Diffuse Cutaneous Systemic Sclerosis

Diffuse cutaneous systemic sclerosis (dcSSc) is the severe subset of systemic sclerosis with skin thickening proximal to the elbows and knees (trunk), early rapid progression, and high risk of visceral involvement.

• Autoantibodies: anti-topoisomerase I (Scl-70), anti-RNA polymerase III (renal crisis, malignancy), anti-U3RNP/fibrillarin.

• Pathogenesis: vasculopathy, immune activation and fibrosis driven by TGF-beta.

• Early phase (first 3 to 5 years) carries the highest risk: interstitial lung disease (most), scleroderma renal crisis (10 to 15%), cardiac involvement, gastrointestinal failure.

• Mortality 50% at 10 years; ILD and PAH are leading causes of death.

• Raynaud (often brief before skin disease), puffy hands, rapid skin thickening of fingers, forearms, face, trunk; tendon friction rubs, joint contractures, digital ulcers, pigmentation changes (salt and pepper).

• Dyspnoea, dry cough, bibasal crackles (ILD).

• Scleroderma renal crisis: abrupt hypertension, headache, visual changes, acute kidney injury, microangiopathic haemolytic anaemia.

• Dysphagia, malabsorption, pseudo-obstruction, arrhythmia, heart failure.

• ACR/EULAR classification criteria; modified Rodnan skin score (0 to 51) for severity and trend.

• Antibody profile (anti-topoisomerase I, anti-RNA polymerase III), nailfold capillaroscopy.

• HRCT chest, full PFTs, echocardiography, NT-proBNP, ECG, Holter, cardiac MRI, troponin.

• Blood pressure monitoring (home), creatinine, urinalysis; renin elevation in crisis.

• Cancer screening with anti-RNA polymerase III positivity.

• Endoscopy, manometry as needed.

• Early skin and ILD disease: mycophenolate mofetil 1 to 1.5 g twice daily (first line), cyclophosphamide 2 mg/kg orally or 600 mg/m2 IV monthly for 6 months, tocilizumab 162 mg SC weekly (stabilises FVC), rituximab 1 g twice 2 weeks apart, nintedanib 150 mg twice daily, methotrexate 15 to 25 mg weekly for skin.

• Autologous haematopoietic stem cell transplantation (cyclophosphamide conditioning) for rapidly progressive disease in selected patients: survival benefit.

• Avoid high dose steroids (prednisolone over 15 mg/day) because of renal crisis risk.

• Scleroderma renal crisis: start ACE inhibitor immediately (captopril 6.25 to 12.5 mg, increase to 50 mg every 6 to 8 hours; or enalapril) titrated to lower blood pressure by 10 to 20 mmHg daily; add amlodipine, IV iloprost; dialysis if needed (renal recovery up to 2 years); continue ACE inhibitor.

• Raynaud, digital ulcers, PAH, gastrointestinal disease: as for limited disease.

• Physiotherapy, skin care, psychosocial support, pulmonary rehabilitation.

• Monitor skin score, PFTs every 3 to 6 months.