Diagnostic Accuracy of a Specific Cytokine Pattern in Hemophagocytic Lymphohistiocytosis in Children

• Published in: The Journal of pediatrics Vol. 160; no. 6; pp. 984 - 990.e1
• Main Authors: Xu, Xiao-Jun, MD, Tang, Yong-Min, MD, Song, Hua, MD, Yang, Shi-Long, MD, Xu, Wei-Qun, MD, PhD, Zhao, Ning, MD, Shi, Shu-Wen, MD, Shen, He-Ping, MD, Mao, Jun-Qing, MD, Zhang, Ling-Yan, MD, Pan, Bin-Hua, MD
• Format: Journal Article
• Language: English
• Published: Maryland Heights, MO Mosby, Inc 01.06.2012; Elsevier
• Subjects: Adolescent; Biological and medical sciences; Biomarkers - blood; blood serum; Child; Child, Preschool; children; Cytokines - blood; Diagnosis, Differential; Female; fever; Follow-Up Studies; General aspects; Humans; Infant; Infant, Newborn; interferon-gamma; Interferon-gamma - blood; interleukin-10; Interleukin-10 - blood; interleukin-2; interleukin-4; interleukin-6; Interleukin-6 - blood; Lymphohistiocytosis, Hemophagocytic - blood; Lymphohistiocytosis, Hemophagocytic - diagnosis; Male; Medical sciences; patients; Pediatrics; Prospective Studies; Reproducibility of Results; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - blood; FUO; Interferon-gamma; CBA; sCD25; IL; HLH; Cytometric bead array; Interleukin; ROC; Soluble interleukin-2 receptor; Hemophagocytic lymphohistiocytosis; IFN-γ; Tumor necrosis factor-alpha; Receiver operating characteristic; TNF-α; Fever of unknown origin; Human; Immunopathology; Pediatrics; Accuracy; Cytokine; Diagnosis; Child
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2011.11.046

Objective The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children. Study design In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. Results Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. Conclusions The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.