Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis characterized by an inflammatory infiltrate composed of neutrophils with fibrinoid necrosis and "leukocytoclasia", a term that refers to nuclei disintegration into fragments. LCV is related to multiple conditions including ANCA-associated vasculitis, cryoglobulinemia, IgA vasculitis, infectious and systemic diseases such as rheumatoid arthritis and systemic erythematous lupus (SLE) as well as infections and malignancy. We describe the clinical case of severe systemic vasculitis in a young male patient with secondary syphilis and HIV coinfection manifested by cutaneous and neurological involvement, as well as peripheral necrosis that requires bilateral lower limb amputation. The skin biopsy revealed histopathological changes compatible with endarteritis obliterans and LCV related to treponemal infection. This case highlights the plethora of clinical manifestations of treponemal infection and the diagnostic challenge this poses in current clinical practice.