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

CREST Syndrome: Definition and Clinical Entity

CREST syndrome is the limited cutaneous variant of systemic sclerosis, defined by five classic clinical features: Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. 1

Core Definition and Classification

• CREST syndrome is synonymous with limited cutaneous systemic sclerosis (lcSSc), representing a distinct subset of systemic sclerosis where skin fibrosis is restricted to areas distal to elbows and/or knees, though facial and neck involvement may occur 1

• The acronym CREST was coined in 1964, though the first case was described by French physicians Thibierge and Weissenbach in 1910 2

• Diagnosis requires the presence of at least three of the five clinical criteria, though full expression of all five features is uncommon and typically develops gradually over many years 3, 4

The Five Clinical Features

Calcinosis

• Calcinosis appears to be the key distinguishing element of CREST syndrome, as it is less common in other SSc subsets and its presence in association with other features is characteristic 4
• Manifests as dystrophic calcium deposits in subcutaneous tissues, often in fingers and extremities 3
• No proven medical therapy exists for calcinosis—surgical options should be considered early for symptomatic cases 5

Raynaud's Phenomenon

• Episodic vasospasm of digital arteries triggered by cold or stress, causing color changes (white, blue, red) in fingers and toes 6
• Present in the vast majority of CREST patients and often the earliest manifestation 3

Esophageal Dysmotility

• Results from atrophy and fibrosis of esophageal smooth muscle, causing severe hypomotility and incompetent lower esophageal sphincter 7
• Leads to gastroesophageal reflux, dysphagia, and risk of strictures 5
• Malnutrition from gastrointestinal involvement is a leading cause of mortality 5

Sclerodactyly

• Thickening and tightening of skin on fingers and hands, causing flexion contractures and functional impairment 3
• Represents the limited skin involvement characteristic of this variant 1

Telangiectasia

• Dilated superficial blood vessels appearing as small red spots, typically on face, hands, and mucous membranes 3
• Cosmetically significant but not life-threatening 7

Serologic Markers

• Anti-centromere antibodies are characteristic of CREST syndrome and present in more than 50% of cases 2, 3
• Antinuclear antibodies (ANA) are typically positive 3

Natural History and Prognosis

• The prognosis of CREST syndrome is relatively good with prolonged disease duration exceeding 10 years 2
• Disease progression is typically slower compared to diffuse cutaneous systemic sclerosis 1
• However, patients with long-standing limited sclerosis have higher likelihood of developing isolated pulmonary arterial hypertension (PAH) 1

Life-Threatening Complications

Pulmonary Arterial Hypertension (PAH)

• PAH is a cause of death in up to 50% of patients who die from scleroderma-related complications in limited sclerosis 1
• Occurs in 3-14% of CREST patients as a very late event 2
• When PAH develops, prognosis is severe with 50% mortality at 2 years 2
• The vasculopathy in CREST-associated PAH is very similar to idiopathic PAH 1

Digital Gangrene

• Seldom associated but can lead to finger losses 2
• Results from severe, recalcitrant Raynaud's phenomenon and digital ulcerations 6

Critical Clinical Pitfalls

• Do not assume CREST syndrome only overlaps with limited SSc—recent evidence suggests these features can occur in diffuse SSc as well, contrary to traditional teaching 4
• Do not delay screening for PAH and interstitial lung disease—these complications determine mortality and require early detection through pulmonary function tests, high-resolution CT, and echocardiography 5
• While full manifestation of all five features is classic, rapidly progressive cases with early complete clinical expression can occur, though this is atypical 3
• The presence of Raynaud's phenomenon, sclerodactyly, and esophageal dysmotility alone does not define CREST syndrome, as these features are common in other SSc subsets 4