Hemophagocytic Lymphohistiocytosis Associated with Adult Vaccination: A Case of Cytokine Flurries

Hemophagocytic Lymphohistiocytosis (HLH) is an often-fatal condition characterized by an overactive but ineffective immune response. Secondary HLH in adults is often caused by infection, autoimmune disease, and malignancy. A 67-year-old woman presented to hospital with a five-day history of malaise beginning hours after receiving influenza and pneumococcal vaccinations. Her medical history was significant for rheumatoid arthritis, controlled with methotrexate and prednisone. In hospital, she was found to have a new febrile pancytopenia that persisted despite empiric antibiotics and discontinuation of methotrexate. The patient did not have any additional clinical or laboratory evidence of an infectious focus or rheumatoid arthritis flare. She had splenomegaly, but there was no definitive evidence of malignancy. Further testing revealed hepatitis, coagulopathy, and an elevated ferritin. Bone marrow biopsy demonstrated hemophagocytosis, and a diagnosis of HLH was made. She was successfully treated with a modified HLH 94 protocol, using dexamethasone and etoposide. Unfortunately, following hospital discharge after being well for 18 months with no HLH relapses, the patient was diagnosed with anaplastic T-cell lymphoma. HLH was likely secondary to a two-hit process with vaccinations in the context of immune dysregulation secondary to rheumatoid arthritis and subclinical lymphoma. To the best of our knowledge, vaccinations have not been linked to adult HLH; therefore, this case illustrates a potentially novel association in a susceptible patient. We propose that HLH should be considered in all patients with unexplained fever and cytopenias, and diagnosis should prompt evaluation for underlying causes, including vaccinations.