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Abstract: Oral geotrichosis is an uncommonopportunistic infection caused by Geotrichum candidum,a habitual contaminant and component of the flora ofvarious parts of the body. This communication reportsboth a 20-year retrospective study of clinically andmycologically proven cases of oral geotrichosis, and aprospective study of fungal oral flora in 200 individualsdivided into two groups: normal individuals andindividuals with associated conditions. Twelve patientswith proven oral geotrichosis were included: 9 femalesand 3 males, with a mean age of 48.5 years; theassociated conditions were diabetes mellitus (66.6%),leukemia, Hodgkin’s lymphoma and HIV/AIDSinfection. The oral geotrichoses showed three clinicalvarieties: pseudomembranous (75%), hyperplastic,and palatine ulcer. G. candidum was isolated in 11cases and G. capitatum in one. Positive fungal cultureswere obtained from the two groups, and 48% and 78%of cultures were positive, respectively, for Candida spp.In 2.8% and 6.33% of the cases, G. candidum wasisolated, respectively, together with one strain of G.capitatum. Oral geotrichosis is an exceptional infectionthat clinically presents, and is treated, as oralcandidiasis. G. candidum may be isolated from the oralflora of a small proportion of patients, either normalindividuals or those with associated conditions. (J OralSci 52, 477-483, 2010)

Keywords: oral geotrichosis; Geotrichum candidum;Geotrichum capitatum; Candida albicans;diabetes; leukemia.

IntroductionGeotrichosis is an infrequent opportunistic mycosis

caused by yeasts. The main etiologic agent is Geotrichumcandidum, which belongs to the class Hemiascomycetaceae,order Saccharomycetales, family Dipodascaceae. It hasbeen reported to pathologically affect the bronchi, lungs,and bowel, and only seldom the mouth, skin and nails. Twoother species have also been reported to affect the lung:Geotrichum capitatum and Geotrichum clavatum (1-4).

G. candidum is a cosmopolitan microorganism andhabitual contaminant. It has been isolated from varioussources such as fruits and vegetables, soil, and plants.Several studies have proven that it is a commensal inhumans and part of the normal flora of the skin, mouthand gastrointestinal tract (3). G. candidum has been isolatedfrom 29% of fecal samples (5,6), and from 18-31% of morethan 2,000 specimens of sputum, feces, urine and vaginaldischarge. No studies specifically aimed at isolatingGeotrichum spp. from the normal oral flora have beenreported.

Most of the reported clinical cases have occurred inimmunosuppressed patients or immunosuppressivedisorders, and have affected the respiratory tract (bronchiand lungs); superficial skin infections and, recently, invasiveinfections have also been reported (7-9). In earlier reportswe described cases of oral geotrichosis associated withdiabetes mellitus (4,10).

Here we present a retrospective report of cases of oral

Journal of Oral Science, Vol. 52, No. 3, 477-483, 2010

Correspondence to Dr. Alexandro Bonifaz, Hospital General deMéxico OD, Sánchez Azcona 317 int. 202, Col. del Valle,México D. F., CP 03020Tel: +52-55-5761-3923Fax: +52-55-5761-3923E-mail: a_bonifaz@yahoo.com.mx

Oral geotrichosis: report of 12 cases

Alexandro Bonifaz1,2), Denisse Vázquez-González2), Berenice Macías1,3), Fernando Paredes-Farrera3), Marco A. Hernández1), Javier Araiza1)

and Rosa M. Ponce2)

1)Department of Mycology, General Hospital of Mexico, Col. Doctores, Mexico D. F.2)Dermatology Service, General Hospital of Mexico, Col. Doctores, Mexico D. F.3)Stomatology Service, General Hospital of Mexico, Col. Doctores, Mexico D. F.

(Received 23 March and accepted 29 July 2010)

Original

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geotrichosis we have experienced, as well as details of astudy of this habitual contaminant in normal subjects andpatients with various conditions. Our principal aim wasto present a case series and detail the clinical behavior ofthe disease, as well as the diagnostic mycological aspects,in order to document the most effective techniques not onlyfor oral cases, but also deep and systemic infections. Oursecondary aim was to demonstrate the presence ofGeotrichum spp. as a habitual contaminant in healthyindividuals and patients with several diseases.

