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Vol	
  5,	
  No	
  1	
  (2017)	
  
ISSN	
  2167-­‐8677	
  (online)	
  

DOI	
  10.5195/d3000.2017.74	
  	
  

	
  

	
  

	
  

http://dentistry3000.pitt.edu	
  

	
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  articles	
  in	
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  journal	
  are	
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  Creative	
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  Attribution	
  4.0	
  United	
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  License.	
  

	
  
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  journal	
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  University	
  of	
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  cosponored	
  
by	
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  University	
  of	
  Pittsburgh	
  Press.	
  

	
  

Oral	
  candidiasis:	
  relation	
  to	
  systemic	
  diseases	
  and	
  medications	
  
Xiaozhu	
  Chu1	
  
	
  
	
  1University	
  of	
  Pi.sburgh,	
  School	
  of	
  Dental	
  Medicine

Abstract	
  

Background:	
  Oral	
  candidiasis	
  is	
  by	
  far	
  the	
  most	
  common	
  oral	
  fungal	
  infec!on	
  in	
  humans.	
  It	
  is	
  caused	
  by	
  the	
  fungal	
  or-­‐
ganism	
  Candida	
  albicans.	
  When	
  the	
  host	
  is	
  debilitated	
  by	
  other	
  diseases	
  and	
  condi!ons,	
  C.	
  albicans,	
  which	
  is	
  usually	
  a	
  
part	
  of	
  the	
  normal	
  oral	
  flora,	
  can	
  turn	
  pathogenic	
  and	
  invade	
  the	
  host	
  2ssue	
  to	
  cause	
  the	
  infec2on.	
  The	
  purpose	
  of	
  
this	
   paper	
   is	
   to	
   inves-gate	
   the	
   role	
   of	
   systemic	
   diseases	
   and	
  medica-ons	
   in	
   the	
   development	
   of	
   oral	
   candidiasis.	
  
Methods:	
  A	
  total	
  of	
  12	
  cases	
  with	
  code	
   indica2ng	
  oral	
  candidiasis	
  were	
  collected	
   from	
  the	
  University	
  of	
  Pi.sburgh	
  
School	
  of	
  Dental	
  Medicine	
  Dental	
  Registry	
  and	
  DNA	
  Repository.	
  The	
  systemic	
  diseases	
  and	
  medica*ons	
  were	
  descrip-­‐
!vely	
  analyzed.	
  Results:	
  50%	
  of	
  the	
  subjects	
  had	
  more	
  than	
  two	
  systemic	
  diseases.	
  The	
  most	
  prevalent	
  diseases	
  were	
  
mental	
   illnesses	
   (50%),	
   cardiovascular	
   diseases	
   (41.7%),	
   and	
   respiratory	
   system	
   diseases	
   (33.3%).	
   50%	
   of	
   subjects	
  
were	
  on	
  polypharmacy	
  therapies	
  and	
  75%	
  of	
  subjects	
  were	
  taking	
  medica-ons	
  that	
  may	
  contribute	
  to	
  oral	
  candidiasis.	
  
Among	
   the	
  medica!ons,	
   an!depressants	
   and	
   inhala#onal	
   cor#costeroids	
  may	
   have	
   strong	
   poten#als	
   to	
   cause	
   oral	
  
candidiasis.	
  Conclusion:	
  Oral	
  candidiasis	
  is	
  associated	
  with	
  having	
  systemic	
  diseases	
  and	
  intake	
  of	
  medica.on,	
  espe-­‐
cially	
  with	
  those	
  medica!ons	
  can	
  cause	
  xerostomia.	
  As	
  the	
  number	
  of	
  systemic	
  diseases	
  and	
  medica!ons	
  increases,	
  
the	
  risk	
  of	
  developing	
  oral	
  candidiasis	
  may	
  increase	
  too.	
  

Cita%on:	
  Chu,	
  X.	
  (2017)	
  Oral	
  candidiasis:	
  rela,on	
  
to	
   systemic	
  diseases	
  and	
  medica-ons.	
  Den$stry	
  
3000.	
  1:a001	
  doi:10.5195/d3000.2017.74	
  
Received:	
  	
  May	
  5,	
  2017	
  
Accepted:	
  	
  May	
  26,	
  2017	
  
Published:	
  	
  June	
  19,	
  2017	
  
Copyright:	
  ©2017	
  Chu,	
  X.	
  This	
  is	
  an	
  open	
  access	
  
ar!cle	
   licensed	
   under	
   a	
   Crea!ve	
   Commons	
  
A!ribu%on	
  Work	
  4.0	
  United	
  States	
  License.	
  
