Canker Sores (Aphthous Ulcers): Overview and Management 

 

Definitions 

• Canker Sores (Aphthous Ulcers): Painful sores of the oral mucosa which have the propensity to recur (Plewa & Chatterjee). 
• Recurrent aphthous stomatitis (RAS): A chronic inflammatory condition in which patients develop recurrent Canker Sores (Scully & Porter, 2008). 

Background 

• Symptoms: Canker sores are small, shallow, painful oral ulcers which form inside of the mouth. These ulcers typically present as round ulcerations with a white or yellowish center and an erythematous border (Plewa & Chatterjee) 

Subtypes of Aphthous Ulcers 

• Minor Aphthous Ulcers: Minor RAS is the most common form of RAS (Field et al., 2008) accounting for roughly 80% of the RAS population. These ulcers are less than 5mm in diameter and are round with a grey, white pseudomembrane and an erythematous border. These ulcers typically affect non-keratinized surfaces and heal within 10-14 days (Scully & Porter, 2008). See figure 1 (Florian Brandt) 

Figure 1

• Major Aphthous Ulcers: Major RAS is a more severe form that affects roughly 10% of the RAS population. These ulcers exceed 1 cm in diameter and can occur on keratinized surfaces. These ulcers can take up to 6 weeks to heal and can leave a scar (Scully & Porter, 2008).  
• Herpetiform Aphthous Ulcers: Herpetiform ulcers are the least common form of RAS developing in roughly 1-10% of RAS patients. These ulcerations tend to start as many small ulcers (up to 100 at any given time) which fuse together over time becoming a large, irregularly shaped, ulcer (Scully & Porter, 2008). Despite their name, there is no association with the herpes virus (Plewa & Chatterjee). See figure 4 (Altenberg et. Al, 2014) 

Prevalence 

• Canker sores are widespread, affecting approximately 25% of the population (Ship, 1972). 

Etiology 

• Immunologic factors 
  • The etiology of recurrent aphthous stomatitis is not perfectly understood. In susceptible individuals, the development of aphthous ulcers is related to the body’s lymphocytic response which is mediated by TNF-alpha (Taylor et al.). TNF-alpha causes a cytokine-mediated inflammatory reaction driving the expression of MHC complexes (Savage et al.). Increased MHC expression culminates with CD8+ T-cells targeting epithelial cells leading to ulceration. 
• Genetic predisposition 
  • Although the genetic etiology is not fully understood at this time, it has been estimated that 46% of patients with recurrent aphthous stomatitis ulcers have a positive family history (Chiang et al., 2019). It has also been suggested that there could be a genetic association between RAS and HLA-B51 (Shohat Zabarski et al.). 
• Environmental triggers 
  • Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell & Henricsson, 1985; Dorsey, 1964). 
• Systemic predisposing factors 
  • Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV. 

Prognosis and Treatment 

• Type A 
  • Patients with type A RAS experience episodes of aphthous ulcers a 2-3 times per year. Their ulcers are minimally painful and recover within 2-3 days without the need for medical intervention typically. The goal of treatment for Type A RAS is to identify triggers and try to avoid them (Scully et al., 2003). 
• Type B 
  • Patients with type B RAS experience more painful ulcerations which can last up to 10 days at a time. Generally, these patients have already attempted to identify trigger avoidance and have not seen any relief. These patients may require treatment with chlorhexidine mouthwash and a short course of steroids at the onset of symptoms (Scully et al., 2003). If using steroids, patients should be monitored for yeast superinfection (Anonymous, 1994). 
• Type C 
  • Patients with type C RAS have constant aphthous ulcers. When an aphthous ulcer heals in these patients, a new one forms almost immediately. These patients require medical intervention by an oral medicine specialist. These specialists may use topical corticosteroids, systemic corticosteroids, azathioprine, or other immunosuppressants for treatment. Patients can also get intralesional corticosteroid injections from oral medicine specialists and may benefit from assistance by a dental hygienist frequently to avoid infection (Scully et al., 2003). 

Differential Diagnosis of Patients with Mouth Sores 

• Behcet Disease: Aphthous ulcers are a cardinal feature of Behcet disease and are a part of the diagnostic criteria (Krause et al., 1999). 
• MAGIC Syndrome: Thought to be a variant of Behcet disease. MAGIC syndrome presents with major aphthous ulcers and generalized inflammation of cartilage (Orme et al., 1990). 
• PFAPA Syndrome: This disorder is characterized by periodic fever, aphthous ulcers, pharyngitis, and cervical adenitis. Typically presents in children (Scully & Porter, 2008). 
• HIV: Oral ulceration can be a symptom of HIV infection. Although these are not aphthous ulcers, they can look similar. 
• Cold Sores: Cold sores are derived from the Herpes Simplex virus and are very prevalent around the world. Unlike aphthous ulcers, cold sores are fluid-filled blisters on the outside of the mouth and the lips (National Institute of Dental and Craniofacial Research). 

