Objective. To quantify the burden of cancer in systemic sclerosis (SSc). Methods. Standardized incidence ratios (SIRs) and standardized mortality ratios relative to the general Australian population were derived. Cox proportional hazards regression was used to estimate survival in patients with SSc with cancer compared to patients without. Determinants of cancer were identified using logistic regression. Health care cost was quantified through cross-jurisdictional data linkage. Results. This SSc cohort of 1,727 had a cancer incidence of 1.3% per year and a prevalence of 14.2%, with a SIR of 2.15 (95% confidence interval [95% CI] 1.84-2.49). The most common cancers were breast, melanoma, hematologic, and lung. Anti-RNA polymerase III (RNAP) antibody was associated with an increased risk of cancer (odds ratio [OR] 2.9, P = 0.044), diagnosed within 5 years of SSc disease onset. Calcium-channel blockers were associated with a higher risk of overall cancer (OR 1.47, P = 0.016), breast cancer (OR 1.61, P = 0.051), and melanoma (OR 2.01, P = 0.042). Interstitial lung disease (ILD) was associated with lung cancer (OR 2.83, P = 0.031). Incident SSc cancer patients had >2-fold increased mortality compared to patients with SSc without cancer (hazard ratio 2.85 [95% CI 1.51-5.37], P = 0.001). Patients with SSc and cancer utilized more health care than those without cancer, with an excess annual health care cost of $1,496 Australian (P < 0.001). Conclusion. SSc carries an increased risk of developing cancer, particularly lung cancer associated with ILD, and breast cancer and melanoma occurring close to SSc disease onset in association with RNAP antibodies. Compared to those patients without cancer, patients with SSc and cancer had higher mortality and an increased health care cost, with an annual excess per patient cost of $1,496 (Australian) (P < 0.001).

Objective To quantify the burden of interstitial lung disease (ILD) in SSc. Methods Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008–2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild <10%, moderate 10–30%, severe >30%). Determinants of healthcare cost were estimated using logistic regression. Results SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230–93 615) vs AUD$33 657 (15 144–66 905), P<0.001) between 2008–2015. Healthcare utilization was associated with an annual median (25th–75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807–1212), P<0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645–1846), P<0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P<0.001, and OR 2.6, P=0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P<0.001], with a progressive decline with increasing ILD severity (P=0.002). Conclusion SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost.

Objective To determine the frequency of self-reported occupational exposure to silica in SSc patients enrolled in the Australian Scleroderma Cohort Study, and to compare the disease characteristics of the silica-exposed patients with those of the non-exposed patients. Method Data collected over a 12-year period from 1670 SSc patients were analysed. We compared the demographic and clinical characteristics of those who reported occupational silica exposure with those who did not. A subgroup analysis of male patients was performed, as well as a multivariable analysis of correlates of silica exposure. Results Overall, 126 (7.5%) of the cohort reported occupational silica exposure. These individuals were more likely to be male (73 of 231, i.e. 31.6% males exposed) and to have worked in mining and construction industries. Those who reported silica exposure were younger at the onset of SSc skin involvement [odds ratio (OR) 0.9, P = 0.02], of male gender (OR 14.9, P &lt; 0.001), have joint contractures (OR 1.8, P = 0.05) and have higher physical disability as defined by scleroderma HAQ (OR 1.4, P = 0.01). Conclusion The highest percentage of silica exposure was found in males. These patients were more likely to have the presence of certain clinical manifestations and Scl-70 antibody, which is known to confer a poor prognosis. These findings support the association between occupational silica exposure and the subsequent development of SSc. Further investigation is required to describe the range of clinical manifestations and disease course, including prognosis and treatment response, in those diagnosed with occupationally induced SSc compared with idiopathic SSc.

Objective To describe the clinical characteristics and outcomes of systemic sclerosis–mixed connective tissue disease (SSc–MCTD) and SSc overlap syndrome. Methods We included patients from the Australian Scleroderma Cohort Study who met American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc. Three mutually exclusive groups were created: SSc–MCTD, SSc overlap, and SSc only. Univariate comparison of clinical features was performed by analysis of variance or chi‐square test. Survival analysis was performed using Kaplan‐Meier (KM) curves and Cox proportional hazards regression models. Results Of 1,728 patients, 97 (5.6%) had SSc–MCTD, and 126 (7.3%) had SSc overlap. Those with MCTD–SSc were more commonly Asian (18.3% versus 10.1% in SSc overlap, and 3.6% in SSc only; P < 0.0001) and younger at disease onset (38.4 years versus 46.5 or 46.8 years, P < 0.0001). Those with SSc–MCTD or SSc overlap were more likely to have limited cutaneous SSc. All 3 groups had similar frequency of interstitial lung disease (ILD), although pulmonary arterial hypertension (PAH) was less common in SSc overlap. Synovitis and myositis were more common in SSc overlap and SSc–MCTD than in SSc only. KM curves showed better survival in SSc–MCTD than SSc overlap or SSc only (P = 0.011), but this was not significant after adjustment for sex and age at disease onset. SSc‐specific antibodies were survival prognostic markers, with antinuclear antibody centromere or anti‐RNP conferring better survival than anti–Scl‐70 or anti–RNA polymerase III (P = 0.005). Patients with SSc–MCTD and SSc overlap had lower mortality following diagnosis of ILD and PAH than patients with SSc only. Conclusion This study provides insights into the clinical characteristics of patients with SSc–MCTD, SSc overlap, and SSc only and shows that anti‐RNP antibodies are associated with better survival than anti–Scl‐70 and anti‐RNA polymerase III antibodies.

Objectives Cardiac complications of systemic sclerosis (SSc) are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of cardiac arrhythmias or future cardiac failure. The aim of this study was to quantify the burden of asymptomatic fibro-inflammatory myocardial disease using cardiac magnetic resonance imaging (CMR) and assess the relationship between asymptomatic myocardial fibrosis and cardiac arrhythmias in SSc. Methods Thirty-two patients with SSc with no documented history of pulmonary vascular or heart disease underwent CMR with gadolinium and 24-h ambulatory electrocardiography (ECG). Focal myocardial fibrosis was assessed using post-gadolinium imaging and diffuse fibro-inflammatory myocardial disease quantified using T1 and T2-mapping. CMR results were compared with an age and sex-matched control group. Results Post-gadolinium focal fibrosis was prevalent in SSc but not controls (30% vs 0%, p&lt; 0.01) and its presence was associated with impaired left ventricular strain (p= 0.009). T1 mapping values (as a marker of diffuse fibrosis) were greater in SSc than controls (SASHA : 1584 ms vs 1515 ms, p&lt; 0.001; ShMOLLI : 1218 ms vs 1138 ms, p&lt; 0.001). More than one-fifth (22.6%) of the participants had ventricular arrhythmias on ambulatory ECG, but no associations between focal or diffuse myocardial fibrosis and arrhythmias were evident. Conclusion In SSc patients without evidence of overt cardiac disease, a high burden of myocardial fibrosis and arrhythmias was identified. However, there was no clear association between focal or diffuse myocardial fibrosis and arrhythmias, suggesting CMR may have limited use as a screening tool to identify SSc patients at risk of future significant arrhythmias.