Clinical features, treatment strategies, and long-term outcomes of Blau syndrome: a 10-year experience from a Chinese cohort.

Abstract

OBJECTIVES: Blau syndrome (BS) is a rare autoinflammatory disorder characterized by the clinical triad of uveitis, dermatitis, and arthritis. While the clinical spectrum is well-documented, data on the longitudinal efficacy and durability of tumor necrosis factor-α (TNF-α) inhibitors remain limited. This study aimed to evaluate the longitudinal treatment trajectories, safety, and long-term outcomes of TNF-α inhibitors in a Chinese cohort. METHODS: This longitudinal observational cohort study analyzed clinical data from 13 Chinese patients diagnosed with BS at Peking Union Medical College Hospital between 2015 and 2025. Whole-exome sequencing was performed in all cases. The cohort was comprehensively evaluated in terms of demographic characteristics, clinical manifestations, genetic findings, genotype-phenotype correlations, and treatment outcomes (specifically focusing on the long-term durability and treatment switching of TNF-α inhibitors). Statistical analyses were performed to assess long-term efficacy and safety. RESULTS: The cohort included 7 (53.8%) females and 6 (46.2%) males. The median age of onset was 2 years (IQR: 1–5 years), while the median age at diagnosis was 23 years (IQR: 18.5–26.5 years). The substantial diagnostic delay (median: 19 years, range: 7–29 years, IQR: 18.5–21 years) likely contributed to the high prevalence of clinical manifestations, including arthritis (13,100%), ocular involvement (12, 92.3%), joint deformity (10, 76.9%), and the full classical triad (9, 69.2%). Genetic analysis revealed 8 NOD2 substitutions, with p.R334W being the most recurrent (6, 46.2%). Regarding treatment, 12 (92.3%) patients received TNF-α inhibitors, either as monotherapy or in combination with conventional DMARDs or corticosteroids. These agents demonstrated robust initial efficacy: complete remission was consistently achieved with infliximab (4 patients, 30.8%), etanercept (3 patients, 23.1%), and adalimumab (3 patients, 23.1%). However, long-term follow-up revealed the complexity of management. While 6 (46.2%) patients achieved sustained stability, relapse or secondary loss of efficacy occurred in 6 (46.2%) patients, necessitating treatment adjustments. Additionally, alternative therapies (tofacitinib, canakinumab) showed promise in refractory cases. Safety was generally manageable, with only one patient (7.7%) experiencing adverse effects from TNF-α inhibitors. Stratified analysis based on the NOD2 genotype revealed no significant differences in clinical severity or treatment efficacy. CONCLUSIONS: This study provides real-world observations from a single-center cohort of Chinese patients with Blau syndrome. Our findings suggest that early recognition and timely therapeutic intervention are essential to prevent irreversible organ involvement. TNF-α inhibitors represent a feasible therapeutic option for achieving symptom control, particularly in cases refractory to conventional treatments. However, observed variability in therapeutic responses and the occurrence of secondary loss of efficacy highlight the complexity of long-term management. These preliminary results underscore the need for individualized treatment strategies and call for larger, prospective, controlled studies to validate the potential benefits of early biologic intervention.