Postgrad Med J 2002;78:455-459 doi:10.1136/pmj.78.922.

455
ttp://pmj.!mj."om/"o#te#t/78/922/455.$%&&
Review
Oral candidiasis
1. A Akpan,
2. R Morgan
1. 'rro(e Par) *ospita& +*, -r%st. /pto#. 0irra&. /1
1. Correspondence to: Dr A Akpan, Arrowe Park Hospital NHS r!st, "pton, #irral
CH$% &P', "() asang*at+doctors.org.!k
Received 1$ Nove,-er 2..1
Accepted 11 Marc/ 2..2
Abstract
0ral candidiasis is a co,,on opport!nistic in1ection o1 t/e oral cavit2 ca!sed -2 an
overgrowt/ o1 2a#dida species, t/e co,,onest -eing 2a#dida a&!i"a#s. /e incidence
varies depending on age and certain predisposing 1actors. /ere are t/ree -road gro!pings
consisting o1 ac!te candidiasis, c/ronic candidiasis, and ang!lar c/eilitis. Risk 1actors incl!de
i,paired salivar2 gland 1!nction, dr!gs, dent!res, /ig/ car-o/2drate diet, and e3tre,es o1
li1e, s,oking, dia-etes ,ellit!s, C!s/ing4s s2ndro,e, ,alignancies, and i,,!nos!ppressive
conditions. Manage,ent involves taking a /istor2, an e3a,ination, and appropriate
anti1!ngal treat,ent wit/ a 1ew re5!iring sa,ples to -e taken 1or la-orator2 anal2sis. 6n
certain /ig/ risk gro!ps anti1!ngal prop/2la3is red!ces t/e incidence and severit2 o1
in1ections. /e prognosis is good in t/e great ,a7orit2 o1 cases.
oral candidiasis
0ral candidiasis is an opport!nistic in1ection o1 t/e oral cavit2. 6t is co,,on and
!nderdiagnosed a,ong t/e elderl2, partic!larl2 in t/ose w/o wear dent!res and in ,an2 cases
is avoida-le wit/ a good ,o!t/ care regi,en. 6t can also -e a ,ark o1 s2ste,ic disease, s!c/
as dia-etes ,ellit!s and is a co,,on pro-le, a,ong t/e i,,!noco,pro,ised. 0ral
candidiasis is ca!sed -2 an overgrowt/ or in1ection o1 t/e oral cavit2 -2 a 2east8like 1!ng!s,
candida.
1,2
/e i,portant ones are 2 a&!i"a#s 9t/e co,,onest) see 1ig 1:, 2 tropi"a&is, 2
g&a!rata, 2 pse%dotropi"a&is, 2 g%i&&ierimo#dii, 2 )r%sei, 2 &%sita#iae, 2 parapsi&osis, and 2
ste&&atoidea. 2 a&!i"a#s, 2 g&a!rata, and 2 tropi"a&is represent ,ore t/an ;.< o1 isolates
1ro, clinical in1ection.
=
0ral candidiasis is t/e ,ost co,,on /!,an 1!ngal in1ection
$,&

especiall2 in earl2 and later li1e. 6n t/e general pop!lation, carriage rates /ave -een reported
to range 1ro, 2.< to >&<
$
wit/o!t an2 s2,pto,s. /e incidence o1 2 a&!i"a#s isolated 1ro,
t/e oral cavit2 /as -een reported to -e $&< in neonates,
?
$&<@?&< o1 /ealt/2 c/ildren,
>

=.<@$&< o1 /ealt/2 ad!lts,
;,%
&.<@?&< o1 people w/o wear re,ova-le dent!res,
%
?&<@
;;< in t/ose residing in ac!te and long ter, care 1acilities,
%@12
%.< o1 patients wit/ ac!te
le!kae,ia !ndergoing c/e,ot/erap2,
1=
and %&< o1 patients wit/ H6A.
1$
2 a&!i"a#s is a nor,al
co,,ensal o1 t/e ,o!t/ and generall2 ca!ses no pro-le,s in /ealt/2 people. 0vergrowt/ o1
candida, /owever, can lead to local disco,1ort, an altered taste sensation, d2sp/agia 1ro,
oesop/ageal overgrowt/ res!lting in poor n!trition, slow recover2, and prolonged /ospital
sta2. 6n i,,!noco,pro,ised patients, in1ection can spread t/ro!g/ t/e -loodstrea, or !pper
gastrointestinal tract leading to severe in1ection wit/ signi1icant ,or-idit2 and ,ortalit2.
S2ste,ic candidiasis carries a ,ortalit2 rate o1 >1< to >%<.
1&
Figure 1
2a#dida a&!i"a#s as seen !nder lig/t ,icroscop2 9co!rtes2 o1 Dr C!nnli11e, Cons!ltant
Micro-iologist, #irral NHS r!st:.
Box 1: 6ntrod!ction
0ral candidiasis is t/e co,,onest /!,an 1!ngal in1ection.
"ntreated, t/is can lead to poor n!trition and prolonged recover2.
6n e3tre,e cases can -e 1atal w/en it -eco,es disse,inated.
6t is i,portant 1or all p/2sicians looking a1ter older patients to -e aware o1 t/e risk 1actors,
diagnosis, and treat,ent o1 oral candidiasis. 6n a recent st!d2 =.< o1 doctors said t/e2 wo!ld
prescri-e n2statin 1or oral candidiasis on t/e re5!est o1 n!rsing sta11 wit/o!t e3a,ination o1
t/e oral cavit2.
1?
/is is !n1ort!nate as ot/er pat/olog2 ,a2 -e ,issed, t/e diagnosis ,a2 -e
incorrect, and 1ail!re to address risk 1actors ,a2 lead to rec!rrence o1 t/e candidiasis.
CLASSIFICATION
/ere are a n!,-er o1 di11erent t2pes o1 orop/ar2ngeal candidiasis incl!ding ac!te
pse!do,e,-rano!s, ac!te atrop/ic, c/ronic /2perplastic, c/ronic atrop/ic, ,edian r/o,-oid
glossitis, and ang!lar c/eilitis.
1>
/e ,ost discrete lesion represents conversion 1ro, -enign
colonisation to pat/ological overgrowt/.
