Optimizing hemophagocytic lymphohistiocytosis screening in children: validation of the HLH-Screen score.

Abstract

Purpose:  A previously study proposed a three-step screening procedure for pediatric hemophagocytic lymphohistiocytosis (HLH). This procedure includes an HLH screening model referred to as HLH-screen. This study aims to validate the three-step screening procedure and the HLH-Screen in an independent cohort of children, as well as to optimize the screening process for HLH. Patients and methods. A multicenter retrospective study was conducted on children with fever or splenomegaly hospitalized in three hospitals in Hunan Province. The screening performance of the three-step screening procedure and the simplified procedure using HLH-Screen alone were evaluated. Clinical characteristics of patients misclassified as false negatives or false positives by HLH-Screen were analyzed. Results. Medical records of 5294 children with fever or splenomegaly were collected. The overall sensitivity and specificity of the three-step screening procedure were 91.0-93.7% and 91.5-91.7%, respectively. When directly applying the HLH-Screen to the study population, the sensitivity was 89.7-93.7%, and the specificity was 92.2-92.4%. Four false-negative cases lacked cytopenias, two lacked splenomegaly, and all four experienced less severe organ damage. The most common false positive diagnoses were malignancy complicated with sepsis (25.4%), infectious mononucleosis (23.9%), and malignancy complicated with respiratory infections (7.9%). Conclusion. Both screening procedures showed strong and consistent performance in screening for pediatric HLH. While the sensitivity of the three-step procedure slightly outperformed that of the HLH-Screen alone, using the HLH-Screen directly is more convenient. The HLH-Screen-based HLH screening procedure uses simple parameters to rapidly identify high-risk HLH patients, making it applicable in resource-limited settings.