Underlying etiologies of oral ulcers require attention

Rochester, Minn. - When managing complex oral ulcers, an expert says, taking a systematic approach helps guide treatment of the ulcers and any conditions that contribute to them.

Although some patients complain that they have canker sores all over the mouth, they usually don’t, says Alison Bruce, M.D., associate professor of dermatology, Mayo Clinic, Rochester, Minn.

“Aphthous ulcers tend to occur on soft, non-keratinized mucosal surfaces - typically the underside of the tongue, inside the lips and inside the cheeks, but usually not the dorsum of the tongue or the hard palate,” she says.

In terms of appearance, aphthous ulcer classifications include minor, major and herpetiform. Minor aphthous ulcers heal within seven to 10 days, she says, while major ones, which can possess a necrotic appearance, take much longer due to their size. While still remaining on soft mucosal surfaces, she adds, “Often these larger aphthous ulcers tend to occur more posteriorly, such as on the soft palate.”

Herpetiform aphthous ulcers appear in clusters, but have nothing to do with the herpes virus, she says. Ulcers associated with herpes virus infection have a punched-out appearance and tend to occur on well-keratinized surfaces such as the gums, the dorsum of the tongue and especially the lips, she explains.

“The other way that aphthous ulcers are classified is by their behavior - is it simple or complex aphthosis (Rogers RS 3rd. Postgrad Med. 1992;91(6):141-148, 151-153. Review)?” In the former condition, Dr. Bruce says, canker sores appear perhaps a few times yearly and resolve with little trouble. In complex aphthosis, also called recurrent aphthous stomatitis (RAS), “Patients have severe aphthous ulcers that last a long time - no sooner has one episode healed than they move into another episode” elsewhere in the mouth. These patients can also have associated genital ulcers, she adds.

“We need to recognize that canker sores are very common. Probably about 50 percent of people suffer from them. They can be a manifestation of a multitude of different diseases. And it’s our job to figure out which patients have simple primary aphthosis, and which have canker sores occurring as a result of other pathology,” Dr. Bruce says.

Although aphthous ulcer etiology can be complex, she says, it’s relatively easy to determine through patient history and simple tests.

“Behcet’s disease can uncommonly be the diagnosis in patients who present with oral or genital ulcers. But they also have other things going on,” she says. “So on review of systems, you can determine if they have ocular inflammation,” or systemic manifestations such as a history of thrombophlebitis, pustular skin lesions, strokes or central nervous system problems, any of which could suggest Behcet’s disease.

Gut check

Similarly, Dr. Bruce says that because the mouth is the start of the alimentary canal, “Some diseases that affect the gut - such as inflammatory bowel disease - can start off with aphthous ulcers.” However, she says, such patients also can have swollen, edematous appearing and granulomatous inflammation in the mouth. Accordingly, she says that when taking histories, “Ask your patients about anything bowel-related - diarrhea, constipation and abdominal pain.”

Celiac disease (CD) may occasionally present with aphthous ulcers. A tissue transglutaminase test can exclude CD, Dr. Bruce says. Blood tests also can screen for HIV, and for vitamin or IgA deficiencies, which may also be unusual causes of aphthous ulcers.

Conversely, “Cyclic neutropenia - another cause of recurrent oral ulcers - is a disorder of the neutrophils in which they don’t mature properly. So people are predisposed to infections, and have cyclical development of canker sores.”

Clinicians may figure out which patients need to be referred if they take a thorough history and perform simple bloodwork, Dr. Bruce says.

“That’s really our job - to do a thorough review of systems, refer patients if they have other systemic manifestations, and perform a very simple workup which will include routine bloodwork in anticipation of medication use. Screening for vitamin deficiencies is also very important because this is an easily correctable problem, and deficiencies can increase susceptibility to canker sores,” she says.

Treating RAS requires addressing existing ulcers and attempting to minimize future recurrences, Dr. Bruce says. Moreover, “Treating the acute episode is quite different from impacting the natural history.”

Active ulcers

To manage active ulcers, Dr. Bruce says that among topical antibiotics, “Tetracycline suspension has a very low pH and can burn. It’s also not that stable in an aqueous medium, so sometimes you have to get pharmacies to compound it, and to me that sounds too complicated.” On occasion, Dr. Bruce says she would consider oral minocycline, although there’s little data behind its use for RAS.

Among analgesics, “Lidocaine is very helpful,” but she cautions patients not to overuse it before eating because they could do further damage without feeling it. Patients also can use over-the-counter topical anesthetics such as benzocaine and chamomile, Dr. Bruce says. However, she says, patients should avoid alcohol vehicles because alcohol tends to dry the mucosa.

