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Treatment of Recurrent Aphthous Stomatitis. a Literature Review J Clin Exp Dent. 2014;6(2):e168-74. Treatment of recurrent aphthous stomatitis Journal section: Oral Medicine and Pathology doi:10.4317/jced.51401 Publication Types: Review http://dx.doi.org/10.4317/jced.51401 Treatment of recurrent aphthous stomatitis. A literature review Irene Belenguer-Guallar 1, Yolanda Jiménez-Soriano 2, Ariadna Claramunt-Lozano 1 1 Degree in Dental Surgery. Master in Oral Medicine and Surgery 2 Assistant Professor. University of Valencia. Valencia, Spain Correspondence: Unidad de Medicina Bucal. Departamento de Estomatología Facultad de Medicina y Odontología C/ Gascó Oliag, 1 46010, Valencia, Spain [email protected] Belenguer-Guallar I, Jiménez-SorianoY, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent. 2014;6(2):e168-74. http://www.medicinaoral.com/odo/volumenes/v6i2/jcedv6i2p168.pdf Received: 28/11/2013 Accepted: 23/12/2014 Article Number: 51401 http://www.medicinaoral.com/odo/indice.htm © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488 eMail: [email protected] Indexed in: Pubmed Pubmed Central® (PMC) Scopus DOI® System Abstract Recurrent aphthous stomatitis (RAS) is the most common chronic disease of the oral cavity, affecting 5-25% of the population. The underlying etiology remains unclear, and no curative treatment is available. The present review examines the existing treatments for RAS with the purpose of answering a number of questions: How should these patients be treated in the dental clinic? What topical drugs are available and when should they be used? What systemic drugs are available and when should they be used? A literature search was made of the PubMed, Cochrane and Scopus databases, limited to articles published between 2008-2012, with scientific levels of evidence 1 and 2 (metaanalyses, systematic reviews, phase I and II randomized clinical trials, cohort studies and case-control studies), and conducted in humans. The results obtained indicate that the management of RAS should be based on identification and control of the possible predisposing factors, with the exclusion of possible underlying systemic causes, and the use of a detailed clinical history along with complementary procedures such as laboratory tests, where required. Only in the case of continuous outbreaks and symptoms should drug treatment be prescribed, with the initial appli- cation of local treatments in all cases. A broad range of topical medications are available, including antiseptics (chlorhexidine), antiinflammatory drugs (amlexanox), antibiotics (tetracyclines) and corticosteroids (triamcinolone acetonide). In patients with constant and aggressive outbreaks (major aphthae), pain is intense and topical treatment is unable to afford symptoms relief. Systemic therapy is indicated in such situations, in the form of corticosteroids (prednisone) or thalidomide, among other drugs. Key words: Recurrent aphthous stomatitis, treatment, clinical management. e168 J Clin Exp Dent. 2014;6(2):e168-74. Treatment of recurrent aphthous stomatitis Introduction • Major RAS: This is the most severe presentation of Recurrent aphthous stomatitis (RAS) is characterized the disease, representing 10% of all cases. In this by the appearance of initially necrotic ulcers, with well subtype the ulcers measure over 1 cm in size and defined limits surrounded by an erythematous halo. The tend to appear on the lips, soft palate and pharynx. lesions are located on the oral mucosa, but are infrequent The lesions persist for over 6 weeks and can leave on the gums (1,2). The disease manifests in the form of scars. outbreaks, with a chronic and self-limiting course in most • Herpetiform RAS: This subtype accounts for 1-10% cases (3,4). RAS is the most frequent chronic disease of of all cases and is characterized by recurrent out- the oral cavity, affecting 5-25% of the population (3-6). breaks of small, deep and painful ulcers. Up to 100 It is more common in patients between 10-40 years of aphthae can develop simultaneously, measuring 2-3 age, and predominantly affects women and individuals mm in size, though they tend to merge to form larger of higher socioeconomic levels (1,3,7). ulcerations with an irregular contour. This presenta- The underlying etiology is not clear, though a series of tion is more often seen in women and in patients of factors are known to predispose to the appearance of older age, in contrast to the other two clinical subty- oral aphthae, including genetic factors, food allergens, pes of the disease (3,4,9,12). local trauma, endocrine alterations (menstrual cycle), The diagnosis of RAS is based on the patient anam- stress and anxiety, smoking cessation, certain chemical nesis and clinical manifestations. There is no specific products and microbial agents (2-5,8,9). Immune altera- diagnostic test, though it is essential to discard possible tions have been observed, beginning with an unknown underlying systemic causes – particularly in the case of antigenic stimulation of the keratinocytes, and resulting adults who suffer sudden outbreaks of RAS. It is advi- in the activation