- Email: [email protected]
Dental enamel defects in adult coeliac disease: Prevalence and correlation with symptoms and age at diagnosis
European Journal of Internal Medicine 24 (2013) 832–834
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original article
Dental enamel defects in adult coeliac disease: Prevalence and correlation with symptoms and age at diagnosis Lucia Trotta a, Federico Biagi a,⁎, Paola I. Bianchi a, Alessandra Marchese a, Claudia Vattiato a, Davide Balduzzi a, Vittorio Collesano b, Gino R. Corazza a a b
Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy Dentistry and Dental Prosthesis, Faculty of Medicine, University of Pavia, Italy
a r t i c l e
i n f o
Article history: Received 25 February 2013 Received in revised form 12 March 2013 Accepted 12 March 2013 Available online 6 April 2013 Keywords: Celiac disease Malabsorption Enamel defects
a b s t r a c t Background: Coeliac disease is a condition characterized by a wide spectrum of clinical manifestations. Any organ can be affected and, among others, dental enamel defects have been described. Our aims were to study the prevalence of dental enamel defects in adults with coeliac disease and to investigate a correlation between the grade of teeth lesion and clinical parameters present at the time of diagnosis of coeliac disease. Methods: A dental examination was performed in 54 coeliac disease patients (41 F, mean age 37 ± 13 years, mean age at diagnosis 31 ± 14 years). Symptoms leading to diagnosis were diarrhoea/weight loss (32 pts.), anaemia (19 pts.), familiarity (3 pts.); none of the patients was diagnosed because of enamel defects. At the time of evaluation, they were all on a gluten-free diet. Enamel defects were classified from grade 0 to 4 according to its severity. Results: Enamel defects were observed in 46/54 patients (85.2%): grade 1 defects were seen in 18 patients (33.3%) grade 2 in 16 (29.6%), grade 3 in 8 (14.8%), and grade 4 in 4 (7.4%). We also observed that grades 3 and 4 were more frequent in patients diagnosed with classical rather than non-classical coeliac disease (10/32 vs. 2/20). However, this was not statistically significant. Conclusion: This study confirms that enamel defects are common in adult coeliac disease. Observation of enamel defects is an opportunity to diagnose coeliac disease. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction Coeliac disease is a chronic enteropathy precipitated by exposure to dietary gluten. Its prevalence in the Western world is very high (1/150) and it is characterized by serious complications that double its mortality rate [1–3]. The histopathological hallmark of coeliac disease is represented by a variable degree of small intestinal villous atrophy that can reduce the absorptive function of the gut. This reduction can be so significant that a frank malabsorption syndrome with diarrhoea, weight loss and nutritional deficiency can develop. Moreover, coeliac patients can complain of symptoms due not only to malabsorption but also to associated conditions. Coeliac disease can therefore present with both gastrointestinal and non gastrointestinal symptoms [1]. From a clinical point of view, it is nowadays quite common to recognise three different forms of coeliac disease: classical, non classical and asymptomatic [4]. Among non classical symptoms, dental enamel defects were described by Aine et al. who observed that more than ⁎ Corresponding author at: Coeliac Centre/1st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, P.le Golgi, 19, I-27100 Pavia, Italy. Tel.: +39 0382 502973; fax: +39 0382 502618. E-mail address: [email protected] (F. Biagi).
