CREST Syndrome Does Not Cause Scleroderma—It IS a Subtype of Scleroderma
CREST syndrome is not a cause of scleroderma; rather, it represents the limited cutaneous variant of systemic sclerosis (scleroderma) itself. The term CREST is an acronym describing five clinical features that characterize this specific presentation of the disease 1.
Understanding the Relationship
CREST syndrome is synonymous with limited cutaneous systemic sclerosis (lcSSc), one of the two main subsets of scleroderma 1. The classification works as follows:
- Systemic sclerosis (scleroderma) is the overarching autoimmune connective tissue disease characterized by fibrosis and vasculopathy 1
- Limited cutaneous SSc (CREST syndrome) involves skin fibrosis distal to the elbows/knees without truncal involvement, though facial and neck skin may be affected 1
- Diffuse cutaneous SSc involves skin both distal and proximal to the knees/elbows and/or truncal areas 1
Clinical Features of CREST Syndrome
The acronym CREST describes five characteristic manifestations 2, 3, 4:
- Calcinosis (dystrophic calcium deposits)
- Raynaud's phenomenon
- Esophageal dysmotility
- Sclerodactyly (skin thickening of fingers)
- Telangiectasia
Diagnosis requires only three of the five features to be present, though complete manifestation of all five is uncommon and typically develops gradually over years 2, 4.
Key Distinguishing Characteristics
CREST syndrome (limited cutaneous SSc) is strongly associated with anti-centromere antibodies, which are present in more than 50% of cases 1, 5. This serologic marker helps distinguish it from diffuse systemic sclerosis 1.
The prognosis of CREST syndrome is generally more favorable than diffuse scleroderma, with disease duration often exceeding 10 years 5. However, serious complications can occur:
- Pulmonary arterial hypertension (PAH) develops in 7-12% of patients with systemic sclerosis, occurring most frequently in the limited cutaneous variant 1. In limited scleroderma, PAH is the cause of death in up to 50% of patients who die of scleroderma-related complications 1.
- Digital gangrene with finger loss can occur 5
- Interstitial lung disease is common (40-75% of all SSc patients) but less severe in limited disease 1
Clinical Pitfalls to Avoid
Do not confuse the temporal relationship: CREST syndrome does not precede or cause scleroderma—it is the disease itself in its limited cutaneous form 1, 6.
Three of the five CREST features (Raynaud's phenomenon, sclerodactyly, and esophageal dysmotility) are common in both limited and diffuse SSc subsets, so their presence alone does not define CREST syndrome 4. Calcinosis appears to be the key distinguishing element that, when present with other features, more specifically characterizes CREST syndrome 4.
Screening for complications is essential: Echocardiographic screening for pulmonary hypertension is recommended in symptomatic patients with scleroderma spectrum diseases 1. Given that PAH can develop as a late complication with severe prognosis (50% mortality at 2 years), early detection through regular monitoring is critical 1, 5.