Background/Purpose: Systemic sclerosis (SSc) associated gastroesophageal reflux disease (GERD) can cause symptoms of dysphagia and heartburn, and is associated with esophagitis, stricture, Barrett’s esophagus, and esophageal adenocarcinoma. A genealogic resource, the Utah Population Database (UPDB) has successfully identified systemic sclerosis (SSc) pedigrees and comparable hereditable risk for this disease. We hypothesized that these pedigrees could be used to assess for the hereditability of esophageal disease in order to risk stratify SSc patients with esophageal symptoms and inform their monitoring needs.

Methods: SSc (ICD-9 710.1 and ICD-10 M34.0, M34.1, and M34.9), GERD (ICD-9 530.1 and ICD-10 K21.9), dysphagia (ICD-9 787.20), esophageal stricture (ICD9 530.3 and ICD10 K 22.2), Barrett’s esophagus (ICD-9 530.85 and ICD-10 K22.7), and esophageal adenocarcinoma (ICD-9 150.9 and ICD-10 C15.9) was identified from statewide discharge data, the University of Utah Health Science Center Enterprise Data Warehouse, and death certificates and were linked to the UPDB for analysis. SSc probands that had pedigree information for first, second, and third degree relatives were analyzed for the presence of each of the aforementioned diagnostic codes. Inheritance was evaluated by familial standardized incidence ratio and relative risks (RR) to first, second, third, fourth degree relatives and spouses for cases of SSc. Five matched controls were selected from the statewide UPDB population file without replacement in a Monte Carlo method to simulate random sampling in this low penetrate disease. The controls were matched on gender, birth year, and whether they were born in Utah.

Results: A software kinship analysis tool analyzed 2227 unique SSc patients and 11136 controls. In this study, 15% of the SSc from the Utah population is familial based on calculated population attributable risk. The SSc proband had a significant presence of esophageal symptoms and disease: GERD (RR: 3.28), dysphagia (RR 5.58), esophageal stricture (RR: 5.16), esophagitis (RR: 4.86), and Barrett’s (RR: 4.52 (all p<2e-16) as expected. In a first-degree relative of a SSc proband GERD (RR: 1.14, p=6.85e-05), dysphagia (RR: 1.22 p=0.002), and esophagitis (RR: 1.37, p=2.10e-06) were significantly seen in SSc first degree relatives (parents and children). Esophagitis and dysphagia was significantly seen in first cousins (RR: 1.09, p=0.03) and spouses (RR; 1.37, p=0.02), suggesting that both genetics and similar exposures (ie, diet) may play a role in pathogenesis. Esophageal stricture and Barrett’s esophagus do not appear to be hereditable and were also not seen in spouses. None of the SSc cases had esophageal adenocarcinoma.

Conclusion: The UPDB is a resource that allows for meaningful inheritance analysis. These data suggest that independent of GERD, esophagitis in SSc patients and their relatives may have both a hereditable and environmental etiology. Importantly, there does not seem to be a heritable component to Barrett’s esophagus in this population suggesting that modulation of reflux may play an important role in prevention.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/esophageal-disease-in-systemic-sclerosis-does-heritability-play-a-role/