80% of coeliac patients presented this kind of defect. More precisely, in coeliac disease dental enamel defects are systematic, being symmetrically and chronologically distributed in all four hemiarches. On the other hand, lesions found on only one side of the hemiarch leaving the other side intact, the so called unsystematic and unspecific defects, were not increased in coeliac disease [5]. Finally, Aine classified enamel defects in five degrees (Table 1). The original work of Aine was performed in Finland and it was later confirmed in other Western countries [6–10]. Dental enamel defects were shown to be associated with HLA-DR3 [9]. In performing this work, we had a twofold aim. First of all we wanted to confirm the high prevalence of dental enamel defects in coeliac patients. Second, we wanted to see whether there is a relationship between enamel defects, classified according to Aine, and clinical features and age at diagnosis of coeliac disease. 2. Patients and methods Between Oct. 2010 and Sept. 2011, eighty-one consecutive patients, attending our out-patient clinic, were invited to take part in this study by undergoing a dental examination. Fifty-four of them (41 F, mean age 37 ± 13 years, mean age at diagnosis 31 ± 14 years) accepted. At this time, they were all on a gluten-free diet. They had been found
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.03.007
L. Trotta et al. / European Journal of Internal Medicine 24 (2013) 832–834
833
Table 1 Classification of enamel defects according to Aine [11]. Grade 0 Grade 1 Grade 2 Grade 3
Grade 4
No defect Defects in colour of enamel. Single or multiple cream, yellow or brown opacities with clearly defined or diffuse margins. Slight structural defects. Rough enamel surface filled with horizontal grooves or shallow pits. Evident structural defects; a part or the entire surface of the enamel is rough and filled with deep horizontal grooves which have large vertical pits. Severe structural defects. The shape of the tooth is altered; the tips of cusps are sharp pointed and/or the incisal edges are unevenly thinned and rough. The thinning of the enamel material is easily detectable and margins of the lesions are well defined.
to be affected by coeliac disease on the basis of small bowel biopsy showing villous atrophy and positive endomysial antibodies [11]. Thirty-two patients were affected by a classical form of coeliac disease, 19 by a non classical for and 3 by an asymptomatic form. None of them was diagnosed because of enamel defects. Patients were seen in the department of Dentistry and Dental Prosthesis of the University of Pavia. After providing written informed consent, teeth were carefully examined. The colour, type and site of dental enamel defects were recorded and classified according to Aine (Table 1) (VC). Dental enamel defects were compared with the clinical type of coeliac disease (classical, non classical, asymptomatic) and age at diagnosis by means of Chi square test. Clinical findings and demographic data were anonymised and recorded in a database. The study was approved by the local ethics committee at the Fondazione IRCCS Policlinico San Matteo. 3. Results Table 2 shows that systematic dental enamel defects were found in 46 out of 54 patients (85.2%). Aine grade 1 type lesion was the most common, being present in 33.3% of the patients. Fig. 1 shows the relationship between degree of Aine lesions and type of clinical presentation. Lesions type 3 and 4, the most severe ones, were mainly found among coeliac patients affected by a classical form of coeliac disease rather than non-classical coeliac disease (10/32 vs. 2/20). However, we have to underline that the difference was not statistically significant and that we studied many more patients with classical than non classical and asymptomatic coeliac disease. Fig. 2 shows the relationship between degree of Aine lesions and age at diagnosis of coeliac disease. Dental enamel defects were more common among patients found to be affected by coeliac disease between the age of 21 to 40 years. However, this difference is not statistically significant and, again, most patients were found to be affected by coeliac disease in that age range.
Fig. 1. Frequency of dental enamel defects according to Aine classification and clinical type of coeliac disease. Patients with non classical and asymptomatic coeliac disease were pooled together. White columns, Aine type 0 lesion; white and grey, Aine 1; grey, Aine 2; grey and black Aine 3; black, Aine 4.
most commonly affected by dental enamel defects are, therefore, incisors, followed by molars, premolars and canines. Moreover, our results seem to suggest that the most severe lesions are mainly found in patients with classical coeliac disease. However, we cannot forget that only 54 out of 81 patients accepted our invitation to undergo a dental examination. We cannot exclude that patients accepting our invitation were those with the most important lesions. The mechanism of development of dental enamel defects in coeliac patients is not yet fully understood. Coeliac disease is well known to induce calcium malabsorption and this can influence the enamel formation which occurs in the first years of life [8]. Since it was suggested that in patients with a classical form of coeliac disease lesions are more extended along the small intestine than in patients with a non classical form [12], we can hypothesise that in patients with classical coeliac disease the more extended lesions resulted in a more severe calcium malabsorption and thus severe dental enamel defects formation. Conversely, patients with non classical and asymptomatic coeliac disease present less diffuse lesions that do not cause significant calcium malabsorption and thus only mild dental enamel defects. So, we can think that dental enamel defects could indicate a hidden form of malabsorption. Starting a strict gluten-free diet as soon as possible is thus likely to protect the patients from this problem too. On the other hand, the presence of dental enamel defects in coeliac patients could indicate that calcium malabsorption started in the first years of life while enamel formation was going on. This is only a hypothesis that needs the study of large sample of coeliac patients diagnosed in different ages to be verified. Finally, we cannot forget that dental enamel defects are not specific to coeliac disease. They can be found not only in other forms of
4. Discussion Our results confirm that dental enamel defects can be found in most coeliac patients. Dental enamel defects are systematic, showing a symmetrical and chronological distribution in all four hemiarches. Teeth Table 2 Prevalence of dental enamel defects in patients affected by coeliac disease (CD), according to the Aine classification [11]. Number of patients affected by CD
54
Unspecific defects Aine 0 Aine 1 Aine 2 Aine 3 Aine 4
2 (3.7%) 6 (11.1%) 18 (33.3%) 16 (29.6%) 8 (14.8%) 4 (7.4%)
Fig. 2. Frequency of dental enamel defects according to Aine classification and age at diagnosis of coeliac disease. Patients with non classical and asymptomatic coeliac disease were pooled together. White columns, Aine type 0 lesion; white and grey, Aine 1; grey, Aine 2; grey and black Aine 3; black, Aine 4.
