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Article

Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis

by
Judit Bajor
1,*,
Zsófia Vereczkei
2,3,
Réka Bencs
4,
Enikő Nagy
5,
Míra Zsófia Peresztegi
6,
Ivett Hegedűs
7,
Nelli Farkas
8,
András Tárnok
9,
Nóra Szigeti
4 and
Zsolt Szakács
1
1
First Department of Medicine, Medical School, University of Pécs, Ifjúság Str. 13, H-7624 Pécs, Hungary
2
Institute for Translational Medicine, Medical School, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary
3
Department of Sport Nutrition and Hydration, Institute of Nutritional Science and Dietetics, Faculty of Health Sciences, University of Pécs, Vörösmarty Mihály Str. 4, H-7621 Pécs, Hungary
4
Second Department of Internal Medicine and Nephrological Centre, Medical School, University of Pécs, Pacsirta Str. 1, H-7624 Pécs, Hungary
5
Department of Emergency Medicine, Medical School, University of Pécs, Ifjúság Str. 13, H-7624 Pécs, Hungary
6
Medical School, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary
7
Department of Pathology, Medical School, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary
8
Institute of Bioanalysis, Medical School, University of Pécs, Szigeti Str. 12, H-7624 Pécs, Hungary
9
Department of Paediatrics, Medical School, University of Pécs, József Attila Str. 7, H-7623 Pécs, Hungary
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2025, 15(2), 55; https://doi.org/10.3390/jpm15020055
Submission received: 26 November 2024 / Revised: 20 January 2025 / Accepted: 27 January 2025 / Published: 29 January 2025
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
Browse Figure
Versions Notes

Abstract

:
Background: The clinical presentation of coeliac disease (CD) is various and may influence disease course. We aimed to investigate the associations of clinical presentation with comorbidities and disease complications in a cohort of Hungarian coeliac patients. Methods: In this retrospective study, data of consecutive CD patients were analysed. Clinical presentation (classical vs. non-classical), extraintestinal manifestations and comorbidities (anaemia, metabolic bone disease, dermatitis herpetiformis, IgA deficiency, chromosomal abnormalities, autoimmune diseases and malignancy) were assessed. Student’s t-test (for age at diagnosis) and the Chi-squared test or Fisher’s exact test (for categorical variables) were applied as analyses. Results: A total of 738 patients were included. In classical vs. non-classical comparisons, classical presentation was significantly associated with metabolic bone disease (59 vs. 36%, respectively, p < 0.001), anaemia (47 vs. 38%, respectively, p = 0.027) and malignancy (6 vs. 2%, respectively, p = 0.006); however, autoimmune diseases and dermatitis herpetiformis were more common with non-classical presentation (23 vs. 31%, p = 0.02, and 5 vs. 16%, p = 0.014, respectively). Conclusions: Our findings confirm that clinical presentation is associated with certain comorbidities and complications in CD. More personalised follow-up may be recommended based on clinical presentation.

1. Introduction

Coeliac disease (CD) is one of the most common immune-mediated disorders, which develops as a response to gluten among genetically predisposed individuals. The overall worldwide disease prevalence is currently about 1%, yet it shows an increasing tendency, likely due to improving testing methodology and rising disease awareness among healthcare providers [1]. Historically, CD has been characterised by malabsorption, including diarrhoea, weight loss, failure to thrive and various nutritional deficiencies. However, these cases represent only the ‘tip of the iceberg’ because many patients are diagnosed based on atypical symptoms, extraintestinal manifestations, associated immune-mediated diseases or are detected by serological screening while being asymptomatic. The active case-finding strategy recommended by the guidelines might miss some cases due to the high proportion of subclinical presentation [1,2]. Diagnostics, treatment and follow-up are managed according to well-defined, uniform principles, regardless of whether the initial clinical symptoms were classical, non-classical or asymptomatic [3,4,5]. In addition to maintaining adherence to a gluten-free diet (GFD), the biggest challenge in patient care is currently the management of comorbidities and complications. There is no evidence on to what extent clinical symptoms at the time of the diagnosis determine the further fate of the patient. One might reasonably assume that the more severe, classical symptoms are associated with more severe intestinal histological damage and a higher anti-tissue transglutaminase (tTG) antibody titre, and that these patients are potential candidates for more serious outcomes during the disease course [6,7]. However, total villous atrophy and a high antibody titre may be present in an asymptomatic patient, which questions a direct correlation between clinical presentation and histological severity [8].
The question arises as to whether the assessment of clinical presentation at the time of diagnosis helps to determine which patients should be followed up more closely and which are at a higher risk of developing complications. Concerning this, data are scant and the literature is inconsistent. In a paediatric study, the extent of villous atrophy did not correlate with clinical severity, but long-term complications or comorbidities did so. [9]. The results of a large multi-centre study indicate that being diagnosed at a late age and having a classical clinical presentation phenotype are predictive of the development of severe complications later in life, which emphasises the need for personalised care and follow-up [10].
This study aimed to investigate the associations of clinical presentation with comorbidities and disease complications in a cohort of Hungarian coeliac patients.

2. Materials and Methods

The study is reported in conformity with the STROBE Statement [11]. The study was conducted in accordance with the Declaration of Helsinki and approved by the Regional and Local Research Ethics Committee of University Pécs, Pécs, Hungary (ref.no 6918).

2.1. Study Design and Data Source

The University of Pécs is the regional referral centre for coeliac patients throughout southwest Hungary, Baranya County. In this retrospective cohort study, data collection was performed using the medical record database of the University of Pécs (eMedSolution, T-Systems Hungary Ltd., Budapest, Hungary, Version: 2023/Q1/1 (20230127151442)).

