Behçet’s syndrome is classically characterized as a triad of symptoms that include recurring crops of mouth ulcers (aphthous ulcers, canker sores), genital ulcers, and inflammation of a specialized area around the pupil of the eye termed the uvea.
The inflammation of the area of the eye that is around the pupil is called uveitis. Behçet’s syndrome is also sometimes referred to as Behçet’s disease.
The cause of Behçet’s syndrome is not known. The disease is relatively rare but is more frequent and severe in patients from the Eastern Mediterranean and Asia than those of European descent.
Both inherited (genetic) and environmental factors, such as microbe infections, are suspected to be factors that contribute to the development of Behçet’s syndrome. Behçet’s syndrome is not proven to be contagious.
What are symptoms of Behçet’s syndrome?
The symptoms of Behçet’s syndrome depend on the area of the body affected. Behçet’s syndrome can involve inflammation of many areas of the body.
These areas include the arteries that supply blood to the body’s tissues. Behçet’s syndrome can also affect the veins that take the blood back to the lungs to replenish oxygen.
Other areas of body that can be affected by the inflammation of Behçet’s syndrome include the back of the eyes (retina), brain, joints, skin, and bowels.
The mouth and genital ulcers of Behçet’s syndrome are generally painful and tend to recur in crops (many shallow ulcers occur at the same time).
They range in size from a few millimeters to 20 millimeters in diameter. The mouth ulcers occur on the gums, tongue, and inner lining of the mouth.
The genital ulcers occur on the scrotum and penis of males and vulva of women and can leavescars.
Inflammation of the eye, which can involve the front of the eye (uvea) causing uveitis, or the back of the eye (retina) causing retinitis, can lead to blindness. Symptoms of eye inflammation include pain, blurred vision, tearing, redness, and pain when looking at bright lights. It is very important for patients with BBehçet’s syndrome to have this sensitive area monitored by an eye specialist (ophthalmologist).
If the arteries become inflamed (arteritis) from Behçet’s syndrome, it can lead to death of the tissues whose oxygen supply depends on these vessels.
This could cause a stroke if it is affecting the brain vessels, belly pain if affecting the bowel, etc.
When veins become inflamed (phlebitis), the inflammation can involve large veins that develop blood clots which can loosen and migrate to cause pulmonary embolisms.
Symptoms of inflammation of the brain or tissue that covers the brain (meninges) include headaches, neck stiffness, and is often associated with fever.
Inflammation of the brain (encephalitis) and/or the meninges (meningitis) can cause damage to nervous tissue and lead to weakness or impaired function of portions of the body.
This can result in confusion and coma. Typically these features occur later in the disease course, years after the diagnosis.
Joint inflammation (arthritis) can lead to swelling, stiffness, warmth, pain, and tenderness of joints with Behçet’s syndrome.
This occurs in about half of patients with Behçet’s syndrome at sometime during their lives. Knees, wrists, ankles, and elbows are the most common joints affected.
The skin of patients with Behçet’s syndrome can develop areas of inflammation that spontaneously appear as raised, tender, reddish nodules (erythema nodosum), typically on the front of the legs.
Some patients with Behçet’s syndrome develop a peculiar red or blistery skin reaction in places where they have been pierced by blood-drawing needles (see pathergy test in diagnosis section).
Research has found that acne occurs more frequently in patients with Behçet’s syndrome that also have arthritis as a manifestation.
Ulcerations can occur at any location in the stomach, large or small bowel in patients with Behçet’s disease.
Who gets Behcet’s Disease (the “typical” patient)?
Behcet’s disease is most common along the “Old Silk Route,” which spans the region from Japan and China in the Far East to the Mediterranean Sea, including countries such as Turkey and Iran.
Although the disease is rare in the United States, sporadic cases do occur in patients who would not appear to be at risk because of their ethnic backgrounds (e.g., in Caucasians or African–Americans).
