Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Antineutrophil cytoplasmic antibody testing is sensitive and specific in active Wegener granulomatosis

ACP J Club. 1996 Mar-April;124:48. doi:10.7326/ACPJC-1996-124-2-048

Source Citation

Rao JK, Weinberger M, Oddone EZ, et al. The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis. Ann Intern Med. 1995 Dec 15;123:925-32. [PubMed ID: 7575046]



To determine the usefulness of antineutrophil cytoplasmic antibody (c-ANCA) testing for the diagnosis of Wegener granulomatosis.

Data Sources

Searches were done in MEDLINE (1966 to 1993) using the terms antineutrophil cytoplasmic antibody, anticytoplasmic antibody, antineutrophil antibody, antibodies, neutrophils, pulmonary-renal system, Wegener granulomatosis, vasculitis, and glomerulonephritis. Bibliographies of relevant studies, review articles, and standard texts were also reviewed.

Study Selection

Studies were selected if they specified the patient selection method, if they included standard reference criteria for the definition of Wegener granulomatosis, and if a 2 × 2 contingency table could be constructed to calculate the operating characteristics of the test in patients with and without Wegener granulomatosis. Each study was reviewed in a 4-stage process by independent reviewers to determine eligibility for inclusion. Of 747 potential studies identified, 15 met the inclusion criteria and comprised 13 562 patients, including 736 with Wegener granulomatosis.

Data Extraction

A quality assessment score based on methodologic rigor was determined for each study (13 possible points). Sensitivity and specificity were calculated for overall Wegener granulomatosis (either classic or limited disease), for active and inactive Wegener granulomatosis, and for high-quality studies using indirect immunofluorescence assay results and considering tests to be positive if there were any positive titers.

Main Results

Summary estimates of sensitivity and specificity obtained by pooling averages weighted by study size for the 15 studies, studies of active Wegener granulomatosis (468 patients), studies of inactive Wegener granulomatosis (468 patients), and studies with scores ≥ are displayed in Table. 3 studies achieved ≥ 10 points on the quality assessment score (1384 patients); their sensitivities were 39%, 46%, and 92%, respectively.


Antineutrophil cytoplasmic antibody is a sensitive and specific test for active Wegener granulomatosis, but it is less sensitive in patients who have inactive disease.

Source of funding: Department of Veterans Affairs.

For article reprint: Dr. J. Rao, Health Care and Aging Studies Branch, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Mailstop K-45 Atlanta, GA 30341-3724 USA. FAX 770-488-5964.

Table. Diagnostic test characteristics for antineutrophil cytoplasmic antibody testing of Wegener granulomatosis*

Studies Weighted sensitivity (95% CI) Weighted specificity (CI) +LR -LR
All studies (n = 15) 66% (57 to 74) 98% (96 to 99.5) 33 0.35
Active Wegener granulomatosis (n = 4) 91% (87 to 95) 98% (97 to 100) 65 0.09
Inactive Wegener granulomatosis (n = 4) 63% (57 to 69) 99.5% (99.1 to 99.7) 126 0.37
High quality studies (score > 7) (n = 7) 71% (49 to 89) 96% (92 to 99) 18 0.30

*LRs defined in Glossary; and calculated from data in article.


This meta-analysis and another recent report by Rao and colleagues (1) raise concerns about the overly confident application of ANCA testing in clinical decision making. Because testing with ANCA is increasingly used to rule in or rule out Wegener granulomatosis, other vasculitides, and certain types of glomerulonephritis in patients with a spectrum of disease more varied than that included in initial studies of ANCA, examination of the operating characteristics of this test is important. In a prospective study of c-ANCA in patients evaluated by a rheumatologist for possible vasculitis, Rao and colleagues found that the overall sensitivity of c-ANCA for Wegener granulomatosis, as defined by clinical criteria of the American College of Rheumatology, was only 28% (83% in patients with biopsy-confirmed evidence of Wegener granulomatosis) with an overall false-negative rate of 72% (1). As in the meta-analysis, the c-ANCA test was highly specific, but the positive predictive value was only 50% because the prevalence of Wegener granulomatosis was still relatively low in this selected population.

In patients with active, biopsy-documented Wegener granulomatosis, a positive c-ANCA test result adds nothing further diagnostically because the diagnosis is already established, and a negative result is likely to be ignored. If the pretest probability of Wegener granulomatosis is low, a positive c-ANCA test result is probably false-positive, again limiting the test's value. The greatest utility of c-ANCA is in determining which patients with an intermediate pretest likelihood of Wegener granulomatosis need more invasive diagnostic studies. In most patients, neither clinical judgment nor c-ANCA alone, nor even the combination of the two, appears to provide sufficient diagnostic accuracy to justify immunosuppressive therapy without biopsy confirmation of disease.

Jeffrey S. Berns, MD
The Graduate HospitalPhiladelphia, Pennsylvania, USA


1. Rao JK, Allen NB, Feussner JR, Weinberger M. A prospective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical criteria in diagnosing Wegener's granulomatosis. Lancet. 1995; 346:926-31.