Email:	
  xic81@pi(.edu

	
  

Introduction	
  

Candidiasis	
  is	
  by	
  far	
  the	
  
most	
  common	
  oral	
  fungal	
  infec-­‐
tion	
  in	
  humans	
  and	
  has	
  a	
  variety	
  
of	
  clinical	
  manifestations.	
  It	
  is	
  the	
  
infection	
  caused	
  by	
  the	
  yeast-­‐like	
  
fungal	
  organism	
  Candida	
  albicans.	
  
As	
  many	
  other	
  pathogenic	
  fungi,	
  
C.	
  albicans	
  can	
  exist	
  in	
  two	
  
forms—the	
  yeast	
  form	
  and	
  the	
  
hyphal	
  form.	
  The	
  hyphal	
  form	
  is	
  
believed	
  to	
  be	
  able	
  to	
  invade	
  the	
  
host	
  tissue	
  and	
  cause	
  the	
  infec-­‐
tion.	
  [1]	
  C.	
  albicans	
  is	
  considered	
  
as	
  part	
  of	
  the	
  normal	
  oral	
  flora	
  
and	
  the	
  prevalence	
  of	
  oral	
  Can-­‐
dida	
  carriage	
  in	
  the	
  healthy	
  popu-­‐
lation	
  has	
  been	
  estimated	
  to	
  range	
  
from	
  23%	
  to	
  68%.	
  [2]	
  Candidiasis	
  
used	
  to	
  be	
  considered	
  as	
  only	
  an	
  
opportunistic	
  infection	
  but	
  it	
  has	
  
been	
  recognized	
  that	
  people	
  who	
  
are	
  otherwise	
  healthy	
  can	
  develop	
  
oral	
  candidiasis	
  too.	
  However,	
  as	
  a	
  

result	
  of	
  complex	
  host	
  and	
  organ-­‐
ism	
  interaction,	
  a	
  large	
  percentage	
  
of	
  patients	
  with	
  candidal	
  infection	
  
are	
  still	
  individuals	
  who	
  are	
  debili-­‐
tated	
  by	
  another	
  diseases	
  and	
  
conditions.	
  Many	
  risk	
  factors	
  can	
  
modify	
  an	
  individual’s	
  susceptibil-­‐
ity	
  to	
  oral	
  candidiasis,	
  including	
  
compromised	
  autoimmunity,	
  to-­‐
bacco	
  consumption,	
  hyposaliva-­‐
tion,	
  denture	
  wearing,	
  systemic	
  
disease,	
  and	
  medication.	
  

Compromised	
  autoimmunity	
  	
  

T-­‐cell	
  immunity	
  has	
  a	
  criti-­‐
cal	
  role	
  in	
  host	
  defense	
  against	
  
candidal	
  infection.	
  Chronic	
  muco-­‐
cutaneous	
  candidiasis	
  (including	
  
oral	
  candidiasis)	
  is	
  an	
  infectious	
  
phenotype	
  in	
  patients	
  with	
  inher-­‐
ited	
  or	
  acquired	
  T-­‐cell	
  deficiency.	
  
Studies	
  have	
  shown	
  that	
  Th17	
  cell,	
  
as	
  well	
  as	
  other	
  cell	
  expressing	
  ret-­‐
inoic	
  acid-­‐related	
  orphan	
  receptor	
  

γT	
  (RORγT),	
  produce	
  interleukin	
  
(IL)-­‐17,	
  which	
  has	
  an	
  essential	
  role	
  
in	
  defensing	
  against	
  candidal	
  in-­‐
fections	
  in	
  humans.	
  Four	
  genetic	
  
etiologies,	
  AR	
  IL-­‐17	
  receptor	
  A,	
  IL-­‐
17	
  receptor	
  C	
  and	
  ACT1	
  deficien-­‐
cies,	
  and	
  AD	
  IL-­‐17F	
  deficiency,	
  are	
  
identified	
  as	
  underlying	
  risk	
  fac-­‐
tors	
  for	
  chronic	
  mucocutaneous	
  
candidiasis.	
  Each	
  of	
  these	
  gene	
  
defects	
  has	
  a	
  direct	
  negative	
  effect	
  
on	
  IL-­‐17	
  signaling.	
  Patients	
  with	
  
these	
  gene	
  defects	
  may	
  have	
  se-­‐
verely	
  reduced	
  frequencies	
  of	
  cir-­‐
culating	
  IL-­‐17-­‐producing	
  T	
  cells.	
  Or	
  
they	
  may	
  produce	
  neutralizing	
  au-­‐
toantibodies	
  against	
  IL-­‐17.	
  As	
  a	
  
result,	
  the	
  ability	
  of	
  neutrophil	
  
cells	
  to	
  kill	
  C.	
  albicans	
  is	
  impaired	
  
and	
  chronic	
  mucocutaneous	
  can-­‐
didiasis	
  may	
  develop.	
  [3]	
  	
