single drug does not work, a combination of drugs may be used.

Lithium and valproate are the drugs most studied in children and adolescents. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination, weight gain (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate). Side effects of risperidone may include drowsiness, fatigue, increased appetite, nausea, dizziness, dry mouth, tremor, and rash.

Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.

Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. Electroconvulsive therapy (ECT) may benefit adolescents with bipolar I disorder who suffer severe episodes of mania or depression and who have not been helped by medication.

Medications

Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:

Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
It helps to prevent relapses.
It helps psychosocial functioning.
It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
It works well for most patients even if they have discontinued taking it and wish to restart treatment.

Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:

Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.

In addition to drugs, several factors may affect lithium levels:

Seasonal change -- lithium levels may be higher in summer.
Menstrual cycle -- lithium levels may drop during the premenstrual phase.
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.

Lithium Toxicity. Evidence of moderate toxicity include:

Trembling hands
Nausea
Increased urine output
Blurred vision
Some loss of coordination

Severe reactions occurring at higher blood levels, include:

Vomiting
Convulsions
Uncontrolled jerky movements in arms and legs
Stupor
Coma

Very high blood levels of lithium can be fatal. If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:

Patients are given fluids and drugs to increase excretion of lithium salts.
Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:

An unpleasant taste in the mouth
Hair loss
Skin eruptions that can resemble acne and make psoriasis worse
Low thyroid function
An increased risk for diabetes
A blunted sexual drive
Dulled emotions and lack of mental clarity
Memory loss
Lack of motor coordination
Increased sensitivity to light

In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

The risks associated with these drug interactions are very low, but caution is needed.

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.

Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.

Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.

Antiseizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. These drugs may be an alternative for patients (especially substance abusers) who do not tolerate or respond to lithium. They also may be used in combination with lithium, atypical antipsychotics, or other drugs.

Standard Antiseizure Drugs.

Valproate (Depakote), also called valproic acid or divalproex, is now a first option for many bipolar disorder patients. It works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Valproate also helps migraine headaches, a common problem among patients.
Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers.
Carbamazepine (Epitol, Tegretol), a standard alternative antiseizure drug used for mood stabilizing, is usually the second anti-seizure medication of choice. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Another drug, oxcarbazepine (Trileptal), is similar to carbamazepine.
Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.

General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:

Gastrointestinal problems such as nausea, vomiting, and heartburn
Headaches
Visual disturbances
Ringing in the ear
Hair loss
Weight gain (a significant problem with valproate)
Agitation
Odd movements
Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
Birth defects when taken by pregnant women
Cognitive impairment and symptoms of Parkinson's disease

Very serious side effects are possible. Stevens-Johnson syndrome (SJS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. The risk of serious skin reactions is 10 times higher for patients of Asian ancestry than Caucasians. The FDA recommends that people of Asian ancestry get a genetic test before starting carbamazepine to determine if they are at risk for this side effect.

Other serious side effects, also rare, may include liver damage, convulsions, coma, and pancreatitis.

Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon).

Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Paliperidone (Invega), which is chemically related to risperidone, was approved in 2007 for treatment of schizophrenia but has not yet been approved for bipolar disorder.
Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
Clozapine has not been approved for treatment of bipolar disorder, but has shown promise in investigational studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis).

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include:

Nasal congestion or runny nose
Drooling
Dizziness
Headache
Drowsiness -- however, these drugs may also cause restlessness and insomnia.
Constipation
Rapid heart beat
Difficulty urinating
Skin rash
Increased body temperature
Confusion, short-term memory problems, disorientation, and impaired attention
Weight gain -- risk is highest with clozapine and olanzapine, lowest with aripiprazole and ziprasidone

More serious risks include:

Diabetes (See Diabetes Risk and Atypical Antipsychotics)
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
Seizures
Heat stroke
Sudden drop in blood pressure (hypotension)
A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
Extrapyramidal side effects, which are lack of motor coordination and involuntary movements
Cataracts and worsening of any existing glaucoma
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.

Diabetes Risk and Atypical Antipsychotics. In 2003, the FDA requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:

Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They may trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. Another antidepressant, venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.

Side effects of SSRIs include:

Nausea and gastrointestinal problems, which usually wear off over time
Agitation, insomnia, mild tremor, and impulsivity
Dry mouth, which can increase the risk for cavities and mouth sores
Headache
Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Other Treatments

Electroconvulsive therapy (ECT) is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.

Research suggests ECT may be particularly beneficial for:

Patients who need immediate stabilization of their condition and who cannot wait for medications to work
Most patients with mania -- especially elderly patients with severe mania
Patients who suffer suicidal thoughts and guilt during the depressive phase
Pregnant patients
Patients who cannot tolerate drug treatments
Patients with certain types of heart problems
Young patients

In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.

