A prospective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical criteria in diagnosing Wegener's granulomatosis.

Antineutrophil cytoplasmic antibody (c-ANCA) has a reported sensitivity and specificity greater than 90% for active Wegener's granulomatosis in selected patients with previously-defined disease. Because of these reports, some clinicians believe that a positive c-ANCA result provides strong circumstantial evidence for the diagnosis of Wegener's granulomatosis in patients with compatible clinical symptoms. However, this approach has not been examined prospectively. We prospectively studied 346 consecutive patients suspected of having vasculitis; those with previously established Wegener's granulomatosis (n = 29) or receiving immunosuppressives other than corticosteroids (n = 65) at baseline were excluded. Measures included a baseline c-ANCA, blinded chart reviews to record symptoms, physical findings, and corticosteroid use at baseline, and 2 to 8 months later to record final diagnoses and biopsy results. Wegener's granulomatosis was defined using the 1990 American College of Rheumatology (ACR) criteria, which does not require a biopsy. Follow-up information was available for 212 (84%) of the 252 patients eligible for this study (no corticosteroids: n = 174; corticosteroids: n = 78). 25 patients with compatible symptoms were classified with Wegener's granulomatosis by ACR criteria; only 6 of the 25 had biopsy-proven disease. 14 of these 212 patients had positive c-ANCA results. The overall sensitivity and specificity of c-ANCA for ACR-defined Wegener's granulomatosis were 28% (95% CI, 10%-46%) and 96% (93%-99%) respectively. The positive and negative predictive values were 0.50 and 0.91. The specificity remained greater than 90% regardless of baseline corticosteroid use or disease activity; however, the sensitivity and positive predictive value remained poor. For Wegener's granulomatosis defined by biopsy criteria and compatible clinical symptoms, the sensitivity was 83% (53%-100%); however, the positive predictive value was 36%. These results raise serious questions about the use of positive c-ANCA tests in diagnosing Wegener's granulomatosis in patients with clinical symptoms alone.