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

Yong-Ping Xie; Yan-Wen Xu; Yan Li; Hu Zhang; Shan-Shan Xu; Mei-Na Lu; Yi-Ping Chen; Jian-Mei Tian; Xin-Fang Huang; Zhi-Feng Liu; Zhi-Gang Gao; Li-Su Huang

doi:10.2147/JIR.S504413

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

J Inflamm Res. 2025 Mar 24:18:4307-4318. doi: 10.2147/JIR.S504413. eCollection 2025.

Authors

Yong-Ping Xie^#¹, Yan-Wen Xu^#², Yan Li^#¹, Hu Zhang³, Shan-Shan Xu², Mei-Na Lu¹, Yi-Ping Chen³, Jian-Mei Tian⁴, Xin-Fang Huang⁵, Zhi-Feng Liu⁶, Zhi-Gang Gao⁷, Li-Su Huang¹

Affiliations

¹ Department 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.
² Department of Infectious Disease, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
³ Department of Pediatric Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
⁴ Department of Infectious Disease, Children's Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
⁵ Department of Rheumatology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.
⁶ Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
⁷ General Surgery Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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: CD4+ T-lymphocytes; Kikuchi-Fujimoto disease; children; ferritin; histiocytic necrotizing lymphadenitis; recurrence.

Grants and funding

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.