834
L. Trotta et al. / European Journal of Internal Medicine 24 (2013) 832–834
malabsorption but also in other conditions such as dental fluorosis and tetracycline therapy during dental enamel formation [13]. In conclusion, although our results do not allow us to recommend screening for coeliac disease in all the patients with dental enamel defects, our study confirms that the Aine classification is a helpful and easy tool that can lead to the suspicion of coeliac disease in the dental field. Learning points • Coeliac disease is a frequent condition characterized by a wide spectrum of clinical manifestations, including dental enamel defects. • Enamel defects were observed in the vast majority of patients. • The most severe lesions were found in patients diagnosed with classical rather than non-classical CD, although this was not statistically significant. • This study confirms that enamel defects are associated with adult CD. • Observation of enamel defects is an opportunity to diagnose CD. Conflict of interests The authors have no conflict of interest. This work received no funding. Acknowledgement We are grateful to Susan West for reading and correcting the article and to Mr. Mattia Gasparella for technical assistance.
References [1] Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet 2001;358: 356–61. [2] Biagi F, Klersy C, Balduzzi D, Corazza GR. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med 2010;42:557–61. [3] Biagi F, Lorenzini P, Corazza GR. Literature review on the clinical relationship between ulcerative jejunoileitis, coeliac disease and enteropathy associated T cell lymphoma. Scand J Gastroenterol 2000;35:785–90. [4] Ludvigsson JF, Leffler DA, Bai J, Biagi F, Fasano A, Green PHR, et al. The Oslo definitions for coeliac disease and related terms.Gut 2013;62:43–52 [2]. [5] Aine L, Mäki M, Collin P, Keyriläinen O. Dental enamel defects in celiac disease. J Oral Pathol Med 1990;19:241–5. [6] 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. [7] Aguirre JM, Rodriguez R, Oribe D, Vitoria JC. Dental enamel defects in celiac patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:646–50. [8] Cheng J, Malahias T, Brar P, Minaya MT, Green PH. The association between celiac disease, dental enamel defects, and aphthous ulcers in a United States cohort. J Clin Gastroenterol 2010;44:191–4. [9] Mariani P, Mazzilli MC, Margutti G, Lionetti P, Triglione P, Petronzelli F, et al. Coeliac disease, enamel defects and HLA typing. Acta Paediatr 1994;83:1272–5. [10] Aine L. Permanent tooth dental enamel defects leading to the diagnosis of coeliac disease. Br Dent J 1994;177:253–4. [11] Biagi F, Pezzimenti D, Campanella J, Vadacca GB, Corazza GR. Endomysial and tissue transglutaminase antibodies in coeliac sera. A comparison not influenced by previous serological testing. Scand J Gastroenterol 2001;36:955–8. [12] Macdonald WC, Brandborg LL, Flick AL, Trier JS, Rubin CE. Studies of celiac sprue. IV. The response of the whole length of the small bowel to a gluten-free diet. Gastroenterology 1964;47:573–89. [13] Ralph PM, Troutman KC. The oral manifestations of intestinal lymphangiectasia: case report. Pediatr Dent 1996;18:461–4.
