Ulcerations in the oral cavity - Clinical Advisor

Ulcerations in the oral cavity


  • Case #1

  • Case 2

Case #1

An Asian woman, aged 25 years, has had recurrent oral ulcerations for three years. On average, the oral ulcerations appeared every two months and healed spontaneously within two weeks.

Several 2-mm to 6-mm shallow ulcerations with a white pseudomembrane and surrounding erythematous halo were appreciated on her labial mucosa, buccal mucosa, and soft palate. The woman complained of similar lesions in the anogenital region and periorbital pain with photophobia. A review of systems was otherwise negative. 

Case #2

A man, aged 34 years, presented with painful ulcerations on his labial mucosa, soft palate, and lateral tongue of two weeks’ duration. A history of recurrent painful ulcerations that would usually heal within two to three weeks was noted.

The man had received no previous treatment and felt that the ulcerations were beginning to heal spontaneously. A review of systems was otherwise negative. Large ulcerations with a white pseudomembrane and minimal surrounding erythema were noted on his left lateral tongue, labial mucosa, and soft palate. 

HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Small brown spots on the lower shins and Elevated iron levels and erosions on the hands.

Case #1: Behçet's disease In 1924, a Turkish dermatologist named Huluis Behçet treated two individuals for loss of vision, oral aphthae, and genital aphthae.1 In 1931, a Greek physician named Benedict Adamantiades reported a patient with iritis, oral and genital...

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Case #1: Behçet’s disease

In 1924, a Turkish dermatologist named Huluis Behçet treated two individuals for loss of vision, oral aphthae, and genital aphthae.1 In 1931, a Greek physician named Benedict Adamantiades reported a patient with iritis, oral and genital ulcers, phlebitis, and arthritis and ever since, the disorder has been known as Behçet’s disease.

Behçet’s disease is a rare disorder with approximately 0.12 cases occurring per 100,000 individuals in the United States and Europe. Internationally, the disease is most prominent along the ancient Silk Road, which encompasses the Middle East, Turkey, Saudi Arabia, Iran, China, and Japan. In these regions, the disease affects 1 out of every 1,000 individuals and is most prevalent among young men between the ages of 25 and 30 years.2,3

The precise pathogenesis of Behçet’s disease remains unknown. Evidence suggests that it is an autoimmune systemic vasculitis that may be triggered by immunologic or infectious agents. A strong association has been linked to the histocompatability antigen B-51.

The manifestations of Behçet’s disease are often intermittent. Patients complain of clinically evident exacerbations and remissions with an unpredictable frequency and duration. Approximately 99% of patients will develop oral aphthae, and this may be the presenting sign in 25% to 75% of cases. Oral lesions occur most commonly in the oropharynx and soft palate and can last anywhere from one to three weeks, with spontaneous resolution and no scarring.4

The aphthae usually occur in groups of five or more, vary in size (no larger than 6 mm in diameter), and are surrounded by diffuse erythema. Genital ulcerations are clinically similar to those in the oral cavity and are most commonly found on the perianal area, penis, vagina, vulva, and scrotum.

Ocular involvement may take the form of posterior uveitis, corneal ulceration, papilledema, and/or arteritis. Other signs of Behçet’s disease include erythema nodosum-like or pustular skin lesions, arthritis, renal disease, thrombophlebitis, central nervous system involvement, and GI symptoms.

Clinicians may perform a pathergy test by obliquely inserting a sterile 20-guage needle into the skin and reading the test one to two days later.1 A positive test is indicated by a pustule that will appear at the site within 24 hours. If the test is negative, repeat it at two to five points before accepting the results as negative.

The subsequent skin hyper-reactivity, or pathergy, is a feature of Behçet’s disease that occurs in 40% to 88% of patients. However, this test may also be positive in such other diseases as pyoderma gangrenosum, acute febrile neutrophilic dermatosis, and bowel-associated dermatosis-arthritis syndrome.

Histologically, the oral ulcerations are characterized by a central diffuse neutrophilic infiltrate with necrosis of the epithelium. The periphery of the lesion typically shows a lymphocyte-predominant infiltrate both in an extravascular and perivascular distribution with variable lymphocytic exocytosis.

Genital aphthae have a similar appearance. Cutaneous lesions show a range of cutaneous vasculopathy that includes a mononuclear cell vasculitis with variable mural and luminal fibrin deposition; a paucicellular thrombogenic vasculopathy; and a neutrophilic vascular reaction, which involves capillaries and veins of all calibers.

The diagnosis of Behçet’s disease may be difficult to make, as there are no pathognomonic diagnostic tests available. The diagnosis is based on the presence of oral aphthae that occur at least three times during a one-year period. The individual must also have at least two of the following criteria: retinal vasculitis, anterior uveitis, and/or posterior uveitis; recurrent genital aphthae; erythema nodosum-like or pustular skin lesions; and a positive pathergy test.5

Aphthous stomatitis, herpes simplex virus, pemphigus, erythema multiforme, Stevens-Johnson syndrome, pyoderma gangrenosum, and erythema nodosum are often considered in the differential diagnosis.

The ulcerations of Behçet’s disease usually heal spontaneously. When ulcers are present, advise the patient to avoid vigorous tooth-brushing and to use mild mouthwashes and toothpastes. Topical anesthetics may help to alleviate the associated pain. Colchicine (Colcrys), dapsone, and thalidomide (Thalomid) have all been used for the prevention of mucocutaneous lesions.

Such other systemic treatments as methotrexate (Rheumatrex, Trexall), corticosteroids, azathioprine (Azasan, Imuran), chlorambucil (Leukeran), cyclosporine (Gengraf, Neoral, Sandimmune), interferon-alpha, tumor necrosis factor antagonists, and cyclophosphamide (Cytoxan) should be reserved for severe refractory cases.

