Oral Candidiasis- A Review - WebmedCentral.com ID: WMC002498 ISSN 2046-1690 Oral Candidiasis- A Review Corresponding Author: Dr. Sameer Parihar, Assistant professor, Oral & Maxillofacial

Article ID: WMC002498 ISSN 2046-1690

Oral Candidiasis- A ReviewCorresponding Author:Dr. Sameer Parihar,Assistant professor, Oral & Maxillofacial surgery,G.D.C. Jaipur, S-29/A,Krishna marg,shyam nagar,jaipur, 302019- India

Submitting Author:Dr. Sameer Parihar,Assistant professor, Oral & Maxillofacial surgery,G.D.C. Jaipur, S-29/A,Krishna marg,shyam nagar,jaipur, 302019- India

Article ID: WMC002498

Article Type: Review articles

Submitted on:23-Nov-2011, 02:08:13 PM GMT Published on: 24-Nov-2011, 04:40:49 PM GMT

Article URL: http://www.webmedcentral.com/article_view/2498

Subject Categories:DENTISTRY

Keywords:Candidiasis, Oral candidiasis, Candida albicans.

How to cite the article:Parihar S. Oral Candidiasis- A Review. WebmedCentral DENTISTRY2011;2(11):WMC002498

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Oral Candidiasis- A ReviewAuthor(s): Parihar S

Oral Candidiasis- A review

Dr. Sameer1, Dr. Pooja Narain2, Dr. V N Jhameria3, Dr D K Gupta4,

Dr Farzan Rahman5,

Dr. Juhi Narain6

Assistant Professor, Oral & Maxillofacial Surgeon,1.Department of Oral & Maxillofacial Surgery,Government Dental College & Hospital, Jaipur,India.Senior Lecturer, Oral Pathologist, Department of2.Oral Pathology & Microbiology, Rajasthan DentalCollege & Hospital, Jaipur, India.Professor, Paediatric Surgeon, Department of3.Paediatric Surgery, J K Lon Hospital, Jaipur, India.Professor, Oral & Maxillofacial Surgeon,4.Department of Oral & Maxillofacial Surgery,Government Dental College & Hospital, Jaipur,India.Professor, Oral Pathologist, Department of Oral5.Pathology & Microbiology, Jaipur Dental College &Hospital, Jaipur, India.Dental Surgeon, Dental Clinic, Jaipur, India.6.

Abstract

Candidiasis, a common opportunistic fungal infectionof the oral cavity, may be a cause of discomfort indental patients. The article reviews common clinicaltypes of candidiasis, its laboratory diagnosis currenttreatment modalities. The majority of infections aredue to Candida albicans (C. albicans) although otherspecies such as C. glabrata, C. tropicalis, C. kruseiand C. parapsilosis are increasingly isolated. In fact, C.albicans may be a component of normal oralmicroflora, with as many as 30% to 50% of peoplesimply carrying the organism in their mouths withoutclinical evidence of infection. The frequency ofinvasive fungal infections has increased over the lastdecade with the rise in at risk populations of patients.Keywords: candidiasis, oral candidiasis, candidaalbicans.

Introduction

Infection with the yeast like fungal organism Candidaalbicans is termed as candidiasis.[1] The first knowndescription of Candida infections, oral candidiasis

(thrush) in two patients with other underlying diseasesmay be found in Hippocrate's "Epidemics" from thefourth century B.C.[2] “Thrush” one form of oralcandidiasis is perhaps one of the earliest oral diseasesdocumented. Derivation of this term is rather obscure,but according to the Oxford Dictionary, it probablyoriginated from the old Danish Torsk which issynonymously used both for the disease and the birdof that name. Rosen von Rosenstein (1771) was thefirst to attempt to divide the disease into categoriesbased on the severity and distribution of the lesions.[3]The fungus now known as Candida albicans wasisolated by Bennett (1844) from the sputum of atuberculosis patient, by Wilkinson (1849) from vaginalcandidiasis. Robin (1853) was the first to observeconcomitant thickening of the epithelium in lesionsresembling thrush.[4]ClassificationThe taxonomic position and classification of the thrushfungus was the subject of much debate andcontroversy for several decades as a result of differentmorphologic forms of the organism and differentsynonyms for the same fungus.[5] Robin (1853) hadnamed it Oidium albicans, Quinquaud (1868)sy r ingospora rob in i i and Reess (1875)Saccharomyces albicans. The first binomial to gainwide acceptance over a long period and whichsometimes is still albeit wrongly used was Moniliaalbicans, which was suggested by Zopf in 1890.Berkhout in 1923, after recognizing the differencesbetween Monilia species isolated from rotting plantsand fruits and the yeasts isolated from medical cases,established the genus Candida to accommodate thelatter. This was accepted as the official name of thegenus by the Eighth Botonomical Congress in Paris in1954.[4] Berkout5 proposed the name Candida fromthe Latin toga candida, which referred to the whiterobe worn by candidates for the Roman senate.Albicans also comes from the Latin albicare whichmeans "to whiten". This translation corresponds wellwith what is considered traditionally and reportedclinically as a presentation of candidal mucosalinfection characterised as a white milk curd likecovering of the mucosa, which wipes off easily.[6] TheIndex Medicus has not recognized the genus Moniliaor the term Moniliasis in reference to human diseasesince 1981.[5] There have been around 166synonyms being recognized for Candida albicansworldwide.7 The genus Candida is within the classDeuteromycetes and has been described as a



