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Recurrent Aphthous Ulcers

Prevention and Treatment

 

Recurrent aphthous ulcers (RAU) or recurrent aphthous stomatitis, referred to as canker sores, are among the most common oral mucosal diseases. Recurrent aphthous ulcer disease is characterized by outbreaks with periods of remission that last weeks or years. This chronic, incurable condition can make it uncomfortable to speak, eat, and/or drink. Since some oral healthcare products are catalysts in the development of RAU, and some patients experience difficulty in maintaining oral hygiene, dental professionals play an important role in the oral healthcare of patients with RAU.

Students seeking more information about Aphthous Ulcers are encouraged to visit This Link to hear a podcast by Brian Muzyka about this topic.

 

Clinical Features

Aphthous ulcers typically develop on nonkeratinized oral-lining mucosa, the tongue, or more rarely, on genital mucosa. The development of an aphthous ulcer is usually preceded by burning, tingling, swelling, or mucosal erythema approximately 24 hours prior to its appearance. The ulcer develops without vesicle (ie, blister) formation.

There are three major types of aphthous ulcers: minor, major, and herpetiform. Most patients have minor oral aphthous ulcer disease, which may not require treatment. Minor aphthous ulcers are generally solitary and exhibit a round to oval appearance with a gray to white fibrinous cap, and a halo of mucosal erythema surrounding the intact mucosa (Figures 1 and 2). These ulcers will heal without scarring in seven to 14 days. The frequency of minor RAU can vary from one to 12 episodes per year and decreases with age, unless the onset is later in life.

Major aphthous ulcers (also known as Sutton’s disease or periadenitis mucosa necrotica recurrens) present as deep, crateriform, irregular lesions, which often measure 1 cm in diameter (Figure 3). Multiple ulcers can last for weeks or months before healing and may be accompanied by scarring. It is important to consider possible underlying systemic conditions such as nutritional deficiency or hematologic disorders (Table 1).

Herpetiform RAU is characterized by the development of one or more crops composed of dozens of small (1 mm to 3 mm in diameter), superficial, yet very painful ulcerations, which may coalesce to form large ulcers with irregular borders (Figure 4). Herpetiform RAU, which occurs more often in females,1,2 is not related to a herpes simplex virus infection, and the ulcers do not respond to specific antiviral therapy such as acyclovir. Herpetiform ulcerations may respond to tetracycline treatment or corti­costeroid therapy (Figure 5).1,2

 

Etiology

While the etiology of RAU is unknown, it appears to be related to genetic, immunologic, environmental, or systemic factors. Genetic factors include a familial tendency, although there has been no clear association with specific human leukocyte antigen (HLA) groups. Immunologic evidence includes an increase in mast cell numbers3 and degranulation in prodromal lesions with an increase in peripheral lymphocyte populations.4 Systemic conditions must be considered, especially in the patient with late-in-life onset, frequent, or herpetiform RAU, which requires long-term prescription medication (Table 1). The use of oral hygiene products (eg, dentifrices and mouthwash) that contain sodium lauryl sulfate (SLS)5 and/or cessation of tobacco use should be considered, as both these environmental factors can exacerbate RAU.

 

Environmental Factors

Mechanical trauma from a toothbrush or a sharp piece of food may elicit ulcer development. Avoiding SLS in dentifrices and mouthrinses has been reported to result in a 64% decrease in the occurrence of aphthous ulcers.6 Mouthrinses that contain triclosan, however, have been shown to reduce oral aphthous ulcers and counteract the effect of SLS.7,8  

 

Systemic Associations

Nutritional deficiencies or hematologic diseases have been documented in 20% of patients with RAU. When patients are referred to physicians for treatment for deficiencies of iron, folate, and vitamin B12, a 71% improvement in aphthous ulcers has been reported following replacement therapy.9

