Abstract | November 8, 2021
Dialing in the Immune System: Too Low, Too High, or Just Right?
Learning Objectives
- To highlight the importance of considering HLH as a differential in patients with unexplainedvfevers, cytopenias, highly elevated ferritin, acute liver failure and splenomegaly.
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition classified as either primary (genetic/familial) and secondary (acquired).
Case Presentation: A 36-year-old Caucasian male presented with four days of fever, chills, cough, myalgia. PMH includes chronic pontine inflammation treated with methotrexate for 13 years and had been weaning for the last 12 months. Vital signs include a temperature of 101.5, HR 110, BP: 90/50. Labs: WBC-2.1, Hb-6.9, Platelets-26 were low, ALT-634, AST- 491, Ferritin- 1,643, Triglycerides-366 were elevated. He was started on broad-spectrum antibiotics but remained febrile. Infectious disease workup for TB, influenza, COVID-19, HIV, Hepatitis A/B/C, CMV, EBV, Mycoplasma, Cryptococcus, Legionella, Strep pneumonia, Histoplasma was negative. Autoimmune workup included IgG, rheumatoid factor, ANA, antimitochondrial Abs, anti-sm muscle Ab were also negative.
Working diagnosis: Given that ferritin and triglycerides were elevated and infectious/autoimmune etiology was ruled out, HLH was being considered and workup was broadened. Soluble IL-2 receptor was high; peripheral smear showed T cell lymphoproliferative disorder, bone marrow biopsy had normocellular marrow with megakaryocytic hyperplasia and a mild increase in T lymphocytes. Lung biopsy showed dense atypical T cell lymphocytic infiltrates consisting of small lymphocytes and larger histiocytes.
Management and follow up: We deduced that decreasing the methotrexate dose caused a gradual reduction in his chronic immunosuppression, thus leading to activation of the immune system causing HLH. He was started on steroids following which his labs improved. He was discharged with a prolonged steroid taper and is currently doing well. HLH is a hyperinflammatory syndrome with an incidence estimated to be 1.2 cases per 1 million individuals per year. Diagnosis of HLH is often delayed and challenging due to its rare occurrence, variable presentation, and diagnostic criteria. Prognosis is poor due to diagnostic difficulty. Mortality in secondary HLH is estimated at 10-15%. Treatment includes immunosuppression and potentially bone marrow transplant.
