Behçet Disease: An Update for Dermatologists

Abstract

Behçet disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology with the clinical features of oral and genital ulcers, cutaneous vasculitic lesions, ocular, articular, vascular, gastrointestinal, neurologic, urogenital and cardiac involvement. BD usually appears around the third or fourth decade of life. Gender distribution is roughly equal. The disease is much more frequent in populations along the ancient 'Silk Road', extending from Eastern Asia to countries in the Middle East and the Mediterranean, compared with Western countries, but has universal distribution. Mucocutaneous manifestations are the clinical hallmarks of BD. The diagnostic criteria widely used in the disease's diagnosis are based on mucocutaneous manifestations because of their high sensitivity and/or specificity. Genetic factors are the key driver of BD pathogenesis, and HLA-B51 antigen is the strongest genetic susceptibility factor. Streptococcus sanguinis (S. sanguinis) or microbiome change can trigger innate immune system-mediated inflammation sustained by adaptive immune responses. Epistatic interaction between HLA-B51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) in antigen-presenting cells disrupt T-cell homeostasis leading to downregulation of Tregs and expansion of Th1 and Th17. Thus, neutrophil activation and intense neutrophil infiltration of the affected organs develop in the early stage of inflammation. BD has a variable clinical course with unpredictable exacerbations and remissions. The disease is associated with a high mortality rate, especially in young male patients, and large-vessel, neurological, gastrointestinal system and cardiac involvement are the most important causes of death. The principal aim of treatment should be to prevent irreversible organ damage, especially during the disease's early, active phase. A better understanding of the disease's pathogenesis has provided important information on its management. New drugs, especially apremilast and anti-TNF-α agents are effective in the management of BD and have the potential to improve patients' quality of life, prognosis and survival.