2.2. Data Collections, Study Population and Definition of Study Variables

In our analysis, we searched the electronic database between 1 January 2007 and 31 December 2019. We identified all coeliac patients who attended the clinics in this period using the International Classification of Diseases, 10th Revision coding of CD (ICD-1 K90.0). All patients (without age restriction) registered at any time with a primary or secondary diagnosis of CD were included in this study. Social Security Numbers were used to identify duplicate records. The diagnosis of CD was reassessed by checking the original data on CD-specific serology and intestinal histology according to the valid guidelines in the year of the diagnosis. The incorrect or uncertain cases were excluded. Only the patients with a well-definable clinical phenotype were included in the study. The collected data were filled into the pre-defined data collection table. A total of five investigators were involved in the acquisition of data.
This study population (or a part of it) has been analysed in previous works of our study group, yet with different clinical questions [12,13].
Patients’ data were systematically collected. Information referencing the gender, age at diagnosis, clinical phenotype, diagnostic histology, serology, extraintestinal manifestation (anaemia, metabolic bone disease), coexistent immune-mediated diseases (dermatitis herpetiformis (DH), autoimmune diseases (AD)), chromosomal abnormality and malignancy were obtained manually and stored in a database.
Regarding the clinical presentation at diagnosis, we divided this into classical and non-classical as per the Oslo criteria; the classical presentation was defined based on the presence of signs and symptoms of malabsorption, diarrhoea, weight loss and failure to thrive [14]. Silent cases were included in the non-classical group. Diagnostic histological samples were described at the time of the diagnosis by a gastrointestinal histopathologist using the modified Marsh classification [15]. Commercially available ELISA kits (Orgentec Diagnostika GmbH, Mainz, Germany) for the assay of tTG antibodies were used. A tTG level > 10 U/mL was considered positive. A high tTG level was defined as being greater than 10 times the upper limit of normal (ULN). In seronegative cases, the diagnosis was made based on histology. Haemoglobin levels < 130 g/L and < 120 g/L indicated anaemia in males and females, respectively. Metabolic bone disease (including osteopenia and osteoporosis) was defined by measuring a T-score < −1.0 or < −2.0 standard deviation by dual-energy X-ray absorptiometry (DEXA). IgA deficiency was defined as a condition in which total serum IgA level, measured by nephelometry, was below 0.07 g/L. Concurrent AD, malignancies and DH and chromosomal abnormality (Down’s or Turner syndrome) were assessed as well.

2.3. Statistical Analysis

In descriptive statistics, age at diagnosis was handled as a continuous variable and the mean with standard deviation was calculated. Categorical variables were described with absolute counts and relative frequencies (%). To examine the association between clinical presentation and other variables through comparative analysis, Student’s t-test (for age at diagnosis) and the Chi-squared test or Fisher’s exact test (for categorical variables) were applied. p ˂ 0.05 indicated statistical significance. All calculations were made using IBM-SPSS ver. 28 (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY, USA: IBM Corp).

3. Results

3.1. Patients’ Characteristics

As a result of searching the database, we acquired 8334 cases, from which a balance of 1889 remained after excluding duplicate records. In the reassessment of the search yield, 654 cases of coeliac disease were excluded from the study (usually due to miscoding or misdiagnosis) and further 237 cases could not be evaluated for the study due to uncertain diagnosis. Among 260 patients, the classification of clinical presentation was ambiguous, so they were also excluded from the study. The flowchart of the search and selection is presented in Figure 1.
A total of 738 patients were included in the analysis. Patients’ characteristics are summarised in Table 1. Approximately one-fourth of the patients were males. Out of the 738 patients, 290 (39%) had classical and 448 (61%) patients had non-classical CD (55 silent cases).

3.2. Association of Clinical Presentation with Metabolic Bone Disease, Anaemia and IgA Deficiency

Table 2 summarises the data of comorbidities and complications. Metabolic bone disease and anaemia were more common with classical presentation (p < 0.001 and p = 0.027, respectively). The proportion of IgA deficiency did not significantly differ between the groups (p = 0.089).

3.3. Association of Clinical Presentation with Immune-Mediated Comorbidities

A total of 207 patients (28%) were affected by another AD, of which 164 had 1 (22.2%) and 43 had more than 1 (5.8%) ADs. The most frequent AD was thyroid disease, which occurred in 12.3% of all patients and accounted for 44.3% of all ADs. The prevalence of AD was found to be significantly higher among CD patients with a non-classical presentation compared to those with a classical presentation (p = 0.025) (Table 2). DH occurred in 61 patients (8.3%); however, its frequency was significantly higher with non-classical presentation (p = 0.014). The type and frequency of immune-mediated diseases are presented in Table 3. The clinical characteristics of CD patients with multiplex ADs are presented in Table S1.

3.4. Association of Clinical Presentation with Chromosomal Abnormalities

In our cohort of patients, ten had Down’s syndrome (1.4%) and six had Turner syndrome (0.8%). All patients with Turner syndrome and 60% of the patients with Down’s syndrome had non-classical presentations, but the difference between groups was non-significant (p = 0.237) (Table 2).

3.5. Association of Clinical Presentation with Malignancies

Malignancy was diagnosed in a total of 23 patients (3.1%) (the male-to-female ratio was 8 to 15). The mean age upon CD diagnosis in patients with malignancy was 34.9 years (vs. 22.8 in those without malignancy). The mean age at diagnosis of malignancy was 43.0 years (five cases were under 18 years). Malignancy was diagnosed prior to the CD diagnosis in three cases, and simultaneously in three cases. The type of malignancy and characteristics of the patients with malignancy are summarised in Table S2. Classical clinical presentation was significantly associated with malignancies (p = 0.006) (Table 2).

