The U.S. Drug Enforcement Agency reports that approximately 5 million Americans use cocaine regularly.5,6 As of 2011, about 89% of seized cocaine in the United States was tainted with levamisole (ergamisole).5-7 Levamisole potentiates the euphoric effect of cocaine, explaining its use as a cutting agent.7,8 However, the association between levamisole-contaminated cocaine use and an associated vasculopathy has only recently been noted. Levamisole is an antihelminthic agent used in veterinary medicine.6,7 It also stimulates T cells and macrophages, enhances B-cell production, and upregulates the expression of major histocompatability complex class I genes, vascular cell-adhesion molecule-1, and intercellular adhesion molecule 1, as well as the production of interferon-gamma and interleukin-2.2,6,7,9,10 Levamisole potentiates the pressor responses to noradrenaline, angiotensin, and acetylcholine, likely due to the inhibition of monoamine oxidase, catechol-O-methyltransferase, and catecholamine uptake mechanism.6, 7, 9-11 Levamisole can be detected in urine; however, it has a very short half life of about six hours, so it may become undetectable within 48 hours of exposure. Negative toxiciology testing from levamisole therefore should not be deemed as absence of exposure17.It was withdrawn from the U.S. market in 1999 due to the risk of serious side effects.2,3,5-7,9
It is strongly suspected that levamisole in cocaine induces the observed pseudovasculitis, although the exact underlying mechanism is unknown. Similar necrotic skin lesions with a predilection for face, ears, and cheeks were previously noted in children with nephrotic syndrome treated with levamisole.8,12-15 The dermal pathology demonstrated a wide variety of vasculopathic reactions ranging from thrombotic vasculitis to bland vascular occlusive disease without a true vasculitis. In addition, hypersensitivity vasculitis in superficial and deep dermis with neutrophilic infiltration and fibrinoid necrosis has been observed.4,8,12-14
In ANCA-associated vasculitides, autoantibodies are usually directed against PR3/c-ANCA and MPO/p-ANCA. However, atypical ANCAs directed against other neutrophil protein components, including CG and human NE have been reported in cases of cocaine-related vasculopathy.2,8,14,16 It is proposed that levamisole use stimulates the production of autoantibodies, including ANA, LAC, and ANCA.2,9 Whether levamisole-induced ANCAs are directly pathogenic remains to be determined.2
