Rheumatology · Systemic Sclerosis
The facts most likely to be tested
CREST syndrome is a limited form of systemic sclerosis characterized by calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
The most specific serologic marker for CREST syndrome is the anti-centromere antibody.
Raynaud phenomenon is typically the initial presenting symptom and may precede other clinical manifestations by years.
Esophageal dysmotility results from atrophy and fibrous replacement of the smooth muscle in the lower esophagus, leading to gastroesophageal reflux disease (GERD) and dysphagia.
Patients with CREST syndrome are at a significantly higher risk for developing pulmonary arterial hypertension (PAH) compared to diffuse systemic sclerosis.
Sclerodactyly involves the thickening and tightening of the skin on the fingers and toes due to excessive collagen deposition.
Telangiectasias are commonly found on the face, palms, and mucosal surfaces and represent dilated superficial blood vessels.
Vignette unlocked
A 52-year-old woman presents with a 3-year history of fingertip color changes triggered by cold exposure. She reports increasing difficulty swallowing solids and frequent heartburn. Physical examination reveals tight, shiny skin on her fingers, small calcium deposits on her elbows, and multiple dilated capillaries on her cheeks. Laboratory testing is positive for anti-centromere antibodies.
Which of the following complications is this patient at the highest risk of developing, necessitating periodic screening with echocardiography?
Pulmonary arterial hypertension
The patient's presentation of CREST syndrome (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia) and positive anti-centromere antibodies confirms the diagnosis, and these patients require regular screening for pulmonary arterial hypertension.
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High yield triage
Etiology / Epidemiology
Limited systemic sclerosis occurring primarily in middle-aged women. Associated with anti-centromere antibodies.
Clinical Manifestations
Defined by CREST: Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia.
Diagnosis
Diagnosis is clinical; Anti-centromere antibodies are the most specific serologic marker.
Treatment
Manage symptoms: Calcium channel blockers for Raynaud; Proton pump inhibitors for esophageal reflux.
Prognosis
Monitor for pulmonary arterial hypertension; it is the leading cause of mortality.
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Epidemiology & Etiology
CREST syndrome, or limited cutaneous systemic sclerosis, predominantly affects women between 30 and 50 years old. It is an autoimmune connective tissue disorder characterized by localized skin thickening. Unlike diffuse systemic sclerosis, skin involvement is restricted to the face and distal extremities.
Pertinent Anatomy
The disease primarily targets the microvasculature and connective tissue of the skin, esophagus, and pulmonary arteries. Fibrosis of the esophageal smooth muscle leads to dysphagia and gastroesophageal reflux. Pulmonary vascular remodeling results in increased resistance and subsequent pulmonary arterial hypertension.
Pathophysiology
The process begins with endothelial cell injury leading to vascular inflammation and intimal proliferation. This triggers fibroblast activation and excessive collagen deposition in the skin and internal organs. The presence of anti-centromere antibodies is highly specific and correlates with a lower risk of renal crisis compared to diffuse disease.
Clinical Manifestations
Patients present with Raynaud phenomenon as the initial symptom, often preceding other signs by years. Sclerodactyly (thickening of finger skin) and telangiectasias on the face and palms are classic. Pulmonary arterial hypertension is a critical, life-threatening complication that may present with exertional dyspnea.
Diagnosis
Diagnosis is based on the presence of at least 3 of the 5 CREST features. Anti-centromere antibodies are the gold-standard serologic test. Echocardiography is the screening tool of choice for suspected pulmonary arterial hypertension.
Treatment
Management is supportive and organ-specific. Calcium channel blockers (e.g., nifedipine) are first-line for Raynaud. Proton pump inhibitors are used for esophageal dysmotility and reflux. Avoid systemic corticosteroids as they may precipitate scleroderma renal crisis.
Prognosis
The prognosis is generally better than diffuse systemic sclerosis, but pulmonary arterial hypertension remains the primary cause of death. Patients require annual pulmonary function tests and echocardiograms to monitor for disease progression.
Differential Diagnosis
Diffuse systemic sclerosis: rapid skin thickening and early internal organ involvement
Systemic lupus erythematosus: malar rash and positive anti-dsDNA
Mixed connective tissue disease: positive anti-U1 RNP and features of multiple rheumatic diseases
Eosinophilic fasciitis: skin induration sparing the hands and feet
Raynaud disease: primary vasospasm without underlying connective tissue disease