Abstract
Aim
The oral cavity is part of the gastrointestinal system and as such the presence of alterations in this district can be the first sign of both systemic and gastrointestinal diseases. As such alterations are very common, especially in children, it is important for the dentist to distinguish when they are the expression of a gastrointestinal condition. The aim of this review is to provide the dental practitioner with useful data for the diagnosis, treatment and management of the most common conditions, such as Crohn’s disease, ulcerative colitis, gastro-esophageal reflux disease, and celiac disease.
Results
One of the most common oral alterations is tooth erosion, with enamel loss and an increased risk of dental caries, which have been reported in children and adolescents with gastro-esophageal reflux. Dental enamel hypoplasia and aphthous ulcers have been found to be more common in children with celiac disease than in the general population.
Another very common oral alteration is gingivitis, which is reported to affect 9-95% of children in Europe and in North America and more than 60% of adolescents [Italian Ministry of Health, Guidelines 2013].
Pyostomatitis vegetans can be a sign of ulcerative colitis and Crohn’s disease, the latter has also been related to diffuse mucosal swelling, cobblestone mucosa, localized muco-gingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, and aphthous-like ulcers.
Conclusion
A prompt recognition of systemic and gastrointestinal diseases through a careful examination of the oral cavity could be the first step of further investigations that may lead to an early diagnosis and timely treatment.
Keywords
Alterations of the oral cavity, Celiac disease, Crohn’s disease, Gastro-esophageal reflux disease, Gastrointestinal diseases, Ulcerative colitis.
Introduction
Correlations between alterations in the oral cavity and systemic conditions have been widely reported (Chi, 2010; Majorana, 2010) and during the oral examination it is also possible to detect signs and symptoms of systemic diseases, such as mucocutaneous, immunologic disorders, hormone diseases, haematological conditions, systemic infections, and nutritional problems (US Department of Health, 2000). In particular, alterations in the oral cavity, as it is part of the gastrointestinal (GI) system, may reveal a GI disease, such as celiac disease, gastroesophageal reflux disease or inflammatory bowel disease.
Oral manifestations include dental enamel defects, dental caries and aphthous ulcers which have been reported to occur in subjects with celiac disease and to regress with a gluten-free diet [Pastore, 2008]. Tooth erosion can be a consequence of gastroesophageal reflux disease [Tolia, 1997; Bishop, 1994; Schroeder, 1995], and the latter can be diagnosed in 25–83% of patients with caries, many of whom are children [-Smith, 2015]. It is worthwhile mentioning that in recent years an increase in tooth erosion has been highlighted (Mulic et al., 2013); in Europe its prevalence has been reported to be higher than 50% in young adults (age 18-35 years) (Bartlett et al., 2013).
Other oral manifestations common in Crohn’s disease include geographic tongue, ulcers, stomatitis and periodontal disease [Bishop, 1972; Stankler, 1972; Van Dyke, 1986]. Moreover, oral alterations can be detected in up to one-third of pediatric patients with ulcerative colitis and are usually nonspecific [Katsanos, 2015].
The spectrum of oral lesions is wide, especially in children, and therefore it is important for the dentist to understand which are most commonly associated with GI diseases as well as their approach and management, in order to make a correct differential diagnosis and provide adequate treatment. The role of the dentist is very important in these situations, as symptoms are often unrecognized or overlooked by gastroenterologists (Harty et al., 2005) and in many cases diagnosis is made when a specialist in oral medicine or dentistry is involved (Pittock et al., 2001; Campbell et al., 2011; Lankarani et al., 2013).
The aim of this article is to review the literature on oral lesions associated with GI diseases, in order to provide useful data for the diagnosis, treatment and management of the most common conditions, such as Crohn’s disease, ulcerative colitis, gastro-esophageal reflux disease, and celiac disease.
Crohn’s disease
Since the mid-1970s the Incidence of Crohn’s disease (CrD), a chronic relapsing inflammatory condition, has increased in Western countries (Hovde and Moum, 2012), with a prevalence varying from less than 10 to about 150 per 100,000 inhabitants in European countries (Yapp et al., 2000; Gheorghe et al., 2004). CrD has a complex aetiology and its pathogenesis is still uncertain (Crippa et al. 2016).