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original article
Dental enamel defects in adult coeliac disease: Prevalence and correlation with symptoms and age at diagnosis Lucia Trotta a, Federico Biagi a,⁎, Paola I. Bianchi a, Alessandra Marchese a, Claudia Vattiato a, Davide Balduzzi a, Vittorio Collesano b, Gino R. Corazza a a b
Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy Dentistry and Dental Prosthesis, Faculty of Medicine, University of Pavia, Italy
a r t i c l e
i n f o
Article history: Received 25 February 2013 Received in revised form 12 March 2013 Accepted 12 March 2013 Available online 6 April 2013 Keywords: Celiac disease Malabsorption Enamel defects
a b s t r a c t Background: Coeliac disease is a condition characterized by a wide spectrum of clinical manifestations. Any organ can be affected and, among others, dental enamel defects have been described. Our aims were to study the prevalence of dental enamel defects in adults with coeliac disease and to investigate a correlation between the grade of teeth lesion and clinical parameters present at the time of diagnosis of coeliac disease. Methods: A dental examination was performed in 54 coeliac disease patients (41 F, mean age 37 ± 13 years, mean age at diagnosis 31 ± 14 years). Symptoms leading to diagnosis were diarrhoea/weight loss (32 pts.), anaemia (19 pts.), familiarity (3 pts.); none of the patients was diagnosed because of enamel defects. At the time of evaluation, they were all on a gluten-free diet. Enamel defects were classified from grade 0 to 4 according to its severity. Results: Enamel defects were observed in 46/54 patients (85.2%): grade 1 defects were seen in 18 patients (33.3%) grade 2 in 16 (29.6%), grade 3 in 8 (14.8%), and grade 4 in 4 (7.4%). We also observed that grades 3 and 4 were more frequent in patients diagnosed with classical rather than non-classical coeliac disease (10/32 vs. 2/20). However, this was not statistically significant. Conclusion: This study confirms that enamel defects are common in adult coeliac disease. Observation of enamel defects is an opportunity to diagnose coeliac disease. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction Coeliac disease is a chronic enteropathy precipitated by exposure to dietary gluten. Its prevalence in the Western world is very high (1/150) and it is characterized by serious complications that double its mortality rate [1–3]. The histopathological hallmark of coeliac disease is represented by a variable degree of small intestinal villous atrophy that can reduce the absorptive function of the gut. This reduction can be so significant that a frank malabsorption syndrome with diarrhoea, weight loss and nutritional deficiency can develop. Moreover, coeliac patients can complain of symptoms due not only to malabsorption but also to associated conditions. Coeliac disease can therefore present with both gastrointestinal and non gastrointestinal symptoms [1]. From a clinical point of view, it is nowadays quite common to recognise three different forms of coeliac disease: classical, non classical and asymptomatic [4]. Among non classical symptoms, dental enamel defects were described by Aine et al. who observed that more than ⁎ Corresponding author at: Coeliac Centre/1st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, P.le Golgi, 19, I-27100 Pavia, Italy. Tel.: +39 0382 502973; fax: +39 0382 502618. E-mail address: [email protected] (F. Biagi).
80% of coeliac patients presented this kind of defect. More precisely, in coeliac disease dental enamel defects are systematic, being symmetrically and chronologically distributed in all four hemiarches. On the other hand, lesions found on only one side of the hemiarch leaving the other side intact, the so called unsystematic and unspecific defects, were not increased in coeliac disease [5]. Finally, Aine classified enamel defects in five degrees (Table 1). The original work of Aine was performed in Finland and it was later confirmed in other Western countries [6–10]. Dental enamel defects were shown to be associated with HLA-DR3 [9]. In performing this work, we had a twofold aim. First of all we wanted to confirm the high prevalence of dental enamel defects in coeliac patients. Second, we wanted to see whether there is a relationship between enamel defects, classified according to Aine, and clinical features and age at diagnosis of coeliac disease. 2. Patients and methods Between Oct. 2010 and Sept. 2011, eighty-one consecutive patients, attending our out-patient clinic, were invited to take part in this study by undergoing a dental examination. Fifty-four of them (41 F, mean age 37 ± 13 years, mean age at diagnosis 31 ± 14 years) accepted. At this time, they were all on a gluten-free diet. They had been found
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.03.007
L. Trotta et al. / European Journal of Internal Medicine 24 (2013) 832–834
833
Table 1 Classification of enamel defects according to Aine [11]. Grade 0 Grade 1 Grade 2 Grade 3
Grade 4
No defect Defects in colour of enamel. Single or multiple cream, yellow or brown opacities with clearly defined or diffuse margins. Slight structural defects. Rough enamel surface filled with horizontal grooves or shallow pits. Evident structural defects; a part or the entire surface of the enamel is rough and filled with deep horizontal grooves which have large vertical pits. Severe structural defects. The shape of the tooth is altered; the tips of cusps are sharp pointed and/or the incisal edges are unevenly thinned and rough. The thinning of the enamel material is easily detectable and margins of the lesions are well defined.
