Quality Resource Guide –

Oral Ulcerative and Vesiculobullous Diseases Part 1 - 4th Edition

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(>1.0 cm) and more painful and persist longer

than minor aphthae, typically six weeks or longer,

with a post-pubertal onset. Because of the depth,

extent and duration of inflammation, major

aphthous ulcers appear as a crater clinically and

typically heal with scar formation. Lesions may

take up to 6 weeks or longer to heal, and as soon

as one ulcer disappears, another one often starts.

In patients who experience an unremitting course

with significant pain and discomfort, systemic

health may be comprised because of difficulty in

eating and psychological stress. The predilection

for movable oral mucosa is typical for major

aphthous ulcers as it is for minor aphthae while

HIV-positive patients may have aphthous lesions

at any intraoral site.

Herpetiform Aphthous Ulcers

Herpetiform aphthous ulcers present clinically as

recurrent crops of small ulcers (Figure 4) and arise

in 1-10% of those with aphthous ulcers. Although

movable mucosa is predominantly affected,

palatal and gingival mucosa may also be involved,

often characterized by coalescence and formation

of larger, more irregular ulcers. Pain may be

considerable, and healing generally occurs in

1 to 2 weeks. Unlike herpes infections themselves,

herpetiform aphthous ulcers are not preceded by

vesicles (as a key distinguishing feature from

recurrent primary herpes simplex infections) and

exhibit no viral-infected cells. Other than the

clinical feature of crops of oral ulcers, there has

been no finding that can link this disease to a

viral infection.

Histopathology

Aphthous ulcers have nonspecific microscopic

findings, with no histologic features that are

diagnostic. Virus-infected cells are not evident.

Essentially, the same nonspecific microscopic

changes are found in all forms of aphthous

ulcers.

Differential Diagnosis

Diagnosis of aphthous ulcers is generally based on

history and clinical appearance. Lesions of secondary

(recurrent) oral herpes can mimic aphthous ulcers

but can usually be distinguished from them based on

history and physical examination (Table 2).

A history

of vesicles preceding ulcers, location on the attached

gingiva and hard palate, and crops of lesions indicate

herpetic rather than aphthous ulcers. Other painful

oral ulcerative conditions that may simulate the

various forms of aphthous ulcers include traumatic

ulcers, pemphigus vulgaris, mucous membrane

pemphigoid, enterovirus infections (hand, foot,

mouth disease) and neutropenia-related ulceration.

Treatment

In most patients with an occasional or a few

minor aphthous ulcers, no treatment is usually

indicated apart from a bland mouthrinse such as

sodium bicarbonate in warm water to keep the

mouth clean. Over the counter preparations such

as amlexanox may be effective. However, when

patients are more severely affected, other forms of

prescription level treatment can provide significant

control (but not necessarily a cure) of this disease.

Rational treatment would include drugs that can

manipulate or regulate immune and inflammatory

responses including corticosteroids (triamcinolone

acetonide, fluocinonide gel), diaminodiphenyl

sulfone

and others (Table 2). In this category

corticosteroids currently offer the best chance for

disease containment. In severely affected patients

systemic steroids may be used for immediate

control. A low to moderate dose of prednisone

for a short period is effective. A typical regimen

might be 20 to 40 mg. daily for one week,

followed by another week at half the initial dose

before discontinuation. However, for patients with

mild to moderate disease, topical mono-therapy

only, paired with topically placed lidocaine, is

usually effective. Topically applied steroids, if used

judiciously, can be relatively efficacious and safe.

Although nearly all topical steroid compounds

have been developed for use on skin, it has been

standard practice to prescribe these agents for use

on mucous membranes for limited periods of time.

Intralesional injection of triamcinolone may be used

for individual or focal problematic or recalcitrant

lesions.

Other Drugs

Recent studies indicate that thalidomide may

provide relief to severely affected patients,

especially AIDS patients. This drug is considered

to reduce TNF-alpha levels, inhibit neutrophil

chemotaxis, stabilize lysosomal membranes and

reduce local free radical formation, among other

properties. Two other drugs that have shown some

therapeutic efficacy at the systemic level for oral

ulcerations as a component of a complex aphthous

stomatitis are pentoxifylline (a drug that has

properties that include an influence on chemical

and cellular mediators of inflammation)

Figure 4

Herpetiform aphthous ulcers are present over

the anterior ventral tongue surface.

The

ulcerations are small, clustered and tender,

but are not preceded by a vesicular phase.

Table 2 - Aphthous Ulcers vs. Secondary Herpes Simplex Infection

Aphthous Ulcers

Herpes Simplex

Etiology

Immune dysfunction

HSV1

Triggers

Stress, trauma, diet, hormones,

depressed immunity

Stress, trauma, ultraviolet light,

depressed immunity

Prodrome

Little prodrome

Prodromal symptoms

Appearance

Nonspeciﬁc microscopy, no

vesicles, single, oval ulceration

Viral cytopathic changes, vesicles pre-

cede ulcers, multiple, confulent ulcers

Sites

Nonkeratinized mucosa

Keratinized mucosa

Treatment

Corticosteroids, topical tetracycline

rinses

Antiviral treatment