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Literature Review
PEDIATRIC DENTISTRY V 34 / NO 7 NOV / DEC 12
ORAL MANISFESTATIONS OF CELIAC DISEASE 485
Celiac disease (CD) is an enteropathy that affects genetically
susceptible individuals, following exposure to gluten, and is
present in proteins in wheat (gliadin), rye (secalin), and barley
(hordein) in the diet.1-4 e gluten triggers an autoimmune dis-
order due to the presence of autoantibodies. is leads to his-
topathologic injury in the small bowel mucosa, with crypt
hyperplasia, villous atrophy of the intestinal mucosa, and an
inammatory inltrate in the adjacent connective tissue, associ-
ated with an increased number of intraepithelial lymphocytes.5-7
e proximal duodenum and jejunum are the locations of
major injury; after gluten is removed from the diet, the intes-
tinal mucosa typically recovers. Intolerance to gluten, however,
is permanent (ie, the condition will return if these proteins are
reintroduced into the diet).5,8-9 e damage caused by CD can
have various consequences, such as poor digestion, malabsorp-
tion of nutrients, and poor nutritional status, as digestion and
absorption of carbohydrates, proteins, fats, iron, calcium, zinc,
vitamins (D, E, K, and B12), and folic acid occur in the duo-
denum and jejunum.10
CD, described as a rare condition, is a form of food hyper-
sensitivity that is more common in children than adults. It
usually presents after the sixth month of life, which coincides
with the introduction of cereals in the diet.3,10,11 Some studies
show that genetic and environmental factors play an important
role in the pathogenesis of CD, although the exact mechanism
has not yet been elucidated.12 CD is strongly linked to genetic
factors encoded by the complex human leukocyte antigen (HLA)
class II, mainly HLA-DQ2 and HLA-DQ8. e development
of the disease is a result of an innate and adaptive immune re-
sponse without control, triggered by the ingestion of gluten.
us, the main function of the HLA complex is in the presen-
tation of exogenous antigens represented by these proteins.3,6
Although CD presents as a malabsorption syndrome, it is
now known that this presentation is not common and that
many CD patients show no atypical gastroenterologic symp-
toms and may also be completely asymptomatic. This com-
plicates and delays the disease’s diagnosis.13,14 The lack of
diagnosis may have important consequences, especially when
there are delays in removing gluten from the diet. Several pre-
sentations may arise in these patients, such as: refractory anemia;
osteoporosis; neurologic and dermatologic disorders; growth
impairment; low weight and height; association with diabetes;
thyroiditis and other autoimmune disorders; and intestinal
neoplasia.2
CD is often not recognized by clinicians due to the varia-
bility of its clinical features and symptoms.12,15 In children,
symptomatic malabsorption syndrome can be easily diagnosed;
however, in most cases the signs are variable. Although some
patients develop the disease in childhood, others may ingest
gluten for many years before the disease becomes apparent.3
The clinical manifestations of the disease include diarrhea,
weight loss, abdominal pain, iron deficiency, anemia, and
malabsorption.11,12,16 e diagnosis of CD is based on labora-
tory examination for detection of serum markers—more recently,
antibodies anti-transglutaminase (TTG) and anti-endomysial
(EMA)—and proved by histopathology of the duodenal
mucosa.11,17
Although the immunology and pathophysiology of CD
are known, the impact of the disease on the patient’s life has
received less attention. Furthermore, the chronic nature of the
disease—associated with the limitations imposed by the need
to follow a restrictive diet permanently, the substantial numbers
of physician visits, and the risk of associated diseases and po-
tential complications—can have a considerable negative impact
on the health and quality of life of these patients.18
In order to develop this report on oral manifestations of
celiac disease, a comprehensive literature search was carried
out using the terms oral manifestations of celiac disease, dental
enamel defects, and oral ulcer from the following databases:
1 Dr. Ferraz is a PhD student, 2Dr. Campos is a professor, and 3Dr. Sarmento is an asso-
ciate professor, all in the Department of Propedeutics and Integrated Clinic, School of
Dentistry; and 4Dr. Silva is a titular professor, Department of Pediatric Gastroenter-
ology and Hepatology of the Professor Edgar Santos Teaching Hospital and the Professor
Hosannah de Oliveira Pediatrics Center, School of Medicine, all at Federal University
of Bahia, Salvador, Bahia, Brazil.
