Cocaine-Levamisole Thrombovasculopathy: A Report From the Southern Network On Adverse Reactions (SONAR) Project

In 2008, five emergency department patients with unexplained neutropenia and thrombovasculitis were reported from Vancouver, Canada. Similar reports have appeared from San Francisco, Denver, Providence, Chicago, New York, and Los Angeles.

156 case reports of patients of unexplained thrombovasculopathy were identified from the published literature or by SONAR.

The average patient age was 44 years old (SD, 11 years); 65% were female. The earliest time to symptom onset was 12 hours following last cocaine use. Dermatologic findings included retiform purpura, purpuric rash, hemorrhagic bullae, or skin necrosis (59% of cases), and lesions on the ears (35% of cases), upper extremities (33% of cases), torso (22% of cases), and the nose (10% of cases). Of 79 patients with available data, 72% presented with severe neutropenia (<1500cells/μl). Among 80 persons who had serologic studies, 95% demonstrated anti-neutrophil cytoplasmic antibodies, 31% were positive for proteinase 3 antibodies, 40% were positive for myeloperoxidase antibodies, 32% were positive for IgM cardiolipin antibodies, and 20% were positive for lupus anti-coagulant. Biopsies (primarily skin) revealed thrombosis in 25%, vasculitis in 6%, and both vasculitis and thrombosis in 20%. Thirty cases tested positive for levamisole. All patients reported recent cocaine use. Treatment of 63 neutropenic patients included supportive care (6 patients; one death; 83% recovery; and 50% spontaneous relapse); G-CSF (15 patients; 100% response; 40% relapse), antibiotics (25 patients; 100% recovery; 28% relapse rate), and corticosteroids (14 patients; 100% recovery; 28% relapse rate). Among 30 persons with skin biopsies identifying thrombosis, treatments included conservative management (5 patients; 100% response rate; 33% relapse) and corticosteroids (13 patients; 100% recovery; 22% relapse rate); among 9 persons with vasculitis, treatments included conservative treatment (2 patients, both recovered no relapses) and corticosteroids (4 patients; 100% response; and 50% relapse). Among 27 persons with thrombosis and vasculitis, treatments included conservative treatment (6 patients; 100% recovery; 50% relapse) and corticosteroids (10 patients; 100% response rates; 40% relapse rate). Severe skin necrosis treatment included skin allografts (6%), above the knee amputation (1 case) and a nose amputation (1 case). One patient with agranulocytosis died of infectious complications. The DEA reports that since 2008, 93% of intercepted cocaine is contaminated with levamisole, a colorectal cancer and anti-helminthic agent.

Cocaine-levamisole thrombovasculopathy is a new and increasingly seen syndrome seen among emergency department patients in major cities. A high index of suspicion is essential, as cocaine use may not be obvious and expensive testing and therapies initiated. Appropriate treatment would include withdrawal of cocaine, evaluation of urine samples for levamisole, and conservative management.

Gilbert:Allergan: Consultancy; Merz Aesthetics: Consultancy; Johnson & Johnson: Consultancy.