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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 2  |  Page : 67-71

Alternatives to antifungal therapy for denture stomatitis: A systematic review and meta-analysis


1 Department of Oral Health, National University, Suva, Fiji
2 Department of Health Sciences, National University, Suva, Fiji

Date of Web Publication25-Jul-2017

Correspondence Address:
Gowri Sivaramakrishnan
Department of Oral Health, Fiji National University, Brown Street, Suva
Fiji
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjos.SJOralSci_22_17

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  Abstract 

Denture stomatitis presents with inflammation of the oral mucosa beneath the denture. 90% of the cases identified Candida as a causative organism, and antifungal therapy is being commonly advocated. This systematic review and meta-analysis aim to identify disinfection of dentures as a mode of prevention of denture stomatitis to avoid the adverse effects of antifungal therapy. Literature search was performed on electronic databases. Cochrane's tool was used for assessing the risk of bias. Forest plot was generated for heterogeneity with I2 statistics and Chi-square test for the following outcome measures: Candida count, clinical improvement, recurrence of stomatitis, and adverse events. A total of five studies were found to be eligible, and the pooled estimate for Candida count was 0.39 (0.03, 0.75) was statistically significant favoring antifungal therapy. Forest plot of the relative risk of clinical cure was not significant between the groups with the pooled estimate of 1.38 (0.87, 2.18), and recurrence of stomatitis was 1.06 (0.79, 1.43). To conclude disinfectants, microwave and photodynamic therapy had similar effects on Candida in comparison to antifungal therapy. These techniques could be used as effective alternatives to antifungal therapy which aids in the prevention of adverse effects due to antifungal therapy.

Keywords: Antifungal, Candida, denture stomatitis, disinfection


How to cite this article:
Sivaramakrishnan G, Sridharan K. Alternatives to antifungal therapy for denture stomatitis: A systematic review and meta-analysis. Saudi J Oral Sci 2017;4:67-71

How to cite this URL:
Sivaramakrishnan G, Sridharan K. Alternatives to antifungal therapy for denture stomatitis: A systematic review and meta-analysis. Saudi J Oral Sci [serial online] 2017 [cited 2017 Nov 21];4:67-71. Available from: http://www.saudijos.org/text.asp?2017/4/2/67/211563




  Introduction Top


Denture stomatitis is a clinically evident chronic inflammatory condition of the oral mucosa, especially in the maxilla, caused due to continuous wearing of complete or partial dentures. The possible factors identified are trauma due to ill-fitting dentures, rough denture surface, poor oral hygiene, and night time wearing of dentures, all these superimposed by infection by Candida.[1],[2] This leads to redness and inflammation of the mucosa in contact with the dentures. The condition is more pronounced in immune-compromised patients (steroid therapy or immunosuppressive disorders), leading to a more serious opportunistic Candida infection.[3] Because of the fungal etiology, antifungal agents such as nystatin, amphotericin B, and miconazole are being traditionally used for the treatment of denture-induced stomatitis. However, they cause adverse effects on long-term use.[4],[5] Prevention of denture stomatitis would be the most appropriate measure to prevent the additional burden caused by the adverse effects to antifungal agents. Disinfection of dentures using agents such as chlorhexidine and other anti-microbial agents, microwave disinfection, and use of photodynamic therapy have been tried in various randomized controlled trials to identify its role in the prevention of denture stomatitis by decreasing the Candida load.[6],[7],[8] If these disinfection techniques could reduce the Candida load as effectively as antifungal agents, they could be used as probable alternatives to antifungal agents, thereby eliminating the adverse effects of antifungal therapy. Hence, the aim of this systematic review and meta-analysis is to identify the efficacy of various disinfection techniques in reducing Candida load in comparison to antifungal agents with the aim of minimizing the use of antifungal agents and its adverse effects caused.


