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

Management of CREST Syndrome

CREST syndrome requires a systematic, manifestation-specific treatment approach prioritizing early screening for life-threatening complications (pulmonary arterial hypertension, interstitial lung disease, and scleroderma renal crisis), followed by targeted therapy for each component using calcium channel blockers for Raynaud's, proton pump inhibitors for esophageal symptoms, and surgical excision for symptomatic calcinosis. 1

Immediate Screening and Risk Stratification

All patients require baseline screening for organ-threatening complications regardless of symptom severity:

• Perform pulmonary function tests, high-resolution CT, and echocardiography to detect interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), as these determine mortality 1
• Establish regular blood pressure monitoring protocols, particularly in patients with anti-RNA polymerase III antibodies, to catch scleroderma renal crisis early 1
• While ILD occurs in 40-75% of systemic sclerosis patients, only 15-18% have progressive disease requiring treatment, making screening essential for risk stratification 1

Treatment Algorithm by Clinical Manifestation

Raynaud's Phenomenon

Start with dihydropyridine calcium channel blockers as first-line therapy:

• Nifedipine (10-20 mg three times daily) reduces frequency and severity of ischemic attacks with a weighted mean difference of -10.21 attacks over 2 weeks compared to placebo 2
• PDE-5 inhibitors (sildenafil or tadalafil) serve as equally effective first-line alternatives or additions when calcium channel blockers provide inadequate response 1, 3
• Intravenous iloprost should be reserved for severe Raynaud's phenomenon that fails oral therapy 1, 3

Common pitfall: Hypotension, dizziness, flushing, dependent edema, and headaches are frequent side effects of calcium antagonists that may limit tolerability 2

Digital Ulcers

Treat active ulcers and prevent new ones with different strategies:

• Use PDE-5 inhibitors and/or intravenous iloprost for healing existing digital ulcers 1
• Prescribe bosentan specifically for preventing new digital ulcer formation, not for healing current ulcers 1
• In severe cases with gangrene or osteomyelitis, amputation may be necessary 3

Esophageal Dysmotility

Address gastroesophageal reflux and motility disturbances aggressively:

• Prescribe proton pump inhibitors for gastroesophageal reflux disease and prevention of esophageal ulcers and strictures 2, 1
• Add prokinetic drugs for symptomatic motility disturbances including dysphagia, early satiety, bloating, and pseudo-obstruction 2, 1
• Use intermittent or rotating antibiotics to treat symptomatic small intestine bacterial overgrowth 2

Critical consideration: Malnutrition from gastrointestinal involvement is a leading cause of mortality, requiring aggressive nutritional support 1

Sclerodactyly and Skin Fibrosis

Initiate immunosuppressive therapy within the optimal treatment window:

• Consider methotrexate, mycophenolate mofetil, or rituximab for skin fibrosis in patients with early disease and significant skin involvement 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

Surgical excision is the only effective treatment for symptomatic calcinosis:

• Medical therapy has minimal effectiveness for calcinosis, making surgical removal the primary option for symptomatic lesions 1, 4, 5
• Simple removal suffices for minor outpatient cases, while radical debridement is required for major, painful masses 4
• For thumb involvement, use a kite flap reconstruction to provide soft, sensate tissue with appropriate dimensions 4
• Complete resection with adequate reconstruction improves quality of life and typically provides total resolution of pain 4, 5

Important note: Calcinosis appears to be the key distinguishing element of CREST syndrome, as the other features commonly occur in both limited and diffuse systemic sclerosis 6

Interstitial Lung Disease

If screening detects ILD, initiate immunosuppression promptly:

• Mycophenolate mofetil should be considered as first-line therapy for ILD 1
• Cyclophosphamide or rituximab serve as alternatives for first-line treatment 2, 1
• Nintedanib should be added alone or in combination with mycophenolate mofetil for progressive fibrotic ILD 1

Pulmonary Arterial Hypertension

Use combination therapy from the start for PAH:

• Initiate combination therapy with PDE-5 inhibitors and endothelin receptor antagonists as first-line treatment 1
• Reserve intravenous epoprostenol for advanced PAH (WHO functional class III and IV) 1
• Consider prostacyclin analogues or riociguat as additional options 1

Critical pitfall: Do NOT use anticoagulants (warfarin) for systemic sclerosis-associated PAH, as this differs from management of idiopathic PAH 1

Scleroderma Renal Crisis

ACE inhibitors must be started immediately upon diagnosis:

• Begin ACE inhibitors at the first sign of scleroderma renal crisis 2, 1
• Monitor blood pressure and renal function carefully in patients receiving glucocorticoids, as retrospective studies suggest glucocorticoids increase risk of scleroderma renal crisis 2, 1

Key Clinical Pitfalls

• Do not delay organ screening: ILD and PAH determine mortality, and early intervention changes natural history 1
• Do not assume predictable disease course: Many patients with diffuse disease do not improve after 4 years and may worsen later 1
• Do not pursue prolonged medical management of symptomatic calcinosis: Surgical excision should be considered early rather than continuing ineffective medical therapy 1, 4, 5
• Do not overlook nutritional status: Gastrointestinal involvement causing malnutrition is a leading cause of mortality 1