Vasculopathy and vasculitis associated with levamisole-adulterated cocaine: a systematic review

Objective: Levamisole, once used as anthelminthic or immunomodulator, is now a common cocaine adulterant. It is linked to a systemic vasculopathy/vasculitis. Our purpose was to review its clinical, serological, and histopathological features. Methods: We conducted a registered systematic review (CRD42024558898) across three databases, without language or date restrictions. Reports documenting a vasculopathy/vasculitis temporally associated with levamisole — either prescribed or as a cocaine adulterant — were included. Results: 172 reports describing 302 patients were included. Most cases (N = 282; 93 %) involved cocaine adulterated with levamisole. The skin was involved in 274 (91 %) and the kidney in 64 (21 %) cases. Purpura (228; 83 %) and necrosis (141; 51 %) were the most common skin lesions, predominantly affecting ears and extremities. Among 186 classifiable skin biopsies, a thrombotic vasculopathy was detected in 65, a leukocytoclastic vasculitis in 52, and both a thrombotic vasculopathy and a vasculitis in 70 cases. Among 37 renal biopsies, a pauci-immune crescentic glomerulonephritis and a membranous nephropathy were the most detected features. Leukopenia occurred in 100 (33 %) cases. Among tested cases, anti-neutrophil cytoplasmic antibodies were detected in about 89 % of cases, mostly with a perinuclear (71 %) or an atypical (25 %) pattern. Antibodies targeting the myeloperoxidase were detected in 73 % of the cases. In patients receiving levamisole for therapeutic purposes, the vasculopathy resolved after levamisole withdrawal. A relapse of the vasculopathy was observed after re-exposed to levamisole. Conclusions: Levamisole-induced vasculopathy/vasculitis is a distinctive skin-predominant condition with characteristic clinical and serological features. Withdrawal of levamisole is the cornerstone of management.