Abstract
BackgroundEtiological 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).MethodsA 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.ResultsA 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).ConclusionWe 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.
Highlights
Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging
Four out of 79 cases (5.1%) were diagnosed with severe bacterial infection (SBI): two of them were catheter-related bacteremia, one Streptococcus pneumoniae bacteremic pneumonia and one Escherichia coli urinary tract infection (UTI). Another patient was diagnosed with Escherichia coli UTI, but she had a viral detection in a respiratory sample at the same time and, she was considered a bacterial-viral coinfection and excluded from the subanalyses
When comparing the baseline characteristics among cases with SBI, viral infection (VI) and the rest of patients with no proven infection (NPI) (Additional file 1: Table S1), no statistically significant differences were found, except for the presence of central venous catheter (CVC) and hypertransfusional regimen, which were more frequent in the SBI group (50% vs 9.8% vs 36.4%, p = 0.011 and 50% vs 4.9% vs 15.2%, p = 0.018, respectively)
Summary
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). Febrile episodes are common in children with sickle cell disease (SCD), often with challenging etiological diagnosis. These patients are at risk of severe bacterial infections (SBI), they have become less frequent in high-income countries in recent years [1,2,3,4,5]. The aim of this study was to analyze the pattern of inflammatory biomarkers, including pro-inflammatory cytokines, in SCD children with fever of different etiologies, in order to find useful parameters to discriminate the patients at risk of SBI. Since SBI has become less frequent in well-controled SCD children in recent years, this could help to guide the management of these patients, reducing unnecessary antibiotic treatments and hospital admissions
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