4. Discussion

Our study aimed to find associations of clinical presentation with comorbidities and disease complications in CD. We analysed data from a cohort of CD patients who attended our hospitals at the University of Pécs (Pécs, Hungary) between 2007 and 2019.
The number of CD patients has grown significantly in recent decades. This tendency has been observed worldwide [16,17,18,19]; yet, some studies have reported a stagnation in the growth rate [20,21]. A true increase in incidence, better awareness and efficacy of screening programmes are behind this phenomenon [22,23,24]. In our case, many factors including the introduction of modern serology methods, standardisation of patient care, the establishment of a Coeliac Centre, the active case-finding strategy, cooperation with other specialists and propagation of family screening have led to a more efficient diagnostic efficacy. We observed a marked shift in clinical presentation in the last several decades: non-classical CD became significantly more prevalent [12]. This change in phenotype was also observed in many other studies in children [25,26,27] and adults [24,28,29,30,31]. The mean age at diagnosis of CD was quite low in our mixed-age (children–adults) study population, as nearly half of the patients were diagnosed in childhood. Surprisingly, our patients with classical CD were slightly older than those with the non-classical phenotype. This is not in line with the literature’s data, which, rather, shows that the dominance of classical CD is limited to children under 3 years of age [32,33] and to some countries beyond Europe [34,35]. In our cohort of patients, female predominance is also remarkably prominent (73.7%), which is in line with international trends [19].
The analysis of the comorbidities led to various results. There are little data regarding chromosomal abnormalities (Down’s syndrome, Turner syndrome) in CD; however, these conditions are more common among coeliac patients than in the average population (the prevalence of Down’s syndrome is about 1.4%, that of Turner syndrome is 0.26% in CD). Therefore, screening for CD is highly recommended in this population [36,37,38]. In our study, Down’s syndrome was associated mostly with non-classical presentation. In patients with Turner syndrome, CD manifested exclusively with non-classical presentation. Even so, we could not establish a significant difference between the groups due to the small number of cases. This needs further investigation, but this experience underlines the importance of screening of CD in these groups, even in the absence of typical symptoms.
Regarding IgA deficiency, we failed to reveal an association with clinical presentation.
Extraintestinal manifestations are common in patients with CD, affecting many organs and organ systems [39,40]. It is not clear what factors predispose their development; however, it is advisable to identify and treat them as soon as possible. It is not known whether they have a prognostic role in the disease course. It is reasonable to think that patients with more severe symptoms and generalised malabsorption are expected to have more complications. This is supported by the study of Nurminen et al. reporting more frequent complications among patients who developed more severe clinical symptoms and histology [41].
According to a recently published reviews, the frequency of anaemia varies in CD (ranging from 12% up to 85%) [42,43]. The prevalence of anaemia in our patient population is high (41%), which underlines the importance of routine monitoring of the anaemia-related parameters (vitamin levels, iron homeostasis-related parameters) upon diagnosis and during the GFD. The cause of anaemia in CD is complex, but malabsorption logically has a pivotal role [44]. Results of a Finnish study reporting that anaemia is more frequent in cases with severe symptoms corroborate this hypothesis [45].
Metabolic bone disease also occurs in a high percentage of our cohort (47.5%), more commonly than in other reports. These findings highlight the need of osteodensitometry at the time of diagnosis, and also to treat the metabolic bone disorder and to monitor the effectiveness of the therapy [29,46,47]. The results of our study suggest that bone metabolism disorders are more likely to develop among patients with classical symptoms; therefore, these patients require special attention. This conclusion is not surprising because bone metabolism disorders are likely due to the generalised malabsorption typically occurring in classical CD.
The prevalence of ADs among individuals with CD is nearly three times higher than that expected in the general population, with 20–30% of CD patients having at least one AD [19,48]. With a worldwide increasing trend in the rate of ADs, it imposes a real burden on society [18]. We detected ADs in 28% of patients, which is comparable with data reported from other centres [28,29,46,49,50,51]. Among our patients, the most common AD was autoimmune thyroiditis, with a similar rate to that previously published in a Hungarian university clinic study [50,52]. The prevalence of DH was also similar to that previously reported [49,50,52].
In our study, non-classical clinical presentation was associated with the development of ADs. In another study, it was also observed that family history of AD, being overweight upon diagnosis and delay of diagnosis were associated with an increased risk of the development of another AD [49]. However, in other reports, gender, coeliac symptoms, serology titre, HLA type and histopathological stage had no predictive role for the coexistence of AD among patients with CD [53,54].
The role of age upon diagnosis in the development of AD is deemed controversial. In addition, is it not obvious that early diagnosis of CD prevents the development of ADs [55,56]. The most common belief says that gluten exposure predisposes to autoimmunity and most ADs improve with a GFD [39,57,58]. This hypothesis supports the benefit of early diagnosis. Our study suggests that ADs should be expected to occur among individuals with non-classical symptoms.
Patients affected by CD have a higher risk of developing tumours, confirmed by a recent Swedish study encompassing a large patient population [59]. Although the risk is mitigated during a GFD, it remains high regardless of mucosa healing, which does not significantly modify the risk [60,61]. GFD seems to work against the development of lymphomas and small bowel tumours, yet, some other types of tumours (colon, breast) occur less frequently in untreated CD patients [62]. Diagnosis at a higher age (the role of chronic inflammation) and male gender can also be prognostic factors for malignancy [29].
The scientific literature on the role of clinical presentation on tumour risk is controversial. In Rampertab’s study, clinical presentation (classical or not) was not proven to be a predictor of tumour development [30]. In contrast, in a large Italian study consisting of 2225 (adult CD) patients with classical presentation, the incidence of complicated CD (refractory CD, lymphoma, small bowel tumour) was seven times higher with classical presentation [10]. Complications were associated with an early age upon diagnosis and classical clinical presentation. In our study, the classical clinical presentation was also associated with tumours. The CD-specific types of tumours (small bowel tumour and enteropathy-associated T-cell lymphoma) did not occur. However, a few rare tumour types (embryonal testicular carcinoma, testicular teratocarcinoma, osteogenic sarcoma, atypical teratoid rhabdoid brain tumour) were also observed, usually developing at an early age, prior to the diagnosis of CD. These patients had predominantly non-classical presentation. In contrast, patients with a classical presentation were characterised by tumour types being not common among the general population. This seems to be in contradiction with the scientific literature, where it is believed that untreated CD may be protective due to the impaired absorption of carcinogens [63].
There are many challenges during the follow-up of patients with CD. Currently, the main purpose of the therapy is to maintain and adhere to a GFD and to monitor antibody titres. With a well-managed diet, in most cases, the symptoms disappear, the mucosa regenerates, coeliac-specific antibodies normalise and deficiency states resolve. Our study shows that up to more than 40% of patients had comorbidities or complications that require an intervention from the treating physician (e.g., management of anaemia, bone diseases and ADs). In some patients, these comorbidities, especially ADs, may appear during the follow-up, even years or decades after CD diagnosis. These conditions should be actively searched for, e.g., by regularly monitoring the patient’s thyroid function. Clinical guidelines make recommendations for monitoring, yet now, the optimal follow-up strategy is unclear and there is no consensus [1,3,4]. The guidelines recommend that strict adherence to a GFD is important to prevent complications; however, there are no differences in the recommendations for therapy and follow-up based on the clinical presentation (whether malabsorption is present at diagnosis or not). Only the British guideline mentions that “symptomatic patients should be evaluated more thoroughly than asymptomatic” [64]. Our results suggest that there is a need for the focus of patient care needs to become slightly different: a personalised management approach is likely to be more beneficial. We highly agree with Dr Biagi and colleagues’ proposal stating that personalised follow-up based on clinical parameters already available at the time of the diagnosis is recommended (to fit a model to assess the combined prognostic role of age at diagnosis and clinical type of CD) [10].
The strength of this study is the size of the population and its coverage (the study reports data of all coeliac patients of one of the four university centres of Hungary). To date, this is the largest study describing data referencing Hungarian coeliac patients in such vivid clinical detail. A descriptive analysis of 178 CD patients of another Hungarian university centre was published earlier [50,52]. We analysed CD patients at any age: both children and adults were included. Systematic patient selection and consecutive inclusion of all appropriate patients mitigated the selection bias. Internationally, relatively few large studies are available describing the clinical presentation of CD. In the literature, the association between clinical phenotype and other clinical parameters has already been analysed; however, only in a few instances [7,10].
A limitation of this study is, obviously, its retrospective nature. Missing data were common prior to 2007 because the electronic clinical databases were harmonised in this year. Where the original data (histological or serological tests, osteodensitometry results, haemoglobin level, etc.) were not available, an analysis could not be performed. A further limitation was that we did not investigate the chronological relation across the diseases. We have not evaluated GFD adherence, which may also influence the incidence of complications.

