A new low for an old high: neutropenia induced by levamisole-adulterated cocaine.

Recently, both the media and medical literature have directed attention towards neutropenia associated with levamisole-adulterated cocaine. Levamisole, available in South America as an anti-helminthic veterinary agent, was previously used in the United States (US) for treatment of colon cancer and rheumatoid arthritis. Due to its well-established adverse effect of reversible neutropenia in approximately 20% of patients exposed, levamisole was voluntarily removed from the US market in 2000. Despite this known complication, levamisole has been isolated in up to 70% of cocaine seized by the Drug Enforcement Administration (DEA) in recent years. Evidence suggests traffickers in supply countries adulterate cocaine with levamisole, likely due to a known stimulatory synergism between the two drugs. Since 2009, nearly 100 cases of neutropenia associated with levamisole-adulterated cocaine have been reported in medical literature in North America and Europe. These patients, variably testing positive for cocaine and/or levamisole, have presented with symptoms including fever, generalized lymphadenopathy, oral ulcers, opportunistic infections, retiform purpura and, in at least one case, death. Exposure to levamisole can be tested by urinary gas chromatography, but this assay is not widely available and is of limited utility given the short urinary half-life of levamisole (5-6 hours). While the exact mechanism of levamisole-induced neutropenia remains unknown, reports of HLA-B27, lupus anticoagulant and anti-neutrophil cytoplasmic antibody (ANCA) positivity among neutropenic patients exposed to levamisole suggest a potential autoimmune pathophysiology. G-CSF has been proposed as a treatment to shorten the duration of levamisole-induced neutropenia and minimize associated complications, but its relative efficacy for this purpose has not been firmly established.