Simon Jonathan Bowman

Objectives: To examine associations between smoking and Sjögren’s disease (SjD) diagnosis, compared with non-Sjögren’s sicca syndrome (sicca) and population controls, and to explore immunomodulatory effects of smoking on disease phenotype. Methods: Adults referred for suspected SjD to the OASIS cohort from 2014 until 2023 were classified as SjD or sicca. Smoking status, exposure (pack-years), and passive smoking history were recorded through standardised questionnaires. Associations with diagnosis, clinical and serological parameters, and patient-reported outcomes were analysed using multivariate logistic and linear regression. Smoking patterns were further compared to matched controls from the 2018 UK Annual Population Survey. Results: 317 SjD patients and 170 sicca controls were included. Of these, 257 SjD met 2016 classification criteria, and were used for primary analyses. Smoking data were available for 85.0% of the cohort. SjD patients were more frequently never smokers than sicca (70.5% vs 53.1%, p = 0.002). In the multivariate analysis, current smoking (OR 0.37, 95%CI 0.15–0.92) was independently associated with lower odds of SjD. Never smokers exhibited higher IgG levels (p = 0.003) and more frequent biological ESSDAI activity (p = 0.038). Smoking exposure correlated with reduced IgG, rheumatoid factor levels, and seropositivity, independent of DMARD use. Compared with population controls, sicca, but not SjD, showed higher ever-smoking rates (49.6% vs 39.1%, p = 0.049). Conclusion: Smoking was negatively associated with SjD diagnosis compared to sicca, but not population controls. Smoking exposure linked to lower immunoglobulin and autoantibody levels, suggesting an immunomodulatory effect rather than true disease protection. Findings support a potential metabolically-influenced, non-autoimmune, sicca phenotype linked to smoking.

Primary Sjögren’s disease (SjD) is a systemic autoimmune disease with heterogeneous clinical manifestations, ranging from isolated glandular dysfunction to multisystem involvement and severe complications. This variability complicates disease management, particularly the assessment of disease activity and long-term outcomes. Disease activity in SjD encompasses both systemic manifestations and patient-reported outcomes (PROs). The EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) remains the standard for systemic activity, while the ESSPRI complements these scores by capturing subjective symptom burden. These tools have limitations because they do not evaluate the same manifestations of SjD and may therefore respond differently to treatment. Thus, composite outcomes such as the Sjögren’s Tool for Assessing Response (STAR) and the Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) have been developed. They integrate improvements in ClinESSDAI, PROs, biological parameters and objective dryness, providing a more comprehensive measure of disease activity. Assessment of damage, defined as irreversible sequelae, remains an unmet need in SjD. Damage is a reflection of the natural evolution of the disease, and is also relevant to measuring the impact and health economic effects of therapeutic interventions. Existing measures, including cumulative ESSDAI, track longitudinal activity and reflect the severity of the disease, but do not specifically capture damage. In summary; SjD assessment requires complementary tools for systemic activity and PROs, with composite scores a recent innovation. An important remaining gap is a validated method to evaluate damage, essential to fully evaluate disease progression.

Primary Sjogren’s Disease (SjD) is characterized by features of dryness arising from inflammation in the secretary glands, particularly the salivary and lachrymal glands. Generalized symptoms of fatigue and limb pain are very common but, in addition, about 40% of patients have one or more features of organ-specific systemic disease. This review goes through the background of SjD including diagnosis and classification, epidemiology, impact and investigations such as ultrasound and lip biopsy. It then focuses in detail on each of the systemic organ-specific features, principally using the European League against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index (ESSDAI) along with some non-ESSDAI domains, before concluding with comments on disease heterogeneity, treatment, vaccination, pregnancy and surgery along with observations on patient perspectives. The aim is to provide a general overview of these aspects of the disease to complement other chapters in this monograph.

The most widely used classification criteria for Sjögren disease (SjD) are the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) Classification Criteria (AECC),¹ which built on the previously developed Revised American-European Consensus Group (AECG) Criteria.² The AECC require specific evidence of autoimmunity in the form of either positive anti-Ro antibodies and/or a positive minor labial salivary gland biopsy showing features of focal periductal lymphocytic sialadenitis, which is the hallmark histological feature of SjD.

Objectives The Plutocratic Proposal is a novel method of funding early phase clinical trials where a single donor funds the entire trial and in so doing secures a place on it. The aim of this study was to identify and explore concerns that may be raised by UK research ethics committees (RECs) when reviewing clinical trials funded in this way. Design Empirical ethics combining ethical analysis and qualitative data from three focus groups held online using Frith’s symbiotic approach. Data were analysed using inductive thematic approach informed by the study aims and ethical analysis. Participants 22 participants were recruited: 8 research patient public involvement group members, 7 REC chairs and 7 clinical researchers. All were based in the UK. Results With one exception, participants thought the Plutocratic Proposal may be ‘all things considered’ acceptable, providing their concerns were met, primary of which was upholding scientific integrity. Other concerns discussed related to the acceptability of the donor securing a place on the trial including: whether this was an unfair distribution of benefits, disclosing the identity of the donor as the funder, protecting the donor from exploitation and funding a single study with multiple donors on the same terms. Some misgivings fell outside the usual REC purview: detrimental impact of donors of bad character, establishing the trustworthiness of the matching agency and its processes and optimising research funding and resources. Despite their concerns, participants recognised that because the donor funds the whole trial, others would also potentially benefit from participating. Conclusions We identified concerns about the Plutocratic Proposal. UK RECs may be open to approving studies if these can be addressed. Existing governance processes will do some of this work, but additional REC guidance, particularly in relation to donors securing a place on the trial, may be necessary to help RECs navigate ethical concerns consistently.