Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: a case–control study

Author:

Rincón-López Elena María,Navarro Gómez María Luisa,Hernández-Sampelayo Matos Teresa,Aguilera-Alonso David,Dueñas Moreno Eva,Saavedra-Lozano Jesús,Santiago García Begoña,Santos Sebastián María del Mar,García Morín Marina,Beléndez Bieler Cristina,Lorente Romero Jorge,Cela de Julián Elena,Hernanz Lobo Alicia,Garrido Colino Carmen,Huerta Aragonés Jorge,Mata Fernández Cristina,Bardón Cancho Eduardo,Míguez Navarro Concepción,Mora Capín Andrea,Marañón Pardillo Rafael,Rivas García Arístides,Vázquez López Paula,Jiménez Fuentes José Luis,Muñoz Fernández Maria Ángeles,Zamarro Arranz Rosario,

Abstract

Abstract Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively). Conclusion We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Funder

European Society for Paediatric Infectious Diseases

Publisher

Springer Science and Business Media LLC

Subject

Infectious Diseases

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