Correspond with Dr. Sarmento at viviane.sarmento@gmail.com
The Oral Manifestations of Celiac Disease: Information for the Pediatric Dentist
Eduardo Gomes Ferraz, DDS, MSc1 • Elisângela de Jesus Campos, DDS, MSc 2 • Viviane Almeida Sarmento, DDS, MSc, PhD3 • Luciana Rodrigues Silva, MD, MSc, PhD4
Abstract: Purpose: The purpose of this article was to present a literature review of oral manifestations reported by celiac disease patients. Methods: A
review of the published literature for oral manifestations present in celiac disease patients was conducted from the following databases: PubMed
®
;
MEDLINE; Web of Science; Science Direct; and Scielo. Results: According to some literature studies, prevalence of enamel defects and recurrent aphthous
stomatitis was observed in approximately 10% to 96% and 4% to 41% of 2- to 86-year-old celiac patients, respectively. Conclusion: The presence of
these clinical features in children may signal the need for early investigation of possible celiac disease, especially in asymptomatic cases. (Pediatr Dent
2012;34:485-8) Received October 4, 2011 | Last Revision November 30, 2011 | Accepted Dec 2, 2011
KEYWORDS: CELIAC DISEASE, MOUTH DISEASES, DENTISTRY
486 ORAL MANISFESTATIONS OF CELIAC DISEASE
PEDIATRIC DENTISTRY V 34 / NO 7 NOV / DEC 12
PubMed®; MEDLINE; Web of Science; Science Direct; and
Scielo.
Oral manifestations of CD. Some signs and symptoms in
CD patients are related to mineralized tissues, such as dental
enamel defects (eg, enamel hypoplasia, amelogenesis imperfecta,
stains for calcium deciency or excess, uorosis, and erosions).
In relation to soft tissues, recurrent aphthous stomatitis (RAS),
angular cheilitis, and atrophic glossitis are important features in
the clinical diagnosis of CD.11,17,19 In some situations, the mal-
absorption seen in CD contributes to the development of mal-
nutrition and, depending on the age at which it is established,
is related to the onset of changes in oral health, such as delayed
tooth eruption, decreased size of teeth, enamel formation
problems, or even dysfunction of the salivary glands.11,17
Dental enamel defects. Mineralization disorders may be
classied as qualitative (eg, discoloration) or quantitative, such
as those associated with loss of tooth substrate (eg, hypopla-
sia).20 Hereditary, systemic, or local agents acting in the stages of
dental organ development can cause disturbances during matrix
formation and teeth mineralization. When there is an injury to
ameloblasts—the cells that produce the enamel matrix—there
is a reduction in this production, which later calcies and leads
to a quantitative defect called enamel hypoplasia. When the
injury occurs during the maturation phase, resulting in hypo-
calcied areas, the qualitative defect is characterized.21
In this context, Aine22 defined a classification system to
include ndings on CD children. Opacity of the enamel and
hypoplasia and its associations were grouped according the
lesion’s clinical appearance, and its intensity was classied into
5 categories with progressive values. e distribution of enamel
defects in a study by Aine22 followed a systematic chronolog-
ical pattern affecting all 4 quadrants of the oral cavity. This
nding denes enamel hypoplasia as a standard nding in CD.
In the presence of posteruptive alterations, such as attrition, de-
cayed teeth, or white spots, diagnosing enamel defects becomes
more dicult.23
Enamel hypoplasia is the most common abnormality in the
development of tooth enamel. It can be associated with several
causes, often systemic, especially those related to nutritional dis-
orders during enamel formation, such as hypocalcemia, mal-
nutrition, and vitamin D deciency.11,24 Clinically, the defect
appears as a circle, in a band or with minor cracks, and gener-
ally presents as yellow or brown due to deposition of extrinsic
pigment.17
According to some studies, enamel defects are more prev-
alent in CD patients vs the general population.20,22,24,25 Thus,
dentists can play an important role in recognizing CD, particu-
larly in patients with dental enamel defects and, when there
are CD symptoms, in the medical history of a child.26 The
cause of enamel defects associated with CD, however, remains
uncertain.2,9,24–26
Enamel defects in CD patients have been associated with
a change in the metabolism of calcium or phosphate in the
formation of antibodies against the matrix of the enamel organ.19
Thus, antigen molecules correlated with class II major histo-
compatibility complex could direct immunity against the enamel
organ, causing a disturbance in mineralization. ere is strong
evidence that these anomalies are correlated with nutritional
status, vitamin D deficiency, or an excess of fluoride uptake,
and may represent conditions associated with CD.19
Some studies in the literature showed a prevalence of ena-
mel defects in approximately 10% to 96% of CD patients.8,19,24-27
Aine27 observed enamel defects in 96% of children and 83%
of adults with CD vs only 4% of control patients, noting that
these enamel changes follow systematic chronological patterns
that aect all 4 quadrants of the oral cavity, which is character-
ized as a standard nding in CD.
