S2646 A Case of Hemophagocytic Lymphohistiocytosis (HLH) Secondary to Hepatic Mycobacterium Tuberculosis

Abstract

INTRODUCTION: Hemophagocytic Lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation causing increased systemic cytokine production. Patients can present with non-specific symptoms and signs including fever, hepatosplenomegaly, lymphadenopathy, and cytopenias, often leading to a delay in diagnosis. Here we present a rare case of HLH secondary to hepatic Mycobacterium tuberculosis (TB). CASE DESCRIPTION/METHODS: A 72-year-old woman presented with fevers, chills, and lethargy of two days duration. The patient was febrile to 102.9oF with elevated liver biochemistries (aspartate aminotransferase 162 IU/L; alanine aminotransferase 112 IU/L; alkaline phosphatase 79 IU/L, total bilirubin 4.7 mg/dL) and lactate of 3.7 mmol/L. The patient urgently underwent an Endoscopic Retrograde Cholangiopancreatography; there were no findings to suggest cholangitis. Despite broad-spectrum antibiotics, the patient remained febrile with clinical decompensation leading to respiratory failure and shock requiring intubation and vasopressors. During this time, all liver biochemistries continued to rise. A computed tomography scan of the abdomen was unremarkable without hepatosplenomegaly or cirrhosis. An extensive hepatic serologic analysis including autoimmune, metabolic, and viral studies were unrevealing. However, her ferritin was elevated to 16,854 ng/mL with a white blood cell count of 1.9 B/L and platelet count of 31 B/L. A liver biopsy revealed cholestatic hepatitis with multiple necrotizing and non-necrotizing granulomas on hematoxylin and eosin staining consistent with miliary TB. Acid fast bacilli were confirmed on immunofluorescence. The patient was initiated on a four drug TB therapy with Rifampin, Ethambutol, Levofloxacin, and Amikacin as well as dexamethasone. However, the patient’s clinical course continued to decline and the patient expired 11 days after admission. DISCUSSION: Triggers for HLH most commonly involve infections, particularly viral, but can also be bacterial. A 2015 review of 70 cases of TB-associated HLH noted a mortality rate of 49%. A ferritin >10,000ng/mL is 90% sensitive and 96% specific for HLH. Treatment for HLH includes steroids and an immunomodulator. In TB-associated HLH, initiation of antibiotics is key to remove the stimulus for the immune response. This case highlights the importance of identifying TB on histopathology and recognizing the infection as a potential cause of HLH. Prompt initiation of therapy is vital in a disease that carries a mortality rate approaching 50%.Figure 1.: Hematoxylin and eosin staining of the patient's liver biopsy showing cholestatic hepatitis with multiple necrotizing and non-necrotizing granulomas.Figure 2.: Trend of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlkP) during hospitalization.Figure 3.: Trend of total and direct bilirubin during hospitalization.