Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease

Abstract

Background 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 2009 and 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.

Conclusions: We 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.

Figure 1.

(A) Kidney biopsy. The glomerulus reveals fibrinoid necrosis of the central part of the tuft associated with focal leukocytoclasia and a small cellular crescent filling the upper portion of Bowman's space; there is no significant hypercellularity of the uninvolved segments of the tuft. (Periodic acid-Schiff). (B) Kidney biopsy. The cortex shows an active glomerulitis with a small cellular crescent that has resulted in prominent bleeding into Bowman's space and the tubules. Mild interstitial inflammation is also present. (Hematoxylin & eosin). (C) Necrotic skin lesions. Large areas of full thickness, necrotic ulceration, near circumferential over both lower extremities. (D) Earlobe vasculitis. Purpuric violaceous lesion is seen with surrounding erythema. Biopsy revealed leukocytoclastic vasculitis. (E) Skin biopsy. The small vessel in the dermis shows active inflammation, with associated fibrinoid necrosis of the wall, leukocytoclasia, and thrombosis. The perivascular space reveals edema and extravasation of red blood cells. (Hematoxylin & eosin).

Figure 2.

New cases of cocaine-associated antineutrophil cytoplasmic antibodies diagnosed per quarter, March 2009 to November 2010.