"taxonomic pit" into which yeasts without a knownsexual stage or other remarkable phenotype characterhave been thrown. Its members are biologicallydiverse and include yeasts with ascomycetous andbasidiomycetous affinities. There are currentlybetween 150 and 200 species recognized in thegenus . [8 ] The genus Cand ida inc ludescharacteristically white asporogenous (imperfect)yeasts capable of forming pseudohyphae. Within thegenus, species are characterized primarily by colonialmorphology, carbon utilization, and fermentation.[9]There are seven Candida species of major medicalimportance, the most important being Candidaalbicans, the one most frequently isolated. It isbelieved to be the most virulent in man and can beisolated from human body as a commensal or as anopportunistic pathogen.[10]The other Candida species encountered in humaninfections are C. tropicalis, C. glabrata, C. parapsilosis,C. stellatoidea, C. pseudotropicalis, C. guillermondii, C.krusei, and C. kyfer. These species are usuallyregarded as opportunists.[10,11]CLINICAL SPECTRUMThe oral lesions of candidiasis have a differentappearance and occur in several clinical forms.Several attempts have been made to classify theseforms.[12] By tradition the most frequently adoptedclassification has been the one proposed by Lehner(1966)[13] who classified it based on clinical,mycological, histological, serological and therapeuticcriteria. He divided oral candidiasis into acute andchronic types and further subdivided each of the latteras follows:Acute:Acute Pseudomembranous Oral Candidiasis. (Thrush)Acute Atrophic Oral CandidiasisChronic:Chronic Hyperplastic Oral CandidiasisChronic Atrophic Oral CandidiasisChronic hyperplastic candidiasis was furthersubdivided into 4 groups based on localization patternand endocrine involvement as follows:1. Chronic oral candidosis (candidal leukoplakia)2. Endocrine candidosis syndrome3. Chronic localized mucocutaneous candidiasis4. Chronic diffuse candidosisChronic atrophic candidosis includes denture soremouth and angular cheilitis caused by Candida.Lehner has suggested the following diagnostic criteriaof oral candidosis1. White plaques or diffuse erythematous areas2. Culture of Candida from the saliva3. Presence of the mycelium on direct examination ofa smear from the lesion

4. Biopsy examination showing hyphae in theepithelium5. Characteristic histologic changes and6. Serum fluorescent antibody titre against Candidaalbicans greater than 1:16 and a positive antibody testwith neat saliva.Samaranayake and Yaccob[14] noted that thesubdivision of chronic hyperplastic candidosisgenerates confusion particularly because it lumpstogether candidosis that are localized in the oral cavityalone and oral manifestations of mucocutaneouscandidosis. It was therefore suggested that oralcandidiasis should have dichotomatous classification,delineating primary oral candidiasis, that is infectionsexclusively confined to oral and perioral tissues(category 1) from secondary oral candidosis which arepresent in cutaneous as well as mucosal surfaces ofthe body. (Table 1)Holmstrup and Besserman (1983)[15] noted thatPseudomembranous candidiasis is not always acutebut may last for many months in certain categories ofpatients (such as AIDS patients). Also the value ofusing the term atrophic to describe erythematousareas is limited since the redness of the oral mucosamay be caused by increased vascularity with orwithout reduced thickness of epithelium.Holmstrup and Besserman suggested futurec lass i f i ca t ion be based on c l in ica l andhistopathological terms like erythematous, plaque likeand nodular lesions. (Table 2)They proposed that a future revised clinicalclassification of primary oralcandidosis should comprise the following entities asshown in the above table.Furthermore, in 1990 Holmstrup and T Axell[16] madean attempt to reclassify oral candidiasis mainly basedon clinical terms. (Table 3)Recently, T Axell, Samaranayaka and Reichart(1997)[17], have proposed a reclassification of oralcandidiasis first because according to them there hasbeen an almost indiscriminate application of thenomenclature related to the clinical subdivision of oralcandidiasis and second because unusual clinicalvariants have appeared with the pandemicprogression of the HIV infection.There are great clinical similarities between theplaque-like and nodular lesions and different forms oforal leukoplakias. The latter are often super infectedwith Candida and are then called candidalleukoplakias. Previous classifications do not clearlytake into consideration superinfection of other lesionswith Candida. Such lesions are often keratinized.To minimize diagnostic confusion they haveintroduced and added another entity to the clinical



