Development of a screening score for Hemophagocytic Lymphohistiocytosis among pediatric patients with acute infection of Epstein-Barr virus

Abstract

Background and aimsDeciding when to suspect hemophagocytic lymphohistiocytosis (HLH) and perform diagnostic tests in patients with acute infection of Epstein-Barr virus (EBV) is challenging, given the high prevalence of EBV infection, the life-threatening risk of EBV-HLH, the relatively low incidence of EBV-HLH, and the wide spectrum of disease presentations. The aim of this study was to develop an EBV-HLH screening model for pediatric patients diagnosed with acute infection of EBV.MethodsAn inpatient cohort with 3183 pediatric patients who were diagnosed with active infection of EBV was used to construct and validate the EBV-HLH screening score model. The model parameters were selected from common laboratory parameters using the method of Akaike Information Criterion-optimal selection through cross-validation under logistic regression. Performance of the score was evaluated and compared with the performance of screening methods using the number of cytopenias lineages.ResultsThe EBV-HLH screening score has five parameters, including hemoglobin, platelet, neutrophil, albumin, and lactate dehydrogenase. Using a cut-of value of 29, the scoring model had a sensitivity of 89.2% and a specificity of 89.5% in the validation set. The false negative rate, false positive rate, positive predictive value, and negative predictive value in the validation set was 10.8%, 10.5%, 26.8%, and 99.5%, respectively, similar to that of the training set.ConclusionsWith five common laboratory parameters, the EBV-HLH score provides a simple tool to assist the identification of EBV patients who require further evaluation of HLH. Further studies are needed to evaluate the generalizability of the score and optimize the diagnose process for EBV-HLH.

Development of an early mortality risk prediction model for pediatric hemophagocytic lymphohistiocytosis

“…Most current prediction model were tailored to adult patients with HLH [16], or pediatric patients with speci c etiologies, such as EBV-HLH [17]. Comparing adult patients with HLH, pediatric patients experience higher morbidity and early mortality: A recent long-term retrospective study from China involving adult HLH patients reported the 30-day mortality rate of 16.35% between 2013 and 2018 [18]; in our study, 20% of the pediatric HLH patients died within 28 days since diagnosis, as approximately consistent with results from previous studies [19].…”

Comparative study of biomarkers for the early identification of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in infectious mononucleosis

“…Although our study indicated that ferritin had good specificity and sensitivity in separating the two diseases at an early stage, some infants with HLH did not exhibit typical symptoms of elevated ferritin at that time; therefore, a comprehensive diagnosis model with multiple indicators is required. Li et al developed an EBV-HLH score with five parameters, including hemoglobin, platelet, neutrophil, albumin, and LDH, which has a sensitivity of 89.2% and a specificity of 89.5%, to help identify EBV patients that need additional HLH screening [ 12 ]. Smits et al discovered a minimal parameter set consisting phagocytosis, splenomegaly, cytopenia, increased ferritin, and increased triglycerides that can predict HLH with a sensitivity of 95% and a specificity of 94% [ 13 ].…”

“…Our team has used a cytokine profile as a supplementary instrument for rapidly evaluating HLH [ 10 , 11 ], and it is essential to discover other clinical or laboratory markers that aid in the early identification of HLH in patients with childhood EBV-IM in addition to the cytokine pattern. Li et al and Smits et al have developed predict models to early identify HLH patients from those with acute EBV-infection or suspected HLH, which include clinical, biologic, and cytologic variables but without cytokine profile [ 12 , 13 ].…”