Behçet’s Disease: Autoimmune or Autoinflammatory?

Behçet's disease (BD) is a systemic inflammatory disease characterized by recurrent oral aphthae, genital ulcers, ocular inflammation and skin lesions. Involvement of large vessels, central nervous system, and gastrointestinal tract, and thrombotic events are less frequent but can be life threatening. Ocular complications of BD are some of the most devastating for patients with a major impact on quality of life. Eye involvement, which affects 50-90% of BD patients, is characterized by intraocular inflammation and occlusive retinal vasculitis. 1 The etiology of BD is still unknown, but both genetic background and environmental factors are thought to be important in its pathogenesis. 2 BD has long been regarded as an autoimmune disease; however, it has recently been found that it shares several clinical features with autoinflammatory diseases. Autoinflammatory diseases are a group of inherited disorders caused by dysfunction of innate immunity and characterized by recurrent self-limited inflammatory attacks occurring at variable intervals without evident precipitating events. 3 The inflammatory process most commonly involves the skin, serous membranes, joints, gastrointestinal tract and eyes, and is associated with elevated levels of acute phase reactants but relative lack of high-titer autoantibodies or antigen-specific T cells. 4 The concept of " autoinflammatory " disease was introduced at the end of the 1990s and has grown rapidly in recent years as a result of advancements in molecular biology and genetics. Familial Mediterranean fever (FMF) is the prototype of this group of disorders which is characterized by recurrent painful attacks of fever and inflammation in the peritoneum, synovium, or pleura. FMF is an autosomal recessive disorder commonly found among individuals of Mediterranean descent and caused by MEFV gene mutations. 5 This gene encodes pyrin, which normally assists in keeping inflammation under control by deactivating the immune response. Without this control, an inappropriate full-blown inflammatory reaction occurs. 6 Autoinflammatory and autoimmune disorders are both characterized by aberrant chronic activation of the immune system eventually leading to tissue inflammation. However, the pathogenesis underlying this damage differs such that the innate immune system directly causes tissue inflammation in an autoinflammatory disease, whereas activation of the adaptive immune system in autoimmune disease is responsible for the inflammatory process. 7 Although autoinflammatory and autoimmune diseases are currently divided into two different subgroups, regarding their similarities they might be considered as a single spectrum of disorders with a wide range of manifestations including pure autoinflammatory diseases at one end and pure autoimmune diseases …