CREST Syndrome

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Description

CREST syndrome (calcinosis and sclerodactyly)

CREST syndrome (also known as Cutaneous systemic sclerosis) is an autoimmune disease that has been defined as a subtype of progressive systemic sclerosis (SSc) with limited skin involvement. The word "CREST " is an acronym for the clinical features that are seen in a patient with this disease:

• Calcinosis- when calcium salts are deposited into the skin and subcutaneous tissue.
• Raynaud's phenomenon.
• Esophageal dysmotility-which can cause difficulty in swallowing.
• Sclerodactyly- scleroderma in which the fingers become thin and shiny with sclerotic skin at the tip due to subcutaneous and intracutaneous calcinosis and diffused fibrosis of the collagen.
• Telangiectasia-small widened blood vessels on the skin.

Epidemiology

Wide  variation  in  prevalence of systemic sclerosis was observed, with slightly higher estimates reported in North America (13.5–44.3 per 100,000 individuals) compared to Europe (7.2–33.9 per 100,000 individuals), which may be a true reflection of epidemiological variation or an artifact of clinical data analyses. The apparent increase in both incidence and prevalence over the last 50 years is most likely due to improved classification, earlier diagnosis, and survival. CREST syndrome may account for 22-25% of all occurrences of systemic sclerosis, according to serum antibody investigations; however, epidemiologic research specifically looking at CREST syndrome are missing. SSc diagnosis was reported to occur at the ages of 33.5-59.8 years in Europe and 46.1-49.1 years in North America, and to occur more commonly in women (female:male ratio of 3.8-11.5:1 in Europe and 4.6-15:1 in North America). Women have continuously greater prevalence and incidence rates, indicating a clinically significant difference in the occurrence of SSc across genders.

Pathophysiology

The pathogenesis of SSc is a self-amplifying process that begins with microvascular/endothelial damage, then progresses to an immunological response and inflammation, and lastly to diffuse fibrosis.Routine histology can be used to visualise the key pathophysiological events of SSc. The endothelial cells enlarge first, followed by a lympho-histiocytic inflammatory infiltration around the damaged blood vessels. Later, a dense extracellular matrix deposition with activated myofibroblasts and homogenised collagen bundles occurs.

Although the primary cause of CREST syndrome is unknown, it is reasonable to speculate that vascular endothelial cell abnormalities induce mononuclear infiltration, and that the resulting changes in TH1 and/or TH2 cell and cytokine balance result in abnormal fibroblast activity and increased collagen deposition.

Diagnosis

In the absence of a diagnostic test proving the absence or presence of SSc, the diagnosis is based on a combination of clinical and laboratory findings. According to the latest classification scheme from 2013, SSc is confirmed by:

Major Criteria:

• skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints (MCP) is sufficient to classify a subject as having SSc.
• skin thickening sparing the fingers’ are classified as not having SSc.

Minor criteria:

1. Skin thickening of the fingers -Puffy fingers and Sclerodactyly of the fingers (distal to the metacarpophalangeal joints but proximal to the proximal interphalangeal joints)
2. Fingertip lesions -Digital tip ulcers and Fingertip pitting scars
3. Telangiectasia
4. Abnormal nailfold capillaries
5. Pulmonary arterial hypertension and/or interstitial lung disease
6. Raynaud’s phenomenon
7. SSc-related autoantibodies:

• Anticentromere.
• Anti–topoisomerase I [anti–Scl-70].
• Anti–RNA polymerase III.