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Future Trends in the Diagnosis and Management of Celiac Disease
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Future Trends in the Diagnosis and Management of Celiac Disease

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (24 July 2025) | Viewed by 6732

Special Issue Editors

Prof. Dr. Carolina Ciacci

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry, Medical School of Salerno, 84131 Salerno, Italy
Interests: celiac disease; non-celiac gluten/wheat sensitivity; inflammatory bowel disease; irritable bowel syndrome; nutrition
Dr. Antonella Santonicola

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, 84081 Salerno, Italy
Interests: celiac disease; inflammatory bowel disease; irritable bowel syndrome; eosinophilic gastrointestinal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Celiac disease (CeD) is an autoimmune disorder induced by dietary gluten that occurs in genetically predisposed individuals, with a ~1% prevalence in the general population. The clinical picture for the wide spectrum of possible symptoms has changed over the past few decades, from a malabsorptive syndrome of childhood to a disease which can be diagnosed at any age, with chameleon-like manifestations from one person to another.

This Special Issue’s focus is on the future trends in CeD, within which several topics can be addressed, including the following: What are the current clinical features of more recent celiac disease diagnoses? What are the unsolved health issues left after an appropriate gluten-free diet? What about new biomarkers or new approaches to the use of old ones? Also, CeD diagnosis in adults relies on detecting serum gluten-related antibodies in conjunction with intestinal biopsies. However, recent studies have proposed a non-biopsy serological diagnosis of CeD based on detecting high-title tTG IgA. How will this information change the guidelines for adult diagnosis ? At present, the lifelong exclusion of gluten-containing cereals from one’s diet represents the only available therapeutic strategy for celiac disease. However, new therapeutic options, substituting or accompanying a gluten-free diet, are emerging.

This Special Issue aims to provide a comprehensive overview of the recent advances in the diagnosis and management of CeD. We would therefore like to invite all colleagues in this field to contribute reviews or original data to this new SI.

Prof. Dr. Carolina Ciacci
Dr. Antonella Santonicola
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • celiac disease
  • gluten
  • autoimmune disease
  • extraintestinal manifestations
  • serologic diagnosis
  • gluten-free diet

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Published Papers (7 papers)

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Research

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14 pages, 415 KiB  
Article
Cellular Recovery and Body Composition Changes in Pediatric Celiac Disease After the Start of a Gluten-Free Diet: A Prospective Cohort Study
by Teresa Nestares, María Jiménez-Muñoz, Encarnación Torcuato-Rubio, Laura Tamayo Pérez, Marta de la Flor Alemany, Marta Herrador-López, Víctor Navas-López and Rafael Martín-Masot
J. Clin. Med. 2025, 14(14), 5061; https://doi.org/10.3390/jcm14145061 - 17 Jul 2025
Viewed by 385
Abstract
Background/Objectives: Celiac disease (CD) alters nutrient absorption and body composition, especially during childhood. Although adherence to a gluten-free diet (GFD) promotes mucosal recovery, its impact on cellular functionality and metabolic balance remains underexplored. This study aims to evaluate the utility of bioelectrical impedance [...] Read more.
Background/Objectives: Celiac disease (CD) alters nutrient absorption and body composition, especially during childhood. Although adherence to a gluten-free diet (GFD) promotes mucosal recovery, its impact on cellular functionality and metabolic balance remains underexplored. This study aims to evaluate the utility of bioelectrical impedance vector analysis (BIVA) in assessing nutritional status, inflammatory improvement, and body composition changes in pediatric patients with CD following a GFD. Methods: Seventy-nine children aged 5–14 years were studied. Three groups were analyzed: (1) 25 children with newly diagnosed CD, evaluated at diagnosis and after 12 months of GFD (prospective cohort); (2) 25 CD patients on a GFD for over 24 months (cross-sectional); and (3) 29 healthy controls. Body composition (fat mass (FM), fat-free mass (FFM), body cell mass (BCM), phase angle (PhA), and Na+/K+ ratio) was measured. GFD adherence was assessed and a dietary assessment was also performed. Results: After 12 months on a GFD, newly diagnosed CD patients showed significant increases in FM (from 8.2 to 10.1 kg, p = 0.001), FFM (p = 0.001), and BCM (p = 0.0001), along with a significant decrease in the Na+/K+ ratio (p = 0.015). Compared to healthy controls, CD children on GFD for more than 24 months had higher FM (12.2 vs. 8.8 kg, p = 0.013) and lower Na+/K+ ratios (p = 0.006). PhA increased slightly over time but did not reach statistical significance. Conclusions: Our study suggests that the adherence to a GFD leads to improved body composition and cellular homeostasis in children with CD, as reflected by increases in BCM and reductions in Na+/K+ ratio, making it a promising biomarker for monitoring inflammation and cellular recovery. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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20 pages, 890 KiB  
Article
Effects of a Gluten-Free Diet on Brain Bioelectrical Activity and Neurological Symptoms in Children with Celiac Disease: A Study Using EEG Assessment
by Milena Zochowska-Sobaniec, Elzbieta Jarocka-Cyrta, Joanna Maria Lotowska and Piotr Sobaniec
J. Clin. Med. 2025, 14(3), 725; https://doi.org/10.3390/jcm14030725 - 23 Jan 2025
Viewed by 1171
Abstract
Celiac disease (CeD), also known as gluten enteropathy, is an immune-mediated inflammatory enteropathy triggered by intolerance to gluten. It presents with a spectrum of symptoms, including both gastrointestinal and extraintestinal manifestations, as well as neurological symptoms. A review of the literature indicates that [...] Read more.
Celiac disease (CeD), also known as gluten enteropathy, is an immune-mediated inflammatory enteropathy triggered by intolerance to gluten. It presents with a spectrum of symptoms, including both gastrointestinal and extraintestinal manifestations, as well as neurological symptoms. A review of the literature indicates that 10–22% of patients with CeD present with neurological symptoms. The objective of this study is to assess the influence of a gluten-free diet (GFD) on brain bioelectrical activity and neurological symptoms in children with CeD. Methods: The study was conducted using a multidisciplinary approach, encompassing a comprehensive array of clinical data gathered alongside laboratory test results, questionnaires, and electroencephalogram (EEG) assessments. The study population included 85 children: 18 newly diagnosed cases of CeD patients (NDC), subsequently reassessed after 6 months on a GFD as a celiac disease on diet (CDD); 27 CeD patients on a GFD for over 12 months (CDD2); and 40 healthy individuals in the comparison group (CG). Results: It was observed that over half of the NDC group exhibited neurological symptoms, particularly headaches. Following a six-month period on a GFD, there was a notable reduction in symptom severity. In comparison to the CG, the NDC patient group exhibited a higher prevalence of abnormalities in EEG recordings (p = 0.032), including focal sharp waves or slow waves. Conclusions: The results demonstrate that a GFD has a positive impact on the neurological condition of children with CeD. The clinical improvements correspond with EEG normalization, which supports the hypothesis that dietary intervention plays a role in mitigating CeD-associated neurological dysfunction. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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Review

