Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

Abstract

Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV.

Refractory Adult Primary Autoimmune Neutropenia that Responded to Alemtuzumab

“…ANCA and neutropenia have also been reported in other autoimmune diseases such as autoimmune hepatitis, primary sclerosis cholangitis, and Sjögren's syndrome in the absence of vasculitis (14). The significance of lupus anticoagulant in the development of AIN in our patient also remains to be elucidated.…”

Agranulocytosis Induced by Vancomycin. Case Report and Literature Review

“…Despite an extensive list of medications that cause neutropenia, only propylthiouracil, methimazole, cocaine/levamisole, minocycline, and hydralazine were associated with ANCA and neutropenia [ 8 , 10 ]…”

“…The specific mechanisms behind the development of this complication have not been fully elucidated, although the hypotheses include immune-mediated neutropenia and direct toxicity of bone marrow [ 3 , 6 , 10 , 14 ]. The development of antineutrophil antibodies, and more rarely ANCA supports the immune origin of agranulocytosis by drugs [ 5 , 9 , 10 , 15 , 16 ].…”

“…However, the direct role of the ANCA in the development of neutropenia is not entirely clear. The migration of cytoplasmic antigens proteinase 3 (PR3), myeloperoxidase (MPO), and cathepsin G to the neutrophil cell surface promoted by endogenous pyrogens, allow exposure to the immune system [ 8 , 10 ]. Other mechanisms possibly involved are suppression of granulocytes production, complement dependent cytotoxicity, and agglutination of neutrophils by antineutrophil antibodies [ 10 , 17 ].…”

“…Grayson et al reported a case of vasculitis ANCA-associated autoimmune neutropenia with specificity against PR3 and MPO. They found only 24 cases in the literature of neutropenia associated with ANCA secondary to drugs, none of which was vancomycin [ 10 ].…”