classification of oral candidiasis - keratinized primarylesions super infected with Candida. This entity wouldcomprise leukoplakia, lichen planus and lupuserythematosus. Leukoplakias are infected withCandida in about 10% of the cases, lichen planus in40 % and lupus erythematosus in 50%.Cheilocandidosis described by Reade et al (1982)[18]and Juvenile Juxtavermillion Candidosis discovered byBouquot and Fenton (1988)[19] are newer clinicalentities, which manifest around the lips of affectedindividuals and respond well to antifungal therapy; arethought to be due to either primary or secondaryinfection by Candida species. Samaranayake andYaacob (1990)[14] suggested that further clinical andmicrobiological evidence is required to justify theirinclusion in a standard classification of oral candidiasis.Diagnosis of oral yeast infections should be based ona combination of laboratory methods as well as clinicalsigns and symptoms.[20] Oral candidiasis is dividedinto primary and secondary infections (Table 5). Theprimary infections are restricted to the oral and perioralsites, whereas secondary infections are accompaniedby systemic mucocutenous infections.[21]

Methods

L A B O R A T O R Y D I A G N O S I S O F O R A LCANDIDIASIS A correct diagnosis provides the specific treatment ofa fungal infection and may prove life saving or staveoff the complications produce there in.[22] Olsen andStenderup, (1990)[20] stated laboratory findingsshould be correlated with the severity of clinical signsand symptoms. Effectiveness of anti fungal medicationalso aids in diagnosis.[23]The following are the guidelines for specimencollection.[23]1. The specimen should be collected from an activelesion; old 'burned out' lesions often do not containviable organisms.2. Collect the specimen under aseptic conditions.3. Collect sufficient specimen.4. Use sterile collection devices and containers5. Label the specimen appropriately; all clinicalspecimens should be considered as potentialbiohazards and should be handled with care usinguniversal precautions.The specimen should be kept moist or in a transportmedium and stored in a refrigerator at 4ºC.[20] Ifsampled patients have infectious diseases such astuberculosis, hepatitis, AIDS, etc., the diagnosticmicrobial laboratory must be informed about it so thatspecimens can be processed with caution and without

risks of infection to the technical staff. Due to variety ofclinical forms of oral candidiasis a number of differenttypes of specimens may be submitted to thelaboratory.[20]1. Smear: Smears are taken from the infected oralmucosa, rhagades and the fitting side of the denture,preferably with wooden spatulas. Fixed immediately inether/alcohol 1:1 or with spray fix. Dry preparationsmay be examined by Gram stain method and PeriodicAcid Schiff (PAS) method.2. Swabs: Swabs are seeded on Sabouraud’s agar(25ºC or room temperature), on blood agar (35ºC), onPagano-Levin medium (35ºC) or on Littmann’ssubstrate (25ºC). Incubation at 25ºC is done to ensurerecovery of species growing badly at 35ºC.Sabouraud’s dextrose agar is frequently used as aprimary culture medium. Since mixed yeast infectionsare seen in the oral cavity more frequently thanp r e v i o u s l y t h o u g h t , p a r t i c u l a r l y i nimmunocompromised or debilitated patients,Pagano-Levin agar or Littmann’s substrate, are usefulsupplements, because they enable distinction ofyeasts on the basis of difference in colony color.3. Biopsy: Biopsy specimen (either excisional orincis ional) should in addi t ion be sent forhistopathological examination when chronichyperplastic candidosis is suspected.4. Imprint Culture Technique: Sterile, square (2.2 x 2.5cm), plastic foam pads are dipped in peptone waterand placed on the restricted area under study for 30 –60 seconds. Thereafter the pad is placed directly onPagano-Levin or Sabouraud's agar, left in situ for thefirst 8 hours of 48 hours incubation at 37ºC. Then, thecandidal density at each site is determined by aGallenkamp colony counter and expressed as colonyforming units per mm2 (CFUmm-2).[20,24] Thus ityields yeasts per unit mucosal surface.[25] It is usefulfor quantitative assessment of yeast growth in differentareas of the oral mucosa and is thus useful inlocalizing the site of infection and estimating thecandidal load on a specific area (Budtz-Jorgensen,1978, Olsen and Stenderup A, 1990).[20,26]5. Impression Culture Technique: It involves takingmaxillary and mandibular alginate impressions,transporting them to the laboratory and casting in 6%fortified agar with incorporated Sabouraud's dextrosebroth. The agar models are then incubated in a widenecked, sterile, screw-topped jar for 48-72 hours at37ºC and the CFU of yeasts estimated.6. Saliva: This simple technique involves requestingthe patient to expectorate 2ml of mixed unstimulatedsaliva into a sterile, universal container, which is thenvibrated for 30 seconds on a bench vibrator for optimaldisaggregation. The number of Candida expressed as