  

Tobacco	
  consumption	
  



E!ology	
  and	
  familial	
  inheritance	
  of	
  pleomorphic	
  adenomas	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.73	
  

	
  http://dentistry3000.pitt.edu	
  

	
  Tobacco	
  smoking	
  has	
  been	
  
considered	
  as	
  one	
  of	
  the	
  many	
  
factors	
  that	
  can	
  predispose	
  indi-­‐
viduals	
  to	
  oral	
  candidiasis.	
  Litera-­‐
tures	
  revealed	
  that	
  the	
  rate	
  of	
  oral	
  
candidal	
  carriage	
  in	
  tobacco	
  
smokers	
  is	
  significantly	
  higher	
  
than	
  in	
  non-­‐smokers.	
  Besides	
  C.	
  
albicans,	
  the	
  oral	
  carriage	
  of	
  other	
  
species	
  such	
  as	
  C.	
  glabrata,	
  C.	
  
dubliniensis	
  and	
  C.	
  tropicalis	
  are	
  
also	
  associated	
  with	
  smoking.	
  The	
  
observation	
  is	
  even	
  more	
  striking	
  
in	
  HIV-­‐infected	
  individuals.	
  It	
  has	
  
been	
  reported	
  that	
  HIV-­‐positive	
  
smokers	
  are	
  50	
  times	
  more	
  likely	
  
to	
  be	
  oral	
  candidal	
  infection	
  posi-­‐
tive	
  compared	
  to	
  HIV-­‐infected	
  
non-­‐smokers.	
  It	
  has	
  not	
  been	
  
cleared	
  yet	
  that	
  why	
  tobacco	
  con-­‐
sumption	
  can	
  increase	
  candidal	
  
carriage.	
  However,	
  there	
  are	
  stud-­‐
ies	
  suggesting	
  that	
  smoking	
  may	
  
lead	
  to	
  localized	
  epithelial	
  altera-­‐
tions,	
  which	
  facilitate	
  candidal	
  
colonization.	
  Another	
  hypothesis	
  
is	
  that	
  cigarette	
  smoke	
  may	
  con-­‐
tain	
  nutritional	
  factors	
  for	
  C.	
  albi-­‐
cans.	
  [4]	
  	
  

Hyposalivation	
  

Adequate	
  salivation	
  is	
  es-­‐
sential	
  for	
  oral	
  health,	
  since	
  it	
  pro-­‐
vides	
  support	
  for	
  the	
  microbial	
  
population	
  of	
  the	
  mouth,	
  while	
  at	
  
the	
  same	
  time	
  containing	
  antimi-­‐
crobial	
  products	
  that	
  control	
  these	
  
microbial	
  populations.	
  Histatin	
  5	
  
(Hst	
  5)	
  is	
  an	
  important	
  salivary	
  an-­‐
timicrobial	
  protein.	
  It	
  has	
  been	
  
shown	
  that	
  Hst	
  5	
  has	
  potent	
  and	
  
selective	
  antifungal	
  activity.	
  After	
  
coupling	
  with	
  the	
  carrier	
  molecule	
  
spermidine,	
  Hst	
  5	
  significantly	
  en-­‐
hances	
  the	
  killing	
  of	
  C.	
  albicans.	
  
[5]	
  Reduced	
  salivary	
  secretion,	
  as	
  
occurred	
  in	
  patients	
  with	
  Sjögren's	
  
syndrome,	
  can	
  re-­‐
sult	
  in	
  a	
  significant	
  
increase	
  in	
  oral	
  
candidal	
  carriage.	
  
The	
  prevalence	
  of	
  
oral	
  candidal	
  car-­‐
riage	
  among	
  
Sjögren's	
  syndrome	
  
patients	
  is	
  estimat-­‐
ed	
  to	
  range	
  from	
  
68%	
  to	
  100%,	
  com-­‐
pared	
  to	
  the	
  range	
  
from	
  23%	
  to	
  68%	
  in	
  
normal	
  population	
  
[2].	
  	
