Aphthous Ulcers

Aphthous Ulcers 

Small painful ulcers predominantly of the oral mucosa

Synonyms

  • Aphthae
  • Canker sores
  • Recurrent aphthous stomatitis (RAS)
  • Recurrent oral aphthae

Epidemiology & Demographics

Prevalence

One in five individuals in their lifetime

Predominant Sex and Age

Most commonly affects women, adolescents, and adults under the age of 40

Peak Incidence

Adolescence

Risk Factors

Genetic factors, stress, trauma, tobacco, viral and bacterial infections, nutritional deficiencies, endocrine and autoimmune diseases

Genetics

Up to 40% of patients have a family history of aphthous ulcers

Physical Findings & Clinical Presentation

  • •Aphthous ulcers, also known as canker sores, are typically small round or oval-shaped lesions with a gray-white or yellow pseudomembranous base and erythematous halo. Aphthous ulcers can affect any age group. However, they generally appear in childhood and subside by the third decade of life. The exact cause is poorly understood, but multiple factors may play a role in their occurrence. These include, but are not limited to, trauma, nutritional deficiencies, viral and bacterial infections, medications, food hypersensitivities, hormonal or endocrine changes, and tobacco use. In the absence of systemic disease and in cases where aphthae reoccur, it is termed Recurrent Aphthous Stomatitis (RAS).
  • •Recurrent aphthous stomatitis is further divided into three subtypes:
    • 1.Minor RAS (80%): Classification dependent on the number and size of the ulcers. Generally, 1 to 5 superficial aphthae less than 10 mm in size and localized to the lips, buccal mucosa, tongue, and floor of the mouth. Lesions tend to self-resolve in 4 to 14 days and leave no scarring.
    • 2.Major RAS (10%): Similar in appearance to minor RAS except that their size, number, and location increase. Generally, they are greater than 10 mm in diameter. They are deeper, extend to the gingiva and pharyngeal mucosa, last for weeks to months, and have a higher risk for scarring.
    • 3.Herpetiform RAS (10%): Herpetiform lesions which are often smaller, 1 to 3 mm, deeper and occur in greater numbers (5 to 100). Ulcers are generally gray with irregular and nonerythematous borders. Smaller ulcers may cluster and coalesce to form larger ulcers. Ulcers are generally very painful, involve the floor of the mouth and ventral surface of the tongue, resolve within 14 days, and generally leave no visible scar.

Etiology

Both hereditary and environmental causes may contribute to the disease process.

Differential Diagnosis

  • •Behçet syndrome
  • •Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome
  • •Systemic lupus erythematosus
  • •Gluten-sensitive enteropathy
  • •Inflammatory bowel disease
  • •Human immunodeficiency virus infection
  • •Herpes simplex virus
  • •Cyclic neutropenia
  • •Periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA)
  • •Hyperimmunoglobulin D syndrome
  • •Agranulocytosis
  • •Autoimmune bullous disease
  • •Oral erosive lichen planus
  • •Drug-induced mucosal ulcers

The below table summarizes the etiologies and differential diagnosis of recurrent aphthae.

Recurrent Aphthae—Etiologies and Differential Diagnosis

Modified from Bolognia J et al: Dermatology, ed 4, Philadelphia, 2018, Elsevier.

Etiologies
•Idiopathic (immune-mediated)•Related to an underlying systemic disorder: Inflammatory bowel disease, systemic lupus erythematosus, HIV infection, Behçet syndrome, reactive arthritis, cyclic neutropenia, PFAPA (p eriodic f ever, a phthous stomatitis, p haryngitis, and a denitis) syndrome, certain hereditary periodic fever syndromes (e.g., HIDS, NOMID)•Possibly related to an underlying nutritional disorder (controversial): Vitamin B12, folate, or iron deficiency
Differential Diagnosis
•Recurrent erosions and ulcerations due to an inflammatory disorder, e.g., erythema multiforme, fixed drug eruption, contact stomatitis: Less pain at onset, less peripheral erythema•Recurrent herpes simplex viral infection: Only involves keratinized mucosa (hard palate, attached gingiva) in immunocompetent hosts•Trauma: Less pain at onset, less peripheral erythema, more ragged edges

HIDS, Hyperimmunoglobulinemia D with periodic fever syndrome; HIV, human immunodeficiency virus; NOMID, neonatal-onset multisystem inflammatory disease.

∗ Previously referred to as Reiter disease.

Workup

  • •Clinical history: A detailed history includes associated symptoms, family history, frequency of ulceration, number and size ofulcers, duration of the outbreak, and location of ulcers including any nonoral lesions.
  • •Physical examination: Aphthous ulcers are well-circumscribed small round or oval-shaped lesions with gray-white or yellow pseudomembranous bases with an erythematous halo. RAS may be further broken down into its subtypes as outlined in the below table.
  • •RAS is generally a clinical diagnosis; however, if RAS is persistent, further laboratory testing may be considered.
  • •Biopsy: Typically not required; however, in more severe or persistent cases a biopsy may aid in ruling out other mucosal pathologies.

