Professor Christopher Denton, consultant rheumatologist at the Royal Free Hospital in London, led a recent British Society for Rheumatology guideline working group on managing systemic sclerosis. Here, as lead author of the published recommendations, he explains key aspects of the guideline and highlights new and emerging advances in treatment for this challenging condition.
Systemic sclerosis is a severe and incurable autoimmune rheumatic disease that causes damage and fibrosis in the skin, blood vessels and vital organs. It also impacts hand function, and almost all aspects of everyday living are affected.
It is uncommon, affecting around one in 10,000 of the population. Unfortunately, it has a high mortality and even greater morbidity through its impact on the lungs, heart, kidneys and gastrointestinal tract.1
The first guideline covering the management of systemic sclerosis in all age groups were published in September 2024 by the British Society for Rheumatology following working group discussions among healthcare professionals with expertise in systemic sclerosis, people with lived experience of the condition and patient organisation representatives.2 This is an updated version of an earlier 2015 guideline that only covered adults with this complex disease.3
What challenges does the systemic sclerosis guideline address?
Systemic sclerosis is a diverse disease, so guidelines need to consider the differences in how people may present with it. Often it takes time to make a firm diagnosis, which can lead to treatment delays.
Early diagnosis using techniques such as capillaroscopy and antinuclear autoantibody testing is important and allows stratification of risk for future complications, including lung fibrosis and severe renal involvement.4
Once diagnosed, there should be a systematic baseline assessment of all the organs that might be affected and regular follow-up testing through the disease course. A particular group highlighted in the new guideline is the subset of cases associated with concurrent malignancy.
This group has certain characteristics that allow for early recognition, including certain antibody associations and clinical features. The approach to these cases is analogous to that taken with adult-onset dermatomyositis.
In line with other recently published recommendations and aligned with the British Society for Rheumatology guideline protocol, young people with systemic sclerosis are included in the recommendations for the first time. This was achieved through strong engagement with the paediatric rheumatology community. For each of the evidence-based recommendations, a statement about relevance to children and adolescent patients is included.
Structure of the guideline
The British Society for Rheumatology guideline includes four key sections:
- Diagnosis and assessment of people with systemic sclerosis
- Overview of management
- Organ-based and specific disease complications
- Service delivery.
Each section is framed around key questions that are front and centre of systemic sclerosis management, such as the best approaches to treating heart, lung or gastrointestinal complications. There is also much emphasis on non-lethal manifestations such as digital ulcers as well as non-pharmacological treatments.
The fourth section of the guideline covers specific aspects of service delivery within the NHS. It will help to plan the recommended practice and provide templates and standards for service and patient-specific future audit.
Recent progress in systemic sclerosis
There has been nearly a decade of progress in managing systemic sclerosis, which is captured in the updated guideline.
There are now evidence-based treatments, approved drugs for interstitial lung disease in systemic sclerosis, and more robust support for approaches such as autologous haematopoietic stem cell transplantation. The latter has been shown in robust trials to have a profound benefit for appropriate cases, and the guideline includes specific expert direction on the assessment and evaluation of cases for this procedure.
There is growing support for the treatment of vascular disease, including pulmonary arterial hypertension, and the updated guideline complements guidance from other relevant bodies such as the World Symposium for Pulmonary Hypertension.5
- Cellular therapies
The first major area of progress has been advances in cellular therapy. Large, robust clinical trials and registry studies have confirmed the long-term benefit of autologous haematopoietic stem cell transplantation in poor prognosis systemic sclerosis.6 The new guideline covers this for adults and highlights that it is also a treatment option for juvenile-onset systemic sclerosis.
Critical guidance to help select and evaluate patients so that maximum benefit and minimal harm are achieved is included with simple summaries for case selection. This treatment shows what can be accomplished and provides a pivotal demonstration of disease modification.
- Vasculopathies
Progress has also been made in managing vasculopathy in systemic sclerosis and therefore scleroderma renal crisis, digital ulcer disease, Raynaud’s phenomenon and pulmonary hypertension are all covered clearly in the guideline. These sections summarise evidence-based practice and highlight that systemic sclerosis is as much a cardiovascular disease as a fibrotic condition.7
However, fibrosis of the lung is now the most frequent cause of systemic sclerosis-associated death, and there have been studies providing evidence for treatment.
The guideline includes expert direction on the evaluation and treatment of interstitial lung disease, including a combination of immunosuppression with antifibrotic treatment (nintedanib) in cases of progressive disease.8
Other approaches have been approved based on clinical trial results, including biological therapy with tocilizumab and rituximab.9 These may be especially effective in certain stages and subsets of systemic sclerosis, as indicated in the guideline.
While not yet routinely available in the NHS, it is hoped that the growing evidence base for these biological agents and general utilisation in other global healthcare settings will facilitate access to these treatments in the future. It is likely that, at present, the use will generally be restricted to cases of sclerosis fulfilling the requirements to access rituximab or tocilizumab for other manifestations of overlap syndrome such as arthritis, myositis or vasculitis.
Future challenges and opportunities in systemic sclerosis
Despite progress in treatment for some of the most serious aspects of systemic sclerosis, including interstitial lung disease, pulmonary hypertension and scleroderma renal crisis, there is still much more to address.
As survival overall has improved, the importance of non-lethal burden is pivotal for people living with systemic sclerosis. Inclusion of people with lived experience in the guideline working group highlighted this challenge, as did the strong involvement and endorsement of the guideline by the charity Scleroderma and Raynaud’s UK.
The British Society for Rheumatology guideline protocol includes an expectation that the guideline will be revised and updated. There is unprecedented interest in systemic sclerosis and its complications from the pharmaceutical industry and many clinical trials are ongoing.
The results of such trials, generally adding new potential treatments to background standard of care immunosuppression, will provide the evidence base for future guidelines. Still, it is likely that as one therapeutic mountain is scaled, another challenging peak will emerge. The updated guideline for systemic sclerosis represents an important milestone in the journey but the final destination is still some way off.
Author
Christopher Denton PhD FRCP FMedSci
Consultant rheumatologist, Royal Free London NHS Foundation Trust, UK
References
- Denton CP, Khanna D. Systemic sclerosis. Lancet 2017 Oct 7;390(10103):1685–99.
- Denton CP et al. The 2024 British Society for Rheumatology guideline for management of systemic sclerosis. Rheumatology (Oxford) 2024 Nov 1;63(11):2956–75.
- Denton CP et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford) 2016 Oct;55(10):1906–10.
- Ross RL et al. Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS). Rheumatology (Oxford) 2024 Dec 19:keae698.
- Chin KM et al. Treatment algorithm for pulmonary arterial hypertension. Eur Respir J 2024 Oct 31;64(4):2401325.
- Sullivan KM et al; SCOT Study Investigators. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. N Engl J Med 2018 Jan 4;378(1):35-47.
- Hughes M et al. Raynaud phenomenon and digital ulcers in systemic sclerosis. Nat Rev Rheumatol. 2020 Apr;16(4):208–21. [Erratum in: Nat Rev Rheumatol 2021 Apr;17(4):246].
- Distler O et al; SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med 2019 Jun 27;380(26):2518–28.
- Khanna D et al. Systemic Sclerosis-Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration-Approved Therapies in Clinical Practice. Arthritis Rheumatol 2022 Jan;74(1):13–27.
