Recurrence of Histiocytic Necrotizing Lymphadenitis in Children: A 10-year Multicenter Retrospective Study

Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi-Fujimoto disease, is prone to recurrence in children. However, the frequency and risk factors associated with recurrence remain unclear.

This study included all children with pathology-confirmed HNL from five hospitals over ten years (2013-2023). This study employed STROBE analysis to investigate the association between clinical characteristics and HNL, which was subsequently verified through in both a derivation group and a validation group. Initial clinical features were collected, and data were randomly divided into derivation and validation sets (3:2 ratio). Cox regression analysis identified risk factors, and receiver operating characteristic curves were used to develop a prediction model. Flow cytometry focused on assessing CD4⁺ T-lymphocytes in lymphoid tissue.

Of the 593 HNL cases, 88 (14.8%) experienced recurrence during a median follow-up of 3 years. Cumulative recurrence rates at the first, fifth, and ninth years were 8.7%, 20.0%, and 32.2%, respectively. Factors associated with recurrence included age ≤ 6-year-old (Hazard ratio [HR] 3.6, 95% confident interval [CI], 2.0-6.4), C-reactive protein > 16 mg/L (HR, 1.9, 95% CI, 1.0-3.6), blood CD4⁺ T-lymphocytes ≤ 30% (HR, 4.4, 95% CI, 1.0-18.7), ferritin > 150 μg/L (HR, 2.3, 95% CI, 1.1-5.3) and platelets ≤ 200×10⁹/L (HR 1.8, 95% CI, 1.0-3.2). The prediction model demonstrated areas under the curve of 0.81 for the derivation dataset and 0.77 for the validation dataset, classifying patients into low, medium, and high-risk categories, with corresponding recurrence rates of 5.2%, 19.0%, and 42.9%. Lower lymphoid CD4⁺ T-lymphocyte counts were also observed in the recurrent group.

The recurrence of HNL increases over time. Key factors, including C-reactive protein (CRP) levels, CD4⁺ T-lymphocyte counts, ferritin, platelets, and age at diagnosis may contribute to recurrence risk.