Unmasking Idiopathic Secondary Hemophagocytic Lymphohistiocytosis in a Young Female: A Diagnostic Challenge Presenting as Pyrexia of Unknown Origin

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that can present as prolonged fever of unknown origin (FUO). We describe the case of a 26-year-old woman who presented with two months
of intermittent high-grade fever, joint pain, and transient salmon-colored skin rashes. Laboratory investigations revealed cytopenia, elevated triglycerides, abnormal liver enzymes, and a markedly elevated serum ferritin level (>10,000 ng/mL). Extensive evaluation for infectious and autoimmune causes was negative.
Whole-body PET-CT demonstrated diffusely increased marrow activity with small mesenteric lymph nodes, while bone marrow examination confirmed hemophagocytosis. The patient met six of the HLH-2004 diagnostic criteria, and her HScore was calculated at 228, indicating a high probability of HLH. In the absence of any identifiable trigger, a diagnosis of idiopathic secondary HLH was made. She was treated with dexamethasone monotherapy, which led to rapid resolution of fever, normalization of laboratory parameters, and sustained
remission at three-month follow-up. This case underscores the importance of considering HLH early in adults with unexplained fever, cytopenia, and extreme hyperferritinemia, and highlights that corticosteroid monotherapy may be sufficient in selected idiopathic cases.