CFU/ml of saliva is estimated by counting the resultantgrowth on Sabouraud's agar using either the spiralplating or Miles and Misra surface viable countingtechnique.[27] Patients who display clinical signs oforal candidiasis usually have more than 400CFU/mL.[28]7. Oral Rinse Technique: It was first described byMckendrik, Wilson and Main (1967) and later modifiedby Samaranayake et al (1968).[29]8. Paper Points: An absorbable sterile point is insertedto the depth of the pocket and kept there for 10 secand then the points are transferred to a 2ml vialcontaining Moller's VMGA III transport medium, (whichalso facilitates survival of facultative and anaerobicbacteria).[20]9 . Commerc ia l Iden t i f i ca t ion K i t s : TheMicrostix-candida (MC) system consists of a plasticstrip to which is affixed a dry culture area (10 mm x 10mm) of modified Nickerson medium (Nickerson, 1953)and a plastic pouch for incubation. The O Yeast-I dentsystem is based on the use of chromogenicsubstances to measure enzyme activities. ricult-N dipslide technique is similar to, but of higher sensitivitythan M-C system. Yeast-I dent system is based on theuse of chromogenic substances to measure enzymeactivities.[20]Histological Identification of Candida species inBiopsy SpecimensDemonstration of fungi in biopsy specimens mayrequire several serial sections to be cut.[20] Becauseof their s ize morphological d iversi ty andpolysaccharide content, fungi can be easilydemonstrated and studied in tissue sections withspecial stains. The routinely used Haematoxylin andEosin stain poorly stains Candida species. Hence theymay be overlooked in tissue sections. The specificfungal stains such as Periodic Acid Schiff stain (PAS),Grocott-Gomori's Methenamine Silver (GMS) andGridley stains are widely used for demonstrating fungiin the tissues, which are coloured intensely with thesestains.[24] Calcoflour White Stain30 staining can bedone in formalin fixed paraffin embedded specimensbut a fluorescence microscope is required forvisualization.Physiological testsThe main physiological tests used in definitiveidentification of Candida species involve determinationof their ability to assimilate and ferment individualcarbon and nitrogen sources. These should besupplemented with morphological test observationssuch as germ tube formation for a rel iableidentification of Candida species.[24]A) Carbohydrate Assimilation Test[31]Carbohydrate utilization tests are the most widely used

methods for the definitive identification of clinicallyimportant yeasts. (Sandven P, 1990)[31]B) Nitrate AssimilationMethods used are the same as for carbon assimilationtests, but in these tests basal media must be nitrogenfree and must include glucose as a carbon source.C) Carbohydrate FermentationCarbohydrate fermentation tests are useful tests fordifferentiating species and can be used to supplementcarbohydrate utilization test results, for differentiatingspecies and thus making a definitive identification ofan organism. (Sandven P 1990)[31]The assimilation reactions and fermentation reactionsof Candida species are tabulated in Table 6 and Table7.Note: Glu = Glucose, Mal = Maltose Suc = Sucrose Lac = Lactose Cel = Cellobiose, Gal = Galactose, Tre= Trehalose, Raf = Raffinose, Mel = Melibiose, Xyl =Xylose, Ino = Inositol, Dul = Dulcitol; + = Positivereaction, -- = Negative reaction,Note: Glu = Glucose, Mal = Maltose Suc = Sucrose Lac = Lactose+ = Positive reaction, -- = Negative reaction, A= AcidProduction G = Gas Production.STRAIN DIFFERENTIATION OF CANDIDAALBICANS[32]As Candida albicans is both a commensal and apathogen, there is every need to identify thepathogenic strain and the virulence factor in it so thatthe diagnosis of carrier state and infection becomesclearly delineated. Ideally, a method for differentiatingCandida albicans at a subspecies level should be ableto discriminate between strains which areepidemiologically unrelated & be highly reproducibleboth intra, and inter laboratory, take minimal time, becapable of processing a large number of strains,require a minimum of specialized equipment, and berelatively inexpensive.Phenotypic methods1. Serotyping: Serotyping is limited to the twoserotypes (A and B), a fact that makes it inadequateas an epidemiologic tool. Furthermore, it has recentlybeen shown that there can be wide discrepancies inthe results obtained with different methods ofserotyping, making it difficult to compare resultsobtained with different methods of serotyping.2. Resistogram typing: It has been shown thatresistograms do not correlate with pathogenic potential,and even though improvements have been made inthe method growth end-points often present problemsbecause of inoculum size, interpretation, andreproducibility.3. Yeast ‘Killer Toxin’ typing: These authors initiallyused nine killer strains, developing a triplet code to



distinguish between 100 strains of C albicans, andfound 25 killer- sensitive types. This method wasexpanded by using 30 killer strains and threeantifungal agents, which appeared to discriminatebetween sufficient numbers of strains of C. albicans.4. Morphotyping:This method has been used in astudy of the morphotypes of 446 strains of C.albicansisolated from various clinical specimens.[33]5. Biotyping:They utilized proteinase and lipaseproduction to distinguish four biotypes. Williamson(1987)[34] has proposed a simpler method. Thissystem comprised three tests, the APIZYM system,the API 20C system, and a plate test for resistance toboric acid. This system was found to distinguish apossible 234 biotypes of which 33 were found amongthe 1430 isolates of C. albicans taken from oral,genital and skin sites.6.5Protein typing:Non-lethal mutations of proteinsduring the yeast cell cycle yield proteins of differingphysical properties between strains, which may bedistinguishable by one or two dimensional gelelectrophoresis. These methods have been used toseparate C. albicans at the subspecies level. AntiC.albicans antiserum can be used for furtherdistinction of protein differences between strains andthis may be a useful epidemiologic method.Furthermore, specific isoenzyme differences betweenstrains may be visualized by this method to provide arange of variation sufficient for epidemiologic study.GENETIC METHODSThe earliest molecular methods used for fingerprintingC. albicans strains were karyotyping, restrictionendonuclease analysis (REA), and restriction fragmentlength polymorphism (RFLP). To date, the majority ofstudies have focused on studying C albicans isolatesfrom HIV infected patients. In arbitrarily primedpolymerase chain reaction (AP- PCR) analysis(synonym: randomly amplified polymorphic DNA(RAPD) analysis), the genomic DNA is used as atemplate and amplified at a low annealing temperaturewith use of a single short primer (9 to 10 bases) of anarbitrary sequence. However, the reproducibility ofAP-PCR is dependent upon the care fu lstandardization of the PCR conditions, and thediscriminatory power is dependent on the primer usedand optimization of the assay (Williams et al,1990;Dassanayake & Samaranayake, 2000).[31]Serological Tests[32]:The serological tests are useful for systemic fungalinfections and have both diagnostic and prognosticvalues. (Table 8)Immunodiagnosis[24]:The use of specific antibodies labelled with fluorescentstain permits causative organisms to be diagnosed

accurately within minutes. However, the preparation ofspecific antisera and purified polyclonal or monoclonalantibodies entails a much more extensive technicaloutlay, so the application of these reagents need onlybe considered when a very precise diagnosis is oftherapeutic consequence (Olsen and Stenderup,1990). The usefulness of antibody testing in thediagnosis of oral candidosis when other simpler,sensitive and reliable techniques are available isquestionable (Silverman et al, 1990)[24]THERAPEUTIC ASPECTS[35]:For the normal healthy patient, the treatment of oralcandidiasis is relatively simple and effective. Typically,topical medications are adequate. (Table 9) & (Table10)

References

1. Navejesh M, Brightman VJ. Relationship betweensalivary flow rates and candida albicans counts. OralSurg Oral Med Oral Pathol Oral Endod 1995; 80:284-28.2. Jagadish Chander. Textbook of Medical Mycology2nd edition Mehta Publishers. 2002: 212-230.3. Samaranayake LP Introduction and historicalaspects, in Samaranayake L P and MacFarlane T WOral Candidosis 1sted, Cambridge, Butterworth,1990:1-9.4. Drouchet. In Historical Introduction: Evolution ofKnowledge of the fungi and Mycoses from Hippocratesto the 21st century: Topley & Wilsons:3-42.5. Lynch DP, Memphis, Tenn. Oral Candidiasis:History, classification, and clinical presentation. OralSurg Oral Med Oral Pathol 1994;78:189-93.6. Fotos PG and Hellistein JW. Candida andCandidosis: Epidemiology, diagnosis, and therapeuticmanagement. Dental Cli Of North America 1992:36(4); 857-878.7. Barnett JA, Payne RW, Yarrow D. Yeasts:Characteristics and identification. Cambridge:Cambridge University Press, 1983:5-9.8. Akpan A and Morgan R. Oral Candidiasis. PostgradMed J 2002; 78: 455-459.9. Shepherd MG et al. Candida albicans: biology,genetics and pathogenicity. Ann Rev Microbiol1985;39:579-614.10. Cannon RD, Holmes A.R, Mason A.B and MonkB.C. Oral Candida: Clearance, colonization, orcandidiasis? J dent Res 1995; 74(5): 1152-1160.11. Clark TA, Hajjeh RA. Recent trends in theepidemiology of invasive mycoses. Curr Opin InfectDis 2004;17:511–5.12. Holmstrup P and Axell T. Classification and clinical



