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Washington University Experience | VASCULAR | Hypoxia-Ischemia, fetal-neonatal | Cerebellum | 5A0 Case 5 History
Case 5 History ---- The decedent was a 5 month old male infant who was a 32-week EGA, with delivery complicated by placental abruption and 3 week NICU admission. He was otherwise healthy until mid-May, when he developed fevers up to 104oF. He was diagnosed with upper respiratory infection, croup, and otitis media. In early June 2015, he presented to an OSC with fever, neutropenia, pancytopenia, hypoalbuminemia, coagulopathy, hypofibrinogenemia, and hypertriglyceridemia. He also had a serum ferritin level of 16,555 ng/mL (reference range 30-400 ng/mL) and serum soluble IL-2 receptor level of 43,800 pg/mL (nl <1033 pg/mL). A bone marrow biopsy and LP led to a diagnosis of hemophagocytic lymphohistiocytosis (HLH) with CNS involvement. Molecular genetic testing at Cincinnati Children's Hospital Medical Center showed two different mutated alleles of the HLH susceptibility gene MUNC13-4, predictive of familial HLH type 3. There is a positive family history of HLH involving a maternal cousin who had absent NK cell function, increased perforin expression, and decreased CD107a expression. At the OSC, HLH treatment protocol was initiated along with cefepime and fluconazole and intrathecal chemotherapy due to the CNS involvement. Worsening respiratory and renal function resulted in transfer to SLCH. At SLCH, he continued to worsen despite being treated on the HLH-2004 protocol, developing multiple organ system failure and requiring hemodialysis, mechanical ventilation, vasopressors, and plasmapheresis. He also developed toxic epidermal necrolysis, secondary to Bactrim treatment, for which he was treated with IVIG, with improvement. Initially at transfer, he was severely hypertensive and needed vasodilators, but later in the course of his hospitalization, required vasopressors to maintain blood pressure. He developed Stenotrophomonas maltophilia tracheitis and bacteremia, septic shock, and acute respiratory distress syndrome. In July 2015, he acutely developed worsening hypotension, desaturation, and bradycardia. Resuscitation efforts were unsuccessful. ---- At postmortem examination, there was widespread evidence of active HLH. Bone marrow showed a profound lack of normal hematopoietic elements, replaced largely by fat and histiocytes, with histologic presence of hemophagocytosis, also present in the liver, spleen, and lymph nodes. Active disease was not readily appreciated in the CNS, only a few histiocytes in the SAH. The anatomic cause of death in this case is consistent with acute lung and cardiac injury in the setting of systemic infection and septic shock. In the lungs, bacterial colonies were numerous and disseminated throughout the lungs, and there was concurrent widespread hemorrhage, cell death, and inflammation. Also seen at postmortem examination was evidence for focal acute myocardial ischemia. Likely the ischemic injury was secondary to increased cardiac demand in the setting of septic shock.
