Information on the following diseases can be found in the Related Disorders section of this report:

• Reiter's syndrome
• Stevens-Johnson syndrome
• Sweet syndrome

The earliest symptom of Behcet'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 weeks without scarring, but frequently recur. They may precede other symptoms of Behcet’s syndrome by a number of years. Sometimes similar sores may appear on the genitals, specifically the scrotum and penis in males and the vulva in females. The sores are also round and painful, but are also larger and deeper than those affecting the mouth. These sores also recur, but, unlike oral sores, may tend to scar.

Behcet's syndrome also affects the eyes. Symptoms may include inflammation of the outer fibrous layers of tissue (tunic) that surround the eyes (posterior uveitis) and inflammation of the middle muscular and vascular layers of the eyes (iridocyclitis). Inflammation of the iris accompanied by pain, tearing (lacrimation), and the accumulation of pus (transient 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 after approximately four to eight years. In some cases, eye abnormalities may be the first symptom of Behcet’s syndrome. In other cases, they may not develop until several years later.

Individuals with Behcet’s syndrome may also exhibit the formation of small, pus-filled growths (pustules). Some affected individuals, especially females, may develop lesions that resemble those associated with 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 Behcet’s syndrome, especially males, may develop small eruptions that resemble acne (acneiform eruptions) and/or inflammation of the hair follicles on the skin (pseudofolliculitis).

In approximately 50 percent of cases of Behcet'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 Behcet'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 Behcet'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 (ulcerative colitis). Areas of inflammation of the small intestine (regional enteritis) and the impaired ability to absorb nutrients properly by the small intestine (malabsorption) may also occur.

Approximately 10%-20% of individuals with Behcet's syndrome also have involvement of the central nervous system. These symptoms usually appear about 16 months after the initial symptoms of Behcet's syndrome. Recurring attacks of inflammation of the membranes that surround the spinal cord (meningoencephalitis) or brain (meningitis) can result in neurological damage. Symptoms may include the inability to coordinate voluntary movement (cerebellar ataxia), impaired muscle movements of the face and throat (pseudobulbar palsies), and/or seizures.

Behcet's syndrome may also cause inflammation of the blood vessels (vasculitis). Inflammation of the large veins, particularly those in the legs, may occur along with the formation of blood clots (thrombophlebitis). If a blood clot breaks away from the lining of the vein, it can travel to an artery, causing that vessel to become blocked (embolus). The walls of the artery may bulge forming a sac and obstructing other vessels (aneurysm). In rare cases, blood clots travel to the lungs (pulmonary emboli) resulting in episodes of chest pain, coughing, difficult or labored breathing (dypsnea), and coughing up blood (hemoptysis).

In rare cases, individuals with Behcet’s syndrome may develop abnormalities affecting the kidney and urinary tract including inflammation of the filtering structures (glomeruli) or the kidneys (glomerulonephritis).
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The exact cause of Behcet's syndrome is not known. Some 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.

Other research suggests that Behcet's syndrome may be an autoimmune disease. 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. Viral infections have also been suggested as a possible cause for the disorder.

In addition, researchers have demonstrated that certain individuals with Behcet’s syndrome, especially those of Middle Eastern and Asian descent, have an increased frequency of certain "human leukocyte antigens" (HLAs) in the blood. Antigens are any substance that stimulates the body’s immune system to produce certain antibodies in response to perceived invaders, such as microorganisms or foreign tissues. Individuals with Behcet’s syndrome are more likely to have HLA-B51 than the general population. The possible role of HLA-B51 in predisposing individuals to Behcet’s syndrome and its overall association with the disorder is unknown.

Behcet'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, once known as the Silk Road. Turkey has the highest prevalence rate (80-370 cases per 100,000); Japan, Korea, China, Iran, and Saudi Arabi 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 are more commonly affected in Middle Eastern countries. About 15,000 individuals may be affected by Behcet's syndrome in the United States. Central nervous system involvement is more common among native populations of northern Europe and the United States.