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27 pages, 2740 KiB  
Review
Outcomes in Adults with Celiac Disease Following a Gluten-Free Diet
by Daniel Vasile Balaban, Iulia Enache, Marina Balaban, Răzvan Andrei David, Andreea-Diana Vasile, Alina Popp and Mariana Jinga
J. Clin. Med. 2025, 14(14), 5144; https://doi.org/10.3390/jcm14145144 - 20 Jul 2025
Viewed by 324
Abstract
Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to [...] Read more.
Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to synthesize current evidence regarding histological outcomes after GFD treatment in adult CD, focusing on mucosal healing rates, assessment methods, and remission criteria. Methods: We conducted a literature search with extraction and analysis of published cohort studies that included adult patients with CD on GFD with follow-up biopsy data. Extracted parameters included demographic details, baseline histology, GFD duration and adherence, serologic status, and histologic recovery rates with corresponding remission criteria. Results: Data from 46 studies comprising 15,530 patients were analyzed. The overall mean age was 41 years, and 73.3% were female. Mean histologic remission across cohorts was 58.8%, with considerable interstudy variation. Remission criteria also varied widely, ranging from strict Marsh 0 control histology to more inclusive definitions that considered Marsh 1 or even non-atrophic mucosa (Marsh < 3) as indicative of recovery, while some studies relied on quantitative villous height-to-crypt depth ratio thresholds, substantially influencing reported remission rates. Longer GFD duration and rigorous diet adherence assessment using validated questionnaires and accurate laboratory tools were associated with higher remission rates. Conclusions: Histologic remission in GFD-treated adult patients with CD is highly variable and strongly influenced by remission definitions and adherence assessment methods. Standardized reporting using validated metrics for histologic outcome and dietary compliance is essential for harmonizing follow-up strategies in adult CD. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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11 pages, 879 KiB  
Review
The Implications of Type 1 Diabetes Mellitus Associated with Coeliac Disease
by Geoffrey Holmes and Peter Gillett
J. Clin. Med. 2025, 14(14), 5129; https://doi.org/10.3390/jcm14145129 - 18 Jul 2025
Viewed by 375
Abstract
T1D and CD commonly occur together. This association has received increasing attention from researchers and is considered in detail in this review. Since CD is over-represented in T1D, it may cause ill health with attendant complications, but because there is an effective dietary [...] Read more.
T1D and CD commonly occur together. This association has received increasing attention from researchers and is considered in detail in this review. Since CD is over-represented in T1D, it may cause ill health with attendant complications, but because there is an effective dietary treatment, screening has been recommended in children and adults. However, there are many unknowns regarding this association, and understanding the why, when, and how with regard to screening and managing those with dual diagnoses requires thorough consideration when introducing the concept of screening to patients. It is important that patients and, where appropriate, carers are put at the heart of the decision-making process with careful discussion of the issues involved before undertaking screening that might uncover a second life-changing diagnosis, for which, without preparatory preparation and support, individuals may be ill-prepared, causing mental health issues. For some patients, an initial policy of monitoring rather than moving to immediate small bowel biopsy and exposure to a gluten-free diet (GFD) will be appropriate. The correct management of patients will ultimately improve their quality of life medically and socially. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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11 pages, 245 KiB  
Review
Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview
by Herbert Wieser, Carolina Ciacci, Carlo Soldaini, Carolina Gizzi and Antonella Santonicola
J. Clin. Med. 2024, 13(15), 4579; https://doi.org/10.3390/jcm13154579 - 5 Aug 2024
Cited by 5 | Viewed by 2744
Abstract
Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a [...] Read more.
Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)

