Behcet's syndrome is a disease that involves vasculitis, which is inflammation of the blood vessels. It causes problems in many parts of the body. The most common symptoms are

• Sores in the mouth
• Sores on the sex organs
• Other skin sores
• Swelling of parts of the eye
• Pain, swelling and stiffness of the joints

More serious problems can include meningitis, blood clots, inflammation of the digestive system and blindness.

Doctors aren't sure what causes Behcet's. It is rare in the United States, but is common in the Middle East and Asia. It mainly affects people in their 20s and 30s. Diagnosing Behcet's can take a long time, because symptoms may come and go, and it may take months or even years to have all of the symptoms. There is no cure. Treatment focuses on reducing pain and preventing serious problems. Most people can control symptoms with treatment.

Behçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects small blood vessels in the mouth, genitals, skin, and eyes.

Painful mouth sores called aphthous ulcers are usually the first sign of Behçet disease. These sores can occur on the lips, tongue, inside the cheeks, the roof of the mouth, the throat, and the tonsils. The ulcers look like common canker sores, and they typically heal within one to two weeks. About 75 percent of all people with Behçet disease develop similar ulcers on the genitals. These ulcers occur most frequently on the scrotum in men and on the labia in women.

Behçet disease can also cause painful bumps and sores on the skin. Most affected individuals develop pus-filled bumps that resemble acne. These bumps can occur anywhere on the body. Some affected people also have red, tender nodules called erythema nodosum. These nodules usually develop on the legs but can also occur on the arms, face, and neck.

An inflammation of the eye called uveitis is found in more than half of people with Behçet disease. Eye problems are more common in younger people with the disease and affect men more often than women. Uveitis can result in blurry vision and an extreme sensitivity to light (photophobia). Rarely, inflammation can also cause eye pain and redness. If untreated, the eye problems associated with Behçet disease can lead to blindness.

Joint involvement is also common in Behçet disease. Often this affects one joint at a time, with each affected joint becoming swollen and painful and then getting better.

Less commonly, Behçet disease can affect the brain and spinal cord (central nervous system), gastrointestinal tract, large blood vessels, heart, lungs, and kidneys. Central nervous system abnormalities can lead to headaches, confusion, personality changes, memory loss, impaired speech, and problems with balance and movement. Involvement of the gastrointestinal tract can lead to a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be life-threatening.

The signs and symptoms of Behçet disease usually begin in a person's twenties or thirties, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores in the mouth and on the genitals. Others have more severe symptoms affecting various parts of the body, including the eyes and the vital organs. The features of Behçet disease typically come and go over a period of months or years. In most affected individuals, the health problems associated with this disorder improve with age.

Behçet disease is most common in Mediterranean countries, the Middle East, Japan, and other parts of Asia. However, it has been found in populations worldwide.

The highest prevalence of Behçet disease has been reported in northern Turkey, where the disorder affects up to 420 in 100,000 people. The disorder is rare in northern European countries and the United States, where it generally affects fewer than 1 in 100,000 people.

What is Behcet's disease?

Behcet's disease is a rare, chronic inflammatory disorder. The cause of Behcet's disease is unknown, but current research suggests that both genetic and environmental factors play a role. Behcet's disease generally begins when individuals are in their 20s or 30s, although it can happen at any age. It tends to occur more often in men than in women. Symptoms of Behcet's disease include recurrent ulcers in the mouth (resembling canker sores) and on the genitals, and eye inflammation. The disorder may also cause various types of skin lesions, arthritis, bowel inflammation, meningitis (inflammation of the membranes of the brain and spinal cord), and cranial nerve palsies. Behcet's is a multi-system disease; it may involve all organs and affect the central nervous system, causing memory loss and impaired speech, balance, and movement.

The effects of the disease may include blindness, stroke, swelling of the spinal cord, and intestinal complications. The disease is common in the Middle East, particularly in Turkey, and in Far Eastern nations such as Japan and Korean, but is less common in the United States.

Is there any treatment?

Treatment for Behcet's disease is symptomatic and supportive. Medication may be prescribed to reduce inflammation and/or regulate the immune system. Immunosuppressive therapy may be considered.

What is the prognosis?

Behcet's disease is a lifelong disorder that comes and goes. Permanent remission of symptoms has not been reported.