Symptoms of the following disorders can be similar to those of Behcet's syndrome. Comparisons may be useful for a differential diagnosis:

Reiter's syndrome is a rare infectious disorder characterized by arthritis, inflammation of the urinary tract (non-gonococcal urethritis), and inflammation of the membranes that line the eyes (conjunctivitis). Lesions may also appear on the skin and mucous membranes. The symptoms may not all appear at once. There may by spontaneous remissions and recurrences. Symptoms may include blood in the urine (hematuria), swollen painful joints, and ulcers in the mouth. Occasionally the iris of the eyes may become inflamed (iritis). This disorder can be transmitted through sexual contact. (For more information on this disorder, choose "Reiter" as your search term in the Rare Disease Database.)

Stevens-Johnson syndrome is a rare skin disorder characterized by large bullous lesions on the skin and mucous membranes of the mouth, throat, nose, eyes, and genitals. The lesions are typically painful. Inflammation of the membranes that line the eyes (conjunctivitis) may also occur and be accompanied by a discharge. This can lead to scarring of the cornea and loss of vision. Some people may experience fever and fatigue. (For more information on this disorder, choose "Stevens-Johnson" as your search term in the Rare Disease Database.)

Sweet Syndrome is a rare skin disorder characterized by painful red eruptions usually on the arms, face, neck, and legs. Major symptoms of Sweet syndrome are tender or painful skin eruptions and general feeling of discomfort (malaise). Skin lesions usually occur on the arms, but also on the face, neck, legs, and occasionally the thighs and trunk. The lesions may be up to an inch in diameter. They are usually bluish-red, irregular, flat or raised, sharply outlined, circular, and/or hardened, with a rounded edge. Scarring is usually absent. Remission may occur after a few weeks, but recurrences are possible. On rare occasions, the female genital tract (vagina and uterus) may be involved. The exact cause of this disorder is not known. (For more information on this disorder, choose "Sweet" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of Behcet’s syndrome is made based upon the identification of recurrent oral ulcerations (aphthous stomatitis) that occur along with at least two of the following: eye lesions, skin lesions, 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 growth (erythematous nodule or pustule) greater than 2 millimeters in diameter forms between 24-48 hours after the prick.

Treatment
The treatment of Behcet’s syndrome is directed toward the specific symptoms that are apparent in each individual. Specific therapies for Behcet’s syndrome are symptomatic and supportive.

Spontaneous remission is common for individuals with Behcet's syndrome. Corticosteroid creams that are applied to the skin may relieve the pain of ulcers. Mouthwashes that contain a local anesthetic, such as xylocaine or lidocaine, may temporarily relieve pain. Eye drops that contain corticosteroids may help relieve pain affecting the eyes. Continuing therapy with the drug colchicine may be effective in preventing recurring attacks of oral and genital ulcers and uveitis.

Inflammation of the joints, skin, and/or mucous membranes may be reduced with high-dose oral corticosteroid drugs. However, corticosteroids do not prevent recurring episodes of symptoms and questions exist as to their effectiveness in treating posterior uveitis associated with Behcet's syndrome. The drug chlorambucil has been successful in treating uveitis, but the possible harmful side effects of this drug must be carefully evaluated.

Arthritis associated with Behcet’s syndrome may also be treated with cholchicine and nonsteroidal anti-inflammatory drugs (NSAIDs). Sulfasalazine and corticosteroids may be administered to treat inflammatory bowel disease and gastrointestinal lesions associated with Behcet’s syndrome. Central nervous systems abnormalities may be treated with corticosteroids as well. Anticoagulants and antiplatelets agents should be given to individuals with clotting of major blood vessels.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Research published in the February 17, 2000, issue of The Lancet suggested that low-dose interferon-alpha might play a role in reducing symptoms associated with Behcet's disease. In the study, newly diagnosed patients with no history of eye problems were given interferon in addition to the more conventional drugs used to prevent retinal damage. The results were promising enough to suggest that additional research on this treatment approach would be warranted.

