Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine

Abstract

Objective. To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine.Methods. All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits.Results. The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase.Conclusion. Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine.

Levamisole-Contaminated Cocaine Use in HIV-Infected and Uninfected Unstably Housed Women

“…While neutropenia has been cited as a concern in case reports of persons seeking treatment for conditions linked to levamisole, 9,14,16,35,36 we did not find significant differences in neutrophil count by cocaine and levamisole status (Table 2). Furthermore, adjusted models suggested mediation of cocaine/ levamisole effects on white blood cell count by lymphocyte count, but not by neutrophil count (Table 3).…”

“…Based on prior research suggesting the important role of white blood cell count in negative health outcomes linked to levamisole among women, particularly neutrophil count, 15,16 we assessed unadjusted and adjusted odds between clinically low white blood cell count (<3.8 · 10 3 /lL) and white blood cell differentials (lymphocyte count and neutrophil count) by cocaine/levamisole status.…”

“…[14][15][16] Furthermore, women have higher rates of stimulant dependence, more severe forms of stimulant addiction and lower rates of treatment than men, [20][21][22][23] which may result in differential levamisole exposure. In addition, sex differences in both the pharmacokinetics of HIV medication 24 and the natural course of HIV disease 25 have been identified.…”

“…Harmful effects include agranulocytosis, necrotizing vasculitis, fixed drug eruptions and pruritic rashes, [7][8][9][10][11][12][13] and levamisole-toxicity cases are disproportionately described among women. [14][15][16] Accurately identifying levamisoleinduced health complications is essential for discontinuing exposure, and preventing unnecessary use of other treatments with potentially strong side effects such as immunosuppressive therapy. 17 While the number of case reports appearing in the medical literature has increased, the population-level clinical and socioeconomic correlates of levamisole-contaminated cocaine use are not well established.…”

“…16 In response, Lynch et al developed mass spectrometry-based methods for the detection of levamisole in urine 4 to begin investigating the link between cutaneous skin necrosis and levamisole-induced toxicity. 16 The current study leveraged these mass spectrometry methods, and an existing community-based study conducted during the same time period, to assess associations between the presence of levamisole and inflammation, immune and social factors. The objective was to better understand exposures and potential subclinical outcomes outside of extreme acute health consequences like necrotizing vasculitis in a population identified as being at disproportionately high risk.…”