Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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Sandra A. Kopp and Justin J. Green
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Recurrent aphthous stomatitis (RAS) is the most common cause of oral ulceration. Aphthae, or ‘canker sores’, are characterized by the recurrence of one or more painful, shallow, sharply marginated ulcerations with a fibrinous base and surrounding erythematous halo on mobile, non-keratinized, oral mucosa. Three main types include minor, major, and herpetiform aphthae, which differ in size, duration, number, potential for scarring, and location of ulcerations. The etiology remains unclear; however, genetic predisposition, nutritional deficiencies, infections, hormonal changes, immunodeficiency, and environmental agents have been implicated. It is important to differentiate aphthae from other mucosal ulcerations, including herpes simples virus (HSV), other viral and bacterial infections (Epstein-Barr virus, cytomegalovirus, varicella zoster virus, coxsackie virus, syphilis, gonorrhea, tuberculosis), erythema multiforme, lichen planus, autoimmune bullous diseases (pemphigus vulgaris and cicatricial pemphigoid), contact dermatitis, chronic ulcerative stomatitis, and trauma before therapy is initiated. Malignancy and systemic vasculitis must also be considered in lesions that are not self-resolving.
The therapeutic approach to aphthae is dependent on the frequency of recurrence, duration, and severity of symptoms. In addition, underlying hematologic abnormalities, nutritional deficiencies, and medications should be considered as causative agents, as well as many systemic disorders such as inflammatory bowel disease, Crohn disease, Behçet disease, mouth and genital ulcers with inflamed cartilage syndrome (MAGIC syndrome), cyclic neutropenia, Sweet syndrome, reactive arthritis, HIV infection, and auto-inflammatory syndromes such as periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA syndrome). Stress is also thought to play a role in exacerbation of the disease. Unfortunately, because there is no curative treatment to date, the emphasis of treatment is on measures that may afford symptomatic relief and decrease occurrence, without significant adverse effects.
Topical corticosteroids are the mainstay of therapy. For milder disease, corticosteroids such as fluocinonide can be used. More potent corticosteroids such as clobetasol or halobetasol are appropriate for more severe episodes. Most practitioners suggest the use of topical therapy after meals. These can be applied in equal parts with an occlusive dressing such as Orabase for better adherence. Drug delivery can be enhanced by cotton-tip applications for 30 seconds and avoidance of eating and drinking for 30 minutes after application. Initial concentrations of 3–10 mg/mL of intralesional triamcinolone acetonide are helpful for major aphthae. Repeat injections over 2- to 4-week intervals are advised. Dexamethasone elixir 0.5 mg/5 mL three times daily used as a mouthwash or beclomethasone dipropionate aerosol spray can target ulcers on the soft palate or oropharynx. Elixirs can be combined with sucralfate or kaopectate to improve adhesion to ulceration. When used for less than 3 weeks, systemic absorption and hypothalamic-pituitary-adrenal axis suppression are unlikely.
RAS that elicits severe pain may require intermittent systemic corticosteroid therapy. Prednisone 1 mg/kg (40–60 mg) daily can be given with a 2-week taper or as ‘burst therapy’ for shorter periods. Concomitant therapy with topical corticosteroids may be helpful. Colchicine 0.6 mg two to three times daily and thalidomide 50–200 mg daily are the most effective steroid-sparing agents. Thalidomide is the only FDA-approved treatment for major aphthae in HIV-positive patients. Dapsone 100 mg daily, pentoxifylline 400 mg three times daily, and clofazimine 100 mg daily may also lead to suppression of aphthae. Anti-tumor necrosis factor (TNF-α) therapies may be effective in recalcitrant cases. Those patients who require suppressive therapy but cannot tolerate the side effects of systemic agents can try medications such as topical cyclosporine rinse 500 mg/5 mL three times daily, or interferon–α2a 1200 IU daily as a 1-minute rinse and swallow.
Application of amlexanox 5% paste four times daily has been shown to reduce aphthous ulcer healing time, and the application of amlexanox OraDisc four times daily to prodromal areas of the buccal mucosa has shown promise in the prevention of recurrent minor aphthous ulceration.
