CREST SyndromeDz

Synonyms: Limited scleroderma (see discussion of diffuse scleroderma).

ICD-9 Code: 710.1
ICD-10 Code: M34.1

Definition: “CREST syndrome” is more appropriately referred to as “limited scleroderma.” In this variant of systemic sclerosis, skin thickening (sclerodactyly) is found distal to the elbow or knee and rarely affects the face or neck. The CREST constellation of findings includes: Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias. Calcinosis is the least common of these findings. All of these manifestations occur in both limited and diffuse scleroderma; hence the term CREST is mainly of historic interest, yet the acronym has great instructive value. The table  below compares features of limited and diffuse scleroderma.

Etiology: Unknown (see etiology of scleroderma)

Demographics: Both diffuse and limited forms of scleroderma affect females more than males, with a female:male ratio of 3:1. The limited variant of scleroderma is more prevalent than the diffuse form. Of note, Raynaud’s phenomenon is quite common in both PSS and CREST, and can be seen ini up to 10% of female non- smokers.  Only a very small minority of persons who have Raynaud’s ultimately develop limited or diffuse scleroderma.

Cardinal Findings: Virtually all patients manifest sclerodactyly and Raynaud’s phenomenon. This should prompt a search for esophageal dysmotility or cutaneous telangiectasias, often found over the lips, tongue, hands, and face. Tight skin is usually most prominent in the fingers and toes and is less common over the hand or wrist. If severe, skin thickening may lead to problematic ischemic/traumatic ulcerations over the distal fingertips or DIP or PIP joints. Tendon friction rubs are rarely seen in limited scleroderma. Esophageal dysmotility manifests as food “sticking” substernally at the lower esophageal sphincter.  Subcutaneous calcinosis is found in 30% to 40% of patients. Calcific deposits are usually “hard”; are located over the fingers, forearms, or lower extremities; and may be painful, intermittently inflamed, or ulcerate.

Uncommon Findings: Small bowel disease is infrequently encountered in those with longstanding CREST syndrome and may manifest as bloating, cramping, diarrhea, or malabsorption. Interstitial lung fibrosis is much more common in diffuse scleroderma but has been described in the limited form. Those with longstanding CREST syndrome are at greatest risk for developing progressive pulmonary hypertension, usually late in the disease.

Diagnostic Testing: The majority of patients are ANA positive. Anticentromere antibodies are found in more than 50% of patients with limited scleroderma but only 10% of those with diffuse disease. Anticentromere antibodies may also be found in patients with primary biliary cirrhosis. A minority of CREST patients have anti-RNP or anti-SCL-70 antibodies. Pulmonary function test (PFT) results are abnormal in two-thirds of patients, with a reduced forced vital capacity or DLCO. Nailfold capillaroscopy is usually abnormal.

Imaging: Chest radiography (CXR) is indicated in those with pulmonary symptoms. Up to one-third of patients may show evidence of pulmonary fibrosis. High-resolution computerized tomography is more sensitive than plain radiography and can be used to evaluate pulmonary symptoms.

Differential Diagnosis: CREST should be distinguished from diffuse scleroderma, other limited forms of scleroderma (e.g., morphea, linear scleroderma), eosinophilic fasciitis, overlap syndrome, drug-induced sclerodactyly, primary biliary cirrhosis, and other causes of pseudosclerodactyly (e.g., diabetes, hypothyroidism).

Therapy: Treatment of limited scleroderma is primarily directed at symptomatic relief of joint pain, Raynaud’s phenomenon, and esophageal reflux and dysmotility (see “Scleroderma, Therapy”). Smoking cessation, hand warming (mittens, hand warmers, etc.), vascular health and care of the distal extremities should be emphasized. There is no proven role for corticosteroids, penicillamine or other disease-modifying or biologic therapies in limited scleroderma. However, in children with morphea, methotrexate has been shown to improve cutaneous findings. Some clinicians will try methotrexate or mycophenolate or other immunomodulators for skin manifestations of scleroderma. Cutaneous ulcerations may pose a therapeutic challenge. Treatment should hinge on warm soaks, local and vasodilator and antiplatelet agents, and treatment of superinfection.  Treatment and prevention of digitial ulcers may include the use of topical nitroglycerin, calcium channel blockers, sildenafil, and the endothelin receptor antagonist bosentan.  There are many treatments for pulmonary artery hypertension (see Scleroderma).

BIBLIOGRAPHY

Furst DE, Clements PJ, Saab M, et al. Clinical and serological comparison of 17 chronic progressive systemic sclerosis (PSS) and 17 CREST syndrome patients matched for sex, age, and disease duration. Ann Rheum Dis 1984;43:794–801. PMID: 6335385

Mitchell H, Bolster MB, LeRoy EC. Scleroderma and related conditions. Med Clin North Am. 1997;81:129-49.  PMID:9012758

Torok KS, Arkachaisri T.  Methotrexate and corticosteroids in the treatment of localized scleroderma: a standardized prospective longitudinal single-center study. J Rheumatol. 2012;39:286-94. PMID: 22247357