Behçet's syndrome is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as ocular involvement. The diagnosis is clinical and based on internationally agreed diagnostic criteria (Table 327-1).
Table 327-1 Diagnostic Criteria of Behçet's Disease
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Table 327-1 Diagnostic Criteria of Behçet's Disease
Recurrent oral ulceration plus two of the following:
Recurrent genital ulceration
The syndrome affects young males and females from the Mediterranean region, the Middle East, and the Far East, suggesting a link with the ancient Silk Route. Males and females are affected equally, but males often have more severe disease. Blacks are very infrequently affected.
The etiology and pathogenesis of this syndrome remain obscure. The main pathologic lesion is systemic perivasculitis with early neutrophil infiltration and endothelial swelling. In some patients, diffuse inflammatory disease, involving all layers of large vessels and resulting to formation of pseudoaneurysms, suggests vasculitis of vasa vasorum. Apart from neutrophils, increased numbers of infiltrating CD4+ T cells are observed. Circulating autoantibodies against α-enolase of endothelial cells, selenium binding protein and anti-Saccharomyces cerevisiae antibodies (ASCA—characteristic of Crohn's A recent genome-wide association study, confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. In addition, an association with IL10 and the IL23R-IL12RB2 locus were also observed. Interestingly, the disease-associated IL10 variant was correlated with diminished mRNA expression and low protein production.
The recurrent aphthous ulcerations are a sine qua non for the diagnosis. The ulcers are usually painful, are shallow or deep with a central yellowish necrotic base, appear singly or in crops, and are located anywhere in the oral cavity. Small ulcers, less than 10 mm in diameter are seen in 85% of patients, while large or herpetiform lesions are less frequent. The ulcers persist for 1–2 weeks and subside without leaving scars. The genital ulcers are less common but more specific, are painful, do not affect the glans penis or urethra, and produce scrotal scars.
Skin involvement is observed in 80% of patients and includes folliculitis, erythema nodosum, an acne-like exanthem, and, infrequently, vasculitis, Sweet's syndrome, and pyoderma gangrenosum. Nonspecific skin inflammatory reactivity to any scratches or intradermal saline injection (pathergy test) is a common and specific manifestation.
Eye involvement with scarring and bilateral panuveitis is the most dreaded complication, since it occasionally progresses rapidly to blindness. The eye disease, occurring in 50% of patients, is usually present at the onset but may also develop within the first few years. In addition to iritis, posterior uveitis, retinal vessel occlusions, and optic neuritis can be seen in some patients with the syndrome.
Non-deforming arthritis or arthralgias are seen in a 50% of patients and affects the knees and ankles.
Superficial or deep peripheral vein thrombosis is seen in 30% of patients. Pulmonary emboli are a rare complication. The superior vena cava is obstructed occasionally, producing a dramatic clinical picture. Arterial involvement occurs in less than 5% of patients and presents with aortitis or peripheral arterial aneurysm and arterial thrombosis. Pulmonary artery vasculitis presenting with dyspnea, cough, chest pain, hemoptysis, and infiltrates on chest roentgenograms has been reported in 5% of patients and should be differentiated from thromboembolic disease since it warrants anti-inflammatory and not thrombolytic therapy.
Neurologic involvement (5–10%) appears mainly in the parenchymal form (80%); it is associated with brainstem involvement and has a serious prognosis (CNS-Behçet's syndrome). IL-6 is persistently raised in cerebrospinal fluid of these patients. Dural sinus thrombi (20%) are associated with headache and increased intracranial pressure. MRI and/or proton magnetic resonance spectroscopy (MRS) are very sensitive and should be employed if CNS-Behçet's syndrome is suspected.
Gastrointestinal involvement is seen more frequently in patients from Japan and consists of mucosal ulcerations of the gut, resembling Crohn's disease.
Epididymitis is seen in 5% of patients, while amyloidosis of AA type and glomerulonephritis are uncommon.
Laboratory findings are mainly nonspecific indices of inflammation, such as leukocytosis and elevated erythrocyte sedimentation rate, as well as C-reactive protein levels.
Treatment: Behçet's Syndrome
The severity of the syndrome usually abates with time. Apart from the patients with CNS-Behçet's syndrome and major vessel disease, the life expectancy seems to be normal and the only serious complication is blindness.
Mucous membrane involvement may respond to topical glucocorticoids in the form of mouthwash or paste. In more serious cases, thalidomide (100 mg/d) is effective. Thrombophlebitis is treated with aspirin, 325 mg/d. Colchicine can be beneficial for the mucocutaneous manifestations and arthritis. Uveitis and CNS-Behçet's syndrome require systemic glucocorticoid therapy (prednisone, 1 mg/kg per day) and azathioprine (2–3 mg/kg per day). Cyclosporin (5mg/kg) has been used for sight-threatening uveitis, alone or in combination with azathioprine. Pulse doses of cyclophosphamide are useful early in the course of the disease, for pulmonary or peripheral arterial aneurysms. Recent recommendations for anti–tumor necrosis factor therapy suggest that they may serve as an add-on immunosuppressive therapy in patients with panuveitis refractory or intolerant to other immunosuppressives.
Al-Araji A, Kidd DP: Neuro- Behçet's disease: Epidemiology, clinical characteristics, and management. Lancet Neurol 8:192, 2009
Hatemi G et al: Eular recommendations for the management of Behçet's disease. Ann Rheum Dis 67:1656, 2008
Kural-Seyahi E et al: The long-term mortality and morbidity of Behçet syndrome: A 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore) 82:60, 2003
Lee KH et al: Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease. Arthritis Rheum 48:2025, 2003