Interferon-alpha was designated an orphan drug by the U.S. Food and Drug Administration (FDA) in 2000. Additional study of this drug continues through a partnering agreement between Amarillo Biosciences, Inc., of Texas and Atrix Laboratories, Inc. For information, contact:

Atrix Laboratories, Inc.
2579 Midpoint Drive
Fort Collins, CO 80525
Tel: (970) 482-5868

Immunosuppressive drugs such as azathioprine (Imuran), chlorambucil (Leukeran), cyclophosphamide (Cytoxan), and cyclosporine (Sandimmune) have being studied for use as treatments for Behcet's syndrome. 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 Behcet's syndrome return quickly when the drug is stopped.

Researchers are studying the use of azathioprine (Imuran) to control the progression of eye disease in people with Behcet's syndrome. More research is needed to determine the long-term safety and effectiveness of this drug as a treatment for Behcet's syndrome.

Celgene Corporation has filed an Investigational New Drug Application (IND) for the use of the orphan drug thalidomide as a treatment for Behcet's syndrome. Thalidomide can have severe effects on a developing fetus and must be administered with extreme caution. More studies are needed to determine the long-term safety and effectiveness of this treatment. For more information, physicians can contact:

Celgene Corporation
7 Powder Horn Drive
Warren, NJ 07059
Tel: (732) 271-1001
Tollfree: (888) 423-5436

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Behcet Syndrome. Entry No: 109650; Last Update:10/24/2003.

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REVIEW ARTICLES
Uzun S, Alpsoy E, Durdu M, et al. The clinical course of Behcet’s disease in pregnancy: a retrospective analysis and review of the literature. J Dermatol. 2003;30:499-502.

Yazici H. Behcet’s syndrome: an update. Curr Rheumatol Rep. 2003;5:195-99.

Hirohata S, Kikuchi H. Behcet’s disease. Arthritis Res Ther. 2003;5:139-46.

Nussenblatt RB. Bench to bedside: new approaches to the immunotherapy of uveitic disease. Int Rev Immunol. 2002;21:273-89.

Andrews J, Haskard DO. Current management options in Behcet’s disease. Minerva Med. 2002;93:335-45.

Goker B, Goker H. Current therapy for Behcet’s disease. Am J Ther. 2002;9:465-70.

Shek LP, Lim DL. Thalidomide in Behcet’s disease. Biomed Pharmacother. 2002;56:31-35.

Bang D. Clinical spectrum of Behcet’s disease. J Dermatol. 2001;28:610-13.

JOURNAL ARTICLES
Tugal-Tutkin I, Urgancioglu M. Childhood-onset uveitis in Behcet disease: a descriptive study of 36 cases. Am J Ophthalmol. 2003;136:1114-19

Inomata H, Yoshikawa H, Rao NA. Phacoanaphylaxis in Behcet's disease: a clinicopathologic and immunohistochemical study. Ophthalmology. 2003; 110:1942-45.

Altiparmak MR, et al. Glomerulonephritis in Behcet’s disease: report of seven cases and review of the literature. Clin Rheumatol. 2002;21:14-18.

Sakane T, et al. Behcet’s disease. N Engl J Med. 1999;341:1284-91.

Filali-Ansary N, et al. Behcet disease. 162 cases. Ann Med Interne. 1999;150:178-88.

FROM THE INTERNET
NINDS Behcet’s Disease Information Page. Reviewed 09-04-2003. 2pp.
www.ninds.nih.gov/health_and_medical/disorders/behcet_doc.htm

Questions and Answers About Behcet’s Disease. NIAMS National Institute of Arthritis and Musculoskeletal and Skin Diseases. Publication Date: January 1999. 8pp.
www.niams.nih.gov/hi/topics/behcets.htm

Lisse. JR. Behcet Disease. emedicine. Last Updated: March 1, 2004. 23pp.
www.emedicine.com/med/topic218.htm

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www.emedicine.com/derm/topic/topic49.htm

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Diagnosis. Last Updated: November 8, 2002. 2pp.
Most Common Symptoms and Signs. Last Updated April 1, 2002. 2pp
www.behcets.com