Pse%domem!ra#o%s "a#didiasis 3tr%s4 is c/aracterised -2 e3tensive w/ite
pse!do,e,-ranes consisting o1 des5!a,ated epit/elial cells, 1i-rin, and 1!ngal /2p/ae 9see
1ig 2:. /ese w/ite patc/es occ!r on t/e s!r1ace o1 t/e la-ial and -!ccal ,!cosa, /ard and
so1t palate, tong!e, periodontal tiss!es, and orop/ar2n3. /e ,e,-rane can !s!all2 -e
scraped o11 wit/ a swa- to e3pose an !nderl2ing er2t/e,ato!s ,!cosa. Diagnosis is !s!all2
straig/t1orward as it is easil2 seen and is one o1 t/e co,,onest 1or,s o1 orop/ar2ngeal
candidiasis acco!nting 1or al,ost a t/ird.
1;
Diagnosis can -e con1ir,ed ,icro-iologicall2
eit/er -2 staining a s,ear 1ro, t/e a11ected area or -2 c!lt!ring a swa- 1ro, an oral rinse.
Predisposing 1actors incl!de e3tre,es o1 age, dia-etes ,ellit!s, patients w/o /ave H6ABA6DS
or le!kae,ia, t/ose !sing steroid aerosol in/alers, -road spectr!, anti-iotics, and
ps2c/otropic dr!gs, and patients w/o are ter,inall2 ill. 0t/er conditions t/at can give rise to
w/ite patc/es in t/e ,o!t/ are lic/en plan!s, s5!a,o!s cell carcino,a, lic/enoid reaction,
and le!koplakia.
Figure 2
Ac!te pse!do,e,-rano!s candidiasis.
Ac!te atrop/ic candidiasis is !s!all2 associated wit/ a -!rning sensation in t/e ,o!t/ or on
t/e tong!e. /e tong!e ,a2 -e -rig/t red si,ilar to t/at seen wit/ a low ser!, C12, low
1olate, and low 1erritin. Diagnosis ,a2 -e di11ic!lt -!t s/o!ld -e considered in t/e di11erential
diagnosis o1 a sore tong!e especiall2 in a 1rail older patient wit/ dent!res w/o /as received
anti-iotic t/erap2 or w/o is on in/aled steroids. A swa- 1ro, t/e tong!eB-!ccal ,!cosa ,a2
/elp diagnosis.
2ro#i" 5perp&asti" "a#didiasis c/aracteristicall2 occ!rs on t/e -!ccal ,!cosa or lateral
-order o1 t/e tong!e as speckled or /o,ogeno!s w/ite lesions 9see 1ig =:. /e lesions !s!all2
occ!r on t/e -!ccal ,!cosa or lateral -orders o1 t/e tong!e. /ere is an association wit/
s,oking
1%
and co,plete resol!tion appears to -e dependent on cessation o1 s,oking. /is
condition can progress to severe d2splasia or ,alignanc2 and is so,eti,es re1erred to as
candidal le!koplakia. 2a#dida spp are not alwa2s isolated 1ro, lesions o1 oral le!koplakia
and it /as -een s!ggested t/at t/e 1inding o1 2a#dida spp in t/ese pre,alignant lesions is a
co,plicating 1actor rat/er t/an a ca!sative one.
2.
/is condition ,a2 -e con1!sed wit/ lic/en
plan!s, pe,p/igoidBpe,p/ig!s, and s5!a,o!s cell carcino,a.
Figure 3
C/ronic /2perplastic candidiasis.
2ro#i" atropi" "a#didiasis also known as Ddent!re sto,atitisE is c/aracterised -2 localised
c/ronic er2t/e,a o1 tiss!es covered -2 dent!res. Fesions !s!all2 occ!r on t/e palate and
!pper 7aw -!t ,a2 also a11ect ,andi-!lar tiss!e. Diagnosis re5!ires re,oval o1 dent!res and
care1!l inspection) swa-s ,a2 -e taken 1or con1ir,ation. 6t is 5!ite co,,on wit/ incidence
rates o1 !p to ?&< reported.
Media# rom!oid g&ossitis is a c/ronic s2,,etrical area on t/e tong!e anterior to t/e
circ!,vallate papillae. 6t is ,ade !p o1 atrop/ic 1ili1or, papillae. Ciops2 o1 t/is area !s!all2
2ields candida
21
in over ;&< o1 cases. 6t tends to -e associated wit/ s,oking and t/e !se o1
in/aled steroids.
'#g%&ar "ei&itis is an er2t/e,ato!s 1iss!ring at one or -ot/ corners o1 t/e ,o!t/ 9see 1ig $:,
and is !s!all2 associated wit/ an intraoral candidal in1ection. 0t/er organis,s i,plicated are
stap/2lococci and streptococci. 6n t/e case o1 stap/2lococci t/e reservoir is !s!all2 t/e
anterior region o1 t/e nostrils and spread to t/e angles o1 t/e ,o!t/ /as -een con1ir,ed -2
p/age t2ping.
22,2=
Gacial wrinkling at t/e corners o1 t/e ,o!t/ and along t/e nasola-ial 1old
especiall2 in older people leads to a c/ronicall2 ,oist environ,ent t/at predisposes to t/is
lesion.
2$
/is wrinkling is worse in long ter, dent!re wearers -eca!se t/ere is resorption o1
-one on w/ic/ t/e dent!res rest leading to a red!ction in /eig/t o1 t/e lower 1ace w/en t/e
,o!t/ is closed.
2&
0t/er 1actors i,plicated in t/e aetiolog2 o1 t/is condition are iron
de1icienc2 anae,ia and vita,in C12 de1icienc2.
Figure 4
Ang!lar c/eilitis.
IS! FACTOS
"1# $at%ogen
Candida is a 1!ng!s and was 1irst isolated in 1;$$ 1ro, t/e sp!t!, o1 a t!-erc!lo!s patient.
2?

Fike ot/er 1!ngi, t/e2 are non8p/otos2nt/etic, e!kar2otic organis,s wit/ a cell wall t/at lies
e3ternal to t/e plas,a ,e,-rane. /ere is a n!clear pore co,ple3 wit/in t/e n!clear
,e,-rane. /e plas,a ,e,-rane contains large 5!antities o1 sterols, !s!all2 ergosterol.
Apart 1ro, a 1ew e3ceptions, t/e ,acroscopic and ,icroscopic c!lt!ral c/aracteristics o1 t/e
di11erent candida species are si,ilar. /e2 can ,eta-olise gl!cose !nder -ot/ aero-ic and
anaero-ic conditions. e,perat!re in1l!ences t/eir growt/ wit/ /ig/er te,perat!res s!c/ as
=>HC t/at are present in t/eir potential /ost, pro,oting t/e growt/ o1 pse!do/2p/ae. /e2
/ave -een isolated 1ro, ani,als and environ,ental so!rces. /e2 can -e 1o!nd on or in t/e
/!,an -od2 wit/ t/e gastrointestinal tract, t/e vagina, and skin -eing t/e ,ost co,,on sites
and 2 a&!i"a#s -eing t/e co,,onest species isolated 1ro, t/ese sites. /e2 re5!ire
environ,ental so!rces o1 1i3ed car-on 1or t/eir growt/. Gila,ento!s growt/ and apical
e3tension o1 t/e 1ila,ent and 1or,ation o1 lateral -ranc/es are seen wit/ /2p/ae and
,2celi!,, and single cell division is associated wit/ 2easts.
2>
Several st!dies /ave de,onstrated t/at in1ection wit/ candida is associated wit/ certain
pat/ogenic varia-les. Ad/esion o1 candida to epit/elial cell walls, an i,portant step in
initiation o1 in1ection, is pro,oted -2 certain 1!ngal cell wall co,ponents s!c/ as ,annose,
C=d receptors, ,annoprotein, and sacc/arins.
22,2;@=.
/e degree o1 /2drop/o-icit2
=1
and
a-ilit2 to -ind to /ost 1i-ronectin
=2
/as also -een reported to -e i,portant in t/e initial stages
o1 in1ection. 0t/er 1actors i,plicated are ger, t!-e 1or,ation, presence o1 ,2celia,
persistence wit/in epit/elial cells, endoto3ins, ind!ction o1 t!,o!r necrosis 1actor, and
proteinases.
==@=;
P/enot2pic switc/ing w/ic/ is t/e a-ilit2 o1 certain strains o1 2 a&!i"a#s to
c/ange -etween di11erent ,orp/ologic p/enot2pes /as also -een i,plicated.
=%
"2# &ost
Local 'actors
6mpaired sa&i7ar5 g&a#d $%#"tio# can predispose to oral candidiasis.
1,$.
Secretion o1 saliva
ca!ses a dil!tional e11ect and re,oves organis,s 1ro, t/e ,!cosa. Anti,icro-ial proteins in
t/e saliva s!c/ as lacto1errin, sialopero3idase, l2soI2,e, /istidine8ric/ pol2peptides, and
speci1ic anticandida anti-odies, interact wit/ t/e oral ,!cosa and prevent overgrowt/ o1
candida. /ere1ore conditions s!c/ as S7Jgren4s s2ndro,e, radiot/erap2 o1 t/e /ead and neck,
or dr!gs t/at red!ce salivar2 secretions can lead to an increased risk o1 oral candidiasis.
8r%gs s!c/ as in/aled steroids /ave -een s/own to increase t/e risk o1 oral candidiasis
$1
-2
possi-l2 s!ppressing cell!lar i,,!nit2 and p/agoc2tosis. /e local ,!cosal i,,!nit2
reverts to nor,al on discontin!ation o1 t/e in/aled steroids.
$2
8e#t%res predispose to in1ection wit/ candida in as ,an2 as ?&< o1 elderl2 people wearing
1!ll !pper dent!res.
2.
#earing o1 dent!res prod!ces a ,icroenviron,ent cond!cive to t/e
growt/ o1 candida wit/ low o32gen, low pH, and an anaero-ic environ,ent. /is ,a2 -e d!e
to en/anced ad/erence o1 2a#dida spp to acr2lic, red!ced saliva 1low !nder t/e s!r1aces o1
t/e dent!re 1ittings, i,properl2 1itted dent!res, or poor oral /2giene.
1,2
Box 2: Classi1ication
0ral candidiasis can -e classi1ied as 1ollows:
1. Acute candidiasis
o Ac!te pse!do,e,-rano!s candidiasis 9t/r!s/:.
o Ac!te atrop/ic 9er2t/e,ato!s: candidiasis.
2. C%ronic candidiasis
o C/ronic /2perplastic candidiasis 9candidal le!koplakia:.
o Dent!re ind!ced candidiasis 9c/ronic atrop/ic 9er2t/e,ato!s: candidiasis:.
o Median r/o,-oid glossitis.
=. Angular c%eilitis "sto(atitis#
9ter $a"tors are oral cancerBle!koplakia and a /ig/ car-o/2drate diet. Krowt/ o1 candida in
saliva is en/anced -2 t/e presence o1 gl!cose and its ad/erence to oral epit/elial cells is
en/anced -2 a /ig/ car-o/2drate diet.
$=
S)ste(ic 'actors
:;tremes o$ &i$e predispose to in1ection -eca!se o1 red!ced i,,!nit2.
2
Box 3: Risk 1actors 1or orop/ar2ngeal candidiasis
Pat/ogen /as pec!liar properties t/at increase its in1ectivit2 rate in t/e rig/t
environ,ent.
Host 1actors co!ld -e local andBor s2ste,ic.
Focal 1actors incl!de wearing dent!res, i,paired salivar2 gland 1!nction, in/aled
steroids, and oral cancer.
S2ste,ic 1actors incl!de e3tre,es o1 age, s,oking, dia-etes ,ellit!s, C!s/ing4s
s2ndro,e, i,,!nos!ppression, ,alignancies, n!tritional de1iciencies, and anti-iotics.
8r%gs s!c/ as -road spectr!, anti-iotics alter t/e local oral 1lora creating a s!ita-le
environ,ent 1or candida to proli1erate.
$$
/e nor,al oral 1lora is restored once t/e anti-iotics
are discontin!ed. 6,,!nos!ppressive dr!gs s!c/ as t/e antineoplastic agents /ave -een
s/own in several st!dies to predispose to oral candidiasis -2 altering t/e oral 1lora, disr!pting
t/e ,!cosal s!r1ace and altering t/e c/aracter o1 t/e saliva.
1=,$&,$?
