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

Abstract

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.

Cocaine adulterant linked to neutropenia

“…The mechanism by which levamisole causes these antibodies to occur is not well understood. 10 Notably, tests for HLA-B27 in three of four of our affected patients were positive -a finding that was consistent with data reported in the literature on rheumatoid arthritis. In all but one of these patients, the presence of levamisole was confirmed either by tests of samples of the cocaine used CMAJ 59 before a neutropenic episode or by urine assay.…”

“…7 Several small studies involving patients with rheumatoid arthritis and related disorders reported a strong association between the development of agranulocytosis and the presence of HLA-B27. [8][9][10] A case series involving six patients with levamisoleinduced agranulocytosis found that the patients had either induced leukocyte-agglutinating antibodies or lymphocytotoxic antibodies, or both. The mechanism by which levamisole causes these antibodies to occur is not well understood.…”

Drug-Induced Glomerular Disease

“…The mechanism of levamisole-associated AAV is unclear. HLA B27 positivity has been shown to increase the risk of levamisole-associated agranulocytosis (22,23), but its association with AAV has not been explored.…”

Immune-Mediated Agranulocytosis Caused by the Cocaine Adulterant Levamisole: A Case for Reactive Metabolite(s) Involvement

“…As indicated earlier, the association between levamisole use and agranulocytosis is greater in patients carrying the HLA B27 genotype, thereby indicating a possible genetic predisposition to the condition Hodinka et al, 1981). HLA B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6, and it is involved in the encoding of cell-surface receptors that capture and present self-and pathogen-derived peptides to T cells as part of an immune surveillance.…”