Physician shares lessons on aphthosis

Delivering the Everett C. Fox, M.D., Memorial Lecture at Academy '05, Dr. Rogers told attendees his first discovery in this field was that aphthosis has an immunological basis. However, another fundamental lesson and one that has been a basis for years of continued research is that aphthosis is a multifactorial disease.

Decades of research

Dr. Rogers began research related to aphthosis in the early 1970s with studies supported through a grant from the National Institute of Dental and Craniofacial Research. Investigating - via an in vitro assay - lymphocyte-epithelial cell interactions in a series of patients with various oral inflammatory diseases, Dr. Rogers and colleagues demonstrated that lymphocytes obtained from patients with recurrent aphthous stomatitis (RAS) exhibited cytotoxicity for gingival epithelial target cells.

Lymphocytes harvested from patients with active disease showed the highest cytotoxicity, whereas those from patients with a history of recurrent canker sores but no active lesions had an intermediate level of cytotoxicity. No substantial cytotoxicity was demonstrated by lymphocytes from normal subjects and controls with other oral diseases but not canker sores.

"Over the next 15 to 20 years, other investigators have confirmed these findings through their research and identified the lymphocytes involved as T-lymphocytes," Dr. Rogers says.

Etiologies, classifications, manifestations

The immunological basis of aphthosis provides a rationale for therapy, but another lesson learned is that classification is helpful for diagnosis, prognosis and determining treatment.

One classification considers severity, and in 1992, Dr. Rogers introduced the term "simple aphthosis" to describe the condition of recurrent aphthous stomatitis (RAS) that occurs in the absence of severe or continuous oral ulcerations and in the absence of Behcet's disease.

That category includes the vast majority of RAS sufferers who typically may experience one to four annual episodes of aphthous stomatitis with one to four lesions per outbreak. The lesions are generally shallow, less that one centimeter in size, and last four to 10 days, although larger lesions that are also deeper can take longer to heal. The sores are initially painful, but after several days the discomfort turns more into an ache as healing occurs.

"Simple aphthosis is generally a disease of younger people. It affects 20 percent to 50 percent of the population 5 to 25 years old, but the tendency for recurrent episodes usually remits in five to 15 years in persons who develop minor, smaller lesions," Dr. Rogers says.

Management/prevention principles

Management of simple RAS may include application of topical fluorinated corticosteroids if the ulcer is in its prodromal or preulcerative stage, topical analgesics (NSAIDs or anesthetics), or amlexanox 5 percent oral paste (Aphthasol, Access Pharmaceuticals, Inc.), which has been shown in vitro to inhibit the formation and release of inflammatory mediators and in clinical use to hasten healing.

Patients should also be counseled on strategies for reducing oral trauma that might initiate ulcer development, including not talking while chewing, avoiding eating sharp-surfaced foods, maintaining good oral hygiene and repairing any irregular dental surfaces.

The concept of "complex aphthosis" was introduced by Jorizzo et al. in 1984 and describes patients with recurrent oral and genital aphthous ulcers or almost constant, multiple oral aphthae in the absence of Behcet's disease. The aphthae may be very large, are slow healing, and the remissions between episodes are short.

"Fortunately, complex aphthosis represents a small subset of patients with RAS, but the pain associated with it can cause terrible suffering and major disability," Dr. Rogers says.