Pathomechanistic evolution rule and stratified management of Sjögren′s disease from the perspective of "Bi of both body and viscera"

To investigate the clinical subtypes and pathomechanistic evolution of Sjögren′s disease (SjD) based on the traditional Chinese medicine theory of "Bi of both body and viscera," and to provide objective evidence for clinical prevention and treatment.

Clinical data was collected from 545 patients with SjD who were newly registered in the China Rheumatology Registry Research Information Platform for Chinese Medicine between June 1, 2023 and June 30, 2025. The collected data included demographic characteristics, namely sex, age at onset, age at diagnosis, and disease duration; traditional Chinese medicine syndrome patterns; laboratory indicators; EULAR Sjögren′ s Syndrome Patient Reported Index (ESSPRI); EULAR Sjögren′s Syndrome Disease Activity Index (ESSDAI); and systemic involvement. A total of 24 clinically relevant variables were prespecified, including sex, age at diagnosis, traditional Chinese medicine syndrome patterns, the three ESSPRI domain scores for dryness, fatigue, and pain, involvement of the 12 ESSDAI systemic domains, immunoglobulin G (IgG) stratification, decreased C4, rheumatoid factor (RF) stratification, and positivity for anti-Sjögren′ s syndrome-related antigen A (SSA) antibody, anti-Sjögren′s syndrome-related antigen B (SSB) antibody, and anticentromere antibody. Multiple correspondence analysis (MCA) and hierarchical clustering were used to identify clinical subtypes of SjD. Based on the theory of " Bi of both body and viscera," and in combination with body-orifice involvement, visceral involvement, syndrome patterns, and immunological characteristics of different subtypes, their disease-location hierarchy and pathomechanistic transmission features were interpreted and named as the body Bi subtype, Bi of both body and viscera subtype, and viscera Bi subtype. Clinical characteristics, syndrome distribution, ESSPRI, ESSDAI, and laboratory indicators were further compared among the subtypes. Patients were grouped according to baseline disease duration to compare the distribution of clinical subtypes across different disease-duration groups. Starting from the date of initial registration, patients were followed up for 18 months. Newly developed extraglandular involvement and time to event were recorded, and the Kaplan-Meier method was used to analyze event-free survival for newly developed extraglandular involvement among different subtypes.

Based on MCA and hierarchical clustering, 545 patients with SjD were classified into three clinical subtypes: body Bi subtype(n= 150), Bi of both body and viscera subtype (n= 254), and viscera Bi subtype (n= 141). The body Bi subtype was mainly characterized by body-orifice involvement, with higher ESSPRI scores but lower ESSDAI scores (P<0.05). The predominant syndrome patterns were yin deficiency with fluid depletion and dryness-dampness interaction, and disease duration was relatively shorter. The Bi of both body and viscera subtype was characterized by the coexistence of body-orifice damage and mild visceral involvement, with lower ESSPRI scores but with ESSDAI scores higher than those of the body Bi subtype and lower than those of the viscera Bi subtype (P<0.05). This subtype also showed features of B-cell activation. The predominant syndrome patterns were dual deficiency of qi and yin, dryness-blood stasis interaction, and dryness-dampness interaction, and the disease duration was relatively longer. The viscera Bi subtype was mainly characterized by multi-organ and multisystem involvement, with higher ESSPRI fatigue domain scores and ESSDAI scores (P<0.05), accompanied by elevated erythrocyte sedimentation rate and hypocomplementemia (P<0.05). The predominant syndrome patterns were dryness-blood stasis interaction and yin deficiency with internal heat, and disease duration was also longer than that of the body Bi subtype. Significant differences were observed among the three subtypes in demographic characteristics, distribution of traditional Chinese medicine syndrome patterns, ESSPRI, ESSDAI, systemic involvement, and laboratory indicators (P < 0.05). As disease duration increased, the proportion of the body Bi subtype showed a decreasing trend, whereas the proportion of the viscera Bi subtype gradually increased (P<0.05). Event-free survival for newly developed extraglandular involvement differed significantly among the subtypes, with patients in the Bi of both body and viscera subtype showing a relatively lower event-free survival rate (P<0.05).

Guided by the theory of "Bi of both body and viscera," SjD can be classified into three clinical subtypes with distinct pathomechanistic features and stages of disease progression: body Bi subtype, Bi of both body and viscera subtype, and viscera Bi subtype. This classification reflects the dynamic evolution of SjD from body involvement to visceral involvement and from the qi level to the blood level. It may help deepen the understanding of the clinical heterogeneity of SjD from the perspective of body-viscera interaction and serve as an important basis for stratified integrative prevention and treatment.