  Materials and Methodology Top


Information sources and search strategy

The protocol for this review was registered with the International prospective register of systematic reviews (PROSPERO) with the registration number CRD42016037910. The review protocol can be accessed at http://www.crd.york.ac.uk/PROSPERO/register_new_review.asp?RecordID=37910&UserID=16309. A thorough literature search was conducted and was completed on 18th April 2016. The primary database used was Medline (via PubMed), Cochrane Central Register of Clinical Trials, and Database of Abstracts of Reviews of Effects. The key words used were denture [tiab] AND (stomatitis [tiab] OR candidiasis [tiab]). This search was further supplemented by hand searching of relevant references from review articles and other eligible studies. No limits were applied to the year of study, but only studies published in English language were included in the present review.

Eligibility criteria

Only those studies with randomized controlled design with the following requirements were included in the present study:

  • Type of participants - patients wearing removable partial or complete dentures diagnosed with denture stomatitis
  • Type of intervention - denture treatment using disinfectant such as sodium hypochlorite, chlorhexidine, microwave, photodynamic therapy, or any others with no adjuvant antifungal therapy either systemic or local
  • Comparison - antifungal agents given either locally or systemically
  • Outcome - the principal outcome was the assessment of Candida load using mycological assay. The secondary outcomes were clinical evaluation of stomatitis, allergic reaction if any and recurrence of stomatitis.


Study procedure

Both the authors independently screened the above-mentioned databases for studies and independently screened the abstract for suitability. Full-texts articles were obtained for those found to be eligible. A pretested data extraction form was created and both the authors independently extracted the following data from each eligible study: Trial site, year, trial methods, participants, interventions, and outcomes. Disagreement between the authors was resolved through discussion. The extracted data were analyzed using non-Cochrane mode in RevMan 5.3 software. The methodological quality of eligible trials was independently assessed by both the authors using the Cochrane collaboration's tool for assessing the risk of bias. We followed the guidance to assess whether trials took adequate steps to reduce the risk of bias across six domains: Sequence generation, allocation concealment, blinding (of participants, personnel, and outcome assessors), incomplete outcome data, selective outcome reporting, and other sources of bias. The judgment was categorized into low, high, or unclear risk of bias.[9] Percent difference between the disinfection of denture (experimental) and antifungal (control) groups were assessed from each of the eligible studies and the mean difference in the percent and percent standard error were considered for final assessment. The heterogeneity between the studies were assessed using the Forest plot visually, I2 statistics wherein more than 50% was considered to have moderate to severe heterogeneity and Chi-square test with a statistical P < 0.10 to indicate statistical significance. Random-effect models were used in case of moderate heterogeneity. Considering the presence of very few trials that can be included in the review, publication bias could not be assessed. The present meta-analysis was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.[10]


  Results Top


Search results

The above-mentioned search strategy led to a hit of studies, of which 5 studies was finally eligible to be included in the present review. However, the outcome measures reported in one of the studies [6] could not be used for quantitative analysis in the present study, thus leaving a final of four studies to be included in the meta-analysis. [Figure 1] depicts the study flow diagram and [Figure 2] depicts the risk of bias of the included studies as assessed using Cochrane's tool of risk of bias. Three studies compared the antifungal therapy with microwave while one each with photodynamic therapy and topical antiseptic. [Table 1] lists the key characteristics of the included studies.[6],[7],[8],[11],[12]
Figure 1: Study flow diagram

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Figure 2: Risk of bias of the included studies. Of the total 5 studies included in the present review, none of the studies reported the method used for generating randomization sequence and concealment of the allocation. No other bias was observed for the included studies

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Table 1: List of included studies

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Pooled results

Candida colony count

A total of three studies that had evaluated microwave and one with photodynamic therapy had compared the changes of Candida colony count with antifungal therapy. The pooled estimate was 0.39 (0.03, 0.75) and was statistically significant favoring antifungal therapy. However, the subgroup analysis was not significant for either microwave or photodynamic therapy in comparison to antifungal therapy [Figure 3].
Figure 3: Forest plot of Candida colony count. A statistically significant reduction in the colony count was observed with antifungal therapy with no significant difference in the subgroup analyses

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Clinical improvement of stomatitis

Only two studies reported clinical improvement of denture stomatitis. Forest plot of the relative risk of clinical cure was not significant between the groups with the pooled estimate of 1.38 (0.87, 2.18) [Figure 4].
Figure 4: Forest plot of clinical improvement in patients with stomatitis. No significant difference was observed in the risk of cure between the interventions

