2Aphthous Ulcers Pathogenesis Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease with evidence of an inappropriate innate immune response. The stages in which it progresses:*Preulcerative stageT-lymphocytic infiltrate into epithilium. Cytokines involved: TNF-a, IL-2,IL-10.*Papular swelling with erythematous haloLocalized keratinocyte vacuolization with surrounding vasculitis.
3Although the exact cause for the exaggerated immune response Pathogenesis*UlcerationPapular ulceration, covered by a fibrinous exudate.*Healing with epithelial regeneration.Although the exact cause for the exaggerated immune responseIs not known, there are a few known predisposing/precipitating factors.
4Pathogenesis: Predisposing/Precipitating Factors *Heredity-42% of patients have +ve family history.-90 of likelihood of developing lesions when both parents affected.*Psychologic factorsStress and anxiety been implicated in development of aphthous ulcers.*Mechanical trauma
5Pathogenesis *Endocrine Association of RAS with the menstrual cycle, pregnancy, use of oral contraceptives - suggest a possible relation to hormonal imbalance.*Systemic Conditions-Behçet syndrome-Crohn disease-Immune disturbances (HIV, cyclic neutropenia), Viral infection (HSV1)-Drug exposure (NSAIDs, alendronate, nicorandil)
6Pathogenesis *Dietary deficiencies Iron, folate or vit B12 deficiency in patients increases chances of developing aphthae (replacement therapy often improves the condition).*AllergyPatients with known allergy could benefit from avoiding the allergen.-Common kinds of foods that are potential allergens: milk, cheese, nuts, flour, tomatoes, citrus fruits, shellfish.-Cinnamic aldehyde: artificial cinnamon flavoring-Sodium lauryl sulfate present in toothpaste.
7Aphthous Ulcers Clinical Presentation Painful open sores inside the mouth caused by a break in the mucuous membraneTypically white color / erythematous around lesion.
8Clinical Presentation 4 Types:Recurrent Aphthous Stomatitis (aka Sutton’s Disease)Minor aphthous ulcerations – most common / least severeMajor aphthous ulcerations – greater than 10mm in sizeHerpetiform aphthous ulcerations – most severe formSources:Wikipedia.org
9Clinical Presentation Minor Aphthous UlcersOccur in childhood / adolescenceExclusively on non-keratinized mucosa (floor of mouth, buccal mucosa, soft palate)Usually yellow-grey in color with erythematous halo less than 10 mm around itHerpetiform aphthous ulcerationsOccurs frequently in femalesOnset usually in adulthoodSmall numerous lesions of 1 – 3 mm in clustersYoung, Stephen K.. Canker Sores & Cold Sores: What's the Difference. Continuing Education. University of Oklahoma College of Dentistry. Retrieved on 2006 August 22.
10Clinical Presentation Major Aphthous UlcersTypically up to 10 mm in sizePainful and typically leave a scarTake up to 1 month to healRecurrent Aphthous StomatitisTypically occurs in 10% of the population1 Young, Stephen K.. Canker Sores & Cold Sores: What's the Difference. Continuing Education. University of Oklahoma College of Dentistry. Retrieved on 2006 August 22.
11Aphthous Ulcers Diagnostic Tests Diagnosis of aphthous ulcers is usually based on clinical signs and symptoms.There are tests which may be ordered to rule out other ulcer etiologies:r/o nutritional deficiency of vit B12, folate, ironr/o herpetic stomatitis with cytology smear (-) for cytopathic effects, (-) viral culture/ immunofluoresencer/o HIV for large, slow-healing ulcers
12Diagnostic Testsr/o cancer for non-healing ulcer with biopsyr/o Crohn disease with biopsy (+) for characteristic granulomatous inflammationr/o Behçet syndrome- presence of anogenital or ocular lesions, arthralgia, skin, vascular or neurological involvementr/o cyclic neutropenia with CBCr/o possible drug reaction due to cytopathic drug therapies
13Aphthous Ulcers Histologic Appearance Aphthous MinorFibrinopurulent exudate overlying granulation tissue consisting of many neutrophils, macrophages, and plasma cells. Mast cells and eosinophils are few.Aphthous MajorSame as aphthous minor, plus perivascular lymphocyte infiltration. Inflammation goes deep into underlying connective tissue (CT). CT destruction heavy scar tissue formed upon healing.Herpetiform UlcersIdentical to Aphthous Minor, shallow little CT destruction no scarring.Behçet SyndromeSimilar to aphthous minor, plus severe vasculitis: destruction of blood vessel walls due to inflammatory cell infiltrates.
