NORD gratefully acknowledges Ronald R. Butendieck, MD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, for assistance in the preparation of this report.
The earliest symptom of Behçet’s syndrome is usually painful canker sores on the mucous membranes that line the mouth (aphthous stomatitis). The sores are usually round or oval with reddish (erythematous) borders that may occur anywhere within the mouth. They may be shallow or deep and may appear as a single lesion or a cluster of multiple lesions. The sores typically heal within a few days, up to a week or more, without scarring, but frequently recur. They may precede other symptoms of Behçet’s syndrome by a number of years. Sometimes similar sores may appear on the genitals, specifically the scrotum and shaft of the penis in males and the vulva in females. The sores are also round and painful, but may be larger and deeper than those affecting the mouth. These sores also recur, but unlike oral sores, may tend to scar.
Behçet’s syndrome may also affect the eyes. Symptoms may include inflammation of the back of the eye (posterior uveitis) and inflammation of the anterior chamber (anterior uveitis or iridocyclitis). Inflammation of the iris accompanied by pain, tearing (lacrimation), and the accumulation of pus (hypopyon iritis) may also occur. The retina may become inflamed resulting in blurred vision, abnormal sensitivity to light (photophobia), and/or, inflammation of the thin membranous layer of blood vessels behind the retina (chorioretinitis). Although the lesions that cause inflammation in various parts of the eyes may resolve, repeated recurrences may result in the partial loss of vision (decreased visual acuity) or complete blindness if the disease is uncontrolled. In some cases, eye abnormalities may be the first symptom of Behçet’s syndrome. In other cases, they may not develop until several years later.
Individuals with Behçet’s syndrome may also exhibit the formation of small, pus-filled growths on the skin (pustules). Some affected individuals, especially females, may develop lesions that resemble those of erythema nodosum, a skin disorder characterized by the formation of tender, reddish, inflammatory nodules on the front of the legs. These nodules disappear on their own (spontaneously) sometimes leaving faint scars or discoloration (pigmentation). Some individuals with Behçet’s syndrome may develop small eruptions that resemble acne (acneiform eruptions) and/or inflammation that mistakenly appear to affect the hair follicles on the skin (pseudofolliculitis).
In approximately 50 percent of cases of Behçet’s syndrome, affected individuals experience pain (arthralgia) and swelling in various joints of the body (polyarthritis). This may occur before, during, or after the onset of the other symptoms associated with Behçet’s syndrome. Pain, which can range from mild to severe, typically affects the joints of the knees, wrists, elbows and ankles, and may become chronic. Lasting damage to affected joints is extremely rare.
Individuals with Behçet’s syndrome may also have recurring ulcers in the digestive tract. Symptoms vary from mild abdominal discomfort to severe inflammation of the large intestine and rectum accompanied by diarrhea or bleeding.
Approximately 10%-20% of individuals with Behçet’s syndrome also have involvement of the central nervous system. These symptoms usually appear months or years after the initial symptoms of Behçet’s syndrome. Recurring attacks of inflammation involving the brain (parenchymal Neuro-Behçet) or the membranes that surround the brain or spinal cord (meningitis or meningoencephalitis) can result in neurological damage. Symptoms may include headache, the inability to coordinate voluntary movement (cerebellar ataxia), impaired muscle movements of the face and throat (pseudobulbar palsies), stroke, and/or rarely, seizures.
Behçet’s syndrome causes inflammation of the blood vessels (vasculitis). Involvement of small vessels is thought to drive many of the problems that the disorder causes. In some instances inflammation of the large veins, particularly those in the legs may occur along with the formation of blood clots (thrombophlebitis). The walls of an involved artery may bulge forming a sac (aneurysm). In very rare cases, blood clots from the veins travel to the lungs (pulmonary emboli) resulting in episodes of chest pain, coughing, difficult or labored breathing (dyspnea), and coughing up blood (hemoptysis).
Unlike most diseases which are classified as a vasculitis, involvement of the kidneys or peripheral nerves is very rare.
It is especially important to identify Behçet’s disease when there is ocular, central nervous system or large blood vessel involvement as manifestations are usually the most serious.