  

Denture	
  wearing	
  

	
  Denture	
  stomatitis	
  is	
  con-­‐
sidered	
  to	
  be	
  a	
  form	
  of	
  erythema-­‐
tous	
  candidiasis	
  and	
  it’s	
  a	
  common	
  
inflammatory	
  lesion	
  of	
  the	
  oral	
  
mucosa	
  covered	
  by	
  denture.	
  Epi-­‐
demiological	
  studies	
  show	
  a	
  
prevalence	
  of	
  denture	
  stomatitis	
  
among	
  denture	
  wearers	
  from	
  15%	
  
to	
  over	
  70%.	
  Etiological	
  factors	
  
include	
  poor	
  denture	
  hygiene,	
  
continual	
  and	
  nighttime	
  wearing	
  
of	
  removable	
  dentures,	
  accumula-­‐
tion	
  of	
  denture	
  plaque,	
  and	
  bacte-­‐
rial	
  and	
  yeast	
  contamination	
  of	
  
denture	
  surface.	
  All	
  together,	
  the-­‐
se	
  factors	
  may	
  increase	
  the	
  ability	
  
of	
  C.	
  albicans	
  to	
  colonize	
  both	
  
denture	
  and	
  oral	
  mucosal	
  surfac-­‐
es,	
  exerting	
  its	
  pathogenic	
  effort.	
  
[6]	
  	
  

Systemic	
  diseases	
  Many	
  systemic	
  
diseases	
  have	
  been	
  associated	
  
with	
  oral	
  candidiasis.	
  The	
  primary	
  
cause	
  is	
  attributed	
  to	
  the	
  de-­‐
creased	
  salivary	
  secretion,	
  leading	
  
to	
  the	
  reduced	
  concentration	
  of	
  
immunoglobulin	
  in	
  the	
  saliva	
  and	
  
less	
  efficient	
  humoral-­‐mediated	
  
host	
  defense	
  against	
  C.	
  albicans.	
  



E!ology	
  and	
  familial	
  inheritance	
  of	
  pleomorphic	
  adenomas	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.73	
  

	
  http://dentistry3000.pitt.edu	
  

For	
  patients	
  with	
  diabetes	
  melli-­‐
tus,	
  besides	
  the	
  reduced	
  salivary	
  
flow,	
  the	
  high	
  level	
  of	
  blood	
  glu-­‐
cose	
  also	
  plays	
  a	
  significant	
  role.	
  It	
  
is	
  associated	
  with	
  reduced	
  salivary	
  
pH	
  and	
  facilitates	
  oral	
  candidal	
  
overgrowth	
  and	
  colonization.	
  [7]	
  
As	
  an	
  opportunistic	
  infection,	
  oral	
  
candidiasis	
  is	
  also	
  associated	
  with	
  
a	
  wide	
  spectrum	
  of	
  systemic	
  dis-­‐
eases	
  that	
  suppress	
  the	
  host	
  auto-­‐
immunity	
  [8].	
  	
  

Medication	
  

Several	
  drugs	
  may	
  cause	
  
the	
  development	
  of	
  oral	
  candidia-­‐
sis	
  by	
  many	
  mechanisms.	
  The	
  
pharmacological	
  action	
  of	
  the	
  
broad-­‐spectrum	
  group	
  of	
  antibiot-­‐
ics	
  may	
  break	
  the	
  balance	
  within	
  
the	
  normal	
  oral	
  flora,	
  resulting	
  in	
  
the	
  overgrowth	
  of	
  C.	
  albicans.	
  
Drugs	
  such	
  as	
  corticosteroids	
  may	
  
suppress	
  either	
  the	
  nonspecific	
  
inflammatory	
  response	
  or	
  the	
  T-­‐
cell-­‐mediated	
  immunity,	
  which	
  
can	
  in	
  turn	
  predispose	
  individuals	
  
to	
  oral	
  candidiasis.	
  Drugs	
  that	
  
have	
  xerogenic	
  effects	
  can	
  cause	
  

oral	
  candidiasis	
  by	
  directly	
  reduc-­‐
ing	
  the	
  salivary	
  flow.	
  [8]	
  	
  

It	
  appears	
  that	
  the	
  associa-­‐
tion	
  between	
  oral	
  candidiasis	
  and	
  
systemic	
  diseases,	
  intake	
  of	
  medi-­‐
cations	
  has	
  been	
  well	
  established.	
  