Materials and MethodsRetrospective study of proven cases of oralgeotrichosis

Our report covers a 20-year (1989-2008) retrospectivesurvey of proven cases of oral geotrichosis. The medicalhistory of the patients was taken, and mycologic testswere performed, including direct KOH (20%) and cottonblue stain, and cultures using the following routine media:Sabouraud dextrose agar (DifcoTM Inc., Seneca, KS, USA),yeast extract agar plus chloramphenicol (DifcoTM Inc.), andBiggy-Nickerson agar (DifcoTM Inc.). The resultingorganisms were identified based on their micro- andmacromorphologic features, and proven by biochemicaltests (carbohydrate utilization) using the commercialmethod, API-yeast 20® (Biomérieux Inc., Durham, NC,USA).

Study of the fungal floraFor this study, 200 individuals were selected, and divided

into two groups with age- and gender-matching.Group 1. This comprised 100 normal subjects who were

disease-free, had no associated conditions or immuno-deficiency, and were not receiving treatment with eithersteroids or topical or oral antibiotics.

Group 2. This comprised 100 patients with conditionssuch as type-1 and type-2 diabetes mellitus (both controlledand uncontrolled), hematological cancers (leukemia andlymphoma), HIV/AIDS, and drug-related immuno-suppression (oral steroids and cytostatic agents). None ofthe patients had any oral conditions. An oral specimen wastaken by smearing three sterile swabs on the tongue, thepalatine aspect of the cheeks and the palate. Each of theswabs was seeded in three types of culture media usingthe streaking technique: Sabouraud dextrose agar (DifcoTM

Inc.), +, yeast extract (DifcoTM Inc.), + chloramphenicolagar, and CHROMagar CandidaTM (CHROMagarTM, Paris,France).

The resulting cultures were identified based on theirmicro- and macromorphologic features and colony color(CHROMagar-CandidaTM). Results were verified bybiochemical test identification with the commercial API-yeast 20® method.

ResultsRetrospective study of oral geotrichosis

Twelve cases of clinically and mycologically proven

Table 1 Oral Geotrichosis. Main demographic, clinical and mycologic data

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geotrichosis were included. Table 1 shows the maindemographic, clinical and mycologic data. Nine of the 12patients (75%) were females and the rest were males. Theyoungest patient was 31 years old and the oldest was 72;mean age was 48.5 years. The disease course was: the minorcase of 5 days, and the major one of 15 days, with a meanduration of 8.75 days. Associated conditions included 8cases of diabetes mellitus (66.6%) (type 2, 7 cases; type1, 1 case), 2 cases of type-2 acute lymphocytic leukemia(ALL-2), one case of Hodgkin’s lymphoma, and one caseof HIV infection/AIDS. All the patients enrolled werebeing followed up and treated for their respective conditions.

With regard to the clinical variety, 9 patients (75%) hadthe pseudomembranous form with primary involvementof the tongue; one of them also had associated angularcheilitis (Table 1, Figs. 1-3).

Mycologically, all the cases showed fungal elements;8 (66.6%) of them had thin, septate hyphae with rectangulararthroconidia and, at times, rounded borders (clavata cells),

while in the remaining 4 cases (33.4%), only thin andseptate hyphae were evident. White villous and wet coloniesgrew in all cases, and under the microscope these were seenas having abundant thin, septate filaments with multiplerectangular arthroconidia. Eleven cultures were biochem-ically identified as G. candidum, with the resultingcarbohydrate assimilation of glucose and xylose, and werenegative for galactose, cellobiose, lactose, maltose,melibiose and saccharose. No growth occurred at 40°C,and a strain identified as G. capitatum produced glucose,galactose and xylose, and was negative for cellobiose,maltose and saccharose; growth occurred at 40°C (4,11)(Figs. 4, 5).

Fig. 1 Pseudomembranous form, affecting basically the tongue(Patient 7, Table 1).

Fig. 2 Villous hyperplastic manifestation (Patient 6, Table 1).

