By Gary M. White, MD

Aphthous ulcer of the lip

Aphthous ulcers (AU) are painful superficial oral erosions. They often come in crops. Trauma may induce them. The majority of cases are idiopathic. Some have suggested that recurrent aphthous stomatitis (RAS) may have an immunogenetic background owing to cross-reactivity with Streptococcus sanguis. A small percentage of patients have a hematinic deficiency (e.g., iron, folate, vitamin B-12) [J Oral Pathol Med. 2015 Apr;44(4):300-5]. Case reports of isolated causes include zinc deficiency and fluoride allergy.


Aphthous ulcers appear as white or gray oval areas with a bright red surrounding erythema in the oral cavity. They most commonly occur on the buccal and labial mucosa.

Occasionally, patients may have a more severe presentation with larger or more persistent lesions. The term major aphthous stomatitis has been used and is defined as ulcers greater than 1 cm that are present for more than two weeks and often heal with scarring.

When AU occur in children, PFAPA syndrome should be considered (high fever and AU occuring every 4 weeks).


Many triggers have been reported including spicy foods, citrus, walnuts, pineapple, trauma (e.g., from the toothebrush, self-biting, dental procedures), menstruation, pregnancy, menopause and stress.

Workup for unusually severe (Major) aphthous ulcers

Blood work for HIV, iron, zinc, folate and vitamin B12 may be measured. The history may be reviewed for inflammatory bowel disease or any signs of other skin problems, e.g. vasculitis, genital ulcerations (Behcets Syndrome).


Aphthous ulcers need not be treated if uncommon.

Vitamin B12

Vitamin B12 (cobalamin) has been reported effective in several studies for RAS. It may be taken the standard way as a pill that is swallowed. However, because of concerns about gut absorption, multiple other delivery methods are available including a sublingual tablet (e.g., 1000 mcg/day), lozenge or oral spray, intranasal spray, and by prescription as a subcutaneous weekly injection. In one DBPCT of one sublingual vitamin B12 tablet (1000 mcg of vitamin B12) at bedtime, there was a significant reduction of the number of lesions at 6 months [Evid Based Dent. 2009;10(4):114-5]. This intervention was beneficial regardless of the Vitamin B level. In one DBPCT, topical vitamin B12 greatly reduced pain compared to placebo after 2 days [Pain Manag Nurs. 2015 Jun;16(3):182-7].

Topical Steroids

What follows is off label and the patient should be informed as such and they must accept that this is "experimental". A high-potency topical steroid (e.g., clobetasol ointment) may be applied 3-5 times per day directly to the ulcer. The patient should massage the steroid into the ulcer for 30-60 seconds and then not eat or drink for 30 minutes. There is an increased risk of Candida and the patient should be monitored. If the patient finds it hard to keep the topical steroid on the lesion, applying the steroid to a gauze and applying to the lesion for ten minutes several times a day may be done. Alternatively, Kenalog in Orobase applied QHS and QAM may be tried. Other options include applying a steroid pill directly onto the ulcer and allowing it to dissolve; spraying an asthma steroid inhaler directly onto the ulcer; gargle with tacrolimus solution for 30 seconds and spit; do the same with cyclosporin oral solution; or 5 drops of clobetasol solution in a capful of OTC Biotene oral rinse, swish 3-5 minutes, then spit.

Oral Steroids

A short course of prednisone e.g., 40 mg/day x 4 days can rapidly heal ulcers.


50 mg penicillin G potassium troches (Cankercillin) speeded healing time in a DBPC trial [Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Dec;96(6):685-94]. Alternatively, the contents of a 250 mg capsule of tetracycline mixed in water, swished and held in the mouth for 2-3 minutes TID may be tried. In one DBPCT [Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:440], the contents of a single crushed doxycycline tablet was applied with denture adhesive and a few drops of saline directly to the ulcer(s). Just one application sped healing and reduced pain.

Magic Mouthwash

The Magic Mouthwash can be quite soothing of any oral ulcerations. Various recipes exist. Key ingredients include Maalox, viscous lidocaine, diphenhydramine elixir and dexamethasone. In the case of aphthous ulcers, the contents of tetracycline or doxycycline capsules may be added.


Apremilast cleared one patient with recalcitrant disease completely after 6 weeks [JAAD Case Reports 2017 Sept].

Good oral hygiene and the use of a low allergenic over-the-counter toothpaste has been recommended.

One patient noted with certainty that sweets (e.g., chocolate, cookies) in the diet were positively correlated with outbreaks. Avoiding sweets nearly prevented outbreaks.

Thalidomide is the treatment of choice for severe disease. It may be given at a dose of 100-200 mg/day and 2-3 months may be needed to see an effect. Others start at 300 mg/day. Once controlled, the thalidomide may be tapered to alternate day to every third day dosage as possible. Alternative oral medications that have been tried include azathioprine, cyclosporin, colchicine, pentoxifylline and dapsone.

A DBPCT of a multivitamin as treatment to prevent recurrent aphthous ulcers did not show any benefit [J Am Dent Assoc 2012:143:370].

Additional Pictures

Major aphthous stomatitis
major aphthous stomatitis

Aphthous ulcer in the mouth Aphthous ulcer of the tongue


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