Seasonal fever for 11 years! A presentation of hemophagocytic lymphohistiocytosis secondary to marginal zone lymphoma

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation and immune activation. The syndrome can be triggered by multiple events that disrupt immune homeostasis, including infection, autoimmune diseases, and lymphoma. Although more common in children—which might indicate a genetic cause—HLH can occur in patients of any age. The most common presenting features of HLH are fever, cytopenia, hepatitis, and splenomegaly. Other features include neurologic abnormalities such as altered mental status, seizures, and ataxia. It is a reactive process of antigen-presenting macrophages and CD8+ T‑cell activation and migration. In addition, abnormalities in the action or number of natural killer cells have been observed. Direct cytotoxicity from T cells, along with elevated levels of pro-inflammatory cytokines and interleukins, plays a role in the generation of excessive inflammation that leads to organ dysfunction. We present the case of a 61-year-old female patient with a past history of recurrent self-limiting episodes of fever that occurred two to three times every autumn for the past 11 years. The meticulous thought process that led to her diagnosis with HLH and marginal zone lymphoma is discussed.