What is the management approach for Crest (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia) syndrome?

Management of CREST Syndrome

CREST syndrome (limited cutaneous systemic sclerosis) requires organ-based treatment targeting each manifestation, with Raynaud's phenomenon managed first-line with calcium channel blockers, followed by systematic screening and treatment of life-threatening complications including interstitial lung disease and pulmonary arterial hypertension. 1

Initial Screening and Risk Stratification

Mandatory screening is essential because early intervention changes natural history and reduces mortality:

• Screen all patients for interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) using pulmonary function tests, high-resolution CT, and echocardiography 1
• Monitor blood pressure regularly, especially in patients with anti-RNA polymerase III antibodies, to detect scleroderma renal crisis early 1
• ILD occurs in 40-75% of systemic sclerosis patients but is progressive in only 15-18%, making screening critical for identifying those requiring treatment 1

Treatment Algorithm by Manifestation

Raynaud's Phenomenon (Present in Nearly All Patients)

First-line therapy:

• Dihydropyridine calcium channel blockers (specifically nifedipine) should be used as initial treatment 1
• PDE-5 inhibitors should also be considered as first-line therapy 1

Second-line therapy:

• Intravenous iloprost should be considered for severe Raynaud's phenomenon following failure of oral therapy 1

Digital Ulcers (Occur in 50% of Patients)

• PDE-5 inhibitors and/or intravenous iloprost should be considered for treatment of active digital ulcers 1
• Bosentan should be considered specifically for reduction of new digital ulcer formation (not for healing existing ulcers) 1

Esophageal Dysmotility (Affects 90% of Patients)

• Proton pump inhibitors (PPIs) should be considered for gastroesophageal reflux disease and prevention of esophageal ulcers and strictures 1
• Prokinetic drugs should be considered for symptomatic motility disturbances 1
• Malnutrition is the leading cause of mortality from gastrointestinal involvement, requiring aggressive nutritional support 1

Sclerodactyly and Skin Fibrosis

For patients with early disease and significant skin involvement:

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

Calcinosis (The Defining Feature of CREST)

Important caveat: Calcinosis appears to be the key distinguishing element of CREST syndrome, as the other features commonly occur in both limited and diffuse systemic sclerosis 2

• No effective pharmacological treatments are supported by RCT data 1
• Surgical debridement should be considered for painful or functionally limiting calcinosis, particularly in the digits 3
• For thumb involvement, flap reconstruction (such as kite flap) provides optimal functional and sensory outcomes 3

Telangiectasia

• Pulsed dye laser (PDL) is effective but requires approximately twice as many treatments compared to sporadic telangiectasia (typically 2-fold more sessions needed) 4
• CREST telangiectasia exhibit thickened vessel walls and increased dermal collagen, explaining relative treatment resistance 4

Life-Threatening Complications Requiring Aggressive Management

Interstitial Lung Disease (ILD)

Treatment hierarchy:

• Mycophenolate mofetil (MMF) should be considered as first-line therapy 1
• Cyclophosphamide or rituximab are alternatives for first-line treatment 1
• Nintedanib should be considered alone or in combination with MMF for progressive fibrotic ILD 1
• Tocilizumab should be considered as an additional option 1

Pulmonary Arterial Hypertension (PAH)

PAH occurs in less than 10% clinically but is found in 65-80% at autopsy, emphasizing the importance of screening 1

Treatment approach:

• Combination therapy with PDE-5 inhibitors and endothelin receptor antagonists should be considered as first-line treatment 1
• Intravenous epoprostenol should be considered for advanced PAH (WHO functional class III and IV) 1
• Other prostacyclin analogues or riociguat can be considered 1
• Anticoagulants (warfarin) are NOT recommended for SSc-PAH (differs from idiopathic PAH) 1

Scleroderma Renal Crisis (SRC)

• ACE inhibitors should be used immediately at diagnosis 1
• Patients on glucocorticoids require regular blood pressure monitoring to detect SRC early 1

Critical Pitfalls to Avoid

1. 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 1

3. Do not assume all patients follow typical disease progression - many patients with diffuse disease do not improve after 4 years and may worsen later 1

4. Do not overlook nutritional status - malnutrition from gastrointestinal involvement is a leading cause of mortality 1

5. Recognize that calcinosis has no proven medical therapy - surgical options should be considered early for symptomatic cases rather than prolonged ineffective medical management 1, 3