CREST syndrome, also known as limited cutaneous systemic sclerosis (lcSSc), is a subtype of systemic sclerosis, an autoimmune connective tissue disease. It is characterized by a specific set of clinical features, represented by the acronym CREST: Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. CREST syndrome is strongly associated with secondary Raynaud’s phenomenon, which is a hallmark feature and often the earliest symptom.

Features of CREST Syndrome

1. Calcinosis: Calcium deposits in the skin or subcutaneous tissues, typically on fingers, elbows, or other pressure points, appearing as hard, painful nodules.
2. Raynaud’s Phenomenon: Episodic vasospasm of small blood vessels, usually in the fingers and toes, triggered by cold or stress, causing color changes (white, blue, red), numbness, or pain. In CREST, Raynaud’s is often severe and may precede other symptoms by years.
3. Esophageal Dysmotility: Dysfunction of the esophagus due to fibrosis, leading to acid reflux, difficulty swallowing (dysphagia), or heartburn.
4. Sclerodactyly: Thickening and tightening of the skin on the fingers, causing stiffness, reduced mobility, or a shiny appearance. In CREST, skin involvement is typically limited to the hands, face, and sometimes forearms.
5. Telangiectasia: Dilated small blood vessels visible as red spots, often on the face, lips, hands, or oral mucosa.

Causes of Secondary Raynaud’s in CREST Syndrome

Secondary Raynaud’s phenomenon in CREST syndrome is caused by:

• Vascular Endothelial Damage: Autoimmune-mediated injury to blood vessel walls leads to intimal thickening, fibrosis, and narrowing of small arteries, reducing blood flow.
• Fibrosis and Collagen Deposition: Excessive collagen production by fibroblasts affects blood vessel elasticity, contributing to vasospasm.
• Autoimmune Dysregulation: Autoantibodies, particularly anti-centromere antibodies (highly specific to CREST), are associated with vascular and tissue damage. Other antibodies, like anti-topoisomerase I (anti-Scl-70), are less common in CREST.
• Autonomic Dysfunction: Impaired nervous system control of blood vessels may exacerbate vasospasm.

Raynaud’s in CREST is often more severe than in primary Raynaud’s, with a higher risk of complications like digital ulcers, pitting scars, or, in rare cases, gangrene due to prolonged ischemia.