What Are Systemic Disease Causes of Oral Ulcers?

Patient Presentation
A 10-year-old male came to clinic for his health supervision visit. He and his mother had no questions, but during the physical examination the mother said that he had intermittent oral ulcerations. He had them at least monthly and had had them for years. She had never asked his dentist or pediatrician as she said “she forgot about it” in between the episodes. He said that they were not painful, would occur on different parts of his lips and teeth and would go away in a few days. He denied any lesions any place else. He denied any visual problems including dry or itchy eyes. He was not having any lesions currently. The past medical history and review of systems were negative. The family history was positive for autoimmune hepatitis in his grandmother.

The pertinent physical exam showed a healthy male with normal growth parameters and vital signs. His oral examination was negative.

The diagnosis of a healthy male was made. The pediatrician said that he couldn’t remember too many reasons for chronic ulcers other than Bechet’s disease and ulcerative colitis. Both of these seemed unlikely in the boy because of his own and family history. “He doesn’t seem to have any systemic disease that would cause them, but there are also other causes. However, we probably should get to the bottom of this, so call your dentist the next time this occurs and have him or her take a look at the lesions. Then maybe we can figure out if anything else needs to be done. Maybe they can even take some pictures and if we need to, we can send them to the oral pathologist at the state dental school,” said the pediatrician.

Oral ulcers are common problems seen by dentists but pediatricians also see them. Usually families have are concerned because they are painful and acute. Ulcers are sometime noticed by the physician and not the family as in the case of herpangina or hand-foot and mouth disease. Chronic or recurrent ulcerations present less commonly and therefore it may be more difficult to determine their etiology. Many of the systemic disease causes of oral ulcers are overall infrequent and/or not common in the pediatric age range.

Ulcers can be classified in several ways but acute ulcers are usually painful and last less than 2 weeks and chronic ulcers may or may not be painful and lasts more than 2 weeks. Minor ulcers are considered to be 5 mm, can be deep, usually are single lesions and can heal with scaring. They heal within 7-10 days.

Trauma (e.g. mechanical, heat, chemical) is one of the most common reasons for ulcers. These generally heal quickly unless there is ongoing trauma such as a habit.

Recurrent apthous stomatitis (RAS) or canker sores present clinically as shallow with a necrotic center and red halo surrounding the ulceration. They are very commonly seen in younger children. The cause is unknown but probably the patient has genetic susceptibility with another health problems that exacerbates the stomatitis and/or other agents that trigger then such as medication, food, etc. Herpetiform aphthous ulcers are a variation of RAS that are < 1 mm and occur in clusters.

Treatment for minor ulcers is usually palliative good oral hygiene, and potentially antibiotic oral rinses, silver nitrate cauterization or topical corticosteroids. For major ulcers, corticosteroids or other medications such as azothioprine, mycophelylate, and others are used. Dental referral can be considered if usual treatment does not work or the clinical presentation is not clear.

Learning Point
The differential diagnosis of leukoplakia also overlaps oral ulcers and can be reviewed here.

The differential diagnosis of oral ulcers includes:

  • Trauma – one of most common
  • Recurrent aphthous stomatitis including Herpetiform aphthous ulcers
  • Hormonal
    • Puberty
    • Oral contraceptives
    • Pregnancy
  • Immune problems
    • Lichen planus, oral
    • Pemphigus vulgaris
    • Erythema multiforme
  • Infectious disease
    • Coxsackie A
    • Cytomegalovirus
    • Epstein-Barr virus
    • Herpes simplex 1 and 2
    • Human immunodeficiency virus
    • Varicella
    • Syphilis
    • Tuberculosis
    • Fungal
  • Neoplasm – Squamous cell carcinoma
  • Systemic diseases
    • Acute necrotizing ulcerative gingivitis
    • Bechet’s syndrome
    • Celiac disease
    • Cyclic neutropenia
    • Inflammatory bowel disease – Crohn’s and ulcerative colitis
    • Immunoglobulin A deficiency
    • Iron deficiency anemia
    • Pernicious anemia
    • MAGIC syndrome – oral and genital ulcers with inflamed cartilage
    • Reiter syndrome
    • Sweet syndrome – neutrophilic dermatosis with fever
    • Wegner’s granulomatosis

Questions for Further Discussion
1. How do you treat skin pressure ulcers? A review can be found here
2. How does ulcerative colitis present? A review can be found here
3. How common are gastric ulcers in children? A review can be found here
4. What are indications for referral to a dentist?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Mouth Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Siu A, Landon K, Ramos DM. Differential diagnosis and management of oral ulcers. Semin Cutan Med Surg. 2015;34(4):171-177. doi:10.12788/j.sder.2015.0170

Fitzpatrick SG, Cohen DM, Clark AN. Ulcerated Lesions of the Oral Mucosa: Clinical and Histologic Review. Head Neck Pathol. 2019;13(1):91-102. doi:10.1007/s12105-018-0981-8

Minhas S, Sajjad A, Kashif M, Taj F, Waddani HA, Khurshid Z. Oral Ulcers Presentation in Systemic Diseases: An Update. Open Access Maced J Med Sci. 2019;7(19):3341-3347. doi:10.3889/oamjms.2019.689

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa