Levamisole adulterated cocaine associated ANCA vasculitis: review of literature and update on pathogenesis

Abstract

Levamisole is an antihelminth drug and a common cocaine contaminant, present in an estimated 71% of cocaine samples in the US. Levamisole-contaminated cocaine has been linked to an ANCA-associated vasculitis with cutaneous, renal, and pulmonary manifestations. We report the case of a 46 year old woman with known cocaine exposure who presents with recurrent, large purpuric and maculopapular rash of the extremities and face and review existing cases of levamisole/cocaine-associated ANCA vasculitis, We summarize the clinical presentation, treatment, and outcomes of levamisole induced vasculitis. There is emerging research on pathogenesis relating to neutrophil extracellular traps (NETs). We review studies implicating role of NETs in the pathogenesis of levamisole induced vasculitis. Further research to explore the use of NETs as therapeutic targets in drug induced vasculitis is needed.

Pyoderma gangrenosum–like facial ulcers in a woman associated with cocaine use and cANCA/anti-PR3+, pANCA/anti-MPO– serology

“…Of note, levamisole is an antihelminth drug that was estimated to contaminate approximately 70% of cocaine samples in the United States (Drug Enforcement Administration's Cocaine Signature Program, 2009 data). 3 Levamisole-contaminated cocaine has been associated with development of ANCA-positive disease, particularly the development of vasculitis in the skin, kidney, and lungs. 3 Levamisole has a half-life of approximately 5 hours, and may become undetectable in the urine in as little as 48 hours after exposure.…”

“…3 Levamisole-contaminated cocaine has been associated with development of ANCA-positive disease, particularly the development of vasculitis in the skin, kidney, and lungs. 3 Levamisole has a half-life of approximately 5 hours, and may become undetectable in the urine in as little as 48 hours after exposure. 8 Traditionally, when levamisole was used as a therapeutic, known side effects included neutropenia, liver toxicity, gastrointestinal upset, and development of purpuric and necrotic lesions.…”

“…8 Traditionally, when levamisole was used as a therapeutic, known side effects included neutropenia, liver toxicity, gastrointestinal upset, and development of purpuric and necrotic lesions. 3 Cocaine, independent of levamisole, may itself be associated with development of autoimmunity; thus, both drugs may be contributing to development of ANCA-associated disease via the formation of neutrophil extracellular traps in susceptible individuals. 3 In a case series of 8 patients with cocaineassociated skin disease in Ottawa, Canada, only 1 had purpura of the cheek, and none with necrotic ulcers involving the face.…”

“…3 Cocaine, independent of levamisole, may itself be associated with development of autoimmunity; thus, both drugs may be contributing to development of ANCA-associated disease via the formation of neutrophil extracellular traps in susceptible individuals. 3 In a case series of 8 patients with cocaineassociated skin disease in Ottawa, Canada, only 1 had purpura of the cheek, and none with necrotic ulcers involving the face. 8 Only 3 of the 8 patients lacked a medical history before the development of skin lesions, similar to our patient, whereas some had hepatitis B or C, systemic lupus, or Sweet syndrome documented before their cocaineassociated skin disease.…”

“…Several reports indicate that cocaine use (particularly if levamisole contaminated) is associated with development of vasculopathy, 1 , 2 vasculitis, 2 , 3 , 4 , 5 or skin necrosis. 6 , 7 The classic presentations shown for levamisole-induced skin lesions are of purpuric or necrotic, pyoderma gangrenosum–like lesions involving the ears, face, and extremities.…”