Of all types of nontraumatic ulceration that affect oral mucosa, aphthous ulcers (canker sores) are probably the most common. The incidence ranges from 20% to 60%, depending on the population studied. Prevalence tends to be higher in professional persons, in those in upper socioeconomic groups, and in those who do not smoke.
Although the cause of aphthous ulcerations in unknown, several possibilities have been postulated.
- Immunologic disorder: T cell mediated.
- Neurogenic Inflammation: Neuropeptide (e.g., substance P) induced.
- Mucosal healing defect: Inhibition by cytokines.
- Microbiological: Viral, bacterial.
- Nutritional deficiency: Vitamen B12, folic acid, iron.
- Chemical: preservatives, toothpaste compounds.
Because of the clinical similarity of oral aphthous ulcers to secondary herpes simplex virus (HSV) infection, a number of differences will be stated:
- Aphthous Ulcers
- Cause: Immune Dysfunction
- Triggers: Stress, trauma, diet, hormones, depressed immunity
- Prodrome*: Little prodrome
- Appearance: nonspecifc microsocopy, no vesicles. Single, oval ulcer
- Sites: Nonkeratinized mucosa**
- Treatment: Corticosteroids (cortisol), tetracycline (antibiotic)
- Herpes Infection
- Cause: HSV1
- Trigger: Stress, trauma, ultraviolet light, depressed immunity
- Prodrome: Prodromal symptoms
- Appearance: Viral cytopathic changes. Vesicles precede ulcers. Multiple, confluent ulcers
- Sites: Keratinized mucosa (found on the dorsum of the tongue, hard palate and attached gingiva)
- Treatment: Antiviral treatment
*Prodrome: is an early symptom (or set of symptoms) that might indicate the start of a disease before specific symptoms occur.
** Nonkeratinized mucosa:- Found in:
- Buccal mucosa refers to the inside lining of the cheeks and is part of the lining mucosa.
- Labial mucosa refers to the inside lining of the lips and is part of the lining mucosa.
- Alveolar mucosa refers to the mucosa between the gums and the buccal/labial mucosa.
Deficiencies of Vitamin B12, folic acid, and iron as measured in serum have been found in only a small percentage of patients with aphthous ulcers. Correction of these deficiencies has produced improvement or cure in this small group. Patients with malabsorption conditions such as celiac disease and crohn’s disease have been reported as having occasional aphthous type-ulcers.
In HIV-positive patients, aphthous ulcers could be more severe and protracted aphthous-like ulcers, the possible etiologic role of HIV and other agents is unknown.
Family history represents a risk factor. Over 40% of affected patients have a first-degree relative who is also affected by aphthous ulcers. A 90% degree of risk is present when both parents are affected.
- Clinical Features
Three forms of aphthous ulcers have been recognized: minor, major, and herpetiform aphthous ulcers. All forms present as painful recurrent ulcers. Patients occasionally have prodromal symptoms of tingling or burning before the appearance of the lesions. The ulcers are not preceded by vesicles and characteristically appear on the vestibular and buccal mucosa (cheek), tongue, soft palate (posterior part of the roof of the mouth), fauces (the arched opening at the back of the mouth leading to the pharynx), and floor of the mouth. Only rarely do these lesions occur on the attached gingiva and hard palate, thus providing an important clinical sign for the separation of aphthous ulcers from secondary herpetic ulcers. In patients with AIDS, however, aphthous-like ulcers may occur at any mucosal site.
- Minor Aphthae
- Size: Less than 0.5 cm
- Shape: Oval
- Number: 1-5
- Location: Nonkeratinized mucosa
- Treatment: Topical corticosteriods, tetracycline mouth rinse
- Major Aphthae
- Size: Larger than 0.5 cm
- Shape: Ragged oval, crateriform
- Number: 1-10
- Location: Nonkeratinized mucosa
- Treatment: Topical/systemic/intralesional corticosteroids, immunosuppressives
- Herpetiform Aphthae
- Size: Less than 0.5 cm
- Shape: Oval
- Number: 10-100
- Location: Any intraoral site
- Treatment: Topical/systemic corticosteroids, tetracycline mouth rinse
- Minor Aphthous Ulcers.
