Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 10 3 2025 12 09 103 108 EN Anamitra Hait Department of Internal Medicine, Indian Railways Medical Service, Eastern Railway Production Unit Hospital, Chittaranjan, West Bengal, India. Shridhar Jayagopalan Department of Internal Medicine Central Hospital, Bhandup, Mumbai – 400078, India. Arbind Choudhary Department of Pharmacology, Government Erode Medical College and Hospital, Erode, Tamil Nadu, India. 2025 07 20 2025 09 27 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. https://crcp.tums.ac.ir/index.php/crcp/article/view/1076 https://crcp.tums.ac.ir/index.php/crcp/article/download/1076/727