14Histologic Appearance: Aphthous ulcer biopsy *Inflammation accompanies ulceration: an area of epithelial degeneration.*A diagnosis of aphthous ulcer cannot be based on histological findings alone.*The dark line on right traces the basement membrane outlining intact epithelium.
16Treatment of Aphthous Ulcers Early treatment/avoidance of triggers:Data support that early treatment promotes more rapid healing.1Topical anesthetics including triamcinolone in orabase, fluocinonide gel in orabase.Identify and avoid triggers (physical trauma, emotional stress, food hypersensitivity like chocolate, sodium lauryl sulfate, menstrual cycle association).1. Oral Lesions Goldstein, Beth MD UpToDate.com
17Treatment of Aphthous Ulcers cont’d Supportive Care2Symptomatic reliefAnestheticsOTC BenzocaineCompound anestheticsViscous lidocaineCovering agents/Compound agentsKaolin and Pectin5% amlexanox1:1:1 solution of Milk of Magnesia + Benadryl + Viscous lidocaine
18OTC Treatment of Aphthous Ulcers Herbal remedies-Example: rock rose, 1:1 sage + chamomile mouthwash, echinacea.Cleansing agents-Example: hydrogen peroxideToothpaste without sodium lauryl sulfateVitamins/dietary supplements: vitamin B, vitamin C, zinc lozenges, L-lysine tablets.2. Dr. Younai’s lecture on Immunosurpressive therapeutics.
19Treatment of Aphthous Ulcers in Autoimmune Disease (Behcet’s, Crohn’s disease) Local treatment: same as for other conditions with focus on symptom relief. Topical tetracycline mouthwash may be of benefit in patient’s with Behcet’s disease, although this may cause staining of teeth.Systemic treatment: includes steroids, and immune modulators including cyclophosphamide, azathioprine, thalidomide, and cyclosporine.
20Treatment of Aphthous Major Emphasize on the combined use of short-term systemic drugs and topical steroidsSystemic: thalidomide (200 mg daily x4 weeks) has been studied in HIV positive patients who have severe recurrent aphthous stomatitis and has been shown to improve the chance of healing4. However, recurrence of ulcers is common after stopping treatment.Topical steroids:Ex: Triamcinolone.Antimicrobial rinses to reduce secondary infection.-- Ex: Chlorhexidine gluconateAnti-inflammatory agents including 5% amlexanox.Topical anesthetic to allow for eating3.3. Contemporary oral and maxillofacial pathology nd Editon J. Philip Sapp4. N. Engl. J. Med 1997; 336: 1487.
21References(UCLA Dept. of Medicine 2004)Sapp J, Eversole L., Wysocki G. Contemporary Oral and Maxillofacial Pathology. Mosby Inc nd edition.Burket's Oral Medicine,Diagnosis and TreatmentShafer's Textbook of Oral PathologyWikipedia.orgYoung, Stephen K. Canker Sores & Cold Sores: What's the Difference. Continuing Education. University of Oklahoma College of Dentistry. Retrieved on 2006 August 22.Goldstein, Beth MD. “Oral Lesions” UpToDate.comDr. Younai’s lecture on Immunosupressive Therapeutics
22QUESTIONSWhich test can provide a specific diagnosis of aphthous ulcer? a. immunofluorescence b. acid/base test c. brush biopsy d. there is no specific diagnostic test for aphthous ulcerWhat is the most common form of aphthous ulcers? a. Recurrent Aphthous Stomatitis (aka Sutton’s Disease) b. Minor aphthous ulcerations c. Major aphthous ulcerations d. Herpetiform aphthous ulcerations