5. Conclusions

Our study shows that classical presentation upon diagnosis is associated with more cases of metabolic bone disease, anaemia and malignancies compared to non-classical presentation. However, non-classical presentation was associated with more immune-mediated comorbidities (DH and AD) compared to classical presentation. These imply that CD patients may benefit from a more personalised follow-up tailored by clinical presentation upon diagnosis and highlight the importance of the management of comorbid conditions in CD. Clinicians providing care for CD patients should be aware of comorbidities and disease complications and should perform regular screening accordingly. Our findings should be validated in prospective cohort studies.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jpm15020055/s1, Table S1: Clinical characteristics of CD patients with multiplex autoimmune diseases; Table S2: Clinical characteristics of patients with tumours.

Author Contributions

Concept/design: J.B. and Z.S.; data collection, analysis and interpretation: Z.V., R.B. and E.N.; drafting article: M.Z.P.; critical revision of article: N.S., I.H. and A.T.; statistics: N.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the University of Pécs, Medical School and by the National Research, Development, and Innovation Office (grant FK142942 to J.B.). The study was also supported by the ÚNKP-23-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund (grant EKÖP-24-4-I-PTE-209 to Z.V.).

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Regional and Local Research Ethics Committee of University of Pécs (protocol code: 6918 and date of approval 9 December 2017). At that time, data collection was carried out for the period between 2007 and 2017. Extended data collection was performed for the period between 2017 and 2019 with a renewed approval (protocol code: 6918 and the date of approval is 19 February 2021).

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author. The raw data supporting the conclusions of this article will be made available by the authors on request.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Makharia, G.K.; Singh, P.; Catassi, C.; Sanders, D.S.; Leffler, D.; Ali, R.A.R.; Bai, J.C. The global burden of coeliac disease: Opportunities and challenges. Nat. Rev. Gastroenterol. Hepatol. 2022, 19, 313–327. [Google Scholar] [CrossRef] [PubMed]
  2. Hujoel, I.A.; Reilly, N.R.; Rubio-Tapia, A. Celiac Disease: Clinical Features and Diagnosis. Gastroenterol. Clin. N. Am. 2019, 48, 19–37. [Google Scholar] [CrossRef] [PubMed]
  3. Al-Toma, A.; Volta, U.; Auricchio, R.; Castillejo, G.; Sanders, D.S.; Cellier, C.; Mulder, C.J.; Lundin, K.E.A. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United Eur. Gastroenterol. J. 2019, 7, 583–613. [Google Scholar] [CrossRef]
  4. Husby, S.; Murray, J.A.; Katzka, D.A. AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review. Gastroenterology 2019, 156, 885–889. [Google Scholar] [CrossRef]
  5. Husby, S.; Bai, J.C. Follow-up of Celiac Disease. Gastroenterol. Clin. N. Am. 2019, 48, 127–136. [Google Scholar] [CrossRef]
  6. Loberman-Nachum, N.; Schvimer, M.; Avivi, C.; Barshack, I.; Lahad, A.; Fradkin, A.; Bujanover, Y.; Weiss, B. Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease. Dig. Dis. 2018, 36, 369–376. [Google Scholar] [CrossRef]
  7. Taavela, J.; Kurppa, K.; Collin, P.; Lähdeaho, M.L.; Salmi, T.; Saavalainen, P.; Haimila, K.; Huhtala, H.; Laurila, K.; Sievänen, H.; et al. Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease. Clin. Gastroenterol. Hepatol. 2013, 11, 166–171.e161. [Google Scholar] [CrossRef]
  8. Ciclitira, P.J. Does clinical presentation correlate with degree of villous atrophy in patients with celiac disease? Nat. Clin. Pract. Gastroenterol. Hepatol. 2007, 4, 482–483. [Google Scholar] [CrossRef]
  9. Kröger, S.; Kurppa, K.; Repo, M.; Huhtala, H.; Kaukinen, K.; Lindfors, K.; Arvola, T.; Kivelä, L. Severity of Villous Atrophy at Diagnosis in Childhood Does Not Predict Long-term Outcomes in Celiac Disease. J. Pediatr. Gastroenterol. Nutr. 2020, 71, 71–77. [Google Scholar] [CrossRef]
  10. Biagi, F.; Schiepatti, A.; Maiorano, G.; Fraternale, G.; Agazzi, S.; Zingone, F.; Ciacci, C.; Volta, U.; Caio, G.; Tortora, R.; et al. Risk of complications in coeliac patients depends on age at diagnosis and type of clinical presentation. Dig. Liver Dis. 2018, 50, 549–552. [Google Scholar] [CrossRef]
  11. Ghaferi, A.A.; Schwartz, T.A.; Pawlik, T.M. STROBE Reporting Guidelines for Observational Studies. JAMA Surg. 2021, 156, 577–578. [Google Scholar] [CrossRef] [PubMed]
  12. Szakács, Z.; Farkas, N.; Nagy, E.; Bencs, R.; Vereczkei, Z.; Bajor, J. Clinical Presentation Is Dependent on Age and Calendar Year of Diagnosis in Celiac Disease: A Hungarian Cross-Sectional Study. J. Pers. Med. 2023, 13, 487. [Google Scholar] [CrossRef] [PubMed]
  13. Vereczkei, Z.; Dergez, T.; Fodor, Z.; Szakács, Z.; Bajor, J. Body Mass Index during Gluten-Free Diet in Patients with Celiac Disease. Nutrients 2023, 15, 3517. [Google Scholar] [CrossRef]
  14. Ludvigsson, J.F.; Leffler, D.A.; Bai, J.C.; Biagi, F.; Fasano, A.; Green, P.H.; Hadjivassiliou, M.; Kaukinen, K.; Kelly, C.P.; Leonard, J.N.; et al. The Oslo definitions for coeliac disease and related terms. Gut 2013, 62, 43–52. [Google Scholar] [CrossRef]
  15. Oberhuber, G.; Granditsch, G.; Vogelsang, H. The histopathology of coeliac disease: Time for a standardized report scheme for pathologists. Eur. J. Gastroenterol. Hepatol. 1999, 11, 1185–1194. [Google Scholar] [CrossRef]
  16. Holmes, G.K.T.; Muirhead, A. Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958-2014. BMJ Open Gastroenterol. 2017, 4, e000137. [Google Scholar] [CrossRef]
  17. Burger, J.P.; Roovers, E.A.; Drenth, J.P.; Meijer, J.W.; Wahab, P.J. Rising incidence of celiac disease in the Netherlands; an analysis of temporal trends from 1995 to 2010. Scand. J. Gastroenterol. 2014, 49, 933–941. [Google Scholar] [CrossRef]
  18. Stroud, C.; Almilaji, O.; Nicholas, D.; Kirkham, S.; Surgenor, S.L.; Williams, I.; Snook, J. Evolving patterns in the presentation of coeliac disease over the last 25 years. Frontline Gastroenterol. 2020, 11, 98–103. [Google Scholar] [CrossRef]
  19. Grode, L.; Bech, B.H.; Jensen, T.M.; Humaidan, P.; Agerholm, I.E.; Plana-Ripoll, O.; Ramlau-Hansen, C.H. Prevalence, incidence, and autoimmune comorbidities of celiac disease: A nation-wide, population-based study in Denmark from 1977 to 2016. Eur. J. Gastroenterol. Hepatol. 2018, 30, 83–91. [Google Scholar] [CrossRef]
  20. Bergman, D.; King, J.; Lebwohl, B.; Clements, M.S.; Roelstraete, B.; Kaplan, G.G.; Green, P.H.; Murray, J.A.; Ludvigsson, J.F. Two waves of coeliac disease incidence in Sweden: A nationwide population-based cohort study from 1990 to 2015. Gut 2022, 71, 1088–1094. [Google Scholar] [CrossRef]
  21. Kivelä, L.; Kaukinen, K.; Lähdeaho, M.L.; Huhtala, H.; Ashorn, M.; Ruuska, T.; Hiltunen, P.; Visakorpi, J.; Mäki, M.; Kurppa, K. Presentation of Celiac Disease in Finnish Children Is No Longer Changing: A 50-Year Perspective. J. Pediatr. 2015, 167, 1109–1115.e1101. [Google Scholar] [CrossRef] [PubMed]