Fig. 3 Palatal ulcer. The arrow indicates the initial ulcer(Patient 2, Table 1).

Fig. 4 Geotrichum candidum in Sabouraud dextrose agar(white and villous colony).

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Study of the fungal floraThe results of the flora study in the two groups, normal

individuals and those with associated conditions, are shownin Table 2. Overall, 48% of the cultures were positive inthe first group, with Candida spp. predominant and onlyone isolate of G. candidum (2.8%) being obtained. In thesecond group, 79% of the cultures were positive, withCandida spp. predominant. There were 5 isolates of G.candidum (6.33%), specifically from 4 patients withcontrolled type-2 diabetes, and one with controlled chronicmyelocytic leukemia. One isolate of G. candidum (1.26%)was obtained from one patient with type-2 diabetes mellitus.

DiscussionCiferri and Redaelli were the first to report cases of

geotrichosis in 1935. All were skin infections, and theauthors also carried out a study of the normal flora andisolated Geotrichum from sputum and skin. Some casesreported in the late 20th century seem to have beengeotrichosis (1,3). We have observed cases involving theskin, lungs, bowel and, specifically, two cases of oralgeotrichosis (2,4,10).

G. candidum is a yeast with a teleomorphic status knownas Galactomyces geotrichum (11,12). It is considered tohave low virulence, and is even used regularly for thematuration of cheese (Brie type) and is a contaminant ofwater and milk. However, it may result in severe diseasewhen associated with immunosuppressive conditions ortreatments (3,7,8). G. capitatum is the second medicallyimportant species; it also has a teleomorphic state knownas Dipodascus capitatus (12), and has been reported tocause bowel, bronchial, lung and disseminated infections,as well as fungemias (9,13-16).

We reported oral geotrichosis for the first time in 1987(10), and since then have experienced a series of cases onwhich this clinical mycologic report is based. Most of thecases (75%) showed pseudomembranous manifestations,that is, involvement mainly of the tongue resulting inglossitis, and in some cases the disease affected the palatinearea of the cheeks. All cases presented as easily removablepseudomembranous, creamy, whitish plaques with anerythematous background. In one of the patients, thecondition was associated with angular cheilitis; this wasthe case showing the greatest degree of progression,indicating that greater chronicity may include involvementof the mouth adnexa, i.e., the lips. The most commonsymptoms were burning pain and impaired swallowing.On the basis of the clinical features, this entity is

Fig. 5 Geotrichum candidum, direct examination (cottonblue, ×40).

Table 2 Study of the habitual fungal flora of the mouth

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indistinguishable from pseudomembranous candidiasis, andin fact this was the presumptive diagnosis in all cases.Although there have been only a few reports of oralgeotrichosis, some have resembled the clinical picture inour patients. The presentation is usually one of erythemawith whitish plaques, similar to oral candidiasis; both G.candidum and G. capitatum have been reported as thecausative agents (16-19).

Two cases with a villous hyperplastic manifestation,similar to viral disease and candidiasis, drew our attention.These cases demonstrated that, if a routine mycologicstudy is not performed, and the isolated organisms notproperly identified, oral geotrichosis may easily bediagnosed as candidiasis. Therefore, we think thatgeotrichosis may be more common than generally assumed,and in fact frequently misdiagnosed, mainly because itresponds well to treatment aimed at candidiasis. One ofour patients had a very distinct clinical presentation of asmall localized ulcer on the hard palate; this was animmunosuppressed patient with type-2 acute lymphoblasticleukemia. This clinical manifestation was very differentfrom candidiasis, which is more superficial, and bore a closeresemblance to ulcers caused by zygomycosis andaspergillosis, resulting in a very aggressive palatine-cerebral condition with a poor prognosis (20). This has beenreported for some patients (19) with esophageal ulcerations(21); oral ulcers in dogs have also been reported (22).

