A Complex Case of Behçet’s Disease With Severe Genital Ulceration: Diagnostic Challenges

Behçet's syndrome (BS) is a chronic, multisystem variable vessel vasculitis defined by recurrent oral and genital ulcers, diverse mucocutaneous lesions, and potential involvement of the eyes, joints, vasculature, central nervous system, and gastrointestinal tract. Diagnosis remains a clinical challenge given the absence of pathognomonic laboratory or histological findings. We present a case of a 36-year-old Caucasian male patient with hypothyroidism who developed a severe, rapidly progressive first episode of BS characterized by hemorrhagic vesicular and bullous skin lesions, oral ulceration, and necrotic genital ulceration requiring surgical debridement. Extensive infectious evaluation, including plasma cell-free metagenomic next-generation sequencing (cf-mNGS), was entirely negative. Serologic workup was unremarkable; HLA-B51 was negative, and pathergy was equivocal. Skin punch biopsy demonstrated pan-dermal neutrophilic inflammation with acute vasculitis and focal epidermal necrosis - a critical histopathological feature distinguishing BS from Sweet syndrome, in which true vasculitis is characteristically absent. Under the International Criteria for Behçet's Disease (ICBD), the patient scored ≥4 points (oral ulcers: 2 points; genital ulcers: 2 points; skin lesions: 1 point). He responded to high-dose corticosteroids (prednisone 50 mg daily) and colchicine, achieving full remission within nine weeks with no recurrence. This case illustrates the diagnostic complexity of BS in the absence of classic genetic markers, emphasizes histopathology as the critical discriminator from neutrophilic dermatosis mimics, and underscores the importance of systematic multidisciplinary evaluation before initiating immunosuppressive therapy.