The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:

A muscle relaxant and short-acting anesthetic are given to the patient.
A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
The response to ECT is usually very fast, and the patient often needs less medication afterward.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded.

Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:

Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
Causing various hormonal changes, particularly with thyroid-related hormones.
Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory).

Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.

Transcranial Magnetic Stimulation. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.

Therapy and Lifestyle Changes

Psychotherapy is an important addition to medication. Many approaches are proving to be very useful. Trained mental health professionals can:

Educate patients about bipolar disorder and its treatments
Teach patients to recognize and manage early warning symptoms of imminent manic or depressive episodes
Help them comply with drug regimens
Monitor the patient's on-going status
Intervene early in manic and depressive episodes to reduce the severity of the attack

In addition, psychotherapy can help patients:

Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
Cope with feelings of guilt and remorse that occur after manic episodes
Deal with feelings of imperfection and despair

Therapists trained in cognitive-behavioral therapy (CBT) may be particularly helpful for many patients. CBT is a structured, conscious method that aims to help a patient recognize negative thoughts and behavioral patterns and to change them. CBT is known to be helpful for other mood disorders, including depression and anxiety, and some studies suggest that it benefits bipolar disorder patients as well. For example, in one recent study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.

Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:

Recognize manic episodes before they become full-blown and change behaviors during an episode
Cope with depression by developing behaviors and thoughts that may help offset the negative mood

It is very important that partners, family members, or both be involved in therapy. CBT can help them learn how to accept the condition, the need for medications, and how to protect themselves and the patient financially during manic episodes. In fact, one study indicated that when a spouse of a patient learned ways of coping with the illness, the partner's chances of sticking to a prescribed treatment improved.

Supporting the Patient. Recommendations for supporting the patient include:

Create a treatment contract as a first step. In this contract, the patient and family agree to specific steps for maintaining emotional stability. If such measures fail, all parties agree on further actions to be taken during an acute episode, including requests for hospitalization.
Be supportive. Unlike relatives of patients with alcoholism who may be encouraged to get tough, relatives of patients with bipolar disorder must be strongly supportive because of the high risk for suicide with this disorder. Simply listening attentively and being empathic can help.
Get the patient to comply with treatment, even if it means threatening a hospitalization if the patient fails to comply.
Have ready a hotline number or the telephone number of a psychiatrist authorized to commit the patient. The doctor should be willing to facilitate commitment if a patient becomes violent or the family is on the verge of collapse.
Don't feel guilty and don't make the patient feel guilty. Bipolar disorder results from an imbalance of chemicals in the brain and not from anyone's fault.

Support for the Family. Unfortunately, actions that support a bipolar disorder patient may not be intuitive, and they take their toll. Loved ones must also care for themselves or they may also follow a path to severe depression. They should to boost energy and reduce stress through:

Exercise
Meditation
Relaxation techniques
Holidays away from the patient
Involvement in hobbies
Involvement in support groups, Internet resources with chat rooms, and message boards for bipolar disorder caregivers

Interpersonal problems (such as family disputes) and disruptions in daily routines or social rhythms (such as loss of sleep or changes in meal times) may make people with bipolar disorder more susceptible to new episodes of their illness. A form of psychosocial treatment called interpersonal and social rhythm therapy (IPSRT) focuses on maintaining a regular schedule of daily activities to reduce these potential triggers and improve emotional stability. Patients also learn how to avoid problems with personal relationships. Preliminary evidence suggests that IPSRT combined with drug therapy works better than medication alone. A 2-year study of patients with bipolar 1 disorder indicated that IPSRT may help prevent new manic episodes.

Exercise. Exercise is an important part of treatment, particularly in helping manage weight gain. It also helps increase feelings of well-being.

Sleep Management. Good sleep hygiene is particularly important for patients. One study reported that techniques used to enforce healthy sleep helped reduce mood cycling.

Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. People with bipolar disorder should be sure to maintain a regular healthy diet. They may need to restrict calories if they are on medications that increase weight.

Some research indicates that consumption of omega-3 polyunsaturated fatty acids found in oily fish (such as mackerel, sardines, salmon, and bluefish) may help reduce the symptoms of a variety of mental illnesses, including bipolar disorder. Researchers are investigating the effects of eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) supplements for patients who have not responded to other treatments.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.bpkids.org -- Child & Adolescent Bipolar Foundation
www.dbsalliance.org -- Depression and Bipolar Support Alliance
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

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Review Date:
12/25/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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