INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome involving dangerously dysregulated T-cells, macrophages, and NK cells. The resulting “cytokine storm” can rapidly destroy blood cells and lead to multi-organ failure. Both familial (primary) and acquired (secondary) HLH share this life-threatening pathophysiology, typically presenting with fever, organomegaly, and cytopenias. Although historically deemed rare, HLH may be underdiagnosed due to its broad triggers (e.g., Epstein–Barr virus) and clinical overlap with conditions like sepsis. Mortality can exceed 40% if untreated, highlighting the urgency of prompt diagnosis and therapy.
OBJECTIVES: This study aims to determine the prevalence of HLH among patients with plasma ferritin levels above 2000 µg/L at our institution, while describing their clinical findings, etiologies, treatments, outcomes, and complications. It also investigates potential underdiagnosis or overdiagnosis at our hospital, explores other causes of hyperferritinemia, and sets the stage for possible future comparisons with similar patient groups at national and international treatment centers.
METHODS: We retrospectively reviewed medical records of adults (≥18 years) with serum ferritin ≥2000 μg/L admitted to our hospital from 12.11.22 to 10.01.24. This yielded 98 patients. Demographic, clinical, and laboratory data were assessed to investigate the association between hyperferritinemia and HLH.
RESULTS: Of the 98 patients, malignancies were the most common cause (34.7%), followed by infections (27.6%), liver diseases (21.4%), other etiologies (19.4%), inflammatory conditions (14.4%), sepsis (8.2%), and iron overload (6.1%). Eight patients (8.2%) were diagnosed with secondary HLH, linked to malignancies, infections, or autoimmune disorders, with a median ferritin of 8859 µg/L (IQR 7612–17718). Nearly half of the cohort (46.9%) died, including four in the inflammatory group (three with HLH), with one HLH-related death occurring during admission. Serious complications in HLH included profound cytopenias, secondary infections, and multi-organ failure, underscoring the severity of this hyperinflammatory syndrome.
CONCLUSION: This study highlights the difficulty of distinguishing HLH from other hyperinflammatory syndromes, emphasizing that ferritin, while crucial, must be interpreted alongside organ involvement, cytopenias, and histopathology. The high mortality observed in HLH and related hyperferritinemic conditions highlights the need for prompt recognition, multidisciplinary collaboration, and standardized diagnostic and treatment protocols. Prospective research on novel biomarkers and emerging therapies may further improve outcomes in these hyperinflammatory disorders.