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Aphthous Ulcers

Definition and Epidemiology

Recurrent aphthous ulcers (RAU) or recurrent aphthous stomatitis (RAS) are painful oral ulcerations that characteristically recur at intervals ranging from days to months or even years. They represent the most common lesion of the oral mucosa with an overall prevalence ranging from 15% to 30%. Females are more commonly affected than males. Although the lesions may appear at any age. they usually present during the second and third decades of life. Familial occurrence is common and about 30-40% of the patients with RAU have another affected family member.

Etiology

RAU is one of the oldest oral diseases, to be known since the time of Hippocrates, yet its etiology still remains unclear. Many predisposing factors have been incriminated such as genetics, trauma, food hypersensitivities, stress, infections (Streptococcus sanguis and S. mitis, herpes simplex virus [HSV]-1, varicella zoster virus [VZV], cytomegalovirus), and systemic factors. Although predisposing factors may play a role in the development of RAU the disease is idiopathic and its etiology remains unknown. Accumulated data support the concept that the pathophysiology of RAU is immunologically mediated, and involves dysregulation of the cell-mediated immune response.

Main Clinical Features

Based on clinical criteria, recurrent aphthae are classified into minor, major, and herpetiform ulcers (Table 1).

The main clinical features of the three forms are painful, recurrent oral ulcerations at intervals ranging from days to weeks or even months. The prodromal stage is variable and is usually characterized by discomfort and occasionally erythema of 1-3 days duration. This stage is soon followed by a painful oral ulcer.

The lesions are usually confined to movable nonkeratinized or poorly keratinized oral mucosa, e.g., buccal mucosa, labial mucosa, tongue, floor of the mouth, soft palate, and uvula.

Clinicians should bear in mind that RAU may be associated with several systemic disorders.

Systemic Disorders Associated with RAU

•Behçet disease

•Sweet syndrome

•Crohn disease

•Ulcerative colitis

•Celiac disease

•HIV infection

•Malabsorption syndromes

•Hematinic deficiencies

•Neutropenia

•FAPA syndrome

Diagnosis

The diagnosis of all three forms of RAU is based exclusively on clinical criteria, as there is no specific test, unless there is an underlying systemic disease.

Differential Diagnosis

•Traumatic ulcer

•Primary and secondary herpetic stomatitis

•Hand, foot, and mouth disease

•Herpangina

•Stomatitis medicamentosa

•Erythema multiforme

•Pemphigus

•Pemphigoid

•Syphilis (chancre and mucous patches)

•Behçet disease

•Crohn disease

•Ulcerative colitis

•Cyclic neutropenia

Treatment

Basic Guidelines

•When managing RAU, it is important to rule out aphthous-like ulcers associated with systemic diseases. The great majority of patients with RAU are healthy individuals with no history or signs of systemic disease.

•Successful therapy of RAU requires correct diagnosis and control of the contributing etiologic factors.

•A wide spectrum of therapeutic regimens or agents has been recommended, but the management of RAU is unsatisfactory, as there is no cure and all attempts at treatment are palliative.

•The goal of treatment should be a) elimination of pain and discomfort, b) shortening of the course of the disease, and c) avoiding recurrences.

Suggested Therapies

•Control of the contributing etiologic factors

•Topical treatment

•Systemic treatment

Control of Possible Contributing Etiologic Factors

Patients should be encouraged to keep a food diary in an attempt to identify a potential precipitating link with the onset of aphthous ulcers. Patients should avoid minor trauma of the oral mucosa. Stress and female sex hormonal fluctuations should also be monitored and if possible controlled. A gluten-free diet may be useful in controlling lesions even in the absence of celiac disease.

Topical Treatment

Topical medications may reduce pain and shorten the course, but they do not prevent recurrence.

Topical anesthetics such as 2% viscous lidocaine, benzocaine, and benzydamine hydrochloride may reduce pain only for a short time. Recently, 5% amlexanox oral paste and 3% diclofenac in 2.5 % hyaluronan have also been employed to reduce pain with partial success. Topical tetracyclines have also been used with partial success. A 250 mg capsule is dissolved in 30 ml of water, and 5 ml of this solution is used to rinse the lesion four to six times a day. This is repeated for 3-5 days. Many other anti-inflammatory and antimicrobial agents (chlorhexidine, listerine) have also been used with unsatisfactory results. The most effective topical agents are 0.1 % triamcinolone acetonide in an oral adhesive base (Orabase), 0.5% fluocinonide gel (Lidex gel) or 0.05% clobetasol propionate gel (Temovate) applied to the ulcer three to six times a day for 4-6 days. Intralesional injection of triamcinolone acetonide retard or betamethasone dipropionate and sodium phosphate retard may be successful for major aphthous ulcers only.

Systemic Treatment

Systemic corticosteroids (prednisone and betamethasone in an average dose of 20-30 mg and 2-3 mg, respectively) for 4-8 days are very helpful for major ulcers or herpetiform ulcers. In cases of repeated episodes and when new ulcers occur before the previous ones have healed, systemic medications may prove useful in preventing new lesions. In our experience, 20 mg prednisone or 2 mg betamethasone for 10-15 days and then an injection of betamethasone di-propionate and sodium phosphate retard (Cele-stone Chronodose) every 2 weeks for a period of 2 months may significantly increase the periods between recurrences. Long-term systemic corticosteroids are contraindicated because of their side effects.

In severe cases with a high recurrence rate and in HIV-infected patients, thalidomide 100-300 mg/day for 2-3 months may result in complete remission of the ulcers for a long time. However, teratogenesis and polyneuropathy preclude the routine use of thalidomide.

Clinicians should be aware that safe prophylaxis for prevention of recurrences of RAU in the long term is not possible.

Alternative Therapies

In severe cases many other systemic medications have been used with ambiguous results. These include dapsone, levamisole hydrochloride, colchicine, azathioprine, interferon alpha, cyclosporine, pentoxifylline, and recently rebamipide, a gastroprotective drug.

References

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Haeyrinen-lmmonen R, Sorsa T, Pettilae J, et al. Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers. J Oral Pathol Med 1994;23:269–272.

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