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Gastrointestinal Diseases & Their Oral Manifestations General Medicine Dental Correlations Course Christopher S. Huang, MD Clinical Associate Professor of Medicine Boston University Chobanian & Avedisian School of Medicine Introduction • Several gastrointestinal diseases have unique oral manifesta...

Gastrointestinal Diseases & Their Oral Manifestations General Medicine Dental Correlations Course Christopher S. Huang, MD Clinical Associate Professor of Medicine Boston University Chobanian & Avedisian School of Medicine Introduction • Several gastrointestinal diseases have unique oral manifestations, which may provide insight into the state of the underlying disease • Recognizing these oral manifestations may have significant implications on health and treatment • The underlying GI disease may have important implications on dental management Objectives • To discuss the following GI disorders and their oral manifestations: • • • • • Inflammatory bowel disease Gastroesophageal reflux disease Polyposis syndromes (FAP, PJS, Cowden) and colorectal cancer Malabsorption syndromes (celiac disease) Cirrhosis • To discuss implications these conditions may have on management of the dental patient Clinical scenario #1 • A 19 year old college student presents with recurrent painful oral ulcers Clinical scenario #1 • Reports chronic intermittent RLQ pain, diarrhea, and unintentional weight loss • CT scan shows inflammation of the terminal ileum Clinical scenario #1 • Colonoscopy revealed multiple linear and irregular ulcers in the colon and terminal ileum Diagnosis: Crohn’s disease, with aphthous stomatitis Inflammatory Bowel Disease • Chronic idiopathic intestinal inflammation • Major types: • Ulcerative colitis (UC) • Crohn's disease (CD) • Indeterminate colitis IBD Epidemiology ©2012 UpToDate® IBD Etiology - High concordance in twins (CD>UC) - Increased risk in first degree relatives (3-20X risk) - Genome wide association studies: >200 distinct susceptibility loci Genetic susceptibility - Dysregulated or inappropriate immune response to luminal bacteria/ other trigger in a susceptible patient Immune dysregulation Environmental triggers Smoking – ↑ CD, ↓UC Appendectomy – ↓UC Altered gut microbial flora, gut infection Medications – OCPs, NSAIDs Urban > rural Developed >underdev North climates>South Ulcerative Colitis Pattern of inflammation: Continuous Layers involved: Mucosa Sites involved: Rectum + variable length of colon Location and Extent (UC) Percentages based on extent of disease at diagnosis Clinical Presentation (UC) • Symptoms • Diarrhea, rectal bleeding, tenesmus, passage of mucus, crampy abdominal pain • Extraintestinal manifestations • Severity of symptoms correlates with the extent of disease Clinical Presentation (UC) Mild Moderate Severe BMs/ day <4 4-6 >6 Blood in stool +/- ++ +++ Systemic signs * none minimal Inflammatory markers Normal present High, ESR > 30 Endoscopic appearance * Tachycardia, fever, anemia Gross Pathology (UC) Histology (UC) mucosa submucosa muscularis propria Inflammation largely limited to mucosal layer Crohn’s Disease Pattern of inflammation: Segmental Layers involved: Transmural Sites involved: Any location from mouth to anus Location and Extent (CD) Clinical Presentation (CD) • Fever, abdominal pain, vomiting, fatigue, weight loss, diarrhea, bleeding • Perianal disease • Strictures, bowel obstruction • Fistulae • Abdominal mass, intra-abdominal abscess Endoscopic Appearance (CD) British Dental Journal 2016;221:794-799 Gross Pathology (CD) Histology (CD) Transmural inflammation Granulomas Fissuring ulcer Nature 