Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
I Have Just Been Told That I Have Scleroderma and It Can Affect the Esophagus. What Should I Expect?
Review of the Literature
Scleroderma is a complex autoimmune disease of unclear etiology . 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.
How Commonly Does It Involve the Esophagus?
The likelihood of scleroderma affecting the esophagus varies by the type of assessment used to define esophageal involvement. In a recent study combining newly and previously diagnosed patients with scleroderma, esophageal symptoms were present in 39 cases (69.6%), reflux esophagitis in 17 cases (32.7%), manometric abnormalities in 32 cases (68.1%), and abnormal reflux in 33 cases (80.5%) on ambulatory pH monitoring . In another study using high-resolution manometry, esophageal body dysmotility was present in 33 patients (67.3%) while symptoms were present in 87.5% . Interestingly, correlation between the presence of symptoms and manometric abnormalities was poor. On biopsy, atrophy in the circular smooth muscle was found in 93% of cases . Diffuse esophageal skin involvement, presence of Scl70, and absence of ACA are associated with esophageal involvement.
What Are the Symptoms of Scleroderma When It Involves the Esophagus?
Scleroderma specifically affects esophageal function by reducing and often eliminating esophageal peristalsis and by decreasing lower esophageal sphincter pressure. As a result, patients most commonly develop symptoms of heartburn and regurgitation due to an incompetent lower esophageal sphincter and poor esophageal clearance. Dysphagia is due to poor esophageal transit and sometimes peptic strictures developing as a result of acid reflux.
How Is Esophageal Involvement Diagnosed, What Tests Should Be Done?
The tests used to diagnose esophageal involvement are those used to typically evaluate esophageal symptoms in general. In contrast to most patients, however, scleroderma patients commonly undergo a staging esophageal manometry to determine the presence of gut involvement even without esophageal symptoms. Endoscopy is routinely performed to assess for the high prevalence of erosive esophagitis. Barium esophagography is helpful to better assess the degree of esophageal dilation-associated global esophageal hypokinesis as an adjunct to high-resolution esophageal impedance manometry. Ambulatory pH/impedance monitoring is not as often needed in scleroderma patients due to the high prevalence of esophagitis and the common baseline of esophageal involvement compared to patients with suspected idiopathic gastroesophageal reflux .