57. Drug Associated ANCA Vasculitis: A Single Center Experience

Background/ Objectives: The trigger that induces antineutrophil cytoplasmic antibodies (ANCA) that lead to systemic vasculitis is largely unknown. Over the years, there have been associations noted between certain drugs and ANCA associated vasculitis; primarily hydralazine, propylthiouracil (PTU), methimazole, cocaine adulterated with levamisole, minocycline, and more recently, allopurinol. The aim of this study was to further elucidate the characteristics of the correlation between these drugs and detection of ANCA.

Methods: We conducted a retrospective analysis of 3997 patients from 1989-2021 with a newly detected ANCA test for myeloperoxidase (MPO) and/or proteinase-3 (PR3) antibodies at the Massachusetts General Hospital (MGH) ANCA laboratory. For each new ANCA-positive patient, a limited discussion was held with the ordering clinician to review implications of the positive test and to identify exposure to any suspected culprit drugs at the time of positive ANCA test. Electronic medical records of cases managed at MGH were also reviewed.

Results: Of the 3997 patients (mean age: 73 years, 60% female) with a newly positive ANCA test from 1989 to 2021, 434 patients (mean age: 68 years, 63% female) were found to have exposure to one or more culprit drugs prior to detection of ANCA, representing 11% of the total cohort. Hydralazine exposure was noted in 149/434 (34.3%) of patients, cocaine/levamisole exposure in 107/149 (24.7%) patients, with the remainder of patients with PTU (50/434, 11.5%), minocycline (46/434, 10.6%) and methimazole (14/434, 3.2%) exposure. We found 68 of 434 patients (15.7%) were treated with allopurinol prior to a positive ANCA test. MPO-ANCA positivity was a predominant feature in the drug-associated cohort, representing 378/434 (87%) of drug associated cases. The median MPO titer in the drug-associated cohort was 5 times higher compared to the median MPO titer of the total ANCA positive cohort. The median MPO titer of the hydralazine group was 15 times higher compared to the entire cohort. 34 of 59 patients (57.6%) with double positive MPO and PR3-ANCA had a culprit drug exposure prior to ANCA detection. 

Conclusions: The true prevalence of drug-associated cases is likely underrepresented as medication exposure at the time of a positive ANCA test were unknown in many cases. Our data suggest that patients with high MPO-ANCA titers and/or double positive MPO and PR3-ANCA should be investigated for any of these likely culprit drugs.

Disclosures: None