2007;448:427 Extraintestinal Manifestations • Dermatologic • Erythema nodosum • Pyoderma gangrenosum • Sweet’s syndrome Erythema nodosum Sweet’s syndrome Pyoderma gangrenosum Extraintestinal Manifestations • Hepatobiliary • Gallstones (ileal CD) • Primary sclerosing cholangitis (PSC) • Urologic • Calculi (Ca oxalate, uric acid) • Ureteral obstruction • Thromboembolic • Hypercoagulable state • Increased risk of DVT, PE, CVA Extraintestinal Manifestations • Ocular • Episcleritis • Uveitis • Rheumatologic • Peripheral arthritis • Ankylosing spondylitis • Sacroiliitis • Oral • • • • • • • Aphthous stomatitis Mucogingivitis Cobblestoning Deep fissuring ulcers Mucosal tags Cheilitis Pyostomatitis vegetans Oral manifestations of IBD • More common in CD, correlates with perianal disease • Usually parallel bowel activity B C A - lip swelling, fissures B - cobblestoning C - linear ulceration D - mucosal tag E - mucogingivitis Harty S, et al. Clin Gastro Hepatol 2005;3:886-891. Daley TD, Armstrong JE. Can J Gastroenterol 2007;21:241 British Dental Journal 2016;221:794-2799 Oral Manifestations of IBD Pyostomatitis vegetans Oral aphthous ulcer After treatment with prednisone Greenwood M, Meechan JG. Br Dental Journal 2003;194:659-663 Stricker T, Braegger CP. NEJM 2000;342:1644 Daley TD, Armstrong DE. Can J Gastroenterol 2007;21:241-4 Kalman R et al. CGH 2013;11:A24 Oral Manifestations of IBD A – Asymmetric lip swelling with fissures B - Gingival hyperplasia, soft-tissue tags C - Granulomatous inflammation on biopsies N Engl J Med 2015;373:1250 Oral Manifestations of IBD Tonsillar Crohn’s disease After treatment Clinical Gastroenterology and Hepatology 2017 15, A31-A32DOI: (10.1016/j.cgh.2017.03.038) Oral Manifestations of IBD Pyostomatitis vegetans Am J Gastroenterol 2020;115:1385 Oral Manifestations of IBD Macrochelia American Journal of Gastroenterology114(7):1022, July 2019 Differential Diagnosis for Recurrent Aphthous Stomatitis • Inflammatory bowel disease • Celiac disease • Vitamin and mineral deficiencies • • • • B vitamins Iron Folic acid Zinc • Behcet’s disease • Stress, hormonal factors, food sensitivity, infections, familial tendency GI Complications of IBD • Colon cancer • Risk related to extent and duration of disease • Pancolitis: 5-15x risk • Incidence ~ 0.5%/year with duration 10-20 years, then 1%/year thereafter • Perforation • Hemorrhage – acute or chronic-> anemia • Stricture formation, bowel obstruction • Fistula (Crohn’s) • Toxic megacolon Medical Treatment of IBD Biologics Steroids Immunomodulators Anti-inflammatory (Mesalamine) Medical Treatment of IBD Mesalamine - anti-inflammatory - topical or oral - induction/maintenance of remission for mild/moderate UC Biologics Steroids Immunomodulators Anti-inflammatory (Mesalamine) Medical Treatment of IBD Steroids - Oral, topical or IV - Useful for induction of remission, but NOT for maintenance therapy - High side effect profile Biologics Steroids Immunomodulators Anti-inflammatory (Mesalamine) Medical Treatment of IBD Immunomodulators - Azathioprine, 6-MP, MTX - Bone marrow suppression, risk of infection, malignancy Biologics Steroids Immunomodulators Anti-inflammatory (Mesalamine) Medical Treatment of IBD Biologics - - TNF antagonists - Potent immune suppressants - Risk of serious infections - Risk of malignancy - Anti-IL12/23 Ab - Anti-⍺4-β7 integrin Ab Biologics Steroids Immunomodulators Anti-inflammatory (Mesalamine) IBD – Implications for Management of Dental Patients • Caution with NSAIDs • use may exacerbate IBD in a small percentage of patients • Risks of IBD therapy: • More prone to infection (e.g. candidiasis) • Thrombocytopenia (with immunomodulators 6-MP, azathioprine) Clinical Scenario #2 • 36 year old woman with severe erosion of the molar enamel. • Denies excessive soda or citrus ingestion, Vit C supplementation • Frequent heartburn Schroeder PL, et al. Ann Int Med 1995;122:809-815 Diagnosis: Dental erosion secondary to GERD GERD Definition • Symptoms or complications caused by the abnormal reflux of gastric contents into the esophagus Pathogenesis of GERD Impairment of: • Lower Esophageal Sphincter competence, Transient LES relaxation • Esophageal clearance mechanisms • Gastric emptying • Mucosal integrity Conditions Associated with GERD • Hiatal hernia • Pregnancy • Obesity • Lifestyle & Iatrogenic GERD: Lifestyle & Iatrogenic Contributors • Foods • Habits • Medications GERD: Lifestyle & Iatrogenic causes • Foods • Habits • Medications Coffee Chocolates Mints Fatty/ fried foods Tomatoes/Citrus fruits Black pepper GERD: Lifestyle & Iatrogenic causes • Foods • Habits • Medications Smoking Alcohol Late night snacks/meals (then lying supine) Large meals GERD: Lifestyle & Iatrogenic causes • Foods • Habits • Medications Nitrates Anticholinergics Calcium channel blockers β2 agonists Theophylline Antispasmodics Antiemetics Tricyclic antidepressants Narcotics Neuroleptic antipsychotics GERD Symptoms • Heartburn • Acid regurgitation • Water brash • Dysphagia • Extraesophageal manifestations • • • • • Laryngitis, hoarseness Cough Asthma, chronic bronchitis Chest pain Dental erosion Complications of GERD • Erosive esophagitis • Peptic stricture • Barrett’s metaplasia • Esophageal adenocarcinoma Complications of GERD • Erosive esophagitis • Peptic stricture • Barrett’s metaplasia • Esophageal adenocarcinoma Oral manifestations of GERD Symptoms • • • • • Burning/itching mouth sensation Tongue sensitivity Halitosis Impaired taste (dysgeusia) Water brash Signs Dental erosion Painful oral ulcers Dental hypersensitivity Loss of vertical dimension of occlusion • TMJ pain, ?bruxism • Esthetic disfigurement • • • • Farrokhi F, Vaezi MF. Oral Diseases 2007;13:349-359. Ranjitkar S, Smale RJ, Kaidois JA. J Gastro Hepatol 2012;27:21-27. Oral manifestations of GERD Dental erosion • Most common sign (found in up to 55% of GERD patients) • Main mechanism of injury: direct contact of acid • Hydroxyapatite crystals in enamel dissolve with pH<5.5 • GERD may be silent Schroeder PL, et al. Ann Int Med 1995;122:809-815 Farrokhi F, Vaezi MF. Oral Diseases 2007;13:349-359. Ali DA, et al. J Am Dent Assoc 2002;133:734-737. Oral manifestations of GERD Distribution of Erosions GERD – posterior teeth, lingual and occlusal surfaces Extrinsic source – anterior teeth, labial surfaces, with severity decreasing posteriorly Ali DA, et al. J Am Dent Assoc 2002;133:734-737. Management of GERD • Aim at relief of symptoms, prevention of complications • Begin with lifestyle modifications • Medications • Antacid therapy • H2RA therapy • Proton Pump Inhibitor (PPI) therapy • Surgery Lifestyle Modifications • Avoid lying down for 3 hours after eating • Raise the head of the bed 6 inches • Avoid foods that induce symptoms • Lose weight, avoid overeating, stop smoking, drinking Medications • Antacids – for infrequent symptoms • H2 blockers – for mild cases, longer relief • PPIs – for frequent/severe symptoms • Potent anti-secretory agents, inhibit proton pump of gastric parietal cells (final pathway of acid secretion) • Dose should be given 30 minutes prior to a meal; not effective if taken prn or not followed by eating/drinking Surgery • Nissen fundoplication • Stomach wrapped around LES • 90% experience symptomatic improvement • But 10-65% still require