The	
  purpose	
  of	
  this	
  study	
  is	
  to	
  
analyze	
  the	
  12	
  cases	
  collected	
  
from	
  the	
  University	
  of	
  Pittsburgh	
  
School	
  of	
  Dental	
  Medicine	
  Dental	
  
Registry	
  and	
  DNA	
  Repository,	
  and	
  
further	
  investigate	
  which	
  systemic	
  
diseases	
  and	
  medications	
  may	
  be	
  
potent	
  and	
  contribute	
  to	
  the	
  de-­‐
velopment	
  of	
  oral	
  candidiasis.	
  

Methods	
  

By	
  the	
  time	
  of	
  the	
  study	
  started,	
  
5,869	
  subjects	
  from	
  the	
  University	
  
of	
  Pittsburgh	
  School	
  of	
  Dental	
  
Medicine	
  Dental	
  Registry	
  and	
  DNA	
  
Repository	
  were	
  available	
  for	
  
analysis.	
  Since	
  the	
  September	
  of	
  
2006,	
  the	
  registry	
  invited	
  all	
  pa-­‐
tients	
  who	
  seek	
  treatment	
  at	
  the	
  
University	
  of	
  Pittsburgh	
  School	
  of	
  
Dental	
  Medicine	
  to	
  participate	
  and	
  
give	
  written	
  consent	
  to	
  authorize	
  
their	
  clinical	
  information	
  to	
  be	
  

used	
  for	
  academic	
  research	
  pur-­‐
pose.	
  12	
  cases	
  with	
  codes	
  indicat-­‐
ing	
  oral	
  candidiasis	
  were	
  collected	
  
from	
  the	
  5,869	
  subjects.	
  Com-­‐
pared	
  to	
  the	
  estimated	
  prevalence	
  
of	
  oral	
  candidal	
  carriage,	
  which	
  
ranges	
  from	
  23%	
  to	
  68%	
  in	
  the	
  
normal	
  population	
  [2],	
  the	
  number	
  
12	
  in	
  5,869	
  subjects	
  (0.2%)	
  seems	
  
to	
  be	
  unreasonably	
  small.	
  	
  This	
  can	
  
be	
  a	
  result	
  of	
  the	
  inconsistent	
  re-­‐
port	
  of	
  the	
  oral	
  lesions	
  by	
  clinical	
  
faculty	
  members	
  and	
  student	
  den-­‐
tists.	
  For	
  the	
  12	
  cases	
  with	
  oral	
  
candidiasis,	
  the	
  data	
  on	
  current	
  
(i.e.	
  time	
  of	
  examination)	
  systemic	
  
diseases/medical	
  conditions,	
  daily	
  
intake	
  of	
  prescribed	
  or	
  OTC	
  medi-­‐
cations	
  were	
  obtained	
  from	
  the	
  
registry.	
  The	
  total	
  number	
  of	
  sys-­‐
temic	
  diseases	
  and	
  medical	
  condi-­‐
tions	
  were	
  counted.	
  All	
  medica-­‐
tions	
  were	
  categorized	
  by	
  using	
  
the	
  internationally	
  approved	
  Ana-­‐
tomical	
  Therapeutic	
  Chemical	
  
(ATC)	
  classification	
  system.	
  And	
  
their	
  impacts	
  on	
  oral	
  hygiene	
  and	
  
dental	
  treatment	
  were	
  obtained	
  
from	
  the	
  website	
  Lexicomp	
  Online	
  
for	
  Dentistry	
  
(http://www.wolterskluwercdi.co
m/online-­‐for-­‐dentistry/).	
  All	
  data	
  
then	
  were	
  descriptively	
  analyzed.	
  	
  

Results	
  

Characteristics	
  of	
  the	
  12	
  study	
  
samples	
  are	
  presented	
  in	
  Table	
  1.	
  
Among	
  the	
  12	
  cases,	
  only	
  one	
  par-­‐
ticipant	
  	
  (8.3%)	
  did	
  not	
  report	
  any	
  
systemic	
  disease	
  or	
  medical	
  condi-­‐
tion.	
  For	
  the	
  other	
  11	
  cases,	
  the	
  
number	
  of	
  systemic	
  diseas-­‐
es/medical	
  conditions	
  reported	
  by	
  
the	
  participants	
  varied	
  from	
  1	
  to	
  8	
  
(33.3%	
  reporting	
  more	
  than	
  four	
  
diseases).	
  The	
  highest	
  scores	
  by	
  



E!ology	
  and	
  familial	
  inheritance	
  of	
  pleomorphic	
  adenomas	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.73	
  