Recurrent Aphthous Stomatitis (RAS) Subtypes

Minor RASMajor RASHerpetiform RAS
DESCRIPTIONRound or oval lesions with gray, white, or yellow bases and erythematous borderRound or oval lesions with gray, white, or yellow bases and erythematous borderSmall, deep ulcers, may cluster and coalesce to form larger irregular shaped ulcers
LOCATIONLips, cheeks, tongue, the floor of mouthLips, pharynxLips, cheeks, tongue, the floor of mouth
SIZE OF ULCERS<10 mm>10 mm1-3 mm
NUMBER OF ULCERS1-51-1010-100
DURATION4-14 days; without scarring>4 wk; possible scarring<4 wk; without scarring

Laboratory Tests

If RAS is severe, persistent, or occurs at a later age of onset, it is reasonable to investigate further for other potential causes.

Laboratory screening for other causes includes a complete blood count, inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein, and nutritional deficiency markers such as serum B12, folate, and iron.

Imaging Studies

No imaging studies indicated.

Treatment

Given the etiology of aphthous ulcer remains unclear, the first-line treatment modalities are aimed at supportive care. Treatment is based on low-quality studies, and there are no curative pharmacological treatments. If aphthae are secondary to an underlying disease, treatment of the primary disease may reduce the duration of the aphthae. Treatment is a stepwise approach and includes good oral hygiene, avoiding trauma (e.g., biting lips or cheeks, oral hardware including braces) and known drug or food triggers, topical anesthetics, topical corticosteroids, topical antimicrobials, and systemic medications.

Therapeutic Ladder for Complex Aphthosis

Adapted from Letsinger JA et al: Evaluation and management of complex aphthosis. J Am Acad Dermatol 52:500-8, 2005, with permission. In Bolognia J et al: Dermatology, ed 4, Philadelphia, 2018, Elsevier.

Local therapy (agents may be used in combination)
Local anesthetics (2)
Superpotent topical corticosteroids (1 /2) or corticosteroid inhalers (2)
Intralesional corticosteroids (2)
Topical tacrolimus (3)
Systemic therapy
Colchicine (1 /2)
Dapsone (1 /2)
Combination of colchicine and dapsone (2)
Thalidomide (1)

Key to evidence-based support: (1) prospective controlled trial; (2) retrospective study or large case series; (3) small case series or individual case reports.

∗ Clobetasol propionate in an adhesive denture paste.

† In patients with Behçet syndrome.

Acute General Treatment

  • •Topical anesthetics: Can be used before eating for temporary relief:
    • 1.2% viscous lidocaine applied directly or used as “swish and spit.”
    • 2.Diphenhydramine liquid (12.5 mg/5 ml): Use 5 ml as “swish and spit.”
  • •Topical corticosteroids: First-line treatment for mild to moderate RAS:
    • 1.Dexamethasone elixir (0.5 mg/5 ml): Use 5 ml as “swish and spit.” Repeat three to four times daily.
  • •Topical antimicrobial: Consider in more severe cases or in immunosuppressed individuals to help prevent secondary infections:
    • 1.Chlorhexidine 0.12% mouth rinse: Use 15 ml as “swish and spit” twice daily.
    • 2.Nystatin suspension: “Swish and swallow” four times daily.

Chronic Treatment

Oral options may be tried in patients reporting no benefit with topical treatment alone or in case of severe RAS.

  • •Oral prednisone 20 to 40 mg daily for 4 to 7 days is the first-line treatment of acute severe RAS.
  • •Montelukast 10 mg daily may be a safe alternative when severe RAS is not well controlled with oral corticosteroids.

Complementary & Alternative Medicine

  • •Ascorbic acid 2000 mg/day may be considered as an adjunct to topical therapy in minor RAS.
  • •Zinc 50 mg/day may also be beneficial in wound healing.

Nonpharmacologic Therapy

Laser therapy or chemical cauterization have been cited as an adjunct to the above therapies to help reduce acute pain; however, their efficacy is unclear.

Disposition

Although a painful condition, aphthous ulcers and RAS are generally self-resolving with an average healing time of 2 week and carry an excellent prognosis.

Consider an alternative etiology if the patient exhibits systemic symptoms or has other pertinent past medical history.

Referral

Referral to a specialist is recommended if an alternative diagnosis is more likely. Severe or persistent cases of RAS may be referred to dermatology.

Prevention

Practice good oral hygiene.

Patient & Family Education

Educate patients and families on pain control with the use of topical anesthetics before eating or drinking to prevent dehydration.

Topical pain control is also beneficial before performing basic dental hygiene. Avoid citrus, spicy, or salty foods.

Educate regarding return precautions including worsening pain, the spread of ulcers (especially beyond oral mucocutaneous membranes), fever, decreased fluid intake, or other systemic symptoms.

Suggested Readings

  • Baccaglini L., et al.: Urban legends: recurrent aphthous stomatitis. Oral Dis 2011; 17 (8): pp. 755-770.
  • Belenguer-Guallar I., et al.: Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent 2014; 6 (2): pp. 168-174.
  • Edgar N.R., et al.: Recurrent aphthous stomatitis: a review. J Clin Aesthet Dermatol 2017; 10 (3): pp. 26-36.
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