Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need

Abstract

Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality resulting from early internal-organ involvement. Clinicians therefore tend to focus on early diagnosis and treatment of potentially life-threatening cardiorespiratory and renal disease. However, the rapidly progressive painful, itchy skin tightening that characterizes dcSSc is the symptom that has the greatest effect on patients’ quality of life, and there is currently no effective disease-modifying treatment for it. Considerable advances have been made in predicting the extent and rate of skin-disease progression (which vary between patients), including the development of techniques such as molecular analysis of skin biopsy samples. Risk stratification for progressive skin disease is especially relevant now that haematopoietic stem-cell transplantation is a treatment option, because stratification will inform the balance of risk versus benefit for each patient. Measurement of skin disease is a major challenge. Results from clinical trials have highlighted limitations of the modified Rodnan skin score (the current gold standard). Alternative patient-reported and other potential outcome measures have been and are being developed. Patients with early dcSSc should be referred to specialist centres to ensure best-practice management, including the management of their skin disease, and to maximize opportunities for inclusion in clinical trials.

Abstract

The quality of life of patients with diffuse cutaneous systemic sclerosis is greatly affected by progressive painful and itchy skin tightening. Here, Herrick, Assassi and Denton describe skin involvement, the prediction of progression, outcome measures, imaging techniques and best-practice management.

Key points

• Much of the pain and disability of early diffuse cutaneous systemic sclerosis (dcSSc) results from skin thickening (scleroderma), which can be rapidly progressive, commencing distally then extending proximally.

• ‘Progressors’ in terms of skin disease can now be identified by considering disease duration, extent of skin disease, autoantibody status and (potentially) gene-expression profiling of skin biopsy specimens.

• Improvement in the ability to predict progressive skin disease will inform the selection of patients for haematopoietic stem-cell transplantation, as well as more targeted inclusion of patients in clinical trials.

• Limitations of the modified Rodnan skin score are stimulating development of other outcome measures of skin disease, including patient-reported outcome measures, non-invasive imaging methods and composite scores.

• Best-practice management of early dcSSc includes early referral to a specialist centre, pain management, multidisciplinary input, immunosuppressive therapy and, when at all possible, inclusion in a clinical trial.