Chapter 357: Behçet’s Syndrome

DEFINITION, INCIDENCE, AND PREVALENCE

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 357-1).

The syndrome affects young males and females from the Mediterranean region, the Middle East, and the Far East. The frequency of Behçet’s syndrome increases from north to south Europe. Males and females are affected equally. Males often have more severe disease. The syndrome is rare in Sub-Saharan Africa.

PATHOGENESIS

The etiology and pathogenesis of this syndrome remain obscure. The disease appears to be in the crossroads of autoinflammatory and autoimmune disorders. 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 activated neutrophils, increased numbers of infiltrating T_H1, T_H17, cytotoxic CD8+, and γδ T cells are observed, supporting a link between innate and adaptive autoreactive immune response. Circulating autoantibodies against α-enolase of endothelial cells, selenium binding protein, and anti-Saccharomyces cerevisiae antibodies have been observed, but their pathogenic role remains unclear. A recent genome-wide association study confirmed the known association of Behçet’s syndrome with HLA-B*51 and identified a second, independent association within the major histocompatibility complex (MHC) class I region. In addition, an association with interleukin (IL) 10 and the IL-23R–IL-12RB2 locus was also observed. Interestingly, the disease-associated IL-10 variant was correlated with diminished mRNA expression and low protein production.

CLINICAL FEATURES

The recurrent oral aphthous ulcerations are a sine qua non for the diagnosis. The ulcers are usually painful, shallow or deep with a central yellowish necrotic base, appear singly or in crops, and can be located anywhere in the oral cavity. Small ulcers, <10 mm in diameter, are seen in 85% of patients, whereas 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 and vulvar scars.

Skin involvement is observed in 80% of patients and includes folliculitis, erythema nodosum, acne-like rashes, and, infrequently, vasculitis, Sweet syndrome, and pyoderma gangrenosum. Nonspecific skin inflammatory reactivity to scratch or intradermal saline injection (pathergy test) is a specific manifestation.

Eye involvement with scarring and bilateral panuveitis is the most dreaded complication, since it occasionally progresses rapidly to blindness. Uveitis occurs in 10–15% of patients, primarily ...