Pediatric Aphthous Ulcers: Background, Pathophysiology, Epidemiology

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Sections Pediatric Aphthous Ulcers
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
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References

Overview

Background

Commonly termed canker sores, aphthous ulcers, or aphthous stomatitis, have been the focus of study and research for many years, although the exact etiology of the lesions has yet to be identified. Categorized as an idiopathic disease, aphthous ulcers are frequently misdiagnosed, treated incorrectly, or simply ignored.

Recurrent aphthous ulcer (RAU), or recurrent aphthous stomatitis (RAS), represents a chronic inflammatory disease characterized by painful oral ulcers recurring with varying frequency. Examples of aphthous ulcers are shown in the images below.

Recurrent aphthae in floor of mouth, showing ovoid ulcer with inflammatory halo.

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Typical aphthous ulcer in a common site, showing inflammatory halo surrounding a yellowish, round ulcer.

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Children with recurrent aphthous ulcers (canker sores) may reduce their oral food and fluid intake because of the associated pain and subsequently become dehydrated; therefore, aggressive therapy for the lesions can be important.

Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. The 3 categories of recurrent aphthous ulcers (canker sores) are as follows:

Minor aphthous ulcers (80-85% of recurrent aphthous ulcers [canker sores]) are 1-10 mm in diameter and heal spontaneously in 7-10 days.
Major aphthous ulcers (also called Sutton disease) constitute 10-15% of recurrent aphthous ulcers (canker sores). These lesions are greater than 10 mm in diameter, take 10-30 days or more to heal, and may leave scars.
Herpetiform ulcers (5-10% of recurrent aphthous ulcers [canker sores]) are multiple, clustered, 1-mm to 3-mm lesions that may coalesce into plaques. These usually heal in 7-10 days.

Pathophysiology

The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring.

Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8⁺ cells and decreased numbers of helper CD4⁺ cells in peripheral blood.^[1] Antithyroid and antigastric parietal cell antibodies may also play a role.^[100]Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5;^[2]they have a functional deficit of IL-10. Some lesions have also had mast-cell activation and degranulation. In vitro cytotoxicity to oral keratinocyte targets is greater in patients with active recurrent aphthous ulcers (canker sores) than in control subjects or in patients with traumatic ulcers. As expected with this abnormal immunologic activity, corticosteroids are effective therapy.

Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. Lesions have increased expression of an adhesion molecule termed vascular cell adhesion molecule-1 (VCAM-1), E selectin, and keratinocyte intercellular adhesion molecule-1 (ICAM-1).^[3]Connexins (markers for the presence of gap junctions) are present in the oral mucosa of patients with recurrent aphthous ulcers (canker sores) in amounts similar to those present in normal mucosal tissue. Experimental treatment with irsogladine maleate, which reinforces gap junctional intercellular communication, is effective.

The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested.^[93] Helicobacter pylori may or may not be involved in aphthous ulcer formation.^{[4, 5, 91]}

Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress,^{[6, 7]}poor nutritional status, thiamine deficiency,^[8]vitamin B12 deficiency, zinc deficiency,^[92] malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow's milk),^[9]allergic reaction, low antioxidant levels,^[90] emotional stress,^[95] and exposure to toxins (eg, nitrates in drinking water). Aphthous ulcers (canker sores) are more prevalent in nonsmokers and in smokers who quit but are diminished with nicotine replacement therapy.

Frequency

United States

Although recurrent aphthous ulcers (canker sores) are commonly believed to occur in approximately 20% of the general population, a study of medical and dental students revealed a prevalence of 31-66%.

International

The worldwide incidence is similar to that in the United States. Aphthous ulcers (canker sores) are found in all ethnic groups and geographic locations. The prevalence may be increased in affluent countries and socioeconomic classes.

Mortality/Morbidity

Aphthous ulcers (canker sores) are associated with local pain and discomfort. Symptoms usually last 2-10 days with minor and herpetiform ulcers and as long as 30 days with major ulcers. Most cases are self-limited and heal without sequelae in 7-14 days; however, major ulcers heal slowly (10-30 days or longer).

Major aphthous ulcers (canker sores) have been known to leave substantial scars.
The primary morbidity with any type of aphthous ulcer (canker sore) in the pediatric population is dehydration due to poor oral intake.
Secondary bacterial infections are uncommon.

Race

Race does not appear to influence the frequency or severity of recurrent aphthous ulcers (canker sores).

Sex

Aphthous ulcers (canker sores) may be slightly more common in female individuals than in male individuals. Outbreaks occur most frequently during ovulation or before menstruation, and remissions are common during pregnancy.

Age

Recurrent aphthous ulcers (canker sores) begin in childhood or adolescence, with peak onset in persons aged 10-19 years. Frequency and severity diminish with age. Major aphthous ulcers (canker sores) may begin soon after puberty. Herpetiform recurrent aphthous ulcers (canker sores) tend to affect older persons.

Clinical Presentation

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Media Gallery

Recurrent aphthae in floor of mouth, showing ovoid ulcer with inflammatory halo.
Typical aphthous ulcer in a common site, showing inflammatory halo surrounding a yellowish, round ulcer.

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Sections Pediatric Aphthous Ulcers
Overview
Presentation
- History
- Physical
- Causes
- Show All
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Workup
Treatment
Medication
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