Use of anti-neutrophil cytoplasmic antibody assay to distinguish between vasculitic disease activity and complications of cytotoxic therapy

Anti–neutrophil cytoplasmic antibody (ANCA) determinations appear to be useful in the diagnostic evaluation and therapeutic monitoring of patients with necrotizing vasculitis. The purpose of this study was to determine whether semiquantitative ANCA measurements are useful in distinguishing between increases in primary disease activity and complications of cytotoxic or immunosuppressive therapy. The authors reviewed clinical data from 27 consecutive ANCA-positive patients who had at least three ANCA determinations performed at the University of Michigan Medical Center. Eleven patients had Wegener’s granulomatosis (WG), 3 had “limited” WG; 9 had “ANCA-positive” vasculitis; and 4 had “pauciimmune” rapidly progressive glomerulonephritis. During a period of 3 months to 3.8 years, 159 ANCA determinations were performed, primarily for the purposes of diagnosis and monitoring disease activity. Eleven episodes were identified in which a single ANCA assay was used to distinguish between increased primary disease activity and a suspected therapeutic complication. The suspected therapeutic complications included pneumonia (8 of 11), bacterial sinusitis (1 of 11), cyclophosphamide-induced pneumonitis (1 of 11), and cyclophosphamide-induced vestibular toxicity (1 of 11). In 10 of 11 instances in which an ANCA assay was used to distinguish between an exacerbation in vasculitic disease activity and a therapeutic complication, interpretation of the ANCA titer was pivotal in arriving at a therapeutically appropriate decision either to increase or discontinue cytotoxic therapy. This study suggests that ANCA determinations can be used reliably to distinguish between increased primary disease activity and complications of therapy that mimic an increase in disease activity.