An autoimmune connective tissue disorder associated
with anticentromere antibodies. A form of scleroderma associated with
esophageal dysmotility. CREST is an acronym for calcinosis, Raynaud
phenomenon, esophageal dysmotility, sclerodactyly, telangiectasis.
Limited Scleroderma; Thibièrge-Weissenbach Syndrome
(some authors use Thibièrge Weissenbach Syndrome to describe the
calcinosis of the hand in combination with ischemia in the context of
First described in 1910 by G. Thibièrge and
R.J.E. Weissenbach, two French physicians.
The incidence of CREST syndrome is not known. The
incidence of systemic sclerosis in the general population is in the range of
approximately 2-7:1,000,000 (with geographical differences). All
ethnicities can be affected. Females are affected two to four times more
often than males.
Although a few cases with an inheritance
pattern have been described, in most cases autoimmune processes appear to be
involved in the pathogenesis of this disorder. A genetic predisposition may
The three primary pathologic processes of
scleroderma are initially perivascular infiltration with predominantly
lymphocytes and macrophages, followed by collagen (including fibronectin and
proteoglycans) deposition with tissue thickening and fibrosis secondary to
chronic activation of skin fibroblasts, and vascular changes mainly
affecting the small arteries and presenting 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 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.
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 (i.e., 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 approximately 20% test positive
for scleroderma antibody (SCL-70/topoisomerase I). However, overall the
sensitivity and specificity of these antibodies are limited.
Two different forms of scleroderma have been
recognized. The localized form includes morphea and linear scleroderma
(“sclérodermie en coup de sabre” if located in the facial area) and
does not result in visceral organ involvement. The two types of systemic
scleroderma are limited scleroderma (80% of patients) and diffuse
scleroderma (20%). In limited scleroderma, the disease usually progresses
slowly (over several years) and, by definition, the skin involvement remains
distal to elbows and knees (however, involvement of the face and neck may
occur). In more than two ...