medications (PPIs) Nissen Fundoplication before after GERD – Implications for Management of Dental Patients • Potential drug interactions: • Antacids with calcium can interfere with fluoride absorption • Omeprazole inhibits metabolism of diazepam, increases sedative effect • Patients may develop GERD symptoms in the fully supine position Clinical Scenario #3 • 28-year-old man presents to dentist with complaint of persistent swelling of his jaw • Reports 8 month history of rectal bleeding • Mother died of ‘intestinal cancer’ in her 40’s Butler J, et al. Oral Oncology Extra 2005;41:89-92 Clinical Scenario #3 • Orthopantomograph reveals large osteoma at angle of left mandible • Unerupted mandibular right canine Butler J, et al. Oral Oncology Extra 2005;41:89-92 Clinical Scenario #3 • Colonoscopy revealed innumerable adenomatous polyps throughout colon Diagnosis: Familial Adenomatous Polyposis, “Gardner Syndrome” variant Familial Adenomatous Polyposis • Rare autosomal dominant condition • Mutation of APC gene (chr. 5) • Prevalence 1/10,000, M=F • Main clinical feature: multiple (hundreds to thousands) colorectal adenomas • Average age of polyp formation: 16 years • Cancer risk 100%, average age 39; life expectancy 42 years without treatment FAP “Gardner’s syndrome” • FAP with prominent extraintestinal manifestations • Bony tumors (osteomas, frequently on jaw/skull) • CHRPE • Pancreas, thyroid, liver tumors • Epidermal cysts • Abdominal desmoid tumors • Dental abnormalities • May precede colonic polyps Oral manifestations of Gardner’s • • • • Supernumerary teeth Unerupted teeth Odontomas Osteomas Wijn MA, et al. Oral Diseases 2007;13:360-365. Hamartomatous polyposis syndromes • Peutz-Jeghers Syndrome (PJS) • Cowden Syndrome Peutz-Jegher’s Syndrome • Rare autosomal dominant disorder • Germline mutation of serine threonine kinase gene (STK11) on Chr 19 • Multiple hamartomatous polyps in GI tract • Intussusception, obstruction, bleeding • Significant risk of GI and non GI malignancies (93% by age 65) • Small intestine, stomach, colon, pancreas • Testicular, ovarian, uterine, cervical, breast British Dental Journal 2017;222:214-217 Oral signs of PJS • Flat, blue/gray - brown spots, 1-5 mm size • Most commonly located on lips/ perioral region • Also buccal mucosa, hands and feet • Typically fade after puberty, except for buccal mucosa lesions Pounder, RE, Allison, MC, Dhillon, AP. A Color Atlas of the Digestive System, Wolfe, London, p. 118. British Dental Journal 2017;222:214-217 Cowden Syndrome • Rare autosomal dominant condition • Germline mutation in PTEN gene (tumor suppressor) • Characterized by multiple hamartomatous lesions • • • • Skin Oral mucosa Intestine Breast • Increased risk for breast (25-50%) and thyroid cancers (10%) Oral signs of Cowden Syndrome • Papillomas on lips, mucous membranes • Cobblestoning of tongue Med Oral Patol Oral Cir Bucal 2006;11:E319-24. Importance of Oral Findings • May be the presenting sign of a syndrome that carries significant risk for malignancy • Detection of any of these signs should prompt thorough history, physical examination and Genetics consultation Frequency of sporadic, familial, and genetic syndromes of CRC 25% 1% 3% 1% Sporadic Cases with familial risks 70% FAP HNPCC Hamartomatous polyposis syndrome Burt. Gastroenterol Clin N Amer 1996;25:793. Epidemiology of CRC • CRC is common and lethal • ~149,000 people will be diagnosed, and ~53,000 will die of CRC each year (in US) • Lifetime risk of developing CRC: ~ 4% • Incidence increases with age; median age at diagnosis is 67 years • Recent trends show increasing rates in young individuals Average Annual