“My next strategy is usually to give some form of topical corticosteroid. Typical steroids formulated in Orabase Protective Paste (Colgate-Palmolive) include triamcinolone. You’ll probably need something a little stronger,” such as fluocinonide or clobetasol, which can be compounded in this vehicle if desired. “Dental pastes like Orabase are designed to stick to the ulcer and make it feel better. However, I’m not a big fan of Orabase because it is somewhat grainy and sticky.”

Therefore, Dr. Bruce says she prefers gels, as they can be applied a little easier than pasty vehicles. Accordingly, Dr. Bruce has patients apply fluocinonide gel several times daily as soon as they feel ulcers developing. For ulcers in the back of the throat, “You can prescribe a spray such as Beconase (beclomethasone, GlaxoSmithKline) or a dexamethasone swish that patients can gargle and spit out.”

In the office, she adds, physicians can inject submucosal triamcinolone, or clinicians can cauterize with a chemical agent.

Less frequent outbreaks

For patients with occasional outbreaks, “Canker sores should melt away with a short (less than three-week) course of systemic prednisone.” For patients with recurrent cases, she typically uses systemic drugs including colchicine - which she says is well-suited for canker sores because they have a substantial neutrophilic infiltrate - to try to reduce frequency of outbreaks.

“The biggest problem with colchicine is that it causes diarrhea,” Dr. Bruce says. She suggests starting slowly - with one dose nightly for a week - and ramping up to two or three times daily. Dr. Bruce says that in her experience, “At least half the patients I see will do well on colchicine and won’t need anything additional.”

Systemic dapsone also works well because it’s an anti-neutrophilic agent, she says. Added to colchicine, “The two seem to have a synergistic effect. Dapsone is a little more complicated to use because it requires lab monitoring. And generally you should start low on the dapsone dose and work up to about 125 to 150 mg, in addition to colchicine, daily.”

It’s also important to warn patients that dapsone will reduce their hemoglobin levels, although most healthy patients can tolerate hemoglobin levels of 10 or 11 g/dL, Dr. Bruce says. Additionally, “Trental (pentoxifylline, Sanofi-Aventis) probably helps.”

In a 24-patient, six-week study, between 61 and 64 percent of men and women with recurrent oral ulcers responded positively to oxypentoxifylline, dosed at 400 mg three times daily for one month (Chandrasekhar J, Liem AA, Cox NH, Paterson AW. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87(5):564-567).

“The advantage of Trental is that you can add it to your other drugs and it usually doesn’t require lab monitoring,” Dr. Bruce says, adding that some of her patients have pronounced the drug a life-changer.

Singulair (montelukast sodium, Merck) inhibits leukotriene, thereby impacting the inflammatory cascade, Dr. Bruce says. “It’s simple to use - 10 mg a day, no lab monitoring. Many patients use it for asthma. So I don’t have a problem adding this to a regimen for recurrent canker sores.”

Likewise, she says that tumor necrosis factor (TNF) inhibitors have been reported to be effective in Behcet’s disease. “Using them makes sense because we know that TNF is upregulated in patients with aphthous ulcers. In those patients who have very severe, complex aphthosis who fail my treatment algorithm, I would consider these,” as well as interferon.

Looking ahead

To minimize future outbreaks, dermatologists should try to engage their patients in what they can do to help combat their disease, according to Dr. Bruce.

“We know that trauma triggers canker sores. So tell patients to be careful about chewing and chatting at the same time. And watch the foods they eat - generally, a soft, bland diet is helpful,” as is avoiding foods with sharp edges, she says.

When brushing teeth, she says, patients should use soft-bristle toothbrushes or gentle techniques such as a WaterPik (WaterPik Inc.) on a low setting. “And you may need to refer patients to their dentist if needed.”

Dr. Bruce also suggests that her patients avoid toothpastes that contain sodium lauryl sulfate (SLS). “SLS makes toothpaste frothy, and it’s thought to possibly trigger canker sores (Herlofson BB, Barkvoll P. Acta Odontol Scand. 1996;54(3):150-153).” Conversely, she says that antiseptic mouthwashes that contain chlorhexidine or triclosan can be helpful.

Assuming patients have no other vitamin deficiencies, she adds, “You can tell them to take vitamin B12 - even if their B12 tests normal.” In one such study, researchers found that giving super-normal levels of B12 - 1,000 mcg daily for six months - seemed to help patients who suffer from canker sores (Volkov I, Rudoy I, Freud T, et al. J Am Board Fam Med. 2009;22(1):9-16). DT

Disclosures: Dr. Bruce reports no relevant financial interests.