A chronic, relapsing multisystemic autoinflammatory condition with a genetic predisposition.
Behçet Disease; Adamantiades-Behçet Disease; Oculo-Orogenital Syndrome; Silk Road Disease.
The disorder is named after the Turkish dermatologist Hulusi Behçet, who described it in 1937. However, the Greek ophthalmologist Benedikt Adamantiades described the first patient with this disease in 1931 (and orally presented the findings at a meeting already in 1930). To be historically correct though, it should be noted that Hippocrates described this disease already in the fifth century BC. Thus, the disease should correctly be named Hippocrates-Adamantiades-Behçet Disease/Syndrome.
The prevalence is highest in Turkey (20-420:100,000 in the general population), the Middle East and in Asia along the Silk Road. However, it has been reported from many parts of the world and in Europe the prevalence is in the range of 0.6 to 2.5 in 100,000 and 0.1 to 0.3 in 100,000 in the United States. Male gender is predominant, especially for severe BS.
The majority of cases are sporadic, but familial forms have been described. BS has been associated with HLA-B51 in up to 80% of patients (highest rate along the Silk Road), but the significance of this finding for the pathogenesis has not been established, yet. It may play a role in the exaggerated activation of neutrophils (with increased phagocytosis, chemotaxis, superoxide, and lysosomal enzyme production). Other factors that have been implicated in the pathogenesis of BS are tumor necrosis factor (TNF)-alpha-1031C allele and polymorphisms in interleukin 8, 10, 17, 21, and 23.
Behçet Syndrome: Ulcerations on the mucosa of the lower lip of a patient with Behçet disease.
The hallmark of BS is a multisystemic vasculitis involving large and small vessels to various degrees. The cause has not been defined, but an autoimmune pathogenesis, including an abnormal T-cell response to microbial antigens and cross-reaction toward body tissue, has long been suspected. The immunological and inflammatory processes are promoting a hypercoagulable state with increased risk for thrombosis due to impaired fibrinolysis and endothelial cell damage and dysfunction resulting in decreased endothelial nitric oxide production and increased platelet aggregation. Platelet-neutrophils complex formation may play an important pathogenetic role in the thrombosis-inflammation progression. Elevated levels of thrombomodulin (a cofactor for thrombin), von Willebrand factor and plasminogen activator inhibitor in combination with low tissue plasminogen activator and antithrombin-III levels help sustain the prothrombotic state with decreased fibrinolysis. The chronic recurrent thromboses eventually lead to scaring of the affected vessels allowing the thrombus to adhere tightly to the vessel wall with a low risk for embolism. The skin pathergy test consists of 3 to 6 bilateral forearm skin micropunctures on the flexor side with a sterile ...