9ter $a"tors are s,oking, dia-etes, C!s/ing4s s2ndro,e, i,,!nos!ppressive conditions
s!c/ as H6A in1ection, ,alignancies s!c/ as le!kae,ia, and n!tritional de1icienciesLvita,in
C de1iciencies /ave -een partic!larl2 i,plicated. Ninane 1o!nd t/at 1&<@?.< o1 people wit/
,alignancies will develop oral candidiasis w/ile t/e2 are i,,!nos!ppressed.
$>
6n t/ose wit/
H6A in1ection rates o1 -etween >< to $;< /ave -een 5!oted and ,ore t/an %.< /as -een
reported in t/ose wit/ advanced disease. Relapse rates are -etween =.< and &.< on
co,pletion o1 anti1!ngal treat,ent in severe i,,!nos!ppression.
$;
*ANA+,*,NT
aking a /istor2 1ollowed -2 a t/oro!g/ e3a,ination o1 t/e ,o!t/, looking at t/e so1t and
/ard palate, and e3a,ining t/e -!ccal ,!cosa in t/ose wearing dent!res a1ter t/e2 /ave -een
re,oved are !s!all2 good starting points. Predisposing 1actors are identi1ied as ,entioned
a-ove and resolved i1 possi-le, and t/e t2pe, severit2, and c/ronicit2 o1 t/e in1ection are
assessed.
/e rig/t diagnosis is !s!all2 ,ade on 1inding t/e c/aracteristic lesion, r!ling o!t ot/er
possi-ilities, and t/e response to anti1!ngal treat,ent. Ac!te pse!do,e,-rano!s and c/ronic
atrop/ic candidiasis can -e treated -ased on clinical 1eat!res -!t c!lt!re and sensitivit2
testing s/o!ld -e !ndertaken i1 initial t/erap2 is !ns!ccess1!l. 6,print c!lt!res,
&
w/ere sterile
1oa, pads dipped in Sa-o!ra!d4s -rot/ are placed 1or =. seconds on t/e lesion and t/en
placed on Sa-o!ra!d4s agar containing c/lora,p/enicol 1or an /o!r a1ter w/ic/ t/e2 are
inc!-ated, /ave also -een !sed 1or identi1ication o1 2a#dida spp. Ac!te atrop/ic and c/ronic
/2perplastic 1or,s ,a2 ,i,ic ot/er lesions and a -iops2 is reco,,ended in addition to
e,pirical t/erap2 to r!le o!t ,ore serio!s lesions s!c/ as s5!a,o!s cell carcino,a.
0ral /2giene and topical anti1!ngals are !s!all2 ade5!ate 1or !nco,plicated oral candidiasis.
9ra& 5gie#e involves cleaning t/e teet/, -!ccal cavit2, tong!e, and dent!res, i1 present,
dail2. Dent!res s/o!ld -e cleaned and disin1ected dail2 and le1t o!t overnig/t or 1or at least
si3 /o!rs dail2. /e dent!res s/o!ld -e soaked in a dent!re cleaning sol!tion s!c/ as
c/lor/e3idine as t/is is ,ore e11ective in eli,inating candida t/an -r!s/ing.
$%
/is is -eca!se
dent!res /ave irreg!lar and poro!s s!r1aces to w/ic/ candida easil2 ad/eres and -r!s/ing
alone cannot re,ove t/e,. #/en rinsing t/e ,o!t/ wit/ t/e topical anti1!ngal, dent!res
s/o!ld -e re,oved to allow contact -etween t/e ,!cosa and t/e anti1!ngal. /e patient
s/o!ld ens!re t/at t/e w/ole ,!cosa is coated wit/ t/e anti1!ngal and /eld in t/e ,o!t/ 1or a
1ew ,in!tes. /e incorporation o1 an anti1!ngal wit/ a dent!re liner /as -een reco,,ended
1or patients wit/ dent!res w/o 1ind it di11ic!lt to /old t/e anti1!ngal in t/eir ,o!t/ 1or a 1ew
,in!tes. Also t/e ,!cosal s!r1ace s/o!ld -e -r!s/ed reg!larl2 wit/ a so1t -r!s/. A1ter
disin1ection, dent!res s/o!ld -e allowed to air dr2 as t/is also kills ad/erent candida on
dent!res.
&.
C/lor/e3idine can discolo!r -ot/ dent!res and nat!ral dentition i1 not re,oved
ade5!atel2 a1ter disin1ection. A re1erral to a dentist ,ig/t -e necessar2 1or t/ose wit/ poorl2
1itting dent!res as t/ese predispose to in1ection -2 -reaking down t/e epit/elial -arrier. 0t/er
dent!re cleaning ,et/ods not ro!tinel2 !sed -!t s/own to -e e11ective are !ltrasonic cleaning
tanks wit/ a s!ita-le sol!tion.
&1
Box 4: Manage,ent
Diagnosis is !s!all2 ,ade on clinical gro!nds wit/ la-orator2 testing to e3cl!de
potentiall2 ot/er serio!s oral lesions especiall2 s5!a,o!s cell carcino,a.
Predisposing 1actors s/o!ld -e treated or eli,inated w/ere 1easi-le.
Kood oral /2giene is i,portant.
opical anti1!ngals given 1or two weeks are !s!all2 e11ective.
S2ste,ic anti1!ngals s/o!ld -e given in certain circ!,stances.
Reg!lar oral and dental /2giene wit/ periodic oral e3a,ination will prevent ,ost cases o1
oral candidiasis in t/ose wit/ dent!res. Co,-ining n2statin wit/ c/lor/e3idine digl!conate,
an antiseptic !sed to disin1ect dent!res, inactivates -ot/ dr!gs
&2,&=
t/ere1ore t/is co,-ination
s/o!ld not -e !sed. /e dent!res s/o!ld -e re,oved eac/ ti,e t/e ,o!t/ is rinsed wit/ t/e
oral anti1!ngal preparation in esta-lis/ed cases o1 dent!re sto,atitis and t/e dent!res soaked
in c/lor/e3idine -e1ore p!tting t/e, -ack in t/e ,o!t/.
-opi"a& a#ti$%#ga& terap5 is t/e reco,,ended 1irst line treat,ent 1or !nco,plicated oral
candidiasis and w/ere s2ste,ic treat,ent is needed topical t/erap2 s/o!ld contin!e as t/is
red!ces t/e dose and d!ration o1 s2ste,ic treat,ent re5!ired.