Lesions within the oral cavity can represent an initial and primary manifestation of CrD [Daley, 2007; Hussey, 2011; Boirivant, 2012] or may occur concurrently, or follow the onset of GI involvement [Kalmar, 2000]; however oral lesions without gastrointestinal involvement are rarely reported in the literature [Zbar, 2012; Fatahzadeh, 2009; Chi, 2010; Daley, 2007]. These lesions may be a consequence of low serum levels of micronutrients and macronutrients secondary to malabsorption [Jacobs, 1968] or to local immune reactions to oral antigens typical of CrD [Lehner, 1972; Basu, 1976].
Oral CrD can be detected in the buccal mucosa, lips, tongue, hard and soft palate, salivary glands, gingiva and teeth with alterations that can either be typical and pathognomonic, in most cases associated with or highly suspicious for inflammatory bowel disease, or nonspecific [Katsanos, 2015].
The prevalence of Oral CrD is about 20%, but it has been reported as high as 50% (Laube et al, 2017; Pittock et al., 2001; Rowland et al., 2010; Lankarani et al., 2013) especially in the younger age groups, as these subjects seem to have a lower age of manifestation with respect to the average CrD population (Mahid et al., 2008).
In up to 5-15% of subjects affected by CrD a typical acute oral manifestation, defined orofacial CrD, may arise and show as recurrent or persistent lip swelling, cobblestone of the oral mucosa, stomatitis, mucogingivitis, deep linear or serpiginous ulcerations surrounded by epithelial hyperplasia, tissue tags or polyps, often related to Candida-associated angular cheilitis [Boirivant, 2012; Fatahzadeh, 2009; Katsanos, 2015; Tilakaratne, 2008; Kolho, 2011; Wiesenfeld, 1985; Van der Waal, 2002]. Macroscopic and histological characteristics of this manifestation are similar to those found in the gastrointestinal tract [Stankler, 1972] and can be associated with pain on touch or on eating acidic or spicy foods, impairment of oral function, eating, speaking, and psychosocial stress [Plauth, 1991]. Characteristic oral alterations of CrD include orofacial CrD, granulomatous cheilitis and pyostomatitis vegetans.
Diagnosis can be very difficult, since orofacial CrD is undistinguishable from orofacial granulomatosis, which can be detected in several conditions (such as sarcoidosis, Miescher’s cheilitis granulomatosa, Melkersson-Rosenthal syndrome, foreign body granuloma, rosacea, and various granulomatous infectious diseases) [Wiesenfeld, 1985; Bogenrieder, 2003]. Up to 40-50% of young patients with orofacial granulomatosis might develop CrD and it may be noticed even years after the first appearance of oral symptoms [Rowland, 2010].
Harty et al. [2005] reported that granulomatous inflammation was present in 100% of biopsies collected in their study, thus underscoring that oral mucosa represents an easily accessible site for harvesting diagnostic material.
Granulomatous cheilitis is a sub-acute uncommon granulomatous inflammation involving the lip area [Allen, 1990] and is described as an initial sudden swelling of the lips, mainly the lower one, which resolves within hours or days, but is followed by permanent edema and lumpy swelling [Friedrich, 1990; Alawi, 2005]. This condition can also be a sign of other diseases such as allergy, sarcoidosis, Melkersson-Rosenthal syndrome, relapsing herpes simplex, relapsing erysipelas, cancers and genetic disorders [Katsanos, 2015].
Pyostomatitis vegetans is a rare manifestation showing thickened and erythematous oral mucosa covered with pustules and superficial erosions with a ‘snail tracks’ pattern. It has been associated in 75% of cases with inflammatory bowel disease [Ayangco, 2002; Lankarani, 2013; Delaporte, 1998] and can also be an expression of autoimmune pemphigoid diseases and infections [Hansen, 1983].
Other oral lesions suggestive of CrD are cobblestoning, mucogingivitis, gingival hypertrophy, lip swelling with vertical fissures, midline lip fissuring, deep linear ulcers of the buccal and labial mucosa and indurated tag-like lesions [Greenstein, 1976; Lisciandrano, 1996; Field, 1989; Colella, 1971; Lourenço, 2010].
CrD has also been related to non-specific lesions such as recurrent aphthous stomatitis (RAS), dry mouth, salivary duct fistula, recurrent buccal infections, persisting buccal space, aseptic abscesses, pustular ulcerations, erythema, swelling and cobblestoning of the gingiva, mandibular osteomyelitis [Correl, 1981; Delaporte, 1998; Gargiulo, 1989; Ciantar, 2007].
