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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

          Male, 36 FINAL DIAGNOSIS: Levamisole-induced vasculopathy Symptoms: Purpuric skin lesions Medication: Levamisole Clinical Procedure: - Specialty: Internal Medicine.

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          Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease.

          Tamara Isakova, John Niles, Catherine M McGrath … (2011)
          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.

            Elaine Jaffe, Paul L Kimmel (2006)
            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.

              John Imboden, N Richman, Thuy Nguyen … (2011)
              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
                Journal ID (iso-abbrev): Am J Case Rep
                Title: The American journal of case reports
                Publisher: International Scientific Information, Inc.
                ISSN (Electronic): 1941-5923
                ISSN (Print): 1941-5923
                Publication date (Electronic): 2013
                Volume: 14
                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.
                Article
                Publisher Item ID: 889731
                DOI: 10.12659/AJCR.889731
                PMC ID: 3905810
                PubMed ID: 24478818
                SO-VID: 7b4e18dc-9a0c-4ae8-85c6-99fab466b65d
                History

                Keywords: cocaine,levamisole,nephrotic syndrome,vasculitis
                Data availability:
                Keywords: cocaine, levamisole, nephrotic syndrome, vasculitis

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