Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course

ABSTRACT

Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking.

KEYWORDS:

• Systemic sclerosis
• scleroderma
• organ involvement
• mortality
• pulmonary hypertension
• skin thickening
• fibrosis
• predictive factors

Financial & competing interests disclosure

MO Becker has received consultancy fees from Actelion Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Major organ involvement, such as pulmonary, cardiac, renal and gastrointestinal involvement, determines mortality in systemic sclerosis.

• The skin, that is, the extent and progression of skin fibrosis, is also a prognostically important parameter. This is reflected by two subsets with limited cutaneous and diffuse cutaneous involvement (lSSc and dSSc).

• Autoantibody specificities, partly overlapping with the lSSc and dSSc subsets, such as anti-centromere, anti-topoisomerase I and anti-RNA polymerase III antibodies, have the capacity to predict morbidity and mortality. More biomarkers are being detected, amongst them functional autoantibodies, for example, against angiotensin and endothelin receptors, that are also associated with complications and mortality.

• Potent screening algorithms have been developed that allow the detection of pulmonary arterial hypertension (PAH) patients (e.g. DETECT, ASIG, Cochin risk score), and they seem superior to the current European Society of Cardiology/ European Respiratory Society guidelines.

• Within patients with pulmonary involvement (both PAH and interstitial lung disease), responders to therapy are still ill-defined. Further markers for risk stratification are needed in this setting.

• Diagnostic criteria and screening methods for cardiac and gastrointestinal involvement have to be improved. This could lead to the development of meaningful markers for risk stratification and prediction of the disease course.

• For all forms of organ involvement, new markers are being developed and tested that are associated with fibrotic, vasculopathic or (auto-)immune features of the disease.