Microsoft Word - D3000 2017.docx   Vol  5,  No  1  (2017)   ISSN  2167-­‐8677  (online)   DOI  10.5195/d3000.2017.59           http://dentistry3000.pitt.edu     New  articles  in  this  journal  are  licensed  under  a  Creative  Commons  Attribution  4.0  United  States  License.     This  journal  is  published  by  the  University  Library  System,  University  of  Pittsburgh  as  part  of  its  D-­‐Scribe  Digital  Publishing  Program  and  is  cosponored   by  the  University  of  Pittsburgh  Press.     Oral  mucosal  lesions  in  patients  with  pemphigus  and  pemphigoid   skin  diseases:  a  cross  sectional  study  from  southern  India     Arvind  Babu  Rajendra  Santosh1,    Venkat  Ramana  Reddy  Baddam2,  Chigurupa(  Anuradha  3,  Chandrashekar  Poosarla2      1Den$stry  Programme,  Faculty  of  Medical  Sciences,  The  University  of  the  West  Indies,  Mona,  Jamaica,  West  Indies.    2Department  of  Oral  and  Maxillofacial  Pathology,  SIBAR  Ins'tute  of  Dental  Sciences,  Guntur,  Andhra  Pradesh,  India.   3Department  of  Oral  and  Maxillofacial  Pathology,  Panineeya  Ins*tute  of  Dental  Sciences  and  Research  Centre,  Hyderabad,  India.   Abstract   Objec&ve:To  assess  the  prevalence  of  oral  mucosal  lesions  in  pa3ents  with  pemphigus  and  pemphigoid  diseases  from   Southern  India.  Design  and  Methods:  A  cross-­‐sec$onal  hospital  based  study  was  conducted  from  August  2010  to  July   2011.  Pa(ents  with  confirmed  pemphigus  and  pemphigoid  skin  disease  were  selected  and  informed  to  par(cipate  in   the  study.  Oral  examina2on  of  all  par2cipants  were  done  to  document  site  and  type  of  oral  manifesta3on  and  diag-­‐ nos$c  procedures  such  as  histopathological  and  Immunofluorescence  methods  were  performed  to  confirm  the  diag-­‐ nosis.  Demographic  details  such  as  age,  gender  and  occupa5on  were  also  documented.  The  results  of  the  study  were   analyzed  by  SPSS  so.ware  version  19.0  (Armonk,  NY)  and  presented  as  descripBve  staBsBcs.  Results:  Sixty  percent  of   the  pa'ents  exhibited  oral  mucosal  manifesta'ons.  A  higher  female  (86.66%)  predilec'on  of  autoimmune  blistering   disease  was  observed  in  the  study.  A  slightly  higher  number  of  pemphigoid  pa8ents  (53.33%,  16  out  of  30)  were  re-­‐ ported  than  pemphigus  (46.66%,  14  out  of  30  cases).  The  most  common  subtypes  of  pemphigus  is  Pemphigus  vulgaris   71%  (10  out  of  14)  among  pemphigus,  and  bullous  pemphigoid  87.5%(14  out  of  16)  among  pemphigoid.  Buccal  muco-­‐ sa   (92.85%)   is   the  most  common  site   in  pemphigus  pa7ents,  where  as  hard  palate   (12.5%)   is  mostly  commonly   re-­‐ ported   site   in  pemphigoid  pa/ents.   Ini/al   involvement  of  oral  'ssue   in  disease  process  was  observed   in  78.57%  of   pemphigus,  and  12.5%  of  pemphigoid  pa5ents.  Conclusion:  Oral  mucosal   lesions  are  more   frequently  associated   in   pemphigus  pa+ents.  Oral  mucosal  lesions  are  the  ini+al  site  of  disease  process  in  pemphigus  pa+ents.  The  significance   of  diagnosis  of  oral  lesions  at  earlier  stage  of  disease,  specifically  pemphigus  may  help  in  early  interven7on  of  disease   and  help  to  reduce  the  morbidity  and  mortality  state.  The  study  emphasizes  mul6disciplinary  approach  in  diagnosis   and  management  of  both  pemphigus  and  pemphigoid.       