Anyone can develop Behçet’s disease, but it is more common among:

• People in the Middle East, Asia, and Japan, as compared with the United States.
• Women than men in the United States.
• Men than women in Middle Eastern and Asian countries.

Behçet’s disease tends to develop in people in their twenties or thirties, but people of all ages can develop this disease.

The cause of Behçet disease is unknown. The condition probably results from a combination of genetic and environmental factors, most of which have not been identified. However, a particular variation in the HLA-B gene has been associated with the risk of developing Behçet disease.

The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-B gene called HLA-B51 increases the risk of developing Behçet disease by about a factor of six, although the mechanism is not well understood. One-third to two-thirds of people with Behçet disease have the HLA-B51 variation, but most people with this version of the HLA-B gene never develop the disorder.

Other genetic and environmental factors likely contribute to the risk of Behçet disease. Researchers are studying several genes related to immune system function. It also appears likely that environmental factors, such as certain bacterial or viral infections, play a role in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear.

Normal Function

The HLA-B gene provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.

HLA is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. Genes in this complex are categorized into three basic groups: class I, class II, and class III. In humans, the HLA-B gene and two related genes, HLA-A and HLA-C, are the main genes in MHC class I.

MHC class I genes provide instructions for making proteins that are present on the surface of almost all cells. On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC class I proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.

The HLA-B gene has many possible variations, that result in the production of proteins that differ by changes in at least one protein building block (amino acid). This variety allows each person's immune system to react to a wide range of foreign invaders. Most HLA-B gene alleles are rare, while others do not affect protein function or change the structure of the protein. Hundreds of versions (alleles) of the HLA-B gene are known, each of which is given a particular number (such as HLA-B27). Closely related alleles are categorized together; for example, more than 60 very similar alleles are subtypes of HLA-B27. These subtypes are designated as HLA-B*2701 to HLA-B*2763.

Health Conditions Related to Genetic Changes

Ankylosing spondylitis

Variants in the HLA-B gene, particularly a version called HLA-B27, significantly increase the risk of developing ankylosing spondylitis. This condition is a form of painful, ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine. It is uncertain how the HLA-B27 gene variant causes the increased risk. Researchers speculate that HLA-B27 may abnormally display peptides that trigger an immune reaction, resulting in the inflammatory process that causes arthritis. Other research suggests that the joint inflammation characteristic of this disorder may result from improper folding of the HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. It is possible that HLA-B27 may increase the risk of ankylosing spondylitis through more than one mechanism, or by different mechanisms in different individuals based on their genetic and environmental background.

Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disorder. It is estimated that among those with the HLA-B27 allele, only one to five percent develop ankylosing spondylitis. Additional HLA-B alleles play a smaller role in disease risk: the HLA-B47 and HLA-B51 alleles can contribute to increased risk, whereas the HLA-B7 and HLA-B57 alleles might provide some small amount of protection against developing the condition. Other genetic and environmental factors, many of which are unknown, affect the chances of developing ankylosing spondylitis and influence its progression.

Behçet disease

Several versions of the HLA-B gene, particularly HLA-B51, are associated with an increased risk of developing Behçet disease, a chronic inflammatory condition that affects many parts of the body. This association is strongest in people from Japan, the Middle East, and other parts of Asia. Researchers do not know how HLA-B51 increases the risk of this disorder. Although many people with Behçet disease have the HLA-B51 variation, most people with this version of the HLA-B gene never develop the condition. It appears likely that other factors, such as viral or bacterial infections and changes in other genes, also influence the development of this complex disorder.

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Stevens-Johnson syndrome/toxic epidermal necrolysis

Several variations of the HLA-B gene have been studied as risk factors for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a potentially life-threatening skin reaction most often triggered by medications. For example, the variation HLA-B*1502 increases the risk of SJS/TEN in people taking certain medications used to treat seizures, particularly a drug called carbamazepine. This version of the gene is most common among people of Han Chinese or southeast Asian descent. Another version of the gene, HLA-B*5801, increases the risk of SJS/TEN in people treated with allopurinol (a drug used to treat kidney stones and gout, which is a form of arthritis caused by a buildup of uric acid in the joints). This association has been confirmed in southeast Asians and in people of non-Asian ancestry, although HLA-B*5801 occurs less frequently in non-Asian populations.

Studies suggest that the HLA-B gene variations associated with SJS/TEN cause the immune system to react abnormally to some medications. In a process that is not well understood, the triggering drug causes immune cells called cytotoxic T cells and natural killer (NK) cells to release a substance called granulysin. This substance destroys cells in the skin and mucous membranes, including the lining of the mouth and the airways. The death of these cells causes severe blistering and peeling that can have life-threatening effects.

Most people who have variations in the HLA-B gene that are associated with an increased risk of SJS/TEN never develop the condition, even if they are exposed to drugs that can trigger it. Researchers believe that additional genetic and nongenetic factors, many of which are unknown, likely play a role in whether a particular individual develops SJS/TEN.

Other disorders

The HLA-B27 variant is associated with a group of inflammatory joint diseases related to ankylosing spondylitis. These conditions are known as spondyloarthropathies. Some of these disorders are associated with a common skin condition called psoriasis or with chronic disorders that cause inflammation of the intestinal walls (inflammatory bowel disease). One of the spondyloarthropathies, reactive arthritis, is typically triggered by bacterial infections of the gastrointestinal or genital tract. Following an infection, affected individuals may develop arthritis, back pain, and eye inflammation. Like ankylosing spondylitis, many factors probably contribute to the development of reactive arthritis and other spondyloarthropathies.

Among people with human immunodeficiency virus (HIV) infection, a version of the HLA-B gene designated HLA-B*5701 increases the risk of an adverse reaction (hypersensitivity) to the drug abacavir. This medication slows the spread of the HIV-1 virus in the body. People with abacavir hypersensitivity often develop a fever, chills, rash, upset stomach, and other symptoms when treated with this drug.

Several variations of the HLA-B gene appear to play a role in the progression of HIV infection to acquired immunodeficiency syndrome (AIDS). AIDS is a disease that damages the immune system, preventing it from effectively defending the body against infections. The signs and symptoms of AIDS may not appear until 10 or more years after infection with HIV. Studies suggest that people with HIV infection who have HLA-B27 or HLA-B57 tend to progress more slowly than usual to AIDS. On the other hand, researchers believe that HIV-positive individuals who have HLA-B35 tend to develop the signs and symptoms of AIDS more quickly than usual. Other factors also influence the progression of HIV infection to AIDS.

Another version of the HLA-B gene, HLA-B53, has been shown to help protect against severe malaria, a disease caused by a parasite that is carried by mosquitoes. HLA-B53 is most common in West African populations, where malaria is a frequent cause of death in children. Studies suggest that this version of the HLA-B gene may help the immune system respond more effectively to the parasite that causes malaria.

Other Names for This Gene

• 1B07_HUMAN
• HLA class I histocompatibility antigen, B alpha chain
• leukocyte antigen B
• MHC class I HLA-B heavy chain

Genomic Location

Most cases of Behçet disease are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance.

Behçet’s disease affects each person differently. You may have only mild symptoms, such as sores in the mouth or on the genitals. Fever, stiff neck, and headaches could be signs of a more severe issue: meningitis (inflammation of the membranes that cover the brain and spinal cord). These more severe symptoms usually appear months or years after the first signs of Behçet’s disease.

Symptoms can last for a long time or may come and go in a few weeks. Symptoms usually appear, disappear, and then reappear. You are going through a “flare” if you are having symptoms. Each flare could have different symptoms. You should keep a record of which symptoms occur and when. This will help your doctor diagnose and follow your disease, especially since many conditions may look like Behçet’s disease.

Common symptoms of Behçet’s disease include the following:

