Importance of celiac disease oral manifestations in pediatric patients: A systematic review

Table 1 Methodological critical appraisal of cross-sectional studies

Ref.	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	N yes
Elbek-Cubukcu et al[13], 2023	Yes	Yes	Yes	Unclear	Unclear	Unclear	Yes	Yes	5
Bıçak et al[15], 2018	Yes	Unclear	Yes	Yes	Unclear	Unclear	Yes	Yes	5
Saraceno et al[8], 2016	Yes	Unclear	Yes	Yes	Unclear	Unclear	Yes	Yes	5
Bramanti et al[17], 2014	Yes	Unclear	Yes	Unclear	Yes	Yes	Unclear	Yes	5

Q1: Were the inclusion criteria for the sample clearly defined? Q2: Were the study subjects and the context described in detail? Q3: Was the exposure measured in a valid and reliable way? Q4: Were objective and standardized criteria used to measure the condition? Q5: Were confounding factors identified? Q6: Were strategies to deal with confounding factors indicated? Q7: Were the outcomes measured in a valid and reliable way? Q8: Was appropriate statistical analysis used?

Table 2 Methodological critical appraisal of cohort studies

Ref.	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Q11	N yes
Ludovichetti et al[12], 2022	Yes	Yes	Yes	Unclear	Unclear	No	Yes	Not applicable	Unclear	Not applicable	Yes	5
Villemur Moreau et al[10], 2021	Yes	Yes	Yes	Unclear	Unclear	No	Yes	Yes	Yes	Not applicable	Yes	7

Q1: Are the two groups similar and drawn from the same population? Q2: Was the exposure measured in a similar way? Q3: Was the exposure measured in a valid and reliable way? Q4: Were confounding factors identified? Q5: Were strategies to deal with confounding factors indicated? Q6: Were the participants free from the condition at the beginning of the study? Q7: Were the outcomes measured in a valid and reliable way? Q9: Was the follow-up sufficiently long for the condition to occur? Q10: Are there strategies to deal with incomplete follow-up? Q11: Was appropriate statistical analysis used?

Table 3 Methodological critical appraisal of case-control studies

Ref.	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	N yes
Alsadat et al[11], 2021	Yes	Yes	Yes	Yes	Yes	Yes	Unclear	Yes	Not applicable	Yes	8
Shahraki et al[7], 2019	Yes	Yes	Yes	Yes	Yes	Yes	Unclear	Yes	Not applicable	Yes	8
Alamoudi et al[23], 2020	Yes	Yes	No	Yes	Yes	Unclear	Unclear	Yes	Not applicable	Yes	6
Macho et al[22], 2020	Yes	Yes	Yes	Unclear	Unclear	Yes	Yes	Yes	Yes	Yes	8
Macho et al[9], 2019	Yes	Yes	Yes	Unclear	Unclear	Unclear	Unclear	Yes	Yes	Yes	6
Zoumpoulakis et al[19], 2019	Yes	Yes	Yes	Unclear	Unclear	Yes	Unclear	Yes	Not applicable	Yes	6
de Carvalho et al[20], 2015	Yes	Yes	Yes	Unclear	Unclear	Yes	Unclear	Yes	Not applicable	Yes	6
Cantekin et al[21], 2015	Yes	Yes	Yes	Unclear	Unclear	Yes	Unclear	Yes	Not applicable	Yes	6

Q1: Are the two groups comparable? Q2: Were the cases and controls appropriately matched? Q3: Were the same criteria used to identify cases and controls? Q4: Was the exposure measured in a valid and reliable way? Q5: Was the exposure measured the same way for cases and controls? Q6: Were confounding factors identified? Q7: Were strategies to deal with confounding factors indicated? Q8: Were the outcomes measured in a valid and reliable way for both cases and controls? Q9: Was the exposure period long enough to be significant? Q10: Was appropriate statistical analysis used?