Age-Specific US Incidence and Mortality Rates of CRC, 1992-1996 Age is the major risk factor for sporadic CRC Number / 100,000 population 600 Incidence in men 500 Incidence in women 400 Mortality in men 300 Mortality in women 200 100 0 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Age group (years) Natl Cancer Inst, SEER Cancer Statistics Review 1973-1996 Risk Factors • Strong • Advanced age • FAP/HNPCC (Lynch syndrome) • Long-standing IBD • Moderate • Personal or family history of adenoma or CRC • Pelvic irradiation • Modest • • • • • High fat diet, red meat diet Smoking, alcohol consumption Cholecystectomy Diabetes mellitus Obesity Protective Factors • NSAID/ Aspirin use • High physical activity • Diet: high fiber, fruits, vegetables • High calcium intake, folate • Hormone replacement therapy CRC presentation • • • • • Rectal bleeding Iron deficiency (occult bleeding) Change in bowel habit/ stool caliber Obstruction May be asymptomatic until advanced/ metastatic • Therefore, important to screen for CRC CRC – Implications for Management of Dental Patients • CRC can metastasize to the oral cavity • Most commonly to posterior mandible • May present with jaw or tooth pain, paresthesia, or loosening of teeth • Neoplasm may be found in a nonhealing extraction socket Clin J Gastro Hepatol 2010;8:A28 CRC – Implications for Management of Dental Patients • CRC associated with oral pathogen Fusobacterium nucleatum • Abundance of F. nucleatum in CRC tissue, mucosa of patients with adenomas • F. nucleatum may have a procarcinogenic effect • More frequent dental visits inversely associated with presence of adenomatous polyps (~ 30% risk reduction) • Maintaining good oral health may be a strategy to prevent colon cancer! Cell Host Microbe. 2013;14:195-206 PLoS One. 2013; 8(1): e53653 Genome Res. 2012. 22: 292-298 Gastroenterology 2019;156:S681-682 Clinical Scenario #4 • 25 yr-old Caucasian woman complains of painful “cracks” at the corners of her lips and a burning sensation on her tongue • Frequent loose, greasy, foul smelling stools Clinical Scenario #4 • Stool studies reveal abnormal amount of fat in stool • She is found to be anemic, deficient in iron and folic acid • Serologic testing shows elevated levels of anti-tissue transglutaminase (TTG) antibodies Diagnosis: Celiac disease Celiac Disease • Inflammatory condition of the small intestine in genetically susceptible individuals • Immune mediated injury in response to ingested gluten (found in wheat, rye, barley) • Occurs primarily in whites of northern European ancestry • Prevalence: 1:120-300 (Europe, N. America) Celiac Disease - Presentation • Classically presents in infancy , but often presents later (ages 10-40) • Malabsorption • Diarrhea/steatorrhea • Weight loss • Signs of nutritional deficiencies • Symptoms can be very mild (subclinical celiac disease) or absent (e.g. asymptomatic iron deficiency) Celiac Disease - Associations • Dermatitis herpetiformis • Diabetes mellitus (Type 1) • Selective IgA deficiency • Down syndrome • Liver disease • Thyroid disease • Infertility • Myocarditis, cardiomyopathy • Lymphoma (EATL) and GI malignancies Dermatitis herpetiformis Oral manifestations of Celiac Disease • Dental enamel defects (enamel hypoplasia) • Bilateral, symmetrical • Recurrent aphthous stomatitis • Delayed tooth eruption • Smaller teeth • Signs of nutrient deficiencies: • Cheilitis • Atrophic glossitis • Gingivitis J Clin Gastroenterol 2008;42:224–232 J Can Dent Assoc 2011;77:b39 Celiac Disease - Diagnosis • Serologic testing • IgA anti-tissue transglutaminase (TTG) antibody • Endoscopy • Scalloped mucosa, flattened villi • Histologic