IgE-Dependent Allergy in Patients with Celiac Disease: A Systematic Review

Abstract

In order to answer the question if an IgE-mediated allergy (A-IgE) may occur in subjects with celiac disease (CD), a systematic review was performed of available publications collected in the United States National Institute for Biotechnology Information/National Institutes of Health/National Library of Medicine/PubMed database up to 28 December 2022, with the use of the following keywords “allergy&celiac/coeliac”, “sensitization&celiac/coeliac”, and “anaphylaxis&celiac/coeliac” compared in the form of a conjunction. In total, the search returned 2013 publications from these keywords in any section of the article. As numerous review articles included the above-mentioned entries in the abstract, we decided to focus on the publications with the entries only in the title (n = 63). After rejecting studies unrelated to the topic, narrative reviews, book chapters, conference abstracts, symposium reports, letters to the editor, or non-English articles, 18 publications (6 observational original studies and 12 case reports describing a total of 15 cases of A-IgE developed after a diagnosis of CD) were included to this review. Our study is the first systematic review on allergy occurrence in CD patients. The analysis indicated that the possibility of a coexistence of A-IgE with any food and inhalant allergens in subjects diagnosed with CD should be considered. A sensitization to wheat was the most frequently described in subjects with CD. The clinical manifestation of A-IgE in CD was similar to that in subjects without CD; e.g., with possible atopic dermatitis, vomiting, urticaria, angioedema, or anaphylactic shock. Screening for allergies in subjects with CD should be considered, especially in those cases where symptoms persist after introducing a gluten-free diet. The elimination of wheat from the diet of patients with CD may lead to a loss of immune tolerance and to the development of sensitization, which may even manifest as anaphylaxis. In conclusion, although there are few studies assessing the occurrence of A-IgE in subjects with CD, they show the possibility of a coexistence of both diseases and the high clinical significance of this phenomenon, which indicates the need for further studies.

Genetic Associations Between Celiac Disease and Type 2 Inflammatory Diseases: A Mendelian Randomization Analysis

“…Our study, utilizing TSMR, offers new insights into the genetic causality between celiac disease and type 2 inflammatory diseases, moving beyond the observational correlations highlighted in prior research (5,11,12,(18)(19)(20)(21)24). Specifically, our findings reinforce the epidemiological evidence for shared genetic pathways in the inflammatory processes of celiac disease and type 2 inflammatory diseases (2,9,12).…”

“…Similarly, Majasiak et al’s systematic review, the first of its kind, underscored the possibility of concurrent allergic IgE-mediated allergy (A-IgE) and CD. This review highlighted cases where CD patients exhibited A-IgE to allergens, particularly wheat, leading to symptoms like atopic dermatitis and anaphylactic shock, even after adopting a gluten-free diet (19). These epidemiological insights, mainly the association of celiac disease with autoimmune disorders and allergies (20,21), reinforce the significance of our genetic analysis, suggesting that the observed genetic links may reflect a broader, clinically relevant interaction between CD and type 2 inflammatory diseases.…”

Sensitization to Food and Aero-Allergens in Children with Coeliac Disease Assessed with the Use of a Multiplex Molecular Diagnostic Technique

“…The extra-gastrointestinal symptoms may include chronic fatigue, headaches, anemia, and elevated liver enzyme levels. Although CD has long been known to co-occur with autoimmune conditions (such as type 1 diabetes mellitus, autoimmune thyroid, or liver diseases) or genetic syndromes (such as Down syndrome, Turner syndrome, and Williams syndrome) [2], there have been few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies [3]. In CD, the sole factor that induces autoimmunity are immunoreactive gluten peptides, whereas in allergies, the causative factors may be either inhalant or food allergens and other (whose route of exposure is other than via inhalation or ingestion, for instance, via insect stings or via direct dermal contact).…”

“…Despite the seemingly mutually exclusive pathogeneses of CD and IgE-mediated allergy, there have been studies indicating the co-existence of both conditions. A systematic review of studies by our research group [3] revealed a handful of original articles [8][9][10][11] in which authors reported that patients with CD may develop an allergy that manifests in a similar way to that in non-CD subjects, i.e., with atopic dermatitis, vomiting, urticaria, angioedema, anaphylactic shock, etc. In those studies, patients with CD were most often allergic to wheat, which may be due to the fact that this allergen was the one most frequently studied.…”

Immunoglobulin E-Mediated Food Sensitization in a Moroccan Pediatric Population with Celiac Disease

“…However, the gluten-free diet (GFD) may not always be effective [7], classically either due to insufficient adherence to the diet [8] or to crosscontamination of naturally gluten-free foods and products labeled gluten-free [6]. Interestingly, some authors have suggested that the persistence of gastrointestinal symptoms may be due to the coexistence of other disorders, which must therefore be considered [8][9][10][11]. Furthermore, it has been hypothesized that abnormal intestinal permeability in patients with CD may enhance the passage of antigenic food proteins through the intestinal wall, thus predisposing the mucosal immune system to allergic reactions [8].…”