Levamisole-associated neutropenia and autoimmune granulocytotoxins.

Drew, SI; Carter, B M; Nathanson, David; Terasaki, P I

doi:10.1136/ard.39.1.59

Cited by 28 publications

(18 citation statements)

References 8 publications

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“…The presence of these antibodies, the hypo-or hyper-regeneratory character of bone marrow, the lack of signs of myelotoxicity and cyclic regeneratory tendencies in the peripheral blood, argued for a peripheral immunological mechanism [6,10,14,17]. Most recently, Drew et al [2] reported on 6 cancer patients with levamisole-induccd granulocytotoxic antibod ies. 3 of them produced severe neutropenia.…”

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confidence: 99%

Levamisole-Induced Neutropenia and Agranulocytosis: Association with HLA B27 Leukocyte Agglutinating and Lymphocytotoxic Antibodies

Hodinka

Géher

Merétey

et al. 1981

Int Arch Allergy Immunol

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Among 37 patients treated with levamisole for rheumatoid arthritis (n = 19), for Reiter’s disease (n = 4) and for chronic articular brucellosis (n = 14) followed up during 6–12 months, 3 developed agranulocytosis and 3 severe neutropenia. Serum samples drawn before and during treatment were tested for leukocyte agglutinating and lymphocytotoxic antibodies. Leukocyte agglutinating antibodies were induced in 8 patients, in 5 of them in association with agranulocytosis or neutropenia. In 1 patient with agranulocytosis and in another one with neutropenia lymphocytotoxic antibodies were also induced. Two agranulocytotic and one neutropenic patient possessed HLA B27 antigen. In altogether 11 HLA B27 carriers the numbers of circulating neutrophils were significantly reduced during levamisole treatment when compared with those of patients lacking HLA B27 antigen.

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Levamisole-Induced Neutropenia and Agranulocytosis: Association with HLA B27 Leukocyte Agglutinating and Lymphocytotoxic Antibodies

Hodinka

Géher

Merétey

et al. 1981

Int Arch Allergy Immunol

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“…central to the pathophysiology of levamisole-associated agranulocytosis, antineutrophil cytoplasmic antibodies (c/p-ANCA) are also commonly detected [21,22]. Previous studies of autoimmune agranulocytosis among therapeutic users of levamisole suggest a genetic predisposition among patients who are human leukocyte antigen (HLA)-B27 positive or have HLA class 1 antigens, but this work has not been replicated among patients with cocaine-associated levamisole exposure [23].…”

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confidence: 95%

Agranulocytosis and other consequences due to use of illicit cocaine contaminated with levamisole

Buchanan¹

2012

Current Opinion in Hematology

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More than three fourths of cocaine users in the United States are exposed to levamisole; a significant minority of these individuals will develop autoimmune-mediated neutropenia, cutaneous vascular complications, and/or leukoencephalopathy. Levamisole exposure should be considered in the differential diagnosis of patients who present with these conditions in the setting of cocaine abuse. Neutropenia appears to resolve rapidly with cessation of exposure, so that GCSF therapy and a work-up for other causes may not be needed in all patients.

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“…18,19 The frequency of levamisole administration appears to be important, with agranulocytosis being more prevalent among those receiving lower doses more frequently. 20 Vasculitis ranks as the second most commonly reported adverse event reported after exposure to cocaine adulterated with levamisole. Typically, this antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis presents with purpura and necrotic lesions that preferentially involve the ears and cheeks.…”

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confidence: 99%

“…In therapeutic dosing, levamisole produced agranulocytosis, possibly secondary to induction of granulocytotoxic antibodies and autoagglutinins. 20 Other theories include direct drug toxicity to neutrophils with sustained high drug doses, hapten formation, leukoagglutination, and potentiation of cold autoantibodies. 16,20,22,23 Bone marrow biopsies in these patients have shown granulocyte maturation arrest and myeloid hypoplasia.…”

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confidence: 99%

“…20 Other theories include direct drug toxicity to neutrophils with sustained high drug doses, hapten formation, leukoagglutination, and potentiation of cold autoantibodies. 16,20,22,23 Bone marrow biopsies in these patients have shown granulocyte maturation arrest and myeloid hypoplasia. 1 Similarly, the putative pathogenesis of vasculitis may involve levamisole functioning as a hapten with antibody generation and deposition in vessel walls.…”

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confidence: 99%

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Levamisole Exposure and Hematologic Indices in Cocaine Users

Chai

Bastan

Machan

et al. 2011

Academic Emergency Medicine

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Objectives: Levamisole is an antihelminthic agent found in nearly 70% of seized U.S. cocaine. Sporadic case literature describes a life-threatening agranulocytosis associated with levamisole exposure secondary to cocaine use. The authors compared the distribution of hematologic indices in a population of cocaine users with and without a confirmed exposure to levamisole. Methods:The records of all patients in the Lifespan hospital system who underwent comprehensive toxicologic testing between September 2009 and December 2009 (n = 799) were reviewed. Of these, 95 patients were eligible for inclusion (cocaine-positive with a simultaneous complete blood count). Patients were grouped into levamisole-positive (n = 47) and -negative (n = 48) groups. The primary outcome measures were total white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC); secondary outcome measures included percent neutrophils, lymphocytes, eosinophils, monocytes, and basophils, as well as identified co-ingestants.Results: Both groups had a similar makeup of age, sex, and race. The total WBC count, ANC, and ALC were not significantly different between the two groups. There was no significant difference in relative proportion of neutrophils, eosinophils, basophils, or monocytes between the groups. There was one neutropenic patient in the levamisole-positive group, while three patients were neutropenic in the negative group. Additionally, a literature review of case reports describing levamisole-induced agranulocytosis (n = 33) was conducted. In 52% of these cases, patients presented with an oropharyngeal chief complaint; in an additional 27%, patients presented with soft tissue infections or purpura. Conclusions:The overall incidence of neutropenia was 4.2% in all cocaine users and 2.1% in the levamisole-positive group. A striking number of the reported patients with levamisole-associated neutropenia have presented to care with oropharyngeal complaints, vasculitis, or fever. A clinical algorithm for identifying levamisole toxicity in the emergency department setting is provided. Further research is necessary to determine the circumstances required for levamisole-associated neutropenia.

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Levamisole-associated neutropenia and autoimmune granulocytotoxins.

Cited by 28 publications

References 8 publications

Levamisole-Induced Neutropenia and Agranulocytosis: Association with HLA B27 Leukocyte Agglutinating and Lymphocytotoxic Antibodies

Levamisole-Induced Neutropenia and Agranulocytosis: Association with HLA B27 Leukocyte Agglutinating and Lymphocytotoxic Antibodies

Agranulocytosis and other consequences due to use of illicit cocaine contaminated with levamisole

Levamisole Exposure and Hematologic Indices in Cocaine Users

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