Abstract
Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such ‘double-positive’ cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.
Highlights
Co-presentation with both anti-neutrophil cytoplasm antibody (ANCA) and anti-glomerular basement membrane (GBM) antibodies is thought to be relatively rare
Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysisdependent after treatment and had intermediate longterm renal survival compared to the single-positive patients
Patients with associated vasculitis (AAV) had a lower hazard ratio of progression to end-stage renal disease (ESRD) or death compared with patients who were double positive (HR: 0.57 [0.35–0.93]; P 1⁄4 0.02). This is the largest published series to compare the outcomes of patients with both ANCA and anti-GBM autoantibodies with patients with single-positive AAV and anti-GBM disease
Summary
Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are rare conditions, with estimated incidences in Europe of 1 and 20 per million population per year, respectively.[1,2] The concurrence of both ANCA and anti-GBM antibodies in individual patients, is well-recognized, and occurs at a much higher frequency than would be expected by chance alone. Comparison between groups by Kruskall–Wallis test with Dunn’s post-test to ascertain differences between individual groups (for continuous data), or by chi-square test (for categorical data). aCalculated for a sample of 48 ANCA cases. bCensored for patients on RRT
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