Management of CREST Syndrome

Initial Screening and Risk Stratification

The European League Against Rheumatism recommends screening all patients for interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) using pulmonary function tests, high-resolution CT, and echocardiography 1, 2
Regular blood pressure monitoring is essential, especially in patients with anti-RNA polymerase III antibodies, to detect scleroderma renal crisis early 1, 2
ILD occurs in 40-75% of systemic sclerosis patients but is progressive in only 15-18%, making screening critical for identifying those requiring treatment 3, 4

The American College of Rheumatology recommends dihydropyridine calcium channel blockers (specifically nifedipine) as initial treatment for Raynaud's phenomenon 5, 6
PDE-5 inhibitors should also be considered as first-line therapy for Raynaud's phenomenon 5, 6
Intravenous iloprost should be considered for severe Raynaud's phenomenon following failure of oral therapy 5, 6

PDE-5 inhibitors and/or intravenous iloprost should be considered for treatment of active digital ulcers 5, 6
Bosentan should be considered specifically for reduction of new digital ulcer formation (not for healing existing ulcers) 7, 5

Proton pump inhibitors (PPIs) should be considered for gastroesophageal reflux disease and prevention of esophageal ulcers and strictures 5
Prokinetic drugs should be considered for symptomatic motility disturbances 5
Malnutrition is the leading cause of mortality from gastrointestinal involvement, requiring aggressive nutritional support 3, 4

Methotrexate, mycophenolate mofetil (MMF), or rituximab should be considered for treatment of skin fibrosis in patients with early disease and significant skin involvement 5
Tocilizumab may be considered for early, inflammatory diffuse cutaneous disease 5
Treatment is most effective within 2-5 years from onset of first non-Raynaud's features 3, 1

Mycophenolate mofetil (MMF) should be considered as first-line therapy for ILD 4, 7, 5
Cyclophosphamide or rituximab are alternatives for first-line treatment of ILD 5
Nintedanib should be considered alone or in combination with MMF for progressive fibrotic ILD 4, 7, 5

The American College of Cardiology recommends combination therapy with PDE-5 inhibitors and endothelin receptor antagonists as first-line treatment for PAH 5
Intravenous epoprostenol should be considered for advanced PAH (WHO functional class III and IV) 5
Other prostacyclin analogues or riociguat can be considered for PAH 5
Anticoagulants (warfarin) are NOT recommended for SSc-PAH (differs from idiopathic PAH) 5

ACE inhibitors should be used immediately at diagnosis of SRC 5, 6
Patients on glucocorticoids require regular blood pressure monitoring to detect SRC early 5

Do not delay screening for ILD and PAH - these complications determine mortality and early intervention changes natural history 1, 2
Do not use anticoagulation routinely for SSc-PAH as you would for idiopathic PAH - evidence does not support this 5
Do not assume all patients follow typical disease progression - many patients with diffuse disease do not improve after 4 years and may worsen later 3
Do not overlook nutritional status - malnutrition from gastrointestinal involvement is a leading cause of mortality 3, 4
Recognize that calcinosis has no proven medical therapy - surgical options should be considered early for symptomatic cases rather than prolonged ineffective medical management 3, 1

Pulsed laser therapy can improve the cosmetic appearance of telangiectasias in patients with CREST syndrome (laser‑based treatment reduces visible lesions). 8
An annual dermatology examination is recommended to assess skin changes and detect new or worsening telangiectasias in CREST patients (routine monitoring facilitates early intervention). 8