Oral Ulceration

These areas include the buccal and labial mucosa, lateral and ventral tongue, floor of the mouth, soft palate, and oropharyngeal mucosa. The only areas in the mouth that are not affected by RAS are the hard palate and attached gingiva. RAS lesions are not confined to the oral cavity, they may be found elsewhere in the digestive tract, but lesions appearing outside the oral cavity are often associated with systemic disorders.

RAS is subdivided into three categories based on the size of the ulcers and the disease severity. Minor aphthae are less than 1cm in diameter and heal completely in 7 to 10 days. The minor aphthae usually involve a prodromal stage of tingling and burning for 1 to 2 days and usually occur in clusters of up to 5 ulcers. These lesions are shallow and round to oval in shape with a gray to yellow membrane. Minor aphthae are very painful for about 4 days, then heal completely without scarring after several more days. Major aphthae are uncommon and involve irregular deep ulcers of 1 to 3 cm in size. They may have a raised border and can take 4 to 6 weeks to heal. Major aphthae can leave extensive scarring and distortion with healing, and patients are rarely lesion free. The irregular and chronic nature of these lesions often necessitates a biopsy to rule out squamous cell carcinoma. Herpetiform aphthae are also uncommon, and consist of crops of up to 150 very small (1-3mm) ulcers that heal completely in 7 to 10 days. This category of RAS is unfortunately named because these ulcers, like all RAS ulcers, are completely unrelated to the herpes virus.

Etiology

Many theories for the etiology of RAS have been proposed and investigated, but none has been proven. A viral association with viruses such as adenovirus, herpes, and varicella-zoster has been suggested, but is not supported by the majority of the literature. These viruses are ubiquitous and there are no reports of successful treatment of RAS with antiviral therapy. A bacterial association has also been proposed due to the fact that streptococcus species have been cultured from patients with RAS and RAS outbreaks have been associated with increased antibody titers. This has not been corroborated, however, and it is clear that antibacterial drugs do not cure RAS. Other theories for the etiology of RAS include association with estrogen and progesterone levels in women, anxiety, stress, and the "type A" personality. There is clearly a higher incidence of RAS among college, medical, and dental students, and there is a higher incidence among elementary students of higher socioeconomic status. The role of nutrition is controversial. Deficiencies in vitamins, zinc, and iron have been implicated as the occurrence of RAS improved somewhat with replacements. Some patients with gluten-sensitivities may experience outbreaks that resolve with a gluten-free diet, but lesions in the majority of patients do not respond with dietary measures. Sensitivities to foods such as nuts, chocolate, cereals, tomatoes, dairy products and citrus fruits have been implicated also, and the avoidance of such foods may decrease outbreaks. Trauma, as mentioned above, may incite outbreaks. Nicotine, interestingly, seems to have a protective effect. Studies have shown that resumption of smoking after cessation caused pre-existing ulcers to heal within a few days. Also, nicotine gum has been shown to cause ulcer healing and prevention when taken for 1 month, with relapse upon discontinuation of the gum. One hypothesis for the protective effect is the keratinizing action of nicotine on the oral mucosa. There are also numerous investigations into the possibility of an immune mechanism. When certain, yet undefined, antigens are presented to lymphocyte subpopulations, there is an autoimmune reaction against targeted epithelial cells. However, the disease is intermittent and does not always reliably respond to immunomodulating drugs. The only clear etiologic factor for RAS is that a family history may increase a person's risk for developing the disease by 20%.

Diagnosis and Management

The diagnosis of RAS is usually made by taking a thorough history and performing a systematic physical exam. The typical presentation and appearance are as described above. Patients may report any of the above mentioned triggering factors. The examination of the patient will show the typical shallow ulcers anywhere in the mouth except for the keratinized mucosa.

Goals in the management of RAS reflect that it is generally mild and self-limiting, and that, currently, there is no treatment widely believed to be curative. Therefore, treatments that reduce pain and maintain function during attacks, or that reduce the severity and frequency of recurrent attacks, are considered successful. Treatments used for this generally benign disease should not be associated with more morbidity that the disease itself. Treatment options are those that either provide palliation or those that truly alter the course of the disease. Palliative medications are generally applied topically and are available over the counter. Preparations of benzocaine, diclonine, or benzydamine can be effective. Also, as described above, mixtures of lidocaine, diphenhydramine, and Kaopectate may provide some relief. Other therapies that have been reported include hydrogen peroxide, phenol, silver nitrate, topical antimicrobials, antivirals, and antiseptic mouthwashes. These treatments are generally not very effective. The mainstay of treatment of RAS is topical steroid application. Triamcinolone 0.1% in a cream, paste or an aqueous base is the most commonly used. If applied in the prodromal stage, outbreaks can be prevented or even aborted. Beclomethasone spray has also been shown to be of benefit in treating RAS. If patients have a large number of lesions or long duration of attacks, a "burst regimen" of systemic steroid treatment may be used in addition to topical therapy. For RAS major that is difficult to control, intralesional triamcinolone injection will often promote ulcer healing. Because oral candidiasis has been reported in patients using steroid sprays and solutions, prophylaxis with antifungal agents should be considered in these patients.

Behçet's Syndrome

In 1937, Behçet described a symptom complex consisting of recurrent aphthous ulcers of the mouth, as well as recurrent painful ulcers of the eyes and genitals. Behçet's disease is a multisystem disorder that tends to affect persons of Mediterranean, Middle Eastern, or Japanese descent. Most of these patients present with the classic triad of aphthous ulcers, genital ulcers and uveitis or conjunctivitis. Other systemic manifestations may include arthritis of the rheumatoid type, neurological, vascular, and gastrointestinal involvement, as well as malaise and fever with ulcer eruptions, papulopustular truncal lesions, or development of a pustule at any site of minor skin trauma. The diagnosis of Behçet's disease is made on the basis of the clinicopathologic findings, which may be confused clinically with Stevens-Johnson syndrome and Reiter's disease. The oral manifestations of Behçet's disease may be treated in the same manner as those not associated with the disease, but these patients need referral for systemic treatment as well.