to be affected by coeliac disease on the basis of small bowel biopsy showing villous atrophy and positive endomysial antibodies [11]. Thirty-two patients were affected by a classical form of coeliac disease, 19 by a non classical for and 3 by an asymptomatic form. None of them was diagnosed because of enamel defects. Patients were seen in the department of Dentistry and Dental Prosthesis of the University of Pavia. After providing written informed consent, teeth were carefully examined. The colour, type and site of dental enamel defects were recorded and classified according to Aine (Table 1) (VC). Dental enamel defects were compared with the clinical type of coeliac disease (classical, non classical, asymptomatic) and age at diagnosis by means of Chi square test. Clinical findings and demographic data were anonymised and recorded in a database. The study was approved by the local ethics committee at the Fondazione IRCCS Policlinico San Matteo. 3. Results Table 2 shows that systematic dental enamel defects were found in 46 out of 54 patients (85.2%). Aine grade 1 type lesion was the most common, being present in 33.3% of the patients. Fig. 1 shows the relationship between degree of Aine lesions and type of clinical presentation. Lesions type 3 and 4, the most severe ones, were mainly found among coeliac patients affected by a classical form of coeliac disease rather than non-classical coeliac disease (10/32 vs. 2/20). However, we have to underline that the difference was not statistically significant and that we studied many more patients with classical than non classical and asymptomatic coeliac disease. Fig. 2 shows the relationship between degree of Aine lesions and age at diagnosis of coeliac disease. Dental enamel defects were more common among patients found to be affected by coeliac disease between the age of 21 to 40 years. However, this difference is not statistically significant and, again, most patients were found to be affected by coeliac disease in that age range.
Fig. 1. Frequency of dental enamel defects according to Aine classification and clinical type of coeliac disease. Patients with non classical and asymptomatic coeliac disease were pooled together. White columns, Aine type 0 lesion; white and grey, Aine 1; grey, Aine 2; grey and black Aine 3; black, Aine 4.
most commonly affected by dental enamel defects are, therefore, incisors, followed by molars, premolars and canines. Moreover, our results seem to suggest that the most severe lesions are mainly found in patients with classical coeliac disease. However, we cannot forget that only 54 out of 81 patients accepted our invitation to undergo a dental examination. We cannot exclude that patients accepting our invitation were those with the most important lesions. The mechanism of development of dental enamel defects in coeliac patients is not yet fully understood. Coeliac disease is well known to induce calcium malabsorption and this can influence the enamel formation which occurs in the first years of life [8]. Since it was suggested that in patients with a classical form of coeliac disease lesions are more extended along the small intestine than in patients with a non classical form [12], we can hypothesise that in patients with classical coeliac disease the more extended lesions resulted in a more severe calcium malabsorption and thus severe dental enamel defects formation. Conversely, patients with non classical and asymptomatic coeliac disease present less diffuse lesions that do not cause significant calcium malabsorption and thus only mild dental enamel defects. So, we can think that dental enamel defects could indicate a hidden form of malabsorption. Starting a strict gluten-free diet as soon as possible is thus likely to protect the patients from this problem too. On the other hand, the presence of dental enamel defects in coeliac patients could indicate that calcium malabsorption started in the first years of life while enamel formation was going on. This is only a hypothesis that needs the study of large sample of coeliac patients diagnosed in different ages to be verified. Finally, we cannot forget that dental enamel defects are not specific to coeliac disease. They can be found not only in other forms of
4. Discussion Our results confirm that dental enamel defects can be found in most coeliac patients. Dental enamel defects are systematic, showing a symmetrical and chronological distribution in all four hemiarches. Teeth Table 2 Prevalence of dental enamel defects in patients affected by coeliac disease (CD), according to the Aine classification [11]. Number of patients affected by CD
54
Unspecific defects Aine 0 Aine 1 Aine 2 Aine 3 Aine 4
2 (3.7%) 6 (11.1%) 18 (33.3%) 16 (29.6%) 8 (14.8%) 4 (7.4%)
Fig. 2. Frequency of dental enamel defects according to Aine classification and age at diagnosis of coeliac disease. Patients with non classical and asymptomatic coeliac disease were pooled together. White columns, Aine type 0 lesion; white and grey, Aine 1; grey, Aine 2; grey and black Aine 3; black, Aine 4.
