CREST syndrome is an autoimmune connective tissue disorder representing a specific, limited form of systemic sclerosis (scleroderma). Scleroderma is characterized by the hardening and tightening of the skin and connective tissues throughout the body. The limited cutaneous form, CREST syndrome, restricts skin thickening mainly to the areas below the elbows and knees, though the face and neck may also be involved. This multisystemic condition is defined by the five features encapsulated in its acronym.
The Five Hallmark Manifestations
The acronym CREST represents the five clinical features of the syndrome. These manifestations typically develop gradually over many years, and a diagnosis may be given even if a patient presents with only two or three of the five features.
- Calcinosis
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasias
Calcinosis
Calcinosis involves the formation of small, hard deposits of calcium salts within the soft tissues, particularly under the skin. These deposits commonly appear on the fingers and around the joints or bony prominences. While often asymptomatic, these nodules can become tender, potentially breaking through the skin and leading to chronic infection.
Raynaud Phenomenon
Raynaud phenomenon is often the earliest sign of CREST syndrome, preceding other symptoms by years. It involves an episodic narrowing of the small arteries in the fingers and toes, usually in response to cold temperatures or emotional stress. This constriction causes a characteristic sequence of color changes: white (pallor), blue (cyanosis), and finally red (reactive hyperemia) as the digits rewarm. Severe episodes can impair blood flow enough to cause painful digital ulcers or lead to tissue death.
Esophageal Dysmotility
Esophageal dysmotility results from the atrophy and fibrosis of the smooth muscle within the lower two-thirds of the esophagus. This damage prevents the coordinated muscle contractions necessary to move food down to the stomach. The resulting weak motility and an incompetent lower esophageal sphincter lead to gastroesophageal reflux, heartburn, and the sensation of food getting stuck (dysphagia).
Sclerodactyly
Sclerodactyly refers to the thickening and tightening of the skin on the fingers and hands. This process begins with an inflammatory phase and results from the overproduction and deposition of collagen in the dermis. The skin becomes shiny and taut, which can limit the range of motion in the joints and cause painful flexion contractures that impair hand function.
Telangiectasias
Telangiectasias are small, dilated capillaries that form visible red spots or spider veins on the skin. They are often found on the face, lips, hands, and the upper trunk. While usually only a cosmetic concern, telangiectasias can also occur on internal mucosal surfaces, such as the gastrointestinal tract, where they may lead to bleeding.
Understanding the Autoimmune Origin
CREST syndrome is classified as an autoimmune disorder because it involves a malfunction in the body’s immune system. The immune system targets the body’s own healthy connective tissues, leading to inflammation and damage to the small blood vessels. This misdirected attack involves the production of autoantibodies.
Damage to the blood vessel lining (endothelium) is thought to be one of the earliest events in the disease process. This vascular injury triggers fibroblasts to become hyperactive and overproduce collagen. The excessive deposition of collagen results in the characteristic hardening and thickening of the skin and internal organs, a process known as fibrosis.
Genetic predisposition plays a role, as individuals with a first-degree relative with scleroderma or other autoimmune diseases are at increased risk. Environmental factors, such as exposure to certain chemicals or viral infections, are also considered potential triggers that initiate the autoimmune response in susceptible individuals.
Identifying CREST Syndrome
Diagnosing CREST syndrome begins with a clinical evaluation by a physician, who assesses the patient for the five manifestations. The physician examines the skin for signs of thickening, swelling, calcium deposits, or telangiectasias. A thorough medical history is also taken, focusing on the onset of Raynaud phenomenon and any difficulties with swallowing or acid reflux.
Laboratory testing is a decisive step in confirming the diagnosis and distinguishing CREST syndrome from other forms of systemic sclerosis. The most specific serological marker is the anti-centromere antibody (ACA), an autoantibody targeting the centromere in the cell nucleus. A positive ACA test is detected in up to 95% of patients with CREST features.
The presence of the ACA, combined with the limited pattern of skin involvement, indicates a more favorable course compared to the diffuse form of systemic sclerosis. Other tests, such as capillaroscopy to examine the small blood vessels at the base of the fingernails or imaging studies like barium swallows for esophageal function, assess the extent of the disease.
Approach to Symptom Management
Since there is no cure for CREST syndrome, treatment focuses on managing individual symptoms, improving quality of life, and preventing complications. Management often requires a multidisciplinary team of specialists.
For Raynaud phenomenon, treatment aims to promote blood flow and prevent vasospasms. This involves behavioral changes, such as avoiding cold exposure and stress, alongside medications like calcium channel blockers. For calcinosis, treatment involves pain relievers or topical antibiotics for open sores. Surgical removal may be considered for large, painful, or frequently infected deposits.
Esophageal dysmotility symptoms are managed with medications that reduce stomach acid, such as proton pump inhibitors, to prevent damage from chronic reflux. For patients with swallowing difficulties, procedures like esophageal dilation may be necessary. Sclerodactyly is addressed with physical and occupational therapy to maintain flexibility and strength in the hands and prevent the development of contractures.
Telangiectasias do not require medical intervention, as they are not a health risk. If they are a cosmetic concern, procedures such as laser therapy or electrocautery can be used to minimize their appearance. Immunosuppressant medications may be used to slow the progression of the underlying autoimmune disease, though their use is weighed against potential side effects.