manifestations of oral yeast infections. Acta OdontolScand 1990; 48: 57-59.1 3 . L e h n e r T . O r a l t h r u s h o r a c u t epseudomembranous candidosis. Oral Surg Oral MedOral Pathol 1964; 18:27-37. 14. Samaranayake LP, Yaacob H. Classification oforal Candidoses: In Oral candidoses. London:Butterworth 1990. Pg No 124-132.15. Holmstrup P and Besserman M. Clinicaltherapeutic and pathogenic aspects of chronic oralmultifocal candidiasis. Oral Surg Oral Med Oral Pathol1983; 56:388-395.16. Holmstrup P and Axell T. Classification and clinicalmanifestations of oral yeast infections. Acta OdontolScand 1990; 48: 57-59.17. Axell T, Samarayanake LP Reichart PA, Olsen I. Aproposal for reclassification of Oral candidosis. OralSurg Oral Med Oral Pathol 1997; 84(2): 111-112.18. Reade P C. Cheilo – candidosis: a possible clinicalentity. Brit Dent J 1982; 152: 305-308.19. Bouquot JE and Fenton SJ. Juvenile,Jurtavermilion Candidiasis: yet another form of an olddisease. J Am Dent Assoc 1988; 116:187-192.20. Olsen I and Stenderup A. Clinical – mycologicdiagnosis of oral yeast infections. Acta Odontol Scand.1990; 48:18.21. Greenberg MS, Glick M and Ship JA.Burket’s OralMedicine 11th edition BC Decker 2008;79.22. Jagadish Chander. Textbook of Medical Mycology2nd edition Mehta Publishers 2002; 40-53.23. Epstein J B, Pearsall N N, Trulove E L. Oralcandidosis: effects of antifungal therapy upon clinicalsigns and symptoms, salivary antibody and mucosaladherence of C.albicans. Oral Surg Oral Med OralPathol 1981; 51:32-38.24. Silverman Jr. S. Laboratory diagnosis of oralcandidosis in Samaranayake L P and MacFarlane T W;oral candidosis, 1sted, Cambridge Butterworth,1990:213-237.25. Samaranayake LP. Oral mycoses in HIV infection.Oral Surg Oral Med Oral Pathol 1992; 73: 171-180.26. Budtz – Jorgensen E. Clinical aspects of Candidainfection in denture wearers. J Am Dent Assoc 1978;96:474-479.27. Farah CS, Ashman RB, Challacombe SJ.Oralcandidosis.Clin Dermatol 2000;18(5):553-562.28. Epstein JB, Pearsall NN, Truelove EL.Quantitativerelationships between candida albicans in saliva andthe clinical status of human subjects. J Clin Microbiol1980;12:475-476.29. Samaranayake L P. Nutritional factors and oralcandidosis. J Oral Pathol 1986; 15:61-65.30. Jagadish Chander.Textbook of Medical Mycology2nd edition Mehta Publishers 2002: 375-419.

31. Sandven P. Laboratory identification andsensitivity testing of yeast isolates. Acta OdontalScand. 1990; 48: 27-36.32. McCullough MJ, Ross BC, Reade PC. Candidaalbicans: a review of its history, taxonomy,epidemiology, virulence attributes, and methods ofstrain differentiation. Int J Oral Maxillofac Surg. 1996;25: 136-144.33. Hunter PR, Fraser CA, Mackenzie DW.Morphotype markers of virulence in human candidalinfections. J Med Microbiol 1989;28:85-9134. Williamson MI, Samaranayake LP, MacFarlaneTW. A new simple method for biotyping candidaalbicans. Microbios 1987; 51: 159-67.35. Dangi YS, Soni ML, Namdeo KP. Oral Candidiasis:A Review. International Journal of Pharmacy andPharmaceutical Sciences 2010; 2(4):36-41.