As for diagnostic examinations, Van der Waal et al. [2002] do not recommend routine investigation of the gastrointestinal tract in patients with a negative history of gastrointestinal conditions, whereas Plauth et al. [1991] recommend exhaustive and repeated investigations for CrD in cases of orofacial granulomatosis even when no gastrointestinal symptoms are present; endoscopy is recommended in patients with bowel symptoms or/and highly specific types of oral lesions [Katsanos, 2015]. Periodical screening of fecal calprotectin, a surrogate marker for mucosal inflammation (e.g. in CrD), is also suggested [Roseth, 1999; Sipponen, 2008].
Oral CrD treatment may include steroid therapy [Hussey, 2011; Harikishan, 2012], tumor necrosis factor-alpha-antagonist agent infliximab (administered promising results in chronic granulomatous cheilitis and in a case of orofacial CrD and lip swelling not responsive to any other treatment) [Peitsch, 2007; Barry, 2005], and, rarely, methotrexate.
Ulcerative colitis
Ulcerative colitis (UC) is considered with CrD the most common type of inflammatory bowel disease, with the highest incidence in subjects aged between 15 and 25 years and a second, smaller peak between 55 and 65 years (Mantegazza et al., 2016a).
Like CrD, also UC is immunologically based [Lourenço, 2010), UC and CrD also share some clinical manifestations, such as mucosal ulcers (Seo, 1992), pyostomatitis vegetans (Alstead, 1991; Calobrisi, 1995), diffuse pustules (O’Laughlin, 1978) and lichen planus (Alstead, 1991; Davies, 1984). In addition, some medications used for the treatment of GI diseases are sometimes responsible for oral side effects (Parvinen, 1984; Sreebny, 1986).
Again, pyostomatitis vegetans manifests as multiple miliary white or yellow pustules that can merge in snail-trail ulcers, with an erythematous and edematous mucosal base involving mostly the labial gingiva and the labial and buccal mucosa. It is can be diagnosed when a combination of clinical features of inflammatory bowel disease, peripheral eosinophilia, histological findings, and negative culture of the exudate are present [Mijandrusi-Sinci, 2010]. Average age at diagnosis is usually about 34 years.
Other non-specific oral manifestations in UC are oral aphthae (5-10% of patients), glossitis, cheilitis, stomatitis, lichen planus, mucosal ulcers, diffuse pustules, and non-specific gingivitis [Folashade, 2008; Lekovi, 2011; Krebs, 2011].
Diagnosis of UC is based on the presence of bloody diarrhea with negative stool cultures and diffuse continuous mucosal inflammation involving the rectum and extending to a point more proximal in the colon at the endoscopic evaluation [Kugathasan, 2003; Bentsen, 2002].
Treatment includes oral steroids [Thrash, 2013]. However, a dental evaluation can be useful during the investigation of patients with suspected UC (Elahi, 2012).
Gastro-esophageal reflux disease
Gastro-esophageal reflux is the physiologic movement of gastric content into the esophagus and oropharynx occurring through the relaxation of the lower esophageal sphincter; it can become pathologic [Colletti, 2003] when repeated regurgitation, nausea, heartburn, coughing, laryngitis, asthma, or pneumonia occur and is therefore defined Gastro-esophageal reflux disease (GERD). It can also be accompanied by secondary complications such as esophagitis, hemorrhage, stricture, Barrett’s esophagus, and adenocarcinoma [Vakil, 2006].
A strong association between GERD and DE has been reported (Pace, 2008). The 2009 NASPGHAN and ESPGHAN guidelines on reflux in children report that oral manifestations have also been described in GERD, and in particular its correlation with dental erosions [Vandenplas, 2009; Pindborg, 1970]; in fact, their prevalence in children with GERD has been reported as high as 83.3% [Dahshan et al., 2010], though in the literature different figures are reported.
It is worthwhile mentioning that in GERD subjects tooth erosion mainly involves the mixed dentition and starts from the posterior area, in particular facial, occlusal, and lingual surfaces [Dahshan et al., 2010]. In these situations, administration of proton pump inhibitors has proven to be effective [Wilder-Smith et al., 2009].