Cita%on:  Santosh,  et  al.  (2017)     Oral  mucosal  lesions  in  pa/ents  with  pemphigus   and  pemphigoid  skin  diseases:  a  cross  sec1onal   study  from  southern  India.   Den$stry  3000.  1:a001   doi:10.5195/d3000.2017.59   Received:    August  12,  2016   Accepted:    February  14,  2017   Published:    March  28,  2017   Copyright:  ©2017  Santosh,  et  al.  This  is  an  open   access   ar!cle   licensed   under   a   Crea!ve   Com-­‐ mons   A"ribu"on   Work   4.0   United   States   Li-­‐ cense.   Email:  arvindbabu2001@gmail.com   Introduction   Mucocutaneous  are  a   group  of  disorders  primarily  ob-­‐ served  in  dermatology  practice.   Oral  mucosal  manifestations  may   be  an  initial  presentation,  most   important  clinical  symptom,  or   often  times  it  is  the  only  sign  of   such  disease  process.  In  most  in-­‐ stances,  the  mucocutaneous  dis-­‐ orders  are  known  to  affect  the   skin  and  mucus  membranes,  with   severe  clinical  manifestations  af-­‐ fecting  the  oral  mucosal  mem-­‐ branes.  The  oral  presentations  of   such  mucocutaneous  are  primarily   as  fluid  filled  blister  such  as  vesi-­‐ cle,  bullae,  erosive  or  ulcerative   conditions.1  Early  identification  of   oral  manifestation  and  correlation   with  dermatological  condition  may   help  in  diagnosis,  treatment  plan-­‐ ning  and  prognosis.     Pemphigus  is  one  of  the   few  potentially  fatal  autoimmune   diseases  affecting  predominantly   skin  and  oral  mucosa.  It  is  an  auto-­‐ immune  disease  characterized  by   the  clinical  presentation  of  fluid   filled  blisters,  and  raw  eroded  sur-­‐ faces  when  the  blister  burst  open.   The  disease  had  been  considered   to  be  associated  with  the  autoan-­‐ tibodies  (IgG)  and  complement   factor  (C3)  against  the  deso-­‐ mosome  structure  at  the  intercel-­‐ lular  components  of  epithelium   and  epidermis.  The  autoimmune   process  that  destructs  the  inter-­‐ cellular  proteins  such  as  desmo-­‐ somes  is  histologically  termed  as   acantholysis.  The  acantholysis  of   epithelial  or  epidermal  cells  are   responsible  for  the  resultant  cleft   formation  above  the  basal  layer.   Epithelial  or  epidermal  blisters  or   bullous  presentation  are  the  hall-­‐ mark  of  this  disease,  however  ero-­‐ sions  or  ulcers  over  the  mucosal   membranes  and  skin  or  epidermis   are  also  classical  clinical  presenta-­‐ tion  of  this  disease  process.2  The   most  commonly  oral  sites  are  pal-­‐ ate,  labial  mucosa,  buccal  mucosa,   ventral  surface  of  tongue,  and  gin-­‐ Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   2   gival.  Pemphigus  includes  three   primary  clinically  recognizable   subsets  such  as  pemphigus  vulgar-­‐ is,  pemphigus  foliaceus,  and  para-­‐ neoplastic  pemphigus.3  Histologi-­‐ cally  the  lesion  is  identified  based   on  the  supra  basal  or  intra  epithe-­‐ lial  cleft  formation,  with  acantho-­‐ lytic  or  tzanck  cells.  Clinical  and   histopathological  findings  are  usu-­‐ ally  confirmed  by  direct  or  indirect   Immunofluorescence  methods.1   Pemphigoid  is  an  autoimmune   disease  characterized  by  the  ve-­‐ siculo-­‐bullous  manifestations  over   skin  and  mucosal  surfaces.  