26th January 2024

Background

Systemic sclerosis is an immune-mediated, multi-system disease that is characterised by fibrosis of the skin and internal organs and widespread vascular dysfunction. The diagnosis and related disorders are based upon clinical findings and supported by specific serological abnormalities. 

Epidemiology

The majority of patients with systemic sclerosis are female and tend to have a younger age of onset, more limited disease and increased risk of peripheral vascular disease and pulmonary hypertension. 

Men have an increased risk of diffuse cutaneous disease, cardiac involvement, renal crisis and frequent interstitial lung disease. 

African Americans tend to have an earlier age at onset, more severe phenotypes and increased risk of pulmonary fibrosis and renal crisis. 

Pathophysiology 

The exact pathogenesis of systemic sclerosis is complex and not fully understood, but immunological and vascular processes are known to play a key role. There is increased production and deposition of structurally normal collagen as a result of extracellular matrix interactions. 

Vascular and endothelial changes cause vasoconstriction, which is mediated by endothelins, nitric oxide, hypoxia, physical stress, and humoral and inflammatory mediators. 

Autoantibodies are present in approximately 90% of patients with systemic sclerosis. The most common include topoisomerase I (previously Scl-70), centromere antigens and RNA-polymerase.

Anti-topoisomerase-I (Scl-70) antibodies are not sensitive but highly specific for systemic sclerosis and are associated with a higher risk of interstitial lung disease, more extensive skin involvement and higher disease activity. 

Anti-centromere antibodies are associated with limited cutaneous involvement.