What causes pediatric aphthous ulcers?

Updated: Feb 25, 2019
  • Author: Michael C Plewa, MD; Chief Editor: Russell W Steele, MD  more...
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Precipitating factors include trauma, salivary gland dysfunction, stress, depression, genetic predisposition, local infections, nutritional deficiencies, GI disorders, systemic disorders, food allergy or hypersensitivity, hormonal fluctuations, and chemical exposure.

  • Trauma: Local injury, such as that caused by an accidental bite, dental injection, toothbrush bristle, or ingestion of sharp food, may precipitate aphthous ulcers in individuals who are susceptible. Traumatic piercing uncommonly occurs in keratinized mucosal epithelium, and recurrent aphthous ulcers (canker sores) are rare in keratinized mucosa.

  • Stress: Psychological and physiologic stress and depression may increase the risk of aphthous ulcers. [19, 20, 10] Individuals with aphthous ulcers have had higher-than-average anxiety scores and cortisol levels. Antidepressant therapy may be effective in some patients.

  • Genetic predisposition: A family history of recurrent aphthous ulcer (canker sore) is common, though familial penetrance has not been identified as a specific category. Recurrent aphthous ulcers (canker sores) may be associated with human leukocyte antigen (HLA) haplotypes B51 (also common in Behçet syndrome), Cn7, A2, B12, and Dr5. A study by Manthiram et al found a familial tie in some patients with periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. The study found that out of 80 patients, 23% had ≥1 family member with PFAPA. [21]

  • Local infection: Several infectious agents have been identified in association with aphthous ulcer lesions, including human herpesvirus (HHV)-6, [22] HHV-8, varicella zoster virus, human papilloma virus (HPV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2, Helicobacter species, and L-forms of streptococci. [23] However, authorities generally agree that aphthous ulcers and RAU do not represent acute infections and are not contagious.

  • Nutritional deficiencies: Deficiencies of iron (in 20%); [3] folic acid; zinc; and vitamins B-1, B-2, B-6, B-12, C and D have all been implicated in recurrent aphthous ulcers (canker sores). Oxidative stress and diminished antioxidant activity (vitamin E and selenium) may also predispose individuals to recurrent aphthous ulcers (canker sores). [24, 16]

  • GI disorders, such as regional enteropathy (Crohn disease), ulcerative colitis, and celiac disease (gluten-sensitive enteropathy), may result in aphthous ulcers. The ulcers may be the only presenting symptom or the only symptom that is evident for a number of years in patients with GI disorders; therefore, a high degree of suspicion should be maintained when patients present with recurrent aphthous ulcers (canker sores).

  • Systemic disorders: Disorders such as cyclic neutropenia, Reiter syndrome, Behçet disease, or HIV infection may result in aphthous ulcers (canker sores).

  • Food allergy and hypersensitivity: Flavoring agents, essential oils, benzoic acid, cinnamon, gluten, cow's milk, [14] coffee, chocolate, potatoes, cheese, figs, nuts, citrus fruits, and certain spices have been implicated in some individuals with recurrent aphthous ulcers (canker sores).

  • Hormonal fluctuations: In some women, recurrent aphthous ulcers (canker sores) are associated with the menstrual cycle, with outbreaks most commonly occurring during ovulation or before menstruation. A diminished incidence of recurrent aphthous ulcers (canker sores) during pregnancy has been reported.

  • Chemical exposures: High levels of nitrates in drinking water have been associated with aphthous ulcers. [25] The nitrates may induce cytochrome b5 reductase activity. Sodium lauryl sulfate (SLS), a detergent commonly used in toothpaste, may be a trigger of aphthous ulceration in some individuals. [26, 27] Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with aphthous ulcers. [28] Smoking and nicotine exposure do not increase, and may actually decrease, the risk of aphthous ulcers.

  • Significant correlations have been shown between the severity of aphthous stomatitis and hygiene of the oral cavity. [29] Good hygiene reduces not only the number of outbreaks but also the severity. [30]

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