eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Eosinophilic Ulcer

Author: Faizan Alawi, DDS, Assistant Professor, Department of Dermatology, Section of Dermatopathology, Hospital of the University of Pennsylvania
Coauthor(s): Paul D Freedman, DDS, Section Chief of Oral Pathology, Assistant Director, Assistant Professor of Surgery, Department of Dental Medicine, The New York Hospital, Cornell University Weill Medical College
Contributor Information and Disclosures

Updated: May 18, 2007

Introduction

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 (EUs) 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.

Riga-Fede disease is a form of EU that develops in infants and usually occurs on the anterior ventral side of the tongue.¹ 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 EUs, 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.² 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. EU has also been reported to occur in association with medication use; therefore, EU also may represent an unusual manifestation of a drug reaction.

Several investigators have proposed that EUs 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 EU.

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 EU, the synthesis of transforming growth factor-alpha and transforming growth factor-beta is not increased in infiltrating eosinophils.³ 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 EU.

EU, tumorlike eosinophilic granuloma of the skin, and transient eosinophilic nodulomatosis have been suggested to represent a mucocutaneous reaction pattern⁴ ; thus, all may share a common pathogenesis.

Frequency

United States

EUs 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

• EUs 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.

Clinical

History

• The most common complaint is that of an asymptomatic or mildly tender, solitary, nonhealing ulcer of variable duration.
• The lesion may be present for as short as 1 week or 12 months or longer.
• Patients with early ulcers often report pain and severe discomfort.
• Patients may have a history of trauma to the affected area.
• Depending on the location of the ulcer, other signs and symptoms may include dysphagia, odynophagia, dysphonia, and dyspnea.
• Occasionally, patients may present with a history of recent weight loss.
• Infants with Riga-Fede disease often experience discomfort while breastfeeding, and they may fail to thrive in the postnatal period.

Physical

• Clinical appearance
  • EU typically presents as an irregular, solitary ulcer with a fibrinous membrane on the surface. A zone of erythema surrounds the ulcer.
  • The margins of the lesion are often raised and usually indurated.
  • Purulence emanating from the ulcer may be noted.
  • EUs may be a few millimeters to as large as 7-8 cm in greatest dimension.
  • In rare reports, multiple synchronous or metachronous lesions have been identified.
  • Occasional ulcers may be macular, whereas others may present as nonspecific erythroplakic or leukoplakic lesions.
  • In rare cases, an EU may present as an elevated, smooth mass that is free of ulceration; however, biopsy reveals the underlying, characteristic, invasive cellular proliferation. In some of these cases, the overlying epithelium may have regenerated without resolution of the underlying inflammation.
• Mucosal sites
  • Any mucosal surface can be affected; however, the tongue is the most common location, accounting for 60% of reported cases.
  • The lateral and dorsal surfaces are usually affected because these are the areas most often traumatized.
  • Lesions on the ventral surface of the tongue more commonly are observed in infants because of contact with the adjacent mandibular incisors during breastfeeding.
  • The dorsal surface of the tongue may also be affected in infants because of irritation associated with maxillary incisors.
  • The buccal mucosa and mucobuccal fold are also particularly susceptible to ulceration; lesions in these locations account for 24% of reported cases.
  • EUs have also been reported (in decreasing order of frequency) on the lips, gingiva, palate, floor of the mouth, and retromolar area.
• In extremely rare cases, cervical lymphadenopathy is reported.

Causes

• Common causes of oral trauma include the following:
  • Self-inflicted injury in which the patient accidentally or deliberately traumatizes the mucosa
  • Injury due to sharp-edged teeth or food
  • Injury due to neonatal or natal teeth (Riga-Fede disease)
  • Toothbrush abrasion
  • Injury due to ill-fitting dentures
  • Injury due to orthodontic or occlusal appliances
  • Iatrogenic injuries (eg, those that occur during dental procedures, such as anesthetic necrosis that occurs during intubation for surgery)
  • Injuries due to accidents
• Certain patients may be inherently predisposed to the development of EUs, although this factor remains controversial.
• The role of drug reactions, if any, is unclear.
• Medical conditions or therapeutic regimens that predispose an individual to immune suppression may also delay healing.

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