Background/Purpose: Neuropathic pain (NeP) is increasingly recognized as a relevant symptom domain in primary Sjögren’s disease (SjD), contributing to the disease burden beyond glandular involvement. Despite its potential impact on quality of life, the clinical and patient-reported (PROs) outcomes associated with NeP in SjD remain incompletely understood.Aim of this study is to investigate the prevalence of NeP in patients with SjD, and identify its associations with clinical features, immunological markers, and PROs including fatigue, pain severity, small fiber symptoms, and emotional distress.

Methods: We conducted a cross-sectional analysis of 112 (105 F:7 M) patients diagnosed with SjD according to ACR/EULAR criteria. NeP was assessed using the DN4 questionnaire (cut-off ≥4). Extra glandular manifestations were prospectively assessed following the ESSDAI. PROs included the ESSPRI, FACIT-Fatigue, VAS items, and the Hospital Anxiety and Depression Scale (HADS). Fibromyalgia was diagnosed according to ACR 2016 criteria. Immunological data included SSA/SSB status, gammaglobulin fractions, complement levels, and histological findings. The SFNSL was administered to assess symptoms related to small fiber neuropathy. Logistic regression models were used to identify independent predictors of neuropathic pain and K-means clustering was applied to DN4 scores to explore phenotypic subgroups.

Results: NeP (DN4 ≥4) was identified in 25% (28/112) of SjD patients. Coexisting fibromyalgia was present in 31.5% (35/112) of the cohort. Patients with NeP had significantly higher fibromyalgia severity scores, ESSPRI, HADSA, HADSD and lower FACIT scores (Fig 1). In multivariate logistic regression, fibromyalgia severity (OR = 1.13, p = 0.017), ESSPRI (OR = 1.99, p = 0.024), and FACIT (OR = 0.91, p = 0.032) emerged as independent predictors of NeP. ESSDAI scores did not differ between groups. Cluster analysis identified three distinct DN4-based phenotypes: high NeP (n=10, DN4≈8), moderate NeP (n=34, DN4≈5), and low/negligible NeP (n=68, DN4≈1) (Table1). These clusters differed significantly in total fibromyalgia score (p < 0.001), fatigue (p < 0.001), VAS pain, dryness, and SFNSL scores (all p < 0.001) (Fig 2). Disease duration was shorter in the high NeP cluster (p = 0.003). No significant differences were observed in systemic disease activity (ESSDAI), complement levels, or focus score. A significant association was found between DN4 clusters and SSA status (p = 0.002), with SSA-negative patients more frequently classified in higher DN4 clusters. Notably, a strong convergence was observed between DN4 and SFNSL scores (r=0.754, p < 0.001), supporting the reliability of NeP identification through both tools in this population.

Conclusion: Neuropathic pain defines a distinct symptomatic phenotype in SjD, associated with greater symptom burden, fibromyalgia, and SSA-negativity. Unsupervised clustering highlights the existence of clinically meaningful subgroups based on NeP severity, which are not mirrored by systemic inflammation. These findings underscore the need for comprehensive symptom profiling in SjD beyond conventional immunological and systemic markers.

Table 1: DN4-based Clusters: Clinical features and Patient-Reported Outcomes

Figure 1: Correlations between DN4 and clinical, histological and laboratory features in SjD

Figure 2: Radar Chart Depicting Differences in Patient-Reported Outcomes Across DN4-Based Clusters”

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/phenotyping-neuropathic-pain-in-sjogrens-disease-a-cluster-based-approach/