&$
/e s2ste,ic adverse e11ects
and dr!g interactions t/at occ!r wit/ t/e s2ste,ic agents do not occ!r wit/ topical agents.
$$

reat,ent in t/e earl2 part o1 t/e 2.t/ cent!r2 was wit/ gentian violet, an aniline d2e, -!t
-eca!se o1 resistance developing and side e11ects, s!c/ as staining o1 t/e oral ,!cosa, it was
replaced -2 a pol2ene anti-iotic, n2statin, discovered in 1%&1 and a,p/otericin C, discovered
in 1%&?. /e2 act -2 -inding to sterols in t/e cell ,e,-rane o1 1!ngi, and, altering cell
,e,-rane per,ea-ilit2.
&&,&?
N2statin and a,p/otericin are not a-sor-ed 1ro, t/e gastrointestinal tract and are !sed -2
local application in t/e ,o!t/. MiconaIole, an i,idaIole, can -e !sed as a local application
in t/e ,o!t/ -!t its !se in t/is wa2 is li,ited -eca!se o1 potential side e11ects s!c/ as
vo,iting and diarr/oea. 0t/er dr!gs -elonging to t/is class are clotri,aIole and
ketoconaIole. N2statin is t/e ,ost widel2 !sed topical agent 1or t/e treat,ent o1 oral
candidiasis.
1,2
6t is availa-le as an oral rinse, pastille, and s!spension. 6t s/o!ld -e !sed as a
rinse 1o!r ti,es a da2 1or two weeks. 6t can ca!se na!sea, vo,iting, and diarr/oea. /e oral
rinse contains s!crose and is !se1!l in edent!lo!s patients and t/ose wit/ 3erosto,ia s!c/ as
patients receiving radiot/erap2 and t/ose wit/ H6A in1ection.
&>
Clotri,aIole troc/e can -e an
alternative 1or t/ose patients w/o 1ind n2statin s!spensions !npalata-le.
,5stemi" a#ti$%#ga& terap5 in oral candidiasis is appropriate in patients intolerant o1 or
re1ractor2 to topical treat,ent and t/ose at /ig/ risk o1 developing s2ste,ic in1ections.
&$
Cot/ n2statin oral rinses and clotri,aIole troc/es /ave a /ig/ s!crose content and i1 toot/
deca2 is a concern or t/e oral candidiasis is co,plicated -2 dia-etes, steroid !se or an
i,,!noco,pro,ised state, triaIoles w/ic/ incl!de 1l!conaIole or itraconaIole once per da2
/as -een 1o!nd to -e e11ective in t/ese cases.
&;
(etoconaIole is also as e11ective as
1l!conaIole and itraconaIole -!t its !se in elderl2 patients is not reco,,ended d!e to dr!g
interactions and side e11ects, w/ic/ incl!de /epatoto3icit2.
Gl!conaIole is a potent and selective in/i-itor o1 1!ngal enI2,es involved in t/e s2nt/esis o1
ergosterol, an i,portant constit!ent o1 t/e plas,a cell ,e,-rane. 6t t/ere1ore disr!pts cell
wall 1or,ation leading to leakage o1 cell!lar contents and cell deat/. 6t is well a-sor-ed -2
t/e gastrointestinal tract and t/e plas,a levels are over %.< o1 t/e levels ac/ieved wit/
intraveno!s ad,inistration and t/e levels in saliva and sp!t!, are also si,ilar to t/at in t/e
plas,a. 6t is pre1erred, as it does not /ave t/e sa,e /epatoto3icit2 as t/e i,idaIoles. 6t is now
listed in t/e dental practitioners4 1or,!lar2 as well as t/e <ritis +atio#a& =orm%&ar5 and is
t/ere1ore widel2 !sed -ot/ in dental as well as ,edical practice -!t t/ere are pro-le,s wit/
resistance.
6traconaIole /as a wider spectr!, o1 activit2 t/an 1l!conaIole and is t/ere1ore val!a-le in
salvage treat,ent o1 t/e i,,!noco,pro,ised patients wit/ 1l!conaIole resistant candidosis.
6ncreasing resistance to anti1!ngals /as -eco,e increasingl2 co,,on since t/e introd!ction
o1 1l!conaIole especiall2 in patients wit/ advanced H6A disease, and rec!rrent and long ter,
treat,ent.
&%,?.
Ang!lar c/eilitis is treated wit/ anti1!ngal steroid crea,s and oint,ents and an2 conc!rrent
intraoral lesion is also treated at t/e sa,e ti,e and dietar2 de1iciencies s/o!ld -e e3cl!ded
and treated i1 1o!nd.
Gail!re to respond to t/erap2 especiall2 in c/ronic atrop/ic candidiasis is !s!all2 d!e to non8
co,pliance wit/ treat,ent.
Prop5&a;is wit/ anti1!ngal agents red!ces t/e incidence o1 oral candidiasis in patients wit/
cancer !ndergoing treat,ent
?1
and 1l!conaIole /as -een 1o!nd to -e ,ore e11ective t/an
topical pol2enes.
?2
Prop/2la3is on eit/er a dail2 or weekl2 -asis wit/ anti1!ngals red!ces t/e incidence o1 oral
candidiasis in patients wit/ H6A wit/ t/e red!ctions -eing ,ost ,arked in t/ose wit/ low
CD$ co!nts and rec!rrent oral candidiasis.
?=@??
/e !se o1 a c/lor/e3idine rinse onl2 in -one
,arrow transplant patients as prop/2la3is was 1o!nd to -e ver2 e11ective.
?>
$O+NOSIS
/e prognosis is good 1or oral candidiasis wit/ appropriate and e11ective treat,ent. Relapse
w/en it occ!rs is ,ore o1ten t/an not d!e to poor co,pliance wit/ t/erap2, 1ail!re to re,ove
and clean dent!res appropriatel2, or ina-ilit2 to resolve t/e !nderl2ingBpredisposing 1actors to
t/e in1ection.
,F,,NC,S
1. Epstein JB. '#ti$%#ga& terap5 i# oropar5#gea& m5"oti" i#$e"tio#s. 9ra& ,%rg 9ra&
Med 9ra& Pato&1990;69:32>41.