In a study of 70 4- to 22-year-old CD patients and 159
4- to 17-year-old controls, Bucci et al.,25 found that 14 (20%)
CD patients and 9 (6%) controls had enamel defects. By asso-
ciating the type of dentition and the presence of the defect in
the 53 CD patients with mixed or permanent dentition, only
13 (~25%) had such changes, as well as 1 (~6%) of 17 CD
children with primary dentition. Compared with the control
group of 145 subjects with mixed or permanent dentition, 9
(~6%) had enamel defects, and those with primary dentition
showed no such defects. ese results demonstrated that enamel
defects occurred more frequently in CD patients (P<.001).
Campisi et al.,2 evaluated the prevalence of oral manifesta-
tions in 197 untreated CD sufferers, 90 18- to 75-year-olds,
and 107 2- to 17-year-olds vs 413 control subjects, 180 19-
to 77-year-olds, and 233 2- to 17-year-olds, who were enrolled
in the study after conrmation of negative serological marker
anti-TTG. e results showed that 46 (23%) CD patients had
enamel defects vs 37 (9%) in the control group (P<.001). De-
layed eruption was observed in 28 (27%) pediatric CD patients
vs 16 (7%) controls (P<.001). According to the authors, hypo-
calcemia caused by malabsorption during tooth development
may be associated with enamel hypoplasia. Regarding the
delay in tooth eruption, this can be seen as a possible sign of
nutritional impairment related to CD.
Wierink et al.,26 compared the prevalence of enamel defects
in 53 CD children and 28 controls born between 1985 and
1996 and found that 29 (55%) CD patients and 5 (18%) con-
trols presented changes. In the CD group, the defects were
diagnosed as specic in 20 (38%) children and in only 1 (4%)
of the control group. ese results suggest that certain enamel
defects do not develop due to malabsorption causing low con-
centrations of serum calcium, since almost half the control
group patients had these symptoms and defects were evident in
just 1.
Oral manifestations in the soft tissues. RAS is one of the
oral manifestations associated with soft tissue most commonly
observed in humans and can aect both genders at any age. e
highest prevalence, however, is observed among children, adoles-
cents, and women, with an average prevalence of approximately
20%.12,15 e cause of RAS is unknown, although local and sys-
temic factors such as stress, allergies, nutritional deficiencies,
trauma, hormone deciencies, and infectious agents have been
associated in certain subgroups of patients. Clinically, ulcers
and painful symptoms are present; histologically, the ulcers are
round or oval and well demarcated, with a necrotic surface in
the center and erythematous halo, in the nonkeratinized mucosa
of the lip, oral mucosa, or soft palate.12,14
ere are 3 clinical variants of RAS: minor; major; and her-
petiformis. e minor form is the most common and is charac-
terized by small sores that heal in 10 to 14 days. In their major
form, the ulcers are larger, may last up to 6 weeks, and often
leave a scar in the mucosa. e third form, called herpetiformis,
presents as multiple lesions which may coalesce and last for 7
to 10 days.12,28
An RAS diagnosis can be accomplished primarily by his-
tory and clinical presentation as well as exclusion of other
ulcerative conditions that may resemble aphthous ulcers. e
PEDIATRIC DENTISTRY V 34 / NO 7 NOV / DEC 12
ORAL MANISFESTATIONS OF CELIAC DISEASE 487
histologic ndings are nonspecic, and patients with mild RAS
usually do not require treatment, while therapy with topical
corticosteroids can be used to reduce the frequency and severity
of injuries.12,15
Oral ulcers are a common condition that affect the gen-
eral population and can manifest as benign lesions,which may
be recurrent, such as RAS, or represent mucocutaneous markers
for a variety of systemic diseases, such as CD.29 Thus, ulcers
may be associated with some gastrointestinal disorders in pa-
tients with a high rate of recurrence or persistent RAS, such as
CD and Crohn’s disease.30
Clinical signs observed in CD patients, such as redness and
pain in the tongue, are related to papillary atrophy due to deci-
ency of vitamin B12, folic acid, and iron, because the process of
absorption by the small intestine is decient in these patients.8,11
It is unclear if oral lesions represent a direct manifestation of
CD or if they occur as a result of indirect eects of malabsorp-
tion on the basal cell layer in the intestinal mucosa of these
patients.31
Some studies in the literature showed a prevalence of RAS
in approximately 4% to 41% of CD patients.8,12,19,25 In a study
of 128 3- to 86-year-old CD patients on a gluten-free diet,
Lähteenoja et al.,8 observed that approximately 80% of CD
patients had lesions in the oral soft tissues. Pain or burning
sensation in the tongue was reported in 38 (30%) of CD group
patients and 3 (10%) of control group subjects. Additionally,
oral mucosal lesions, such as erythema and ulceration located
in the lips, palate, and tongue, were found in 71 (55%) CD
group patients and 7 (23%) control group subjects. According
to the authors, the CD on the duodenal mucosa may impair
the absorption of vitamin B12, folate and iron, which can lead
to signs of redness and sensitivity of the tongue with atrophic
papillae. Although CD patients in this study were advised to
follow a strict diet, it is quite dicult to avoid exposure to small
amounts of gluten, since minute exposure to the food ingested
can cause oral manifestations.8
Sedghizadeh et al.,12 evaluated 61 CD patients on the prev-
alence of RAS vs 62 individuals without CD (controls), all
between 3 and 75 years old, and observed no statistically signi-
cant dierences between the 2 groups in age, gender, and RAS
prevalence. Based on these results, the authors emphasize that
RAS is a risk indicator and not a risk factor for CD.