  22. Tursi, A.; Giorgetti, G.; Brandimarte, G.; Rubino, E.; Lombardi, D.; Gasbarrini, G. Prevalence and clinical presentation of subclinical/silent celiac disease in adults: An analysis on a 12-year observation. Hepatogastroenterology 2001, 48, 462–464. [Google Scholar] [PubMed]
  23. Absah, I.; Choung, R.S.; Murray, J.A. Pediatric Celiac Disease: Increasing Incidence or Increased Awareness? J. Pediatr. Gastroenterol. Nutr. 2018, 67, e42. [Google Scholar] [CrossRef] [PubMed]
  24. Zingone, F.; West, J.; Auricchio, R.; Maria Bevilacqua, R.; Bile, G.; Borgheresi, P.; Erminia Bottiglieri, M.; Caldore, M.; Capece, G.; Cristina Caria, M.; et al. Incidence and distribution of coeliac disease in Campania (Italy): 2011–2013. United Eur. Gastroenterol. J. 2015, 3, 182–189. [Google Scholar] [CrossRef]
  25. Pedretti, M.; Sbravati, F.; Allegri, D.; Labriola, F.; Lombardo, V.; Spisni, E.; Zarbo, C.; Alvisi, P. Is the clinical pattern of pediatric celiac disease changing? A thirty-years real-life experience of an Italian center. Ital. J. Pediatr. 2021, 47, 235. [Google Scholar] [CrossRef]
  26. Steens, R.F.; Csizmadia, C.G.; George, E.K.; Ninaber, M.K.; Hira Sing, R.A.; Mearin, M.L. A national prospective study on childhood celiac disease in the Netherlands 1993-2000: An increasing recognition and a changing clinical picture. J. Pediatr. 2005, 147, 239–243. [Google Scholar] [CrossRef]
  27. Trovato, C.M.; Ferretti, F.; Delli Bovi, A.P.; Elefante, G.; Ancinelli, M.; Bolasco, G.; Capriati, T.; Cardile, S.; Knafelz, D.; Bracci, F.; et al. Clinical Presentations of Celiac Disease: Experience of a Single Italian Center. Nutrients 2024, 17, 129. [Google Scholar] [CrossRef]
  28. Dominguez Castro, P.; Harkin, G.; Hussey, M.; Christopher, B.; Kiat, C.; Liong Chin, J.; Trimble, V.; McNamara, D.; MacMathuna, P.; Egan, B.; et al. Changes in Presentation of Celiac Disease in Ireland from the 1960s to 2015. Clin. Gastroenterol. Hepatol. 2017, 15, 864–871.e863. [Google Scholar] [CrossRef]
  29. Spijkerman, M.; Tan, I.L.; Kolkman, J.J.; Withoff, S.; Wijmenga, C.; Visschedijk, M.C.; Weersma, R.K. A large variety of clinical features and concomitant disorders in celiac disease—A cohort study in the Netherlands. Dig. Liver Dis. 2016, 48, 499–505. [Google Scholar] [CrossRef]
  30. Rampertab, S.D.; Pooran, N.; Brar, P.; Singh, P.; Green, P.H. Trends in the presentation of celiac disease. Am. J. Med. 2006, 119, 355.e9–355.e14. [Google Scholar] [CrossRef]
  31. Lungaro, L.; Costanzini, A.; Manza, F.; Caputo, F.; Remelli, F.; Volpato, S.; De Giorgio, R.; Volta, U.; Caio, G. Celiac Disease: A Forty-Year Analysis in an Italian Referral Center. Nutrients 2024, 16, 2292. [Google Scholar] [CrossRef] [PubMed]
  32. Pérez Solís, D.; Cilleruelo Pascual, M.L.; Ochoa Sangrador, C.; García Burriel, J.I.; Sánchez-Valverde Visus, F.; Eizaguirre Arocena, F.J.; Garcia Calatayud, S.; Martinez-Ojinaga Nodal, E.; Donat Aliaga, E.; Barrio Torres, J.; et al. Spanish National Registry of Paediatric Coeliac Disease: Changes in the Clinical Presentation in the 21st Century. J. Pediatr. Gastroenterol. Nutr. 2022, 74, 805–811. [Google Scholar] [CrossRef] [PubMed]
  33. Kochhar, R.; Jain, K.; Thapa, B.R.; Rawal, P.; Khaliq, A.; Bhadada, S.; Vaiphei, K.; Varma, S.; Dutta, U.; Nain, C.K.; et al. Clinical presentation of celiac disease among pediatric compared to adolescent and adult patients. Indian J. Gastroenterol. 2012, 31, 116–120. [Google Scholar] [CrossRef]
  34. Galvão, L.C.; Brandão, J.M.; Fernandes, M.I.; Campos, A.D. [Clinical presentation of children with celiac disease attended at a Brazilian specialized university service, over two periods of time]. Arq. Gastroenterol. 2004, 41, 234–238. [Google Scholar] [CrossRef]
  35. Imran; Cheema, H.A.; Alvi, M.A.; Rehman, M.U.; Ali, M.; Sarwar, H.A. Spectrum of Clinical Presentation of Celiac Disease in Pediatric Population. Cureus 2021, 13, e15582. [Google Scholar] [CrossRef]
  36. Mårild, K.; Stephansson, O.; Grahnquist, L.; Cnattingius, S.; Söderman, G.; Ludvigsson, J.F. Down syndrome is associated with elevated risk of celiac disease: A nationwide case-control study. J. Pediatr. 2013, 163, 237–242. [Google Scholar] [CrossRef]
  37. Mårild, K.; Størdal, K.; Hagman, A.; Ludvigsson, J.F. Turner Syndrome and Celiac Disease: A Case-Control Study. Pediatrics 2016, 137, e20152232. [Google Scholar] [CrossRef]
  38. Liu, E.; Wolter-Warmerdam, K.; Marmolejo, J.; Daniels, D.; Prince, G.; Hickey, F. Routine Screening for Celiac Disease in Children With Down Syndrome Improves Case Finding. J. Pediatr. Gastroenterol. Nutr. 2020, 71, 252–256. [Google Scholar] [CrossRef]
  39. Durazzo, M.; Ferro, A.; Brascugli, I.; Mattivi, S.; Fagoonee, S.; Pellicano, R. Extra-Intestinal Manifestations of Celiac Disease: What Should We Know in 2022? J. Clin. Med. 2022, 11, 258. [Google Scholar] [CrossRef]
  40. Pop, A.V.; Popa, S.L.; Dumitrascu, D.L. Extra-digestive manifestations of celiac disease. Med. Pharm. Rep. 2024, 97, 249–254. [Google Scholar] [CrossRef]
