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Levamisole is a synthetic imidazothiazole derivative used for its immunomodulatory properties. In fact, during the 80s and 90s, levamisole was used as an immunomodulatory agent for the treatment of a variety of autoimmune conditions and malignancies 1 , 2. Nowadays it is exclusively licensed as an antihelminthic for use in veterinary medicine. However, it is also illicitly employed as a cocaine adulterant 3. It has recently been reported that the consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody ANCA -associated syndromes. Additionally, levamisole causes loss of tolerance to several antigens from within neutrophil granules, eventually resulting in clinical disease 4 , 5. Interestingly, genetic and environmental factors likely play an important role 6. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole 7. Likewise, patients with ANCA-associated vasculitis AAV and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. This phenomenon is likely true in those exposed to levamisole, given the widespread use of cocaine, the high prevalence of it in the drug supply, and the relatively low incidence of their manifestations 6. Here, we report an unusual case of a patient with a membranous glomerulonephritis GNM and cellular crescent associated with levamisole-contaminated cocaine use. The patient was a year-old Caucasian man who was a regular user of intravenous drugs, was infected with the hepatitis C virus HCV , with fibroscan and no sustained elevation of transaminases, was diagnosed with microcytic anemia and had purple skin with ANCA-positive pseudovasculitis from levamisole use a skin biopsy was performed in The man was admitted to the Division of Nephrology with acute oligoanuric renal failure and macroscopic hematuria, and with the appearance of new skin-necrotic lesions on his nose, trunk and extremities. The patient confirmed that the last parenteral cocaine consumption had been days before. In additional tests, renal failure was highlighted with serum creatinine levels of 7. Elevated serum acute phase reactants were also observed, such as C-reactive protein CRP : After recovering diuresis, a proteinuria of 1. An abdominal ultrasound showed kidneys with normal cortico-medullary differentiation and a minimal amount of free fluid in the pelvis with no other pathological findings. The transthoracic echocardiography TTE was negative for endocarditis. Physical examination revealed tense ascites of unknown origin whilst the subsequent peritoneal biopsy showed vasculopathy peritoneal thrombotic vasculitis of probable toxic origin. The kidney biopsy, at which time the serum creatinine level was 2. A total of 17 sessions of hemodialysis via jugular vein catheter were needed. Skin lesions and renal function improved significantly 10 days after starting treatment, in conjunction with the withdrawal from cocaine consumption, and there were residual scars. At the 3-month follow-up after decreasing doses of prednisone and without toxic consumption of levamisole skin lesions had subsided and stable analytical parameters were seen both for anemia Hb: Over the last decade, concern about levamisole-adulterated cocaine consumption has increased, given the exponential growth of its illicit use. The reason for its use is justified by its low price as well as the similar physical characteristics to cocaine. Moreover, levamisole also enhances the biological action of cocaine through aminorex 8. The characteristic cutaneous manifestation after recent cocaine use, i. Interestingly, these skin lesions were previously described in children treated with levamisole, curiously for the treatment of steroid-resistant nephrotic syndrome 10 , The systemic impact of levamisole is of low prevalence but hematological disorders are the most common Furthermore, levamisole is also prothrombotic, lengthening the activated partial thromboplastin time APTT by synthesis of antiphospholipid antibodies The second most frequently associated damage from levamisole consumption is pulmonary disease described as pulmonary arterial hypertension PAH due to aminorex formation and pulmonary hemorrhage Finally, renal disease incidence is in accordance with some other series of cases 6. From a renal point of view, the clinical diagnosis varies from mild disease with hematuria to renal failure with renal biopsy findings in extracapillary focal pauci-immune glomerulonephritis In our case, we worked with several possible diagnoses. The necrotic lesions and the elevation in prothrombotic factors led us to suspect a possible thrombotic microangiopathy. Without knowing the renal function prior to the acute episode, we could not rule out a membranoproliferative glomerulonephritis MPGN or GNM secondary to HCV infection, which had worsened after toxin consumption and resulted in acute renal failure. Other possibilities such as a focal segmental glomerulosclerosis secondary to HCV infection, amyloidosis by chronic infection, or even nephrotic syndrome induced by levamisole itself 15 were dismissed due to clinical presentation. Therefore, renal biopsy findings were quite surprising, becoming the first reported case of GNM and cellular crescents. Although the precise mechanism remains unclear, we determined that the GNM was caused by the deposition of exogenous antigen levamisole. The cellular crescents probably occurred because of the immunomodulator effect of levamisole and its direct endothelial damage. A limitation of this case is the lack of determination of levamisole levels in a biological sample, but sampling for this could not be performed for ethical reasons. In addition, we also assume that cocaine may also provoke damage through a vasoconstriction mechanism. After reviewing the literature, it remains contradictory whether the clinical and analytical parameter improvements were a consequence of the corticotherapy at high doses rather than of levamisole consumption cessation. In our opinion, the kidney biopsy could be modified by the early administration of corticosteroids. Figure 1 Kidney biopsy specimen. B Hematoxylin-eosin stain using an optical microscope, showing a necrotizing crescentic glomerulonephritis induced by inflammation and diffuse thickening of basement membranes with stiffness evident at the top of the sphere. Membranous glomerulonephritis and cellular crescents induced by levamisole-adulterated cocaine abuse: a case report. Ann Transl Med ;3 18

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