Immunopathogenesis of Behcet's disease and treatment modalities

Introduction: Behcet's disease (BD) is an auto-inflammatory disease, primarily characterized by recurrent painful mucocutaneous ulcerations. Methods: A literature search was performed to write a narrative review into the pathogenesis and current treatment options of BD. Results: The pathogenesis of BD remains to be elucidated, but is considered a genetically primed disease in which an external trigger causes immune activation resulting in inflammatory symptoms. GWAS data show an association between multiple genetic polymorphisms (HLA-B51, ERAP1, IL10 and IL23R-IL12RB2) and increased susceptibility to BD. Bacteria as streptococci, an unbalanced microbiome or molecular mimicry trigger the inflammation in BD. Increased production or responsiveness of pro-inflammatory components of the innate immune response (TLR, neutrophils, NK-cells or gd T-cells) to these triggers may be a crucial step in the pathogenesis of BD. Additionally to an increased autoinflammatory response there is evidence of a dysregulated adaptive immune system, with a disturbed Th1/Th2 balance, expansion of Th17 cells and possibly a decrease in regulatory T cells, resulting in a surplus in pro-inflammatory cytokines. The inflammation causes a typical clinical phenotype including orogenital ulcerations, uveitis and skin lesions. Treatment is aimed at the aberrations found in the innate (neutrophils and gd-T cells) and adaptive immune system (TNF-alpha, INF-gamma, IL-1), directed at organ involvement and individualized based on patient characteristics. Conclusion: We presented an extensive review into the pathogenesis and treatment options of BD. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

Behcet's disease is an auto-inflammatory disease characterized by recurrent painful mucocutaneous ulcerations. The pathogenesis involves genetic susceptibility, microbial triggers, and dysregulated immune responses. Treatment focuses on controlling inflammation and managing organ involvement based on individual characteristics.