- Recurrent aphthous ulcers are the most common oral ulcerative ailment, which classically appear as shallow, round or oval ulcers with an inflammatory edge and a faint pseudomembrane.
- Diagnosis may be made by history and physical exam alone, but the presence of systemic symptoms may warrant a broad workup for potential underlying diseases manifesting with oral ulcers
- Treatment is based on limited evidence and focused on symptomatic relief and decreasing ulcer duration, generally with local or topical analgesics or anti-inflammatory medications.
Aphthous ulcers are one of the most common diseases of the oral mucosa. Aphthous ulcerations (also called aphthae or canker sores) occur as shallow, rounded ulcers, with an inflammatory rim or halo, often with a pseudomembrane, which can fade from yellow/green to gray over time. The ulcers preferentially affect nonkeratinized mucosal surfaces, such as the labial or buccal mucosa, the sublingual mouth, or the tongue. Many patients suffer from recurrent lesions, termed recurrent aphthous stomatitis. The first lesions generally begin in childhood, and recurrent aphthous ulcers are more common in women, people under 40, Caucasian patients, nonsmokers, and people of high socioeconomic status. The disease usually remits in adulthood, after age 30. The true prevalence is difficult to say, as aphthous ulcerations are likely underreported; on average the prevalence in the US is estimated to be about 20%. Family history of disease is common. The diagnosis is generally made by history and physical exam alone, though the presence of systemic symptoms may prompt a more comprehensive investigation. A history of recurrent oral mucosal ulcers, generally starting in childhood, and the typical small round or oval ulcers on exam are key. There is likely an underlying genetic predisposition leading to immunologic abnormalities causing the inflammation in the oral cavity. Systemic and local factors may play a role as well, with deficiencies of vitamins (iron, vitamin B, folate), oral trauma, anxiety or stress, food sensitivities, and hormonal changes suggested as possible triggers in subsets of patients, though overall the data is conflicting and there is scarce evidence suggesting a specific cause.
The most common form of recurrent aphthous stomatitis is characterized by minor aphthous ulcers, which comprise about 80% of cases of recurrent aphthous stomatitis. These lesions are between 2 and 8 mm in diameter and heal over a 10- to 14-day period. Major aphthous ulcers are less common, making up 10-15% of cases, but often are more symptomatic and may require more aggressive treatment. Major aphthae are often one centimeter or more in diameter. A third type of aphthous stomatitis is termed herpetiform ulceration (although it is unrelated to herpes virus infection), and is characterized by multiple, pinpoint ulcerations. Approximately 80% of patients suffer from minor aphthae; major and herpetiform ulcerations are more likely to prompt patients to seek treatment, as they may last for weeks with significant discomfort.
Therapy for oral ulcerations is aimed at providing symptomatic relief and promoting ulcer healing. For major disease, systemic medications may diminish the duration or frequency of attacks.
There is an important differential diagnosis when evaluating patients with oral ulcers, even if the history and exam is strongly suggestive of aphthous ulcerations. The differential diagnosis can include oral involvement of inflammatory bowel disease, gluten sensitivity, Behçet’s syndrome, herpes simplex virus infection, other infections including syphilis, gonorrhea, coxsackievirus infection (hand-foot-mouth disease), and other herpes viruses (CMV, EBV, and VZV), HIV (including acute seroconversion), oral lichen planus, autoimmune blistering diseases, or drug eruptions. Any ulcer that lasts for more than three or four weeks requires evaluation to rule out other serious diseases, including local malignancies.
Hand-foot-and-mouth disease (coxsackievirus)
Herpes simplex virus
First-line therapy: Patients with active ulcers should avoid trauma to the oral mucosa (including hard toothbrushes or sharp foods) and limit intake of acidic products which can worsen pain. Topical analgesics and local protective topical medicaments may provide symptomatic relief. Topical corticosteroids can accelerate healing and improve pain. Antimicrobial rinses may reduce the number of outbreaks and increase disease-free periods between ulcerations. Gel-based topical are the easiest to apply and tend to be better tolerate than other vehicles. Topical medicaments may be compounded in alternative vehicles, such as pastes (Orabase, Iso-Dent) to improve adherence to the moist mucosal surfaces. Amlexanox paste is an anti-inflammatory topical which can improve healing and reduce ulcer size. Major aphthae may require systemic therapy. Most of the therapies discussed herein are not FDA approved for this indication; 1% triamcinolone dental paste is approved for relief of inflammatory conditions in the mouth, and 5% amlexanox paste is approved specifically for aphthous ulcerations.
Recurrent aphthous stomatitis, minor ulcerations
- Topical anesthetics (0.15% benzydamine oral rinse, 2-5% lidocaine gel) may be applied to ulcers four times daily for two weeks or until ulcers heal to relieve pain.
