Research Article: Development and validation of a cytokine-based diagnostic model for Kikuchi–Fujimoto disease
Abstract:
The diagnosis of Kikuchi–Fujimoto disease (KFD) is challenging, which is mainly based on typical histopathological findings from a lymph node biopsy. We aimed to develop and validate a predictive model for the diagnosis of KFD based on cytokine profiles and other laboratory findings.
This study included pediatric patients with KFD and controls with other febrile diseases in a retrospective training cohort ( n = 673) and a prospective validation cohort ( n = 116). Clinical data, laboratory parameters, and serum cytokines were collected. Variables with P < 0.05 in univariate analysis and acceptable collinearity were entered into multivariable logistic regression with stepwise selection. A nomogram was constructed based on the final model. Model performance was evaluated using ROC analysis, calibration curves, Hosmer–Lemeshow test, Brier score, and decision curve analysis.
The final model included age, WBC, neutrophil, hemoglobin, platelets, ESR, IL-10, and IFN-?/IL-6, with IFN-?/IL-6 modeled as a 4-knot restricted cubic spline. The derived nomogram showed excellent performance in the training cohort (AUC = 0.989, sensitivity 97.5%, specificity 94.4%) and maintained robust discrimination in the external validation cohort (AUC = 0.971, sensitivity 94.1%, specificity 93.9%). Calibration was good in both cohorts (Hosmer–Lemeshow P = 0.99 and 0.19, external calibration slope 0.88), with low Brier scores (0.025 and 0.060). The model achieved high predictive accuracy, with 0.966 ( ? = 0.836) in the training cohort and 0.931 ( ? = 0.831) in the external cohort.
This study proposes the first validated diagnostic model for KFD, demonstrating excellent performance and highlighting the IFN-?/IL-6 ratio as a key predictor. With further validation, it may serve as a practical decision-support tool to guide clinical management.
Introduction:
Kikuchi–Fujimoto disease (KFD) is a benign, self-limiting inflammatory disease characterized by fever and cervical lymphadenopathy. The clinical presentation of KFD is highly non-specific: patients typically present with lymphadenopathy, fever, night sweats, weight loss, myalgia, and fatigue ( 1 – 3 ). Laboratory findings may include leukopenia, elevated erythrocyte sedimentation rate, and abnormal liver function tests, while imaging features are similarly non-specific ( 1 , 4 , 5 ). As a result, the diagnosis of…
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