normal celiac • small bowel biopsy = gold standard • Intra-epithelial lymphocytes, crypt hyperplasia, villous atrophy British Dental Journal 2017;222:126-129 Celiac disease – Treatment • • • • Dietary counseling, education about disease Gluten-free diet Correction of nutritional deficiencies Prevention of bone loss - Lifelong avoidance - Avoid wheat, rye, malt, barley, brewer’s yeast, oats (unless labeled gluten free) - Read labels on prepared foods and condiments carefully Celiac Disease– Implications for Management of Dental Patients • Evaluation prior to invasive dental procedures: • Patients may have iron deficiency, coagulopathy secondary to vitamin K deficiency • Prophy paste, fluoride treatments may contain gluten Clinical Scenario #5 • 65 yo male presents for evaluation of bleeding gums • Does not regularly brush or floss • Examination reveals severe periodontal disease, sublingual icterus, parotid gland enlargement Clinical Scenario #5 • He reports a long standing history of alcohol use disorder Diagnosis: Alcoholic cirrhosis, with periodontal disease, sialadenosis Dental & Periodontal Disease in Patients with Alcoholic Cirrhosis • Alcohol abuse predisposes to: • • • • • • Poor oral hygiene Caries Periodontal disease Xerostomia Oral cancers Greater loss of attachment • Infrequent professional dental care Novacek G, et al. J Hepatol 1995;22:576-582. Cirrhosis • Late stage of progressive hepatic fibrosis • Causes: • • • • • • • • • • Alcohol abuse Hepatitis C Hepatitis B Non-alcoholic fatty liver disease Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis Hereditary hemochromatosis Wilson’s disease Alpha-1-antitrypsin deficiency http://www.stanford.edu/group/virus/flavi/2004gallo/cirrhosis.jpg Cirrhosis - Complications • Portal hypertension • • • • Ascites Gastroesophageal varices Hepatic encephalopathy Hypersplenism  thrombocytopenia • Impaired synthetic function • Hypoalbuminemia • Coagulopathy • Hepatocellular carcinoma Cirrhosis – Orofacial Manifesations Jaundice Icterus of palate Sialdenosis • • • • • • • Lichen Planus Scleral, oral/sublingual icterus Gingivitis, gingival bleeding Petechiae, bruising Glossitis, cheilitis Sialdenosis (ETOH) HCV: xerostomia, lichen planus, sialdenitis HCC: metastasis to jaw/oral cavity HCC metastasis Cirrhosis – Implications for Management of Dental Patients • Risk of infection (HBV, HCV) – take precautions • Risk of bleeding – check Platelets, coags • Altered drug metabolism • Analgesics – • Acetaminophen: limit to 1-2g/day • NSAIDs: caution; can precipitate kidney failure, GIB • Opioids: increase dose interval, short term • Anesthetics – • Lidocaine, mepivacaine, prilocaine – limit dose • Sedatives – • BZDs – reduce dosage, increase intervals, or avoid if possible Dental drugs metabolized primarily by liver: Local anesthetics: Lidocaine, Mepivacaine, Prilocaine, Bupivicaine Analgesics: Aspirin, acetaminophen, codeine, Demerol, ibuprofen Sedatives: Valium, barbiturates Antibiotics: Ampicillin, Tetracycline, Metronidazole, Vancomycin Cirrhosis – Implications for Management of Dental Patients • Liver Transplant • Pre-transplant: • Comprehensive dental evaluation • Extraction of infected, non-restorable teeth • Oral hygiene instruction • Post-transplant: • No elective dental treatment for 3 months after surgery Summary • Several GI disorders have prominent oral manifestations, and may have important implications on dental management • The oral cavity can be important in detecting and monitoring underlying gastrointestinal diseases • Recognition of abnormalities can lead to identification of underlying illness that may be otherwise clinically silent