|Year : 2019 | Volume
| Issue : 6 | Page : 347-352
Does the introduction of gluten-free diet influence the prevalence of oral soft tissue lesions in celiac disease?
Viviana Macho1, Maria C Manso2, Diana Silva3, David Andrade1
1 Department of Pediatric Dentistry, Faculty of Dentistry, University of Porto, Porto, Portugal
2 Fernando Pessoa Energy, Environment and Health Research Unit (FP-ENAS), Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal; Rede de Química e Tecnologia (REQUIMTE)-University of Porto, Porto, Portugal
3 Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal
|Date of Web Publication||26-Nov-2019|
Dr. Viviana Macho
Rua 31 de Janeiro nº22 1ºandar, 4900-533 Póvoa de Varzim.
Source of Support: None, Conflict of Interest: None
Aims and Objectives: Celiac disease (CD) is characterized by oral manifestations in the soft tissues. The introduction of a gluten-free diet (GFD) may be related to change in the prevalence of oral changes and symptoms. The aim of the study was to evaluate the prevalence of oral soft tissue lesions in a pediatric Portuguese population with CD compared with healthy controls, and secondarily to assess the relationship between the onset of the GDF and the prevalence of oral manifestations. Materials and Methods: A case–control study was performed: 80 patients with CD and 80 healthy subjects as controls, aged 6–18 years. Data were gathered through a structured protocol, consisting of a clinical record (questionnaire) and an intraoral observational examination. For the descriptive analysis of the results, relevant summary statistics were applied. Descriptive and inferential (mainly nonparametric tests) analyses were carried out with the Statistical Package for the Social Sciences software (IBM SPSS) version 24.0. P < 0.05 was considered as significant. Results: Although soft tissue changes such as angular cheilitis, atrophic glossitis, and geographic tongue were found to be more common in the CD group, no differences were found between the two groups. The prevalence of aphthous ulcerations was higher in the CD group, with a highly significant difference between the two groups (P < 0.001). One-third of the patients with CD with aphthous ulcers refer that the beginning of the GFD influenced the improvement of this oral mucosa alteration, with a statistically significant difference (P = 0.007). Conclusion: The Portuguese population with CD had a higher prevalence of aphthous ulcerations and this oral manifestation decreased with the introduction of a GFD.
Keywords: Aphthous ulcerations, atrophy, benign migratory, celiac disease, cheilitis, geographic, glossitis, lip diseases, tongue
|How to cite this article:|
Macho V, Manso MC, Silva D, Andrade D. Does the introduction of gluten-free diet influence the prevalence of oral soft tissue lesions in celiac disease?. J Int Oral Health 2019;11:347-52
|How to cite this URL:|
Macho V, Manso MC, Silva D, Andrade D. Does the introduction of gluten-free diet influence the prevalence of oral soft tissue lesions in celiac disease?. J Int Oral Health [serial online] 2019 [cited 2020 May 25];11:347-52. Available from: http://www.jioh.org/text.asp?2019/11/6/347/271774
| Introduction|| |
The main oral signs associated with celiac disease (CD) are aphthous ulcerations or recurrent aphthous stomatitis (RAS), geographic tongue, atrophic glossitis, and angular cheilitis.,, RAS is characterized by multiple recurrent small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or gray floors, typically presenting first in childhood or adolescence., Some authors suggest that RAS can be considered a sign of the atypical or the silent forms of CD.,,,, The geographic tongue, also known as migratory glossitis, is an inflammatory, chronic, and immune-mediated oral lesion with an unknown etiology., Atrophic glossitis is an inflammatory disorder of the tongue mucosa. The tongue becomes smooth and with a shiny appearance with a red or pink background., The patients referred to chewing, swallowing, and speaking difficulties.,, Angular cheilitis is characterized by erythema, ulceration, diffuse redness with an eroded area, and crusting in the corners of the mouth., The symptomatology is usually associated with a burning sensation.,
The introduction of a gluten-free diet (GFD) may be related to change in the prevalence of oral changes and symptoms., The relationship between the introduction of GFD in CD and the presence of oral manifestations is not very well clear, and there are no articles about this in the Portuguese population, so, these considerations led us to perform the first study in Portuguese children with CD, which evaluated the prevalence of oral soft tissue lesions among patients diagnosed with CD and compared the results with those of healthy controls and secondarily the relationship between the onset of GFD and the prevalence of oral manifestations.
