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
-Behçet 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 Sutton’s 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 Behçet 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.
• Behçet 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: Behcet’s disease, SLE, Crohn’s
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
cont’d
2
2. Supportive Care
•
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. Younai’s lecture on Immunosurpressive therapeutics.
Treatment 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.
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 healing4. 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 eating3.
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. Younai’s 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 Sutton’s
Disease)
b. Minor aphthous ulcerations
c. Major aphthous ulcerations
d. Herpetiform aphthous ulcerations