Pathogenesis of Behçet’s Syndrome

Although vascular injury is quite common in BS and can involve venous and arterial vessels of all sizes, frank necrotizing vasculitis of the small and medium-sized arteries as seen in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides is infrequent in patients with BS. Similarly infrequent are giant cells and immune complex–type cutaneous venulitis. These “negative” findings make the vascular involvement in BS unique. Furthermore, there is little evidence for vasculitis in some common lesions of BS. For example, there is no evidence for vascular injury in the papulopustular lesions of the skin and scanty evidence for a frank vasculitis in the CNS lesions. Conversely, the diffuse inflammatory disease in all layers of the large veins characteristically involving substantial segments of the vessel wall, the pulmonary artery aneurysms specific to this condition, and pseudoaneurysms of the large arteries (most probably secondary to vasculitis of the vasa vasorum) are unique findings.

The genetics of BS are, at present, uncertain. No clear Mendelian pattern has emerged. In endemic areas, approximately one in 10 families have more than one family member who is affected. The most consistent genetic association has been with HLA-B51, which explains only approximately 20% of the disease heritability.

It is currently popular to group BS with autoinflammatory disorders. This categorization is debatable given that most autoinflammatory conditions (with familial Mediterranean fever being a good example) are monogenic and predominantly pediatric conditions.

Recently, it has been noted that there may be some clustering in disease expression in BS. Through a series of mainly clinical observations, two clusters have been defined. The first is the cluster of superficial vein thrombosis, deep vein thrombosis, and dural sinus thrombi; the second cluster is that of acne, arthritis, and enthesitis.4 The association of acne with arthritis and the recent observation of the pustule lesions of BS being nonsterile brings into discussion a reactive arthritis type of disease mechanism, at least for this disease cluster.5 The presence of such clusters may suggest there is more than one disease mechanism involved in this complex disorder.

There are no specific laboratory findings in BS. The erythrocyte sedimentation rate and C-reactive protein level are usually moderately elevated, but these do not correlate well with disease activity. Autoantibodies such as rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, and antineutrophil cytoplasmic antibodies are not seen.

Diagnosis and Clinical Course

The diagnosis of BS is based on the recognition of a group of clinical features because no specific signs or symptoms have been identified. In 1990, the International Study Group published a set of diagnostic (classification) criteria.6 These criteria, with a sensitivity of 91% and specificity of 96%, have been validated and are widely used (see Table 1, above right).