| Materials and Methods|| |
A descriptive observational study was performed in a nonprobabilistic sample included 80 children with CD and 80 controls, aged between 6 and 18 years, in both groups. The patients with CD regularly followed up in the gastroenterology and nutrition department, pediatric hospital in the São João Hospital Center were invited to participate in the study. Data collection was performed between March 2016 and April 2017, through a structured protocol, consisting of a clinical record (questionnaire) and an intraoral observational examination. The control group included 80 children and adolescents followed up in the pediatric dentistry class of the department of dentistry of Oporto University, a choice made on purpose, considering that it was an exclusion factor to present other systemic diseases. If the control group consisted of non-celiac patients who were followed up at the hospital, they could present problems of a nutritional or systemic etiological nature, and thus, alter the results of the study.
The inclusion criteria implemented for the CD group were previous diagnosis of CD, age between 6 and 18 years, and signed informed consent from the children’s legal representatives. Inclusion criteria for the control group were the same except for having CD. The exclusion criteria for the two groups were patients who did not allow a complete examination, the presence of fixed orthodontic appliance, and the presence of systemic diseases. Any child from the control group who reported any gastrointestinal disease and/or having a family history of CD was excluded.
In the questionnaire, it was asked if the patients with CD did the GFD and for how long, and in the clinical history, the immunological markers (anti-transglutaminase antibody) were evaluated to know if the patients with CD complied the GFD. The clinical examination of all the participants was carried out by a certified dentist. To clinically observe the patients, an Asa dental mirror, an Asa probe, and sterile gauzes or cotton were used. The observation was made using artificial and natural light. The observation of the oral cavity began with the view of oral mucosa. Concerning soft tissue alterations, lesions were recorded at the moment of the examination, and information was collected during the anamnesis. This observation was initiated by the upper and lower labial rouge, followed by the upper and lower labial mucosa, followed by the jugal mucosa, the buccal mucosa, the gingiva, and the palate, ending at the level of the tongue. The oral parameters evaluated in this study were aphthous ulcerations or RAS, geographic tongue, atrophic glossitis, and angular cheilitis.
This study was approved by the Ethics Committee of the Faculty of Dentistry of Porto University (ref. certificate no. 001429) and by the Ethics Committee of the São João Hospital of Porto, Portugal (ref. certificate no. 157/15). Informed consent was obtained from the legal representatives of all individual participants included in the study, according to the Declaration of Helsinki of 2002.
All intraoral observations were performed by a single examiner; however, it was necessary to verify the degree of intra-observer reliability over time and the reproducibility of the examination. For this purpose, 16 double observations were performed, which corresponded to approximately 10% of the total intraoral observations performed. All double observations were made in the control group. Cohen’s Kappa coefficient for dichotomous observations and weighted Cohen’s Kappa coefficient for ordinal observations were used to calculate the intra-observer agreement, with a value of 0.875 and 0.915, respectively, being obtained with a 95% confidence interval of 0.811−0.921. This value can be considered as “near-perfect” as it corresponds to a range of values between 0.81 and 1.00. For the assessment of the examiner and confirmation of the calibration of the observer, observations were made in the control group by another dentist trained to verify if the assessments of the principal examiner would be correct. To verify the interobserver agreement, a random sample of 16 patients was selected and a clinical examination was repeated by both. The double observations were, where possible, performed on different days. However, the distance between the observations was not too much (at most 30 days) so no significant changes were observed in oral health status. The Kappa test for an agreement was 0.83, with a standard error of 0.04.
For descriptive analysis of the results, relevant summary statistics were applied. The qualitative nominal and ordinal variables were described using counts and its relativity as percentages (%), whereas age was described using the mean and respective standard deviation. Inferential analysis was performed using the chi-square test and binomial test for qualitative data and t-test for continuous data (age) as normality was present in both groups. Statistical significance was set to P < 0.05. The analysis was performed using the statistical analysis software IBM SPSS Statistics for Windows, Version 24.0 (Armonk, NY: IBM Corp., USA).
| Results|| |
It is a homogeneous sample of 80 patients with CD and 80 control patients aged 6–18 years, of both genders, with no significant difference between groups regarding the variables age (P = 0.172) and gender (P = 0.631) [Table 1].