MCrossRe1N MMedlineN M#e- o1 ScienceN
2. Guida RA. 2a#didiasis o$ te oropar5#; a#d oesopag%s. :ar +ose -roat
J1988;67:832>40.
MMedlineN
=. Odds FC. 2a#dida a#d "a#didiasis. 2nd 'd. Fondon: Cailliere indall, 1%;;.
$. +%annou( *A, Radwan SS. 2a#dida adere#"e to epite&ia& "e&&s. Coca Raton, GF:
CRC Press, 1%%..
&. Abu-Elteen KH. '!%-'&tee# ?M. -e pre7a&e#"e o$ "a#dida a&!i"a#s pop%&atio#s i#
te mo%ts o$ "omp&ete de#t%re (earers. +e( Mi"ro!io&1998;21:41>8.
MMedlineN
?. Manning DJ. 2o%g&i# ?P. Pos)it :M. 2a#dida i# mo%t or o# d%mm5@ 'r" 8is
2i&d1985;60:381>2.
M A-stract BGR'' G!ll te3t N
>. Berdicevsky I. <e#-'r5e *. ,aAarge& ?. et a&. 9ra& "a#dida i# "i&dre#. 9ra& ,%rg
9ra& Med 9ra& Pato&1980;57:37>40.
;. Lucas !. 'sso"iatio# o$ ps5"otropi" dr%gs. pre7a&e#"e o$ de#t%re-re&ated stomatitis
a#d ora& "a#didosis. 2omm%#it5 8e#t 9ra& :pidemio&1993;21:313>16.
MCrossRe1N MMedlineN M#e- o1 ScienceN
%. Arend"r# $M. 0a&)er 8M. -e pre7a&e#"e a#d i#tra-ora& distri!%tio# o$ 2a#dida
a&!i"a#s i# ma#. 'r" 9ra& <io&1980;25:1>10.
MCrossRe1N MMedlineN M#e- o1 ScienceN
1.. Aldred MJ. 'dd5 M. <agg J. et a&. 9ra& ea&t i# te termi#a&&5 i&&: a "ross se"tio#a&
pi&ot s%r7e5. ,pe" 2are 8e#tist1991;11:59>62.
MMedlineN
11. %u&&ing %G. 0igt 2. <&a")(e&& 2B. et a&. 8e#t%re stomatitis i# te e&der&5. 9ra&
Mi"ro!io& 6mm%#o&1990;5:82>5.
MMedlineN M#e- o1 ScienceN
12. H"lbr""k '(. *jor&ei$sdottir 8C. 9""%rre#"e o$ ora& 2a#dida a&!i"a#s a#d oter
5east-&i)e $%#gi i# ede#t%&o%s patie#ts i# geriatri" %#its i# 6"e&a#d.
Derodo#ti"s1986;2;153>6.
MMedlineN M#e- o1 ScienceN
1=. R"du B. 2arpe#ter J-. Jo#es M?. -e patoge#esis a#d "&i#i"a& sig#i$i"a#"e o$
"5to&ogi"a&&5 dete"ta!&e ora& "a#dida i# a"%te &e%)aemia. 2a#"er1988;62:2042>6.
MCrossRe1N MMedlineN M#e- o1 ScienceN
1$. Dup"nt B. Dra5!i&& J?. 'rmstro#g 8. et a&. =%#ga& i#$e"tio#s i# '68, patie#ts. J Med
Cet M5"o&1992; 303s%pp& 14:19>28.
1&. )raser J. Jo#es M. 8%#)e& J. et a&. 2a#didemia i# a tertiar5 "are ospita&:
epidemio&og5. ris) $a"tors. a#d predi"tors o$ morta&it5. 2&i# 6#$e"t 8is1992;15:414>
21.
M A-stract BGR'' G!ll te3t N
1?. M"rgan R. -sa#g J. *arri#gto# +. et a&. ,%r7e5 o$ ospita& do"torEs attit%des a#d
)#o(&edge o$ ora& "o#ditio#s i# o&der patie#ts. Postgrad Med J2001;77:392>4.
M A-stract BGR'' G!ll te3t N
1>. Le-is *AO, Fa,e2 P8O. 2&i#i"a& ora& medi"i#e. 031ord: C!tterwort/8Heine,ann,
1%%&.
1;. !a&aranayake L(. +%tritio#a& $a"tors a#d ora& "a#didiasis. J 9ra&
Pato&1986;15:61>5.
MCrossRe1N MMedlineN M#e- o1 ScienceN
1%. !ilver&an !. B%a#gjarme)or# B. Dree#spa# 8. 9""%rre#"e o$ ora& "a#dida i#
irradiated ead a#d #e") "a#"er patie#ts. J 9ra& Med1984;39:194>6.
MMedlineN
2.. Drei*en !. 9ra& "a#didiasis. 'm J Med1984;30:28>33.
21. Bud*t-J"rgens"n E. :tio&og5. patoge#esis. terap5 a#d prop5&a;is o$ ora& 5east
i#$e"tio#s. '"ta 9do#to& ,"a#d1990;48:61>9.
MMedlineN M#e- o1 ScienceN
22. Kanbe $. Bi ?-1. 0ads(ort :. et a&. :7ide#"e $or e;pressio# o$ te 23d re"eptor o$
"a#dida a&!i"a#s i#-7itro a#d i#-7i7o o!tai#ed !5 imm%#o$&o%res"e#"e a#d
imm%#oe&e"tro# mi"ros"op5. 6#$e"t 6mm%#1991;59:1832.
M A-stract BGR'' G!ll te3t N
2=. Mac)arlane $'. *e&#ars)a ,J. -e mi"ro!io&og5 o$ a#g%&ar "ei&itis. <r 8e#t
J1968;140:403>6.
2$. !+ay K. -r%&ar M?. ?e##er ?P. 9ropar5#gea& "a#didosis i# te o&der patie#t. J 'm
Deriatr ,o"1997;45:863>70.
MMedlineN M#e- o1 ScienceN
2&. (en+all B. Pre7e#ti7e meas%res to "o#tro& $%rter !o#e &oss a#d so$t tiss%e damage i#
de#t%re (eari#g. '%st 8e#t J1980;25:319>24.
