MPO-ANCA Positivity in IgA Nephropathy: Deceptor or Consequence?

Background: Immunoglobulin A (IgA) nephropathy is the most prevalent primary glomerulonephritis (GN). Antineutrophil cytoplasmic-associated vasculitis (AAV) is the most common cause of rapidly progressive crescentic GN. IgA nephropathy is the most common primary glomerulonephritis, while the most common cause of rapidly progressive glomerulonephritis (RPGN) is pauci immune crescentic glomerulonephritis (GN), followed by Immune complex-mediated GN and anti-Glomerular basement membrane (GBM) disease. Anti-neutrophil cytoplasmic autoantibody (ANCA) is characterised by crescentic necrotizing GN on renal biopsy with minimal deposits. Immunoglobulin A (IgA) nephropathy may present as crescentic GN with mesangial IgA deposits and sometimes around capillary as well. The co-existence of circulating ANCA in a patient of IgA nephropathy with RPGN presentation is a rare phenomenon and very little literature is available on the same.

Case Presentation: This case describes a rare presentation of RPGN which was myeloperoxidase (MPO) positive on enzyme immunoassay (EIA) with central nervous system (CNS) vasculitis presenting as hemiparesis. The patient was treated with ANCA vasculitis, with plasmapheresis (PLEX) and Cyclophosphamide as the Standard of care as KDIGO suggests the treatment may be initiated without biopsy when the presence of RPGN picture with circulating ANCA. However, renal biopsy, later revealed features of crescentic IgA nephropathy but the presence of systemic symptoms makes IgA nephropathy as the sole diagnosis highly unlikely, hence the possibility of MPO IgA concurrence remains high. Hence our case was treated in the lines of ANCA vasculitis with IV cyclophosphamide according to EUVAS protocol. Our case is at sustained remission at 6 months after 10 doses of cyclophosphamide as SOC and has now been shifted to maintenance therapy on Azathioprine (Aza), given the possibility of relapse.

Conclusion: Hence MPO ANCA vasculitis and IgA nephropathy is a very rare concurrence. The presence of CNS vasculitis in this background is never reported. However, this case drastically improved with Pulse cyclophosphamide and corticosteroids. Further investigations are needed to study the role of ANCA in the development and progression of IgAN, whether the presence of ANCA is merely coincidental or the damage caused by IgAN results in neutrophil priming and generation of ANCAs.