Although soft tissue changes, such as angular cheilitis, atrophic glossitis, and geographic tongue, were found to be more common in the CD group, no differences were found between the two groups. Concerning aphthous ulcerations, there was a higher presence in the CD group (56.3%) versus the control group (20%) with a highly significant statistical difference between the two groups (P < 0.001) [Table 2], [Figure 1] and [Figure 2].
|Table 2: Comparison of the presence of oral soft tissue lesions in the celiac disease and control group|
Click here to view
|Figure 1: Presence of aphthous ulcers in upper lip in a patient with celiac disease|
Click here to view
|Figure 2: Presence of aphthous ulcers in jugal mucosa in a patient with celiac disease|
Click here to view
Compared to the location of aphthous ulcers, 28 (62.2%) of the patients with CD reported being more frequent in the jugal mucosa, with a statistically significant difference (P < 0.010) between the two groups [Table 3].
|Table 3: Comparison of the location of aphthous ulcerations in the celiac disease and control group|
Click here to view
[Table 4] shows the results regarding the frequency of aphthous ulcers, where 23 (51.1%) of the patients with CD reported monthly or twice monthly, with a statistically significant difference (P < 0.032) between the two groups. The majority of the control group who reported having RAS (68.8%) were not aware of the frequency of this soft tissue alteration [Table 4].
|Table 4: Comparison of the frequency of aphthous ulcerations in the celiac disease and control group|
Click here to view
In the CD group, those who reported having aphthous ulcerations, 13 patients (28.9%) reported that the onset of the GFD influenced the improvement of this oral mucosa alteration, emphasizing that the frequency decreased (P = 0.007) [Table 5].
|Table 5: Study of association between decreased frequency of aphthous ulcerations and the introduction of a gluten-free diet in the celiac disease group|
Click here to view
| Discussion|| |
In this study, many soft tissue changes were not found, although there were more soft tissue changes such as angular cheilitis, atrophic glossitis, and geographic tongue in the CD compared to that in the control group, no significant differences were observed between the two groups (P = 0.059, P = 0.059, P = 0.117, respectively). Although the study did not find statistically significant differences between the two groups, the results were similar to the studies already referenced in the literature,,,,, where there was a tendency for these alterations to appear in greater numbers in the CD group. In a study by Bramanti et al., the geographic tongue was found in 5/50 (10%) ascertained patients with CD, 4/21 (19%) potential patients with CD, and 2/54 (3.7%) control subjects. Cigic et al. found that 9 (15%) patients with geographic tongue were positive for IGA transglutaminase and in those patients, histological changes consistent with CD were confirmed by duodenal biopsy. Only two of the patients reported gastrointestinal symptoms., In a study by Bramanti et al., atrophic glossitis was observed in 7/50 (14%) ascertained patients with CD and 5/21 (23.8%) potential patients with CD versus 1/54 (1.85%) controls., Angular cheilitis was recorded in 3/50 (6%) ascertained patients with CD and 2/21 (9.5%) potential patients with CD versus 2/54 (3.7%) patients of the control group., A burning tongue was registered in 7/50 (14%) ascertained patients with CD, 2/21 (9.5%) potential patients with CD, and 3/54 (5.55%) control patients., Patients reported difficulties in chewing, swallowing, and speech. Lähteenoja et al. evaluated the presence of some soft tissue changes (burning tongue and atrophic glossitis) and verified that these changes were more present in the CD group. Campisi et al. found that the prevalence of soft tissue oral lesions was 42% in patients with CD and 2% in the control group (P < 0.001). The geographic tongue may be asymptomatic, but sometimes a burning sensation is reported after consuming spicy foods and salted as well as alcoholic drinks. The discomfort can be treated with an oral mouthwash containing antiseptic agents, anesthetic, or topical corticosteroids. The condition may spontaneously display periods of remission and exacerbation.
RAS is characterized by one or multiple painful ulcers in the oral mucosa, either circular or ovoid, presenting an erythematous halo.,, Data collection for RAS was made through clinical observation, but also the medical history of each patient regarding the presence and frequency of recurrences of oral ulcers. This study protocol agrees with the literature because only clinical evaluation at the precise moment would not reflect the true presence and frequency of this alteration in the tissues of the CD.,,, This oral pathology usually occurs in the non-keratinized oral mucosa and affects the feeding, the speech, and the swallowing as well as the toothbrushing. It also causes emotional instability because it can be the reason for considerable pain.
