Contrary to early beliefs, celiac disease (CD) is relatively common; however, it still remains underdiagnosed since most cases are atypical, with predominance of extra intestinal manifestations [
Available data showed that the prevalence of CD is around 1% of the general population [
As abnormalities of the oral cavity have been reported in CD, clinical examination of the oral cavity can help to identify patients with atypical or silent CD [
Enamel mineralization disturbances secondary to CD do not occur before a period of gluten intake coinciding with enamel mineralization. A possible explanation for the enamel defects could be hypocalcemia or, more likely, a particular genetic condition that leads to a specific immune response to gluten [
The aim of this work was to assess the frequency and predictors of CD among children with dental enamel defects as a step to decide whether these patients are candidates for routine celiac screening.
This longitudinal clinical study was conducted in the General Pediatric Clinic, Dentistry Pediatric Clinic, and Pediatric Gastroenterology Unit, Children’s Hospital, Ain Shams University from May 2008 to April 2011.
The recruitment plan started with diagnosis of DED by the dentists in the general pediatric and pediatric dentistry clinics of Ain Shams University. They were referred to pediatric gastroenterology unit to complete the study provided they fulfilled the inclusion criteria and were free of the exclusion ones.
Patients with DED.
Patents age between 4–12 years.
Patients with chronic illness other than gastrointestinal symptoms.
Patients on inhalation therapy for bronchial asthma.
The study included 140 patients with DED defined and classified according to Aine et al. [
A cohort of 720 healthy, age- (4–12 years), and sex- (371 males and 349 females) matched children was included as a control group. They were recruited among normal children coming for routine checkup in children’s hospital in the well child clinic.
The study was approved by the local ethics committee of the Pediatrics Department, Faculty of Medicine, Ain Shams University. Informed consents were obtained from the legal guardians of the included subjects after explaining the nature of the study to them. This was done once DEDs were diagnosed. Children were subjected to full history taking with special emphasis on dietetic history, gastrointestinal symptoms, dental hygiene, and dentist visits. All included subjects underwent abdominal examination and anthropometric studies (weight and length) and evaluated on WHO growth curves [
Oral examination for hard tissue changes (i.e., DED) was done. Examination was carried out at the Pediatric Dentistry Department at Ain Shams Faculty of Dentistry by a pediatric dentist. Most of the patients did not need sedation. Only few patients (below the age of 6 years) required chloral hydrate sedation. In order to avoid masking of defects by dental plaque, teeth were cleaned with a toothbrush [
Laboratory assessment of celiac disease was based on the quantitative determination of antitissue transglutaminase IgA and IgG (anti-tTG IgA and anti-tTg IgG) using a sandwich Enzyme-Linked Immune-Sorbent Assay (ELISA) kit manufactured by Orgentec, Diagnostika GmbH, (Mainz, Germany). In this technique, anti-tTG IgA and anti-tTG IgG in the samples or standards bind to the microwells coated with human recombinant tTG IgA and tTG IgG. Horseradish peroxidase conjugated to tTG IgA and tTg IgG is added together with its substrate resulting in color development. The intensity of this color, which is proportional to the concentration of anti-tTG IgA and anti-tTg IgG, is measured photometrically at a wavelength of 450 nm. According to the manufacturer’s instructions a value above 10 U/mL was used as cutoff value to identify both anti-tTG IgA and anti-tTg IgG positivity.
Total serum IgA was measured, as well, by a radial immunodiffusion method (Diffu-Plate, Biocientífica, Buenos Aires, Argentina). Results were evaluated by using a reference table (routine determination). 5 mg/dL was used as cutoff value to identify IgA deficiency, in which a value below 5 mg/dL was considered to be IgA deficiency [
Positive serology (values ranged between 60–120 U/mL) patients (with either one or 2 positive antibodies) were subjected to esophagogastroduodenoscopy and intestinal biopsy from the second part of the duodenum (minimum of 4 biopsies) that were assessed histopathologically for features of celiac disease. The diagnosis of celiac cases was made according to Hill et al. [
Complete blood count was done on Cell-Dyn-1800 (Abbott Park Illinois, 100 Abbott Park road, 60064-3500 USA). Serum calcium, phosphorus and alkaline phosphatase was done on Synchron Cx9-Pro auto-analyzer (Beckmann instruments Inc. CA, USA).