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Recurrence of stomatitis

Three of the five included studies evaluated the recurrence of stomatitis compared with antifungal therapy. Forest plot of the risk ratio of recurrence of stomatitis was not statistically significant between the interventions with the pooled estimate 1.06 (0.79, 1.43) [Figure 5].
Figure 5: Forest plot of stomatitis recurrence. No significant difference was observed in the risk of recurrence between the interventions

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Adverse effects

None of the studies reported any adverse events to the study participants in either group precluding any inference on the same.


  Discussion Top


The present systematic review and meta-analysis aim to identify denture disinfection techniques which could be as effective as antifungal agents in reducing Candida load. This will also reduce or eliminate the adverse side effects caused due to antifungal therapy and help in the prevention of denture stomatitis.

Denture stomatitis also called denture sore mouth, denture-related stomatitis, or Candida-associated denture stomatitis is a very common condition presented in denture wearers. It presents as mild inflammation and redness of the oral mucosa, especially the palate, beneath the maxillary complete denture.[13] The association between denture stomatitis and Candida has been attributed to be almost 90%.[14],[15] Other contributing factors are old age, immune compromised medical condition, improper denture and oral hygiene, and wearing dentures constantly during the day and night.[16] The treatment of denture stomatitis with oral disinfectant mouth rinses, systemic and topical anti-fungal therapy, microwave disinfection and photodynamic therapy have been tested in various randomized controlled trials depending on the severity of denture stomatitis.[6],[7],[8],[11],[12] However, majority resolves after systemic or topical antifungal therapy in addition to maintaining appropriate denture and oral hygiene, but taking into consideration the adverse side effects caused due to antifungal therapy.[17] If the condition could be prevented using appropriate denture disinfection techniques which could be equally effective against Candida, the side effects caused by antifungal therapy could be eliminated.

The present systematic review and meta-analysis compared the effect of disinfection techniques using disinfectants, microwave, and photodynamic therapy to topical or systemic antifungal therapy. A similar systematic synthesis of evidence was attempted by Emami et al.[18] for denture stomatitis, but the review was associated with the following pitfalls: Individual analysis of various disinfection techniques was not attempted and the authors pooled the results. Heterogeneity was not assessed between the studies. Both of these have a huge impact on the credibility of the study results. Individual analysis of various disinfection techniques in the present study does not show a statistically significant improvement of the Candida load with various disinfection techniques compared to antifungal agents. However, a study by Epstein et al. evaluating the Candida count accounting to clinical improvement reported that a Candida load of <400 would count to clinical improvement in stomatitis.[19] Although the results show a significant result favoring the antifungal therapy, the disinfectants used could lessen the Candida count to <400 which could be considered as a clinical improvement of candidiasis. This would be beneficial when the side effects caused due to antifungal therapy are taken into consideration. As regards to clinical improvement observed on photographs and the recurrence rate, no significant difference was found between the groups. The study is limited in not having assessed other databases of medical literature such as EMBASE.


  Conclusion Top


Disinfectant mouth rinses, microwave disinfection, and photodynamic therapy could be considered as a mode of prevention of denture stomatitis on the basis of the observed clinical improvement. This would prevent as well as avoid the use of antifungal therapy which would be required only in severe cases of denture stomatitis.

Acknowledgment

We acknowledge Cochrane reviews for utilizing RevMan software for generating the pooled results and Forest plots.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gendreau L, Loewy ZG. Epidemiology and etiology of denture stomatitis. J Prosthodont 2011;20:251-60.  Back to cited text no. 1
    
2.
Ramage G, Tomsett K, Wickes BL, López-Ribot JL, Redding SW. Denture stomatitis: A role for Candida biofilms. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98:53-9.  Back to cited text no. 2
    
3.
Dorocka-Bobkowska B, Zozulinska-Ziolkiewicz D, Wierusz-Wysocka B, Hedzelek W, Szumala-Kakol A, Budtz-Jörgensen E. Candida-associated denture stomatitis in type 2 diabetes mellitus. Diabetes Res Clin Pract 2010;90:81-6.  Back to cited text no. 3
    