In this study, 56.3% of patients with CD reported RAS compared to 20% of subjects in the control group and with a highly significant difference (P < 0.001). Campisi et al. completed a study with a group of 269 patients (3–17 years) with CD and compared them with a group of 575 healthy individuals. RAS was more frequently found in children with CD (22.7% vs. 7.1% of controls)., In a study by Procaccini et al. the prevalence of RAS was 26% in patients with CD. Bucci et al. found a prevalence of 33.3% of RAS in patients with CD and reported that more than one-third of the coeliac subjects having RAS benefited from a GFD., In a study by Bramanti et al. RAS was found in 26/50 (52%) ascertained patients with CD, 14/21 (66.7%) potential patients with CD, and 4/54 (7.4%) controls. This study also reported that RAS was more frequent in silent patients with CD, who did not report any gastrointestinal symptoms before the diagnosis of CD., Nieri et al. performed a systematic review and a meta-analysis of controlled studies on the presence of RAS in CD versus healthy individuals. In a total of 1129 with CD and 1408 healthy individuals that were examined, it was found that 46% with CD had RAS compared to 8% of the healthy group, this difference was highly significant. de Carvalho et al. conducted a study with 52 children with CD and 52 control children, both aged 2–15 years. The prevalence of aphthous ulcers was 40.38% in patients with CD and 17.31% in the control group.
This study also evaluated the location of the oral cavity and the frequency of aphthous ulcers. It was found that the jugal mucosa was where the aphthae appeared more in the CD group (P = 0.010). As regards the frequency of aphthous ulcers, in the CD group the frequency was monthly or bimonthly, and in the control group was rare or did not know how to be precise, with a significant difference between the two groups (p = 0.032). Adequate treatment of aphthous ulcers depends on the frequency, location, number, size, and orofacial pain. In general, patients with mild-to-moderate symptoms are medicated with topical treatment only to control pain. Systemic therapy is used in the case of patients with severe symptoms.,
After diagnosing the disease and implementing a GFD, RAS tends to decrease in incidence.,, In this study, one-third (28.9%) of the patients with CD who reported having aphthous ulcerations improved after the introduction of GFD. Just like this study, Bucci et al. found a 33.3% prevalence of RAS in the patients with CD and reported that more than one-third of the patients with CD having RAS have benefited from a GFD. A possible correlation between CD and RAS is given by the observation of the effect of a GFD in the control of these ulcerations. A significant improvement of oral aphthous is reported in patients with CD following a GFD and may reappear on reintroduction of gluten. The literature reports that deficiencies of iron, folic acid, and vitamin B12 because of intestinal malabsorption of CD may be a possible cause of oral manifestations and appear to play a role in the pathogenesis of aphthous ulcers.,, Vitamin deficiencies are common in patients with CD who are newly diagnosed and the literature suggested that these patients continue to have a vitamin deficiency even after 10 years with GFD.,,
RAS is more prevalent in a Portuguese population with CD than in the general population. Thus, this study, as reported in the literature, suggests that aphthous ulcerations may be a CD signal, and therefore, individuals with oral soft tissue lesions, especially aphthous ulcerations, should be well evaluated and to consider, in the clinical history, the possibility of having CD.
The results of this study were obtained through a transversal evaluation, through the previous clinical history, and few were observed in the oral cavity at the time of clinical examination. Therefore, it would be essential to carry out a long-term follow-up to establish, with greater precision, the relationship between the occurrence of RAS and CD.
Aphthous ulcerations are more prevalent in a Portuguese population with CD than that in the general population. The incidence of aphthous ulcerations in CD tends to decrease after implementing a GFD. Therefore, it is essential for the dentist to be alert to this manifestation, which may be important in a possible diagnosis in atypical forms of the disease, and to highlight the importance of compliance with GFD for better oral health.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chavan M, Jain H, Diwan N, Khedkar S, Shete A, Durkar S. Recurrent aphthous stomatitis: A review. J Oral Pathol Med 2012;41:577-83.
Macho VMP, Coelho AS, Veloso E Silva DM, de Andrade DJC. Oral manifestations in pediatric patients with coeliac disease—A review article. Open Dent J 2017;11:539-45.
Cervino G, Fiorillo L, Laino L, Herford AS, Lauritano F, Giudice GL, et al
. Oral health impact profile in celiac patients: Analysis of recent findings in a literature review. Gastroenterol Res Pract 2018;2018:7848735.
