Practice Essentials
Eosinophilic ulcers are self-limited, and even recurrent cases have been reported as ultimately self-limited. [1] The ulcers often result from oral trauma. The tongue is the most frequent location of occurrence.
Eosinophilic ulcers of the mucosa are typically solitary ulcers with elevated borders of induration. However, a case is recorded of a man who presented with 4 synchronous eosinophilic ulcers of the tongue. [2] The ulcers commonly occur on the lip, [3] tongue, or buccal mucosa. A grayish-pink base is a common feature. [4] Ulcerations of the oral mucosa are relatively common clinical findings. Oral ulcers may be related to the following:
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Trauma (eg, physical, chemical, thermal)
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Infectious agents (eg, viral, bacterial, fungal, mycobacterial)
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Contact or systemic allergy (eg, allergy to medication)
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Neoplastic disease
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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. [5, 6]
Riga-Fede disease is a form of eosinophilic ulcer that develops in infants and usually occurs on the anterior ventral side of the tongue. [7] 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.
Prognosis
The prognosis is excellent, even with conservative treatment. Most eosinophilic ulcers will resolve spontaneously. [8] Recurrence is rare; however, the source of the chronic irritation should be eliminated to ensure that the ulcer does not recur. 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.
Complications
If the ulcer does not resolve, even after biopsy and removal, the patient may have an underlying systemic condition that prevents the lesion from healing. The patient should be referred for a medical workup. Pilolli et al emphasize the importance of a differential diagnosis and a thorough evaluation. [9]
Clinicians should remember that deliberate self-mutilation may be a symptom of an underlying emotional disturbance. In cases of self-mutilation, patients may inflict injury to themselves to seek attention and sympathy or to obtain prescription medications. Psychiatric or psychological counseling is often necessary for these patients. Also see Malingering.
Diagnostic considerations
Also consider noma (necrotizing stomatitis), Epstein-Barr virus infection, and atypical herpes stomatitis (in patients who are immunocompromised).
Occasionally, lesions may demonstrate atypical histologic features. These lesions have been misdiagnosed as non-Hodgkin lymphoma and squamous cell carcinoma, and unnecessary radical treatment may result. [10, 11] Conversely, CD30-positive anaplastic lymphomas have been misdiagnosed as eosinophilic ulcers; therefore, immunohistochemical studies may be needed to confirm the diagnosis. [12]
Palliative care
Nonsteroidal anti-inflammatory drugs (NSAIDs) or topical anesthetics (eg, viscous lidocaine, benzocaine, dyclonine) may be used to provide temporary relief and comfort when the patient eats. A magic mouthwash may also provide symptomatic relief.
Therapeutic care
Some clinicians suggest that the use of corticosteroids may delay healing; however, a mixture of Orabase and a topical corticosteroid ointment (eg, clobetasol, fluocinonide, triamcinolone) is often effective. Dexamethasone elixir is also effective. Although unnecessary, systemic or intralesional corticosteroids may be used.
A 65-year-old woman with eosinophilic ulcer of the lateral tongue was treated with hyaluronic acid 0.6% and salicylic acid 0.5% with no improvement. The ulcer later resolved with no further treatment and did not recur at 12 months' follow-up. [13]
Surgical care
As a rule, if the lesion does not resolve or if it continues to appear ominous after 2 weeks of treatment, biopsy is warranted. After biopsy, rapid healing of the ulcer is often typical, even with large eosinophilic ulcers, and no further treatment is necessary.
Occasionally, lesions may have to be surgically excised.
Consultations
Consultation with a dentist may be indicated to evaluate and repair fractured teeth or restorations or to alter dentures.
Consultation with an internist may be indicated for the evaluation of an underlying systemic condition in cases in which the ulcer persists, even after biopsy.
Diet
Advise patients to maintain hydration and nourishment. A soft diet is recommended for patients with painful ulcers and to avoid any further irritation. Nutritional supplements, such as Ensure or Boost, may be necessary. Advise patients to avoid eating acidic or spicy foods because they may cause additional discomfort.
Prevention
Patients should eliminate the source of the chronic irritation to prevent recurrence (see Causes).
Long-term monitoring
Once treatment is initiated, advise patients to return in 2 weeks for reevaluation. Biopsy is warranted if the lesion does not appear to be resolving with either topical steroid use or removal of the traumatic irritant.
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. [14] 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.
The eosinophil presence is not fully understood, as most traumatic ulcers do not develop an eosinophilic infiltrate. 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. [15] 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 ulcers, the synthesis of transforming growth factor-alpha and transforming growth factor-beta is not increased in infiltrating eosinophils. [16] 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 [17] ; thus, all may share a common pathogenesis.
Epidemiology
Eosinophilic ulcers are not uncommon; however, they are infrequently reported in the literature. The frequency with which these lesions develop is unknown. The sex prevalence varies from study to study; however, no overall sex predilection is apparent. 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. [18]
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A 47-year-old African American woman with an eosinophilic ulcer on the lateral surface of the tongue. The anterior border of the lesion is raised. Courtesy of Dr Paul D. Freedman.
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Raised, indurated, nonhealing ulcer on the lateral surface of the tongue. The lesion was related to an adjacent fractured tooth. Courtesy of Dr Paul D. Freedman.
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Ulcer on the ventrolateral surface of the tongue. The differential diagnosis should include squamous cell carcinoma or an infectious etiology. Courtesy of Dr Paul D. Freedman.
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Lesion on the lateral surface of the tongue. Courtesy of Dr Paul D. Freedman.
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Low-power view showing an ulcerated surface epithelium with a dense cellular inflammatory infiltrate underlying the mucosal surface (original magnification X40). Courtesy of Dr Paul D. Freedman.
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Cellular infiltrate composed mainly of large mononuclear cells, including histiocytes and submucosal dendrocytes, eosinophils, and scattered T lymphocytes (original magnification X400). Courtesy of Dr Paul D. Freedman.
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Inflammatory infiltrate extending through and between muscle bundles (original magnification X400). Courtesy of Dr Paul D. Freedman.
