Behçet’s SyndromeDz

Definition: Behçet’s syndrome is a syndrome of recurrent, painful oral and genital lesions associated with uveitis and other forms of systemic inflammation.

ICD-9 Codes: 136.1; with arthropathy, 711.2.
ICD-10 Codes: M35.2

Etiology: Behçet’s syndrome is a relapsing small vessel vasculitis of uncertain etiology. There is evidence suggesting immune-complex deposition, hyperfunctioning neutrophils, increased levels of circulating IL-6, and a decreased CD4:CD8 T cell ratio. HLA-B5 and subtype HLA-B51 may be risk factors in afflicted Japanese patients.

Pathology: Histology of skin lesions may show perivascular inflammation or vasculitis, with both neutrophilic and monocytic infiltrates.

Demographics: Behçet’s syndrome is most common in the eastern Mediterranean (Turkey) and Japanese (prevalence approximately one in 1,000) populations. In the United States, the prevalence is 0.3 to 6.6 cases per 100,000. The male:female ratio is 2:1 to 5:1, and the mean age of onset is approximately 40 years. Behçet’s syndrome is one of the leading causes of acquired blindness in Japan.

Cardinal Findings: The prevalence of findings ranges widely betwen nonendemic (i.e. North American) and endemic (i.e. Turkish) populations. Aphthous stomatitis (100% prevalence) is usually the first manifestation. Very painful lesions occur in crops and may last 1 to 2 weeks and often heal with scarring. Oral ulcers are most commonly found on the buccal or gingival mucosa or tongue. Painful genital ulcers (70%–100%) occur on the vulva or vagina in women (often during menses) and penis or scrotum in men. Genital ulcers resemble oral aphthae but tend to recur less frequently. Ocular findings (50%–90%) are usually bilateral and occur 2 to 3 years after initial symptoms. Anterior uveitis, with hypopyon (pus in anterior chamber of the eye), and posterior uveitis may result in visual loss and be caused by retinal, macular, or choroidal vessel vasculitis. Arthritis (40%–50%) is usually episodic, monarticular, or oligoarticular. Large joints are more commonly affected than small joints. Arthralgias are more common than frank arthritis. Cutaneous lesions (30%–65%) include pustules, erythema nodosum, papules/pseudofolliculitis, and severe acneform lesions. Nodules are also seen secondary to superficial phlebitis. Pathergy, nearly unique to Behçet syndrome, occurs when pricking the skin with a needle leads to development of a sterile pustule. Central nervous system (5%–30%) manifestations of headaches, meningoencephalitis, ocular and other cranial nerve palsies, seizures, cerebrovascular insufficiency, brainstem syndrome leading to cerebellar ataxia, and pseudobulbar palsy have all been reported. Phlebitis/arteritis (25%) with thromboses of large veins/ arteries and aneurysms (of the aorta and pulmonary arterial tree) may occur. Chiari syndrome, dural sinus thrombosis, limb ischemia, stroke, and renovascular hypertension have been reported.

Uncommon Findings: Colitis and epididymitis are seen in a minority of patients. Nephritis and amyloidosis have rarely been noted. The rarely seen MAGIC syndrome (mouth and genital ulceration with inflamed cartilage) has overlapping features of Behçet’s syndrome and relapsing polychondritis.

Complications: The most feared common complication is blindness from eye manifestations. Neurologic and vascular complications (thrombotic events) are responsible for most of the severe morbidity and potential mortality.

Diagnostic Testing: Nonspecific measures of systemic inflammation include elevated acute-phase reactants (ESR and CRP), leukocytosis, anemia of chronic inflammation, and thrombocytosis. With significant CNS involvement, the cerebrospinal fluid (CSF) typically shows a mononuclear cell pleocytosis and elevated protein levels. Patients with thromboses may have APL antibodies.

Differential Diagnosis: Other forms of systemic vasculitis [polyarteritis nodosa (PAN)] and SLE should be considered. Oral and genital lesions may be confused with inflammatory bowel disease or reactive arthritis. The oral ulcers of SLE or reactive arthritis are usually painless and palatal. Uveitis should raise the possibility of other inflammatory disease (i.e., SpA) as well as infectious causes. Skin manifestations resemble those of Sweet’s syndrome, disseminated gonococcus or Stevens-Johnson syndrome. Large vessel vasculitis may mimic Takayasu’s arteritis.

Keys to Diagnosis: Look for the triad of oral ulcers, genital lesions, and uveitis. Although pathergy is nearly pathognomonic, it is infrequently seen among North American whites.

Diagnostic Criteria: Criteria of the International Study Group are

A. Recurrent oral ulceration (at least three times in 1 year), plus

B. Two of the following four criteria:

1. Recurrent genital ulcerations

2. Eye lesions-uveitis or retinal vasculitis

3. Skin lesions-erythema nodosum, pseudofolliculitis, papulopustular lesions, or unexplained acne

4. Pathergy

Therapy: Intermittent prednisone (10–40 mg/day) is effective in the control of recurrent ulcerations, but long-term use should be discouraged because of the risk of steroid toxicity. Colchicine, dapsone, and levamisole may also be used to treat skin/mucocutaneous manifestations. Active uveitis or CNS disease merits aggressive therapy with high-dose corticosteroids, cytotoxic agents (e.g., azathioprine, chlorambucil, cyclophosphamide), or cyclosporine. Thalidomide and TNF inhibitors have been used successfully for refractory oral and genital ulcers and sight-threatening eye disease. Colchicine, NSAIDs, or sulfasalazine may be effective for Behçet’s syndrome–associated arthritis. Chronic anticoagulation may be required for thrombotic complications.

Prognosis: Oral and genital lesions frequently predate vascular and neurologic manifestations by months or years. Relapses are common over a 5- to 7- year period before a reduction in disease activity may occur.

BIBLIOGRAPHY

International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990;335:1078–1080. PMID:1970380

Yazici H. Behçet’s syndrome: an update. Curr Rheumatol Rep 2003;5:195–199.PMID:12744810