#2950 IGA NEPHROPATHY: PUTTING THE A IN THE UNACQUAINTED

Abstract

Abstract Background and Aims IgA nephropathy (IgAN) is a common glomerulonephritis. Rarely it can be associated with other diseases and screening for these associations can be missed. We present 2 cases diagnosed as IgAN which were associated with rare underlying conditions. The first (patient X) is a 51-year-old female, who presented with new onset haematoproteinuria on a background of inflammatory arthritis, interstitial lung disease (ILD) and a recurrent maculopapular rash. The second case (patient Y) is a 34-year-old male, who presented with unexplained rapidly progressive chronic kidney disease and proteinuria. He had a background of hidradenitis suppurativa, acne rosacea, Crohn's disease and recurrent infections. Method X's immunology was negative aside from a weakly positive ANA and p-ANCA but negative ELISA. Her myositis panel was positive for PM/ScL antibody. Imaging showed multifocal ground glass opacification, consistent with ILD. Her renal function was normal, but renal histology demonstrated IgAN, without evidence of vasculitis. With these findings in mind, a diagnosis of anti-synthetase syndrome (AS) with IgAN was proposed. Y, conversely, had abnormal renal function, with significant proteinuria. Immunology screen was unremarkable other than a raised serum IgA, weakly positive MPO and equivocal PR3. Renal biopsy showed IgAN with severe interstitial fibrosis and tubular atrophy, and over 50% sclerosed glomeruli. Y later developed haemolytic anaemia; his neutrophil oxidase activity was absent, raising the possible diagnosis of chronic granulomatous disease (CGD). This was subsequently confirmed with genetic testing demonstrating an autosomal recessive gene for CGD. Results Both X's proteinuria and symptomatic burden significantly improved with methotrexate. Y was commenced on antibiotics and antifungals in light of the heightened risk of infection which CGD carries. He is now on maintenance haemodialysis. The only curative treatment for CGD is allogenic hematopoietic stem cell transplantation from a matched donor, for which he is being considered. Conclusion AS is a poorly defined, rare syndrome characterised clinically by ILD, arthritis and myositis. It is immunologically characterised by autoantibodies against aminoacyl tRNA synthetases; whilst X did not test positive, this does not preclude AS, as autoantibody titres fluctuate depending on disease activity [1]. Renal involvement in AS is extremely rare, or so the data would suggest. Couvrat-Desvergnes et al. examined 14 biopsies of patients with inflammatory myopathies plus renal involvement. Only 3 had AS; of these, 2 had IgAN. Other cases of IgA are described only in case reports. In all cases, immunosuppressive treatments were effective in achieving remission. Some cases describe other renal implications in AS, namely TMA and amyloidosis (Table 1). CGD is a rare primary immunodeficiency caused by genetic defects in the NADPH oxidase complex, which is critical in the destruction of phagocytes. Consequently, patients have recurrent infections and abnormal inflammatory responses result in granuloma formation. The incidence of renal disease in CGD has been suggested by some papers as being as low as 2.7% [2]. From review of the other cases of CGD with associated IgAN, it seems the patient we present is the oldest (Table 2). Interestingly, only 1 other case reports glomerulonephritis as the presenting complaint for CGD [3]. These cases highlight that, while IgAN is a disease in its own right, its diagnosis may shine light on other associated pathologies. It is crucial for nephrologists to be aware of rare associations as often it has impact on further management.