Minor aphthous ulcers are the most commonly encountered form. This type usually appears as a single, painful, oval ulcer that is less than 0.5 cm in diameter, covered by a yellow fibrinous membrane and surrounded by an erythematous halo (Figure 2 & 3).
Multiple oral aphthae may be seen. When the lateral or ventral surfaces of the tongue are affected, pain tends to be out of proportion to the size of the lesion (Figure 4).
Minor aphthous ulcers generally last 7 to 10 days and heal without scar formation. Recurrences vary from one individual to another. Periods of freedom from disease may range from a matter of weeks to as long as years.
In some patients with recalcitrant aphthae, a diagnosis of Crohn’s disease may be considered. This granulomatous disease affect the gastrointestinal tract from mouth to anus. Oral manifestations include mucosal fissures and small, multiple, hyperplastic (increase number of cells) nodules on the buccal mucosa, producing a cobblestone appearance (Figure 5 & 6).
HIV positive patients may develop minor aphthous ulcers, although proportionately more have major or herpetiform lesions. Aphthous-like ulcers may be seen as an initial manifestations of the periodic fever syndromes; rare noninfectious disorders are related to genetic disturbances in the mechanisms/proteins that control inflammation.
- Major Aphthous Ulcers.
Major aphthous ulcers is the most severe expression of aphthous stomatitis. Lesions larger than 0.5 cm and more painful and persist longer than normal aphthae (Figure 7).
Because of the depth of inflammation, major aphthous ulcers appear crateriform clinically and heal with scar formation. Lesions may take as long as 6 weeks to heal, and as soon as one ulcer disappears, another one starts. In patients who experience an unremitting course with significant pain and discomfort, systemic health may be compromised because of difficulty in eating and psychological stress. The predilection for movable oral mucosa is as typical for major aphthous ulcers as it is for minor aphthae. 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 8 & 9).
Although movable mucosa is predominantly affected, palatal and gingival mucosa may also be involved. Pain may be considerable, and healing generally occurs in 1 to 2 weeks. Unlike herpes infection, herpetiform aphthous ulcers are not preceded by vesicles and exhibit no virus-infected cells. Other than the clinical feature of crops of oral ulcers, no finding can link this disease to a viral infection.
Because the diagnosis of these ulcers is usually evident clinically, biopsies usually are unnecessary and therefore rarely performed. Aphthous ulcers have nonspecific microscopic findings, and no histologic features are diagnostic.
- Differential Diagnosis
Diagnosis of aphthous ulcers is generally based on the history and clinical appearance. Lesions of secondary (recurrent) oral herpes are often confused with, but usually can be distinguished from, aphthous ulcers. A history of vesicles preceding ulcers, location on the attached gingiva and hard palate (anterior part of the roof of the mouth), and crops of lesions indicate herpetic rather than aphthous ulcers. Other painful oral ulcerative conditions that may stimulate the various forms of aphthous ulcers include trauma, pemphigus vulgaris*, mucous membrane pemphigoid**, and neutropenia***.
*Pemphigus vulgaris is an autoimmune disorder that involves blistering and sores (erosions) of the skin and mucus membranes.
**Mucous membrane pemphigoid is a group of rare chronic autoimmune disorders characterized by blistering lesions that primarily affect the various mucous membranes of the body.
***Neutropenia: is an abnormally low count of neutrophils, a type of white blood cell that helps fight off infections, particularly those caused by bacteria and fungi.
In patients with occasional or few minor aphthous ulcers, usually no treatment is necessary apart from a bland mouth rinse such as sodium bicarbonate (Baking soda) in warm water to keep the mouth clean. However, when patients are more severely affected, some forms of treatment can provide significant control (but not necessarily a cure) of this disease.
Rational treatment would include drugs that can manipulate or regulate immune responses. In this category, corticosteroids (cortisol) 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 1 week, followed by another week at half the initial dose. However, for patients with mild to moderate disease, only topical therapy appears justified. Topical steroids, if used judiciously, can be relatively efficacious and safe.
- Effects & Side effects of Corticosteroids
A- Topical Steroids. Topical corticosteroids may be used intraorally as an adjunct to systemic therapy, with possible concomitant lower dose of systemic corticosteroids. Side effects of topical steroids may occur after prolonged or intense dermatologic use. However, with judicious intraoral use for short periods, it is unlikely that significant systemic effects will occur. Because topical steroids can facilitate Candidiasis orally (Oral Thrush), antifungal therapy may be needed, especially with use of high-potency corticosteroids.
