Systemic Sclerosis: Prognosis and Mortality

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Age at Onset
Fear of Progression
Cardiac Involvement
Causes of Death
Lung Involvement
Nailfold Indicators
Prognostic Markers
Skin Thickness Progression
Symptoms of Systemic Scleroderma


Years ago, only the worst cases of systemic sclerosis (scleroderma) were diagnosed, thus leading to the widespread belief that systemic scleroderma was always progressive and fatal.

Now that the full range of types and severity of scleroderma are being recognized and diagnosed, there is increasing awareness that many people have a milder type of illness with a much rosier longterm prognosis. (Also see What is Scleroderma?, Types of Scleroderma and Systemic Symptoms)

First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non–Raynaud's phenomenon may be considered of poor prognosis. PubMed, Clin Rheumatol, 12/07/2017.

Age at Onset

Systemic sclerosis has a better prognosis when it onsets in the elderly.

There is a need for new systemic sclerosis (SSc) subset criteria. A content analytic approach. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies). PubMed, Scand J Rheumatol, 2018 Jan;47(1):62-70. (Also see Systemic Sclerosis)


Antibodies and Scleroderma. Dozens of antibodies can occur in systemic scleroderma patients. They can be useful for diagnosing, categorizing and predicting the likelihood of certain complications. ISN.


Blood Levels of CD163 Protein May Be a Biomarker to Detect Systemic Sclerosis, Study Shows. Researchers emphasized that additional studies are needed to determine the exact role of CD163 in the development of systemic sclerosis. Scleroderma News, 06/05/2018.

High acute phase protein levels correlate with pulmonary and skin involvement in patients with diffuse systemic sclerosis. High serum amyloid A (SAA) and C-reactive protein (CRP) levels could serve as biomarkers for pulmonary involvement. PubMed, J Int Med Res, 2018 Apr;46(4):1634-1639. (Also see Prognosis of Pulmonary Hypertension)

Potential biomarkers in patients with systemic sclerosis (SSc). Endostatin, elastase and the soluble adhesion molecules (sICAM-1 and sVCAM-1) are potentially involved in the pathogenesis of SSc. PubMed, Int J Rheum Dis, 10/11/2017.

The role of microRNA-5196 in the pathogenesis of systemic sclerosis (SSc). These results suggest that microRNA-5196 can be used as a potential biomarker characterising SSc. PubMed, Eur J Clin Invest, 06/21/2017.

A Proteome derived longitudinal pharmacodynamic biomarker for diffuse systemic sclerosis (SSc) skin. In this study a large array of proteins were discovered, not previously associated with SSc, that provide insights into pathogenesis and potential targets for therapeutic intervention. PubMed, J Invest Dermatol, 09/14/2016.

Protagen and Inova Diagnostics Partner to Advance New Systemic Sclerosis Biomarker. The newly discovered anti-BICD2 autoantibodies are found in about 30% of patients with systemic sclerosis (SSc) and are highly associated with limited forms of the disease. Scleroderma News, 09/01/2016.

Increased risk of digital vascular events in scleroderma patients who have both anti–centromere (CENP) and anti–nterferon–inducible protein 16 (IF–16) antibodies. This study provides further evidence that anti–CENP and anti–IFI–16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma. PubMed, Arthritis Care Res (Hoboken), 07/07/2016. (Also see Antibodies in Systemic Scleroderma)

Biomarkers in systemic sclerosis (SSc): Their potential to predict clinical courses. Biomarkers that can predict clinical features, disease progress, therapeutic response and prognosis are heterogeneous among patients with systemic sclerosis. Wiley Online Library, 01/04/2016.

Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity? The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations. PubMed, BMJ, 2015 Nov 26;351:h5079.

Cardiac troponin (cTnT) testing in idiopathic inflammatory myopathies and systemic sclerosis–spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low–grade skeletal muscle disease activity. We propose two pragmatic clinical pathways using cardiac troponins to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity. PubMed, Ann Rheum Dis, 2015 May;74(5):795-8. (Also see Myopathy and Myositis)

Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis. PubMed, Pathol Biol (Paris), 2015 Apr;63(2):61-8.

