Cocaine and Kidney: An Unusual Target?

BACKGROUNDLevamisole is a veterinary antihelminthic agent, previously used to treat nephrotic syndrome, various autoimmune disorders and cancers in humans (colon and breast). Because of its adverse side effect profile, levamisole was withdrawn for use in humans in United States in 1999 but is still available for veterinary use. United States Drug Enforcement Agency first detected levamisole in cocaine in April 2005 [1] and first report of cocaine/ levamisole-induced vasculopathy (LIV) was in June 2010. [2]According to 2009 estimates, approximately two thirds of the cocaine entering United States was contaminated with levamisole. [3] In Europe, levamisole has been detected in seized cocaine samples in United Kingdom, Italy and Spain. During second semester of 2009, surveillance programme results suggest a widespread cocaine consumption in Spain, with levamisole ranging 3-20%. [4]Levamisole may have an inhibitory action on monoamine oxidase and catechol-O-methyltransferase, the enzymes that metabolize catecholamine neurotransmitters. It is theoretically possible that cocaine and levamisole may have a synergistic action at nicotinic acetylcholine receptors resulting in increased nicotinic and dopaminergic effects. Recent reports have suggested that, due to its ability to act as a hapten, levamisole may cause increased formation of antibodies to various antigens and therefore lead to an immune response. [5]Cocaine itself has been reported to be associated with an antineutrophil cytoplasmic antibodies (ANCA)-positive pseudovasculitis. [3]LIV is a diagnosis of exclusion, but this entity should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of: cutaneous manifestations consisting of palpable retiform purpura (lesions tend to be stellate with a bright erythematous border and necrotic appearing center [6]) or bullae, with ear involvement (the most pathognomonic site), arthralgias, leukopenia, and positive ANCA in high titers (although not specific for the condition), when other infectious or idiopathic vasculitides have been excluded. [7] Biopsy findings range from leukocytoclastic and thrombotic vasculitis to vascular occlusion without true vasculitis. Although neutropenia is an expected and well-recognized association with LIV, it is not necessary to make the diagnosis, nor is it an inevitable consequence of levamisole exposure. [2]The time from last cocaine use to onset the condition may be relatively rapid, but many of these affected individuals are chronic, habitual cocaine users, suggesting a large cumulative exposure to cocaine and, by association, levamisole, possibly over an extended period of time. [8]CASE REPORT GUIDED ISSUE DESCRIPTIONIn a previous published paper, we described a case report about nephrotic syndrome developed in the setting of ANCA-positive vasculitis induced by levamisole-adultered cocaine. [9]A 36-year-old Caucasian man with history of antibodies to hepatitis C infection (negative hepatitis C virus RNA and negative HIV serology), smoking and intravenous use of cocaine and brown heroin, on treatment with methadone, presented to the hospital with purpuric skin lesions on extremities and earlobes. The patient had been admitted to the hospital four months before, due to intravenous drug-induced cellulitis and abscess on his forearms and legs. He had received treatment with amoxicillin-clavulanic acid, and skin lesions had improved. At that time, the patient had reported anorexia and weight loss and blood tests had revealed leukopenia and iron deficiency anemia (attributable to inadequate diet and malnutrition). A transthoracic echocardiogram had ruled out infectious endocarditis. One month before the current presentation, purpuric lesions on extremities and earlobes had appeared and a skin punch biopsy had been performed. The histopathologic findings were suggestive of mixed cryoglobulinemia. Blood tests showed polyclonal hypergammaglobulinemia and deterioration of renal function (serum creatinine 1. …