Oral Medicine Block Presentation:

Aphthous Ulcers
Submitted by
Rita Chen
Diana Craft
Sujain Dissanayake
Neil Patel
Asha Sethu Madhavan

Aphthous 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 stage
T-lymphocytic infiltrate into epithilium. Cytokines
involved: TNF-a, IL-2,IL-10.
*Papular swelling with erythematous halo
Localized keratinocyte vacuolization with
surrounding vasculitis.

Pathogenesis

*Ulceration
Papular ulceration, covered by a fibrinous exudate.

*Healing with epithelial regeneration.

Although the exact cause for the exaggerated immune response
Is not known, there are a few known predisposing/precipitating factors.

Pathogenesis: Predisposing/Precipitating Factors

*Heredity
-42% of patients have +ve family history.
-90 of likelihood of developing lesions when both parents affected.

*Psychologic factors
Stress and anxiety been implicated in development of aphthous ulcers.

*Mechanical trauma

Pathogenesis

*Endocrine
Association of RAS with the menstrual cycle, pregnancy, use of oral
contraceptives - suggest a possible relation to hormonal imbalance.

*Systemic Conditions
-Behet syndrome
-Crohn disease
-Immune disturbances (HIV, cyclic neutropenia), Viral infection (HSV1)
-Drug exposure (NSAIDs, alendronate, nicorandil)

Pathogenesis
*Dietary deficiencies
Iron, folate or vit B12 deficiency in patients increases chances of
developing aphthae (replacement therapy often improves the
condition).
*Allergy
Patients 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.

Aphthous Ulcers
Clinical Presentation

Painful open sores inside the mouth caused by a

break in the mucuous membrane
Typically white color / erythematous around lesion.

Clinical Presentation

4 Types:
Recurrent Aphthous Stomatitis (aka Suttons Disease)
Minor aphthous ulcerations most common / least severe
Major aphthous ulcerations greater than 10mm in size
Herpetiform aphthous ulcerations most severe form

Clinical Presentation
Minor Aphthous Ulcers
Occur in childhood / adolescence
Exclusively on non-keratinized mucosa (floor of
mouth, buccal mucosa, soft palate)
Usually yellow-grey in color with erythematous halo
less than 10 mm around it

Herpetiform aphthous ulcerations

Occurs frequently in females
Onset usually in adulthood
Small numerous lesions of 1 3 mm in clusters

Clinical Presentation

Major Aphthous Ulcers

Typically up to 10 mm in size
Painful and typically leave a scar
Take up to 1 month to heal

Recurrent Aphthous Stomatitis

Typically occurs in 10% of the population

Aphthous 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, iron
r/o herpetic stomatitis with cytology smear (-) for
cytopathic effects, (-) viral culture/
immunofluoresence
r/o HIV for large, slow-healing ulcers

Diagnostic Tests
r/o cancer for non-healing ulcer with biopsy
r/o Crohn disease with biopsy (+) for
characteristic granulomatous inflammation
r/o Behet syndrome- presence of anogenital or
ocular lesions, arthralgia, skin, vascular or
neurological involvement
r/o cyclic neutropenia with CBC
r/o possible drug reaction due to cytopathic drug
therapies

Aphthous Ulcers
Histologic Appearance
Aphthous Minor
Fibrinopurulent exudate overlying granulation tissue consisting
of many neutrophils, macrophages, and plasma cells. Mast cells
and eosinophils are few.

Aphthous Major
Same as aphthous minor, plus perivascular lymphocyte
infiltration. Inflammation goes deep into underlying connective
tissue (CT). CT destruction heavy scar tissue formed upon
healing.

Herpetiform Ulcers
Identical to Aphthous Minor, shallow little CT destruction no
scarring.

Behet Syndrome
Similar to aphthous minor, plus severe vasculitis: destruction of
blood vessel walls due to inflammatory cell infiltrates.

Histologic 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.

Differential Diagnosis of Aphthous

Ulcers
Infection: HSV, CMV, HIV, Coxsackie virus,
syphilis, histoplasmosis
Autoimmune: Behcets disease, SLE, Crohns
disease, bullous pemphigoid, pemphigous
vulgaris, cicatricial pemphigoid, erythema
multiforme.
Neoplasms: squamous cell carcinoma.
Medications: methotrexate, chemotherapy.
Poor nutrition: including vitamin deficiencies.

Treatment of Aphthous Ulcers

1. Early treatment/avoidance of triggers:

Data support that early treatment promotes

more rapid healing.1
Topical 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

Treatment of Aphthous Ulcers

contd

2. Supportive Care2

Symptomatic relief
Anesthetics

OTC Benzocaine
Compound anesthetics

Viscous lidocaine

Covering agents/Compound agents

Kaolin and Pectin

5% amlexanox
1:1:1 solution of Milk of Magnesia + Benadryl + Viscous
lidocaine

OTC Treatment of Aphthous Ulcers

Herbal remedies
-Example: rock rose, 1:1 sage + chamomile
mouthwash, echinacea.
Cleansing agents
-Example: hydrogen peroxide
Toothpaste without sodium lauryl sulfate
Vitamins/dietary supplements: vitamin B, vitamin
C, zinc lozenges, L-lysine tablets.
2. Dr. Younais lecture on Immunosurpressive therapeutics.

Treatment of Aphthous Ulcers in

Autoimmune Disease (Behcets,
Crohns disease)

Local treatment: same as for other

conditions with focus on symptom relief.
Topical tetracycline mouthwash may be of
benefit in patients with Behcets disease,
although this may cause staining of teeth.
Systemic treatment: includes steroids,
and immune modulators including
cyclophosphamide, azathioprine,
thalidomide, and cyclosporine.

Treatment of Aphthous Major

Emphasize on the combined use of short-term systemic drugs and
topical steroids
Systemic: 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 healing 4. However, recurrence of
ulcers is common after stopping treatment.
Topical steroids:
Ex: Triamcinolone.

Antimicrobial rinses to reduce secondary infection.

-- Ex: Chlorhexidine gluconate
Anti-inflammatory agents including 5% amlexanox.
Topical anesthetic to allow for eating 3.

3. Contemporary oral and maxillofacial pathology

4. N. Engl. J. Med 1997; 336: 1487

2nd Editon

J. Philip Sapp

References

www.med.ucla.edu/modules/wfsection/article.php (UCLA Dept. of Medicine 2004)

Sapp J, Eversole L., Wysocki G. Contemporary Oral and Maxillofacial Pathology. Mosby Inc.
2004. 2nd edition.

Burket's Oral Medicine,Diagnosis and Treatment

Shafer's Textbook of Oral Pathology

Wikipedia.org

Young, 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.com

Dr. Younais lecture on Immunosupressive Therapeutics

http://www.dentistry.ubc.ca/research/priddy/HTMLS/MIC1RAU.HTM

QUESTIONS
Which 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 ulcer
What is the most common form of aphthous ulcers?
a. Recurrent Aphthous Stomatitis (aka Suttons
Disease)
b. Minor aphthous ulcerations
c. Major aphthous ulcerations
d. Herpetiform aphthous ulcerations