Sensitivity to foods, preservatives, or other agents has been identified in 35% to 50% of patients with RAU.10 Patients can be referred to an allergist to identify the allergens. Alternatively, an elimination diet may be of benefit in identifying foods or additives that may precipitate aphthous ulcers in sensitive individuals.11

Stress has been implicated as a precipitating factor in the onset of RAU, although this has not been clearly defined.12 Some patients, however, have benefited from the empirical use of anxiolytic or antidepressant agents.13  

Patients with Behçet’s disease frequently have oral aphthous-type ulcers. There is an association with HLA types including: HLA types B12 (mucocutaneous), B5 (ophthalmic), and B27 (arthritic). The mucocutaneous type exhibits oral and genital ulcerations and skin pustules. Other types of Behçet’s disease may include lesions of the eye, joints, nervous system, or gastrointestinal tract.

 

Diagnosis

The diagnosis of RAU is primarily clinical. In cases where ulcers fail to heal, supplemental diagnostic laboratory tests (eg, cytology, biopsy, and culture) can be administered. These supplemental tests, while not definitive for RAU, may exclude other disease processes such as viral or fungal infection and malignant disease. Cytologic features consistent with RAU include the Anitschkow-like nuclear chromatin bar seen in the nuclei of epithelial cells.14 Cytology may also detect viral features suggestive of herpes simplex or varicella zoster virus ulcers. The microscopic features of biopsied aphthous ulcers are that of a non­specific ulcer. Biopsy can be used to rule out deep fungal infection or neoplastic disease. A culture could identify specific viral or bacterial infection.

 

Prevention

In the absence of predisposing systemic conditions, prevention of RAU involves meticulous oral hygiene and avoidance of foods known to precipitate ulcers, such as citrus fruits, tomatoes, and walnuts. Avoidance of oral hygiene products containing SLS may be warranted, and utilizing a soft toothbrush and a gentle brushing technique may help. A daily multi­vitamin is a safe recommendation for most patients.

The patient with an onset of RAU linked to tobacco cessation may require nicotine supplements. Recommendations about the use of supplemental nicotine should be made in consultation with the dentist and/or a physician.

In the case of frequent ulcers, prophylactic prescription 0.12% chlorhexidine mouthrinse may be of benefit in prevention, as well as the reduction of secondary infection and the promotion of healing.15

(Continued from page 1 )

Oral Hygiene Treatment

The goal of treatment is to provide the patient with control over this condition by increasing comfort, decreasing the frequency of future ulcers, and promoting healing of existing ulcers (Table 2). Several over-the-counter preparations and prescription medications can temporarily alleviate the pain associated with RAU (Tables 3 and 4).

Nonprescription lysine, used as a dietary supplement at 500 mg daily, 1000 mg daily if prodromal symptoms develop, and 1000 mg four times daily if an aphthous ulcer develops, has been helpful in decreasing ulcer frequency and severity in some individuals.16

Topical amlexanoxpaste 0.5% (available by prescription) has been shown to reduce the duration and pain of aphthous ulcers in clinical studies.17-19 Amlexanox, which has antiallergic properties, is applied four times daily until the ulcer is healed.

Topical corticosteroids are the mainstay of treatment for recurrent aphthous ulcers unresponsive to amlexanox. Topical triamcinolone (0.1% oral paste) or fluocinonide (0.05% gel) used either two or four times daily are effective when applied in a thin film to a dried lesion.20

A tetracycline suspension 125 mg/5cc or 250-mg capsule one to three times daily can be helpful, especially for patients with herpetiform RAU. Tetracycline reduces the severity of aphthous ulcers, but may not reduce the frequency of occurrence.21

Less frequently used medications such as colchicine, pentoxifylline,22 dapsone, and thalidomide may be indicated for cases that do not respond to traditional approaches.

As no single treatment has been found to be uniformly effective in all patients with RAU, it may be necessary to try several types of medication and/or behavior modifications. Patient education about the chronic nature of the disease and its association with precipitating factors is critical. Clinical evaluation of aphthous ulcer patients should occur at least annually if patients require prescription medication.

