Sjögren disease and idiopathic inflammatory myopathy overlap presenting as complement-mediated thrombotic...

Complement-mediated thrombotic microangiopathy (CM-TMA) is often triggered by autoimmune diseases; however, reports of CM-TMA in patients with Sjögren disease (SjD) and idiopathic inflammatory myopathy (IIM) are limited. We describe the case of a 48-year-old woman with overlapping SjD and IIM who presented with interstitial lung disease. After initiation of combination therapy with calcineurin inhibitor, intravenous cyclophosphamide, and glucocorticoids, she developed progressive thrombocytopenia with schistocytosis, haemolytic anaemia, and acute renal dysfunction. Laboratory testing revealed preserved disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity (49%) with negative ADAMTS13 inhibitor and Shiga toxins. Despite therapeutic plasma infusion and plasma exchange, she developed severe cardiac dysfunction and abdominal pain, with progressive haematologic and renal dysfunctions requiring haemodialysis. Based on a clinical diagnosis of CM-TMA, eculizumab was initiated, resulting in gradual improvement in haemolysis markers and platelet counts. However, she developed severe multiorgan complications, including cerebellar haemorrhage, acute pancreatitis and coagulopathy, and ultimately died. Genetic testing performed during the clinical course identified a complement factor B (CFB) p.Arg74His variant. This case represents an instance of CM-TMA associated with a SjD/IIM overlap and a CFB variant of uncertain pathogenic significance, suggesting that multiple converging factors may contribute to CM-TMA development.