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PH-IM13

Systemic sclerosis

How injury to small vessels, autoimmunity and overactive fibroblasts combine to thicken the skin and scar the oesophagus, lungs, heart and kidneys in systemic sclerosis, and why Raynaud’s phenomenon usually comes first.

By the end, you can

  • Describe the three linked processes of systemic sclerosis: small-vessel injury, immune activation and fibrosis.
  • Explain Raynaud’s phenomenon, digital ulcers and capillary loss in terms of vascular injury.
  • Explain how activated fibroblasts thicken the skin and cause sclerodactyly and contractures.
  • Relate the limited and diffuse subsets and their autoantibodies to the organs they tend to affect.
  • Explain how interstitial lung disease, pulmonary arterial hypertension and scleroderma renal crisis develop.
  • Recognise the classic skin, kidney, oesophageal and lung appearances, the antibodies and tests of systemic sclerosis, and explain how vasodilators, ACE inhibitors, immunosuppressants and antifibrotics act on the mechanism.

What it is

Systemic sclerosis (scleroderma) is a chronic autoimmune connective tissue disease in which injury to small blood vessels, activation of the immune system and excess collagen production by fibroblasts thicken the skin and scar internal organs. It is divided by the extent of skin involvement into limited and diffuse cutaneous forms. Localised scleroderma (morphoea), which affects only the skin and the tissue beneath it, is a different condition.

3 types to tell apart
Limited cutaneous systemic sclerosis
Skin thickening of the fingers, hands, forearms below the elbows, feet and face; Raynaud’s phenomenon often for years beforehand; usually anti-centromere antibodies; pulmonary arterial hypertension is a late risk. The older name CREST syndrome lists its features: calcinosis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia.
Diffuse cutaneous systemic sclerosis
Skin thickening also above the elbows and knees and on the trunk, spreading fast in the first years, with earlier internal organ disease; often anti-topoisomerase I (anti-Scl-70) antibodies, linked to lung fibrosis, or anti-RNA polymerase III antibodies, linked to renal crisis.
Systemic sclerosis sine scleroderma
Internal organ disease and typical antibodies with little or no skin thickening.

US spelling: fibres → fibers, oesophagus → esophagus.

Normal function

Skin, small vessels and fibroblasts in balance

The dermis gives skin its strength and stretch. In the , fibroblasts lay down bundles of collagen (mainly types I and III) and elastic fibres, and enzymes remodel them at about the same rate, so the skin stays supple and slides over the .

Small arteries and control blood flow to the skin, and exchange nutrients and waste. Their endothelium balances vasodilators (nitric oxide and prostacyclin) against the vasoconstrictor endothelin-1. In the fingers, sympathetic nerves narrow the vessels in the cold to save heat, and they reopen on warming.

The same elements, endothelium, fibroblasts and smooth muscle, keep the walls of the oesophagus, the alveoli and the small arteries of the kidney thin and supple.

Point to it on the model