Table 4 Summary of the selected articles

Ref.	Objective	Study sample	Assessment technique	Results
Elbek-Cubukcu et al[13], 2023	Presence of molar-incisor hypoplasia and RAU, the level of caries experience, and oral hygiene status, and measuring salivary flow, salivary buffering capacity, and cariogenic salivary microflora with Marsh types	62 pediatric patients with CD, 64 controls	The clinical identification of hypoplasia was performed according to the criteria of the European Academy of Pediatric Dentistry. The assessment of caries experience was conducted using the DMFT index. Oral hygiene was assessed through the IHO-S record. CRT® Bacteria and Buffer Test was used to examine the cariogenic microflora of each child	The prevalence molar-incisor hypoplasia was 61%. RAU > CD. A positive relationship was found between disease duration and the severity of hypoplasia. Higher counts of S. mutans. Salivary flow was very low in CD. A positive correlation was found between poor dietary adherence and worse oral hygiene. CD group exhibited a higher DMFT index
Ludovichetti et al[12], 2022	Investigate the correlation between CD and specific oral lesions	114 pediatric patients. Three groups: Celiac patients (CD group). Patients with malabsorption without CD (non-celiac group). Healthy controls	The DED were classified according to Aine's classification. Possible lesions in oral soft tissues were investigated, along with the concomitant presence of glossodynia	The findings revealed that children with CD had a higher prevalence of DEDs compared to the control group. However, no significant difference was observed between the two groups regarding the occurrence of RUA and other oral lesions. In the CD group and the control group, the teeth most prone to dental defects were incisors and molars simultaneously (about 54% in both groups), or incisors only (about 30% in the CD group and about 36% in the control group). All oral lesions considered were more frequent in the CD group
Alsadat et al[11], 2021	Compare the oral manifestations of children with CD to a healthy control group	208 participants: 104 patients CD. 104 in the control group	The DED were evaluated according to Aine's classification. The assessment of caries experience was conducted using the DMFT index. The presence of RAU at the time of clinical evaluation was recorded, and the history of ulcers was collected during the anamnesis. The oral consequences of advanced stages of untreated caries were measured using the PUFA index. Malocclusion was assessed using the DAI index	CD presented more RAU than controls (42.3% vs 15.4%) and more DED than controls (70.2% vs 34.6%). No significant difference was found between CD cases and controls in the frequency of malocclusion. In children with CD, the caries index was lower in the primary dentition compared to the control group; in permanent dentition, the caries index was higher for the CD group. Regarding the PUFA index, in primary dentition, CD was lower than in controls, while in permanent dentition, it was higher in the CD group than in controls
Villemur Moreau et al[10], 2021	Compare the frequency of DED, RAU, and dental eruption delay between children with CD and a healthy group	28 children CD. 59 controls	DED were classified from grades I to IV according to Aine's classification. RAS were assessed through clinical observation supplemented by information from parents	The extent of DED in CD was as follows: 67.86% had Grade I defects. The difference between the groups was significant. RAU in children with CD was 3.86, compared to 0.72 in the control group
Alamoudi et al[23], 2020	Assess the prevalence of dental maturity in patients with CD	208 participants: 104 children with CD. 104 in the control group	A panoramic radiograph and a comprehensive oral examination were performed for each participant. Dental age was measured according to the Demirjian method, and dental maturity was calculated by subtracting chronological age from dental age	CD had a higher prevalence of delayed dental maturity compared to controls (62.5% vs 3%). The delay in dental maturity was greater than in the controls (7.94 ± 10.94 vs 6.99 ± 8.77). Children in the younger age group (6-7 years) had a significantly advanced dental maturity of 16.21 ± 2.58 months compared to children aged 11-14 years
Macho et al[22], 2020	Evaluate the symmetry of DED in children with CD	160 participants: 80 children with CD. 80 in the control group	The DED were evaluated according to Aine's classification (grades I to IV)	DED were found in 55% of patients with CD and 27.5% in the control group. Grade I according to Aine was the most prevalent in both groups, but it was higher in the CD group in both dentitions. Grade II was found only in the CD group. The DED in CD were symmetrical, and the most affected teeth were the permanent first molars and permanent incisors
Macho et al[9], 2019	To evaluate the prevalence of soft tissue oral lesions in a pediatric CD with healthy controls. To assess the relationship between the onset of a gluten-free diet and the prevalence of oral manifestations	80 patients with CD. 80 healthy individuals as controls	Clinical record (questionnaire) and an intraoral observational examination	Although changes in soft tissues such as angular cheilitis, atrophic glossitis, and geographic tongue were 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)
Shahraki et al[7], 2019	To investigate the frequency and distribution of DED and dental caries in children with CD and compare them to healthy group	65 individuals with CD. 60 healthy individuals matched by age and sex	The DED were classified according to Aine's criteria, and dental caries was recorded by calculating the DMFT indices. The presence of other oral findings, such as aphthous ulcers and xerostomia, was recorded in the clinical record	Grade I was the most common enamel defect in both groups. Symmetrical and nonspecific DED were observed in 45% and 14% of individuals with CD, and in 12% and 12% of the control group (P = 0.001). The location of DED in permanent and primary teeth was more prominent in the anterior teeth, with a coronal distribution involving the incisal and middle portions of the teeth
