Approach

The main goals are to exclude serious and/or systemic disease, and to provide therapy to achieve pain relief, reduction of ulcer duration, and reduction in frequency of episodes.[44]

Initial treatment consists of simple options, including changing the patient's toothpaste to a sodium lauryl sulfate-free formulation, antibacterial mouthwash (e.g., chlorhexidine), and symptom relief (e.g., topical lidocaine). Patients should be instructed to avoid recognized trigger foods, and acidic foods and drinks.[1]

If simple measures alone do not work to reduce the symptoms, topical corticosteroids are still the mainstay of treatment, with adjunctive topical antimicrobials, which may reduce the inflammatory component. However, if recurrent aphthous stomatitis (RAS) fails to respond to topical therapies, systemic therapies may be required.[3][45]

For all patients, the possibility of local trauma (e.g., from sharp and/or broken teeth, dentures and orthodontic appliances, and biting during chewing) should be assessed and appropriate dental treatment undertaken.[3] There is some evidence of benefit from vitamin B12, even in the absence of any deficiency; supplementation with oral vitamin B12 (cyanocobalamin) has been shown to be effective in studies, irrespective of serum B12 levels.[46][47][48]

Consider iron supplements if iron deficiency anemia occurs.[37][49] However, it is important to consider the cause of iron deficiency before treating it because this can often be the first sign of malabsorption or occult blood loss. Iron supplementation in adults and children may be necessary to prevent ulcers that are a result of iron deficiency anemia. Initial treatment is daily oral iron replacement therapy.[49]

Topical therapies

Topical corticosteroids are the mainstay of treatment when simple measures alone do not work to improve the symptoms. A variety of different agents can be used, including a corticosteroid paste (a combination of a potent topical corticosteroid such as triamcinolone and dental paste), hydrocortisone buccal tablets, and betamethasone soluble tablets.[50] However, these specific formulations of hydrocortisone and betamethasone are not available in the US and corticosteroid mouth rinses may need to be specially compounded. More potent topical corticosteroids (such as betamethasone dipropionate, clobetasol, or fluocinonide) may also be used.[3] Treatment duration is case-dependent but there is no evidence of adrenal suppression with low-potency corticosteroids.

Topical therapies for symptom relief may be of benefit. These include topical anesthetics (e.g., lidocaine) and topical anti-inflammatory agents. Adjunctive antimicrobial agents may also be of some value, in part by reducing secondary infection. These may reduce the severity and pain of ulceration. For example, randomized controlled trials have shown that chlorhexidine oral solution may reduce the duration of RAS and increase the number of ulcer-free days.[51][52][53][54] Topical tetracyclines used as rinses may also be effective.[55][56] However, they must be compounded, and they should be avoided in children less than 8 years of age as they may cause tooth discoloration.[57]

Systemic therapies

If RAS fails to respond to topical therapies, systemic therapies may be required. However, studies are lacking to assess their efficacy (or their adverse effects).[58] For patients with severe RAS, a short course of systemic corticosteroids, systemic immunomodulators, or anti-inflammatory agents, such as colchicine, azathioprine, or thalidomide, may be necessary.[1][3][45][59][60]

Oral prednisone as a 1-week course tapered over a second week is one suggested regimen.[3]

The first-line systemic immunomodulator used in RAS and the mucocutaneous manifestations of Behcet syndrome is colchicine.[61] There is weak evidence to support the use of azathioprine.

Thalidomide is rarely used; great caution is required for its use, and specialist referral and prescription is recommended.[1][3] However, the use of thalidomide in RAS is supported by data in both RAS and in patients with aphthous-like ulceration in HIV infection.[62][63] In these patient groups, open and double-blind studies have shown that thalidomide is an effective agent available for the management of severe, refractory RAS.[6][59] Thalidomide would never be commenced in primary care - there is tight legislation around prescribing of it. For example, in the UK its use is approved only on case-by-case discussion with various health boards/trusts.

Results with other immunomodulatory agents used to treat severe or refractory RAS, such as levamisole or pentoxifylline, have shown either poor clinical response or a significant incidence of treatment-related adverse effects.[6]

Management of children under the age of 12 years

As with adults, the first-line treatment in children is the introduction of simple measures (i.e., change of toothpaste, avoidance of triggers, or assessment for trauma). In addition to this, there are a number of over-the-counter anti-inflammatory treatments available for the relief of symptoms. A suitable formulation that is licensed for use in children should be selected.[64]

There are a limited number of topical corticosteroids that are licensed for oral use in children. If topical corticosteroids are needed, they can be used off-label, but only in children who can follow instructions with regards to spitting out the medication. This means that they usually cannot be used in children under 6 years of age. These treatments should only be started under specialist care after the child has been assessed and other causes of oral ulcers have been excluded. Oral asthma inhalers have been used off-label as a topical application for this indication.[64]

Systemic treatments for RAS are rarely used in children under the age of 12 years, and are only commenced under specialist care.

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