GERD may also be the cause of changes in soft tissues and salivary flow [Silva, 2001]; Di Fede et al. [2008] reported a significant association of GERD with oral acid⁄burning sensation, xerostomia, subjective halitosis and soft⁄hard palate and uvula mucosal erythema.
Celiac disease
Celiac disease (CD) is an autoimmune condition that may develop as a consequence of the consumption of gluten [Barker and Liu, 2008] in genetically susceptible subjects. Its incidence has increased over the last decades, and presently it is one of the most common, lifelong disorders worldwide (Mantegazza et al. 2016b), with an estimated mean prevalence of 0.9% [Lionetti, 2014].
Oral alterations related to CD include: dental enamel defects, delayed eruption, recurrent aphthous stomatitis, atrophic glossitis, xerostomia, cheilosis and oral lichen planus [Rashid, 2011; Tack, 2010].
As dental enamel defects are more common in patients with CD than in the general population [Rashid, 2011], the presence of specific dental enamel defects is considered suggestive of the disease [Hill, 2005], especially when they appear symmetrically and chronologically in all 4 quadrants, with more defects in the maxillary and mandibular incisors and molars that often show intact cusps [Rashid, 2011]. A classification of the localized enamel defects in CD was developed by Aine et al. in 1990, including pitting, grooving and sometimes complete loss of enamel.
Campisi et al. [2008] and Condò et al. (2011) observed a higher occurrence of delayed eruption in children with CD in comparison with healthy children.
Another very common condition in CD is recurrent aphthous stomatitis. This oral ulcerative disease affects 10%–20% of the general population and, according to Sedghizadeh et al. (2002), 41% of CD subjects have a history of this oral alteration compared to 27% of the healthy controls. It manifests with single or multiple recurrent ulcers on the oral mucosa, with a round or ovoid shape and an erythematous halo and a yellow or gray floor.
Atrophic glossitis is a condition characterized by red, smooth, shiny tongue caused by vitamin B12 deficiency [Trandafir, 2014]; xerostomia due to salivary gland dysfunction with diminished salivary flow that develops after gluten exposure [Lähteenoja, 1998; Shetyer, 2013; Ertekin, 2005]; angular cheilitis due to malabsorption [Rashid, 2011].
Until 2012, positivity for anti-transglutaminase and/or anti-endomysium antibodies associated with characteristic histological findings based on multiple biopsies of duodenum were required to diagnose CD [Benkebil, 2013]. Currently an algorithm which can be found In the European pediatric guidelines permits to avoid biopsy in children with typical clinical symptoms, >10-fold anti-transglutaminase antibody titer with positive anti-endomysium antibodies and a genotype compatible with CD development [Husby, 2012].
In all cases, a gluten-free diet is the most effective treatment for CD [Husby, 2012].
Conclusion
Considering the high frequency of alterations that can arise in the oral cavity of children, the dentist should be able to detect those lesions that need a thorough diagnostic work-up. In these cases a multidisciplinary approach, including gastroenterologists, radiologists and surgeons as well as dentists and oral medicine specialists, could improve diagnosis and patient management (Laube et al., 2018).
Oral mucosal lesions, especially in children, are important clues to diagnose systemic diseases of which they may be the primary presenting sign, preceding gastrointestinal symptoms. One of the first steps to diagnosis of GI diseases begins with a clinical dental examination of the whole oral cavity and a detailed medical history (Mantegazza et al., 2016c); therefore, dentists are encouraged to inquire about symptoms associated to these disorders and family history of GI diseases that represent potential etiological factors associated with oral disease. As the presence of suspicious oral alterations requires interdisciplinary cooperation, communication between gastroenterologists and dentists is mandatory for the success of the treatment.
References
- Italian Ministry of Health, Guidelines. Linee guida nazionali per la promozione della salute orale e la prevenzione delle patologie orali in età evolutiva, 2014 Ministero del lavoro, della Salute e delle Politiche Sociali. 2013.
- Chi AC, Neville BW, Krayer JW, Gonsalves WC. Oral manifestations of systemic disease. Am Fam Physician 2010 Dec 1;82(11):1381-8.
- 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 Jul;110(1):e13-8. doi: 10.1016/j.tripleo.2010.02.025. Epub 2010 May 10.
- US Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health: 2000; 1–308.
