Hemophagocytic Lymphohistiocytosis: An Underrecognized Complication of Pediatric Crimean‐Congo Hemorrhagic Fever
Kubra Aykac, Ozlem Cakici, Aylin Irmak Kuruc, Canan Ozlu, Pınar Koc, Bera Enes Seyrek, Tekin Aksu, Selin Aytac, Hanife Avci, Ali Bulent Cengiz, Yasemin OzsurekciABSTRACT
Aim
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life‐threatening hyperinflammatory complication of Crimean‐Congo hemorrhagic fever (CCHF), yet pediatric data remain limited. This study aimed to characterize the clinical phenotype of pediatric CCHF‐associated sHLH and to identify early clinical features associated with sHLH development.
Methods
PCR‐confirmed pediatric CCHF cases from four tertiary centers in Türkiye (2018–2025) were retrospectively analyzed, and clinical characteristics, laboratory findings, treatment, and outcomes were compared between children with and without sHLH.
Results
Of 79 patients, 27 (34.2%) fulfilled the diagnostic criteria for sHLH. Compared with children without sHLH, these patients more frequently presented with hemorrhagic findings (44.4% vs. 11.5%, p = 0.002), diarrhea (37.0% vs. 7.7%, p = 0.004), and bradycardia (25.9% vs. 1.9%, p = 0.002), and had lower platelet and fibrinogen and higher ferritin, AST, ALT, and LDH concentrations at diagnosis. On multivariable analysis, bradycardia (OR 11.1, 95% CI 1.7–126.3), hemorrhagic findings (OR 7.1, 95% CI 2.1–26.5), and diarrhea (OR 6.4, 95% CI 1.6–29.0) remained independent predictors; hemorrhagic findings and diarrhea preceded the sHLH diagnosis, whereas bradycardia was identified concurrently. Ferritin and aPTT worsened progressively only in children with sHLH, whereas platelet count declined in both groups. Despite more frequent immunomodulatory therapy and transfusion, no deaths occurred.
Conclusions
Secondary HLH should be actively considered in pediatric CCHF, particularly with hemorrhagic findings, diarrhea, or bradycardia preceding full laboratory evolution to facilitate earlier diagnosis and timely therapy.