Uveitis as a manifestation of celiac disease: a populationbased study

Introduction: The prevalence of celiac disease (CD) in the United States population has been estimated to be 0.71%, or 1 in 141, with the prevalence in first- and second-degree relatives of those affected being 4.55% and 2.59% respectively. Due to the multitude of ways in which this disease may initially present, it is important to screen for CD to avoid the potential consequences of inadequately managed disease. Many ophthalmic conditions have also been implicated as extraintestinal manifestations of CD, including uveitis. Despite several studies and case reports suggesting a positive correlation between CD and uveitis, there has yet to be a nationwide study in the United States quantifying this relationship. Therefore, the aim of this study is to conduct a large-scale multi-center population-based study to assess whether there is a statistically significant increased risk of uveitis in individuals with celiac disease. Methods: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States consisting of data accumulated from 1999 to September 2022 was utilized to construct this study. We excluded patients with a history of autoimmune diseases, cataract surgery, or any type of eye infection. We included a subgroup of patients with a diagnosis of “uveitis” for further analysis. The risk of developing uveitis was calculated using a univariate logistic regression. A multivariate analysis was also done to account for confounding variables including African American ethnicity, male gender, sexually transmitted diseases, and celiac disease. Results: 70,632,440 patients were screened and a cohort of 46,895,750 individuals was selected for the final analysis after accounting for inclusion and exclusion criteria were met. The incidence of uveitis in patients with celiac disease in the past 3 years was 280 per 100,000 people. The prevalence of uveitis in the US population from 1999 to September 2022 was 150 per 100,000 people (0.15%). In order to adjust for confounding variables, a multivariate regression analysis was performed and showed an increased risk of being African-American (OR: 3.20%; 95% CI: 3.14-3.26) and male (OR: 1.13%; 95% CI: 1.12-1.16); and having a diagnosis of celiac disease (OR: 3.80%; 95% CI: 3.35-4.28) and sexually transmitted diseases (OR: 4.12%; 95% CI: 3.96-4.29) in patients with uveitis. Discussion: Recent population-based studies demonstrated that the prevalence of CD in the United States is much greater than previously thought, such that a trend of underdiagnoses is suspected to have occurred for several years. Many newly diagnosed uveitis cases, 48%, have been classified as idiopathic uveitis even after a complete workup was done. Several studies have been published in which a correlation between uveitis and CD is reported. The findings of this study further emphasize the importance of a thorough workup to evaluate for an underlying inflammatory process prior to diagnosing uveitis as idiopathic. Conclusion: In conclusion, we established that patients with celiac disease are at increased risk of developing uveitis after excluding and controlling for any confounding variables. In further studies, it could be interesting to investigate the impact of gluten-free diet in patients with celiac disease on the risk of developing uveitis.