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Washington University Experience | MISCELLANEOUS | Familial erythrophagic lymphohistiocytosis | 4A0 Case 4 History
Case 4 History ---- The patient was a four month old male infant with a family history of hemophagocytic lymphohistiocytosis (HLH), born at 39 weeks gestational age via Cesarean section to a G4P3 33 year old mother. He was born and immediately admitted to the neonatal ICU due to fever, respiratory distress and cyanosis, along with a physical exam showing abdominal distention. Labs were significant for severe thrombocytopenia, low fibrinogen and very elevated ferritin (13,000), and he was transferred to the NICU at SLCH due to concern for HLH. His nine-year-old sister has familial HLH, status post bone marrow transplant (BMT) x2. She also presented with thrombocytopenia & abdominal distension at birth and was found to have PRF1-related familial HLH. The decedent was started on dexamethasone on the first day of life. During this admission, he received multiple blood transfusions and developed hypertension, managed with nicardipine. Genetic testing showed a biallelic mutation in PRF1 with loss of perforin expression, confirming the diagnosis of HLH. He was discharged and was readmitted a month later with an HLH flare. His ferritin levels continued to rise, thrombocytopenia was persistent, and he developed a new anemia. CXCL-9 and sIL2R levels were elevated. He was restarted on steroids and emapalumab, and etoposide were added to his treatment regimen. He was readmitted between 5/5-5/9 due to fever, vomiting and diarrhea; an infectious workup was unrevealing. He returned on 5/19 with worsening irritability and tachycardia, prompting admission to the pediatric ICU. A second infectious work up was negative, and an HLH flare was favored given increasing ferritin. On 6/17 he was noted to have new right arm weakness on examination; a head CT was clinically interpreted as showing a left hemispheric hypodensity. EEG showed a background consistent with encephalopathy and without epileptiform discharges or seizures. A stem cell transplant was performed on 6/19, followed by acute decompensation on 6/26 with high fevers, tachycardia, and ultimately respiratory failure requiring BiPAP with subsequent escalation to intubation and mechanical ventilation on 6/28. A chest x-ray showed pulmonary edema and effusions. Ferritin continued to rise rapidly; treatment was started for a presumed HLH flare, including steroids, gamifant, and eculizamab. On the evening of 6/28, the decedent developed acute desaturations with frothy and pink secretions leading to inadequate oxygenation and ventilation resulting in cardiac arrest.
