What is the recommended management for a typical middle‑aged woman (30‑60 years) with CREST syndrome (calcinosis cutis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia)?

Management of CREST Syndrome (Limited Systemic Sclerosis)

For a middle-aged woman with CREST syndrome, initiate immediate screening for pulmonary arterial hypertension and interstitial lung disease using pulmonary function tests, high-resolution CT, and echocardiography, as these complications determine mortality—particularly PAH, which causes death in up to 50% of CREST patients who die from disease-related complications. 1, 2

Initial Risk Stratification and Screening

All patients require comprehensive baseline evaluation within the first visit:

• Pulmonary screening with pulmonary function tests, high-resolution CT chest, and transthoracic echocardiography to detect interstitial lung disease (occurs in 40-75% of systemic sclerosis patients) and pulmonary arterial hypertension 2
• Blood pressure monitoring at every visit, especially if anti-RNA polymerase III antibodies are present, to detect scleroderma renal crisis early 2
• Autoantibody testing including anticentromere antibodies (present in >50% of CREST syndrome) and antinuclear antibodies 1, 3

The prognosis of CREST syndrome is relatively good with prolonged disease duration exceeding 10 years, but pulmonary arterial hypertension when it develops carries a severe prognosis with 50% mortality at 2 years 1, 3. Patients with long-standing limited sclerosis have higher likelihood of developing isolated PAH compared to diffuse disease 1.

Treatment Algorithm by Manifestation

Raynaud's Phenomenon (Present in Nearly All Patients)

First-line therapy:

• Nifedipine (dihydropyridine calcium channel blocker) as initial pharmacological treatment—reduces both frequency and severity of attacks in approximately two-thirds of patients 2, 4
• Non-pharmacological measures: avoid cold exposure, trauma, stress, smoking, and vibration injury; use mittens (not gloves), insulated footwear, and hand warmers 2, 4

Second-line therapy (if inadequate response to calcium channel blockers):

• Phosphodiesterase-5 inhibitors (sildenafil or tadalafil)—effective for reducing frequency, duration, and severity of attacks 2, 4

Third-line therapy (for severe, refractory disease):

• Intravenous iloprost for severe Raynaud's unresponsive to oral therapies 2, 4

Digital Ulcers

For active digital ulcers:

• PDE-5 inhibitors and/or intravenous iloprost for healing existing ulcers 2, 4

For prevention of new digital ulcers:

• Bosentan (endothelin receptor antagonist) specifically for reduction of new digital ulcer formation, particularly effective if ≥4 digital ulcers present at baseline—does NOT heal existing ulcers 2, 4

Esophageal Dysmotility

Standard management:

• Proton pump inhibitors for gastroesophageal reflux disease and prevention of esophageal ulcers and strictures 2
• Prokinetic drugs for symptomatic motility disturbances 2
• Aggressive nutritional support—malnutrition from gastrointestinal involvement is a leading cause of mortality 2

Sclerodactyly and Skin Fibrosis

For early disease with significant skin involvement (within 2-5 years of first non-Raynaud's features):

• Methotrexate, mycophenolate mofetil, or rituximab should be considered for skin fibrosis 2
• Tocilizumab may be considered for early, inflammatory diffuse cutaneous disease 2

Treatment is most effective within 2-5 years from onset of first non-Raynaud's features 2.

Calcinosis Cutis

Critical management point:

• No proven medical therapy exists for calcinosis 2
• Surgical excision should be considered early for symptomatic, painful, or disabling lesions rather than prolonged ineffective medical management 2, 5
• Complete resection is possible even for large tumoral masses with adequate reconstruction and acceptable postoperative results 5

Interstitial Lung Disease (If Detected on Screening)

First-line therapy:

• Mycophenolate mofetil as first-line treatment 2
• Cyclophosphamide or rituximab as alternatives 2

For progressive fibrotic ILD:

• Nintedanib alone or in combination with mycophenolate mofetil 2

Pulmonary Arterial Hypertension (If Detected on Screening)

This is the most critical complication determining mortality in CREST syndrome.

First-line therapy:

• Combination therapy with PDE-5 inhibitors and endothelin receptor antagonists 2

For advanced PAH (WHO functional class III and IV):

• Intravenous epoprostenol 2

Alternative options:

• Other prostacyclin analogues or riociguat 2

Critical pitfall:

• Do NOT use anticoagulants (warfarin) for SSc-PAH—this differs from idiopathic PAH where anticoagulation is standard; evidence does not support anticoagulation in systemic sclerosis-associated PAH 2

Telangiectasias

• Primarily a cosmetic concern; pulsed laser therapy may improve appearance 6

Ongoing Monitoring Schedule

• Annual pulmonary function tests and echocardiography to detect progressive ILD or development of PAH 2
• Blood pressure monitoring at every visit to detect scleroderma renal crisis 2
• Annual dermatology examination for skin changes 6
• Nutritional assessment at regular intervals given malnutrition as leading cause of mortality from GI involvement 2

Critical Pitfalls to Avoid

1. Do not delay screening for PAH and ILD—these complications determine mortality and early intervention changes natural history; PAH in CREST has 50% mortality at 2 years if untreated 1, 3

2. Do not use anticoagulation routinely for SSc-PAH as you would for idiopathic PAH 2

3. Do not assume calcinosis will respond to medical therapy—consider surgical options early for symptomatic cases 2, 5

4. Do not overlook nutritional status—malnutrition from gastrointestinal involvement is a leading cause of mortality 2

5. Do not delay rheumatology referral—rheumatologists achieve superior outcomes with earlier diagnosis, more frequent disease-modifying therapy prescription, and better prevention of complications 4

Specialist Coordination

Rheumatology should be the primary managing specialty for CREST syndrome, with multidisciplinary input from pulmonology (for PAH/ILD), gastroenterology (for esophageal complications), and dermatology (for skin manifestations) 4. Early rheumatology referral is critical as delays are a major cause of postponed effective treatment 4.