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2012Vol. 2 No. 1:1

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The role of antifungal

drugs in the management of

denture-associated stomatitis

1 Professor, Faculty of dentistry, University of Jordan, Amman, Jordan.

2 Assistant Professor, Faculty of Dentistry, Um Al Qura University, Mecca, Saudi Arabia.

Correspondence: Najla S.Dar-Odeh najla_dar_odeh@yahoo.com

Najla S.Dar-Odeh1, Mohammad Al-Beyari2, Osama A. Abu-Hammad1

Abstract

Background: Denture-associated stomatitis is a chronic infection of the oral cav-ity that may be associated with a number of bacterial and candidal organisms as well as some predisposing factors. Its management may prove to be difficult if the treatment plan was not comprehensive in addressing all the factors involved in its etiology. The aim of this review is to underline the effectiveness of antifungal drugs in the management of denture-associated stomatitis according to our personal experience and the recently published literature.

Methods: Articles were obtained from pubmed as well as by a hand search. Denture stomatitis and antifungal were used as keywords. Only articles written in English and which were published starting from the year 1990 were included.

Conclusions: Antifungal drugs certainly have a place in the management of denture-associated stomatitis. However, their use should be called upon after the control of factors known to cause this infection. Denture and oral hygiene, and management of adverse medical conditions should be the primary goal of treat-ment. This should go hand in hand with the application of topical antifungal agents particularly those in the cream or gel form for better patients’ compliance.

Key words: Denture-associated stomatitis, antifungal drugs.

Introduction

Denture-associated stomatitis (DAS) (Candida-associated denture stomatitis, chronic atrophic candidiasis, denture-sore mouth) is a chronic infection of the oral mucosa caused solely by Candida species or in association with bacteria (1). The role of Candida, and specifically C. albicans, in development of denture stomatitis is associated with pathogenic overgrowth of Candida on denture surfaces and the oral mucosa, and is widely accepted as a leading etiological factor.

It affects 24-60% of denture wearers (2), and it is usually found on the palatal mucosa beneath the fitting surface of the upper denture. Dental prostheses may produce a local

environment of lowered pH and anaerobic conditions by de-creasing the flow of oxygen and saliva to the underlying tissue; these conditions favor fungal overgrowth (3-5). Furthermore, biofilms in denture plaque represent a protective reservoir for oral microbes (6). It has also been demonstrated that Candida organisms have an affinity for the tissue side of the denture and although Candida infection is the primary aetiology of most of these lesions, other factors such as poor denture hygiene and associated bacterial flora, continuous denture wearing, ill-fitting and traumatic dentures, carbohydrate-rich diet and rarely, allergy to denture material are contributory co-factors (7). It was noticed that the prevalence is associated with the amount of tissue covered by dentures (2). It was also found that wearing denture at night and smoking were associated with the most extensive inflammation (8).

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There is chronic erythema and edema of the mucosa in con-tact with the fitting surface of the denture which is usually the maxillary denture. However, mucosa under mandibular dentures is hardly ever involved being protected by salivary flow (1). Clinically, there are three subtypes of DAS; type I is a localized simple inflammation or pinpoint hyperemia, type II is an erythematous or generalized simple type presenting as more diffuse erythema involving a part of or the entire denture-covered mucosa, and type III is a granular or papil-lary type commonly involving the central part of the hard palate and alveolar ridge (Inflammatory Papillary hyperplasia). All three types can be found simultaneously and in varying combinations. (2) Although the lesion is not painful, it might cause some unfavorable complications. The affected mucosa is atrophic providing less support for the dentures. Some pa-tients complain of burning sensation or tingling sensation be-neath the denture. Patients may also complain of associated angular cheilitis (1). Early reports pointed to the carcinogenic potential of candidal infections (9). In some patients with HIV infection, oral candidiasis may also lead to secondary complications such as esophageal candidiasis.(1)

Management of DAS depends upon a compehensive treat-ment plan. Elimination of predisposing factors is considered the first and most crucial step. The use of topical and systemic antifungal drugs is also considered an important measure. The goals of treatment are to identify and eliminate pos-sible contributing factors, prevent systemic dissemination and eliminate any associated discomfort (10).

The aim of this paper is to discuss the management of DAS with special emphasis on antifungal drugs, a rapidly develop-ing field for the treatment of this infection as well as other types of oral candidiasis.

Antifungal therapy of denture-associated stomatitis

Antifungal agents are either polyenes (nystatin and am-photericin B) or azoles which are classified into: imidazoles( clotrimazole, econazole, fenticonazole, isoconazole, ketocon-azole, miconazole, sulconazole, tioconazole); and triazoles (fluconazole, itraconazole) (1). Some of these drugs are used topically, while others are used in a systemic form. Recent re-search has concentrated upon a number of antifungal drugs for the treatment of DAS namely, fluconazole, itraconazole, miconazole and nystatin.

Topical Antifungals

Topical antifungal therapy for oral candidal infections is avail-able in many forms like pastilles, troches, creams, ointments and oral suspensions and remains the cornerstone of treat-ment in mild, localized cases of candidoses in healthy patients (10).

It was shown that most Candida species are susceptible to topical antifungal drugs like amphotericin B, (11, 12) nystatin (13), Miconazole (14-17) and clotrimazole (1). Being recom-mended as the first choice of treatment, (1) Amphotericin B is usually in the form of lozenges or oral suspension, while nystatin can be in the form of cream, pastille and oral sus-pension. On the other hand, clotrimazole is usually presented in a cream or solution form; the cream form also has an antistaphylococcal activity (1). Miconazole can be used as a lacquer (15, 18), gel (12, 17) or cream. The gel form of mi-conazole was shown to be more effective than the lacquer form (17). Chlorhexidine in the form of mouth wash (0.2%) and 2% suspension for overnight denture disinfection, can also be used to supplement antifungal drugs (19).

