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

Yong-Ping Xie,1,* Yan-Wen Xu,2,* Yan Li,1,* Hu Zhang,3 Shan-Shan Xu,2 Mei-Na Lu,1 Yi-Ping Chen,3 Jian-Mei Tian,4 Xin-Fang Huang,5 Zhi-Feng Liu,6 Zhi-Gang Gao,7 Li-Su Huang1 1Department of Infectious Disease, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Infectious Disease, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pediatric Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Infectious Disease, Children’s Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Rheumatology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, People’s Republic of China; 6Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 7General Surgery Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Gang Gao, General Surgery Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Binjiang District, Hangzhou, Zhejiang, 310052, People’s Republic of China, Email [email protected] Li-Su Huang, Department of Infectious Disease, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Binjiang District, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel/Fax +86 0571 86670978, Email [email protected]: 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.Patients and Methods: 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.Results: 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.Conclusion: 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.Keywords: histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto disease, recurrence, CD4+ T-lymphocytes, ferritin, children