Zoumpoulakis et al[19], 2019	To assess the prevalence of oral manifestations and explore whether oral examination can be used as a diagnostic screening tool for atypical or asymptomatic forms	45 patients with CD were classified into three categories of CD (classical, atypical, asymptomatic) 45 healthy individuals	DEDs were evaluated according to Aine's classification (grades I to IV). The assessment of caries experience was conducted using the DMFT index. The evaluation of (nonspecific atrophic glossitis, RAS, geographic tongue, and median rhomboid glossitis) included those observed clinically	The difference is statistically significant for the prevalence of DED between the groups, with systemic DED present in both groups; Grade I at (51.5%), Grade II at (39.2%), and Grade IV at (7.1%). There was a statistically significant correlation between the severity of systemic DED and the form of CD, as well as for the prevalence of RAS (40%) in the CD group. For other tissue lesions, the difference was not statistically significant
Bıçak et al[15], 2018	To examine the changes in the soft and hard tissues of the oral cavity in CD	30 CD. 30 control group	DED was evaluated according to Aine, RASU was detected through clinical assessment, and dental caries was diagnosed using WHO criteria (DMFT). After chewing paraffin wax gum, the children were asked to spit for 5 minutes to detect stimulated salivary flow rates	20 patients with CD had DED, but none in the control group. In the CD group, all DED cases were diagnosed in permanent teeth and were specific to all the children. Grade I DED was primarily found in the incisors. The frequency of ulcers was higher in the control group, but the difference was not statistically significant. The DMFT values were relatively lower in the CD group. The stimulated salivary flow rate was significantly lower in the CD group
Saraceno et al[8], 2016	To evaluate the different prevalences of oral conditions in patients with CD compared to a control group	166 patients, between 2 and 17 years of age and of both genders patients affected by CD were compared with those of a control group	Clinical record	The most common lesions in both groups were RAU (69% in patients with CD vs 43% in the control group), followed by dental diseases (76% in patients with CD vs 65% in the control group)
de Carvalho et al[20], 2015	To assess the oral manifestations of CD, the chemical composition of dental enamel, and the occurrence of CD in children with DED	52 children with CD and 52 controls were examined for DED, RAU, DMFT, and salivary parameters. Additionally, 10 exfoliated primary molars from each group were analyzed. Another sample of 50 asymptomatic children aged 2 to 12 years with DED was included to investigate the occurrence of CD	DEDs were recorded according to Aine's category I-IV classification. The assessment of caries experience was conducted using the DMFT index. The presence of UAR at the time of clinical evaluation was recorded. The chemical composition of dental enamel was evaluated based on energy-dispersive X-ray spectroscopy and Fourier-transform infrared spectroscopy	RAU was present in 40.38% of the CD group and 17.31% of the control group, with a statistically significant difference. Regarding the analysis of salivary parameters, low salivary flow was observed in 36% of the CD group and 10% of the control group, with a significant difference between the groups. The CD group had DED in 61.54% of cases, grade I in 44.24%, and grade II in 15.38%, while only 21.15% of the control group had DED, showing a statistically significant association between the specificity of DED and CD
Cantekin et al[21], 2015	Determining the presence and distribution of DED, RAU, and dental caries in children with CD and comparing the results with a healthy control group	25 patients with CD aged 4 to 16 years. 25 healthy individuals in the control group	Caries experience was assessed using the DMFT index. RAU evaluation included clinically observed lesions. DED assessment was based on presence or absence without defined criteria	The mean DMFT values for the CD group and the control group showed a significant difference. DED were observed in 48% of the CD group and 16% of the control group, with a statistically significant difference between the groups. RAU was detected in 44% of the CD group, while no RAU was found in the control group
Bramanti et al[17], 2014	To investigate hard and soft tissue oral lesions in potential celiac children in comparison to healthy controls	Group A: 50 confirmed celiac patients. Group B: 21 potential celiac patients. Group C: 54 healthy controls	DEDs were recorded according to Aine’s Category I-IV classification. RAU assessment included clinically observed lesions by the examiner and recurrent ulcerative lesions reported by parents, patients, or documented in clinical records. To assess dental maturity, conventional eruption tables for the Caucasian population were used	DEDs were present in 67% of patients in Groups A and B. Grade I: 62.5% in Group A and 50% in Group B. Grade II: 21.17% in Group A and 50% in Group B. RAU was found in 52% of Group A, 66.7% of Group B, and 7.4% of Group C. Burning tongue was recorded in 14% of Group A, 9.5% of Group B, and 5.5% of Group C. Atrophic glossitis was observed in 14% of Group A, 23.8% of Group B, and 1.85% of Group C. Angular cheilitis was recorded in 6% of Group A, 9.5% of Group B, and 3.7% of Group C. Delayed clinical dental eruption was observed in 38% of Group A, with an average delay of 1.4 years, and in 42.8% of Group B, with an average delay of 1.7 years

CD: Celiac disease; DED: Dental enamel defects; DMFT: Decayed, Missing, and Filled; RAU: Teeth recurrent aphthous ulcers.