	
  http://dentistry3000.pitt.edu	
  

number	
  of	
  diseased	
  individuals	
  
were	
  found	
  for	
  neurological	
  sys-­‐
tem	
  disease	
  (58.3%,	
  N	
  =	
  7)	
  includ-­‐
ing	
  depression,	
  epilepsy,	
  and	
  bipo-­‐
lar	
  disorder,	
  cardiovascular	
  system	
  
diseases	
  (41.7%,	
  N	
  =	
  5)	
  including	
  
mainly	
  hypertension,	
  irregular	
  
heartbeat,	
  and	
  heart	
  failure,	
  and	
  
respiratory	
  system	
  disease	
  (33.3%,	
  
N	
  =	
  4)	
  including	
  asthma	
  (Figure	
  1).	
  
Less	
  frequent	
  diagnosis	
  included	
  
gastrointestinal	
  tract	
  and	
  metabo-­‐
lite	
  diseases	
  (liver	
  diseases	
  and	
  
diabetes,	
  25%,	
  N	
  =	
  3),	
  neoplasms	
  
(neuroblastoma	
  and	
  unspecified	
  
throat	
  cancer,	
  16.7%,	
  N	
  =	
  2),	
  geni-­‐
tourinary	
  system	
  diseases	
  (kidney	
  
disease,	
  8.3%,	
  N	
  =	
  1),	
  and	
  muscu-­‐
loskeletal	
  system	
  diseases	
  (pros-­‐
thetic	
  joint,	
  8.3%,	
  N	
  =1).	
  

	
   All	
  the	
  study	
  subjects	
  had	
  
intake	
  of	
  prescribed	
  or	
  OTC	
  (over	
  
the	
  counter)	
  medications.	
  The	
  
number	
  of	
  medications	
  taken	
  on	
  
daily	
  basis	
  varied	
  from	
  1	
  to	
  14.	
  
Among	
  the	
  12	
  cases,	
  three	
  indi-­‐
viduals	
  took	
  only	
  one	
  medication	
  
(25%),	
  three	
  took	
  2-­‐4	
  medications	
  
(minor	
  polypharmacy,	
  25%),	
  and	
  
six	
  took	
  more	
  than	
  4	
  medications	
  
(major	
  polypharmacy,	
  50%).	
  The	
  
distribution	
  of	
  prescribed	
  medica-­‐
tion	
  (Figure	
  2)	
  shows	
  that	
  antihy-­‐
pertensive	
  agents,	
  antidepressant,	
  

systemic	
  hormones,	
  analgesics,	
  
and	
  agents	
  for	
  obstructive	
  airway	
  
diseases	
  predominated.	
  This	
  med-­‐
ication	
  pattern	
  reflected	
  the	
  dis-­‐
ease	
  burden	
  among	
  the	
  study	
  sub-­‐
jects.	
  

	
   Since	
  intake	
  of	
  medication	
  
is	
  an	
  important	
  risk	
  factor	
  to	
  the	
  
development	
  of	
  oral	
  candidiasis,	
  
all	
  the	
  medications	
  taken	
  by	
  study	
  
subjects	
  were	
  analyzed	
  by	
  their	
  
impacts	
  on	
  oral	
  cavity	
  environ-­‐
ment	
  and	
  dental	
  treatment.	
  Based	
  
on	
  the	
  information	
  obtained	
  from	
  
the	
  website	
  Lexicomp	
  Online	
  for	
  
Dentistry,	
  all	
  medications	
  that	
  can	
  
cause	
  xerostomia,	
  change	
  in	
  sali-­‐
vation,	
  candidal	
  infection	
  were	
  
labeled	
  as	
  “may	
  contribute	
  to	
  oral	
  
candidiasis”.	
  The	
  63	
  medications	
  
were	
  fitted	
  into	
  22	
  categories	
  
based	
  on	
  the	
  Anatomical	
  Thera-­‐
peutic	
  Chemical	
  (ATC)	
  classifica-­‐
tion	
  system.	
  Among	
  the	
  predomi-­‐
nated	
  categories,	
  antidepressant	
  
contained	
  10	
  medications,	
  all	
  of	
  
which	
  may	
  contribute	
  to	
  the	
  de-­‐
velopment	
  of	
  oral	
  candidiasis.	
  It	
  
had	
  been	
  followed	
  by	
  agents	
  for	
  
obstructive	
  airway	
  diseases	
  and	
  
analgesics,	
  which	
  had	
  5	
  out	
  of	
  9	
  
(55.5%)	
  and	
  2	
  out	
  of	
  7	
  (28.6%)	
  
medications,	
  respectively,	
  fell	
  into	
  
the	
  category	
  “may	
  contribute	
  to	
  

oral	
  candidiasis”.	
  The	
  other	
  cate-­‐
gories,	
  which	
  contained	
  medica-­‐
tions	
  that	
  may	
  contribute	
  to	
  oral	
  
candidiasis,	
  included	
  anticonvul-­‐
sant,	
  antimanic,	
  antiulcer,	
  hypnot-­‐
ic	
  and	
  immunosuppressant	
  agents.	
  
