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      ANCA-positive vasculitis induced by levamisole-adulterated cocaine and nephrotic syndrome: The kidney as an unusual target

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          Abstract

          Patient: Male, 36

          Final Diagnosis: Levamisole-induced vasculopathy

          Symptoms: Purpuric skin lesions

          Medication: Levamisole

          Clinical Procedure: —

          Specialty: Internal Medicine

          Objective:

          Unusual clinical course

          Background:

          Levamisole has been detected in seized cocaine samples and a levamisole-induced vasculopathy (LIV) has been described, mainly focused on skin.

          Case Report:

          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, presented to the hospital with purpuric skin lesions on extremities and earlobes. One month before the current presentation, a skin punch biopsy of one of these lesions was performed, showing histopathologic findings suggestive of mixed cryoglobulinemia. Laboratory testing revealed leukopenia, renal failure, and nephrotic syndrome. Antimyeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were positive. The previous skin punch biopsy was revised and demonstrated pathologic findings consistent with leukocytoclastic vasculitis. An analysis of a cocaine sample for personal use, provided by the patient, was performed using mass spectrometry-gas chromatography and levamisole was detected. Three boluses of intravenous methylprednisolone were administered, followed by oral prednisone 1 mg/Kg per day. Skin lesions and renal function improved.

          Conclusions:

          To our knowledge, this is the first report of nephrotic syndrome induced by levamisole-adulterated cocaine, proven by cocaine sample toxicology. Lack of renal biopsy is a limitation of this report.

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          Most cited references12

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          Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease.

          Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.
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            Chronic nephropathies of cocaine and heroin abuse: a critical review.

            Renal disease in cocaine and heroin users is associated with the nephrotic syndrome, acute glomerulonephritis, amyloidosis, interstitial nephritis, and rhabdomyolysis. The pathophysiologic basis of cocaine-related renal injury involves renal hemodynamic changes, glomerular matrix synthesis and degradation, and oxidative stress and induction of renal atherogenesis. Heroin is the most commonly abused opiate in the United States. Previous studies identified a spectrum of renal diseases in heroin users. The predominant renal lesion in black heroin users is focal segmental glomerulosclerosis and in white heroin users is membranoproliferative glomerulonephritis. Although the prevalence of heroin use in the United States has increased, the incidence of "heroin nephropathy" has declined. Because reports of heroin nephropathy predated the surveillance of hepatitis C virus and HIV, the varied findings might be related to the spectrum of viral illnesses that are encountered in injection drug users. Socioeconomic conditions, cultural and behavioral practices, or differences in genetic susceptibilities may be more associated with the development of nephropathy in heroin users than the drug's pharmacologic properties. Administration of cocaine in animal models results in nonspecific glomerular, interstitial, and tubular cell lesions, but there is no animal model of heroin-associated renal disease. The heterogeneity of responses that are associated with heroin is not consistent with a single or simple notion of nephropathogenesis. There are no well-designed, prospective, epidemiologic studies to assess the incidence and the prevalence of renal disease in populations of opiate users and to establish the validity of a syndrome such as heroin nephropathy. It is concluded although there is a paucity of evidence to support a heroin-associated nephropathy, the evidence from in vitro cellular and animal studies to support the existence of cocaine-induced renal changes is more convincing.
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              Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine.

              To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine. All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits. The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase. Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine. Copyright © 2011 by the American College of Rheumatology.
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                Author and article information

                Journal
                Am J Case Rep
                Am J Case Rep
                amjcaserep
                The American Journal of Case Reports
                International Scientific Literature, Inc.
                1941-5923
                2013
                30 December 2013
                : 14
                : 557-561
                Affiliations
                [1 ]Department of Internal Medicine, Infectious Diseases Unit, University Hospital of Ferrol, Health Area of Ferrol, SERGAS, A Coruña, Spain
                [2 ]Department of Dermatology, University Hospital of Ferrol, Health Area of Ferrol, SERGAS, A Coruña, Spain
                [3 ]Institute of Forensic Science “Luís Concheiro”, Forensic Toxicology Services, Faculty of Medicine, University of Santiago de Compostela, A Coruña, Spain
                Author notes

                Authors’ Contribution:

                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Corresponding Author: Hortensia Álvarez Díaz, e-mail: hortensia.alvarez.diaz@ 123456sergas.es
                Article
                889731
                10.12659/AJCR.889731
                3905810
                24478818
                7b4e18dc-9a0c-4ae8-85c6-99fab466b65d
                © Am J Case Rep, 2014

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 31 August 2013
                : 29 September 2013
                Categories
                Articles

                vasculitis,levamisole,nephrotic syndrome,cocaine
                vasculitis, levamisole, nephrotic syndrome, cocaine

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