The disease is not rare in regions along the Old Silk Route, but the disease’s epidemiology is not well understood. In Japan, Behcet’s disease ranks as a leading cause of blindness.
Below is a magnetic resonance image (MRI) study of a Behcet’s patient demonstrating central nervous system involvement (white matter changes in the pons).
What causes Behcet’s Disease?
Behcet’s is one of the few forms of vasculitis in which there is a known genetic predisposition. The presence of the gene HLA–B51 is a risk factor for this disease.
However, it must be emphasized that presence of the gene in and of itself is not enough to cause Behcet’s: many people possess the gene, but relatively few develop Behcet’s.
the predisposition to Behcet’s conferred by HLA–B51, familial cases are not the rule, constituting only about 5% of cases.
Thus, it is believed that other factors (perhaps more than one) play a role. Possibilities include infections and other environmental exposures.
How is Behcet’s Disease Diagnosed?
There is not one specific test to diagnose Behcet’s. Rather the diagnosis is based on the occurrence of symptoms and signs that are compatible with the disease.
Tthe presence of certain features that are particularly characteristic (e.g., oral or genital ulcerations), elimination of other possible causes of the patient’s symptom, and if possible, proof of vasculitis by biopsy of an involved organ all would support a diagnosis of Behcet’s.
A positive pathergy test can be supportive of the diagnosis of Behcet’s but is not diagnostic by itself of the conidtion. A pathergy test is a simple test in which the forearm is pricked with a small, sterile needle.
of a small red bump or pustule at the site of needle insertion constitutes a positive test.
Please note, that although a positive pathergy test is helpful in the diagnosis of Behcet’s, only a minority of Behcet’s patients demonstrate the pathergy phenomenon (i.e., have positive tests).
Patients from the Mediterranean region are more likely to demonstrate pathergy. In addition, other conditions can occasionally result in positive pathergy tests, so the test is not 100% specific.
Pictured below is an example of the pathergy test; 1) taken at the time when the patient was “stuck” with the sterile needle; 2) shows the area immediately after the stick; 3) & 4) show the area one day and two days after the needle stick, respectively.
What is the treatment of Behçet’s syndrome?
The treatment of Behçet’s syndrome depends on the severity and the location of its manifestations in an individual patient.
Steroid (cortisone) gels, pastes (such as Kenolog in Orabase) and creams can be helpful for the mouth and genital ulcers. Colchicine (Colcrys) can also minimize recurrent ulcerations.
Trental (pentoxifylline) has also been used in the treatment of oral and genital ulcers.
Joint inflammation can require nonsteroidal anti-inflammatory drugs (such as ibuprofen and others) or oral steroids.
Colchicine and oral and injectable cortisone are used for inflammation involving the joints, eyes, skin, and brain.
Sulfasalazine (Azulfidine) has been effective in some patients for arthritis. Bowel disease is treated with oral steroids and sulfasalazine.
Diligent treatment of eye inflammation is essential. Patients with eye symptoms or a history of eye inflammation should be monitored by an ophthalmologist.
Resistant eye inflammation can often respond to new biologic medications that block a protein that plays a major role in initiating inflammation, called TNF. These TNF-blocking medications, including infliximab (Remicade) and adalimumab (Humira), can also be helpful for severe mouth ulcerations.
Severe disease of the arteries, eyes, and brain can be difficult to treat and require powerful medications that suppress the immune system called immunosuppressive agents.
Immunosuppressive agents used for severe Behçet’s syndrome include chlorambucil (Leukeran), azathioprine (Imuran), and cyclophosphamide (Cytoxan). Cyclosporine has been used for resistant disease.
Studies suggest that thalidomide (Thalomid) may be of benefit for certain patients with Behçet’s syndrome in treating and preventing ulcerations of the mouth and genitals.
effects of thalidomide include promoting abnormal development of fetal growth, nerve injury (neuropathy), and hypersedation.
Trials are currently underway evaluating interferon alpha for the treatment of eye disease in patients with Behçet’s syndrome.