MCrossRe1N MMedlineN M#e- o1 ScienceN
2?. *andell +L, Cennett O', Dolin R. Anti81!ngal agents. Pri#"ip&es a#d pra"ti"e o$
i#$e"tio%s diseases. $t/ 'd. New Pork: C/!rc/ill Fivingstone, 1%%$: $.1@1..
2>. Le+&ann (). =%#ga& str%"t%re a#d morpo&og5. Medi"a& M5"o&og51998;4:57>8.
2;. Brassart D. 0o&tA '. Do&&iard M. et a&. 6#-7itro i#i!itio# o$ adesio# o$ 2a#dida
a&!i"a#s "&i#i"a& iso&ates to %ma# !%""a& epite&ia& "e&&s !5 =%"F1G2Da&H-!eari#g
"omp&e; "ar!o5drates. 6#$e"t 6mm%#1991;59:1605.
M A-stract BGR'' G!ll te3t N
2%. %+ann"u& MA. <%r#s D?. :&tee# '. et a&. :;perime#ta& e7ide#"e $or te ro&e o$
&ipids i# adere#"e o$ "a#dida spp to %ma# !%""a& epite&ia& "e&&s. 6#$e"t
6mm%#1986;54:189.
M A-stract BGR'' G!ll te3t N
=.. D"uglas LJ. ,%r$a"e "ompositio# a#d adesio# o$ 2a#dida a&!i"a#s. <io ,o"
-ra#s1985;13:982.
=1. Ha*en K%. <ra(#er 8B. ?iesse&ma# M*. et a&. 8i$$ere#tia& adere#"e o$
5dropo!i" a#d 5dropi&i" 2a#dida a&!i"a#s 5east "e&&s to mo%se tiss%es. 6#$e"t
6mm%#1991;59:907.
M A-stract BGR'' G!ll te3t N
=2. Kl"t* !A. ,mit ?B. ' $i!ro#e"ti# re"eptor o# 2a#dida a&!i"a#s mediates adera#"e
o$ te $%#g%s to e;tra"e&&%&ar matri;. J 6#$e"t 8is1991;163:604.
M A-stract BGR'' G!ll te3t N
==. !"bel JD. M%&&er D. <%")&e5 *?. 2riti"a& ro&e o$ germ t%!e $ormatio# i# te
patoge#esis o$ "a#dida& 7agi#itis. 6#$e"t 6mm%#1984;44:576.
M A-stract BGR'' G!ll te3t N
=$. !altarelli %G. De#ti&e 1'. Ma#"%so ,2. Beta&it5 o$ "a#dida& strai#s as i#$&%e#"ed
!5 te ost. 2a# J Mi"ro!io&1975;21:648.
MCrossRe1N MMedlineN M#e- o1 ScienceN
=&. S(it% CB. 2a#didiasis: patoge#esis. ost resista#"e. a#d predisposi#g $a"tors. New
Pork: Raven Press, 1%;&.
=?. %utler JE. =riedma# B. Mi&#er 12. <io&ogi"a& a#d "emi"a& "ara"teristi"s o$ to;i"
s%!sta#"es $rom 2a#dida a&!i"a#s. 6#$e"t 6mm%#1972;6:616.
M A-stract BGR'' G!ll te3t N
=>. Riipi L. 2ar&so# :. -%mo%r #e"rosis $a"tor 39-+=4 is i#d%"ed i# mi"e !5 2a#dida
a&!i"a#s: ro&e o$ -+= i# $i!ri#oge# i#"rease. 6#$e"t 6mm%#1990;58:2750.
M A-stract BGR'' G!ll te3t N
=;. K,"n-%+ung KJ. Bema# 8. Dood 2. et a&. De#eti" e7ide#"e $or ro&e o$
e;tra"e&&%&ar protei#ase i# 7ir%&e#"e o$ 2a#dida a&!i"a#s. 6#$e"t 6mm%#1985;49:571.
M A-stract BGR'' G!ll te3t N
=%. !lutsky B. <%$$o J. ,o&& 8?. *ig $reI%e#"5 s(it"i#g o$ "o&o#5 morpo&og5 i#
2a#dida a&!i"a#s. ,"ie#"e1985;230:666.
M A-stract BGR'' G!ll te3t N
$.. (eters"n DE. 9ra& "a#didiasis. 2&i# Deriatr Med1992;8:513>27.
MMedlineN
$1. Milne LJ. 2rompto# D1. <e"&ometaso#e dipropio#ate a#d oropar5#gea&
"a#didiasis. <MJ1974;iii:797>8.
$2. Garber GE. -reatme#t o$ ora& "a#dida m%"ositis i#$e"tio#s. 8r%gs1994;47:734>40.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$=. -+&an !%. Jo#te&& M. -reatme#t o$ a#g%&ar "ei&itis: te sig#i$i"a#"e o$ mi"ro!ia&
a#a&5sis. a#timi"ro!ia& treatme#t. a#d i#ter$eri#g $a"tors. '"ta 9do#to&
,"a#d1988;46:267>72.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$$. Epstein JB. -r%e&o7e :B. 6A%tA% 1B. 9ra& "a#didiasis: patoge#esis a#d ost de$e#se.
?e7 6#$e"t 8is1984;6:96>106.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$&. )rancis (. 0a&s -J. 2%rre#t approa"es to te ma#ageme#t o$ $%#ga& i#$e"tio#s i#
"a#"er patie#ts. 9#"o&og51992;6:81>92.
$?. Berg&an -J. '&teratio#s i# ora& mi"ro$&ora a#d patoge#esis o$ a"%te ora& i#$e"tio#s
d%ri#g remissio#-i#d%"tio# terap5 i# patie#ts (it a"%te m5e&oid &e%)aemia. ,"a#d J
6#$e"t 8is1991;23:355>66.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$>. .inane JA. M%&ti"e#tre st%d5 o$ $&%"o#aAo&e 7ers%s ora& po&5e#es i# te pre7e#tio# o$
$%#ga& i#$e"tio# i# "i&dre# (it aemato&ogi"a& or o#"o&ogi"a& ma&ig#a#"ies.
