Validation and Optimization of Classification Criteria for Childhood-onset Systemic Lupus Erythematosus in a Multi-center Chinese Cohort

Yudi Zhang¹Tian Shen¹Sihao Gao²Junxia Yan³Jingcheng Shi³Xuemei Tang⁴Mo Wang⁴Yang Jun⁵Haiguo Yu⁶Huawei Mao⁷Lanjun Shuai¹Yongzhen Li¹Yan Cao¹Xiaoyan Li¹Wang Ying¹Qian Liu¹Hongmei Song²Xiaochuan Wu^1*

• ¹Second Xiangya Hospital, Central South University, Changsha, China
• ²Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
• ³School of Public Health, Central South University, Changsha, Hunan Province, China
• ⁴Children‘s Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China
• ⁵Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China
• ⁶Nanjing Children's Hospital, Nanjing, Jiangsu Province, China
• ⁷Beijing Children’s Hospital, Capital Medical University, Beijing, Beijing Municipality, China

Objective: This study evaluated the diagnostic accuracy of the 2012 SLICC and 2019 EULAR/ACR criteria in Chinese cSLE patients and aimed to develop an optimized classification schema based on the 2019 EULAR/ACR criteria, specifically tailored for cSLE. Methods: Data from cSLE and control cases were extracted from the CAPRID database. Gold-standard diagnosis were established by consensus among 43 rheumatologists(≥80% agreement). From 1,390 consensus cases, a random selection of 1,045 cases (512 cSLE/533 non-cSLE) were allocated to derivation (n=522) and validation (n=523) cohorts. The 2012 SLICC and 2019 EULAR/ACR criteria were evaluated in the total cohort. Multiple optimization schemes were then developed through LASSO regression with expert consultation in the derivation cohort. All potential optimization schemes underwent validation in the validation cohort, from which the optimal scheme was selected and further evaluated in an ANA-positive subgroup. Results：The 2012 SLICC criteria demonstrated sensitivity of 96.7% and specificity of 96.5%, while the 2019 EULAR/ACR criteria had sensitivity of 95.3% and specificity of 97.8%, with an optimal total score threshold of 10. When both the non-scarring alopecia and arthritis criteria were removed alongside the redefined urinary protein criterion, specificity significantly improved to 99.3% (P < 0.05), while sensitivity remained unaffected at 94.1% (P = 0.210). In the ANA-positive cohort, the optimized integrated scheme significantly improved specificity (97.7% vs. 86.4%, P = 0.012) while maintaining comparable sensitivity (96.2% vs. 97.8%, P = 0.138).Conclusion: Both criteria performed well in Chinese cSLE patients. Optimizing the 2019 EULAR/ACR criteria by removing alopecia and arthritis criteria and modifying the urinary protein criterion enhanced specificity without compromising sensitivity.