The prognosis depends upon the amount of systemic involvement, but patients should expect to have intermittent flares of the disease. Serious complications may include blindness, neurologic impairment, and vascular thrombosis.

The woman in this case was referred to ophthalmology and treated with thalidomide to prevent recurrence of the mucocutaneous disease. For pain control, she was given a mixture of equal parts lidocaine, aluminum and magnesium hydroxide (Maalox), and diphenhydramine. The mixture was held in the mouth for five minutes and then spit out, three times a day.


Case #2: Recurrent aphthous stomatitis

Oral aphthae are also referred to as recurrent aphthous stomatitis (RAS), or more simply, canker sores. Aphthous is the ancient Greek word for ulcer. Documentation of the history of RAS is essentially nonexistent, possibly because it is one of the most common oral mucosal pathologies and may have been considered a normal variant.

RAS affects all races and has been documented to occur in 10% to 50% of the population. It is slightly more prevalent in females than in males, and for the most part, lesions appear during the adolescent years and recur throughout the individual’s life span.

The etiology remains evasive, but some studies have shown RAS to be a multifactorial disorder that is induced by a host of factors. A genetic predisposition has been demonstrated by the fact that children from parents with RAS have a 90% chance of also being affected.

Triggering agents include trauma, hormonal fluctuations, psychological stress, tobacco products, food hypersensitivities, and HIV infection and other infectious agents. Nutritional deficiencies in iron, folate, and vitamin B12 can trigger an episode as well. Immune-system dysfunction is thought to result in mucosal destruction due to a T-cell-mediated immunologic reaction.6

The three categories of simple aphthous ulcers are minor, major, and herpetiform. Minor aphthae, also known as Mikulicz’s aphthae, are the most common type and comprise 80% of cases. The ulcers are round to ovoid, shallow, and 3 mm to 10 mm in diameter. The lesions are covered by a creamy white pseudomembrane and surrounded by an erythematous halo.

Minor aphthae are most commonly found on nonkeratinized oral mucosa, including the buccal and labial mucosa, floor of the mouth, ventral tongue, oropharyngeal mucosa, and soft palate. If keratinized mucosa is affected, it is usually attributable to an extension of the adjacent nonkeratinized tissue. Lesions tend to heal without scarring in one to two weeks. Although most patients experience infrequent recurrences, others may suffer from nearly continuous lesions.

The major form of RAS is deeper and larger, ranging from 1 cm to 3 cm in diameter. Lesions usually occur in groups on the labial mucosa, soft palate, and tonsillar fauces. Patients may experience fever, malaise, and extreme pain. Due to the larger size of major aphthae, scarring may occur, and lesions usually take two to six weeks to heal.

As the name suggests, herpetiform aphthae look similar to a primary herpes infection. The lesions are small in size, ranging from 1 mm to 3 mm in diameter, and usually occur in groups of up to 100 or more. An episode can last from seven to 10 days. These painful ulcers are typically confined to the nonkeratinized tissue and are recurrent, which are features that may help to distinguish them from a primary herpes infection.

Histologic features of RAS are rather nonspecific. Early lesions may demonstrate a central ulcerated region covered by a fibrinopurulent membrane with a neutrophilic vessel-based submucosal infiltrate.

History, physical examination, and long-term follow-up documenting the recurrence course in the absence of other symptoms are the best diagnostic tools. No laboratory test exists for a definitive diagnosis of RAS. Beçhet’s disease, cancers of the oral mucosa, cicatricial pemphigoid, pemphigus, contact stomatitis, erythema multiforme, Stevens-Johnson syndrome, HIV, inflammatory bowel disease, hand-foot-and-mouth disease, herpes simplex, syphilis, candidiasis, lichen planus, and lupus erythematosus are all included in the differential diagnosis.

Treatment may depend on whether the lesions are simple or complex. Simple aphthosis is described as having fewer than three lesions, which tend to heal within one to two weeks and infrequently recur. Complex aphthosis is defined as having three or more lesions that are fairly constant due to the high recurrence rate and longer healing time.

For simple and complex aphthosis, the primary goals of treatment should be pain management, prevention of recurrence, promotion of healing, and proper nutrition.7 At the first signs of an outbreak, the patient should apply a thin film of a superpotent topical corticosteroid gel several times daily to reduce the healing time and associated pain. There are also multiple topical analgesics that may help to temporarily alleviate the associated pain.

Oral colchicine, dapsone, or thalidomide may be required for individuals with complex aphthosis. Correction of folate, iron, and vitamin B12 levels are warranted if found to be abnormal.8 Some studies have even documented improvement with cyanocobalamin when the vitamin B12 levels are normal.

Most people are minimally inconvenienced by RAS because attacks are usually infrequent and heal spontaneously. When present, however, the lesions are painful, and speech and mastication may prove difficult. Luckily, the lesions tend to occur less frequently with age.

The man in this case was diagnosed with a major aphthous ulcer. Since it was healing at the time of presentation, no topical corticosteroid was given. For pain control, he was given a mixture of equal parts lidocaine, aluminum and magnesium hydroxide, and diphenhydramine. The mixture was held in the mouth for five minutes and then spit out, three times a day. 

Kerri Robbins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston. Damjan Jutric is a second-year dental student at The University of Texas School of Dentistry, also in Houston.


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  3. Bardak Y. Epidemiologic and clinical features of Behçet’s disease. J Rheumatol. 2001;28:455-456.
  4. Al-Otaibi LM, Porter SR, Poate TW. Behçet’s disease: a review. J Dent Res. 2005;84:209-222.
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  6. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg. 1997;16:278-283.
  7. Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am. 2005;49:31-47.
  8. Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2010;39:420-423.
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