M%&ti"e#tre st%d5 gro%p. :%r J 2&i# Mi"ro!io& 6#$e"t 8is1994;13:330>7.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$;. (+illips (. Jem"o7 J. Mamood 0. et a&. 6tra"o#aAo&e "5"&ode;tri# so&%tio# $or
$&%"o#aAo&e re$ra"tor5 oropar5#gea& "a#didiasis i# '68,: "orre&atio# o$ "&i#i"a&
respo#se (it i# 7itro s%s"epti!i&it5. '68,1996;10:1369>76.
MCrossRe1N MMedlineN M#e- o1 ScienceN
$%. -d&an (A. -e e$$e"ti7e#ess o$ a# e#A5me "o#tai#i#g de#t%re "&ea#er. K%i#tesse#"e
6#t1992;23:187>90.
MMedlineN
&.. !ta##"rd GD. 're#dor$ D8. *%ggett ?. -e e$$e"t o$ o7er#igt dr5i#g a#d (ater
immersio# o# "a#dida& "o&o#isatio# a#d properties o$ "omp&ete de#t%res. J
8e#t1986;14:52>6.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&1. G,innet AJ. 2ap%to B. -e e$$e"ti7e#ess o$ %&traso#i" de#t%re "&ea#i#g: a s"a##i#g
e&e"tro# mi"ros"op5 st%d5. J Prostet 8e#t1983;50:20>5.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&2. Barkv"ll (. 'ttramada& '. :$$e"t o$ #5stati# a#d "&ore;idi#e dig&%"o#ate o#
2a#dida a&!i"a#s. 9ra& ,%rg 9ra& Med 9ra& Pato&1989;67:279>81.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&=. Barkv"ll (. *%r&e# <.2o#7e#tio#a& treatme#t o$ ora& "a#didiasis. +e( aspe"ts. +or
-a##&aege$ore# -id1989;99:116>19.
MMedlineN
&$. Epstein JB. Po&s)5 <. 9ropar5#gea& "a#didiasis: a re7ie( o$ its "&i#i"a& spe"tr%m
a#d "%rre#t terapies. 2&i# -er1998;20:40>57.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&&. Gupta AK. ,a%der 8+. ,ear +*. '#ti$%#ga& age#ts; a# o7er7ie(. Part 1. J 'm '"ad
8ermato&1994;30:677>98.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&?. Bennett .,. Anti,icro-ial agents, anti1!ngal agents. 6n: Kil,an AK, Rall #, Nies
AS, et a&, eds. Doodma# a#d Di&ma#Es te parma"o&ogi"a& !asis o$ terape%ti"s. ;t/
'd. New Pork: Perga,on Press, 1%%.: 11?&@;1.
&>. Epstein JB. =re&i" MM. Be +8. ?is) $a"tors $or oropar5#gea& "a#didiasis i#
patie#ts (o re"ei7e radiatio# terap5 $or ma&ig#a#t "o#ditio#s o$ te ead a#d #e").
9ra& ,%rg 9ra& Med 9ra& Pato&1993;76:169>74.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&;. Blatc+#"rd .R. -reatme#t o$ ora& "a#didiasis (it itra"o#aAo&e: a re7ie(. J 'm '"ad
8ermato&1990;23:565>7.
MCrossRe1N MMedlineN M#e- o1 ScienceN
&%. Heine G!. ,te7e#s 8,. Dree#spa# 8. =&%"o#aAo&e-resista#t "a#dida i# '68,
patie#ts. 9ra& ,%rg 9ra& Med 9ra& Pato&1993;76:711>15.
MCrossRe1N MMedlineN M#e- o1 ScienceN
?.. Re/ JH. ?i#a&di MD. P$a&&er M'. ?esista#"e o$ "a#dida spe"ies to $&%"o#aAo&e.
'#timi"ro! 'ge#ts 2emoter1995;39:1>8.
M GR'' G!ll te3t N
?1. Clar/son .,, #ort/ington HA, 'den 0C. Prevention o1 oral ,!cositis or oral
candidiasis 1or patients wit/ cancer receiving c/e,ot/erap2 9e3cl!ding /ead and neck
cancer:. /e Coc/rane Fi-rar2, 6ss!e $,2.... 031ord.
?2. Lu&breras %. 2%er7as-Mo#s C. Jara P. et a&. ?a#domised tria& o$ $&%"o#aAo&e 7ers%s
#5stati# $or te prop5&a;is o$ "a#dida i#$e"tio# $o&&o(i#g &i7er tra#sp&a#tatio#. J
6#$e"t 8is1996;174:583>8.
M A-stract BGR'' G!ll te3t N
?=. !c+u&an (. 2apps B. Pe#g D. et a&. 0ee)&5 $&%"o#aAo&e $or te pre7e#tio# o$
m%"osa& "a#didiasis i# (ome# (it *6C i#$e"tio#. ' ra#domised. do%!&e-!&i#d.
p&a"e!o "o#tro&&ed tria&. -err5 <eir# "omm%#it5 programs $or "&i#i"a& resear" o#
'68,. '## 6#ter# Med1997;126:689>96.
MMedlineN M#e- o1 ScienceN
?$. Mac(+ail LA. *i&to# J=. 8odd 2B. et a&. Prop5&a;is (it #5stati# pasti&&es $or *6C-
asso"iated ora& "a#didiasis. J '"I%ir 6mm%#e 8e$i" ,5#dr1996;12:470>6.
?&. (",derly 'G. =i#)&estei# 8M. =ei#!erg J. et a&. ' ra#domised tria& "ompari#g
$&%"o#aAo&e (it "otrimaAo&e tro"es $or te pre7e#tio# o$ $%#ga& i#$e"tio# i# patie#ts
(it ad7a#"ed %ma# imm%#ode$i"ie#"5 7ir%s i#$e"tio#. + :#g& J Med1995;332:700>
5.
MCrossRe1N MMedlineN M#e- o1 ScienceN
??. !&it+ D. Midg&e5 J. DaAAard <. ' ra#domised. do%!&e-!&i#d st%d5 o$ itra"o#aAo&e
7ers%s p&a"e!o i# te treatme#t a#d pre7e#tio# o$ ora& or oesopagea& "a#didiasis i#
patie#ts (it *6C i#$e"tio#. 6#t J 2&i# Pra"t1999;53:349>52.
MMedlineN M#e- o1 ScienceN
?>. )erretti GA. 's ?2. <ro(# '-. et a&. 2&ore;idi#e $or prop5&a;is agai#st ora&
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