4.
Salerno C, Pascale M, Contaldo M, Esposito V, Busciolano M, Milillo L, et al. Candida-associated denture stomatitis. Med Oral Patol Oral Cir Bucal 2011;16:e139-43.  Back to cited text no. 4
    
5.
Gogtay NJ, Kulkarni UP, Panchabhai TS. Adverse reactions to antifungal agents. Adverse Drug React Bull 2008;1:963-6.  Back to cited text no. 5
    
6.
Koray M, Ak G, Kurklu E, Issever H, Tanyeri H, Kulekci G, et al. Fluconazole and/or hexetidine for management of oral candidiasis associated with denture-induced stomatitis. Oral Dis 2005;11:309-13.  Back to cited text no. 6
    
7.
Mima EG, Vergani CE, Machado AL, Massucato EM, Colombo AL, Bagnato VS, et al. Comparison of photodynamic therapy versus conventional antifungal therapy for the treatment of denture stomatitis: A randomized clinical trial. Clin Microbiol Infect 2012;18:E380-8.  Back to cited text no. 7
    
8.
Sanita PV, Machado AL, Pavarina AC, Massucato EM, Colombo AL, Vergani CE. Microwave denture disinfection versus nystatin in treating patients with well-controlled type 2 diabetes and denture stomatitis: A randomized clinical trial. Int J Prosthodont 2012;25:232-44.  Back to cited text no. 8
    
9.
Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. 5.1.0 ed. Available from: http://www.cochrane-handbook.org. [Last accessed on 2015 Oct 15].  Back to cited text no. 9
    
10.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol 2009;62:1006-12.  Back to cited text no. 10
    
11.
Neppelenbroek KH, Pavarina AC, Palomari Spolidorio DM, Sgavioli Massucato EM, Spolidorio LC, Vergani CE. Effectiveness of microwave disinfection of complete dentures on the treatment of Candida-related denture stomatitis. J Oral Rehabil 2008;35:836-46.  Back to cited text no. 11
    
12.
Silva MM, Mima EG, Colombo AL, Sanitá PV, Jorge JH, Massucato EM, et al. Comparison of denture microwave disinfection and conventional antifungal therapy in the treatment of denture stomatitis: A randomized clinical study. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:469-79.  Back to cited text no. 12
    
13.
Calcaterra R, Pasquantonio G, Vitali LA, Nicoletti M, Di Girolamo M, Mirisola C, et al. Occurrence of Candida species colonization in a population of denture-wearing immigrants. Int J Immunopathol Pharmacol 2013;26:239-46.  Back to cited text no. 13
    
14.
Zomorodian K, Haghighi NN, Rajaee N, Pakshir K, Tarazooie B, Vojdani M, et al. Assessment of Candida species colonization and denture-related stomatitis in complete denture wearers. Med Mycol 2011;49:208-11.  Back to cited text no. 14
    
15.
Pereira CA, Domingues N, Araújo MI, Junqueira JC, Back-Brito GN, Jorge AO. Production of virulence factors in Candida strains isolated from patients with denture stomatitis and control individuals. Diagn Microbiol Infect Dis 2016;85:66-72.  Back to cited text no. 15
    
16.
Shulman JD, Rivera-Hidalgo F, Beach MM. Risk factors associated with denture stomatitis in the United States. J Oral Pathol Med 2005;34:340-6.  Back to cited text no. 16
    
17.
Douglas LJ. Candida biofilms and their role in infection. Trends Microbiol 2003;11:30-6.  Back to cited text no. 17
    
18.
Emami E, Kabawat M, Rompre PH, Feine JS. Linking evidence to treatment for denture stomatitis: A meta-analysis of randomized controlled trials. J Dent 2014;42:99-106.  Back to cited text no. 18
    
19.
Epstein JB, Pearsall NN, Truelove EL. Quantitative relationships between Candida albicans in saliva and the clinical status of human subjects. J Clin Microbiol 1980;12:475-6.  Back to cited text no. 19
    


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