Aydemir et al.,15 evaluated the prevalence of CD in 41 pa-
tients with a history of RAS (average age=40 years old) vs 49
control subjects with no history of RAS (average age=38 years
old) from the level of serological markers (IgA-AGA and IgA-
EMA) and biopsies of the intestine. e results demonstrated
the diagnosis of CD in 2 (~5%) of 41 RAS patients and the ab-
sence of conrmation of disease in the control group. According
to the authors, the high prevalence of RAS in CD may aid in
the diagnosis of asymptomatic patients.
In studies on the presence of soft tissue damage, Campisi
et al.,2 reported a prevalence of 82 (42%) adult CD patients vs
9 (2%) controls (P<.001). Among these lesions, RAS was ob-
served in 37 (19%) CD patientsvs 3 (1%) controls. Atrophic
glossitis was found in 31 (16%) CD patients and 1 (0.2%)
control subject (P<.001), and glossitis was observed in 14 (7%)
CD patients and 5 (1%) controls (P<.001). ere was a reduc-
tion in the prevalence of RAS in 89% of patients 1 year after
the start of a gluten-free diet; in the remaining patients, the per-
sistence of the lesions could be regarded as an indicator of lack
of adherence to the diet.
Conclusion
Pediatric dentists must recognize typical oral lesions, especially
those associated with nutritional deciencies, and should sus-
pect the presence of celiac disease, which can change the dis-
ease’s course and patient’s prognosis.
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Abstract of the Scientific Literature
In a pediatric hospital, how important are inpatient dental consults?
This study evaluated results from one year of inpatient dental consults at a pediatric teaching hospital. The retrospective study reviewed
consult records from January 1 to December 31, 2007. Consultations and treatment from the Emergency Department were not included
in this institutionally approved study. All the dental consults were performed by pediatric dentistry attending faculty. Evaluated variables
included demographics, medical and dental diagnoses, reason for the consult, dental treatment needed and post consult follow-up. These
categorical variables were analyzed for the mean, standard deviation, and range computed as frequencies and percentages. Hematology-
Oncology and Transplant-Oncology consults were analyzed separately and the results compared to consults from all the other medical
service areas. There were 133 inpatient dental consults from 10,988 inpatient total admissions in 2007. Dental Consult inpatients were
aged 4 months to 22 years with 57% males and 48% females of diverse ethnicities. Some inpatients received multiple consults. A dental
home was reported for 48% of the subjects and no dental home for 26%, with 27% unrecorded. The most frequent consultations were
for the Hematology-Oncology service (58, 37%) respectively, with the descending order as Transplant–Oncology (27, 17%), Pediatric Med-
icine (19, 12% ), and Rehabilitation Medicine (12, 8%). The most frequent medical diagnoses were in the areas of Hematology-Oncology,
Oncology, and Neurology. Reasons for dental consults, in descending order, are- baseline examination, oral pain/discomfort, to rule out oral
etiology of fever or infection, and self injuries. Treatment ranged from prevention and education to comprehensive care under general anesthesia.
Comments: In the pediatric hospital setting, the Pediatric Dentistry service continues to play a vital role through its contribution to eval-
uating and treating inpatients with diverse medical and dental diseases and disorders. Hematology-Oncology and Transplant-Oncology
Units are the primary areas of our in-house service as practitioners providing input toward the total health of pediatric inpatients. JGJ
Correspond with Dr. Kanuga at: shukandds@gmail.com
Kanuga K, Sheller B, Williams BJ, Mancl L. A one- year survey of inpatient dental consultations at a children’s hospital. Spec Care Dentist
2012;32:26-31.
11 references
