Scleroderma, or systemic sclerosis, is an autoimmune connective tissue disease that involves sclerotic changes of the skin and internal organs. While the etiology remains unknown, the disease is characterized by autoantibody production, collagen deposition, and vascular dysfunction. The disease is observed in all ages and is slightly more common in individuals of African descent and 3-4 times more common in women. The age of onset is usually between 30 and 50 years.
Scleroderma can affect the connective tissue of any organ, including the skin, gastrointestinal tract, lungs, kidneys, joints, muscles, heart, and blood vessels. Pulmonary disease is the leading cause of mortality. Additional common clinical features include esophageal fibrosis and dysmotility, arthralgias, and Raynaud phenomenon. Less common manifestations include hypertensive renal crisis, pulmonary hypertension and interstitial lung disease, and cardiomyopathy.
There are three major clinical subsets of scleroderma:
1) Limited cutaneous systemic sclerosis (distal skin sclerosis, Raynaud phenomenon, frequent severe late-stage complications such as pulmonary hypertension and gastrointestinal involvement). CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) refers to a subset of patients with limited scleroderma.
2) Diffuse cutaneous systemic sclerosis (proximal extremity or trunk skin sclerosis, Raynaud phenomenon of shorter duration, high risk of renal crisis, and cardiac and lung fibrosis).
3) Systemic sclerosis sine scleroderma (Raynaud phenomenon and systemic involvement without skin sclerosis).
The subsets are defined by the degree of skin involvement, so the classification does not predict systemic organ disease. The systemic sclerosis overlap syndrome is characterized by features of one of the scleroderma subsets with those of another autoimmune disease.
Patients of African descent tend to have an earlier onset (35-44 years compared with 45-55 years for all others), a more severe course, and increased mortality. This may be due to their being more likely to have diffuse, rather than limited, cutaneous systemic scleroderma. In addition, lung function is often worse. There is a greater prevalence of anti-topoisomerase I antibodies, anti-RNP, and anti-Ro antibodies in these patients, although the frequency of anticentromere antibodies is less compared with individuals of Northern European descent.
There are reports in the literature of drug-induced scleroderma. The majority of reports point to a scleroderma-like disease rather than true systemic scleroderma. See drug-induced sclerodermoid reactions for further details.
M34.9 – Systemic sclerosis, unspecified
89155008 – Scleroderma
- CREST syndrome
- Generalized morphea – Asymmetric induration, no Raynaud phenomenon, no systemic involvement.
- Scleredema – ANA negative, no Raynaud phenomenon, no systemic involvement.
- Scleromyxedema – ANA and anticentromere negative, no Raynaud phenomenon, no sclerodactyly.
- Generalized myxedema
- Chronic graft-versus-host disease – ANA negative, vascular abnormalities such as Raynaud phenomenon absent.
- Eosinophilic fasciitis – ANA negative, no Raynaud phenomenon, no facial involvement.
- Nephrogenic systemic fibrosis – Assess for recent history of radiologic imaging with gadolinium-based intravenous contrast in patients with renal insufficiency or renal transplant patient; ANA negative, no sclerodactyly, no Raynaud phenomenon.
- Stiff-skin syndrome – Characteristic sparing of the hands and feet, develops during early childhood, systemic involvement rare.
- Porphyria cutanea tarda
- Polyvinyl chloride exposure – ANA negative, cutaneous changes reverse with cessation of exposure.
- Carcinoid syndrome
- Cutaneous T-cell lymphoma
- Bleomycin toxicity
- Radiation effects
- Onchocerciasis can produce similar "salt-and-pepper" skin changes if a patient is from an endemic area.