Acute/Chronic Subgroup Disease state

Acute 1

2

Acute pseudomembranous candidosis

Acute atrophic candidosis

Chronic 3

4

Chronic hyperplastic

Chronic atrophic

Newton’s type I : pin point lesion

Newtons’s type II : diffuse erythema

Newtons’s type III : granular

Acute/chronic 5 Candida - associated angular cheilitis

Illustrations

Illustration 1

Table 1: Category 1 Diseases can be subdivided as follows



Acute: Acute pseudomembranous candidosis

Acute erythematous candidosis

Chronic: Chronic pseudomembranous candidosis

Chronic erythematous candidosis

Chronic plaque like candidosis

Chronic nodular candidosis

Illustration 2

Table 2



Acute types:

Pseudomembranous

Erythematous

Chronic types:

Pseudomembranous

Erythematous

Nodular

Plaque-like

Candida-associated lesions :

Angular cheilitis

Denture stomatitis

Median rhomboid glossitis

Illustration 3

Table 3



Primary oral candidosis ( Group I ) Secondary oral candidoses ( Group II )

Acute Pseudomembranous Erythematous - --------Chronic Erythematous Pseudomembranous Hyperplastic Nodular Plaque-like Candida-associated lesionsAngular cheilitis Denture stomatitis Median rhomboid glossitis Keratinized primary lesions superinfectedwith CandidaLeukoplakia Lichen planus Lupus erythematosus

Oral manifestations of Systemic mucocutaneouscandidosis (due to diseases such as thymic aplasia andcandidosis endocrinopathy syndrome)

Illustration 4

Table 4: Proposed revised classification of Oral Candidosis



Primary Oral Candidiasis Secondary Oral Candidiasis

The “Primary Triad” Condition Subgroup

Acute Familial chronic mucocutenous candidiasis 1

Pseudomembranous Diffuse chronic mucocutenous candidiasis 2

Erythematous Candidiasis endocrinopathy syndrome

Familial Mucocutenous candidiasis

3

4

Chronic Severe combined immunodeficiency 5a

Pseudomembranous Di George syndrome 5b

Erythematous Chronic granulomatous disease 5c

Plaque – like Acquired immune deficiency syndrome (AIDS) 6

Nodular

Candida-associated lesions

Denture stomatitis

Angular cheilitis

Median rhomboid glossitis

Illustration 5

Table 5



Candida species Glu Mal Suc Lac Cel Gal Tre Raff Mel Xyl Ino Dul

C. albicans + + + + + + + - - + - -

C. tropicalis + + + - + + + - - + - -

C. kefyer + - + + + + - + - + - -

C. parapsilosis + + + - - + + - - + - -

C.guilliermondii + + + - + + + + + + - +

C. krusei + - - - - - - - - + - -

C. glabrata

Illustration 6

Table 6 : Assimilation reactions



Candida species Glu Mal Suc Lac

C. albicans AG AG - -

C. tropicalis AG AG AG -

C. kefyer AG AG AG -

C. guilliermondii AG - AG -

C. parapsilosis AG - - -

C. krusei AG - - -

C. glabrata AG - - -

Illustration 7

Table 7:Fermentation reactions



1. Detection of antibodies

1. Slide agglutination

2. Immunodiffusion

3. Phytohaemagglutination

4. Coelectosynersis

5. Immunoprecipitation

6. A and B immunofluorescence.

2. Nonspecific Candida Antigens

1. Latex agglutination

2. Immunobloting

3. Cell Wall Components:

1. Cell Wall Mannoprotein (CWMP)

2. b-(1,3)-D-glucan

4. Candida Enolase Antigen testing

Illustration 8

Table 8: Serological Tests for Invasive Candidiasis



Dosage form/ strength Indication

Miconazole cream 2% (OTC) Angular cheilitis

Clotrimazole cream 1% (OTC) Angular cheilitis

Ketoconazole cream 2% (Prescription) Angular cheilitis

Nystatin ointment 100,000 units/gram(Prescription)

Angular cheilitis

Nystatin topical powder 100,000 units/gram(Prescription)

Denture stomatitis

Nystatin oral suspension 100,000 units/gram(Prescription)

Intraoral candidiasis

Betamethasone dipropionate clotrimazolecream (Prescription)

Chloronic angular cheilitis

Clotrimazole troches 10 mg (Prescription) Intraoral candidiasis

Amphotericin B 100 mg/ml (Prescription) Intraoral candidiasis

Illustration 9

Table 9: Topical antifungal medications



Generic name Formulation

Amphotericin B 100 mg/ml oral suspension

Clotrimazole 10 mg troche

Fluconazole 100 mg tablet

10 mg/ml oral suspension


Itraconazole 100 mg capsule


Ketoconazole 200 mg tablet

Nystatin 100,000 units/ml oral suspension

200,000 units/ml pastille

500,000 units/ml tablet

100,000 units/ml vaginal tablet

Illustration 10

Table 10: Systemic antifungal medications of oropharyngeal candidiasis



Reviews

Review 1

Review Title: Oral CandidiasisPosted by Dr. William J Maloney on 27 Sep 2012 09:12:42 PM GMT

What are the main claims of the paper and how important are they?: The purpose of this article is to provide a review of the literature concerning oral candidiasis.

