CREST syndrome

Scleroderma is a systemic autoimmune disease primarily affecting the skin but often also involving the gastrointestinal tract, the respiratory, renal, cardiovascular, and the genitourinary systems.

Finally, numerous vascular structures are frequently involved. The name comes from the Greek words for hardening of the skin. The symptoms result from inflammation and progressive tissue fibrosis and occlusion of the microvasculature by excessive production and deposition of collagens. Scleroderma can be classified in terms of the degree and location of the skin involvement. Hence, scleroderma can be categorized into two major groups, diffuse and limited (CREST).


The diffuse form of scleroderma (systemic sclerosis) involves symmetric thickening of skin of the extremities, face, and trunk (chest, back, abdomen, or flanks). Organ disease can occur early on and be serious. Organs affected include the esophagus, bowels, and lungs with scarring (fibrosis), heart, and kidneys. High blood pressure can be a troublesome side effect that may lead to kidney damage. This form of scleroderma can be quite disabling.


CREST syndrome is a limited cutaneous form of systemic scleroderma. CREST is an acronym for five cardinal clinical features, i.e.:

  • Calcinosis: calcium deposits in soft tissue
  • Raynaud’s syndrome: a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas
  • Esophageal dysmotility: dysmotility develops as the smooth muscle of the esophagus is replaced by scar tissue, gradually leading to progressive loss of peristalsis
  • Sclerodactyly: localized thickening and tightness of the skin of the fingers or toes
  • Telangiectasia: small dilated blood vessels near the surface of the skin or mucous membranes

The prognosis is generally good for limited cutaneous scleroderma patients who escape pulmonary complications, but is worse for those with the diffuse cutaneous disease, particularly in older age, and for males. Death occurs most often from pulmonary, heart and kidney complications. In diffuse cutaneous disease the five-year survival is about 70%.

Epidemiology

The cause is unknown. Scleroderma runs in families, but the genes have not been identified. This disease is found among all races worldwide, but women are four times more likely to develop scleroderma than men. Children rarely suffer the systemic type, but localized scleroderma is common. Most adults are diagnosed after between the age of 30 and 50. Prevalence of spontaneous scleroderma in the US is 0.026%, compared with 1.6% in families with systemic scleroderma. It is estimated that 20% to 30% of these patients demonstrate CREST syndrome.

Diagnosis

The diagnosis of the scleroderma syndrome is based on the finding of the clinical features of the illnesses. In addition to the clinical picture, nearly all patients with scleroderma are positive for blood tests that suggest autoimmunity, i.e. antinuclear antibodies (ANAs) are usually detectable. The anti-centromere antibody is found almost exclusively in CREST. In contrast, anti-Scl 70 antibody (anti-topoisomerase I antibody) is most often seen in patients with the diffuse form of scleroderma.

Relevant Literature

  1. Akesson A, Wollheim FA. Organ manifestations in 100 patients with progressive systemic sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br J Rheumatol. 1989;28:281-6.
  2. Arnett FC. Is scleroderma an autoantibody mediated disease?. Curr Opin Rheumatol. Nov 2006;18(6):579-81
  3. Cepeda EJ, Reveille JD. Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical indications and relevance. Curr Opin Rheumatol. Nov 2004;16(6):723-32.
  4. Gabrielli A, et al. Scleroderma. N Engl J Med 2009; 360:1989-2003
  5. Jimenez, Sergio A.,Patrick M. Cronin. "Scleroderma." eMedicine.com. Jan. 5, 2010. <http://emedicine.medscape.com/article/331864-overview
  6. Mayes MD. Scleroderma epidemiology. Rheum Dis Clin North Am. Nov 1996;22(4):751-64.
  7. Sapadin A N and Raul Fleischmajer R. Treatment of Scleroderma Arch Dermatol. 2002;138:99-105
  8. Silman AJ, Newman J. Epidemiology of systemic sclerosis. Curr Opin Rheumatol. Nov 1996;8:585-9.
  9. Velayos EE, et al. The 'CREST' syndrome. Comparison with systemic sclerosis (scleroderma). Arch Intern Med. Nov 1979;139:1240-4.