Write a short note on systemic sclerosis (scleroderma).

Definition

Systemic sclerosis is a multisystem connective tissue disease characterised by the triad of excessive collagen deposition (fibrosis) of skin and internal organs, obliterative small-vessel vasculopathy, and autoimmunity. It affects women four times more often than men, with peak onset between 30 and 50 years.

Pathogenesis

Endothelial injury leads to vascular damage with intimal proliferation and luminal narrowing (there is a paucity of vessels, not merely vasospasm), immune activation with autoantibody production, and fibroblast activation with excessive collagen deposition driven by TGF-beta and connective tissue growth factor.

Classification

CREST syndrome describes the limited form: Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia.

Clinical Features

Vascular:

• Raynaud's phenomenon — present in over 95% and usually the first symptom, often preceding other features by years. Triphasic colour change: white (ischaemia) → blue (deoxygenation) → red (reperfusion).
• Digital ulceration, pitting scars of the fingertips, and gangrene from fixed vascular narrowing.
• Abnormal nailfold capillaroscopy — dilated, giant capillaries with dropout; an early and highly useful bedside investigation.

Skin: progressive tightening and thickening; sclerodactyly with tapering fingers and flexion contractures; loss of skin creases and hair; microstomia with a puckered perioral appearance and reduced mouth opening; mask-like facies with beaked nose; salt-and-pepper pigmentation; calcinosis cutis; telangiectasia.

Gastrointestinal (up to 90%): oesophageal dysmotility with reflux, dysphagia and stricture; gastric antral vascular ectasia ("watermelon stomach") causing anaemia; small bowel hypomotility with bacterial overgrowth, malabsorption and pseudo-obstruction; wide-mouthed colonic diverticula; faecal incontinence.

Pulmonary — now the leading cause of death:

• Interstitial lung disease — non-specific interstitial pneumonia pattern, commonest in diffuse disease with anti-Scl-70.
• Pulmonary arterial hypertension — commoner in limited disease, presenting with exertional dyspnoea and a loud P2.

Cardiac: myocardial fibrosis, arrhythmia, conduction defects, pericardial effusion.

Renal: scleroderma renal crisis — see danger box.

Musculoskeletal: arthralgia, tendon friction rubs, myopathy, contractures.

Investigations

• ANA positive in most
• anti-centromere and anti-Scl-70 for subtype
• anti-RNA polymerase III (associated with renal crisis and malignancy).
• Nailfold capillaroscopy.
• HRCT chest and pulmonary function tests with DLCO — a falling DLCO is often the earliest sign of ILD or pulmonary hypertension.
• Echocardiography annually to estimate pulmonary artery pressure, with right heart catheterisation for confirmation.
• Barium swallow or manometry for dysmotility
• renal function and regular blood pressure monitoring
• ECG and NT-proBNP.

Management

There is no cure; management is organ-based, and early detection of organ involvement determines outcome.

• Raynaud's and digital ulcers: keep warm, avoid cold and smoking; calcium channel blockers (nifedipine) first-line; phosphodiesterase-5 inhibitors (sildenafil); intravenous iloprost for critical ischaemia; bosentan to prevent new digital ulcers.
• Skin and early diffuse disease: methotrexate or mycophenolate mofetil; autologous haematopoietic stem cell transplantation in selected rapidly progressive cases.
• Interstitial lung disease: mycophenolate mofetil or cyclophosphamide; nintedanib (antifibrotic) reduces the rate of decline; tocilizumab in selected patients.
• Pulmonary arterial hypertension: endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, managed in specialist centres.
• Gastrointestinal: proton pump inhibitors in high dose for reflux, prokinetics for dysmotility, rotating antibiotics for bacterial overgrowth, nutritional support.
• Musculoskeletal: physiotherapy, hand exercises to preserve function, analgesia.
• Avoid high-dose corticosteroids wherever possible — see the danger box.