Between a Rock and a Hard Place!

Introduction: Hemophagocytic lymphohistiocytosis (HLH) and thrombotic thrombocytopenic purpura (TTP) are rare disorders with high mortality, and rarely occur concurrently. Case Description: 43-year-old male with a history of asthma, depression, migraines, and seizures presented with general malaise and chest pain, along with bruising and skin mottling. He had elevated INR, D-dimers, lactic acid, liver enzymes, ferritin, troponin, creatinine, and thrombocytopenia. Blood cultures showed pneumococcal bacteremia. EBV serology was Negative. An H-score of 235 indicated a high probability of HLH, and was started on empiric steroids. ADAMTS13 activity was 1%, suggesting TTP. He was started on therapeutic plasma exchange (TPE) which improved his platelet count and ADAMTS13 level; also started renal replacement therapy (RRT) for oliguric AKI presumed due to septic acute tubular injury, IL-2 receptor levels were >4000, suggesting HLH. He developed bullous rash w/subcutaneous edema. He continues to receive TPE, steroids, and antibiotics with a bone marrow biopsy planned. Discussion: TTP and HLH are both life-threatening syndromes requiring immediate attention. TTP is diagnosed using a clinical pentad and confirmed with ADAMTS13 assay, and treated with TPE. Accurate diagnosis of HLH relies on meeting five of eight clinical criteria and H-score, with elevated ferritin levels above 7,500-10,000 ng/ml enhancing specificity. Neurological symptoms and thrombocytopenia in both conditions can complicate diagnosis. Both conditions demand aggressive treatment strategies— for TTP, plasma exchange, high-dose corticosteroids, and adjunct therapies like Rituximab; HLH is treated with steroids, IVIG, and addressing underlying etiology such as infection or malignancy. There are case reports of pneumococcal infections separately causing TTP and HLH; and also reports of concurrent HLH and TTP, due to EBV infection or malignancy. This is the first reported case of pneumococcal infection causing concurrent TTP and HLH.