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At a glance

An autoimmune connective tissue disorder associated with anticentromere antibodies. A form of scleroderma associated with esophageal dysmotility. CREST is an acronym that stands for Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasis.

Synonyms

Limited Scleroderma (the now preferred name); Thibièrge-Weissenbach Syndrome (some authors use Thibièrge-Weissenbach Syndrome to describe the calcinosis of the hand in combination with ischemia in the context of scleroderma).

History

First described in 1910 by G. Thibièrge (1856-1926) and R.J.E. Weissenbach (1885-1963), two French physicians.

Incidence

Unknown. The prevalence of systemic sclerosis in the general population is in the range of approximately 30-300:1,000,000 (with geographical differences). It occurs in all ethnicities and females are 2 to 4 times more often affected than males, and during reproductive years, this ratio increases to 10 to 15 times.

Genetic inheritance

Although a few cases with a variable inheritance pattern have been described, in most cases autoimmune processes appear to be involved in the pathogenesis of this disorder, for which a genetic predisposition may be present.

Pathophysiology

The three primary pathologic processes of scleroderma are initially perivascular infiltration predominantly with lymphocytes and macrophages, followed by collagen (including fibronectin and proteoglycans) depositions with tissue thickening and fibrosis secondary to chronic activation of skin fibroblasts. Vascular changes mainly affect the small arteries and present with endothelial injury, intima proliferation, vasospasms, and significantly decreased neovascularization. It has been suggested that several cytokines are involved in the pathogenesis of this disorder, particularly transforming growth factor-β (TGF-β) and interleukin-4, which are both present in increased concentrations in this disorder, while the level of interferon-γ, which acts as an inhibitor of collagen synthesis, is decreased.

Diagnosis

The minimal diagnostic criteria for scleroderma required by the American College of Rheumatology include either the major criterion of proximal cutaneous scleroderma (defined as symmetric thickening, tightening, and induration of the skin of the fingers and the skin proximal to the metacarpophalangeal or metatarsophalangeal joints. The changes may affect the entire limb or spread to head, neck, and trunk) or two of the three minor criteria (ie, sclerodactyly [aforementioned findings, but strictly limited to the fingers], digital [finger pad] pitting scars, or bilateral pulmonary fibrosis with reticular or reticulonodular pattern on the chest radiograph). The presence of anticentromere antibodies in the serum may be helpful for the diagnosis (positive in approximately 50% of patients with CREST Syndrome), while only about 20% test positive for scleroderma antibody (Anti-SCL-70/topoisomerase I). However, overall the sensitivity and specificity of these antibodies are limited.

Clinical aspects

Two different forms of systemic scleroderma can be distinguished: limited scleroderma (80% of patients) and diffuse scleroderma (20%). In limited scleroderma (CREST Syndrome), ...

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