 

 

 

Bibliography 

Altenburg, A., El-Haj, N., Micheli, C., Puttkammer, M., Abdel-Naser, M., & Zouboulis, C. C. (2014). The treatment of chronic recurrent oral aphthous ulcers. Deutsches Ärzteblatt International. https://doi.org/10.3238/arztebl.2014.0665 

Anonymous. (1994). Double-blind clinical trial of 0.05% clobetasol propionate ointment in orabase and 0.05% fluocinonide ointment in orabase in the treatment of patients with oral vesiculoerosive diseases. Oral Surgery, Oral Medicine, Oral Pathology, 77, 598-604. 

Axell, T., & Henricsson, V. (1985). Association between recurrent aphthous ulcers and tobacco habits. Scandinavian Journal of Dental Research, 93, 239-242. 

Chiang, C. P., Chang, J. Y. F., Wang, Y. P., Wu, Y. H., Wu, Y. C., & Sun, A. (2019). Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management. Journal of Formosan Medical Association, 118(9), 1279-1289. 

Dorsey, C. (1964). More observations on relief of aphthous stomatitis on resumption of cigarette smoking. California Medicine, 101, 377-378. 

Ferguson, M. M., Hart, D. M., Lindsay, R., & Stephen, K. W. (1978). Progestin therapy for menstrual related aphthae. International Journal of Oral Surgery, 7, 463-470. 

Florian Brandt (Benutzer:Monti89), Attribution, via Wikimedia Commons 

Field, E. A., Brookes, V., & Tyldesley, W. R. (1992). Recurrent aphthous ulceration in children—a review. International Journal of Paediatric Dentistry, 2, 1-10. 

Huling, L. B., Baccaglini, L., Choquette, L., Feinn, R. S., & Lalla, R. V. (2012). Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. Journal of Oral Pathology & Medicine, 41(2), 149-152. 

Krause, I., Uziel, Y., Guedj, D., et al. (1999). Childhood Behcet's disease: clinical features and comparison with adult-onset disease. Rheumatology (Oxford), 38, 457-462. 

Mcbride, D. R. (2000b, July 1). Management of Aphthous ulcers. American Family Physician. https://www.aafp.org/pubs/afp/issues/2000/0701/p149.html 

Nolan, A., Lamey, P. J., Milligan, K. A., & Forsyth, A. (1991). Recurrent aphthous ulceration and food sensitivity. Journal of Oral Pathology & Medicine, 20, 473-475. 

Orme, R. L., Nordlund, J. J., Barich, L., & Brown, T. (1990). The MAGIC syndrome (mouth and genital ulcers with inflamed cartilage). Archives of Dermatology, 126, 940-944. 

Pedersen, A. (1989). Psychologic stress and recurrent aphthous ulceration. Journal of Oral Pathology & Medicine, 18(2), 119-122. 

Plewa, M. C., & Chatterjee, K. (Last update: November 13, 2023). Recurrent Aphthous Stomatitis. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 

Savage, N. W., Seymour, G. J., & Kruger, B. J. (1986). Expression of class I and class II major histocompatibility complex antigens on epithelial cells in recurrent aphthous stomatitis. Journal of Oral Pathology, 15, 191-195. 

Scully, C., & Porter, S. (2008). Oral mucosal disease: recurrent aphthous stomatitis. British Journal of Oral and Maxillofacial Surgery, 46(3), 198-206. 

Ship, I. I. (1972). Epidemiologic aspects of recurrent aphthous ulcerations. Oral Surgery, Oral Medicine, Oral Pathology, 33, 400-406. 

Shohat-Zabarski, R., Kalderon, S., Klein, T., & Weinberger, A. (1992). Close association of HLA-B51 in persons with recurrent aphthous stomatitis. Oral Surgery, Oral Medicine, Oral Pathology, 74, 455-458. 

Taylor, L. J., Bagg, J., Walker, D. M., & Peters, T. J. (1992). Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration. Journal of Oral Pathology & Medicine, 21, 21-25. 