Decrease of LL-37 in systemic sclerosis (SSc): a new marker for interstitial lung disease (ILD)? The circulating levels of LL–37 in SSc patients were investigated as lower LL-37 levels may be associated with the development of ILD. PubMed, Clin Rheumatol, 01/20/2015. (Also see What is Pulmonary Fibrosis? and Pulmonary Fibrosis Biomarkers)

Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide. The easily obtained biomarkers may be useful for systematic evaluation and stratification of SSc patients, especially to identify those at risk of pulmonary hypertension. PubMed, Arthritis Care Res (Hoboken), 01/20/2015. (Also see Scleroderma Cardiac Involvement)

Fear of Progression

Validity of the Fear of Progression Questionnaire-Short Form in patients with systemic sclerosis. A valid measure is now available to assess fear of disease progression in patients with SSc, which is significant since fear of progression is one of the most important stressors in this patient population. PubMed, Arthritis Care Res (Hoboken).

Cardiac (Heart) Involvement

Systemic-sclerosis-related myocardial disease death was 14% with most causes being related to arrhythmias. Curr Opin Rheumato (Expired Article).

Causes of Death in Systemic Sclerosis

Early mortality in a multinational systemic sclerosis (SSc) inception cohort. Early mortality in SSc is substantial and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease. PubMed, Arthritis Rheumatol, 12/28/2016.

Mortality And Cause Of Death In An Australian Systemic Sclerosis Cohort. Pulmonary involvement in the form of PAH, ILD or both is the leading cause of death among patients in our cohort. Since cancer is the second leading cause of death in SSc, where possible, screening for early detection of malignancy should be considered. M. Nikpour, Ann Rheum Dis.

Infections, Intensive Care Unit

Outcome of patients with scleroderma admitted to intensive care unit. A report of nine cases. The outcome of scleroderma patients admitted to the ICU was extremely poor. Infectious complication was the most common cause of death in our patients. PubMed, Clin Exp Rheumatol. (Also see Pulmonary Fibrosis)

Lung (Pulmonary) Involvement

The utility of comprehensive autoantibody testing to differentiate connective tissue disease (CTD) associated and idiopathic interstitial lung disease (ILD) subgroup cases. Differentiating CTD- and idiopathic-ILD subgroup cases remains problematic and existing comprehensive CTD-specific serology would represent an ideal biomarker tool to enhance ILD subgroup diagnostic accuracy. PubMed, Rheumatology (Oxford), 2017 Aug 1;56(8):1264-1271.

Prospects for improving outcomes in systemic sclerosis-related pulmonary hypertension (PAH). With the advent of evidence-based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. PubMed, Intern Med J, 2015 Mar;45(3):248-54. (Also see Pulmonary Hypertension Prognosis)

Nailfold Indicators

Prevalence and evolution of scleroderma pattern at nailfold videocapillaroscopy in systemic sclerosis patients: Clinical and prognostic implications. The main clinical manifestation correlated with scleroderma pattern is the occurrence of digital ulcers, and their appearance is strictly correlated with the variation of capillaroscopic feature during the time. PubMed, Microvasc Res, 2015 May;99:92-5.

Prognostic Markers

Predictive value of European Scleroderma Group Activity Index (EScSG-AI) in an early scleroderma cohort. Disease activity burden quantified with the adjusted mean EScSG-AI predicted the risk of deterioration in health status and severe organ involvement in diffuse cutaneous systemic sclerosis. PubMed, Rheumatology (Oxford), 2017 Jul 1;56(7):1111-1122.

Disease activity indices (DAI) in systemic sclerosis: a systematic literature review. Future studies are needed to fully validate the European Scleroderma Study Group activity index and the Combined Response Index for Systemic Sclerosis. PubMed, Clin Exp Rheumatol, 07/06/2016.

Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course. 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. PubMed, Expert Rev Clin Immunol, 2015 Dec 2:1–21.

Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients. Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. PubMed, Medicine (Baltimore).


Early mortality in a multinational systemic sclerosis (SSc) inception cohort. Early mortality in SSc is substantial and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease. PubMed, Arthritis Rheumatol, 12/28/2016. (Also see Ethnicity, Race and Geographical Regions)

Skin Thickness Progression

Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course. 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 and tissue fibrosis. PubMed, Expert Rev Clin Immunol, 2016;12(2):115-35.

Symptoms of Systemic Sclerosis (Scleroderma)

Systemic Scleroderma Symptoms. Systemic sclerosis (scleroderma) can affect every part of the body, including the skin, blood vessels, and all of the internal organs. There are also dozens of associated conditions and related autoimmune diseases. ISN.

Autoimmune Diseases
Heart (Cardiac)
Kidney (Renal)
Lung (Pulmonary)
Photos of Symptoms
Similar Skin Diseases
Sjogren's Syndrome
Skeletal (Bones, Muscles)
Skin and Hair

Also See

What is Scleroderma? ISN.

Types of Scleroderma ISN.

Go to Localized: Linear Scleroderma

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