26th February 2025

Systemic sclerosis (SSc)

Overview of systemic sclerosis

Systemic sclerosis is an immune-mediated multisystem connective tissue disease. The main three processes involved are inflammation, vasculopathy and fibrosis. It is classified into limited cutaneous or diffuse cutaneous, depending on the pattern of skin involvement. These are associated with specific antibodies, and the specific autoantibody can predict the pattern of disease.

Clinical features of systemic sclerosis

Scleroderma

This is another name for the condition and describes the most recognised clinical feature where the skin becomes increasingly thickened and hard. Often, in the early stages, this can be very itchy and sometimes swollen. Hypo- and hyperpigmentation, known as salt-and-pepper skin, can occur. Telangiectasia is commonly seen and can be associated with other complications, such as pulmonary hypertension. Calcinosis cutis is also a common feature of systemic sclerosis, describing calcification of soft tissue. Patients often have abnormal nailfold capillaries, which can be seen on capillaroscopy.

Raynaud’s phenomenon

This is also almost universal, and is generally worse than primary Raynaud’s phenomenon. Digital ulcers can occur as a consequence of the underlying vasculopathy. 

Gastrointestinal involvement

Almost all patients will have some form of gastrointestinal involvement. Gastro-oesophageal reflux is common, and micro-aspiration as a result of this increases the risk of ILD. Gastric antral vascular ectasia is associated with certain subtypes and can cause iron deficiency anaemia and bleeding. Small intestinal bacterial overgrowth (SIBO) is also associated with SSc and can cause malabsorption, bloating and diarrhoea.

Pulmonary involvement

This is frequently seen, with ILD and pulmonary arterial hypertension being the most common manifestations. ILD presents with exertional dyspnoea, non-productive cough, fine bibasal inspiratory crackles, and a restrictive pattern on lung function testing. Pulmonary arterial hypertension also presents with exertional dyspnoea. Isolated decrease in DLCO on lung function testing can be an early clue to the development of PAH.

Renal involvement

Renal involvement is common in scleroderma, although it is often subclinical. The most important renal manifestation to be aware of is a renal crisis. This is much more common in patients with diffuse cutaneous scleroderma, particularly early on in the disease course. There has been an association with the use of corticosteroids, and therefore, these are often avoided in patients with susceptible antibodies such as Scl-70 and RNA polymerase III, early in the disease. Scleroderma renal crisis is characterised by acute renal failure with significant hypertension. Management is with ACE inhibitors unless there is evidence of CNS involvement, in which case infusions such as sodium nitroprusside are used to lower blood pressure.

Classification of systemic sclerosis

Table 4 Classification of systemic sclerosis and associated features

Box 2 Raynaud’s phenomenon

References

• Denton CP, Khanna D. Systemic sclerosis. The Lancet [Internet]. 2017 Oct [cited 2022 Feb 2];390(10103):1685–99. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30933-9/fulltext
• Nihtyanova SI, Denton CP. Autoantibodies as predictive tools in systemic sclerosis. Nature Reviews Rheumatology [Internet]. 2010 Feb 1 [cited 2022 Feb 20];6(2):112–6. Available from: https://pubmed.ncbi.nlm.nih.gov/20125179/
• Mouthon L, Bussone G, Berezné A, Noël L-H, Guillevin L. Scleroderma Renal Crisis. The Journal of Rheumatology [Internet]. 2014 Jun 1 [cited 2022 Feb 20];41(6):1040–8. Available from: https://www.jrheum.org/content/41/6/1040
• Varga J. Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults [Internet]. Axford JS, Ramirez Curtis M, editors. UpToDate. 2021 [cited 2022 Feb 20]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-systemic-sclerosis-scleroderma-in-adults
• Trang G, Steele R, Baron M, Hudson M. Corticosteroids and the risk of scleroderma renal crisis: a systematic review. Rheumatology International. 2010 Dec 4;32(3):645–53