Topical anesthetics such as lidocaine gel or spray, dyclonine, diphenhydramine (12.5/5 mL) or benzocaine are helpful for pain reduction. Patients must avoid desensitization of the entire oral vault, which may lead to self-induced trauma. A compounded anesthetic mouthwash (aluminum hydroxide–magnesium hydroxide, diphenhydramine, and lidocaine) has better mucosal adherence. Systemic non-steroidal anti-inflammatory drugs (NSAIDs), sucralfate suspension, 0.2% chlorhexidine gluconate mouthwash, triclosan, or tetracycline suspension (250 mg/5 mL) may provide pain relief and reduce healing time, although these are less effective than potent topical corticosteroids. Bioadhesives such as carboxymethylcellulose provide a protective film and may reduce healing time.
Trigger avoidance can be useful. Predisposing factors include food (nuts, chocolate, tomatoes, citrus fruits, and spices), alcohol and carbonated beverages, trauma, menstruation, and stress. A food diary may be of value in identifying an offending agent. Certain medications, such as β-blockers, NSAIDs, and antioxidants, as well as sensitivity to sodium lauryl sulfate found in toothpaste, may contribute to the recurrence of aphthae. Hormonal therapy may alleviate RAS associated with menstruation. Reassurance of the benignity of this condition is paramount, and relaxation techniques or biofeedback can be discussed if stress is found to be a significant trigger.
Complete blood count
Vitamins B1, B2, B6, and B12, folate, zinc, and iron levels
Culture/polymerase chain reaction of aphthae to exclude herpes simplex virus
Messadi DV, Younai F. Dermatol Ther 2010; 23: 281–90.
Review article containing the summary of possible etiologies and clinical presentations of aphthae, differential diagnosis, and treatment options.
Scully C, Porter S. Br J Oral Maxillofac Surg 2008; 46: 198–206.
Review article highlighting possible etiologies and differential diagnosis of RAS. This article recommends checking complete blood count, folate, iron studies, and B12, as well as excluding infections or systemic diseases that may include aphthae-like ulcerations, namely Behçet disease and HSV.
Compilato D, Carroccio A, Calvino F, Di Fede G, Campisi G. J Eur Acad Dermatol Venerol 2010; 24: 667–73.
Thirty-two patients with RAS and 29 healthy controls were subjected to hematological investigations. Deficiencies were noted in 56.2% of RAS patients and 7% in controls. All patients with a negative family history of RAS showed complete remission after replacement therapy, while patients with a family history of RAS showed reduction in frequency and severity. The authors recommended that routine screening for serum iron, folic acid and vitamin B12 deficiencies should be performed
Baccaglini L, Lalla RV, Bruce AJ, et al. Oral Dis 2011; 17: 755–70.
Review article examining several myths about aphthous ulcerations, with specific emphasis of literature review of treatments in the last 6 years. They concluded that low-dose topical tetracyclines and amlexanox showed possible benefit. Outpatient procedures such as lasers or chemical cauterization provided rapid pain relief, but may not be feasible for frequent episodes.
Pimlott SJ, Walker DM. Br Dent J 1983; 154: 174–7.
In a single-blind clinical trial fluocinonide 0.05% ointment in Orabase applied up to five times daily was more effective than Orabase alone in reducing the duration of ulcers and increasing the number of ulcer-free days.
In some countries, triamcinolone in Orabase is more readily available.
Quijano D, Rodriguez M. Acta Otorrinolaringol Esp 2008; 59: 298–307.
This is a systematic review of published literature evaluating the effectiveness of topical corticosteroids in treating RAS. The authors were able to show a trend toward reduced healing times and decreased pain but commented on the lack of high-quality experiments in the literature.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
Vitamin and mineral deficiency replacement
Topical corticosteroids
Amlexanox 5% paste
Intralesional corticosteroids
Tetracycline suspension
Antimicrobial mouth rinses
Sucralfate
Hydroxypropyl cellulose/carboxymethylcellulose
