ObjectiveWe sought to develop the first Damage Index (DI) in systemic sclerosis (SSc).MethodsThe conceptual definition of ‘damage’ in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI. These steps were used to reduce the items: (1) Expert members of the SCTC (n=331) were invited to rate the appropriateness of each item for inclusion, using a web-based survey. Items with >60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1568 patients, the univariable relationships between the remaining items and the endpoints of mortality and morbidity (Physical Component Summary score of the Short Form 36) were analysed, and items with p<0.10 were retained; (3) using multivariable regression analysis, coefficients were used to determine a weighted score for each item. The DI was externally validated in a Canadian cohort.ResultsNinety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items, with one additional item forced into the multivariable model by experts due to clinical importance, to create a 23-item weighted SCTC DI (SCTC-DI). The SCTC-DI was predictive of morbidity and mortality in the external cohort.ConclusionsThrough the combined use of consensus and data-driven methods, a 23-item SCTC-DI was developed and retrospectively validated.

Ischaemia may play a role in the development of calcinosis in SSc.

Objective Systemic sclerosis (SSc; scleroderma) is associated with a wide periodontal ligament (PDL) and mandibular erosions. We investigated the clinical correlates of SSc with these radiologic abnormalities. Methods Subjects from the Canadian Scleroderma Research Group cohort underwent detailed radiologic examinations. Associations between radiologic abnormalities and clinical manifestations of SSc were examined with univariate and multivariate analyses. Results The study included 159 subjects; 90.6% were women, the mean ± SD age was 56 ± 10 years, diffuse disease was present in 28.3%, and mean ± SD disease duration was 13.7 ± 8.4 years. Widening of the PDL involving at least 1 tooth was present in 38% of subjects, and 14.5% had at least 1 site in the mandible with an erosion. In analyses adjusting for age, disease duration, sex, smoking, and education, we found significant associations between the number of teeth with widening of the PDL and disease severity assessed by the physician global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95% CI] 1.02–1.39, P = 0.028). Analyses replacing the PGA with the skin score, disease subset, or anti–topoisomerase I antibodies confirmed the relationship with indices of disease severity. There was no relationship between either the number of teeth with periodontal disease or the number of missing teeth, and the number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI 0.82–0.97, P = 0.006), but not disease severity, facial skin score, or ischemia was associated with a larger number of erosions. Conclusion In SSc, a wide PDL may reflect generalized overproduction of collagen, and mandibular erosions are related to local factors in the oral cavity.

The prevalence of monospecific anti-PM75 and anti-PM100 antibodies in this large SSc cohort was low. Disease features associated with anti-PM/Scl antibodies may depend on particular and possibly multiple antigen specificities. However, due to the small samples, these results need to be interpreted with caution. International collaborations are key to understanding the clinical correlates of uncommon serological profiles in SSc.

Objectives To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort. Methods SSc subjects with <2 years of disease duration were identified from two multicentre cohorts. Severe GI disease was defined as: malabsorption, hyperalimentation, pseudo-obstruction and/or ⩾10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. Kaplan–Meier, multivariate logistic regression and Cox proportional hazard analyses were performed to determine the cumulative incidence rate, independent clinical correlates and mortality rate associated with severe GI disease. A longitudinal mixed model was used to assess the impact of severe GI disease on the Short Form Health Survey. Results In this inception SSc cohort, the probability of developing severe GI disease was estimated at 9.1% at 2 years and 16.0% at 4 years. In multivariate analysis, severe GI disease was associated with inflammatory myositis (odds ratio 4.68, 95% CI 1.65, 13.24), telangiectasias (odds ratio 2.45, 95% CI 1.19, 5.04) and modified Rodnan skin score (odds ratio 1.03, 95% CI 1.01, 1.07). Severe GI disease was associated with a >2-fold increase in the risk of death (hazard ratio 2.27, 95% CI 1.27, 4.09) and worse health-related quality of life [Short Form Health Survey physical (β = −2.37, P = 0.02) and mental (β = −2.86, P = 0.01) component summary scores]. Conclusion Severe GI disease is common in early SSc and is associated with significant morbidity and increased mortality. More research is needed to understand, prevent and mitigate severe GI disease in SSc.

Data indicate that, for some SSc patients, antibiotics can eradicate SIBO. There is a paucity of data reporting the effectiveness of either prokinetics or probiotics in SSc.

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Objective To examine the clinical correlates and survival in patients with anti-fibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States of America. Methods Baseline clinical data from the prospective cohorts [Canadian Scleroderma Research Group (CSRG), the Australian Scleroderma Cohort Study (ASCS) and the American Genetics versus Environment in Scleroderma Outcome Study (GENISOS)] were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available systemic sclerosis profile line immunoassay (LIA), regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Furthermore, a survival analysis was performed by Cox regression analysis. Results A total of 1506 SSc patients with complete serological profiles were included in the study. Fifty-two (3.5%) patients had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA positive compared to other ethnicities. After adjustment for demographic factors, diffuse involvement and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Furthermore, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11, 2.79, p=0.016). Conclusion In this large multinational SSc cohort, AFA was associated with Native American Ethnicity and was an independent predictor of mortality.