18th January 2024

Background

Systemic sclerosis – also known as Scleroderma – is an autoimmune multi-system connective tissue disease characterised by increased fibroblast activity causing abnormal growth and deposition of collagen, vascular damage and fibrosis of connective tissues. This usually occurs in the skin (hence the name scleroderma) along with internal organs such as the GI tract, lungs and heart. It can also occur in the vasculature, resulting in manifestations such as Raynaud’s, pulmonary arterial hypertension and renal disease. Typical cutaneous features of systemic sclerosis include microstomia and ‘salt-and-pepper’ appearance of skin due to areas of hypo- and hyper-pigmentation.

Classification of systemic sclerosis

Systemic sclerosis has two main subtypes:

1. Limited cutaneous systemic sclerosis (more common type)
   • The areas of skin involved include the face, arms (distal to the elbows) and legs (distal to the knees)
   • Additional features can be summarised as CREST (CREST syndrome is the old name for this sub-type): Calcinosis, Raynaud’s, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
   • Slow onset and progression
2. Diffuse cutaneous systemic sclerosis (less common type)
   • The areas of skin involved include the trunk, proximal arms to the elbow and proximal legs to the knee
   • Higher mortality due to higher incidence of multi-organ involvement
   • Rapid onset with early skin thickening and Raynaud’s

Antibodies

There are a number of antibodies associated with systemic sclerosis, and each has associations with particular complications which can help with screening and prognostication.

• Anti-topoisomerase-1 antibody (also known as anti-Scl-70): strong association with lung fibrosis, renal disease, and poor prognosis.
• Anti-centromere antibody (ACA): seen in patients with limited cutaneous systemic sclerosis; associated with pulmonary hypertension.
• Anti-RNA-polymerase-III antibody: seen in patients with diffuse cutaneous systemic sclerosis and strongly associated with renal disease, and in particular, ‘scleroderma renal crisis’.