  41. Nurminen, S.; Kivelä, L.; Huhtala, H.; Kaukinen, K.; Kurppa, K. Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation. Acta Paediatr. 2019, 108, 681–687. [Google Scholar] [CrossRef] [PubMed]
  42. Montoro-Huguet, M.A.; Santolaria-Piedrafita, S.; Cañamares-Orbis, P.; García-Erce, J.A. Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management. Nutrients 2021, 13, 3437. [Google Scholar] [CrossRef] [PubMed]
  43. Kokoris, S.; Gavriilaki, E.; Vrigκou, E.; Triantafyllou, K.; Roumelioti, A.; Kyriakou, E.; Lada, E.; Gialeraki, A.; Kalantzis, D.; Grouzi, E. Anemia in Celiac Disease: Multiple Aspects of the Same Coin. Acta Haematol. 2023, 146, 82–87. [Google Scholar] [CrossRef] [PubMed]
  44. Seidita, A.; Mansueto, P.; Compagnoni, S.; Castellucci, D.; Soresi, M.; Chiarello, G.; Cavallo, G.; De Carlo, G.; Nigro, A.; Chiavetta, M.; et al. Anemia in Celiac Disease: Prevalence, Associated Clinical and Laboratory Features, and Persistence after Gluten-Free Diet. J. Pers. Med. 2022, 12, 1582. [Google Scholar] [CrossRef]
  45. Saukkonen, J.; Kaukinen, K.; Koivisto, A.M.; Mäki, M.; Laurila, K.; Sievänen, H.; Collin, P.; Kurppa, K. Clinical Characteristics and the Dietary Response in Celiac Disease Patients Presenting With or Without Anemia. J. Clin. Gastroenterol. 2017, 51, 412–416. [Google Scholar] [CrossRef]
  46. Volta, U.; Caio, G.; Stanghellini, V.; De Giorgio, R. The changing clinical profile of celiac disease: A 15-year experience (1998–2012) in an Italian referral center. BMC Gastroenterol. 2014, 14, 194. [Google Scholar] [CrossRef]
  47. Roldan, G.A.; Jamot, S.; Kopec, K.; Charoen, A.; Leffler, D.; Feller, E.R.; Shah, S.A. Celiac Disease Presenting in a Community-Based Gastroenterology Practice: Obesity and Bone Disease Are Common. Dig. Dis. Sci. 2023, 68, 860–866. [Google Scholar] [CrossRef]
  48. Tauschi, R.; Eurén, A.; Vuorela, N.; Koskimaa, S.; Huhtala, H.; Kaukinen, K.; Kivelä, L.; Kurppa, K. Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease. Front. Med. 2022, 9, 1055135. [Google Scholar] [CrossRef]
  49. Conti, L.; Lahner, E.; Galli, G.; Esposito, G.; Carabotti, M.; Annibale, B. Risk Factors Associated with the Occurrence of Autoimmune Diseases in Adult Coeliac Patients. Gastroenterol. Res. Pract. 2018, 2018, 3049286. [Google Scholar] [CrossRef]
  50. Juhász, M.; Kocsis, D.; Zágoni, T.; Miheller, P.; Herszényi, L.; Tulassay, Z. [Retrospective evaluation of the ten-year experience of a single coeliac centre]. Orvosi Hetil. 2012, 153, 776–785. [Google Scholar] [CrossRef]
  51. Sategna Guidetti, C.; Solerio, E.; Scaglione, N.; Aimo, G.; Mengozzi, G. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001, 49, 502–505. [Google Scholar] [CrossRef] [PubMed]
  52. Kocsis, D.; Miheller, P.; Lőrinczy, K.; Herszényi, L.; Tulassay, Z.; Rácz, K.; Juhász, M. Coeliac disease in a 15-year period of observation (1997 and 2011) in a Hungarian referral centre. Eur. J. Intern. Med. 2013, 24, 461–467. [Google Scholar] [CrossRef] [PubMed]
  53. Varol, F.; Çamtosun, E.; Selimoğlu, M.A.; Güngör, Ş. Is There a Predictive Factor for an Association with Autoimmune Glandular Disease in Children Diagnosed with Celiac Disease? J. Clin. Res. Pediatr. Endocrinol. 2022, 14, 409–414. [Google Scholar] [CrossRef] [PubMed]
  54. Salarian, L.; Khavaran, M.; Dehghani, S.M.; Mashhadiagha, A.; Moosavi, S.A.; Rezaeianzadeh, S. Extra-intestinal manifestations of Celiac disease in children: Their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations. BMC Pediatr. 2023, 23, 8. [Google Scholar] [CrossRef]
  55. Kahaly, G.J.; Frommer, L.; Schuppan, D. Celiac Disease and Glandular Autoimmunity. Nutrients 2018, 10, 814. [Google Scholar] [CrossRef]
  56. Canova, C.; Pitter, G.; Ludvigsson, J.F.; Romor, P.; Zanier, L.; Zanotti, R.; Simonato, L. Celiac Disease and Risk of Autoimmune Disorders: A Population-Based Matched Birth Cohort Study. J. Pediatr. 2016, 174, 146–152.e1. [Google Scholar] [CrossRef]
  57. Laurikka, P.; Nurminen, S.; Kivelä, L.; Kurppa, K. Extraintestinal Manifestations of Celiac Disease: Early Detection for Better Long-Term Outcomes. Nutrients 2018, 10, 1015. [Google Scholar] [CrossRef]
  58. Peng, Y.; Liu, C.; Liu, W.; Gan, R. Causal Relationship Between Gluten-Free Diet and Autoimmune-Related Disease Risk: A Comprehensive Mendelian Randomization Study. Int. J. Med. Sci. 2025, 22, 432–440. [Google Scholar] [CrossRef]
  59. Lebwohl, B.; Green, P.H.R.; Söderling, J.; Roelstraete, B.; Ludvigsson, J.F. Association Between Celiac Disease and Mortality Risk in a Swedish Population. JAMA 2020, 323, 1277–1285. [Google Scholar] [CrossRef]
  60. Lebwohl, B.; Green, P.H.R.; Emilsson, L.; Mårild, K.; Söderling, J.; Roelstraete, B.; Ludvigsson, J.F. Cancer Risk in 47,241 Individuals With Celiac Disease: A Nationwide Cohort Study. Clin. Gastroenterol. Hepatol. 2022, 20, e111–e131. [Google Scholar] [CrossRef]
  61. Pelizzaro, F.; Marsilio, I.; Fassan, M.; Piazza, F.; Barberio, B.; D’Odorico, A.; Savarino, E.V.; Farinati, F.; Zingone, F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers 2021, 13, 5288. [Google Scholar] [CrossRef] [PubMed]