Majorana A, Bardellini E, Flocchini P, Amadori F, Conti G, Campus G. Oral mucosal lesions in children from 0 to 12 years old: Ten years’ experience. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:e13-8.
Mina S, Riga C, Azcurra AI, Brunotto M. Oral ecosystem alterations in celiac children: A follow-up study. Arch Oral Biol 2012;57:154-60.
Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med 2010;39:420-3.
Cigic L, Galic T, Kero D, Simunic M, Medvedec Mikic I, Kalibovic Govorko D, et al
. The prevalence of celiac disease in patients with geographic tongue. J Oral Pathol Med 2016;45:791-6.
Erriu M, Canargiu F, Orrù G, Garau V, Montaldo C. Idiopathic atrophic glossitis as the only clinical sign for celiac disease diagnosis: A case report. J Med Case Rep 2012;6:185.
Bramanti E, Cicciù M, Matacena G, Costa S, Magazzù G. Clinical evaluation of specific oral manifestations in pediatric patients with ascertained versus potential coeliac disease: A cross-sectional study. Gastroenterol Res Pract 2014;2014:934159.
Stoopler ET, Nadeau C, Sollecito TP. How do I manage a patient with angular cheilitis? J Can Dent Assoc 2013;79:d68.
Melini V, Melini F. Gluten-free diet: Gaps and needs for a healthier diet. Nutrients 2019;11:E170.
Mager D, Marcon M, Brill H, Liu A, Radmanovich K, Mileski H, et al
. Adherence to the gluten-free diet and health-related quality of life in an ethnically diverse pediatric population with celiac disease. J Pediatr Gastroenterol Nutr 2018;66:941-8.
W.H.O. Oral Health Surveys—Basic Methods. 4th ed. Geneva, Switzerland: WHO; 1997.
Lähteenoja H, Toivanen A, Viander M, Mäki M, Irjala K, Räihä I, et al
. Oral mucosal changes in coeliac patients on a gluten-free diet. Eur J Oral Sci 1998;106:899-906.
Campisi G, Di Liberto C, Carroccio A, Compilato D, Iacono G, Procaccini M, et al
. Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children. Dig Liver Dis 2008;40:104-7.
Scully C, Felix DH. Oral medicine—Update for the dental practitioner. Aphthous and other common ulcers. Br Dent J 2005;199:259-64.
Bucci P, Carile F, Sangianantoni A, D’Angiò F, Santarelli A, Lo Muzio L. Oral aphthous ulcers and dental enamel defects in children with coeliac disease. Acta Paediatr 2006;95:203-7.
Procaccini M, Campisi G, Bufo P, Compilato D, Massaccesi C, Catassi C, et al
. Lack of association between celiac disease and dental enamel hypoplasia in a case-control study from an Italian central region. Head Face Med 2007;3:25.
Krisdapong S, Sheiham A, Tsakos G. Impacts of recurrent aphthous stomatitis on quality of life of 12- and 15-year-old Thai children. Qual Life Res 2012;21:71-6.
Nieri M, Tofani E, Defraia E, Giuntini V, Franchi L. Enamel defects and aphthous stomatitis in celiac and healthy subjects: Systematic review and meta-analysis of controlled studies. J Dent 2017;65:1-10.
de Carvalho FK, de Queiroz AM, Bezerra da Silva RA, Sawamura R, Bachmann L, Bezerra da Silva LA, et al
. Oral aspects in celiac disease children: Clinical and dental enamel chemical evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:636-43.
Mimura MA, Hirota SK, Sugaya NN, Sanches JA Jr, Migliari DA. Systemic treatment in severe cases of recurrent aphthous stomatitis: An open trial. Clinics (Sao Paulo) 2009;64: 193-8.
Pastore L, Carroccio A, Compilato D, Panzarella V, Serpico R, Lo Muzio L. Oral manifestations of celiac disease. J Clin Gastroenterol 2008;42:224-32.
van Gils T, Bouma G, Bontkes HJ, Mulder CJJ, Brand HS. Self-reported oral health and xerostomia in adult patients with celiac disease versus a comparison group. Oral Surg Oral Med Oral Pathol 2017;124:152-6.
Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients 2013;5:3975-92.
Hallert C, Grant C, Grehn S, Grännö C, Hultén S, Midhagen G, et al
. Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years. Aliment Pharmacol Ther 2002;16: 1333-9.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]