Pegcetacoplan for Refractory Digital Ischaemia in C3 Glomerulopathy with Monoclonal Gammopathy: Case Report

BackgroundC3 glomerulopathy is an uncommon form of complement-mediated glomerular disease marked by dysregulation of the alternative complement pathway, sometimes associated with monoclonal light chain deposits driven by a small monoclonal plasma cell or B-cell clone.Digital ischaemia (acral necrosis) is a rarely reported extra-renal manifestation in this setting.With no data on effective therapy for refractory cases, novel complement inhibitors such as pegcetacoplan are a potential therapeutic option. Case presentationWe report the case of a 61-year-old man who presented with proteinuria, preserved renal function, and digital ischemia that repeatedly relapsed leading to autoamputation of ten fingers despite standard immunosuppression, plasma exchange and myeloma therapy (CyBorD).Investigations identified a 4 g/L serum IgG lambda monoclonal protein.Renal histopathology confirmed C3-dominant lambda restricted deposits with subendothelial and mesangial localisation.Serum testing found reduced AH100, elevated Factor H and soluble C5b-9, with normal C3 and C4.In the setting of ongoing digital ischemia with threatened toe autoamputations and worsening proteinuria, the patient was commenced on pegcetacoplan therapy.Renal parameters stabilised (proteinuria resolved), and the ischaemic lesions gradually resolved with revascularisation of the toes.No infectious complications have occurred to date with 20 months follow up. ConclusionsThis is the first reported case of pegcetacoplan achieving clinical reversal of digital ischemia and renal stabilisation in a patient with refractory C3 glomerulopathy, monoclonal gammopathy and severe digital ischaemia.This case underscores the potential utility of targeted complement blockade in severe, extra-renal manifestations of C3 glomerulopathy.