The results were collected, tabulated, and statistically analyzed using computer software: SPSS program for Windows, version 12.0.2. It included description of all qualitative variables in the form of frequency and percentage with comparison by
The study included 140 patients with DED. Their mean age was
Of the 140 patients with DEDs, 5 patients showed deciduous teeth abnormality, whereas 135 had the abnormalities in the permanent teeth. None of them showed mixed involvement. Gastrointestinal symptoms did not show statistical difference between patients and controls. However, underweight was significantly more encountered in patients with DEDs than controls (
Comparison of different variables between patients with dental enamel defects and controls.
Children with dental | Normal children (720) | |||
enamel defects (140) | ||||
Males | 72 (51.43%) | 371 (51.53%) | 0.001 | |
Female | 68 (48.57%) | 349 (48.47%) | ||
Consanguinity | 60 (42.86%) | 169 (23.47%) | 17.71 | |
No consanguinity | 80 (57.14%) | 551 (76.53%) | ||
Recurrent GI symptoms | 25 (17.86%) | 146 (20.28%) | 0.37 | |
No | 115 (82.14%) | 574 (79.72) | ||
Underweight | 45 (32.14%) | 41 (5.69%) | 57.94 | |
Not underweight | 95 (67.86%) | 679 (94.31%) | ||
Celiac | 25 (17.86%) | 7 (0.97%) | 36.95 | |
Nonceliac | 115 (82.14%) | 713 (99.03%) |
On comparing children with and without CD among DED patients, the mean weight and height among children with CD (
There was a significantly lower mean calcium (
No statistically significant difference was found between patients with CD and those without CD as regards gender. Although children with CD had high rates of vomiting, diarrhea, constipation, abdominal pain, and flatulence; these symptoms were not significantly different from those in non-CD patients. The most frequent symptom was abdominal pain (63.6% versus 48.0%), followed by flatulence and diarrhea (45.5% versus 18.0%), vomiting (27.3% versus 13.0%), and constipation (27.3% versus 11.0%) in the celiac and nonceliac children among the case group, respectively.
Consanguinity and underweight were more encountered in patients with CD compared to those without (Table
Comparison between patients with dental enamel abnormalities who are positive for celiac disease versus those without celiac disease.
Dental enamel abnormalities | Dental enamel abnormalities | |||
with celiac disease = 25 | without celiac disease = 115 | |||
Males | 15 (60%) | 60 (52.17%) | 0.51 | |
Female | 10 (40%) | 55 (47.83%) | ||
Consanguinity | 16 (64%) | 44 (38.26%) | 5.56 | |
No consanguinity | 9 (36%) | 71 (61.74%) | ||
Recurrent GI symptoms | 5 (20%) | 20 (17.39%) | 0.10 | |
No | 20 (80%) | 95 (82.61%) | ||
Underweight | 15 (60%) | 30 (26.09%) | 10.83 | |
Not underweight | 10 (40%) | 85 (73.91%) |
There were significantly lower mean serum calcium and higher serum alkaline phosphatase among cases with CD (
After 1-year followup with routine dental care for all patients in addition to GFD in CD, the frequency of improvement of DED was significantly higher in CD compared to non-CD patients (
Grading of dental enamel pathology in patients according to celiac positivity and effect of a GFD for 1 year.
Celiac + DED at | Celiac + DED After | Nonceliac + DED at | Nonceliac + DED | GIa versus GIIa | GIb versus GIIb | |
start of study | 1 year on GFD | start of study | after 1 year | |||
(25) | (25) | (115) | (115) | |||
(GIa) | (GIb) | (GIIa) | (GIIb) | |||
Normal | 0 | 6 (24%) | 0 | 4 (3.48%) | ||
Grade 1 | 7 (28%) | 7 (28%) | 80 (69.57%) | 78(67.38%) | ||
Grade 2 | 10 (40%) | 6 (24%) | 22 (19.13%) | 21 (18.26%) | ||
Grade 3 | 6 (24%) | 4(16%) | 11 (9.57%) | 10 (8.7%) | ||
Grade 4 | 2 (8%) | 2 (8%) | 2 (1.74%) | 2 (1.74%) | ||
Comparison between the degrees of improvement of grade of DED in patients with CD versus patients with non-CD. (DIFF_CD: degree of improvement in CD, DIFNONCD: degree of improvement in non-CD).
