Contribution of HLA and KIR Alleles to Systemic Sclerosis Susceptibility and Immunological and Clinical Disease Subtypes.

Systemic sclerosis (SSc) is an autoinflammatory, fibrotic condition of unknown aetiology. The presence of detectable autoantibodies against diverse nuclear antigens, as well as strong HLA associations with disease, suggest autoimmune involvement, however the links between endogenous and exogenous risk factors and SSc pathology remain undetermined. We have conducted a genetic analysis of inheritance in two independent and meta-analysed cohorts of 1,465 SSc cases and 13,273 controls, including stratified association analyses in clinical and autoantibody positive subgroups of disease.

Rituximab treatment for systemic sclerosis-associated interstitial lung disease: a case series of 13 patients.

Background: Systemic sclerosis (SSc) associated interstitial lung disease (ILD) is a common complication of SSc, with a high mortality, despite current available treatments. Rituximab has shown some promising, although varied, results for the treatment of SSc-ILD.

Aims: To determine whether rituximab stabilised or improved pulmonary function at 12 months, in patients with SSc-ILD.

Gastric antral vascular ectasia in systemic sclerosis: a study of its epidemiology, disease characteristics and impact on survival.

Background: To describe the epidemiology, determinants and survival impact of gastric antral vascular ectasia (GAVE) in systemic sclerosis (SSc).

Methods: Consecutive SSc patients prospectively enrolled in the Australian Scleroderma Cohort Study (ASCS) were included. Univariable and multivariable logistic regression were used to determine the associations of GAVE with clinical manifestations and serological parameters.

47XXY and 47XXX in Scleroderma and Myositis.

Objective: We undertook this study to examine the X chromosome complement in participants with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies.

Methods: The participants met classification criteria for the diseases. All participants underwent single-nucleotide polymorphism typing.

Long-term Clinical Outcomes in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome.

Objective: To assess the outcome of empirical therapeutic interventions for synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Methods: The clinical features and treatment outcomes of a cohort of 21 patients diagnosed with SAPHO in Western Australia were reviewed retrospectively.

Results: All 21 patients met published diagnostic criteria; 20 (95%) were Caucasian, and the median age was 47 years.

Occupational silica exposure in an Australian systemic sclerosis cohort.

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.

Performance of the 2017 EUSTAR activity index in an scleroderma cohort.

Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group (EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort.

Clinical Features of Systemic Sclerosis-Mixed Connective Tissue Disease and Systemic Sclerosis Overlap Syndromes.

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.

Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden.

Background: To determine the frequency and clinical characteristics of systemic sclerosis-related digital ulcers, and associated direct health care costs, quality of life, and survival.

Methods: Digital ulcers (DUs) were defined as an area with a visually discernible depth and a loss of continuity of epithelial coverage. DU severity was calculated based on the physician reported highest number of new DUs at clinical review (mild = 1-5 DUs, moderate 6-10 DUs, severe > 10 DUs).

The economic burden of systemic sclerosis related pulmonary arterial hypertension in Australia.

Background: To quantify the financial cost of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc).

Methods: Healthcare use was captured through data linkage, wherein clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with hospital, emergency department (ED) and ambulatory care databases (MBS) for the period 2008-2015. PAH was diagnosed on right heart catheter according to international criteria.

The clinical and economic burden of systemic sclerosis related interstitial lung disease.

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%).

IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis.

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc).

Incidence, Risk Factors, and Outcomes of Cancer in Systemic Sclerosis.

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.

Can Patient-Reported Symptoms Be Used to Measure Disease Activity in Systemic Sclerosis?

Objective: To evaluate the association between patient-reported symptoms and changes in disease activity over time in systemic sclerosis (SSc).

Methods: Using data from 1,636 patients enrolled in the Australian Scleroderma Cohort Study, we used generalized estimating equations to determine the relationship between patient-reported worsening of Raynaud's phenomenon (RP), skin involvement, and breathlessness in the month preceding each study visit and features of disease activity in the corresponding organ systems. The associations between the following parameters were analyzed: patient-reported worsening RP and the presence of new-onset digital pitting and digital ulcers; patient-reported worsening skin involvement and increasing modified Rodnan skin thickness score (MRSS); new areas of skin involvement and new-onset joint contractures; patient-reported worsening breathlessness and deteriorating respiratory functions test (RFT) results, indicated by a 10% decrease in forced vital capacity (FVC) and a 15% decrease in diffusing capacity for carbon monoxide (DLco), new-onset interstitial lung disease (ILD), and new-onset pulmonary arterial hypertension (PAH).

Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis.

Background: Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality.

The role of inflammatory markers in assessment of disease activity in systemic sclerosis.

Objectives: The role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc) remains controversial. We sought to evaluate the relationship between clinical features of SSc and raised inflammatory markers and to determine if changes in ESR and CRP reflect changes in other disease features over time.

Methods: One thousand, five hundred and forty-five patients enrolled in the Australian Scleroderma Cohort Study were observed over a mean 3.

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations.

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

Objectives: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

Methods: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months).

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.

Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement.

Work productivity in systemic sclerosis, its economic burden and association with health-related quality of life.

Objective: To evaluate work productivity and its economic burden in SSc patients.

Methods: Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study were mailed questionnaires assessing employment (Workers' Productivity and Activity Impairment Questionnaire and a custom-made questionnaire) and health-related quality of life (HRQoL) (36-item Short Form Health Survey and Patient-Reported Outcomes Measurement Information System 29). Linear regression methods were used to determine factors associated with work productivity.

Autologous stem cell transplantation in systemic sclerosis: a systematic review.

Objectives: Haematopoetic autologous stem cell transplantation (ASCT) has emerged as a treatment option for patients with refractory, severe autoimmune disease. This is a systematic review of the current literature on ASCT in adult patients with systemic sclerosis (SSc).

Methods: Original articles published between 2005 and 2016 that evaluated the use of ASCT in patients with SSc were reviewed with respect to the primary outcomes of overall and transplant related mortality (TRM) rates, and secondary outcomes of changes in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), progression/event free survival (P/EFS) and quality of life measures.

Validity of the Workers Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) in patients with systemic sclerosis.

Objectives: To evaluate the construct validity of the Workers Productivity and Impairment Activity Index: Specific Health Problem (WPAI:SHP) in Australian systemic sclerosis (SSc) patients.

Methods: SSc patients, identified through the Australian Scleroderma Cohort Study database, completed the WPAI:SHP and a quality of life instrument (PROMIS-29) cross-sectionally. The construct validity of the WPAI:SHP was assessed by the correlations between the WPAI:SHP and a range of SSc health states.

Long-term efficacy and tolerability of mycophenolate mofetil therapy in diffuse scleroderma skin disease.

Objectives: To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc).

Methods: Patients enrolled in the Australian Scleroderma Cohort study with dcSSc and baseline modified Rodnan skin score (mRSS) ≥ 12 who were treated for a minimum of 12 months with MMF for the primary indication of skin disease were included and their prospectively collected data retrieved. Change in mRSS, the proportion with a clinically significant improvement (reduction in mRSS ≥ 5 from baseline) and adverse effects due to therapy were determined.

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS).

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.

Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening).