Key Points
-
Summarises most up to date information about inflammatory bowel disease.
-
Provides understanding of link between IBD and oral health.
-
Summarises treatments for IBD and how anti-inflammatory medications can have side effects affecting the oral cavity.
Abstract
Inflammatory bowel disease (IBD) mainly comprises of two separate inflammatory conditions: Crohn's disease (CD) and ulcerative colitis (UC). The aetiology of these conditions is still being explored with current evidence pointing towards a combination of environmental and genetic components. However, the pathophysiology is understood as a cytokine driven inflammatory response. There is significant association between IBD and dental conditions such as dental caries, other infections and periodontitis. Anti-inflammatory medications such as 5 aminosalicylic acid (5ASA), steroids and biological therapies are the treatment of choice for these chronic conditions, dependent on aetiology. Therefore, this article aims to educate dentists regarding possible implications IBD and its treatment can have for clinical practice and future research.
Similar content being viewed by others
Introduction
Inflammatory bowel disease (IBD) is an umbrella term mainly comprising of two separate medical conditions: Crohn's disease (CD) and ulcerative colitis (UC). They are chronic inflammatory conditions affecting the digestive system that can lead to acute flare-ups of the respective conditions. CD can affect any part of the GI system (most commonly the small bowel, whereas UC only affects the large bowel.1
The incidence of IBD is beginning to stabilise in Europe with about 2.2 million people suffering from the condition.2 In the UK it is estimated at least 115,000 people have CD and around 146,000 have a diagnosis of UC.3 It is a condition that is most commonly diagnosed during childhood or early adolescence.4
Risk factors involved in IBD
IBD is thought to result from inappropriate and ongoing activation of the mucosal immune system facilitated by defects in both the intestinal epithelium and mucosal immune system.5 There are both genetic and environmental factors implicated in the aetiology of IBD.6 Although traditionally associated with the developed world, recent epidemiological studies suggest an increasing incidence in rapidly developing countries, especially in South-East Asia.7 In addition, the increased risk of IBD in the immigrant populations in the West suggests environment has a role in the development of IBD.8
Genetic
Detailed genetic mapping has identified specific genetic changes on chromosome 16 carried in families which appear linked to CD, however no significant changes have been mapped as of yet to UC.9,10 Specifically, variants of the NOD2 gene provide the strongest association with susceptibility to CD. NOD2 plays a key role in regulating the gut mucosal barrier involving, specifically, the microbiota, as well as the related response by the innate and adaptive immune system. The IBDchip European Project showed NOD2 has been implicated in ileal location colitis with stenosing and penetrating disease behaviour.11 A genome wide association study has also identified a strong link between the IL23R gene and CD.12 The gene in particular codes for interleukin 23 that plays a role in regulating innate immunity within the intestine.13
Cigarette smoking
Unusually, cigarette smoking is associated with decreased rates of incidence of UC and has been associated with protective features to prevent further flare-ups of the condition14,15,16,17,18,19 such as relapses,20 hospitalisations21 and colectomies.22 Also, complications of the condition are reduced in those who do smoke. This raises the concept of encouraging smoking to prevent adverse events occurring. However, there is a plethora of evidence that suggests that smoking has adverse effects on overall morbidity outcomes. In particular, it can increase failure in dental implants,23 increase the risk of oral cancers and increase the incidence of dental infections.24 Guidelines advocate smoking cessation in UC patients. On the contrary CD patients who smoke have a more severe disease course and can increase the incidence of CD with further complications.18,25,26,27 In fact, smoking cessation can provide a 65% reduction in the risk of relapse versus smokers. This is comparable to the reduction of risk attributed to immunosuppressive therapy.28
Other environmental risk factors
In observational studies, appendectomies appear to provide a risk reduction in the development of UC.29 Oral contraceptives statistically significantly increased the risk for developing CD and appeared to increase the risk of UC.30 The other important environmental factor playing on the development of IBD is diet control. The greatest association appears to be between increased sugar intake and developing IBD.31 This is especially important to note considering increased sugar intake can lead to the development of dental caries.32,33 Secondly, increased sugar content will be a contributing factor to diabetes which already has a causal link with periodontal disease.34
Pathology of IBD
The pathophysiology behind IBD has been under intense research scrutiny for the last decade, and much of it is still unknown. However, it is clear that it consists of complex interplay between genetic influences, environmental factors, microbial flora and the host immune system.35 The dysfunction of the innate and adaptive immune system is at the centre of the inflammatory process. The innate immune system is the immediate nonspecific response system of the body with response times ranging from minutes to hours. It consists of the epithelial cells, neutrophils and natural killer Tcells among other cells. The pattern recognition receptors (PCR) such as toll-like receptors and NOD-like receptors recognising valid pathogen associated molecular patterns (PAMPs) are one of the main triggers for this system. However, mutations in underlying genes such as NOD2, that plays a key role in immune tolerance, result in inappropriate immune responses. In addition, it can lead to inappropriate Th1 pathway stimulation due to decreased inhibition of the TLR2 stimulation.36 Other important factors affecting the innate immune system in IBD include autophagy defects due to gene mutations such as in the ATG16L1 gene, which has been implicated in CD.
The adaptive immune system is the specific immune response system, consisting of Bcells and Tcells among others. There have been theories that there are two distinct adaptive immune system pathologies driving CD and UC. It was suggested that the IL12 cytokine stimulation resulting in Th1 mediated upregulation and thereby IFNY could be one of the main players in CD. Likewise, in the case of UC, Th2 mediated inflammation reaction was thought to be a key player. However, recent research has described mixed cytokine profiles in UC, and therefore, it is clear that further research needs to be performed to investigate the specific roles of Th1 and Th2 in IBD.37
Oral presentations of IBD
Current literature suggests that up to 35% of IBD patients will have an extra-intestinal manifestation.38 The oral cavity could potentially be affecting up to 5–50% of patients. The wide range is due to the non-specificity of oral symptoms. However, broadly speaking, this population tends to be made up of CD patients, with children being affected more than adults.39 Older children and adolescents in particular are vulnerable to oral CD manifestations.40 One of the reasons why it is important to be aware of the signs and symptoms of CD is due to the hypothesis that oral inflammation may precede intestinal manifestation of disease.41
In a tertiary centre case-control study conducted in Portugal, consisting of 113 patients with previously diagnosed IBD and 58 healthy controls, there was a significantly increased prevalence of oral symptoms when compared with the control that did not have IBD (54.9% vs. 24.3%, P = 0.011).42 Oral symptoms were also present in a greater proportion within the active phase cohort than in the the remission cohort (70.6% vs. 52.1%, P = 0.001). Moreover, aphthous ulcers had a substantially increased presence within the active phase when compared with remission (35.3% vs. 4.2%, P <0.001).
Signs/symptoms of oro-facial IBD
Signs and symptoms that manifest with IBD are overwhelmingly that of CD. The most common sites involved are the lips, buccal mucosa and gingiva.43 Orofacial CD can present with aphthous ulcerations, angular cheilitis, and cobblestoning with or without oedema of the lips. Figures 1 and 2 demonstrate some of these oral manifestations of CD. Mucosal tags in the gingiva should also be treated with suspicion. The buccal mucosa can also contain abscesses, alongside cobblestone features and ooedema. Pyostomatis vegetans is a rare condition that could indicate the presence of CD as well as UC. It is characterised by dramatic erythematous thickened mucosa with widespread erosions. Case reports44,45 have indicated that oro-facial fistulae can be another rare outcome of IBD often presenting as a discharging abscess on the face. The aetiology of these fistulae is unclear as there appears to be overlap with granulomatous oro-facial disease..46
Conditions associated with IBD
Current research suggests that IBD patients are more likely to undergo dental procedures than a healthy cohort.47 In particular, CD patients were 1.18 times more likely to undergo dental treatment compared to healthy controls (P <0.000). Removable dentures (+65%), front teeth fillings (+52%), and endodontic treatment (+46%), in particular were more prevalent in the CD cohort. Similarly, UC patients were 1.09 times more likely to undergo dental treatment compared to health controls (P <0.005). In particular, these patients were 1.33 times more likely to have fillings in canines and incisors than the healthy controls (P <0.001). The impact of IBD on oral health is thus, well described. However, the exact nature of this relationship is unclear. The underlying inflammatory changes in IBD plays a role in poor oral health, however, the link is not causal aside from in the case of specific oral complications of IBD. The associations mainly appear to be linked to the development of dental caries, periodontal disease and other loosely related conditions through other risk factors associated with the development of IBD, such as high sugar intake.
Dental caries/infection
There appears to be a significant association with tooth caries and oral ulcers in IBD compared to the normal population.48 A case control study consisting of 110 participants49 identified children with IBD had statistically significantly higher rates of delayed, missing and filled teeth (dmft) (2.95 vs 0.91). IBD patients also have increased rates of lactobacilli and streptococcus mutans found in their oral cavity contributing to caries.50 The reasoning behind why these increased rates of caries and infections are not clear, however, proposed arguments include salivary components (increased bacterial concentrations), oral hygiene and diet.51,52 As discussed above, a risk factor for patients developing IBD is the increased sugar intake that can be associated with further infection.
Periodontal disease
The association between IBD and periodontal disease is starting to emerge in recent literature.53 Due to the inflammatory nature of both disorders, it is hypothesised that underlying IBD can trigger a raised basal cytokine response that can induce periodontal disease. Several case control studies have been conducted to explore this relationship further. A German study54 identified that twice as many patients with IBD, compared to those without IBD, had clinic attachment loss >5 mm, however, mean loss was not statistically significant. However, since then further prospective trials have identified that IBD patients have higher provenances of periodontal disease, deeper pocket depth and more clinical attachment loss.55,56
Malnutrition
Malnutrition is very prevalent within the IBD population. Literature has previously estimated this number to be almost one in four outpatients, and almost nine out of ten inpatients.57 This could be due to direct factors such as loss of normal resorptive mechanisms and higher nutritional requirements due to the inflammatory process. Indirect factors can also play a role and this can be due to reduced intake and side effects of concurrent medication. Particularly in CD, involvement of the small bowel can hinder absorption of vital nutrients. Iron malabsorption can occur if the duodenum and upper jejunum is affected, and this can manifest as angular cheilitis and glossitis.58 On a systemic level, low iron gives rise to the microcytic hypochromic anaemia picture. Involvement of the terminal ileum can result in folate and B12 deficiencies causing painful glossitis and stomatitis, among others. This manifests as macrocytic anaemia. Other nutrients prone to deficiencies include magnesium, potassium, vitamin D, selenium and zinc. Malnutrition of these micronutrients often results in non-specific oral lesions.
Medications
The therapeutic route to disease remission in IBD differs slightly between CD and UC. Steroids play an integral role in induction of remission in both conditions. In summary, the NICE-recommended UC pathway59 (as per individual patient needs) is as follows:
-
5-aminosalicylic acid (5ASA) therapy such as sulphasalazine or mesalazine
-
Thiopurine therapy (Azathioprine or 6mercaptopurine)
-
Biologic therapy consisting of infliximab/adalimumab.
Newer monoclonal antibody therapies such as golimumab, vedolizumab and ustekinumab are now in use in specialised cases within tertiary centres.
The corresponding pathway for CD60 (again as per individual patient needs) is as follows:
-
Thiopurine therapy (Azathioprine or 6mercaptopurine)
-
Methotrexate
-
Biologic therapy consisting of infliximab/adalimumab.
In the case of colonic CD, 5ASA therapies may also be used with good efficacy. As the medications overlap largely between the conditions we will explore the dental associations related to these medications. It should be noted that these medications have potent anti-inflammatory and immunosuppressant actions and therefore reduce the body's ability to fight infection, which is an important consideration in an oral health context.
5-ASAs
5 ASAs such as sulphasalazine and mesalazine act as anti-inflammatory medications providing topical relief inside the intestines. They do this by reducing synthesis of inflammatory cytokines and have been used for many years.61 They are medications that can cause a host of side effects from common ones including nausea, vomiting and GI upset.62 However, three are of particular importance and interest to dentists. The first being the risk of drug induced agranulocytosis.63 Agranulocytosis is an acute condition leading to a severe leucopenia where there a reduction in white blood cells affect the way the body can fight infection. Secondly, of interest to the dental profession, 5ASAs have supposedly caused a few cases of parotitis which is a swelling of the parotid gland similar to mumps but it is unclear whether this was due to the medication or progression of the condition, however, it is still noted as a side effect for the medication.64 Thirdly, a few patients have noted taste disturbances which may present to the dentist before the doctor.65
Purine analogues
Azathioprine and 6mercaptopurine are both purine analogues and widely used immune-suppressants to dampen the immune response in both conditions.66 Similarly to 5ASAs, these medications can cause an acute leucopenia which can severely impair the body's effect on fighting infection.67 Secondly, there is a fourfold documented increase in the risk of lymphoma with these medications which can present in the oral cavity.68,69 It should be noted, however, that there is only a very small absolute increase in the risk of lymphoma occurrence.
Methotrexate
The role of methotrexate in IBD management is rare. However, methotrexate can be used as an effective immune-modulator in inflammatory bowel disease.70 Of importance to dentists, methotrexate can commonly cause ulcerative stomatitis71 and recent case reports have identified Epstein-Barr associated lympho-proliferative disorders occurring in the gingiva of patients taking methotroxate, causing gingival ulceration.72,73
Biologic anti-TNF agents
Both infliximab and adalimumab are relatively new antibody-based drugs against TNF (tumour necrosis factor), which is a cytokine agent in the body's immune response, upregulated in inflammatory conditions such as IBD. These medications pose fewer adverse effects related to the oral region, however, they are associated with reactivation of latent TB.74,75 Therefore, it is still worth enquiring about opportunistic dental screenings whether or not these patients have experienced systemic symptoms of TB as it is of public health importance. In addition, as these medications are still relatively new, the long-term risks of them are unknown. Any cause for concern in a patient on biologic treatment should ideally be escalated to the medical team for thorough investigation.
Treatment of oral lesions
The main underlying principle in treating oral lesions in IBD lies in identifying the cause of oral lesions. These could be directly due to IBD, malnutrition or concurrent medication use (as mentioned below)
Oral involvement of IBD revolves around treating the intestinal manifestation of the disease. However, topical and systemic medical treatment modalities are available. Corticosteroid injections can be applied locally to the lesion. In addition, symptomatic relief is available via use of lidocaine 2% in the most severe cases. Less potent treatment modalities take the form of ointments. Evidence shows that topical tacrolimus at relatively low concentrations of 0.5 mg/kg can be potent in oral manifestations of CD.76 Other ointment options include the use of 1% hydrocortisone three times daily. Steroid mouthwashes (dexamethasone elixir) are also available for symptomatic relief. These methods of treatment, particularly topical dexamethasone ointments are effective treatments for refractory apthous ulcers as well.77
Typically, systemic medical treatment is reserved for the most severe of oral cases. Evidence advocating systemic medical treatment to combat oral manifestation of IBD consists largely of low sample size studies. However, it has been shown that combination therapy of steroids and azathioprine can potentially be beneficial.78 Staines et al. 200779 suggested that anti-TNF inhibitors can be of benefit in complex oral manifestations such as fistulating oral disease.
Surgical treatment and biopsy
Surgical modalities for treatment of oral manifestations of IBD are used in cases where complications have developed such as fistulations and abscesses. In these cases, a combination of maxillofacial surgery and plastic surgery may be indicated. Orofacial surgery is relatively more complex in the IBD cohort. There is evidence to suggest that this cohort is at higher risk of oropharyngeal perforation.80 Post-operative recovery may also be impaired in these patients due to concomitant use of systemic steroids and potent immunosuppressants.
Diet
Diet is an important factor that can be overlooked in managing oral health manifestations of IBD. An early study81 identified that strict elimination diets, where a potential trigger in the diet leading to the flare of apthous ulcer is identified and removed, provide symptomatic relief. The management of diet-related oral manifestations largely represents replacing the vitamin or mineral that is depleted. There are known associations between decreased ferritin levels and oral ulcers, therefore, appropriate replacement would help prevent development.82
Take home message
From the literature and clinical experience earlier, there is an evident association between IBD and various dental health conditions. Implications for education, practice and future research should be considered.
Implications for education
Dentists should be aware of the conditions that comprise IBD and their links to dental conditions such as dental caries, periodontitis and other oral infections. Secondly, dentists should be aware of the medications such patients take for the conditions, which in their own right can induce oral signs.
Implications for practice
Dentists should be able to identify oral presentations associated with IBD. Where early oral signs and symptoms exist, especially in young patients without a medical diagnosis, dentists should be implored to refer patients to their GP for further testing. Evidence has shown that early expert oral investigation in children presenting with these signs can be of great diagnostic benefit.83 Patients susceptible to eating high amounts of sugar should also be spoken to further in consultation regarding risk factors to do with IBD. Dentists should use dental check-ups as opportunistic screening moments for patients on these medications to ensure they are not getting any oral side effects.
Implications for further research
As this was a review of the available research to educate dentists it did not act to increase the evidence base in this field. There remains many opportunities to conduct audits and investigations, especially regarding oral side effects of medications as this is a particularly under researched area.
References
Baumgart D C, Sandborn W J, Spehlmann M et al. Crohn's disease. Lancet 2012; 380: 1590–1605.
Loftus E V . Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 2004; 126: 1504–1517.
NICE. Inflammatory bowel disease | introduction. Guidance and guidelines. 2015.
Sawczenko A, Sandhu B, Logan R et al. Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet 2001; 357: 1093–1094.
Podolsky DK . Inflammatory Bowel Disease. N Engl J Med 2002; 347: 417–429.
Ananthakrishnan AN . Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015; 12: 205–217.
Thia K T, Loftus, Jr E V, Sandborn W J, Yang SK . An Update on the Epidemiology of Inflammatory Bowel Disease in Asia. Am J Gastroenterol 2008; 103: 3167–3182.
Probert C S, Jayanthi V, Pinder D, Wicks A C, Mayberry J F . Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. Gut 1992; 33: 687–693.
Hugot J P, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599–603.
Hugot J P, Laurent-Puig P, Gower-Rousseau C et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 1996; 379: 821–823.
Cleynen I, González J R, Figueroa C et al. Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project. Gut 2013; 62: 1556–1565.
Duerr R H, Taylor K D, Brant S R, Rioux J D, Silverberg M S, Daly M J et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314: 1461–1463.
McGovern D, Powrie F . The IL23 axis plays a key role in the pathogenesis of IBD. Gut 2007; 56: 1333–1336.
Harries A D, Baird A, Rhodes J . Non-smoking: a feature of ulcerative colitis. Br Med J (Clin Res Ed) 1982; 284: 706.
Bianchi Porro G, Panza E . Smoking, sugar, and inflammatory bowel disease. Br Med J (Clin Res Ed) 1985; 291: 971–972.
Logan R F, Edmond M, Somerville K W, Langman M J . Smoking and ulcerative colitis. BMJ 1984; 288: 751–753.
Lunney P C, Leong R W L . Review article: ulcerative colitis, smoking and nicotine therapy. Aliment Pharmacol Ther 2012; 36: 997–1008.
Tobin M V, Logan R F, Langman M J, McConnell R B, Gilmore I T . Cigarette smoking and inflammatory bowel disease. Gastroenterology 1987; 93: 316–321.
Aldhous M C, Drummond H E, Anderson N, Baneshi M R, Smith L A, Arnott ID R et al. Smoking habit and load influence age at diagnosis and disease extent in ulcerative colitis. Am J Gastroenterol 2007; 102: 589–597.
Höie O, Wolters F, Riis L, Aamodt G, Solberg C, Bernklev T et al. Ulcerative colitis: patient characteristics may predict 10yr disease recurrence in a European-wide population-based cohort. Am J Gastroenterol 2007; 102: 1692–1701.
Boyko E J, Perera D R, Koepsell T D, Keane E M, Inui T S . Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol 1988; 23: 1147–1152.
Cosnes J . Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice. Best Pract Res Clin Gastroenterol 2004; 18: 481–496.
Chrcanovic B R, Albrektsson T, Wennerberg A . Smoking and dental implants: A systematic review and meta-analysis. J Dent 2015; 43: 487–498.
Virtanen E, Söder B, Andersson L C, Meurman J H, Söder P Ö . History of dental infections associates with cancer in periodontally healthy subjects: a 24-year follow-up study from sweden. J Cancer 2014; 5: 79–85.
Holdstock G, Savage D, Harman M, Wright R . Should patients with inflammatory bowel disease smoke? Br Med J (Clin Res Ed) 1984; 288: 362.
Cottone M, Rosselli M, Orlando A et al. Smoking habits and recurrence in Crohn's disease. Gastroenterology 1994; 106: 643–648.
Duffy L C, Zielezny M A, Marshall J R et al. Cigarette smoking and risk of clinical relapse in patients with Crohn's disease. Am J Prev Med; 6: 161–166.
Johnson G J, Cosnes J, Mansfield J C . Review article: smoking cessation as primary therapy to modify the course of Crohn's disease. Aliment Pharmacol Ther 2005; 21: 921–931.
Koutroubakis I E, Vlachonikolis I G, Kouroumalis E A . Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review. Inflamm Bowel Dis 2002; 8: 277–286.
Godet P G, May G R, Sutherland L R . Meta-analysis of the role of oral contraceptive agents in inflammatory bowel disease. Gut 1995; 37: 668–673.
Riordan A M, Ruxton C H, Hunter JO . A review of associations between Crohn's disease and consumption of sugars. Eur J Clin Nutr 1998; 52: 229–238.
Grossner-Schreiber B, Fetter T, Hedderich J, Kocher T, Schreiber S, Jepsen S . Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study. J Clin Periodontol 2006; 33: 478–484.
Halme L, Meurman J H, Laine P et al. Oral findings in patients with active or inactive Crohn's disease. Oral Surgery Oral Med Oral Pathol 1993; 76: 175–181.
Mealey B L, Statistics NC for H, Association A D et al. Periodontal disease and diabetes. A two-way street. J Am Dent Assoc 2006; 137 Suppl: 26S–31S.
Zhang YZ . Inflammatory bowel disease: Pathogenesis. World J Gastroenterol 2014; 20: 91.
Watanabe T, Kitani A, Murray P J, Strober W . NOD2 is a negative regulator of Toll-like receptor 2–mediated T helper type 1 responses. Nat Immunol 2004; 5: 800–808.
Bernardo D, Vallejo-Díez S, Mann E R et al. IL6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate. Eur J Immunol 2012; 42: 1337–1353.
Ardizzone S, Puttini P S, Cassinotti A et al. Extraintestinal manifestations of inflammatory bowel disease. Dig Liver Dis 2008; 40: S253–S259.
Lenaerts C, Roy C C, Vaillancourt M, Weber A M, Morin C L, Seidman E . High Incidence of Upper Gastrointestinal Tract Involvement in Children With Crohn Disease. Paediatrics 1989; 83: 777–781.
Jose F A, Garnett E A, Vittinghoff E et al. Development of extraintestinal manifestations in paediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 63–68.
Lankarani K B, Sivandzadeh G R, Hassanpour S . Oral manifestation in inflammatory bowel disease: A review. World J Gastroenterol 2013; 19: 8571–8579.
Laranjeira N, Fonseca J, Meira T, Freitas J, Valido S, Leitão J . Oral Mucosa Lesions and Oral Symptoms in Inflammatory Bowel Disease Patients. Arq Gastroenterol 2015; 52: 105–110.
Katsanos K H, Torres J, Roda G, Brygo A, Delaporte E, Colombel J F . Review article: Non-malignant oral manifestations in inflammatory bowel diseases. Aliment Pharmacol Ther 2015; 42: 40–60.
Goel R M, Hullah E . Orofacial Fistulae Associated with Crohn's Disease. N Engl J Med 2015; 372: e29.
Doherty G, Kalachand R, Patchett S . Adalimumab as therapy for fistulizing orofacial Crohn's disease. Inflamm Bowel Dis 2010; 16: 184–185.
Grave B, McCullough M, Wiesenfeld D . Orofacial granulomatosis – a 20-year review. Oral Dis 2009; 15: 46–51.
Johannsen A, Fored M C, Håkansson J, Ekbom A, Gustafsson A . Consumption of dental treatment in patients with inflammatory bowel disease, a register study. PLoS One 2015; 10: e0134001.
Singhal S, Dian D, Keshavarzian A, Fogg L, Fields J Z, Farhadi A . The Role of Oral Hygiene in Inflammatory Bowel Disease. Dig Dis Sci 2011; 56: 170–175.
Koutsochristou V, Zellos A, Dimakou K et al. Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease. Inflamm Bowel Dis 2015; 21: 1839–1846.
Szymanska S, Lördal M, Rathnayake N, Gustafsson A, Johannsen A . Dental caries, prevalence and risk factors in patients with Crohn's disease. PLoS One 2014; 9: e91059.
Rooney TP . Dental caries prevalence in patients with Crohn's disease. Oral Surgery Oral Med Oral Pathol 1984; 57: 623–624.
Sundh B, Emilson C G . Salivary and microbial conditions and dental health in patients with Crohn's disease: a 3year study. Oral Surg Oral Med Oral Pathol 1989; 67: 286–290.
Agossa K, Dendooven A, Dubuquoy L, Gower-Rousseau C, Delcourt-Debruyne E, Capron M . Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence. J Periodontal Res 2016; DOI: 10.1111/jre.12422.
Grössner-Schreiber B, Fetter T, Hedderich J, Kocher T, Schreiber S, Jepsen S . Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study. J Clin Periodontol 2006; 33: 478–484.
Brito F, de Barros F C, Zaltman C et al. Prevalence of periodontitis and DMFT index in patients with Crohn's disease and ulcerative colitis. J Clin Periodontol 2008; 35: 555–560.
Vavricka S R, Manser C N, Hediger S et al. Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 2013; 19: 2768–2777.
Muhvić-Urek M, Tomac-Stojmenović M, Mijandrušić-Sinćić B. Oral pathology in inflammatory bowel disease 2016 Inflammatory Bowel Disease: Global view. World J Gastroenterol 2016; 22: 5655–5667.
Islam N M, Bhattacharyya I, Cohen D M . Common oral manifestations of systemic disease. Otolaryngol Clin North Am 2011; 44: 161–182.
NICE. Ulcerative colitis overview – NICE Pathways. 2016. Available online at https://pathways.nice.org.uk/pathways/ulcerative-colitis#content=view-node%3Anodes-maintaining-remission (accessed March 2017).
NICE. Crohn's disease overview – NICE Pathways. 2016. Available online at https://pathways.nice.org.uk/pathways/crohns-disease (accessed March 2017).
Klotz U, Maier K, Fischer C, Heinkel K . Therapeutic Efficacy of Sulphasalazine and Its Metabolites in Patients with Ulcerative Colitis and Crohn's Disease. N Engl J Med 1980; 303: 1499–1502.
Taffet S L, Das K M . Sulphasalazine. Dig Dis Sci 1983; 28: 833–842.
Keisu M, Ekman E . Sulphasalazine associated agranulocytosis in Sweden 1972–1989. Eur J Clin Pharmacol 1992; 43: 215–218.
Watanabe T . Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signalling and induction of antigen-specific colitis. Immunity 2006; 25: 473–485.
Marcus R W . Sulphasalazine induced taste disturbances. J Rheumatol 1991; 18: 634–635.
Sandborn W J . Azathioprine: state of the art in inflammatory bowel disease. Scand J Gastroenterol Suppl 1998; 225: 92–99.
Pollak R, Nishikawa R A, Mozes M F, Jonasson O . Azathioprine-induced leukopenia—Clinical significance in renal transplantation. J Surg Res 1980; 29: 258–264.
Kandiel A, Fraser A G, Korelitz B I, Brensinger C, Lewis J D . Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6mercaptopurine. Gut 2005; 54: 1121–1125.
Kobler P, Borcic J, Zore I F, Nola M, Sertic D . Primary non-Hodgkin's lymphoma of the oral cavity. 2005; 10.1016/j.ooe.2004.10.002.
Swaminath A, Taunk R, Lawlor G . Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide. World J Gastrointest Pharmacol Ther 2014; 5: 113–121.
Bauer J, Fartasch M, Schuler G, Schell H . [Ulcerative stomatitis as clinical clue to inadvertent methotrexate overdose]. Der Hautarzt; Zeitschrift fu¨r Dermatologie, Venerol und verwandte Gebiete 1999; 50: 670–673.
Horie N, Kawano R, Kaneko T, Shimoyama T . Methotrexate-related lymphoproliferative disorder arising in the gingiva of a patient with rheumatoid arthritis. Aust Dent J 2015; 60: 408–411.
Ishida M, Hodohara K, Yoshii M et al. Case Report Methotrexate-related Epstein-Barr virus-associated lymphoproliferative disorder occurring in the gingiva of a patient with rheumatoid arthritis. Int J Clin Exp Pathol 2013; 6: 2237–2241.
Keane J, Gershon S, Wise R P et al. Tuberculosis Associated with Infliximab, a Tumour Necrosis Factor α–Neutralizing Agent. N Engl J Med 2001; 345: 1098–1104.
Long R, Gardam M . Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ 2003; 168: 1153–1156.
Casson D H, Eltumi M, Tomlin S, Walker-Smith J A, Murch S H . Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's disease. Gut 2000; 47: 436–440.
Keenan AV . Promising results for dexamethasome ointment for treatment of recurrent aphthae. Evid Based Dent 2012; 13: 75–75.
Williams A J, Wray D, Ferguson A . The clinical entity of orofacial Crohn's disease. Q J Med 1991; 79: 451–458.
Staines K S, Green R, Felix D H . The management of fistulizing oral Crohn's disease with infliximab. J Oral Pathol Med 2007; 36: 444–446.
Peix J L, Moulin G, Evreux M, Berger N, Magis M . [Bucco-pharyngeal and esophageal localizations in Crohn's disease]. Gastroenterol Clin Biol 1987; 11: 604–606.
Hay K D, Reade P C . The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surgery Oral Med Oral Pathol 1984; 57: 504–507.
K S, B S, Palaneeswari M S, Devi A J M . Significance of ferritin in recurrent oral ulceration. J Clin Diagn Res 2014; 8: 14–15.
Pittock S, Drumm B, Fleming P et al. The oral cavity in Crohn's disease. J Paediatr 2001; 138: 767–771.
Acknowledgements
We would like to thank the peer reviewers and editors for their comments regarding the paper. Secondly, we would like to thank Dr Neeraj Bhala for taking his time to review and give comments surrounding the paper.
Author information
Authors and Affiliations
Corresponding author
Additional information
Refereed Paper
Rights and permissions
About this article
Cite this article
Chandan, J., Thomas, T. The impact of inflammatory bowel disease on oral health. Br Dent J 222, 549–553 (2017). https://doi.org/10.1038/sj.bdj.2017.318
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bdj.2017.318
- Springer Nature Limited
This article is cited by
-
Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study
BMC Immunology (2024)
-
Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis
Nature Communications (2023)
-
Dental problems and chronic diseases in mentally ill homeless adults: a cross-sectional study
BMC Public Health (2020)
-
Increased risk of periodontitis among patients with Crohn’s disease: a population-based matched-cohort study
International Journal of Colorectal Disease (2018)