The data from our studied cases (Table 1) indicate thatmost cases occurred in females, and that the mean age ofthe patients was 48.5 years. However, associated factorsindicated that most of the cases occurred among diabeticpatients, in addition to patients with leukemias, lymphomasand HIV-AIDS. Most of these conditions have been reportedin the literature (4,16-19), and it is important to emphasizethat they are the background diseases most frequentlyassociated with oral candidiasis. With regard to the courseof the disease, there is a subacute stage that lasts for about8 days, also similar to cases of candidiasis. It is importantto emphasize that the majority of cases were associatedwith diabetes mellitus, and this is probably due to thepresence of higher serum glucose levels, which stimulatethe growth of yeasts such as Candida, Geotrichum andTrichosporon. Recognition of this fact allows the use ofprophylactic treatment, as is also the case for affectedpatients who are immunosuppressed (4,23,24).

From a mycologic standpoint, direct examination andstaining may provide a rapid diagnosis of the infection,particularly when multiple hyphae with arthroconidia areevident, this being the most frequent diagnostic sign weencountered (66.6% of cases). However, some arthroconidiamay have a rounded appearance and may be easily mistaken

for Candida, since the latter may form pseudohyphae,hyphae and blastoconidia. Septate hyphae alone were seenis a smaller proportion of cases but, as mentioned above,the same feature may be observed in many cases of chroniccandidiasis. These circumstances mean that culture alonecan confirm the diagnosis. G. candidum and G. capitatumare easily identifiable, since they present as white,membranous, villous, wet colonies appearing as multiplerectangular arthroconidia under the microscope. Thediagnosis can be easily confirmed with biochemical tests.Currently available chromogenic culture media (CHROMagar-Candida®) can allow easy identification. Their villous wetgrowth with slight pink pigmentation distinguishes themfrom the major Candida species. It is important to stressthat G. candidum is inhibited by cycloheximide (actidione),and therefore culture media containing this antibioticshould never be used (1-4). Molecular biology isundoubtedly the most accurate technique for identifyingboth species by the internal transcriber spacer (rDNA); inorder to identify G. candidum, the most useful sequenceis the D1/D2 domain of the large subunit (26S), and forG. capitatum, the sequences of the ITS-1 and ITS-2 regions(16,25).

Recently Henrich et al. (25) have reported a case ofdisseminated geotrichosis due to G. candidum in a patientwith relapsed leukemia following allogeneic stem celltransplantation, together with an extensive review of casesin the literature, the majority being associated withneutropenia, especially that in diverse types of leukemia.Therefore it is important to be aware that the normal floraof the skin and mouth can lead to contamination of catheters,this condition has been previously (4,17,20,22).

In the second part of the present study, it was evidentthat the number of isolates was significantly smaller amongnormal individuals than among those with associatedconditions, the isolation rates being 48% and 78%,respectively. The isolates obtained showed that most casescorresponded to yeasts of Candida spp., with C. albicanspredominant in both groups. These data reflect those fromsimilar studies, and are indicative of the striking increaseof infections attributable to non-albicans species in recentyears. In our study they accounted for 38.4% and 39.1%,respectively, in the two groups, there being no differencein prevalence between them. The mixed growth obtainedin some cases was noteworthy. Chromogenic culture mediaare useful, and currently allow more than one species tobe identified. Pursuant to the purpose of our study, it wasnoteworthy that although G. candidum was isolated inboth groups, one isolate (2.8%) was obtained in group 1and 5 (6.33%) in group 2, the difference being more thantwo-fold. These results indicate that G. candidum may be

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part of the normal flora or act as a contaminant, and thatwhen it occurs as an infection, it is probably of theendogenous type, similar to the situation in Candida spp.infections. Geotrichum spp. isolates have been obtainedfrom various parts of the body (3-6), and those from theoral flora account for as much as 30% of healthy individuals(26,27); compared with this figure, our isolation rateswere lower (2.8% and 6.33%). A recent study by Goncalveset al. (24) of colonization in diabetic patients (treated withinsulin) found that Geotrichum spp. was isolated at a rateof 0.57%. Thus, although these fungal isolates show greatvariability, they are considered to be part of the oral andintestinal flora.

This report has provided a more accurate picture ofcases of oral geotrichosis, including its clinical andmycological characteristics, which are very similar tothose of oral candidiasis, making it likely to be under- ormisdiagnosed.

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