S SO1,2, B BOSE1,3, K SOL1,3, N WONG1
1Department of Renal Medicine, Nepean Hospital, Kingswood, Australia, 2Department of Renal Medicine, Westmead Hospital, Westmead, Australia, 3University of Sydney, Nepean Clinical School, Kingswood, Australia
Background: Double-seropositive antineutrophilic cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease is increasingly recognised, and is characterised by shared features of both conditions. We report a case of relapsing ANCA-associated disease, with subsequent development of anti-GBM antibody and historic biopsy features consistent with anti-GBM disease.
Case: A 48-year-old man with known granulomatous polyangiitis (GPA) presented with haemoptysis, acute kidney injury, and fever. An initial diagnosis of “Goodpasture’s Syndrome” had been made at 18-years-old, on presentation with haemoptysis, arthritis and haematuria. Anti-GBM antibody serology was negative at the time and ANCA result unavailable. Retrospective renal biopsy review revealed crescentic necrotizing glomerulonephritis with linear immunoglobulin G staining of the GBM. Over 20 years, he had three relapses characterized by haemoptysis and subsequent investigations revealed positive ANCAs directed against proteinase-3 (PR3) at >100 U/L, leading to a diagnosis of GPA. All relapses responded to immunosuppression escalation followed by maintenance cyclophosphamide and prednisolone, until full immunosuppression withdrawal three years prior to current presentation. His cumulative cyclophosphamide dose exceeded recommended lifetime maximum. He is a lifelong non-smoker. On current presentation, chest X-ray demonstrated bilateral nodular opacities with right upper lobe consolidation and Legionella pneumophila infection was confirmed serologically. He demonstrated new positive serology for anti-GBM antibody and persistent anti-PR3 positivity. Remission was induced with plasmapheresis, steroids, and low-dose intravenous cyclophosphamide, with subsequent clinical improvement and concurrent reduction in anti-GBM levels but persistence of anti-PR3 levels.
Conclusions: Although anti-GBM disease is classically a ‘one-hit’ disease, double positivity for ANCA likely infers a multirelapsing course and high initial mortality. This case is meaningful for understanding the pathophysiology of double-positive disease and highlight the considerations of long term immunosuppression.
Dr So is a second-year renal advanced trainee in the Western Sydney renal network.