of T lymphocytes, cytokine secretion sable to request a complete series of laboratory tests, in- (including tumor necrosis factor-alpha (TNF-α)), and cluding a complete blood count, and evaluations of iron, leukocyte chemotaxis. TNF-α is believed to play an im- vitamin B12 and folic acid. A biopsy of the lesions is portant role in the development of new RAS lesions, and only recommended in the case of diagnostic uncertainty, has been found to be increased 2- to 5-fold in the saliva since the findings only indicate a simple nonspecific in- of affected patients (10). Changes have also been repor- flammatory lesion (3,4,12). ted in elements of the salivary defense system, such as Since the cause of the disease is not known, many drugs the enzyme superoxide dismutase (SOD), which parti- have been evaluated in an attempt to palliate the symp- cipates in the inflammatory response of RAS (11). An toms. Treatment used is multifocal and varies according increase is moreover observed in the expression of vas- to the predisposing factors. In all cases management is cular and keratinocyte adhesion molecules. This gives symptomatic, and seeks to reduce inflammation of the rise to the accumulation of lymphocytes and lymphocyte aphthae and afford pain relief by administering topical infiltration of the epithelium, with the induction of ulcer or systemic treatments (1,2). formation (3,4,12). On the other hand, many systemic The present literature review examines the existing diseases are known to be associated with oral aphthae, treatments for RAS with the purpose of answering a including Behçet’s syndrome, hematological disorders, number of questions: How should these patients be trea- vitamin deficiencies, gastrointestinal diseases, cyclic ted in the dental clinic? What topical drugs are available neutropenia, Reiter syndrome, Magic syndrome, PFA- and when should they be used? What systemic drugs are PA (periodic fever, aphthous pharyngitis and cervical available and when should they be used?. adenopathy), Sweet syndrome and immune deficiencies (1,13). Material and Methods As regards the clinical manifestations, the basic lesion A literature search of the PubMed, Cochrane and Sco- is a recurrent, painful, rounded or oval ulcer with a ne- pus databases was made using the key words recurrent crotic base. Three clinical subtypes of RAS have been aphthous stomatitis, treatment and clinical management, established according to the magnitude, number and du- combined and related by means of the boolean operator ration of the outbreaks (12): AND. The search was limited to articles published bet- • Minor RAS: This is the most common presentation ween 2008-2012, with scientific levels of evidence 1 and of the disease, representing 70-85% of all cases. It 2 (metaanalyses, systematic reviews, phase I and II ran- manifests as small rounded or oval lesions covered domized clinical trials, cohort studies and case-control by a grayish-white pseudomembrane and surrounded studies), and conducted in humans. A total of 33 articles by an erythematous halo. Each minor RAS episode were identified: one metaanalysis, one cohort study, 3 usually involves the appearance of 1-5 ulcers mea- systematic reviews and 24 phase I and II randomized suring under 1 cm in diameter. These episodes are clinical trials. We also included four literature reviews, self-limiting and resolve within 4-14 days without due to their interest and recent publication. leaving scars (3-5,7,9). e169 J Clin Exp Dent. 2014;6(2):e168-74. Treatment of recurrent aphthous stomatitis Results and Discussion toothbrush, providing brushing instructions). It is ad- The literature describes different approaches to the ma- visable to question the patient about his or her eating nagement of RAS. As a first consideration, we will des- habits, in order to evaluate possible associations bet- cribe the recommendations on how these patients should ween the disease outbreaks and certain foods. In this be treated in the dental clinic. context, it is generally advisable to avoid hard foods - Initial clinical evaluation and non-pharmacological (e.g., hard toasted bread), all types of nuts (walnuts, treatment hazelnuts, etc.), chocolate, acid beverages or foods A first requirement is a full and detailed clinical history (fruit or citrus juices, tomato), salty foods, very spi- (3,4). Some authors recommend complementary measu- cy food (pepper, curry) and alcoholic and carbonated res such as a complete blood test including red cell count, beverages. folic acid, ferritin and vitamin B12, with the purpose of • Type B: Episodes develop on a monthly basis, lasting discarding possible underlying systemic causes (vitamin 3-10 days, and the pain causes the patient to modify deficiencies, gastrointestinal disease, Behçet’s syndro- habits of hygiene and diet. If a predisposing factor me, immune deficiencies) – particularly in the case of is identified (trauma, stress, diet, hygiene, etc.), it adults who suffer sudden outbreaks of RAS, in patients should be commented with the patient and contro- with major aphthae, or when there are also lesions in lled.
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