The   two  distinct  clinical  forms  of  this   disease  includes  bullous  and  cica-­‐ tricial  pemphigoid.4    The  disease   process  is  known  to  be  mediated   by  autoantibodies  directed  against   components  of  basement  mem-­‐ brane  zone.  The  disease  is  clinical-­‐ ly  recognized  as  bullous  lesions,   which  may  rupture  to  produce  ul-­‐ cers.  The  healing  is  usually  accom-­‐ panied  by  scaring  in  cicatricial  type   of  pemphigoid,  and  not  in  bullous   forms.  Histologically  the  lesion  is   identified  based  on  the  sub-­‐basal   cleft  formation.  Clinical  and  histo-­‐ pathological  findings  are  usually   confirmed  by  direct  or  indirect   Immunofluorescence  methods.1,5     The  main  aim  of  the  present  study   is  to  assess  the  prevalence  of  oral   mucosal  lesions  in  patients  with   pemphigus  and  pemphigoid  dis-­‐ eases  from  Southern  India.     Methods     The  study  was  approved  by   ethics  committee/institutional  re-­‐ view  board  of  the  SIBAR  Institute   of  Dental  Sciences,  Guntur.  The   study  obtained  verbal  consent   from  all  participants  involved;  also   ethics  committee/institutional  re-­‐ view  board  of  the  SIBAR  Institute   of  Dental  Sciences  approval  was   received  on  the  consent  form.  The   present  study  has  been  conducted   in  full  accordance  with  the  World   Medical  Association  Declaration  of   Helsinki.     Sampling,  inclusion  and  exclusion  crite-­‐ ria     The  study  was  conducted   at  the  Dermatology  department  at   Government  General  Hospital,   Guntur,  Andhra  Pradesh,  India   from  the  period  August  2010,  to   July  2011.  All  the  patients  with   pemphigus  or  pemphigoid  disease   were  invited  to  participate  in  the   present  study.  The  participants   who  provided  the  consent  for  clin-­‐ ical  evaluation,  and  histopatholog-­‐ ical  diagnostic  procedures  were   included  in  the  study.  The  confi-­‐ dentiality  of  the  patients’  clinical,   histological,  and  photographic  de-­‐ tails  was  maintained.  The  study   was  conducted  by  a  qualified  den-­‐ tal  surgeon,  and  institutional  eth-­‐ ics  approval  was  received.  During   the  clinical  examination,  patients’   socio-­‐demographic  details  such  as   age,  gender,  occupation,  marital   status,  residential  address,  and   other  oral  hygiene  habits,  primary   site  of  disease  manifestations,  dis-­‐ ease  symptoms,  and  other  under-­‐ Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   3   lying  medical  conditions  (if  any)   were  obtained.  The  patients’  con-­‐ ditions  such  as  pemphigus  and   pemphigoid  were  diagnosed  by   consultant  dermatologist  of  the   hospital,  and  dental  surgeon  per-­‐ formed  oral  examination  and  bi-­‐ opsy  procedure  for  histological   and  Immunofluorescence  exami-­‐ nation.  Examining  dental  surgeon   performed  excisional  biopsy  on  all   the  study  participants.  Tissue  was   anesthetized  using  Lignocaine  HCL   2%  and  biopsy  procedure  was   done  using  scalpel  blade  no.  15.   The  details  of  the  clinical  presen-­‐ tation  of  skin  and  oral  mucosa   were  recorded  in  the  Microsoft   Excel  data  sheet  for  software   analysis.  The  final  histopathologi-­‐ cal  diagnosis  of  the  oral  biopsies   was  given  by  an  expert  oral  and   maxillofacial  pathologist  at  SIBAR   Institute  of  Dental  Sciences,  Gun-­‐ tur,  Andhra  Pradesh,  India.       