Scleroderma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]


Scleroderma is an autoimmune connective tissue disease. The hallmark of the underlying pathophysiology is production of autoantibodies against various cellular antigens, small vessel vasculopathy, fibrosis of skin and internal organs, and excess collagen deposition in the skin and internal organs. Circulating autoantibodies found in patients with scleroderma are anti-topoisomerase I (Scl-70) antibody, anti-centromere antibody, anti-RNA polymerase III antibody, anti-nucleolar antibody. Growth factors and cytokines play an important role in the underlying pathogenesis of scleroderma. Increased fibroblast activity leads to the excessive collagen deposition in scleroderma. Although the hallmark of this disease is skin fibrosis, internal organ involvement is a fatal complication and includes, esophageal dysmotility, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, myocardial fibrosis, pericardial fibrosis and pericardial effusion. Although scleroderma occurs in a sporadic pattern in the general population, variations in the human leukocyte antigen (HLA) genes can predispose an individual to developing scleroderma. On gross pathology, sclerodactyly, skin fibrosis, edema and calcinosis are characteristic findings of scleroderma. On microscopic histopathological analysis, characteristic findings of scleroderma include microvascular damage, perivascular infiltrates of immune cells, loss of microvasculature, perivascular edema, fibrosis, densely packed collagen in the lower dermis and upper subcutaneous layer, atrophy, and loss of cells in the later stages of the disease.




Genetics associated with the development of scleroderma include:[29]

Associated Conditions

Conditions that are associated with scleroderma include:[2]

Gross Pathology

Microscopic Pathology


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