Case Presentation: A 69-year-old female with a medical history of morbid obesity presented to a rural hospital with a one-week history of extreme fatigue, malaise, jaundice, and anorexia. Her initial vital signs were unremarkable. Physical exam revealed a distressed-appearing woman with diaphoresis, scleral icterus, jaundice, and lower extremity edema. Laboratory findings revealed significant elevation of total bilirubin (14.8mg/dL), direct bilirubin (13.6 mg/dL), and alkaline phosphatase (457 IU/L), with only mild elevations in transaminases and mild pancytopenia. Liver failure workup was negative for hepatitis, autoimmune causes, drug injury, or viral infections (EBV, CMV). She made no clinical improvement and was transferred to a tertiary center for further workup of her cholestatic liver failure. The patient’s bilirubins continued to worsen (total 27.5 mg/dL, direct 20.2 mg/dL). She developed hemodynamic instability and multiorgan failure, requiring vasopressor support and hemodialysis. Imaging revealed diffuse hepatic echogenicity, hepatomegaly, and splenomegaly with no biliary ductal dilation or masses. Liver and bone marrow biopsies demonstrated T-cell infiltration, with immunohistochemical negativity for B cell markers. Six of the nine diagnostic criteria for HLH were met: fever, splenomegaly, elevated ferritin (4054 μg/L), IL-2 receptor level 64800 U/mL, hemoglobin 8.1 g/dL with platelets 15 x 109/L, and hypofibrinogenemia (0.72 g/L). She was diagnosed with secondary HLH due to T-cell lymphoma. Dexamethasone and etoposide were started. Despite a complicated hospital course, clinical stabilization was achieved.
Discussion: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder, prevailingly fatal without appropriate treatment. Because of its rapidly fatal course, it is a hospitalist disease. The pathology of both primary and secondary HLH is driven by histiocytic and lymphocytic overactivity, spurring an excessive inflammatory response and ultimately multi-organ failure. Secondary HLH is most commonly a sequela of malignancy, infection, autoimmunity, or medication. Of the 27% of cases of secondary HLH associated with malignancy, T-cell lymphoma is the most common neoplastic process. Although the pathology of our case is fairly classical, secondary HLH in the context of T-cell lymphoma, the presentation is unique. Hepatic biomarker derangement is common in HLH, but acute liver failure as its predominant feature is rare. Cholestasis and hyperbilirubinemia is even less typical.Treatment delay drastically reduces survival in HLH. A Swedish case series on ten patients ultimately diagnosed with HLH found a median time to diagnosis of 20 days after hospital presentation. Our patient, with an atypical HLH presentation, received dexamethasone on her 11th day of admission to the tertiary center, 19 days after presentation to a rural emergency department. In secondary HLH, administration of glucocorticoids and treatment of the underlying inciting factor, potentially with an immunochemotherapy adjunct (such as etoposide and/or CHOP), is the lifesaving mainstay of treatment.
Conclusions: This case of HLH presented atypically, with cholestatic acute liver failure. Prompt recognition and treatment of HLH is crucial, as it is nearly universally fatal without prompt initiation of appropriate treatment. Maintaining a broad differential diagnosis that includes rare and deadly disorders like HLH is necessary to implement lifesaving interventions.