Of all the rheumatological diseases, systemic sclerosis (scleroderma) has the highest case-specific mortality and substantial non-lethal complications. It is a rare multisystem autoimmune disease of the connective tissue, distinguished by prominent fibrosis and vasculopathy of the skin and internal organs. A Seminar by Christopher Denton and Dinesh Khanna is the first comprehensive clinical review on systemic sclerosis since a formal evidence-based management guideline in 2016 and the results of key trials of stem-cell therapy and immunosuppression were published. It provides a roadmap for current best-practice management of a complex disease, and indicates areas for future progress.
20 years ago, the main cause of disease was renal crisis, which was almost always fatal within 3 months of onset. Today, death is caused by lung disease—pulmonary fibrosis and pulmonary hypertension. The major changes in treatment and management are that certain symptoms (heartburn and Raynaud’s phenomenon) and some complications (renal crisis and pulmonary hypertension) are more treatable. In the UK, care is now better organised with a network of specialised centres. This improved mortality, however, translates into potentially longer survival with non-lethal disease.
Since scleroderma is a heterogenous disease, it can be classified into subgroups that have different risks of complications and outcomes, and hence can be treated differently. The authors highlight how molecular classification at early stages and patient autoantibody-based subgrouping could be important advances over the current clinical classification, leading to better stratification and more appropriate treatment. Future research should bring more precise targeted therapies that block disease progression in the skin and organs and better address fibrosis (not just inflammation), so that patients experience fewer side-effects (includ-ing treatment-related death) than with high intensity immunosuppression—the best current treatment.
Although scleroderma is a major challenge for doctors and patients, it is now better understood. With exciting ongoing research, there is much cause for optimism.
