P0882 - Congenital HLH masquerading as breast feeding jaundice in a neonate

Introduction
Hemophagocytic lymphohistiocytosis (HLH) is a severe congenital or acquired disease of immune dysregulation characterized by overactivation of lymphocytes and macrophages with resulting cytokine storm and multi-organ dysfunction. We present a case of a neonate admitted for hyperbilirubinemia who developed progressive multi-organ failure and death due to congenital HLH.

Case
A 4-day-old male presented to our community pediatric hospital from his pediatrician’s office for hyperbilirubinemia. He was born at 39 weeks gestation via vaginal delivery after an uncomplicated pregnancy. Discharge bilirubin at 48 HOL was 10.2mg/dL and transcutaneous bilirubin on day of admission was 19.4mg/dL. Mom reported no fever, irritability, lethargy, or breastfeeding difficulties. On admission he was jaundiced but with an otherwise normal newborn exam. Admission labs were notable for an indirect hyperbilirubinemia (18.9mg/dL), leukocyte count of 5.4K/µL, hemoglobin of 15.8g/dL, and platelets of 89K/µL. Mom and baby were both O+ with negative direct Coombs test, and mom’s infectious prenatal labs were negative.

Despite receiving intensive phototherapy for presumptive breast feeding jaundice, his bilirubin remained around 15mg/dL, and on DOL 7 his platelets decreased to 33K/µL and leukocytes to 5.1K/µL, He developed abdominal distention, splenomegaly, and irritability, though he remained afebrile. Abdominal ultrasound revealed splenomegaly (7cm) with multiple hypoechoic lesions (Figure 1) concerning for abscesses or infarcts. We initiated a partial sepsis workup, administered empiric antibiotics, and transferred him to our tertiary care hospital where further workup revealed hyperferritinemia (17,033ng/mL), hypofibrinogenemia (60mg/dL), and elevated soluble IL-2 receptor (23076 unit/mL), consistent with a diagnosis of congenital HLH. Despite initiation of HLH treatment, he had intractable coagulopathy with progressive respiratory, cardiovascular, liver, and renal failure. He suffered a massive intracranial hemorrhage on DOL 13, a DNR order was placed, and he subsequently died on DOL 14. Genetic testing sent prior to death showed a homozygous mutation in the PRF1 gene, diagnostic of congenital HLH.

Discussion
Congenital HLH is a rare inherited disease typically diagnosed before one year of age and has a 25-55% mortality rate. While mutations in the perforin gene are detected in 20-40% of these patients, results take a couple weeks to return so we must often rely on a clinical diagnosis. To diagnose HLH, a patient must meet at least five of the eight diagnostic criteria (figure 2). At presentation this patient met no criteria; he had hyperbilirubinemia that we attributed to breast feeding jaundice and moderate thrombocytopenia and borderline leukopenia which are both nonspecific and rather common in neonates admitted to the hospital. His rapid clinical decompensation and death highlight the importance of considering HLH in patients with recalcitrant hyperbilirubinemia, thrombocytopenia, and splenomegaly.