 

Oral Hygiene

Achieving and maintaining excellent oral hygiene is important, especially during severe outbreaks. Patients should brush and floss twice daily, in the morning and at bedtime. Oral hygiene procedures may become too painful for patients with frequent outbreaks. Moreover, vigorous oral hygiene practices can precipitate new ulcers. Antimicrobial nonprescription mouthrinses23 and 0.12% chlorhexidine gluconate24 have been helpful in reducing the duration and discomfort of active lesions and, with long-term daily use, reducing recurrences. While active ulcers are present, mouthrinses containing alcohol are the most effective.

 

Conclusion

Recurrent aphthous ulceration is a common, chronic, incurable, oral mucosal disease process of uncertain etiology with multifactorial systemic associations and precipitating factors. Preventive and treatment modalities may reduce the number of future ulcers and facilitate healing of developed lesions. A careful medical and dental history, including the use of oral hygiene products, may aid in detecting systemic or local precipitating factors. Treatment strategies can be followed to give the patient maximum control with the fewest adverse effects. Annual dental evaluation of treatment for aphthous ulcers is recommended.

 

Ed. Note: For more information on this topic, we suggest you read our article entitled Diagnosis and Treatment of Recurrent Aphthous Ulcers

References

  1. Porter SR, Scully C. Orofacial manifestations in primary immunodeficiencies: Polymorphonuclear leukocyte defects. J Oral Pathol Med 1993;22(7):310-311.
  2. Brooke RI, Sapp JP. Herpetiform ulceration. Oral Surg Oral Med Oral Pathol 1976;42(2):182-188.
  3. Natah SS, Häyrinen Immonen R, Hietanen J, et al. Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU). J Oral Pathol Med 1998;27(3):124-129.
  4. Pederson A, Klausen B, Hougen HP, Ryder LP. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration. Acta Odontol Scand 1991;49:203-206.
  5. Herlofson BB, Barkvoll P. The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. Acta Odontol Scand 1996;54(3):150-153.
  6. Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand 1994;52(5):257-259.
  7. Skaare AB, Rölla G, Barkvoll P. The influence of triclosan, zinc or propylene glycol on oral mucosa exposed to sodium lauryl sulfate. Eur J Oral Sci 1997;105(5):527-533.
  8. Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol 1996;23(8):778-781.
  9. Olson JA, Feinberg I, Silverman S Jr, et al. Serum vitamin B12, folate, and iron levels in recurrent aphthous ulceration. Oral Surg Oral Med Oral Pathol 1982;54(5):517-520.
  10. Nolan A, Lamey PJ, Milligan KA, Forsyth A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med 1991;20(10):473-475.
  11. Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol 1984;57(5):504-507.
  12. Miller MF, Ship II. A retrospective study of the prevalence and incidence of recurrent aphthous ulcers in a professional population, 1958-1971. Oral Surg Oral Med Oral Pathol 1977;43(4):532-537.
  13. Yaacob HB, Ab Hamid J. Use of antidepressants in aphthous ulceration—A clinical experience. Dent J Malay 1985;8(1):33-38.
  14. Wood TA Jr, De Witt SH, Chu EW, et al. Anitschkow nuclear changes observed in oral smears. Acta Cytol 1975;19(5):434-437.
  15. Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the manage­ment of minor aphthous ulceration. A double-blind, placebo-controlled cross-over trial. Br Dent J 1987;162(3):106-110.
  16. Wright EF. Clinical effectiveness of lysine in treating recurrent aphthous ulcers and herpes labialis. Gen Dent 1994;42(1):40-42.
  17. Khandwala A, Van Inwegen RG, Alfano MC. 5% Amlexanox oral paste, a new treatment of recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83(2):222-230.
  18. Khandwala A, Van Inwegen RG, Charney MR, Alfano MC. 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: II. Pharmacokinetics and demonstration of clinical safety. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83(2):231-238.
  19. Binnie WH, Curro FA, Khandwala A, Van Inwegan RG. Amlexanox oral paste: A novel treatment that accelerates the healing of aphthous ulcers. Compend Cont Educ Dent 1997;18(11):1116-1118, 1120-1122, 1124 passim.
  20. Pimlott SJ, Walker DM. A controlled clinical trial of the efficacy of topical applied fluocinonide gel in the treatment of recurrent aphthous ulceration. Br Dent J 1983;154(6):174-177.
  21. Hayrinen-Immonen R, Sorsa T, Pettila J, et al. Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers. J Oral Pathol Med 1994;23(6):269-272.
  22. Chandrasekhar J, Liem AA, Cox NH, Paterson AW. Oxipentiyllin in the management of recurrent aphthous oral ulcers: An open clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(5):546-567.
  23. Meiller TF, Kutcher MJ, Overholser CD, et al. Effect of an antimicrobial mouthrinse on recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1991;72(4):425-429.
  24. Matthews RW, Scully GM, Levers BGH, Hislop WS. Clinical evaluation of benzydamine, chlorhexidine, and placebo mouthwashes in the management of recurrent aphthous stomatitis. Oral Surg  Oral Med Oral Pathol 1987;63:189-191.