Other

Jump to: Research, Review

22 pages, 52413 KiB  
Systematic Review
Micronutrient Deficiencies Associated with a Gluten-Free Diet in Patients with Celiac Disease and Non-Celiac Gluten or Wheat Sensitivity: A Systematic Review and Meta-Analysis
by Lindsey A. Russell, Paige Alliston, David Armstrong, Elena F. Verdu, Paul Moayyedi and Maria Ines Pinto-Sanchez
J. Clin. Med. 2025, 14(14), 4848; https://doi.org/10.3390/jcm14144848 - 8 Jul 2025
Viewed by 414
Abstract
Background: A gluten-free diet (GFD) has been shown to be nutritionally inadequate for those with wheat-related disorders. However, the differences in findings and the absence of quantitative analysis limits the interpretation of previous reviews. Objectives: We conducted a systematic review and meta-analysis to [...] Read more.
Background: A gluten-free diet (GFD) has been shown to be nutritionally inadequate for those with wheat-related disorders. However, the differences in findings and the absence of quantitative analysis limits the interpretation of previous reviews. Objectives: We conducted a systematic review and meta-analysis to identify the risk of micronutrient deficiencies in patients with celiac disease (CeD) and non-celiac gluten or wheat sensitivity (NCWS). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science (Ovid) databases. The risk of bias was determined using the ROBINS-1, and the quality of evidence was assessed using the GRADE approach. Results We identified 7940 studies; 46 observational studies (11 cohort, 9 cross-sectional, and 26 case–control) were eligible for analysis. CeD patients had an increased risk of vitamin D and E deficiencies compared with the non-CeD controls. CeD on a GFD had a decreased risk of vitamin D, B12, E, calcium, and iron deficiencies compared with untreated CeD. NCWS had an increased risk of vitamin B12, folate, and iron deficiency compared to the controls. The overall quality of evidence was rated very low. Conclusions: The risk of various micronutrient deficiencies is increased in CeD but is decreased for some after a GFD. Adequately powered studies with a rigorous methodology are needed to inform the risk of nutrient deficiencies in patients with CeD and NCWS. Protocol registration: Prospero-CRD42022313508. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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17 pages, 1536 KiB  
Systematic Review
Prevalence of Joint Complaints in Patients with Celiac Disease: A Systematic Review and Meta-Analysis
by Dimitri Poddighe, Gulsamal Zhubanova, Dinara Galiyeva, Kamilla Mussina and Anders Forss
J. Clin. Med. 2025, 14(11), 3740; https://doi.org/10.3390/jcm14113740 - 27 May 2025
Viewed by 519
Abstract
Background: Current evidence suggests that joint complaints can represent an extra-intestinal manifestation in patients with Celiac Disease (CD) without any rheumatic comorbidity. However, the prevalence of joint complaints in the context of both CD and rheumatic disease is not known. The aim [...] Read more.
Background: Current evidence suggests that joint complaints can represent an extra-intestinal manifestation in patients with Celiac Disease (CD) without any rheumatic comorbidity. However, the prevalence of joint complaints in the context of both CD and rheumatic disease is not known. The aim of this study was to estimate the prevalence of joint complaints in patients with CD. Methods: We searched Medline, Embase, Cochrane, and Web of Science databases for studies reporting joint complaints in patients with CD between 1 January 1990 and 26 November 2024. Search results were screened by two independent reviewers. The pooled prevalence of joint complaints was estimated in meta-analysis using a random effects model. We conducted stratified analyses by region, age (adults vs. children), and study sample size. The Joanna Briggs Institute Critical Appraisal Tool was used to evaluate the quality of included studies, and publication bias was assessed using a funnel plot and Egger’s test. The study protocol was pre-registered in the PROSPERO database and the results were reported according to the PRISMA guidelines. Results: A total of 7414 publications were rendered in the search. Of these, 226 were reviewed in full text and 27 were included in the meta-analysis. Among 6901 patients with CD without any concomitant rheumatic diagnosis, 530 had joint complaints, yielding a weighted pooled prevalence of 10.7% (95%CI: 6.9–15.1). In meta-regression analysis, no association between the prevalence of joint complaints and patients’ clinical characteristics or demographics was found. Conclusions: This meta-analysis indicates that joint complaints in patients with CD without any specific rheumatic comorbidity are not uncommon. Increased awareness of joint complaints in CD is important to improve the diagnosis and clinical care of these patients. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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