Research publication trends regarding the extraintestinal manifestations of celiac disease

Abstract

Introduction: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten that has a poor diagnosis rate and a range of extraintestinal manifestations (EIMs), which vary in prevalence. Increasing the rate of diagnosis of, and possibly developing therapies for, CD relies on our understanding of these EIMs. We therefore tracked trends in research on EIMs of CD from 1960 to 2015, the latest complete year at the time the data were collected. Methods: We selected groups of search terms relating to distinct categories of EIMs of CD, and queried MEDLINE for the number of articles published in each year from 1960 to 2015 that mentioned both CD and any of the terms in each group. Data were normalized to the total number of publications in each year that mentioned either CD or any of those terms. For comparison, we also analyzed inflammatory bowel disease (IBD) for research trends. The resulting time series data were plotted as a five-point moving average and analyzed graphically. Results: Over the analysis time window, the overall normalized publication volume for EIMs was approximately constant for CD, but markedly increased for IBD. Bone manifestations of CD and IBD had simultaneous, comparable peaks in the decade from 2000 to 2010 and decreased since; however, CD had an earlier peak of twice the magnitude in the 1970s. Publication volume regarding central nervous system manifestations varied greatly with multiple peaks for CD, while a peak in IBD occurred in the year 1974, and the trend for IBD has been increasing since the early 1980s. Publication on ataxia has remained low in IBD with marginally increased interest in the past three decades, compared with a rapid increase in publication in the late 1990s for CD. Publication in peripheral nervous system manifestations exhibited bimodal peaks for CD (ca. 1970 and 2008) and a positive trend for IBD. Discussion: The results indicate that there is fluctuating research interest in EIMs of both CD and IBD, with more interest in EIMs of IBD as compared to CD. Publication of both bone and peripheral nervous system manifestations of CD is decreasing, and publication of central nervous system manifestations of CD has fluctuated over time. These patterns suggest that there may be decelerated progress in our understanding of these aspects of CD, and a shift in interest to other EIMs. Notably, the decreased research interest in neurological manifestations is concerning, with respect to the development of therapies for CD-associated neuropathy and gluten ataxia. Redirecting efforts and redistributing resources in CD research according to these results may enhance the development of therapies for these CD related EIMs, and also improve diagnostic methods. Keywords: Celiac disease, Extraintestinal, IBD, Manifestations, MEDLINE