Scleroderma is a complex autoimmune disease of unclear etiology [1]. It consists of an autoimmune-driven chronic inflammatory response that leads to collagen deposition and tissue fibrosis. Environmental factors such as silica, solvents, and other chemicals have been implicated in the pathogenesis but it is likely a genetic predisposition is also present. For example, multiple abnormalities of specific human leukocyte antigen loci have been associated with scleroderma. Although abnormalities in genes that regulate fibrosis have been found in animal models of scleroderma, these have not been consistently found in human studies. More convincing evidence exists for abnormalities in type 1 interferon and genes that are involved in antigen presentation to T and B cells in patients with the disease. STAT4, which plays a major role in an inflammatory model of fibrosis, may also be abnormally expressed. This pathway in coordination with other areas of inflammatory dysregulation leads to fibrosis of skin, tendons, heart, and organs with smooth muscle such as blood vessels, lungs, and gut. It is particularly the hyperreactivity of vasculature with subsequent ischemia and oxidative stress that leads to end-organ injury.

Scleroderma is more common in women than men and more prominent in middle age. Scleroderma may be classified into disorders of limited skin involvement (lSSC), skin and esophageal involvement (calcinosis, Raynaud’s, esophagus, skin, telangiectasias), and diffuse involvement of skin and internal organs (dSSc). The diagnosis is made by the finding of compatible clinical findings in association with Raynaud’s phenomenon and positive antinuclear antibody, Anti-Scl 70 (antitopoisomerase-1), and anti-centromere antibodies in up to 95% of patients. As the distal two-thirds of the esophagus are composed of smooth muscle (as is the remainder of the luminal gastrointestinal tract), esophageal involvement is common.