- Side Effects of Topical Steroids:
- Candidiasis (is a fungal infection that can affect areas such as the: skin, genitals, throat, mouth & blood).
- Epithelial Atrophy (Waste away of body tissue due to degeneration of cells)
- Telangiectasias (a condition characterized by dilation of the capillaries, which causes them to appear as small red or purple clusters, often spidery in appearance, on the skin or the surface of an organ).
- Additional effects on skin-striae, hypopigmentation, acne, folliculitis.
B- Systemic Steroids. Because the systemic effects and complications of glucocorticoids are numerous and can often be profound, it is recommended that they be prescribed by an experienced clinican. Because the adrenals normally secrete most of their daily equivalent of 5 to 7 mg of prednisone in the morning, all prednisone should be taken, when possibly, early in the morning to stimulate the physiologic process, thus minimizing interference with pituitary-adrenal axis and side effects.
In patients requiring high-dose, prolonged, or maintenance steroid therapy, an alternate-day regimen may be used after initial therapy and an appropriate clinical response. A short-acting steroid (24 to 36 hours), such as prednisone, is desired because it allows recovery or near-normal functioning of the pituitary-adrenal axis of the “off” (no prednisone) days.
- Side effects of systemic corticosteroids
- Anti-inflammation: therapeutic
- Immunosuppression (weak immune system): therapeutic
- Gluconeogenesis (generation of glucose): diabetes, bone/muscle loss
- Redistribution of fat: buffalo hump, hyperlipidemia (high lipid levels)
- Fluid retention: moon face, weight gain
- Vasopressor potentiation (inducing vasoconstriction of blood vessels): hypertension worse
- Gastric mucosa effects: peptic ulcer worse
- Adrenal suppression: adrenal atrophy
- Central nervous system effects: psychological changes (e.g.; euphoria)
- Ocular effects: cataracts (a medical condition in which the lens of the eye becomes progressively opaque, resulting in blurred vision), glaucoma (is a term describing a group of ocular “eye” disorders that result in optic nerve damage, often associated with increased fluid pressure in the eye “intraocular pressure”).
Although nearly all topical compounds have been developed for use on skin, it has been standard practice to prescribe these agents for use on mucous membranes.
- Topical Corticosteroids Preparations*
- Clobetasol propionate (Temovate)
- Clobetasol propionate plus “oral adhesive” (50% Temovate ointment plus 50% Orabase)
- Betamethasone dipropionate (Diprosone)
- Fluocinonide (Lidex)
- Betamethsone plus clotrimazole (Lotrisone)
*Listed from high potency to intermediate potency.
Intralesional injection of triamcinolone may be used for individuals or focal problematic lesions. In cases where repeated ulcerative episodes occur and use of systemic steroids is not possible and topical agents are not effective, systemic montelukast (a leukotriene receptor antagonists) administration may be useful.
Antibiotics. Antibiotics have been used in the treatment of aphthous ulcers with fair to good results. Tetracycline and tetracycline congener suspensions, used topically, often produce excellent results. In addition to their antibacterial effect of keeping the mouth clean, tetracyclines speed resolution of the ulcers through local inhibition of matrix metalloproteinases (MMPs). Because tetracyclines readily break down in solution, they must be used within a very short time span. A typical regimen for treating aphthous ulcers consists of emptying a 250-mg capsule of tetracycline into 30 ml (1 fluid ounce) of warm water and then rinsing the mouth for several minutes. This is repeated 4 times a day in 4 days. Results are best if the mouth rinse used on the first day that the ulcers appear, or when they are in a prodromal stage.
Other drugs. Because of their rather profound side effects, immunosuppressive drugs such as azathioprine and cyclophosphamide, are generally justified only for the treatment of severely affected patients (to permit reduced prednisone dosages). Recent studies indicate that thalidomide may provide relief to severely affected patients. Two drugs that have been shown some therapeutic efficacy are pentoxifylline and colchicine.
Reference: Oral Pathology, Sixth Edition, By Regezi, Sciubba, & Jordan.
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