Diagnosing ANCA-associated vasculitis in ANCA positive patients: A retrospective analysis on the role of clinical symptoms and the ANCA titre

Abstract

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered.

Figure 1

Flow chart of the inclusion of ANCA positive patients between February 2005 and February 2015. ANCA = antineutrophil cytoplasmic antibody, MPO = myeloperoxidase, PR3 = proteinase 3.

Figure 2

Percentage of patients with a clinical diagnosis of AAV subdivided by the number of affected organ systems. AAV = ANCA-associated vasculitis.

Figure 3

Receiver operating characteristic curve for distinguishing ANCA-associated vasculitis from other diagnoses using several cut-off values of ANCA titres. ANCA = antineutrophil cytoplasmic antibody.

Figure 4

Number of times the ANCA cut-off in patients with and without a clinical diagnosis AAV in 226 ANCA positive patients. Results are shown for each laboratory test and all test pooled. (A) correlation of anti-MPO (1) with AAV in n = 93. (B) Correlation of anti-PR3 (1) with AAV in n = 91. (C) Correlation of anti-MPO (2) with AAV in n = 21. (D) Correlation of anti-PR3 (2) with AAV in n = 21. 1. AutostatTM II Anti-PR-3 and Anti-MPO ELISAs, Hycor Biomedical Ltd, UK. 2. EliA PR3^S and EliA MPO^S run on a Phadia 250 analyzer, Thermo Fisher Scientific, Immunodiagnostics, Sweden. AAV = ANCA-associated vasculitis, ANCA = antineutrophil cytoplasmic antibody, MPO = myeloperoxidase, PR3 = proteinase 3.

Figure 5

Percentage of patients with a clinical diagnosis of AAV subdivided by the ANCA titre in number of times the cut-off value. ANCA = antineutrophil cytoplasmic antibody. AAV = ANCA-associated vasculitis.