  62. Ivanova, M.; Bottiglieri, L.; Sajjadi, E.; Venetis, K.; Fusco, N. Malignancies in Patients with Celiac Disease: Diagnostic Challenges and Molecular Advances. Genes 2023, 14, 376. [Google Scholar] [CrossRef] [PubMed]
  63. Freeman, H.J. Adult celiac disease and its malignant complications. Gut Liver 2009, 3, 237–246. [Google Scholar] [CrossRef]
  64. Ludvigsson, J.F.; Bai, J.C.; Biagi, F.; Card, T.R.; Ciacci, C.; Ciclitira, P.J.; Green, P.H.; Hadjivassiliou, M.; Holdoway, A.; van Heel, D.A.; et al. Diagnosis and management of adult coeliac disease: Guidelines from the British Society of Gastroenterology. Gut 2014, 63, 1210–1228. [Google Scholar] [CrossRef]
Jpm 15 00055 g001
Figure 1. Flowchart of study.
Figure 1. Flowchart of study.
Jpm 15 00055 g001
Table 1. Characteristics of patients included.
Table 1. Characteristics of patients included.
Number of Cases with Available DataTotal Cohort
of Patients		Patients with Classical
Presentation		Patients with Non-
Classical Presentation
Age at diagnosis
(mean, standard deviation)		73822.8 ± 17.124.4 ± 18.821.8 ± 15.9
Age at diagnosis
<18 years362362 (49%)122 (34%)240 (66%)
≥18 years376376 (51%)168 (45%)208 (55%)
Sex (n)738738290 (39%)448 (61%)
Male194 (26%)67 (35%)127 (65%)
Female544 (74%)223 (41%)321(59%)
Diagnostic histology (n)462
Marsh 16 (1%)2 (33%)4 (67%)
Marsh 211 (2%)4 (36%)7 (64%)
Marsh 3a61 (13%)22 (36%)39 (64%)
Marsh 3b126 (27%)50 (40%)76 (60%)
Marsh 3c258 (56%)103 (40%)155 (60%)
Diagnostic tTG serology (n)566
tTG IgA positive low titre159 (28%)53 (33%)106 (67%)
tTG IgA positive high titre407 (72%)139 (34%)268 (66%)
Table 2. Association of clinical presentation with comorbidities and disease complications.
Table 2. Association of clinical presentation with comorbidities and disease complications.
Number of Cases with Available DataTotal Cohort of PatientsPatients with Classical
Presentation		Patients with Non-Classical Presentationp-Value (Classical vs. Non-Classical Presentation)
IgA deficiency (n)31836/318 (11%) **18/118 (15%)18/200 (9%)0.089
Dermatitis herpetiformis (n)73861/738 (8%)15/290 (5%)46/448 (16%)0.014 *
Anaemia (n)656272/656 (41%)121/259 (47%)151/397 (38%)0.027 *
Metabolic bone disease (n)244116/244 (48%)71/120 (59%)45/124 (36%)<0.001 *
osteoporosis63/244 (26%)46/120 (38%)17/124 (14%)
osteopenia53/244 (22%)25/120 (21%)28/124 (23%)
Autoimmune diseases (n)738207/738 (28%)68/290 (23%)139/448 (31%)0.025 *
one164/207 (79%)55/290 (19%)109/448 (24%)
more than one43/207 (21%)13/290 (5%)30/448 (7%)
Chromosomal abnormality (n)73816/738 (2%)4/290 (1%)12/448 (3%)0.237
Down’s syndrome10/738 (1%)4/290 (1%)6/448 (2%)
Turner syndrome6/738 (1%)0/290 (0%)6/448 (2%)
Malignancy (n)73823/738 (3%)16/290 (6%)7/448 (2%)0.006 *
* indicates statistical significance (p < 0.05); ** indicates percentages are rounded to the nearest whole number.
Table 3. Immune-mediated diseases in patients with CD.
Table 3. Immune-mediated diseases in patients with CD.
Immune-Mediated DiseasesNumber of Patients% of Cohort
(n = 738)
Autoimmune thyroid disease9112.33%
Dermatitis herpetiformis618.26%
Type 1 diabetes mellitus527.04%
Raynaud syndrome304.06%
IBD (11 UC, 4 Crohn’s disease,
1 indeterminate)		162.16%
Sjögren’s disease111.49%
Autoimmune liver diseases
(4 AIH, 5 PBC, 2 PSC)		111.49%
Psoriasis70.94%
Systemic lupus erythematosus50.67%
Alopecia areata50.67%
Rheumatoid arthritis
(RA 1, JIA 2, seronegative RA 1)		40.54%
Vitiligo40.54%
Sarcoidosis30.40%
Antiphospholipid syndrome30.40%
Immune thrombocytopenic purpura20.27%
Dermatomyositis20.27%
Lichen ruber planus20.27%
MCTD20.27%
Pulmonary fibrosis20.27%
Scleroderma20.27%
IgA nephropathy10.13%
Lichen oris10.13%
Myasthenia gravis10.13%
Vasculitis10.13%
Polymyositis10.13%
Autoimmune haemolytic anaemia10.13%
Multiple sclerosis10.13%
IBD: inflammatory bowel disease; UC: ulcerative colitis; RA: rheumatoid arthritis; JIA: juvenile idiopathic arthritis; AIH: autoimmune hepatitis; PBC: primary biliary cholangitis; PSC: primary sclerotizing cholangitis; MCTD: mixed connective tissue disease.
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Bajor, J.; Vereczkei, Z.; Bencs, R.; Nagy, E.; Peresztegi, M.Z.; Hegedűs, I.; Farkas, N.; Tárnok, A.; Szigeti, N.; Szakács, Z. Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis. J. Pers. Med. 2025, 15, 55. https://doi.org/10.3390/jpm15020055

AMA Style

Bajor J, Vereczkei Z, Bencs R, Nagy E, Peresztegi MZ, Hegedűs I, Farkas N, Tárnok A, Szigeti N, Szakács Z. Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis. Journal of Personalized Medicine. 2025; 15(2):55. https://doi.org/10.3390/jpm15020055

Chicago/Turabian Style

Bajor, Judit, Zsófia Vereczkei, Réka Bencs, Enikő Nagy, Míra Zsófia Peresztegi, Ivett Hegedűs, Nelli Farkas, András Tárnok, Nóra Szigeti, and Zsolt Szakács. 2025. "Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis" Journal of Personalized Medicine 15, no. 2: 55. https://doi.org/10.3390/jpm15020055

APA Style

Bajor, J., Vereczkei, Z., Bencs, R., Nagy, E., Peresztegi, M. Z., Hegedűs, I., Farkas, N., Tárnok, A., Szigeti, N., & Szakács, Z. (2025). Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis. Journal of Personalized Medicine, 15(2), 55. https://doi.org/10.3390/jpm15020055

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