Primary Hemophagocytic Lymphohistiocytosis With Prolonged Primary Neurologic Presentation

Primary hemophagocytic lympho-histiocytosis (HLH) is a hyperinflammatory syndrome with devastating consequences. Multisystem involvement is a hallmark of HLH; however, HLH may rarely present with signs and symptoms isolated to the central nervous system (CNS). Within the brain, HLH can mimic demyelination, chronic infection, or vasculitis, leading to a diagnostic delay of months to years. We describe here a 7-year-old boy who presented with a history of prolonged fever and multiple focal neurologic deficits, which were being treated as CNS tuberculosis at the referring hospital. In view of the relapsing course with multiple areas of hemorrhagic tumefactive lesions on neuroimaging, the diagnosis was revised to acquired demyelination, and he received multiple cycles of immunotherapy. A brain biopsy was inconclusive. Subsequently, 13 months after disease onset, the child presented with features of systemic HLH in the form of fever, pancytopenia, splenomegaly, elevated ferritin, and triglycerides. Primary HLH was suspected, and genetic testing revealed a likely pathologic compound heterozygous variation in the PRF1 gene confirming the diagnosis. We planned a hematopoietic stem cell transplant as definitive therapy, but the child succumbed to an episode of sepsis and aspiration pneumonia. We infer from this case that primary HLH is a great mimicker. A high index of suspicion is required to establish a timely diagnosis. Primary HLH may stay isolated to CNS for months and should be considered in the differential diagnosis of all refractory cases of demyelination.