Levamisole was first used as an anthelminthic for human and veterinary use. Initial human use in the 1970s for inflammatory conditions resulted in publications of levamisole-associated agranulocytosis and vasculitis. In 2003, the US Drug Enforcement Agency identified levamisole as an adulterant in cocaine. In 2009, case reports of agranulocytosis and vasculitis associated with levamisole-contaminated cocaine were published. The dermatologic manifestations may include retiform purpura with possible skin necrosis and tend to appear on the ears and nose but can affect any area.
Cases have been reported from both cocaine hydrochloride and crack cocaine and all routes of administration. The reason for adulterating the cocaine with levamisole is not clear. Theories include that the levamisole enhances the effects of cocaine via one of several potential mechanisms: enhancing noradrenergic neurotransmission, inhibiting monoamine oxidase, inhibiting acetylcholinesterase, and stimulating ganglionic nicotinic receptors.
Levamisole-Induced Vasculitis (Ear). The vasculitis associated with levamisole has a predilection for involving the ear. (Photo contributor: Lawrence B. Stack, MD.)
Management and Disposition
Initial considerations for the differential diagnosis for agranulocytosis or the vasculopathy should be broad. The xenobiotic exposure history for the patient must also be carefully reviewed, inclusive of drugs of abuse. For both the agranulocytosis and the cutaneous vasculopathy, serologic testing assists with the differential diagnosis; however, no one classic pattern is diagnostic for levamisole as the etiologic agent.
In the setting of agranulocytosis, neutropenic fever may occur and should be managed accordingly with antibiotics. Deaths from infectious complications have occurred. Cessation of exposure to the levamisole is imperative—which means cessation of cocaine use.
Case reports of levamisole-associated complications suggest that there is a high level of recurrence of complications upon reexposure to levamisole-contaminated cocaine.
Based on case reports, the ears and nose tend to manifest the skin necrosis more often than other areas.
Adulterants such as levamisole are not a part of the routine drug screens. Detection for levamisole requires additional techniques such as gas chromatography–mass spectrometry, liquid chromatography, or tandem mass spectrometry.
Levamisole-Induced Vasculitis (Nose). Levamisole-induced vasculitis can induce significant tissue necrosis requiring reconstructive grafts. (Photo contributor: R. Jason Thurman, MD.)
Levamisole-Induced Vasculitis. Typical appearance of the purpuric lesions of levamisole-induced vasculitis. These lesions were acute and involved the leg of the patient in Fig. 17.17 who also had necrotic lesions from a previous case of levamisole-induced vasculitis. (Photo contributor: R. Jason Thurman, MD.)