P3C269: System Overload: Jaundice in Adolescent Patient Leading to Diagnosis of Hemophagocytic Lymphohistiocytosis from Occult Malignancy

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of dysregulated immunologic activity that can result in multi-system organ failure. Primary HLH is the result of inherited genetic mutations. Secondary HLH, often called macrophage activating syndrome (MAS), is an inappropriate hyper-inflammatory response triggered by infection, malignancy, or autoimmune disease. Reported predominantly in adults 50 and older, it is an uncommon diagnosis in children and adolescents. Here, we describe a rare case of HLH secondary to occult malignancy in a previously healthy adolescent patient.

Case Description: A 17 year-old male presented to the pediatric emergency room for jaundiced skin for one day. This was preceded by diarrhea for six days, a “yellow glow” to his urine, abdominal pain, loss of appetite, and chills. His vital signs and exam were normal aside from notable scleral icterus and jaundice. There was no abdominal tenderness or hepatosplenomegaly. Laboratory findings demonstrated significant transaminitis, direct hyperbilirubinemia, hypoalbuminemia, elevated ferritin and INR. He was admitted to a pediatric intensive care unit for further management of acute liver insufficiency. He tested positive for adenovirus, which was considered a possible cause. He was treated with Vitamin K and Ursodiol and discharged home after labs normalized. One week later, he returned for continued jaundice, fevers, and weakness. His labs mimicked his initial presentation along with a newfound pancytopenia. Hematology/oncology, infectious disease, and rheumatology were consulted. HLH-specific testing confirmed the diagnosis. Bone marrow biopsy demonstrated blast cells and subsequent flow cytometry identified B-cell acute lymphoblastic leukemia (ALL). The patient underwent induction therapy to treat both his malignancy and HLH.

Discussion: HLH is a relatively rare entity that uncommonly presents with jaundice as its primary symptom. Risk of secondary HLH increases with age, making it uncommon in the adolescent population. Literature cites that the most common malignancies associated with secondary HLH are T-cell and NK-cell lymphoid neoplasms, making B-cell ALL an infrequent trigger. In HLH, malignant cells and infections can trigger an overwhelming cytokine storm that infiltrates major organs such as the spleen and liver, subsequently destroying major cell lines. Diagnostic criteria include prolonged fever, organomegaly, cytopenias, hyperferritinemia, hypofibrinogenemia, hypertriglyceridemia, and evidence of hemophagocytosis. Jaundice is a manifestation of liver involvement. Diagnosis can be challenging as these criteria overlap with many other multi-system disease processes. Prompt recognition is necessary, as this overactive immune response can lead to systemic decompensation associated with high morbidity and mortality. Management relies on controlling immune system overload and treating the underlying disease process.

Conclusion: This case of unexplained acute jaundice and pancytopenia in an adolescent patient should prompt physicians to consider a wide array of differential diagnoses. While infection is a likely cause of jaundice, physicians must also suspect more uncommon but nebulous diagnoses such as HLH, along with its potential underlying triggers.