Thrombotic microangiopathy in a patient with systemic lupus erythematosus and systemic sclerosis overlap syndrome: a case report and review of the literature

Background Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy (TMA) caused by autoantibody-mediated severe deficiency of ADAMTS13. Its occurrence in the setting of connective tissue disease (CTD) overlap syndromes presents a significant diagnostic challenge given the broad differential of thrombotic microangiopathy in this population. Case Presentation We report a 32-year-old woman with systemic lupus erythematosus and systemic sclerosis overlap syndrome who presented with microangiopathic hemolytic anemia, severe thrombocytopenia, and neurological symptoms. A PLASMIC score was calculated and returned at a high risk for TTP (6). ADAMTS13 activity was confirmed at < 0.03 IU/mL (< 3% activity) with an inhibitor titer of 9.8 Bethesda units, establishing the diagnosis of iTTP. Systematic exclusion of competing thrombotic microangiopathies including scleroderma renal crisis, catastrophic antiphospholipid syndrome, typical and atypical hemolytic uremic syndrome (HUS), malignant hypertension associated TMA, drug induced TMA, pregnancy associated TMA, and disseminated intravascular coagulation was essential given the distinct and sometimes conflicting therapeutic implications of each diagnosis. Treatment with plasma exchange, corticosteroids, caplacizumab, and rituximab resulted in clinical recovery over a 12-day hospitalization. Conclusions This case highlights the diagnostic complexity of thrombotic microangiopathy in CTD overlap syndromes, the importance of ADAMTS13 testing and systematic exclusion of competing diagnoses, and the critical role of empirical plasma exchange guided by the PLASMIC score while confirmation is pending.