(Figure	
  3)	
  Among	
  all	
  12	
  subjects,	
  9	
  
(75%)	
  were	
  taking	
  medications	
  
that	
  fitting	
  into	
  the	
  “	
  may	
  contrib-­‐
ute	
  to	
  oral	
  candidiasis”	
  category.	
  

Discussion	
  and	
  Conclusion	
  

In	
  my	
  study,	
  50%	
  of	
  the	
  
study	
  samples	
  were	
  having	
  three	
  
or	
  more	
  than	
  three	
  systemic	
  dis-­‐
eases,	
  which	
  is	
  in	
  agreement	
  with	
  
previous	
  observations	
  suggesting	
  
that	
  having	
  multiple	
  systemic	
  dis-­‐
eases	
  and	
  medical	
  conditions	
  is	
  
associated	
  with	
  oral	
  candidiasis.	
  
The	
  most	
  frequent	
  diseases	
  involv-­‐
ing	
  in	
  this	
  study	
  were	
  mental	
  dis-­‐
eases	
  including	
  depression	
  and	
  
bipolar	
  disorder,	
  and	
  obstructive	
  
airway	
  diseases	
  including	
  asthma,	
  
chronic	
  obstructive	
  pulmonary	
  
disease,	
  and	
  an	
  unspecified	
  lung	
  
disease.	
  Those	
  are	
  not	
  diseases	
  
that	
  directly	
  cause	
  change	
  in	
  sali-­‐
vary	
  secretion	
  and	
  salivary	
  glands	
  
or	
  those	
  suppress	
  the	
  host	
  auto-­‐
immunity.	
  Their	
  primary	
  associa-­‐
tion	
  with	
  the	
  development	
  of	
  oral	
  
candidiasis	
  is	
  more	
  attributed	
  to	
  
the	
  medications	
  that	
  were	
  taken	
  
by	
  subjects	
  to	
  treat	
  the	
  systemic	
  
diseases.	
  However,	
  it	
  may	
  not	
  be	
  
true	
  for	
  one	
  subject	
  who	
  was	
  di-­‐
agnosed	
  as	
  insulin-­‐dependent	
  dia-­‐
betes.	
  On	
  the	
  morning	
  the	
  dental	
  
examination	
  was	
  performed,	
  the	
  
subject	
  reported	
  that	
  her	
  blood	
  
glucose	
  level	
  was	
  235mg/dl.	
  Com-­‐
pared	
  with	
  the	
  preferable	
  goal	
  of	
  a	
  
good	
  diabetic	
  management,	
  which	
  
is	
  close	
  to	
  the	
  70	
  to	
  120mg/dl	
  



E!ology	
  and	
  familial	
  inheritance	
  of	
  pleomorphic	
  adenomas	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.73	
  

	
  http://dentistry3000.pitt.edu	
  

range,	
  it’s	
  safe	
  to	
  assume	
  the	
  dia-­‐
betes	
  was	
  not	
  well	
  controlled.	
  Be-­‐
sides	
  all	
  other	
  drugs	
  she	
  took,	
  the	
  
level	
  of	
  blood	
  glucose	
  may	
  play	
  an	
  
important	
  role	
  in	
  the	
  development	
  
of	
  her	
  oral	
  candidiasis.	
  It	
  has	
  been	
  
reported	
  that	
  highest	
  rate	
  of	
  C.	
  
albicans	
  colonization	
  occurs	
  in	
  di-­‐
abetic	
  patients	
  with	
  poor	
  glycemic	
  
control.	
  In	
  addition,	
  subjective	
  oral	
  
dryness	
  is	
  a	
  frequent	
  complaint	
  
among	
  diabetic	
  patients.	
  [7]	
  

