Background Esophageal dysfunction affects the majority of patients with systemic sclerosis (SSc). Gastroesophageal reflux (GERD)-associated microaspiration may serve as an inciting and/or exacerbating factor in the pathogenesis of interstitial lung disease (ILD) in SSc. Few studies have investigated the relationship between objective measures of esophageal involvement in SSc and the progression of SSc-ILD.

Objectives (1) To investigate whether patient-reported symptoms of GERD predict SSc-ILD severity and progression; (2) To explore whether quantitative radiographic measurements of esophageal parameters predict SSc-ILD severity and progression.

Methods Participants of Scleroderma Lung Study (SLS) II (24 months of mycophenolate versus 12 months cyclophosphamide followed by 12 months of placebo in patients with active SSc-ILD) were included.¹ The UCLA SCTC GIT 2.0 was used to assess the severity of reflux at baseline. Quantitative image analysis was used to calculate the diameter and area of the esophagus in the area of maximum dilation. Univariate and multivariable linear regression analyses were used to evaluate the relationship between baseline reflux scores/esophageal parameters and the severity and progression of SSc-ILD based on the quantitative radiographic extent of ILD (QILD) and fibrosis (QLF) in the lobe of maximum involvement (LM). All multivariable models controlled for treatment arm and baseline ILD severity, as well as proton pump inhibitor (PPI) use.

Results Among the 141 of 142 SLS II participants with patient-reported reflux scores at baseline, the mean score was 0.57, indicating moderate reflux. The mean maximal esophageal diameter and area at baseline were 22 mm and 242 mm², respectively. There were no significant correlations between reflux scores, esophageal diameter, esophageal area and QILD-LM and QLF-LM at baseline. However, in the 96 participants with HRCT scans available at 24 months, increased reflux scores were significantly associated with worsening of QLF-LM and QILD-LM (Figure 1). Even after controlling for disease severity at baseline, treatment arm and PPI use, reflux scores remained significantly associated with change in QLF-LM (P-value 0.05) and QILD-LM (P-value 0.003). Neither the maximum esophageal area, nor the maximum esophageal diameter was associated with the change in QILD-LM or QLF-LM in univariate or multivariate analyses.

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Figure 1.

Increased reflux scores at baseline are associated with increased progression (worsening) of QILD (A) and QLF (B) in the lobe of maximum involvement in patients with SSc-ILD.

Conclusion Increased self-reported reflux was independently associated with worsening radiographic fibrosis and ILD in patients receiving treatment for SSc-ILD. The maximum esophageal diameter and esophageal area did not correlate with reflux scores and did not predict severity or progression of SSc-ILD. These findings illustrate the importance of eliciting a careful patient history of reflux symptoms in patients with ILD and further highlight the need for improved objective measures of esophageal dysfunction in SSc.

References [1]Tashkin et al. Lancet Resp Med 2016.

Disclosure of Interests Elizabeth Volkmann Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Forbius, Horizon, Kadmon, Boehringer Ingelheim, Donald Tashkin: None declared, Mei Leng: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Michael Roth Grant/research support from: Genentech