University of California San Francisco Fresno Fresno, CA
Award: Presidential Poster Award
Sunny Sandhu, MD1, Dhuha Alhankawi, MD1, Robert Taguibao, MD2, Marina Roytman, MD3; 1University of California San Francisco Fresno, Fresno, CA; 2Community Regional Medical Center, Fresno, CA; 3University of California San Francisco, Fresno, CA
Introduction: Hemophagocytic Lymphohistiocytosis (HLH) is a rare syndrome that frequently causes liver injury, and is fatal if not diagnosed and treated promptly. Severe immune activation presents as a prolonged febrile illness with multi-organ damage. In adults, HLH is often secondary to infection, malignancy, or autoimmune disorders. We report a patient referred for persistently elevated liver enzymes. We discuss how successful diagnosis and prompt treatment not only led to improvement of hepatitis, but was life-saving.
Methods: A 55-year old previously healthy woman was referred to our center for hepatology evaluation after multiple hospitalizations. She presented 3 months prior to the outside hospital with fevers, elevated liver enzymes, pancytopenia. Labs showed ALT 535 IU/L, AST 554 IU/L, LDH 3,239 U/L, total bilirubin 33 mg/dl (direct bilirubin 25 mg/dl), INR 2.7.Given persistently elevated liver enzymes, minimally elevated smooth muscle antibody titer (1:20) and liver biopsy showing plasma cells, she received multiple courses of high-dose steroids for presumed autoimmune hepatitis (AH) during 3 subsequent admissions for similar presentation. After failure to respond, she was transferred to our center. Given lack of typical AH markers and classic biopsy findings of AH such as interface hepatitis, she was re-evaluated. Workup showed ferritin 10,247 and splenomegaly raising suspicion for HLH. Further labs showed elevated soluble CD25, low NK cell activity, and EBV DNA 3,865. Treatment for HLH and EBV was initiated. Bone marrow biopsy was done, and liver biopsy was re-evaluated by an expert pathologist. Both demonstrated hemophagocytic histiocytosis as well as a rare T-cell lymphoma, confirming diagnosis of HLH likely secondary to lymphoma. CHP-Brentuximab chemotherapy regimen was initiated with near normalization of liver enzymes and resolution of fevers, and the patient was discharged home. Discussion: Liver injury in HLH is common, however the diagnosis is often missed which contributes to the mortality. High index of suspicion by hepatologists can be critical in identifying this rare syndrome. AST and LDH >2 times the upper limit of normal, profound direct hyperbilirubinemia and persistent fevers should prompt consideration of HLH.Targeted serological testing(ferritin, NK cell activity, soluble CD25)andliver biopsy reviewed by expert pathologist aid in expedited diagnosis. We must have a low threshold for further investigation and even empiric treatment, as it can be life-saving.
Image 1. Sections of the liver shows scattered large cells with irregular nuclear contour and prominent nucleoli which are immunoreactive for CD30, consistent with CD-30 positive large cell lymphoma
Image 2. Low power view of the liver shows expanded sinusoids
Image 3. High power view of the expanded sinusoids show hemophagocytic histiocytosis as well as extramedullary hematopoiesis. On the background are a few scattered plasma cells
Disclosures: Sunny Sandhu indicated no relevant financial relationships. Dhuha Alhankawi indicated no relevant financial relationships. Robert Taguibao indicated no relevant financial relationships. Marina Roytman indicated no relevant financial relationships.