	
   The	
  five	
  most	
  commonly	
  
reported	
  medications	
  included	
  
systemic	
  hormones,	
  antidepres-­‐
sants,	
  antihypertensive	
  agents,	
  
agents	
  for	
  obstructive	
  airway	
  dis-­‐
eases,	
  and	
  analgesics.	
  Among	
  the	
  
five	
  categories,	
  the	
  association	
  
between	
  antidepressants	
  and	
  oral	
  
candidiasis	
  has	
  been	
  well	
  estab-­‐
lished.	
  All	
  salivary	
  secretion	
  is	
  me-­‐
diated	
  by	
  neurotransmitters	
  and	
  
relies	
  on	
  stimulations	
  from	
  the	
  
autonomic	
  nervous	
  system.	
  Stimu-­‐
lation	
  of	
  the	
  cholinergic	
  system	
  
leads	
  to	
  secretion	
  of	
  “watery”	
  sali-­‐
va	
  thus	
  anticholinergic	
  drugs	
  re-­‐
duce	
  the	
  secretion.	
  Many	
  antide-­‐
pressants	
  have	
  an	
  anticholinergic	
  
effect	
  that	
  blocks	
  the	
  peripheral	
  
cholinergic	
  innervation,	
  resulting	
  
in	
  hyposalivation	
  and	
  xerostomia.	
  
[9]	
  Among	
  other	
  agents	
  used	
  to	
  
manage	
  obstructive	
  airway	
  dis-­‐
eases,	
  corticosteroids	
  are	
  widely	
  
used	
  as	
  oral	
  inhalers	
  due	
  to	
  its	
  an-­‐
ti-­‐inflammatory	
  and	
  immunosup-­‐
pressive	
  properties.	
  However,	
  the	
  
repeated	
  use	
  of	
  corticosteroids	
  
oral	
  inhalers	
  also	
  suppress	
  an	
  indi-­‐
vidual’s	
  resistance	
  to	
  candidal	
  in-­‐
fection	
  by	
  suppressing	
  either	
  the	
  
nonspecific	
  inflammatory	
  re-­‐
sponse	
  or	
  the	
  T-­‐cell-­‐mediated	
  im-­‐
munity,	
  which	
  predispose	
  the	
  oral	
  

inhaler	
  users	
  to	
  oral	
  candidiasis.	
  
[10]	
  In	
  this	
  study,	
  75%	
  of	
  the	
  study	
  
subjects	
  was	
  on	
  polypharmacy	
  
therapies	
  and	
  took	
  medications	
  
that	
  had	
  xerogenic	
  or	
  immuno-­‐
suppressive	
  properties,	
  including	
  
10	
  antidepressants	
  and	
  2	
  inhala-­‐
tional	
  corticosteroids.	
  The	
  finding	
  
is	
  in	
  line	
  with	
  previous	
  studies	
  in-­‐
dicating	
  that	
  intake	
  of	
  medications	
  
is	
  an	
  important	
  risk	
  factor	
  for	
  the	
  
development	
  of	
  oral	
  candidiasis.	
  

	
   When	
  treating	
  patients	
  
with	
  systemic	
  diseases	
  and	
  taking	
  
multiple	
  medications,	
  the	
  dental	
  
professionals	
  must	
  be	
  able	
  to	
  rec-­‐
ognize	
  the	
  early	
  signs	
  and	
  symp-­‐
toms	
  of	
  oral	
  candidiasis	
  and	
  adjust	
  
the	
  treatment	
  plans	
  to	
  meet	
  the	
  
special	
  needs	
  of	
  those	
  patients	
  
and	
  prevent	
  the	
  development	
  of	
  
oral	
  candidiasis.	
  

	
   In	
  conclusion,	
  based	
  on	
  the	
  
descriptive	
  analysis	
  of	
  12	
  cases	
  
with	
  oral	
  candidiasis,	
  the	
  findings	
  
support	
  the	
  concept	
  that	
  the	
  de-­‐
velopment	
  of	
  oral	
  candidiasis	
  is	
  
associated	
  with	
  having	
  multiple	
  
systemic	
  diseases	
  and	
  intake	
  of	
  
medications.	
  

Acknowledgements	
  

Data	
  from	
  the	
  study	
  was	
  obtained	
  
from	
  the	
  University	
  of	
  Pittsburgh	
  
School	
  of	
  Dental	
  Medicine	
  Dental	
  
Registry	
  and	
  DNA	
  Repository,	
  
which	
  is	
  supported	
  by	
  the	
  Univer-­‐
sity	
  of	
  Pittsburgh	
  School	
  of	
  Dental	
  
Medicine.	
  

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