Background
Ulcerations of the oral mucosa are relatively common clinical findings. Oral ulcers may be related to the following:
- Trauma (eg, physical, chemical, thermal)
- Aphthous stomatitis
- Infectious agents (eg, viral, bacterial, fungal, mycobacterial)
- Contact or systemic allergy (eg, allergy to medication)
- Neoplastic disease
- Systemic diseases (eg, hematologic and autoimmune disorders, vasculitides)
Traumatic oral ulcers tend to have a sudden onset and usually heal within a few days or weeks, often without clinical intervention. Occasionally, ulcers may persist for an extended time. Eosinophilic ulcers are included in this group of nonhealing traumatic ulcers. These lesions are microscopically characterized by a diffuse, pseudoinvasive, mixed inflammatory reaction that includes large mononuclear cells, numerous eosinophils, and T cells. The cellular infiltrate often extends deep into the submucosa to involve the underlying skeletal muscle.[1]
Riga-Fede disease is a form of eosinophilic ulcer that develops in infants and usually occurs on the anterior ventral side of the tongue.[2] The distinctive, self-limiting ulcerations develop as a result of chronic mucosal trauma from adjacent anterior primary teeth and usually occur in association with breastfeeding.
Pathophysiology
In most patients with eosinophilic ulcers, trauma is the etiologic factor, and the apparent source of irritation is easily identified. This mechanism is further supported by findings in rats in which microscopically similar lesions were experimentally induced by chronic mechanical injury.[3] However, in a number of studies, patients with multiple synchronous or metachronous lesions at different mucosal sites were identified. The source of the chronic irritation also is not evident in a number of patients; therefore, factors other than trauma may be involved in the pathogenesis of these ulcers. Eosinophilic ulcer has also been reported to occur in association with medication use; therefore, eosinophilic ulcer also may represent an unusual manifestation of a drug reaction.
Several investigators have proposed that eosinophilic ulcers develop as a result of a T-cell–mediated immune response. In certain predisposed individuals, recurrent trauma may lead to the alteration of tissue antigens or ingress of unknown factors (eg, viral particles, toxic microbial products), which result in a hypersensitivity or allergic reaction. However, neither virally altered cells nor viral DNA is identified in biopsy specimens of typical eosinophilic ulcer.
Tissue eosinophilia is not uncommonly associated with T-cell–mediated immune reactions. Activated T lymphocytes produce a variety of lymphokines that are involved in eosinophilic maturation and act as eosinophil-chemotactic factors. Damage and degeneration of mucosal tissues may be due to a proliferation of cytotoxic T cells or toxic products released by degranulating eosinophils. Constituents of eosinophil secretory granules include a number of highly cytotoxic proteins, including eosinophil cationic protein, major basic protein, and eosinophil-derived neurotoxin.
One study demonstrated that, in most eosinophilic ulcer, the synthesis of transforming growth factor-alpha and transforming growth factor-beta is not increased in infiltrating eosinophils.[4] This observation is in contrast to that of the animal wound-healing model, in which eosinophils that express transforming growth factor are typically recruited to healing tissue sites. These findings may help explain the delayed healing that is characteristic of eosinophilic ulcer.
Eosinophilic ulcer, tumorlike eosinophilic granuloma of the skin, and transient eosinophilic nodulomatosis have been suggested to represent a mucocutaneous reaction pattern[5] ; thus, all may share a common pathogenesis.
Epidemiology
Frequency
United States
Eosinophilic ulcers are not uncommon; however, they are infrequently reported in the literature. The frequency with which these lesions develop is unknown.
Mortality/Morbidity
- Although certain lesions may behave aggressively, overall, these ulcers do not cause significant morbidity.
- Occasionally, lesions may demonstrate atypical histologic features. They have been misdiagnosed as lymphoma, and unnecessary radical treatment can result.
Sex
- The sex prevalence varies from study to study; however, no overall sex predilection is apparent.
Age
- Eosinophilic ulcers develop in individuals of all ages, ranging from infants to those aged 92 years.
- The mean patient age at onset is 46 years.
- Riga-Fede disease typically is seen in children aged 1 week to 1 year.
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