Systemic sclerosis

Systemic sclerosis is a rare multisystem disorder characterised by vascular abnormalities, connective tissue sclerosis and atrophy, and the presence of autoantibodies. There is both cutaneous and systemic involvement, with gastrointestinal, respiratory, cardiac, and renal complications. The early identification, and aggressive treatment, of organ-specific involvement reduces morbidity and mortality.

This chapter is set out as follows:  

• The cause in unknown 

• 85% of cases present between the ages of 20 and 60 years
• There is a female to male ratio of 3-6:1, it usually presents later in men 
• Raynaud's phenomenon is the usual presenting feature, followed by skin changes, then systemic involvement 

Classification

• Limited cutaneous systemic sclerosis (SSc)
• 66% of cases
• ​A long history of Raynaud's phenomenon
• Limited skin involvement (peripheral only)
• Associated with systemic disease 

• Diffuse cutaneous systemic sclerosis (SSc)
• 33% of cases
• ​A short interval (< 1 year) between the onset of Raynaud's phenomenon and the development of skin changes
• Truncal and peripheral skin involvement
• Associated with systemic disease

Early diagnosis

The early identification, and aggressive treatment, of organ-specific involvement reduces morbidity and mortality. The four key early diagnostic features are:

• Raynaud's phenomenon
• Puffy fingers 
• Microvascular alterations in the nailfolds as seen via capillaroscopy (dermoscopy)
• Disease-specific autoantibodies (refer to the section investigations)

Cutaneous changes

In the majority of cases cutaneous changes arise before systemic involvement. The hands and face are the most frequently involved sites, although cutaneous changes can be widespread and 50 % of cases have hyperpigmentation.

Hands

• Atrophy begins first in the nail pulps causing small painful ulcers that leave pitted scars. With time the nails become much smaller and the whole distal finger becomes atrophic 
• Sclerodactyly - fingers become swollen, and the skin feels tight and has a shiny appearance. The fingers become less mobile
• Nailfold changes - include enlargement of capillary loops, disorganisation of the normal distribution of capillaries, budding capillaries, extravasates, and loss of capillaries. There does not appear to be a correlation between the degree of nailfold change and the severity of systemic sclerosis 
• Telangiectases
• Calcinosis (calcium deposits) develops in the skin, particularly the fingers, hands and other bony areas. These can breakdown and discharge chalky material
• Ulceration and gangrene may occur with minor trauma, or at the tips of the fingers, as a result of poor circulation

Face

• ​Small mat-like telangiectases
• The forehead becomes smooth and shiny 
• The nose becomes small and pinched, and the mouth opening constricted
• The lower eyelids cannot be depressed

Other cutaneous features 

• ​40% of cases develop leg ulcers
• Dry eyes and associated eye complications

Systemic features

• Musculoskeletal - arthralgia, reduced movement resulting from contractures
• Gastrointestinal - oesophageal reflux, dysphagia, weight loss, abdominal pain, diarrhoea, constipation, malabsorption 
• Respiratory - diffuse pulmonary fibrosis, pulmonary hypertension, respiratory failure  
• Cardiovascular - pericarditis, arrhythmias, cardiac failure
• Renal - hypertension and renal failure. The severity of renal complications has reduced since the advent of ACE inhibitors
• CNS - is involved in less than 10% of cases. Complications include neuropathy and the Carpal Tunnel syndrome

The CREST syndrome

• CREST = Calcinosis, Raynaud's phenomenon, OEsophgaeal involvement, Sclerodactyly, and Telangiectases (or CRST if there is no oesophageal involvement)
• The CREST syndrome is best viewed as a subgroup of systemic sclerosis, with a better overall prognosis

Associations

• Systemic sclerosis is associated with a number of conditions including Sjögren's syndrome in up to 20% of cases, myaesthenia gravis, lupus erythematosus and dermatomyositis, with the latter two conditions the main association is with limited cutaneous systemic sclerosis ie hand involvement only

• Autoantibodies
  • Centromere, Scl-70, RNA polymerase III, Fibrillarin (U3RNP), and Pm-Scl are the antibodies most commonly associated with systemic sclerosis
  • Individual antibodies can help predict organ-specific complications:
    • SCL-70 - a very high risk of early lung fibrosis
    • RNA polymerase III - a 10 times increased risk of renal crisis
    • Fibrillarin (U3RNP)- a much increased risk of pulmonary hypertension
  • For more information on autoantibodies and other relevant tests refer to the chapter on investigations

• Histology
• The histological findings of morphoea (scleroderma) and systemic sclerosis are similar, with a fundamental process of thickening and homogenisation of collagen bundles. With specific reference to systemic sclerosis, the dermis shows hyalinisation of the collagen, often with associated abnormalities of elastic tissue and reticulin 

• Patients with suspected systemic sclerosis should be referred urgently to Secondary Care

• The early identification, and aggressive treatment, of organ-specific involvement reduces morbidity and mortality


• Management is multidisciplinary