BackgroundEpstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory disorder induced by overactivation of macrophages and T cells. This study aims to identify the risk factors for the progression from infectious mononucleosis (EBV-IM) to EBV-HLH, by analyzing the laboratory parameters of patients with EBV-IM and EBV-HLH and constructing a clinical prediction model. The outcome of this study carries important clinical value for early diagnosis and treatment of EBV-HLH.MethodsA retrospective analysis was conducted on 60 patients diagnosed with EBV-HLH and 221 patients diagnosed with EBV-IM at our hospital between November 2018 and January 2024. Participants were randomly assigned to derivation and internal validation cohorts in a 7:3 ratio. LASSO regression and logistic regression analyses were employed to identify risk factors and construct the nomogram.ResultsFerritin (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001), CD3-CD16+CD56+% (OR, 0.011; 95% CI, 0-0.467; P=0.011), anti-EBV-NA-IgG (OR, 57.370; 95%CI, 2.976-1106.049; P=0.007), IL-6 (OR, 71.505; 95%CI, 2.118-2414.288; P=0.017), IL-10 (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001) were identified as independent predictors of EBV-HLH. The prediction model demonstrated excellent discriminatory capability evidenced by an AUC of 0.997 (95% CI,0.993-1.000). When visualized using a nomogram, the ROC curves for the derivation and validation cohorts exhibited AUCs of 0.997 and 0.993, respectively. These results suggested that the model was highly stable and accurate. Furthermore, calibration curves and clinical decision curves indicated that the model possessed good calibration and offered significant clinical benefits.ConclusionsThe nomogram, which was based on these five predictors, exhibited robust predictive value and stability, thereby can be used to aid clinicians in the early detection of EBV-HLH.