Outcomes of Barrett's oesophagus related to systemic sclerosis: a 3-year EULAR Scleroderma Trials and Research prospective follow-up study.

OBJECTIVE: Barrett's oesophagus (BE) is the major risk factor for oesophageal adenocarcinoma (EAC). SSc is associated with an increased risk of BE related to chronic reflux. The aim of this study is to determine the outcomes of BE and estimate the EAC risk in SSc patients over a 3-year prospective study. METHODS: SSc patients were recruited through EUSTAR network centres. Inclusion criterion was a recent histological finding of BE. The patients were then prospectively followed and, as recommended, a second oesophageal endoscopy was performed according to the presence of BE-related dysplasia at baseline. RESULTS: A total of 50 SSc patients with BE (40 without and 10 with dysplasia) were included and 46 completed the follow-up (138 patient-years). During the 3-year follow-up, 4 of the 46 BE patients (3% per year) were diagnosed with high-grade dysplasia/EAC, of which one developed cardial EAC. EAC incidence in the BE subgroup with dysplasia increased to 4% per year compared with the absence of EAC cases in the BE subgroup without dysplasia at baseline. CONCLUSION: Our results, in accordance with previous published data suggesting an increased risk of EAC or cardial adenocarcinoma in SSc, highlight the need for accurate follow-up of BE SSc patients at risk of developing adenocarcinoma.

Interleukin-1 gene complex polymorphisms in systemic sclerosis patients with severe restrictive lung physiology.

Increased concentrations of interleukin-1 (IL-1) were observed in bronchoalveolar lavage fluids from patients with systemic sclerosis (SSc), and their levels were correlated with the patients' forced vital capacity (FVC). Because IL-1 production is regulated at the genetic level, we hypothesized that IL-1 gene complex single nucleotide polymorphisms (SNPs) might be relevant to the progression of ventilatory restriction in SSc. Two-hundred four Italian SSc patients were genotyped for the following IL-1 gene complex SNPs: IL-1alpha C-889T, IL-1beta C+3962T, IL-1beta C-511T, IL-1R Cpst1970T, and IL-1Ra Cmspal11100T, as well as for the following SNPs of cytokines with regulatory functions on IL-1 production: IFNgamma AUTR5644T, TNFalpha A-308G, and IL-10 A-1082G. The SNPs were inserted in a Cox regression model with disease subset, gender, autoantibodies, age at onset of disease, and prior use of immunosoppresants as covariates and the presence of FVC<55% of predicted values as outcome measure; p values were corrected for the number of pairwise comparisons. Twenty-five patients (12.3%) developed a severe ventilatory restriction after 6.8+/-6.6 years (mean+/-standard deviation) from diagnosis. In our model, the relative risk to develop a severe ventilatory restriction was increased by the antitopoisomerase I antibody (p=0.01; HR=14.67, CI95=1.87-114.92), the dcSSc subset (p=0.007; HR=3.14, CI95=1.36-7.21) and the IL-1beta C+3962T SNP (p=0.003 TT vs CC; HR=6.61, CI95=2.28-19.15). The IL-1beta C+3962T SNP is associated with the presence of severe restrictive lung physiology in Italian SSc patients.