Rheumatology · Connective Tissue Diseases
The facts most likely to be tested
Limited cutaneous systemic sclerosis is associated with CREST syndrome and the presence of anti-centromere antibodies.
Diffuse cutaneous systemic sclerosis involves proximal skin thickening and is strongly associated with anti-Scl-70 (anti-topoisomerase I) antibodies.
Scleroderma renal crisis presents with malignant hypertension and acute kidney injury and is treated with ACE inhibitors.
Pulmonary arterial hypertension is a leading cause of mortality in limited systemic sclerosis and requires screening with transthoracic echocardiography.
Interstitial lung disease is the most common cause of death in diffuse systemic sclerosis and is best evaluated via high-resolution CT (HRCT) and pulmonary function tests.
Esophageal dysmotility occurs due to atrophy and fibrosis of the smooth muscle, leading to gastroesophageal reflux disease (GERD) and dysphagia.
Raynaud phenomenon is the earliest clinical manifestation in the vast majority of patients and is characterized by triphasic color changes (white, blue, red).
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A 45-year-old woman presents with a 6-month history of thickening of the skin on her fingers and face, along with fingertip ulcerations. She reports episodic blanching and cyanosis of her fingers triggered by cold exposure. Physical exam reveals sclerodactyly and telangiectasias on her face and palms. Laboratory studies are positive for anti-centromere antibodies.
Which of the following is the most appropriate next step in the management of this patient to screen for a life-threatening complication?
Transthoracic echocardiography
The patient's presentation of CREST syndrome (limited systemic sclerosis) necessitates screening for pulmonary arterial hypertension, which is a major cause of morbidity and mortality in this subset.
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High yield triage
Etiology / Epidemiology
Primarily affects women 30-50 years old. Characterized by fibroblast activation and excessive collagen deposition.
Clinical Manifestations
Presents with CREST syndrome features: calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
Diagnosis
Diagnosis is clinical; Anti-centromere antibodies are specific for limited disease, Anti-Scl-70 for diffuse.
Treatment
Manage Raynaud phenomenon with Calcium channel blockers. Avoid systemic corticosteroids due to renal crisis risk.
Prognosis
Leading cause of death is pulmonary arterial hypertension and interstitial lung disease.
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Epidemiology & Etiology
Systemic sclerosis is an autoimmune connective tissue disorder with a strong female predominance. Environmental triggers like silica dust or organic solvents may precipitate disease in genetically susceptible individuals.
Pertinent Anatomy
The disease targets the microvasculature and the dermis, leading to skin thickening and visceral organ fibrosis. Esophageal involvement typically affects the distal two-thirds due to smooth muscle atrophy.
Pathophysiology
The process begins with endothelial cell injury, triggering platelet activation and release of growth factors. This stimulates fibroblasts to produce excessive collagen, resulting in tissue fibrosis and vascular obliteration. Chronic ischemia leads to the characteristic Raynaud phenomenon and digital ulcers.
Clinical Manifestations
Patients present with sclerodactyly (thickened, tight skin on fingers) and Raynaud phenomenon, often the earliest sign. Scleroderma renal crisis is a medical emergency presenting with malignant hypertension and rapidly progressive renal failure. Look for telangiectasias on the face and palms as a hallmark of limited disease.
Diagnosis
Diagnosis is primarily clinical based on skin thickening proximal to the MCP joints. Anti-centromere antibodies are highly specific for limited systemic sclerosis, while Anti-Scl-70 (anti-topoisomerase I) is associated with diffuse disease and higher risk of pulmonary fibrosis. Pulmonary function tests with DLCO are essential for monitoring lung involvement.
Treatment
Management is organ-specific: Calcium channel blockers (e.g., nifedipine) are first-line for Raynaud phenomenon. Systemic corticosteroids are contraindicated as they significantly increase the risk of scleroderma renal crisis. For renal crisis, use ACE inhibitors (e.g., captopril) to control blood pressure.
Prognosis
Diffuse disease carries a worse prognosis due to rapid visceral organ involvement. Pulmonary arterial hypertension is the most common cause of mortality; patients require baseline and periodic echocardiography and PFTs.
Differential Diagnosis
Systemic Lupus Erythematosus: malar rash and arthritis
Mixed Connective Tissue Disease: high titers of anti-U1 RNP
Eosinophilic Fasciitis: skin thickening sparing fingers
Nephrogenic Systemic Fibrosis: history of gadolinium exposure
Raynaud Phenomenon (Primary): absence of skin thickening or autoantibodies