Beh？et's disease is a chronic, recurrent, multisystemic, inflammatory disorder affecting mainly the oral and urogenital mucosa and the uveal tract. Although the etiology and pathogenesis of Beh？et's disease are unknown, numerous etiologies have been proposed, including environmental, infectious, and immunological factors; an autoimmune basis, characterized by circulating immune complexes and complement activation, has gained increasing acceptance. To test and understand immunopathogenesis of Beh？et's disease, animal models were developed based on enviromental pollutants, bacterial and human heat shock protein derived peptides, and virus injections. Using these animal models separately and/or concurrently allows for a more effective investigation into Beh？et's disease. Animal models developed in the last 10 years aim at the development of efficient and safe treatment options. 1. Introduction Beh？et’s disease (BD) is a chronic, multisystemic, inflammatory disorder and is characterized by mucocutaneous, ocular, arthritic, vascular, gastrointestinal, and central nervous system involvement. The disease has a chronic course with periodic exacerbations and progressive deterioration [1]. Since the dermatologist Dr. Hulusi Beh？et [2] comprehensively described this disease involving multisystemic organs in 1937, the etiology of BD has still remained unclear. Various hypotheses have been proposed centering on viral infection, autoimmune disease, streptococcal-related antigens, specific alleles of the human major histocompatibility complex, genetic factors, and hazardous chemicals [3–7]. The history and recent developments in the immunopathogenesis of BD are reviewed and discussed in this paper. 2. Short History Viral infection has long been postulated as one of the etiologic and triggering factors. Hulusi Beh？et proposed that the disease was caused by a special virus. Although he was unable to demonstrate one, he had observed intracellular inclusion-like forms in smears from the hypopyon of the anterior chamber and aphthae [2]. In 1953, Sezer [8] was the first to isolate the virus from ocular fluid and serially cultivate it in chorioallantoic membrane of fertile eggs. He inoculated the material from the ocular fluid of patients into brains of mice. Inoculated mice showed manifestation such as roughening of the coat, inactivity or hyperactivity, tremor, circling, paralysis, encephalitis, thrombophlebitis, and swelling. Evans et al. [9] isolated the virus from the eye and brain of a patient who died of the disease. Mortada and Imam [10] found inclusion bodies from
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