Systemic antifungals

Systemic antifungal agents have been recommended for pa-tients with poor compliance such as patients with special needs. They are also recommended for immunocompromised patients (20). Among systemic antifungal drugs, fluconazole and itraconazole have been the most extensively studied and proven as efficient antifungal drugs (21,22). Specifically, flu-conazole is one of the most effective agents for the treat-ment of oropharyngeal candidiasis in HIV-infected patients as well as prophylaxis for fungal infections in neutropenic patients undergoing bone marrow transplantation (23,24). It was shown to be effective, especially when administered with an oral antiseptic such as chlorhexidine.(25) Compared to miconazole, it was demonstrated that fluconazole is more effective (16). It is the drug of choice in the management of HIV-related oral candidiasis and it is superior to other topi-cally administered or systemic antifungals due to its water-solubility, oral bioavailability and good safety profile (26). Fluconazole is usually used in the form of 50 or 100 mg capsules. However, it should be given with caution in certain circumstances as it interacts with anticoagulants among other drugs. It is also contraindicated in pregnancy and liver and renal disease. Itraconazole also was shown to be effective in the management of DAS, (22) and even more effective than fluconazole (21). Martin-Mazuelos et al., (1997) showed

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that itraconazole was effective against 100% of fluconazole-resistant strains (27). Similar to fluconazole, it is usually used in the form of 100 mg capsules.

Discussion

The field of antifungal therapy is rapidly developing, espe-cially that there is a better understanding of the pathogen-esis of disease and the worldwide problem of antimicrobial resistance. The multifaceted nature of DAS etiology involves numerous predisposing factors operating locally and systemi-cally. Consequently, treatment plan should address all pos-sible etiological factors before the decision on the antifungal drug is made. Denture and oral hygiene were found to be of primary importance in healing of lesions and preventing its recurrence (28).

This is to improve prognosis and to prevent the recurrence of infection (29,30). Denture cleaning plays an important role in eliminating the conditions that favor candidal growth. This can be achieved by mechanical means, such as ultrasonic cleaners, or chemical cleansers which are particularly of ben-efit for institutionalized elders or patients who are unable to maintain a proper level of oral hygiene due to mental or physical disability.

Antifungal drugs should be used alongside denture care. However, and despite the availability of a number of antifun-gal drugs, therapeutic failure is not uncommon. This is in part due to the diluent effect of saliva and cleansing action of the oral musculature which often tend to reduce the availability of the antifungal drug below the effective therapeutic con-centration. Another cause of failure is the presence of Can-dida biofilms on mucosal and inert surfaces like prostheses and implants. In response to attachment to a surface, fungal cells produce biofilms, three-dimensional structures made up of cells surrounded by exo-polymeric, mostly polysaccharide matrices that contribute to the infectious process and anti-biotic resistance (31). Biofilms are difficult to eliminate and are a source of many refractory infections (28). It was shown that development of antifungal resistance was associated with increased pathogenicity in systemic infection as well as increased propensity for biofilm formation (32). Furthermore, the use of topical antifungals may be associated with lower patient compliance because it is required from the patient to use multiple daily doses for a relatively long period of time that may extend to three or four weeks (33). Poor patient compliance coupled with possible underlying immunodefi-ciency and emergence of drug resistance are all additional

factors against complete recovery, leading to chronic recur-rences of the disease (1). Another factor that would affect prognosis of this infection is its severity. Mild and moderate types are usually more responsive to antimicrobial therapy than the severe type which usually requires systemic antifun-gals and may need additional surgical treatment to achieve a better prognosis (18).

Other factors that may complicate treatment is the systemic condition of the patient that plays an important role in modi-fying the immune response to different sorts of infections. Medical problems can complicate local infections particulary in immunocompromised patients (28), Diabetes (34), and HIV infection (35), for instance, present a problem when treating oral Candidal infections.

Smoking is considered an important factor in modulating the response of oral mucosa to the different factors (36), however, this relationship was not confirmed in the case of DAS (37).

Pharmacologic treatment should be tailored to the individual patient, based on his/her health status and the clinical pre-sentation and severity of infection. Leaving dentures out at night and improvement of denture hygiene should be the primary therapeutic approach, prior to instituting antifungal therapy.

Antifungal drugs certainly have a place in treating DAS. In healthy patients, the antifungal drugs of choice would be a topical polyene drug. However, if the patient is immuno-compromised, the need to a systemic antifungal drug like fluconazole may arise. It was shown that fluconazole inhibits biofilm formation by both fluconazole-susceptible and fluco-nazole-resistant Candida albicans strains (38). Patient educa-tion regarding denture hygiene, the number of daily doses and duration of therapy is important. Another important aspect is the follow-up of patient’s condition to determine the response to treatment. Failure of treatment may neces-sitate culture and susceptibility testing together with further investigating the patient’s medical condition. Some studies have shown that some C. glabrata strains are developing re-sistance to fluconzole and were detected in association with denture-related stomatitis and among patients treated in in-tensive care units (12, 39). Previous fluconazole use has also been identified as a significant risk factor for development of fluconazole-resistant among non-albicans Candida species, especially Candida glabrata and Candida krusei ( 39 ). There-fore, there is a need to identify patients at risk of developing candidasis caused by species resistant to fluconazole in order to initiate adequate empirical antifungal therapy.

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