The exact cause of Behçet’s syndrome is not known. Studies suggest that some people may have a genetic predisposition to the condition. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. Researchers have demonstrated that certain individuals with Behçet’s syndrome, especially those of Middle Eastern and Asian descent, have an increased frequency of certain “human leukocyte antigens” (HLAs) in the blood. Individuals with Behçet’s syndrome are more likely to have HLA-B51 than the general population. The possible role of HLA-B51 in predisposing individuals to Behçet’s syndrome and its overall association with the disorder is unknown. Other genetic markers and their role in the development of Behçet’s disease are being studied. Viral or bacterial infections have also been suggested as a possible cause for the disorder. Still another theory is that the disease is an auto-inflammatory disorder in which the body loses the ability to appropriately regulate and control inflammation.
Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. While investigation is ongoing, no autoantibodies to date have been identified to suggest that Behçet’s syndrome is an autoimmune disease.
Behçet’s syndrome is a rare disorder in the United States and Western Europe. It occurs most frequently in the Middle East and Asia, along ancient trading routes between the Mediterranean basin and eastern Asia, known as the Silk Road. Turkey has the highest prevalence rate (80-370 cases per 100,000); Japan, Korea, China, Iran, and Saudi Arabia also have high prevalence rates. The disorder is the leading cause of blindness in Japan. The age of onset is typically between 30 and 40 years.
In the United States and Australia, this syndrome is more common in women than men, and the symptoms tend to be less severe. Men may be more commonly affected in Middle Eastern countries and usually have more severe disease. Central nervous system involvement is more common among native populations of northern Europe and the United States.
The diagnosis of Behçet’s syndrome is made based on the clinical judgment of a physician. Criteria have been accepted, based upon the identification of recurrent oral ulcerations (aphthous stomatitis) that occur along with at least two of the following: eye lesions, skin lesions, recurrent genital ulcerations, and a positive pathergy test. (During a pathergy test, a physician pricks an individual with a sterile needle. A positive outcome occurs if a reddish spot (nodule or pustule) forms 48 hours after the prick.) However, these criteria have been formed so that patients might be included in clinical studies (“classification criteria”) and are not really “diagnostic” criteria.
The treatment of Behçet’s syndrome is directed toward the specific symptoms that are apparent in each individual. Specific therapies for Behçet’s syndrome are symptomatic and supportive. Severity of the condition as well as the patient’s age and sex may all affect treatment decisions. Spontaneous remission over time is common for individuals with Behçet’s syndrome.
For recurrent ulcers, the application of corticosteroid-containing preparations to the affected areas may be helpful in aborting developing attacks. Mouthwash containing a local anesthetic such as Xylocaine, lidocaine, or Benadryl may temporarily relieve pain. Arthritis associated with Behçet’s syndrome may be treated with colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs). Continuing therapy with the drug colchicine may be effective in preventing recurring attacks of oral and genital ulcers or arthritis.
Ocular inflammation is treated with eye drops containing corticosteroids to relieve pain. Azathioprine has been used to control the progression of eye disease in people with Behçet’s syndrome. Sulfasalazine, azathioprine, and corticosteroids may be administered to treat inflammatory bowel disease and gastrointestinal lesions associated with Behçet’s syndrome. Central nervous system and vascular abnormalities may be treated with corticosteroids as well, often in conjunction with immunosuppressive agents. In patients with clotting of major blood vessels, systemic anticoagulants and immunosuppressants should be considered.
Inflammation of the joints, skin, and/or mucous membranes or other organs may be reduced with oral corticosteroid drugs. However, corticosteroids do not prevent recurring episodes of symptoms and may not reduce damage when used alone. Therefore, immunosuppressive agents such as azathioprine, methotrexate, cyclosporine, or chlorambucil may be employed for improved control of inflammation and organ protection. Experience is evolving with the use of interferon-alpha and with agents which inhibit tumor necrosis factor (TNF) in the treatment of Behçet’s disease.
There are no FDA approved therapies for the treatment of Behçet’s Syndrome. Immunosuppressive drugs such as azathioprine (Imuran), chlorambucil (Leukeran), cyclophosphamide (Cytoxan), cyclosporine (Sandimmune), interferon alpha, and anti-TNF inhibitors have being studied for use as treatments for the disorder. It has been suggested that cyclosporine may be beneficial for the treatment of oral ulcers, skin lesions, and inflammation of the eyes, but the symptoms of Behçet’s syndrome return quickly when the drug is stopped. Apremilast (Otezla) is currently being studied for use in treatment of recurrent oral and genital ulcerations as well as other manifestations.
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