With regression analysis (at
regression summary for possible predictors of celiac disease in patients with DED.
Item | BETA | Standard error of BETA | Standard error of | |||
---|---|---|---|---|---|---|
Age | −0.344 | 0.117 | −0.074 | 0.025 | −2.947 | 0.005 |
Consanguinity | −0.191 | 0.264 | −0.090 | 0.123 | −0.725 | 0.471 |
Diarrhea | 0.158 | 0.277 | 0.129 | 0.227 | 0.570 | 0.571 |
Abdominal distension | −0.040 | 0.144 | −0.032 | 0.114 | −0.277 | 0.783 |
Z score for weight | −0.120 | 0.121 | −0.020 | 0.012 | −1.658 | 0.104 |
Grade of enamel defects | 0.049 | 0.207 | 0.043 | 0.181 | 0.235 | 0.815 |
Dental plaque | −0.209 | 0.203 | −0.170 | 0.166 | −1.026 | 0.310 |
Hemoglobin | −0.295 | 0.305 | −0.085 | 0.088 | −0.965 | 0.339 |
Calcium level | −0.524 | 0.228 | −0.232 | 0.101 | −2.293 | 0.026 |
Previous studies focused on description of DED in CD. In fact, this will not reflect how much common is CD among patients presenting with DEDs. In the current study, CD was the underlying cause of DEDs in 17.86% of the studied patients compared to 0.97% of normal children without DEDs. This high frequency justifies consideration of DED patients as candidates for screening for CD. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) included the presence of specific dental enamel defects as a risk factor for CD [
Avşar and Kalayci [
Wiernik et al. [
The prevalence of CD in normal children in this cohort was 0.97%, which was a little bit higher than Abu-Zekry et al. [
In our study, grades 1, 2, and 3 of DED are more common than grade 4 pathology. Grades 2 and 3 are more common in CD than nonceliac. Improvement of grades, up to normalization of some cases, was significantly more achieved in CD than nonceliac patients who were maintained on routine dental care. The better improvement can be either attributed to direct effect of GFD on enamel or to improved nutritional status after such a regimen.
Ciacci et al. [
The high mean age of CD patients was in agreement of Kuloğlu et al. [
The Celiac Disease Guideline Committee of the NASPGHAN recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease should have a blood test for antibody to tissue transglutaminase, then those with an elevated TTG be referred for an intestinal biopsy to confirm the diagnosis [
Serum IgA is routinely measured to avoid bias of false-negative tTG IgA type. In our study, there was no difference between children with and without CD as regards serum total IgA level. According to many studies [
In our study, consanguinity is evident in 60 children among cases with dental enamel defects (42.86%), while in controls it was 169 (23.47%) with a
In patients with CD, serum calcium was significantly lower and serum alkaline phosphatase was significantly higher compared to those without CD. Moreover, serum calcium was the most important predictor of celiac pathology in patients with DED as shown by regression analysis.
Compared with controls, Praticò et al. [
In the current study, weight and height were significantly lower in CD patients compared to nonceliac ones. Many studies [
In the present study, celiac patients with DEDs had high rates of vomiting, diarrhea, constipation, abdominal pain, and flatulence but difference from nonceliac patients was not significant. Similar to our results, Rashid et al. [
The variable results reported concerning the frequency of symptoms of CD can be explained by the wide spectrum of classical and nonclassical presentations of CD. Also, the difference in population homogeneity, environmental, dietary, and genetic factors may explain the variable results in each study. However, many studies reported that abdominal pain and diarrhea are the most frequent symptoms in classical CD.
The lack of predictive value of the gastrointestinal manifestations to pick up CD among DED patients is of utmost importance. It is, with the high frequency of CD in this context, a good evidence for a true need for celiac screening among DED patients.
We can conclude that the prevalence of CD, among children with dental enamel defects, is much higher than in the general population. These enamel problems might be the only manifestation of celiac disease. So, screening for CD is highly recommended among those patients especially in presence of underweight and hypocalcemia.
Dental enamel defects are common among celiac compared to nonceliac children.
To take a look at the other face of the coin, what is the magnitude of CD among patients with dental enamel defects? In other words, is CD common enough in this sector of patients to deserve routine screening?
The authors declare that there is no conflict of interest with any authority related the subject of the study.
Mostafa El-Hodhod, the Principal Investigator, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.