 

return to: Therapeutic Agents for Oral Mucosal Disease Treatment Strategies

 

created (December)  by Wilson Fitzgerald BS

 

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September 2018

Cindy Marek, PharmD

Faculty, Dept. of Oral Pathology, Radiology & Medicine

The University of Iowa College of Dentistry

Pathophysiology of Aphthous Stomatitis: Immunologic

• Location: nonkeratinized, unattached mucosal surfaces
  • Typically buccal vestibule, lateral or ventral tongue, floor of mouth
• Heals in a predictable manner
• Types: minor, major, herpetiform
  • Treatment not usually necessary for the common minor type

§  Precipitating Factors:

Cinnamon Oil                                   Medications                                  Sodium Lauryl Sulfate (SLS)

Genetics Stress Estrogen Shifts

Minor Oral Trauma Dentifrices

Primary Prevention Factors:

• Relate to maintenance of salivary pellicle or impeding the recognition of antigens to the immune system

 

Pharmacotherapeutic Management Choices:

§   Topical Route

-    Treatment of choice:  triamcinolone acetonide rinse - alters course of disease, increases healing rates

-    Steroid ointments, pastes

§   Systemic Route

-    Prednisone - for difficult cases, large +/or multiple ulcerations

§   Over-The-Counter Products

 

§   Inappropriate Chronic Treatment

-   Cautery agents - do not affect course of disease (Debacterol®, silver nitrate, Negatan®, laser)

-   Tetracycline rinses, oral antibiotics etc.

 

§   Sodium Lauryl Sulfate (SLS) Free Dentifrices

–         Sodium lauryl sulfate (aka: sodium dodecyl sulfate, SDS) is a surfactant (foaming agent) found in most commercially available toothpastes and gels

◦          Causes dose-dependent epithelial desquamation

◦          Note:  All SLS free products are not appropriate for some patients due to pyrophosphate content

 

–     Cocamidopropyl betaine (CABP or CPB) -  surfactant that is less irritating to tissue than SLS

◦          RX: Previdentâ 5000+ Dry Mouth, 100 g container (only SLS free Previdentâ product)

◦        Note: For overdenture abutments use only Prevident gel (56 g tube), not a dentifrice (does not                      contain surfactants or abrasives)

 

–    OTC dentifrices with CAPB

◦    Biotèneâ (GSK) Fresh Mint Original Formula

◦    Biotèneâ (GSK) Gentle Mint Formula

◦   Sensodyneâ(GSK) products (except Deep Clean which contains SLS)

 

–          Squigleâ Enamel Saver Toothpaste   Our toothpaste of choice

◦   Very mild dentifrice – no tartar control agents or irritating flavors (mild mint)

◦   Uses poloxamer as surfactant – very mild

◦   Can be difficult to find in retail stores, may be obtained online or mailed from D. pharmacy

 

Therapeutic Agents and Treatment Strategies for the Management

of Selected Oral Mucosal Diseases

September 2018

Cindy Marek, PharmD

Faculty, Dept. of Oral Pathology, Radiology & Medicine

The University of Iowa College of Dentistry

Footnote Key:

1.  These medications are all contraindicated in microbial diseases. If given to patients with microbial diseases, microbial proliferation is usually enhanced and systemic dissemination is possible. Candidiasis is a common side effect.

2.  Systemic steroids are contraindicated or must be used with caution in a number of systemic conditions.  Consultation with the patient's physician is recommended before prescribing.  Tapering of prednisone is not necessary with 5-7 day burst therapy. Tapering of prednisone is not necessary with alternate day therapy (QOD) if the dosage does not exceed 20 mg QOD.  In order to reduce the possibility of adrenocortical suppression, it is important that prednisone be taken in harmony with diurnal adrenocortical steroid levels.  In order to accomplish this, prednisone should be taken 1-1/2 hours after normal arising time.  Alternate day AM (QOD) dosage also reduces the possibility of adrenocortical suppression.

3.  Whenever topical mouth rinses or ointments are prescribed, the manner in which the medication is used is very important.  The patient should be advised that the medications are effective on contact and that they should avoid anything by mouth (NPO) for 1/2-1 hour after using them to prolong medication contact time.

4.  Baseline hematology laboratory studies to include platelets are necessary to monitor possible bone marrow suppression.

5.  Hepatotoxicity has been reported.                                                 OPRM Faculty

* Denotes prescription items that must be extemporaneously compounded by a pharmacist. Usually a specialty "compounding pharmacy" is a better choice as they have more experience and knowledge regarding product formulation.

 

Extemporaneously Compounding Medications for Intraoral Conditions

• Few products available in the U.S - ?? limited product demand

• Problems:
  • Difficulty with insurance payments, XIX & Medicare will not reimburse for the full cost
  • Expensive – Dental Pharmacy can mail Rxs to patients living in Iowa – at significantly less cost to patient patients and the products are formulated correctly for improved efficacy
  • “I can do that” - generalized lack of knowledge – many pharmacies incorrectly compound intraoral products causing mucosal irritation, reduced efficacy
• Make sure products are not flavored or sweetened (especially with sucrose) unless necessary!