- Protective films, such as carmellose or Orabase, may be applied to the ulcers to diminish discomfort.
- Topical corticosteroids (1% triamcinolone dental paste, 0.05% fluocinonide in Orabase, 2.5 mg hydrocortisone lozenge, betamethasone aerosol) may be used up to four or five times daily for two weeks or until ulcers resolve to speed healing and decrease pain from ulcers.
- 5% amlexanox paste may be applied four times daily for two weeks or until ulcers heal.
Antimicrobial rinses (chlorhexidine gluconate, triclosan) may decrease bacterial plaques and limit outbreaks in some patients. 0.2% chlorhexidine gluconate mouthwash three times daily or 0.15% triclosan mouthwash twice daily for six weeks can reduce duration of lesions and pain, and lead to fewer outbreaks and fewer total ulcerations. Listerine mouthwash may reduce lesion duration and pain as well.
- Patients may be counseled to avoid foods that may trigger or worsen eruptions, such as nuts, acidic foods or drinks, salty meals, and alcohol. Oral hygiene products containing sodium lauryl sulfate may trigger oral ulcers in some patients as well.
- Systemic therapy is rarely indicated for minor aphthae of recurrent aphthous stomatitis. If local methods fail, physicians should revisit the differential diagnosis and consider extended workup for mimics of aphthous ulcers. Systemic therapies are discussed below, under major aphthae.
- In certain cases physicians may opt to order lab tests to evaluate for nutritional deficiencies or rarer underlying causes of oral ulcerations. This may include evaluation of vitamins including iron, ferritin, total iron-binding capacity, folate, vitamin B levels, zinc, and magnesium, and evaluation of a complete blood count. Depending on the patient’s history and review of systems, further testing for systemic diseases may be indicated, which could include antinuclear antibody and antineutrophilic cytoplasmic antibody levels, tissue transglutaminase antibodies, local or serological viral testing, gastroenterological evaluation, and more.
Severe aphthous stomatitis / major aphthae
Initial management is based on local topical therapies as noted above. Patients with severe recurrent aphthous stomatitis often require systemic therapies to control disease. Oral prednisone (30-60 mg daily) tapered over a two-week course may help heal ulcers more rapidly.
Thalidomide 100 mg daily may reduce ulcer outbreak and can offer significant symptomatic relief to patients who suffer from major aphthous ulcers. Thalidomide may be effective even at lower doses. Due to the potential for serious adverse effects (teratogenicity, deep vein thrombosis, and neuropathy), thalidomide use is tightly regulated by the US government (requiring patients and prescribers to be part of the national STEPS registry program).
Alternative systemic agents have been used in case reports or small case series. These are generally drugs that target neutrophils (colchicine, dapsone) or TNF (pentoxifylline, infliximab, or etanercept).
- Using topical steroids for prolonged periods in the mouth can predispose to oral candidiasis. Long-term use of local steroids can lead to systemic absorption when applied to the mucosa, particularly when the surface is ulcerated.
- Any oral mucosal ulcer which fails to heal after three or four weeks warrants evaluation and possible biopsy to rule out malignancy.
- Aphthae are diagnosed by history and physical exam alone; there is a broad differential for diseases which can manifest with oral ulcerations, and extended work-up is indicated if there are signs or symptoms of a systemic process.
When to refer to a dermatologist
- Any ulcer which fails to heal after three or four weeks warrants evaluation and possible biopsy; this may be managed by a dermatologist or an oral medicine physician.
- Widespread oral erosions, or oral erosions accompanied by cutaneous bullae, should prompt consideration for a mucocutaneous disorder such as pemphigus or a severe drug eruption.
- If the diagnosis is uncertain or there are systemic symptoms suggestive of a more widespread process, referral to a specialist may be appropriate.
- 20-year-old healthy man
- No significant past medical history
- Review of systems is noncontributory, notably negative for fever, joint pains, diarrhea, or weight changes
- Social history is notable for monogamous relationship with one partner, no history of sexually transmitted diseases; does not smoke or drink alcohol
- Presents for management of 7-year history of intermittent painful ulcers in the mouth
- Healthy appearing male
- Four small 4 mm ulcers on the buccal mucosa with a rounded appearance and red border
- No genital ulcerations or other skin lesions
- Diagnosis: aphthous ulceration
- Recommend topical analgesia with 2% lidocaine gel and 1% triamcinolone paste used four times daily
- Gentle oral care recommended: avoiding hygiene products containing sodium lauryl sulfate, avoiding sharp/traumatic foods, avoiding acidic foods
- Follow-up if fails to respond
- Patient notes symptomatic relief and feels the ulcers resolved faster than in the past
- Antimicrobial mouthwash rinses with 0.2% chlorhexidine gluconate mouthwash three times daily
- Follow-up as needed; report any nonhealing ulcers
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