 

 

 

Table 1

Systemic Conditions Associated With RAU

  • Nutritional deficiencies: vitamins B1, B2, B6, B12, or iron
  • Zinc deficiency
  • Hematologic disorders: neutropenia, cyclic neutropenia
  • Fever, aphthous ulcers, pharyngitis, and adenopathy (FAPA) in children
  • Bowel disease: Crohn’s, gluten enteropathy with or without G1 lesions (celiac disease), ulcerative colitis
  • Orofacial granulomatosis
  • Allergies
  • Physical and psychological stress
  • Behcet’s disease
  • Human immunodeficiency virus (HIV) infection
  • Hormonal status in women
  • IgA deficiency
  • Mucosal and genital ulcers with inflamed cartilage (MAGIC syndrome)


Table 2

Levels of Treatment Recommendations for RAU

Condition

Recommendations

Medications

A history of occasional aphthous ulcers

  • Avoid SLS-containing oral hygiene products
  • Avoid precipitating foods and other factors
  • Reassure patient of the benign and noncontiguous nature
 

Use OTC remedies for pain control

Presents with aphthous at the oral examination

  • All previous recommendations
  • Multivitamin daily
  • Achieve and maintain excellent oral hygiene
 

Topical amelanox paste, 4x daily. Topical corticosteroid, 2x daily. Chlorhexidine 0.12% mouthwash, 2x daily.

Frequent recurrences of minor RAU or has major RAU

  • All previous recommendations
  • Evaluate adequacy of oral health
  • Rule out systemic associations
 

Rx: Systemic corticosteroids or other medications if nonresponsive or unable to use steroids

Herpetiform RAU

  • All of the previous recommendations
 

Tetracycline or related antibiotics

 

Table 3

Over-the-Counter Treatments for RAU

  • Ointments, gels, liquids, and pastes containing 10-20% benzocaine
  • Ointments, gels, or liquids containing 2% lidocaine
  • Hydrocortisone ointment 0.5%

 

Table 4

Prescription Medications for the Management of RAU

  • Amlexanox oral paste 5%
  • Topical corticosteroids: fluocinonide, Kenalog in Orabase
  • 0.12% chlorhexidine gluconate mouthrinse
  • Systemic corticosteroids: dexamethasone elixer, prednisone
  • Viscous lidocaine 2%
  • Tetracycline
  • Colchicine
  • Acyclovir
  • Cimetidine
  • Pentoxifyline
  • Azathioprine
  • Dapsone
  • Thalidomine
  • Azelastine
  • Interferon
  • Anxiolytic or antidepressant medication: diazepam, alaprazolam
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