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Updated: Apr 1, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Systemic sclerosis: from pathogenesis to targeted therapy
1Centre for Rheumatology, UCL Division of Medicine, Royal Free Campus, London, UK. c.denton@ucl.ac.uk.
Abstract:
Systemic sclerosis (scleroderma) leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. More than half of those diagnosed ultimately die from the disease. Current treatments focus on broad spectrum immunosuppression or organ-based therapy for complication such as lung fibrosis, pulmonary or systemic hypertension. Targeting peptide mediators such as endothelin-1 have already led to licensed effective therapies for SSc vasculopathy. Outcomes are improving but as well as providing a major clinical challenge there are great opportunities for research translation that can be expected to improve understanding of the pathogenesis of SSc and also develop better and more targeted therapy. Key pathways and mediators can be identified within the skin and blood vessels and these are now being examined in early stage clinical trials. Promising results are emerging from targeting cytokine signalling, including IL-6, and from other immune-inflammatory therapies including lipid mediators such as LPA1. Other approaches to modulate TGFbeta and other profibrotic pathways also have potential although safety and toxicity remain to be determined. Since many profibrotic pathways have important physiological roles the assessment of safety and toxicity will be paramount. Nevertheless, advances in understanding the interplay between different pathological processes and progress in clinical trial design and patients stratification mean that targeted therapies are emerging and likely to be further developed and refined to have application in other important clinical contexts such as lung fibrosis.
Insights
Systemic sclerosis (SSc) causes organ damage via inflammation and fibrosis. Research is translating findings into targeted therapies for better patient outcomes.
Area of Science:
- Rheumatology and Immunology
- Translational Medicine
- Fibrotic Diseases
Background:
- Systemic sclerosis (SSc), or scleroderma, is a severe autoimmune disease characterized by inflammation, fibrosis, and vascular damage.
- SSc significantly impacts internal organs (heart, lungs, kidneys, bowel), leading to high morbidity and mortality.
- Current treatments rely on broad immunosuppression or organ-specific therapies, with limited success for underlying pathology.
Purpose of the Study:
- To explore emerging research and therapeutic targets for systemic sclerosis.
- To identify key pathways and mediators involved in SSc pathogenesis for targeted treatment development.
- To assess the potential of novel therapies in improving patient outcomes and addressing unmet clinical needs.
Main Methods:
- Identification of key molecular pathways and mediators in SSc skin and blood vessels.
- Examination of novel therapeutic targets, including cytokine signaling (e.g., IL-6), lipid mediators (e.g., LPA1), and TGF-beta pathways.
- Evaluation of early-stage clinical trials for targeted therapies and assessment of safety and toxicity profiles.
Main Results:
- Targeting endothelin-1 has yielded effective therapies for SSc vasculopathy.
- Early clinical trials show promising results for therapies targeting IL-6 signaling and LPA1.
- Modulation of TGF-beta and other profibrotic pathways presents potential but requires careful safety evaluation.
Conclusions:
- Advances in understanding SSc pathogenesis are paving the way for more targeted and effective treatments.
- Emerging therapies targeting specific molecular pathways offer hope for improved patient outcomes.
- Continued research, clinical trial design, and patient stratification are crucial for refining SSc therapies and potentially applying them to other fibrotic conditions.
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