June 18, 2021
Systemic sclerosis (SSc), or scleroderma, is a chronic autoimmune connective tissue disease in which gastrointestinal involvement is common. The reported prevalence of SSc is four times greater in women than in men, and up to 98% of patients with SSc report at least one symptom affecting the upper or lower gastrointestinal tract.
Esophageal motor dysfunction characterized by a hypotensive lower esophageal sphincter and absent peristalsis, often called scleroderma esophagus, is a common gastrointestinal manifestation of SSc. Patients with this condition typically have gastroesophageal reflux due to impaired clearance in the lower third of the esophagus and reduced lower esophageal sphincter basal pressure. This condition can lead to reduced quality of life and increased morbidity and mortality.
Some patients with SSc and chronic GERD develop Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia. BE, which can progress to dysplasia, is a known risk factor for esophageal adenocarcinoma.
A handful of older, smaller studies examining BE in women with SSc have reported a wide range of prevalences, from 2% to 37%. To address this issue, Mayo Clinic researchers conducted a study in a large cohort of women with SSc. The results of this study were published in The American Journal of Gastroenterology in 2021.
The aim of the Mayo Clinic study was threefold:
- To assess the prevalence of BE and determine the association between BE in this population with findings of scleroderma esophagus (absent contractility with hypotensive lower esophageal sphincter) on high-resolution manometry (HRM)
- To examine the features of BE (prevalence and incidence of dysplasia) found in women with SSc and compare them to those found in women with BE without SSc
- To compare prevalence of BE in women with SSc with the prevalence of BE in men with SSc
Mayo Clinic researchers used a prospectively maintained and updated database that included patients referred with BE, including those with and without dysplasia. The researchers reviewed the demographic- and endoscopic-related Barrett's characteristics in women, including the presence of dysplasia. Information gathered included the age of diagnosis of BE, dysplasia, number of endoscopies, follow-up (in months), age at first diagnosis of dysplasia, time from first diagnosis of BE to dysplasia, follow-up after dysplasia, and the rate of progression or regression with or without endoscopic treatment.
According to Diana L. Snyder, M.D., lead author of the article published in The American Journal of Gastroenterology, this is the largest study to date focusing on the prevalence of BE in patients with SSc. Dr. Snyder is a gastroenterology fellow at Mayo Clinic's campus in Arizona.
The Mayo Clinic study included 235 women with SSc who completed esophagogastroduodenoscopy (EGD) between 2002 and 2020, and 172 who underwent HRM. The SSc diagnosis was confirmed by an expert rheumatologist, and the BE diagnosis was confirmed by an expert gastrointestinal pathologist.
- Within the group of 235 women with SSc who underwent EGD, 30 had histologically proven BE, representing a prevalence of 12.8%.
- Among the 30 women with histologically proven BE, 13 (43.3%) had dysplasia (four with indefinite, seven with low grade and two with adenocarcinoma).
- The incidence of any dysplasia was 5.3% a year (0.9% a year for adenocarcinoma).
- Within the group of 40 men with SSc who underwent EGD, three had histologically proven BE (two nondysplastic and one high-grade dysplasia), representing a prevalence of 7.5%.
- There was no statistical difference in prevalence rates of BE between women and men with SSc.
- HRM testing revealed that the lower esophageal sphincter mean basal pressure was significantly lower in the patients with SSc and BE than in patients with SSc without BE (10.65 ± 8.50 mm Hg and 18.62 ± 13.43 mm Hg, respectively).
Dr. Snyder notes that the study's large sample size allowed the researchers to better estimate the true prevalence of BE in patients with scleroderma.
"Overall, our results demonstrate that women with SSc and BE are significantly more likely to have absent contractility with hypotensive lower esophageal sphincter findings on HRM," explains Dr. Snyder. "The 12.8% prevalence of Barrett's esophagus found in our study population is much higher than what occurs in the general population."
Beyond providing new data related to BE prevalence, the study looked at the progression from BE to dysplasia and cancer in this patient population. "We also found that patients with scleroderma and Barrett's esophagus are more likely to progress to dysplasia and cancer when compared to results found in previously published literature," says Dr. Snyder.
Dr. Snyder acknowledges that further study is needed to calculate the incidence rates of dysplasia and cancer in a larger sample of patients. But she believes that these findings should encourage a reexamination of established screening guidelines for BE.
"The high prevalence of Barrett's esophagus suggests that women with SSc should be included in the screening recommendations for BE," says Dr. Snyder. "We hope this study will change clinical practice by encouraging those who care for patients with scleroderma, particularly primary care providers, rheumatologists and gastroenterologists, to refer these patients for screening upper endoscopy. We have established surveillance programs for nondysplastic Barrett's esophagus and highly effective ablative modalities for eradication of dysplastic Barrett's that can help prevent these patients from developing cancer. The key is for our colleagues to initiate the screening referral."
For more information
Snyder DL, et al. Prevalence of Barrett's esophagus in female patients with scleroderma. The American Journal of Gastroenterology. 2021;116:517.