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

Management of CREST Syndrome

Begin treatment with dihydropyridine calcium channel blockers (nifedipine) for Raynaud's phenomenon, proton pump inhibitors for esophageal symptoms, and immediately screen all patients for interstitial lung disease and pulmonary arterial hypertension using pulmonary function tests, high-resolution CT, and echocardiography. 1

Mandatory Initial Screening

All patients require immediate risk stratification regardless of symptom severity:

• Perform pulmonary function tests, high-resolution CT chest, and echocardiography at diagnosis to detect interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), as these complications determine mortality 1
• Monitor blood pressure regularly, particularly in patients with anti-RNA polymerase III antibodies who are at highest risk for scleroderma renal crisis 1
• Recognize that ILD occurs in 40-75% of systemic sclerosis patients, though only 15-18% have progressive disease requiring treatment 1

Treatment by Manifestation

Raynaud's Phenomenon (First-Line Therapy)

• Start nifedipine 10-20 mg three times daily, which reduces ischemic attacks by a weighted mean difference of -10.21 episodes over 2 weeks compared to placebo 2
• PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) are equally appropriate as first-line therapy and improve frequency and severity of attacks 2, 1
• Escalate to intravenous iloprost for severe Raynaud's phenomenon that fails oral therapy 1
• Common side effects of calcium antagonists include hypotension, dizziness, flushing, dependent edema, and headaches 2

Digital Ulcers

• Use PDE-5 inhibitors and/or intravenous iloprost for active digital ulcer healing 1
• Add bosentan specifically to prevent new digital ulcer formation, not for healing existing ulcers 1

Esophageal Dysmotility

• Prescribe proton pump inhibitors for all patients with gastroesophageal reflux symptoms to prevent esophageal ulcers and strictures 2, 1
• Add prokinetic drugs (metoclopramide, domperidone) for symptomatic dysphagia, early satiety, bloating, or pseudo-obstruction 2, 1
• Treat small intestinal bacterial overgrowth with intermittent or rotating antibiotics when symptoms suggest this complication 2
• Aggressively support nutrition, as malnutrition from gastrointestinal involvement is a leading cause of mortality 1

Sclerodactyly and Skin Fibrosis

Treatment is most effective within 2-5 years from onset of first non-Raynaud's features 1:

• Consider methotrexate, mycophenolate mofetil, or rituximab for early disease with significant skin involvement 1
• Tocilizumab may be used for early, inflammatory diffuse cutaneous disease 1
• Recognize that treatment efficacy declines substantially after 5 years from disease onset 1

Interstitial Lung Disease

• Mycophenolate mofetil is first-line therapy for ILD 1
• Cyclophosphamide or rituximab are alternative first-line options, though cyclophosphamide has known toxicity concerns 2, 1
• Add nintedanib alone or in combination with mycophenolate for progressive fibrotic ILD 1

Pulmonary Arterial Hypertension

• Start combination therapy with PDE-5 inhibitors plus endothelin receptor antagonists as first-line treatment 1
• Escalate to intravenous epoprostenol for WHO functional class III and IV disease 1
• Do NOT use anticoagulation (warfarin) routinely for SSc-PAH, as evidence does not support this practice unlike idiopathic PAH 1
• Consider prostacyclin analogues or riociguat as additional options 1

Scleroderma Renal Crisis

• Immediately start ACE inhibitors at diagnosis of renal crisis 2, 1
• Monitor blood pressure and renal function closely in patients receiving glucocorticoids, as retrospective studies suggest glucocorticoids increase SRC risk 2, 1

Calcinosis

• No proven medical therapy exists for calcinosis 1
• Consider surgical debridement early for symptomatic cases rather than prolonged ineffective medical management 1, 3
• For thumb involvement, kite flap reconstruction provides soft, sensate tissue with appropriate dimensions and typically requires no further remodeling 3
• Surgical debridement usually provides complete pain resolution with full recovery of motion and grip function 3

Telangiectasia

• Pulsed dye laser effectively clears telangiectasia but requires approximately twice as many treatments (twofold higher) compared to sporadic telangiectasia 4
• The increased resistance relates to thickened vessel walls and collagen fibers in the dermis 4

Critical Pitfalls

• Never delay ILD and PAH screening—these complications determine mortality and early intervention changes natural history 1
• Never assume disease progression follows typical patterns—many patients with diffuse disease do not improve after 4 years and may worsen later 1
• Never overlook nutritional status assessment—gastrointestinal malnutrition is a leading mortality cause 1
• Never apply idiopathic PAH anticoagulation protocols to SSc-PAH—the evidence base differs 1