Pathophysiology
Clinical meaning
Behcet disease (BD) is a chronic, relapsing systemic vasculitis affecting vessels of all sizes, uniquely involving both arterial and venous systems. The NP must understand the immunopathogenesis to guide advanced diagnostic workup and treatment selection. The pathogenesis centers on neutrophilic hyperactivation and aberrant Th1/Th17 immune responses. The strongest genetic risk factor is HLA-B51, a class I MHC allele present in 50-70% of BD patients in endemic regions. HLA-B51 is hypothesized to present microbial peptides (particularly from oral streptococci and HSV-1) that trigger molecular mimicry and cross-reactive T-cell responses against vascular endothelium. Additionally, HLA-B51 misfolding in the endoplasmic reticulum may activate the unfolded protein response, driving IL-23 secretion and downstream Th17 polarization. Neutrophils in BD demonstrate pathological hyperreactivity: enhanced chemotaxis, superoxide generation, and neutrophil extracellular trap (NET) formation. This underlies the pathergy phenomenon (disproportionate pustular response to minor skin trauma) and the perivascular neutrophilic infiltration that damages vessel walls. Endothelial dysfunction from inflammatory cytokines (TNF-alpha, IL-6, IL-17) and oxidative stress promotes thrombosis (venous predominant) and aneurysm formation (arterial). The NP differential diagnosis for recurrent oral ulcers with systemic features includes: reactive...