CREST Syndrome
Definition
Patients with CREST syndrome are a subset of patients with scleroderma. CREST is an acronym for the cardinal clinical features of the syndrome in a given patient: calcinosis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia.
Three primary pathologic features of scleroderma include increased collagen deposition, perivascular mononuclear cell infiltration, and vascular abnormalities.
The pathologic hallmark of scleroderma is progressive fibrosis of tissues. Collagen (types I and III), fibronectin, and proteoglycans are deposited in the interstitium and in the intima of small arteries. Fibrosis is found in clinically affected and unaffected tissue.
Aetiology / Risk Factors
Classified as a connective-tissue disorder, the precise aetiology of scleroderma is not well understood but appears to include both genetic and environmental factors. Immune mechanisms, vascular damage, and a triggering of an overproduction of collagen as well as other extracellular membrane proteins all seem to be involved in the pathogenesis of this disease. Molecular mimicry between infectious agents and potential auto-antigens suggest that this similarity may trigger an autoimmune response in certain cases of scleroderma. In some women, foetal stem cells, which can persist in the maternal circulation for many years postpartum, may be involved in the pathogenesis of systemic sclerosis via a graft-versus-host reaction.
Other exogenous agents have been shown to produce autoantibodies similar to those observed in systemic sclerosis. Examples of environmental factors that have been reported in connection to scleroderma or scleroderma-like illnesses include:
- Silica dust—suggested by increased incidence of scleroderma and scleroderma-like illnesses in coal and gold miners
- Vinyl chloride
- Epoxy resins
- Aromatic hydrocarbons—e.g., benzene and toluene
- L-tryptophan ingestion leading to eosinophilic fasciitis and the eosinophilic-myalgia syndrome (each scleroderma-like disorders)
- Rapeseed oil used for cooking and then ingested caused a scleroderma-like syndrome in 20,000 people in Spain in 1981.
Risk Factors
- Gender—scleroderma occurs in females three times more often than in males, and up to 15 times more often during the childbearing years.
- Age—the condition is relatively rare in children, with peak onset occurring between the ages of 20 and 50.
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Ancestry—young women with African ancestry tend to exhibit systemic sclerosis more frequently and in more severe forms.
Symptoms & Signs
Skin and Soft Tissue
- Raynaud's phenomenon—95% of scleroderma patients
- Oedema of fingers and hands in early disease; may also include forearms, feet, lower legs, and face.
- Thickening of skin, appears distally first (in the digits) and moves proximally, becoming generalised in those with diffuse cutaneous scleroderma. Eventually, the skin binds to the subcutaneous tissue—known as the indurative phase. In limited cutaneous scleroderma, changes are generally confined to digits, extremities, and face.
- Ulcers may appear on volar pads of finger tips or bony prominences; can become infected
- Hyperpigmentation or hypopigmentation of skin as disease progresses
- Telangiectasia—may appear after several years on fingers, face, tongue, and buccal mucosa; telangiectasia of the gastrointestinal tract can lead to bleeding
- Microstomia from facial skin involvement as well as loss of wrinkles and facial expressions
- Subcutaneous calcifications
Joints/Musculoskeletal
- Pain, swelling, and stiffness of fingers and knees—50% of patients with scleroderma
- Symmetric polyarthritis similar to rheumatoid arthritis may be seen
- Carpal tunnel syndrome from involvement of wrist tendon sheaths
Respiratory
- Dyspnoea, particularly exertional
- Nonproductive cough
- Very rarely, haemoptysis as manifestation of alveolitis
Mucosal Membranes
- Dry eyes
- Vaginal dryness and dyspareunia
Urologic
Gastrointestinal
- Dysphagia from loss of oesophageal motility due to neuromuscular dysfunction
- Acid reflux—later in the course of disease secondary to atony and dilatation of the lower oesophagus
- Bloating
- Abdominal pain
- Constipation in the case of colon involvement; may lead to faecal impaction and obstruction
Cardiovascular
- Angina secondary to coronary vasospasm
- Malignant hypertension—sign of renal failure