834
L. Trotta et al. / European Journal of Internal Medicine 24 (2013) 832–834
malabsorption but also in other conditions such as dental fluorosis and tetracycline therapy during dental enamel formation [13]. In conclusion, although our results do not allow us to recommend screening for coeliac disease in all the patients with dental enamel defects, our study confirms that the Aine classification is a helpful and easy tool that can lead to the suspicion of coeliac disease in the dental field. Learning points • Coeliac disease is a frequent condition characterized by a wide spectrum of clinical manifestations, including dental enamel defects. • Enamel defects were observed in the vast majority of patients. • The most severe lesions were found in patients diagnosed with classical rather than non-classical CD, although this was not statistically significant. • This study confirms that enamel defects are associated with adult CD. • Observation of enamel defects is an opportunity to diagnose CD. Conflict of interests The authors have no conflict of interest. This work received no funding. Acknowledgement We are grateful to Susan West for reading and correcting the article and to Mr. Mattia Gasparella for technical assistance.
References [1] Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet 2001;358: 356–61. [2] Biagi F, Klersy C, Balduzzi D, Corazza GR. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med 2010;42:557–61. [3] Biagi F, Lorenzini P, Corazza GR. Literature review on the clinical relationship between ulcerative jejunoileitis, coeliac disease and enteropathy associated T cell lymphoma. Scand J Gastroenterol 2000;35:785–90. [4] Ludvigsson JF, Leffler DA, Bai J, Biagi F, Fasano A, Green PHR, et al. The Oslo definitions for coeliac disease and related terms.Gut 2013;62:43–52 [2]. [5] Aine L, Mäki M, Collin P, Keyriläinen O. Dental enamel defects in celiac disease. J Oral Pathol Med 1990;19:241–5. [6] 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. [7] Aguirre JM, Rodriguez R, Oribe D, Vitoria JC. Dental enamel defects in celiac patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:646–50. [8] Cheng J, Malahias T, Brar P, Minaya MT, Green PH. The association between celiac disease, dental enamel defects, and aphthous ulcers in a United States cohort. J Clin Gastroenterol 2010;44:191–4. [9] Mariani P, Mazzilli MC, Margutti G, Lionetti P, Triglione P, Petronzelli F, et al. Coeliac disease, enamel defects and HLA typing. Acta Paediatr 1994;83:1272–5. [10] Aine L. Permanent tooth dental enamel defects leading to the diagnosis of coeliac disease. Br Dent J 1994;177:253–4. [11] Biagi F, Pezzimenti D, Campanella J, Vadacca GB, Corazza GR. Endomysial and tissue transglutaminase antibodies in coeliac sera. A comparison not influenced by previous serological testing. Scand J Gastroenterol 2001;36:955–8. [12] Macdonald WC, Brandborg LL, Flick AL, Trier JS, Rubin CE. Studies of celiac sprue. IV. The response of the whole length of the small bowel to a gluten-free diet. Gastroenterology 1964;47:573–89. [13] Ralph PM, Troutman KC. The oral manifestations of intestinal lymphangiectasia: case report. Pediatr Dent 1996;18:461–4.