Catastrophic antiphospholipid syndrome accompanied by complement regulatory gene mutation.

Abstract

Background: Antiphospholipid syndrome (APS), particularly the catastrophic antiphospholipid syndrome (CAPS), is one of the rare causes of thrombotic microangiopathy (TMA). CAPS is the most severe form of APS, especially when accompanied by complement dysregulation, causes progressive microvascular thrombosis and failure in multiple organs. In this report, a case of CAPS with TMA accompanied by a genetic defect in the complement system is presented.

Case: A 13-year-old girl was admitted to the hospital with oliguric acute kidney injury, nephrotic range proteinuria, Coombs positive hemolysis, refractory thrombocytopenia, a low serum complement C3 level and anti-nuclear antibody (ANA) positivity. The kidney biopsy was consistent with TMA. She was first diagnosed with primary APS with clinical and pathological findings and double antibody positivity. As initial treatments, plasmapheresis (PE) was performed and eculizumab was also administered following pulsesteroid and intravenous immunoglobulin treatments. Her renal functions recovered and she was followed up with mycophenolate mofetil, hydroxychloroquine, low dose prednisolone and low molecular weight heparin treatments. The patient presented with severe chest pain, vomiting and acute deterioration of renal functions a few months after the diagnosis of TMA. A CAPS attack was considered due to radiological findings consistent with multiple organ thrombosis and intravenous cyclophosphamide (CYC) was given subsequent to PE. After pulse CYC and PE treatments, her renal functions recovered, she is still being followed for stage-3 chronic kidney disease. Complement factor H-related protein I gene deletion was detected in the genetic study.

Conclusions: The clinical course of complement mediated CAPS tends to be worse. Complement system dysregulation should be investigated in all CAPS patients, and eculizumab treatment should be kept in mind if detected.