Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

Abstract

SummaryBackground and objectives Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Design, setting, participants, & measurements Cases were identified between March 2009and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation.Results Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. ConclusionsWe describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.

Nephrotoxic Effects of Common and Emerging Drugs of Abuse

“…An important and interesting association between cocaine use and the development of a systemic syndrome with renal and nonrenal manifestations has come to light in recent years after the discovery that drug dealers were cutting pure cocaine with levamisole (83)(84)(85). Levamisole is a nematode-specific nicotinic acetylcholine receptor antagonist that is used as an antihelminthic agent in animals.…”

“…By 2009, levamisole was detected in 69% of cocaine entering the United States that was seized by law enforcement officials (86,90). A mini-epidemic of complications related to levamisoleadulterated cocaine use ensued (83,84,91). It is thought that cocaine is cut with levamisole because levamisole is a white, odorless powder that may potentiate euphoria.…”

“…In addition, antinuclear autoantibodies, lupus anticoagulant, and low complement levels are detected in most patients. Although testing for autoantibodies to other neutrophil granule constituents is not routine, it appears that autoantibodies are also formed to human neutrophil elastase, cathepsin G, and lactoferrin (83)(84)(85). Furthermore, urine detection of cocaine and levamisole is an important diagnostic step.…”

“…Additional treatment modalities for levamisole-adulterated cocaine-induced ANCA vasculitis often include immunosuppression based on disease severity. However, data on efficacy are limited primarily to a single center, Massachusetts General Hospital, where it appears that treatment typically mirrors that of patients with idiopathic ANCA vasculitis and is necessary and effective in severe cases (83). Furthermore, any potential treatment strategy is limited by struggles with adherence in individuals whose main priorities focus on the use and acquisition of cocaine (85).…”

Levamisole Induced Pauci Immune Focal Necrotizing and Crescentic Glomerulonephritis

“…Study done by McGrath and colleagues described 30 patients with ANCA positivity associated with levamisole contaminated cocaine use; two developed severe acute kidney injury leading to chronic kidney disease [3].…”