Yes

Yes

Yes

If a protocol is provided, for example for a randomized controlled trial, are there any important deviationsfrom it? If so, have the authors explained adequately why the deviations occurred? No

Yes

No

No

Rating: 7

Comment: Candidiasis is a common fungal infection of the oral cavity. It may be a cause of discomfort in dental patients. The frequency of invasive fungal infections has increased over the last decade. The oral lesions occur in severalclinical forms.

Competing interests: None

Invited by the author to make a review on this article? : No

Have you previously published on this or a similar topic?: No

Experience and credentials in the specific area of science: Clinical associate professor

How to cite: Maloney W.Oral Candidiasis[Review of the article 'Oral Candidiasis- A Review ' by].WebmedCentral 1970;3(9):WMCRW002259


http://http://www.webmedcentral.com/Article_Review_View/2259

http://www.webmedcentral.com/user/55


Review 2

Review Title: Oral Candidiasis - A ReviewPosted by Dr. Ravikiran Ongole on 14 Dec 2011 05:03:02 AM GMT

1 Is the subject of the article within the scope of the subject category? Yes

2 Are the interpretations / conclusions sound and justified by the data? Partly

3 Is this a new and original contribution? No

4 Does this paper exemplify an awareness of other research on the topic? No

5 Are structure and length satisfactory? No

6 Can you suggest brief additions or amendments or an introductory statement that will increasethe value of this paper for an international audience?

Yes

7 Can you suggest any reductions in the paper, or deletions of parts? Yes

8 Is the quality of the diction satisfactory? Yes

9 Are the illustrations and tables necessary and acceptable? No

10 Are the references adequate and are they all necessary? No

11 Are the keywords and abstract or summary informative? No

Rating: 2

Comment: 1. The title of the article does not fit the manuscript. This manuscript seems to lay a 'lot' of emphasis on thehistopathological assessment/diagnosis of Candidiasis.

2. A review article is expected to "review" literature up to date on the subject. However of the 35 referencesquoted only ONE reference is later than the year 2005.

3. Suprisingly 7 references are from text books!

4. The clinical features of various types of Candidiasis are not mentioned.

Competing interests: No



Experience and credentials in the specific area of science: Clinical experience of diagnosing and managing patients suffering from oral candidiasis

How to cite: Ongole R.Oral Candidiasis - A Review[Review of the article 'Oral Candidiasis- A Review ' by].WebmedCentral 1970;2(12):WMCRW001240



http://www.webmedcentral.com/review_user/6974/Reviewer


Review 3

Review Title: Oral Candidiasis Posted by Dr. Srikanth N on 13 Dec 2011 10:56:14 AM GMT

1 Is the subject of the article within the scope of the subject category? Yes

2 Are the interpretations / conclusions sound and justified by the data? Partly

3 Is this a new and original contribution? No

4 Does this paper exemplify an awareness of other research on the topic? Yes

5 Are structure and length satisfactory? Yes

6 Can you suggest brief additions or amendments or an introductory statement that will increasethe value of this paper for an international audience?

Yes

7 Can you suggest any reductions in the paper, or deletions of parts? No

8 Is the quality of the diction satisfactory? Yes

9 Are the illustrations and tables necessary and acceptable? Yes

10 Are the references adequate and are they all necessary? Yes

11 Are the keywords and abstract or summary informative? Yes

Rating: 5

Comment: 1. The speciation of the candida can be done using the germ tube growth as well as the colour of the colonies inpaganolevin and chrome agar. Pagano Levin agar has been described in the the article but the fact that thespecies can be identified has to be emphasized.

2. Clinical, Histopathological, special stains, culture plate photographs will greatly improve the article.

3. Recent advances on the detection, variations in the radiation, immunosuppression will improve the article a lot.

Competing interests: nil



Experience and credentials in the specific area of science: I work in the capacity of Reader, in department of Oral Pathology, and have preformed cultures and studiesinvolving candida species.

How to cite: N S.Oral Candidiasis [Review of the article 'Oral Candidiasis- A Review ' by ].WebmedCentral1970;2(12):WMCRW001237



http://www.webmedcentral.com/review_user/6973/Reviewer


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Documents

Oral Candidiasis- A Review - WebmedCentral.com ID: WMC002498 ISSN 2046-1690 Oral Candidiasis- A Review Corresponding Author: Dr. Sameer Parihar, Assistant professor, Oral & Maxillofacial