Sequential Therapy for Remission Induction in Severe Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis.

BACKGROUND: The introduction of combination therapy with glucocorticoids (GC) and cyclophosphamide (CYC) or rituximab (RTX) has resulted in remission rates exceeding 90% in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, early treatment-related mortality remains a major concern and has driven the search for safer induction regimens exploring minimization or avoidance of GC and CYC. Most trials have excluded patients with severe renal disease. We report the outcomes of AAV patients with severe renal disease treated with sequential therapy (ST) starting with (GC) and oral (CYC) followed by transition to (RTX). METHODS: Patients with new or relapsing severe AAV who presented with severe renal disease and/or rapidly progressive glomerulonephritis (RPGN) were identified. RPGN was defined as at least a 20% decrease in estimated glomerular filtration rate (eGFR) over a 2-week period along with hematuria and proteinuria. Induction treatment included pulse (GC) for 3 days followed by oral prednisone tapered to 5 mg by month 6, oral (CYC) adjusted for GFR until improvement in Birmingham Vasculitis Activity Score (BVAS), and serum creatinine at which point (CYC) was stopped and induction dose of (RTX) was given. Use of plasmapheresis (PLEX) was allowed. The primary outcome was complete remission defined as BVAS of zero by 6 months. Descriptive data are presented as median with range and mean with SD. RESULTS: Nine patients met the inclusion criteria. Median age at diagnosis was 63 years. The majority were females, myeloperoxidase ANCA positive, and had a new diagnosis. The mean nadir (SD) eGFR was 12 (5) with 3 requiring dialysis. The median BVAS at the time of diagnosis was 15. All patients received ST and 3 received PLEX. The median exposure to oral CYC was 35 days. The mean (SD) eGFR and median BVAS were 26 (12) and 3, respectively, at the time of switching to RTX. The median prednisone dose at 6M was 5 mg. The median follow-up was 44 months. All patients achieved remission. One patient with relapsing disease reached ESRD. The mean (SD) eGFR in the remaining 8 patients at last FU was 37 (27), and the mean (SD) eGFR rise at 1 year was 26 (25). Adverse events included 2 patients with pneumonia and 3 with bone marrow suppression. There were no deaths. CONCLUSION: ST with GC and CYC followed by RTX is effective for in AAV patients with severe renal disease. Therapy-related adverse events are comparable to other studies, and further modification in ST with decrease in GC dosage should be explored.

Correction to: Uncommon presentations in ANCA vasculitis: clinical characteristics and outcomes.

The family name of the co-author of the article mentioned above was incorrectly spelled. The correct name should have been "Veena S. Katikineni"instead of "Veena Katikeneni". The original article has been corrected.

Uncommon presentations in ANCA vasculitis: clinical characteristics and outcomes.

ANCA-associated vasculitis (AAV) can present in an atypical manner and obscure the clinical picture. We sought to characterize clinical characteristics and outcomes in these uncommon presentations. We conducted a retrospective study of 171 AAV patients in our vasculitis database to identify patients with atypical presentation of AAV. Patient demographics, serologies, renal indices, and treatment regimens were assessed. Of the 171 patients, eight were identified to have uncommon presentations. These patients were usually extremes of age with three being less than 30 years and four being more than 70 years. Six patients were positive for PR3 antibodies. The mean delay in diagnosis from time of symptom development was 12 months. All patients developed acute kidney injury during their clinical course. Pancreatitis was the most frequent atypical presentation (n = 3), with pulmonary pathologies (cystic lung disease and usual interstitial pneumonia) and splenic infarcts being present in two patients each. The diagnosis of AAV was established by positive ANCA serology and renal or lung biopsy evidence of vasculitis. Six patients received induction therapy with steroids and rituximab, while two received steroids and cyclophosphamide. One patient died of respiratory failure in the first month following diagnosis while the remaining patients achieved disease remission. One patient developed end-stage renal disease. Uncommon presentations of AAV afflict extremes of age with a PR3 ANCA predominance and are associated with subsequent development of AKI. This case series demonstrates that a significant delay in diagnosis can be associated with these presentations. KEY POINTS: • Uncommon manifestations of AAV are seen more often with PR3 ANCA disease and respond to standard induction therapy of AAV. • High index of suspicion is required to avoid delays in diagnosis.