SN6 SHORT NOTE 5M

Describe systemic sclerosis with its types, pathogenesis and organ involvement.

Pathology · 2nd Professional — Para-Clinical

Definition

Systemic sclerosis (scleroderma) is a chronic autoimmune disease characterised by excessive fibrosis of skin and internal organs, widespread small-vessel disease, and autoantibodies.

Female to male ratio 3:1; peak in the fourth and fifth decades

Classification

Feature	Limited cutaneous (crest)	Diffuse cutaneous
Skin involvement	Distal to elbows and knees, plus the face	Proximal limbs and trunk as well
Raynaud phenomenon	Precedes by years	Onset close to the skin changes
Antibody	Anti-centromere	Anti-Scl-70 (topoisomerase I); anti-RNA polymerase III
Visceral disease	Late; pulmonary hypertension	Early and severe; pulmonary fibrosis, renal crisis
Prognosis	Better	Worse

Crest — Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia

Pathogenesis

An unknown trigger causes endothelial injury in small vessels → Intimal proliferation and vessel narrowing → chronic ischaemia → Immune activation — T cells and macrophages release cytokines → TGF-beta and PDGF stimulate fibroblasts → Excessive collagen deposition in skin and organs → Progressive fibrosis with vascular obliteration

Three processes act together — vascular damage, autoimmunity and fibrosis; which of them starts the disease is still unknown

Organ Involvement

Organ	Features
Skin	Oedematous then indurated then atrophic; sclerodactyly with tapering fingers; mask-like face with a pinched nose and restricted mouth opening; calcinosis; digital ulcers and pitting scars
Vascular	Raynaud phenomenon in over 95% — the usual first symptom, with the triphasic white-blue-red colour change
Gastrointestinal (90%)	Oesophageal dysmotility with reflux and stricture; the commonest visceral involvement; bacterial overgrowth and malabsorption; wide-mouthed colonic diverticula
Lung	Interstitial fibrosis and pulmonary hypertension — now the leading cause of death
Kidney	Scleroderma renal crisis — malignant hypertension with rapidly progressive renal failure; "onion-skin" intimal thickening
Heart	Myocardial fibrosis, arrhythmia, pericarditis
Musculoskeletal	Arthralgia, tendon friction rubs, myopathy

CLINICAL PEARL

Scleroderma renal crisis was once the commonest cause of death and is now largely treatable.
ACE inhibitors transformed it — and they must be given even when the creatinine is rising, which feels counterintuitive.
Corticosteroids in high dose precipitate it and are therefore avoided in diffuse disease.

Applied Aspects

Nailfold capillaroscopy shows dilated and dropped-out capillaries, and distinguishes primary from secondary Raynaud phenomenon early
Raynaud phenomenon with abnormal capillaroscopy and a positive ANA predicts progression to a connective tissue disease
Annual screening for pulmonary hypertension and interstitial lung disease with echocardiography and lung function is now standard, since early treatment helps
Treatment is largely organ-directed — proton pump inhibitors for reflux, calcium channel blockers for Raynaud, ACE inhibitors for renal crisis, immunosuppression for lung fibrosis
Localised scleroderma (morphoea) affects skin only, has no Raynaud phenomenon or visceral disease, and carries a good prognosis — it must not be confused with the systemic form

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