- Pastore L, Campisi G, Compilato D, Lo Muzio L. Orally based diagnosis of celiac disease: current perspectives. J Dent Res 2008; 87(12): 1100-7.
- Pastore L, Carroccio A, Compilato D, Panzarella V, Serpico R, Lo Muzio L. Oral manifestations of celiac disease. J Clin Gastroenterol 2008;42(3):224-32.
- Tolia V. Evaluation and management of pediatric gastroesophageal reflux. Fam Pract Recert 1997;19:35-57.
- Bishop RP, Brewster AC, Antonioli DA. Crohn’s disease of the mouth. Gastroenterology 1972;62:302-6.
- Bishop K, Briggs P, Kelleher M. The aetiology and management of localized anterior tooth wear in the young adult [review]. Dent Update 1994;21:153-60.
- Schroeder P, Filler S, Ramirez B, Lazarchik D, Vaezi M, Richter J. Dental erosion and acid reflux disease. Ann Intern Med 1995;122:809-15.
- Smith CH1, Materna A2, Martig L3, Lussi A4. Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study. United European Gastroenterol J 2015 Apr;3(2):174-81.
- Mulic A, Tveit AB, Skaare AB. Prevalence and severity of dental erosive wear among a group of Norwegian 18-year-olds. Acta Odontol Scand 2013;71:475-481.
- Bartlett DW, Lussi A, West NX, Bouchard P, Sanz M, Bourgeois D. Prevalence of tooth wear on buccal and lingual surfaces and possible risk factors in young European adults. J Dent 2013;41:1007-1013.
- Stankler L, Ewen SWB, Kerr NW. Crohn’s disease of the mouth. Br J Dermatol 1972;87:501-4.
- Van Dyke TE, Dowell VR Jr, Offenbacher S, Snyder W, Hersh T. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect Immun 1986;53:671-7.
- Katsanos KH, Torres J, Roda G, Brygo A, Delaporte E, Colombel JF. Review article: non-malignant oral manifestations in inflammatory bowel diseases. Aliment Pharmacol Ther 2015 Jul; 42(1): 40-60.
- Harty S, Fleming P, Rowland M et al. A prospective study of the oral manifestations of Crohn’s disease. Clinical Gastroenterology Hepatology 2005; 3 (9): 886–891.
- › Pittock S, Drumm B, Fleming P et al.The oral cavity in Crohn's disease. J. Pediatr 2001; 138: 767–771.
- Campbell H, Escudier M, Patel P et al. Distinguishing orofacial granulomatosis from Crohn's disease: two separate disease entities? Inflamm Bowel Dis 2011; 17: 2109–2115.
- Lankarani KB, Sivandzadeh GR, Hassanpour S. Oral manifestation in inflammatory bowel disease: a review. World J Gastroenterol 2013; 19: 8571–8579.
- Hovde Ø, Moum BA. Epidemiology and clinical course of Crohn's disease: Results from observational studies. World J Gastroenterol. 2012 Apr 21; 18(15): 1723–1731.
- Yapp TR, Stenson R, Thomas GA, Lawrie BW, Williams GT, Hawthorne AB. Crohn’s disease incidence in Cardiff from 1930: an update for 1991-1995. Eur J Gastroenterol Hepatol. 2000;12:907–911.
- Gheorghe C, Pascu O, Gheorghe L, Iacob R, Dumitru E, Tantau M, Vadan R, Goldis A, Balan G, Iacob S, et al. Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study. Eur J Gastroenterol Hepatol 2004;16:1153–1159.
- Crippa R, Zuccotti GV, Mantegazza C. Oral manifestations of gastrointestinal diseases in children. Part 2: Crohn’s disease. Eur J Paediatr Dent 2016;17(2):164-166.
- Daley TD, Armstrong JE. Oral manifestations of gastrointestinal diseases. Can J Gastroenterol 2007; 21: 241-244.
- Hussey S, Fleming P, Rowland M, Harty S, Chan L, Broderick A et al. Disease outcome for children who present with oral manifestation of Crohn’s disease. Eur Arch Paediatr Dent 2011; 12:167–9.
- Boirivant M, Cossu A. Inflammatory bowel disease. Oral Diseases 2012; 18 (1): 1–15.
- Kalmar JR. Crohn’s disease: orofacial considerations and disease pathogenesis. Periodontology 2000 1994; 6: 101–115.
- Zbar AP, Ben-Horin S, Beer-Gabel M, Eliakim R. Oral Crohn’s Disease: is it a separable disease from orofacial granulomatosis? J Crohns Colitis 2012;6:134–42.
- Fatahzadeh M, Schwartz RA, Kapila R, Rochford C. Orofacial Crohn’s disease: an oral enigma. Acta Dermatovenerol Croat 2009;17:289–300.
- Jacobs A, Cavill I. The oral lesions of iron deficiency anaemia: pyridoxine and riboflavin status. Br J Haematol 1968;14:291-5.
- Lehner T. Cell-mediated immune response in oral disease: a review. J Oral Pathol 1972;1:39-58.
- Basu MK. Oral manifestations of Crohn’s disease: studies in the pathogenesis. Proc R Soc Med 1976;69:765-6.
- Mahid SS, Mulhall AM, Gholson RD et al. Inflammatory bowel disease and African Americans: a systematic review. Inflamm Bowel Dis 2008;14: 960–
- Laube R, Liu K, Schifter M, Yang JL, Suen MK, Leong RW. Oral and upper gastrointestinal Crohn's disease. J Gastroenterol Hepatol 2018 Feb;33(2):355-364.
- Rowland M, Fleming P, Bourke B. Looking in the mouth for Crohn's disease. Bowel Dis.2010; 16: 332–337.
- Tilakaratne WM, Freysdottir J, Fortune F. Orofacial granulomatosis: review on etiology and pathogenesis. J Oral Pathol Med 2008; 37: 191–195.
- Kolho KL, Heiskanen K, Verkasalo M, Pitkäranta A. Orofacial granulomatosis in children- a challenge for diagnosis and treatment. Int J Pediatr Otorhinolaryngol 2011 Jun; 75(6): 864-7.
- Wiesenfeld D, Ferguson MM, Mitchell DN et al. Oro-facial granulomatosis – a clinical and pathological analysis. Q J Med 1985; 54: 101–113.
- Van der Waal RIF, Schulten EAJM, van der Meij EH et al. Cheilitis granulomatosa: overview of 13 patients with long-term follow-up – results of management. Int J Dermatol 2002; 41: 225–229.
- Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn’s disease, an analysis of 79 cases. J Clin Gastroenterol 1991; 13: 29–37.
- Bogenrieder T, Rogler G, Vogt T et al. Orofacial granulomatosis as the initial presentation of Crohn’s disease in an adolescent. Dermatology 2003;206: 273–278.
- Allen CM, Camisa C, Hamzeh S, Stephens L. Cheilitis granulomatosa: report of six cases and review of the literature. J Am Acad Dermatol 1990; 23: 444–50.
- Friedrich W, Timmermann J Miescher’s granulomatous cheilitis. Diagnostic and therapeutic aspects.Laryngorhinootologie 1990; 69: 564–8.
- Alawi F. Granulomatous diseases of the oral tissues: differential diagnosis and update. Dent Clin North Am 2005; 49: 203–21.
- Ayangco L, Rogers RS 3rd, Sheridan PJ. Pyostomatitis vegetans as an early sign of reactivation of Crohn’s disease: a case report. J Periodontol 2002; 73: 1512–6.
- Delaporte E, Viget N, Pasturel-Michon U, Catteau B, Hachulla E, Piette F. Pyostomatitis-pyodermatitis vegetans uncovering a case of Crohn disease. Ann Dermatol Venereol 1998;125: 331–4.
- Hansen LS, Silverman S Jr, Daniels TE. The differential diagnosis of pyostomatitis vegetans and its relation to bowel disease. Oral Surg Oral Med Oral Pathol 1983; 55: 363–73.
- Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore) 1976; 55: 401–12.
- Lisciandrano D, Ranzi T, Carrassi A et al. Prevalence of oral lesions in inflammatory bowel disease. Am J Gastroenterol 1996; 91: 7–10.
- Field EA, Tyldesley WR. Oral Crohn’s disease revisited–a 10-year review. Br J Oral Maxillofac Surg 1989; 27: 114–23.
- Colella G, Riegler G, Lanza A, Tartaro GP, Russo MI, Tartaglione M. Changes in the mouth mucosa in patients with chronic inflammatory intestinal diseases. Minerva Stomatol 1999; 48: 367–71.
- Lourenço SV, Hussein TP, Bologna SB, Sipahi AM, Nico MM. Oral manifestations of inflammatory bowel disease: a review based on the observation of six cases. J Eur Acad Dermatol Venereol 2010; 24: 204–7.
- Correll RW, Wescott WB, Jensen JL. Recurring, painful oral ulcers. J Am Dent Assoc 1981; 103: 497–8.
- Gargiulo AV, Ladone JA, Toto PD, Logiudice J. Crohn’s disease: early detection by gingival biopsy. Periodontal Case Rep 1989; 11: 20–2.
- Ciantar M, Adlam DM. Treatment with infliximab: implications in oral surgery? A case report. Br J Oral Maxillofac Surg 2007; 45: 507–10.
- Roseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granylocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol 1999; 34: 50–54.
- Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Fa¨rlkkila¨ M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: corrleation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis 2008; 14: 40–46.
- Harikishan G, Reddy NR, Prasad H, Anitha S. Oral Crohn’s disease without intestinal manifestations. J Pharm Bioallied Sci 2012;4:S431–4.
- Peitsch WK, Kemmler N, Goerdt S, Goebler M. Infliximab: a novel treatment option for refractory orofacial granulomatosis. Acta Dermatol Venereol 2007; 87: 265–266.
- Mantegazza C, Angiero F, Zuccotti GV. Oral manifestations of gastrointestinal diseases in children. Part 3: Ulcerative colitis and gastro-oesophageal reflux disease. Eur J Paediatr Dent 2016a;17(3):248-250.
- Seo JK, Yeon KM, Chi JG. Inflammatory bowel disease in children--clinical, endoscopic, radiologic and histopathologic investigation. J Korean Med Sci 1992 Sep; 7(3):221-35.
- Alstead EM, Wilson AG, Farthing MJ. Lichen planus and mesalazine. J Clin Gastroenterol 1991;13:335–37.
- Calobrisi SD, Mutasim DF, McDonald JS. Pyostomatitis vegetans associated with ulcerative colitis. Temporary clearance with fluocinonide gel and complete remission after colectomy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995 Apr; 79(4):452-4.
- O'Loughlin S, Perry HO. A diffuse pustular eruption associated with ulcerative colitis. Arch Dermatol 1978 Jul; 114(7):1061-4.
- Davies PT, Shadforth MF. Sulphasalazine induced oral lichen planus. Br Med J 1984;288:194.
- Parvinen T, Parvinen I, Larmas M. Stimulated salivary flow rate, pH, and lactobacillus and yeast concentrations in medicated persons. Scand J Dent Res 1984;92:524–32.
- Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth. Gerodontology 1986;5:75–99.
- Mijandrusi-Sinci B, Licul V, Gorup L, Brnci N, Glazar I, Lucin K. Pyostomatitis vegetans associated with inflammatory bowel disease-report of two cases. Coll Antropol 2010; 34 Suppl 2:279-82.
- Folashade AJ, Melvin B. Heymant extraintestinal manifestations of inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2008 Feb; 46(2): 124-133.
- Lekovi Z, Radlovi N, Brdar R, Vuleti B, Jani N, Risti D, Stojsi Z, Radlovi V, Simi D, Nikoli D. Clinical characteristics of idiopathic ulcerative colitis in children. Srp Arh Celok Lek 2011 Mar-Apr;139(3-4):170-3.
- Krebs KT. Case study: aphthous ulcers in a 14-year-old girl. Pediatr Nurs 2011 May-Jun;37(3):115-8.
- Kugathasan S, Judd RH, Hoffmann RG et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr 2003;143:525-31.
- Bentsen BS, Moum B, Ekbom A. Incidence of inflammatory bowel disease in children in southeastern Norway: a prospective popula- tion-based study 1990 – 94. Scand J Gastroenterol 2002; 37:540-5.
- Elahi M, Telkabadi M, Samadi V, Vakili H. Association of oral manifestations with ulcerative colitis. Gastroenterol Hepatol Bed Bench 2012 Summer; 5(3): 155–160.
- Pace F, Pallotta S, Tonini M, Vakil N, Bianchi Porro G. Systematic review: gastro-oesophageal reflux disease and dental lesions. Aliment Pharmacol Ther 2008 Jun;27(12):1179-86.
- Vandenplas Y, Colin DR. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Committee Members: Di Lorenzo C, Hassall E, Liptak G, Mazur L, Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenzl TG. J Pediatric Gastroenterology Nutrition 2009; 49:498-547.
- Pindborg JJ. Chemical and physical injuries. In: Pindborg JJ ed. Pathology of the dental hard tissues. Philadelphia: Saunders; 1970. p 312-325.
- Dahshan A, Patel H, Delaney J, Wuerth A, Thomas R, Tolia V. Gastroesophageal reflux disease and dental erosion in children. J Pediatr. 2002 Apr;140(4):474-8.
- Wilder-Smith CH, Wilder-Smith P, Kawakami-Wong H, Voronets J, Osann K, Lussi A. Quantification of dental erosions in patients with GERD using optical coherence tomography before and after double-blind, randomized treatment with esomeprazole or placebo. Am J Gastroenterol 2009;104:2788-2795.
- Di Fede O, Di Liberto C, Occhipinti G, Vigneri S, Lo Russo F, Fedele S, Lo Muzio S, Campisi G. Oral manifestations in patients with gastro-oesophageal reflux disease: a single-center case–control study. J Oral Pathol Med 2008;37: 336-340.
- Silva MA, Damante JH, Stipp AC, Tolentino MM, Carlotto PR, Fleury RN. Gastroesophageal reflux disease: new oral findings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 91: 301–10.
- Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;101:1900-1920.
- Barker JM, Liu Celiac Disease: Pathophysiology, clinical manifestations and associated autoimmune conditions. Adv Pediatr 2008; 55: 349–365.
- Mantegazza C, Paglia M, Angiero F, Crippa R. Oral manifestations of gastrointestinal diseases in children. Part 4: Coeliac disease. Eur J Paediatr Dent 2016b;17(4):332-334.
- Lionetti E, Catassi C. Co-localization of gluten consumption and HLA-DQ2 and -DQ8 genotypes, a clue to the history of celiac disease. Dig Liver Dis 2014;46(12):1057e63.
- Rashid M, Zarkadas M, Anca A, Limeback H. Oral manifestations of celiac disease: a clinical guide for dentists. J Can Dent Assoc 2011;77:b39
- Tack GJ, Verbeek WHM, Schreurs MWJ, Mulder CJJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol 2010; 7(4): 204-213.
- Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005;40(1):1-19.
- Aine L, Mäki M, Collin P, Keyriläinen O. Dental enamel defects in celiac disease. J Oral Pathol Med 1990 Jul;19(6):241-5.
- 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 Feb;40(2):104-7. Epub 2007 Dec 11.
- Condò R, Costacurta M, Maturo P, Docimo R. The dental age in the child with coeliac disease. Eur J Paediatr Dent 2011 Sep;12(3):184-8.
- Sedghizadeh PP, Shuler CF, Allen CM, Beck FM, Kalmar JR. Celiac disease and recurrent aphthous stomatitis: a report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Oct;94(4):474-8.
- Trandafir LM, Anton-Paduraru DT, Rusu D, Burlea M. Oral manifestations in celiac disease children. Romanian Journal of Oral Rehabilitation 2014 January - March; 6(1): 33-37.
- 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(5): 899-906.
- Shetyer E, Berson T, Lachmanovitz O, Hidas A, Wilschanski M, Meneachem M, Shachar E, Shapira J, Steinberg D, Moskovitz M. Oral health status and salivary properties in relation to gluten free diet in children with celiac disease. J Pediatr Gastroenterol Nutr 2013, 57, 1, 49–52.
- Benkebil F, Combescure C, Anghel SI, Besson Duvanel C, Schäppi MG. Diagnostic accuracy of a new point-of-care screening assayfor celiac disease. World J Gastroenterol 2013;19:5111-7.
- Ertekin V, Selimoglu MA, Kardas F, Aktas¸ E. Prevalence of CD in Turkish children. J Clin Gastroenterol 2005; 39: 689–691.
- Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A,Shamir R et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-60.
- Mantegazza C, Crippa R, Zuccotti GV. Oral manifestations of gastrointestinal diseases in children. Part 1: General introduction. Eur J Paediatr Dent 2016a;17(1):80-82.