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
Students seeking more information about Aphthous Ulcers are encouraged to visit This Link to hear a podcast by Brian Muzyka about this topic.
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
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.
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
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
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
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.
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.
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 )
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.
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.
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
- Porter SR, Scully C. Orofacial
manifestations in primary immunodeficiencies: Polymorphonuclear leukocyte
defects. J Oral Pathol Med 1993;22(7):310-311.
- Brooke RI, Sapp JP. Herpetiform
ulceration. Oral Surg Oral Med Oral Pathol 1976;42(2):182-188.
- Natah SS, Häyrinen Immonen R, Hietanen
J, et al. Quantitative assessment of mast cells in recurrent aphthous ulcers
(RAU). J Oral Pathol Med
A, Klausen B, Hougen HP, Ryder LP. Peripheral lymphocyte subpopulations
in recurrent aphthous ulceration. Acta Odontol Scand 1991;49:203-206.
- 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.
- Herlofson BB, Barkvoll P. Sodium lauryl
sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand
- 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.
- Skaare AB, Herlofson BB, Barkvoll P.
Mouthrinses containing triclosan reduce the incidence of recurrent aphthous
ulcers (RAU). J Clin Periodontol
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
- Nolan A, Lamey PJ, Milligan KA, Forsyth
A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med
- 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.
- 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.
- Yaacob HB, Ab Hamid J. Use of
antidepressants in aphthous ulceration—A clinical experience. Dent J Malay
- Wood TA Jr, De Witt SH, Chu EW, et al.
Anitschkow nuclear changes observed in oral smears. Acta Cytol
- 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.
- Wright EF. Clinical effectiveness of
lysine in treating recurrent aphthous ulcers and herpes labialis. Gen Dent
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
TF, Kutcher MJ, Overholser CD, et al. Effect of an antimicrobial
mouthrinse on recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol
- 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.
Associated With RAU
deficiencies: vitamins B1, B2, B6, B12,
disorders: neutropenia, cyclic neutropenia
aphthous ulcers, pharyngitis, and adenopathy (FAPA) in children
disease: Crohn’s, gluten enteropathy with or without G1 lesions (celiac
disease), ulcerative colitis
and psychological stress
immunodeficiency virus (HIV) infection
status in women
and genital ulcers with inflamed cartilage (MAGIC syndrome)
Levels of Treatment Recommendations for
A history of occasional aphthous ulcers
SLS-containing oral hygiene products
precipitating foods and other factors
patient of the benign and noncontiguous nature
Use OTC remedies for pain control
Presents with aphthous at the oral examination
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
adequacy of oral health
out systemic associations
Rx: Systemic corticosteroids or other medications if
nonresponsive or unable to use steroids
of the previous recommendations
Tetracycline or related antibiotics
Treatments for RAU
gels, liquids, and pastes containing 10-20% benzocaine
gels, or liquids containing 2% lidocaine
Medications for the Management of RAU
oral paste 5%
- Topical corticosteroids:
fluocinonide, Kenalog in Orabase
- 0.12% chlorhexidine gluconate
- Systemic corticosteroids:
dexamethasone elixer, prednisone
- Viscous lidocaine 2%
or antidepressant medication: diazepam, alaprazolam