• Mouth sores affect almost all people with Behçet’s disease. They are probably the first symptom that you noticed and may occur long before any other symptoms appear. The sores usually have a red border and several may appear at the same time. They may be painful and can make eating difficult. Mouth sores go away in 10 to 14 days but often come back. Small sores usually heal without scarring, but larger sores may scar.
• Genital sores affect more than half of all people with Behçet’s disease. They usually appear on the scrotum in men and vulva in women. The sores look similar to the mouth sores and may be painful. They may cause scarring after several outbreaks.
• Skin problems are a common symptom of Behçet’s disease. The sores are red and raised, and may look like a pus-filled bump or bruise. They typically appear on the legs and on the upper torso.
• Inflammation of the middle or back part of the eye (the uvea) and the iris happens in more than half of all people with Behçet’s disease. This is more common among men than women and typically begins within 2 years of the first symptoms. Eye inflammation can cause blurred vision. In rare cases it causes pain and redness. You should immediately tell your doctor if you have these symptoms, since continued eye inflammation can cause vision loss.
• Arthritis occurs in over half of all people with Behçet’s disease. Arthritis causes pain, swelling, and stiffness in the joints, especially in the knees, ankles, wrists, and elbows. The arthritis usually lasts a few weeks and does not cause permanent joint damage.
• Blood clots sometimes form in inflamed veins, usually the legs, of some people with Behçet’s disease. The affected area may be painful, swollen, and warm. Blood clots can cause serious health issues. So, be sure to report any of these symptoms to your doctor right away. Some people may have artery problems such as aneurysms (balloon-like swelling of the artery wall).
• Brain and spinal cord problems occur in about 1 in 4 people with the disease in the United States. Behçet’s disease can cause inflammation of the brain and the thin membrane that covers and protects the brain and spinal cord. Symptoms can include fever, headache, stiff neck, and difficulty coordinating movement. You should immediately report any of these symptoms to your doctor, as a stroke can result if the condition is not treated.
• Digestive tract inflammation and sores occur in rare cases. Symptoms can include stomach pain, diarrhea, and/or bleeding. Your doctor will need to rule out other diseases that have similar symptoms, such as ulcerative colitis and Crohn’s disease.

There is no specific test for Behçet’s disease, which makes it hard to diagnose. Symptoms that help your doctor diagnose the disease include:

• Mouth sores at least three times in 12 months.
• Any two of the following symptoms:
  • Genital sores that keep coming back.
  • Skin sores, or sores that develop after your doctor pricks your skin with a needle. Only up to half of people with the disease will see a bump appear about 1 to 2 days later.
  • Eye inflammation with loss of vision.

Your doctor will need to rule out other conditions that have similar symptoms, such as Crohn’s disease and reactive arthritis. Diagnosis may take some time, as some symptoms may take years to appear.

You may even see different doctors before you are diagnosed. An eye specialist will help identify health issues related to eye inflammation. A dermatologist may examine your mouth, genital, or skin sores to help rule out other disorders.

Although there is no cure for Behçet’s disease, you can control symptoms with proper medication, rest, exercise, and a healthy lifestyle. Treatments make you more comfortable and prevent serious health effects, such as disabling arthritis and blindness. You may need a combination of treatments for your specific symptoms. Make sure you tell all of your doctors about medications you take so your doctors can coordinate treatment.

Medicines

One or more medicines may help treat the various symptoms of Behçet’s disease:

• Rinses, gels, ointments, or creams are applied directly to sores to relieve pain and swelling.
• Corticosteroids are prescribed to reduce pain and inflammation from skin sores or of the joints, eye, or brain and spinal cord. It is important to see your doctor on a regular basis to watch for any side effects from these drugs.
• Immunosuppressive drugs help control an overactive immune system, reduce inflammation, and lessen the number of disease flares. These medicines are very strong and can have serious side effects, so it’s important to see your doctor regularly if you take these drugs.

Rest and Exercise

Rest is important during when you are having symptoms from Behçet’s disease. Moderate exercise, such as swimming or walking, are recommended when the symptoms have improved or disappeared. This can help keep your joints strong and flexible.

Because the disease affects different parts of your body, you will probably see several different doctors. You may find it helpful to coordinate your care through one doctor, who can watch for any side effects from the different medicines you take. Care is often managed by a rheumatologist, a doctor specializing in arthritis and other inflammatory disorders.

The following specialists also treat other symptoms:

• Dermatologists treat skin sores.
• Urologists treat genital sores.
• Gynecologists treat genital sores for women.
• Ophthalmologists treat eye inflammation.
• Gastroenterologists treat digestive tract symptoms.
• Hematologists treat disorders of the blood.
• Neurologists treat disorders of the brain and spinal cord.

Most people with Behçet’s disease can lead productive lives and control symptoms with proper medicine, rest, and exercise. Rest is important when you are having symptoms from Behçet’s disease. Moderate exercise, such as swimming or walking, are recommended when the symptoms have improved or disappeared. This can help keep your joints strong and flexible.