Histopathological  examination  (Hema-­‐ toxylin  and  eosin  stain;  and  Immunoflu-­‐ orescence)     Oral  tissue  biopsies  were   taken  from  the  lesional  areas.  The   tissue  was  fixed  in  formalin  solu-­‐ tion  and  eventually  embedded  in   paraffin  wax.  The  microtomed  tis-­‐ sue  sections  were  statined  with   hematoxylin  and  eosin  (H  and  E)   and  examined  using  bright  field   microscope.  To  evaluate  the  pres-­‐ ence  of  autoantigens  in  the  oral   tissue  sections,  an  Immunofluo-­‐ rescence  procedure  was  conduct-­‐ ed  for  the  part  of  biopsied  speci-­‐ men.  The  tissues  for  Immunofluo-­‐ rescence  procedure  were  stored  in   Michel’s  medium.  Immunofluores-­‐ cence  methods  for  detection  of   auto-­‐antibodies  in  the  tissue  sec-­‐ tions  were  performed  with   thin(less  than  6  micrometer)  cryo-­‐ stat  sections.  The  sections  were   washed  with  0.1M  Phosphate   buffered  saline  with  three  changes   over  a  period  of  thirty  minutes.   Excess  of  the  solution  were   drained  and   covered  with   diluted  conju-­‐ gate  and  al-­‐ lowed  to  react   for  thirty   minutes  at   room  temper-­‐ ature.  Then   sections  were   mounted  by   using  1,4-­‐DIazabicyclooctance   DABCO  solution.  The  preparations   were  examined  using  fluorescent   microscope.     Clinical  and  histopathologi-­‐ cal  data  were  documented  in  the   prescribed  forms.  Data  on  clinical   and  histopathological  details  were   documented  in  Microsoft  2007   Excel  spreadsheets,  followed  by   tabulations  of  various  parameters.   The  descriptive  statistical  analysis   using  SPSS  software  version  19.0   (Armonk,  NY)  was  done  for   presentation  of  study  results.     Results   Age,  gender  and  occupation  de-­‐ mographics  of  the  study  participants   A  total  of  30  patients  were   examined  and  consisted  of  male  4   (13.33%)  and  female  26  (86.66%)   with  pemphigus  or  pemphigoid   had  participated  in  the  present   study  during  the  period  of  August   2011  to  July  2012  (Figure  1a).  In   pemphigus,  1  male  (7.14%)  and  13   female  (92.85%)  patients  were  ob-­‐ served  (Figure  1b).  Whereas  in   Pemphigoid,  3  male  (18.75%)  and   13  female  (81.25%)  were  reported   (Figure  1c).  Female  predilection   was  observed  in  both  pemphigus   and  Pemphigoid.  The  patients  in   Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   4   the  total  study  ranged  between   21-­‐70  years.  The  mean  age  of  the   Pemphigus  patients  were  42  years,   and  pemphigoid  was  48  years.   (Figure  2)  Analysis  of  the  partici-­‐ pants  occupation  showed  farmers   were  11(36.6%),  unemployed   9(30%),  drivers  4(13.33%)  and  self   employed  or  business  6(20%).   (Figure  3).     Prevalence  of  clinical  sub  types  and  oral   mucosal  involvement  in  pemphigus  and   pemphigoid     The  analysis  of  the  clinical   subtypes  of  pemphigus  and  pem-­‐ phigus  in  the  study  population  re-­‐ vealed  that,  pemphigus  vulgaris   10(71.42%),  Pemphigus  vegetans  2   (14.28%),  and  Pemphigus  foliaceus   2(14.28%);  and  Bullous  pemphi-­‐ goid  14(87.5%),  and  Cicatricial   pemphigoid  2(12.5%)  was  ob-­‐ served.  (Figure  4)  A  total  of   53.33%  (16  out  of  30)  patients   showed  oral  mucosal  manifesta-­‐ tions.  Higher  prevalence  of  oral   mucosal  lesions  were  observed  in   Pemphigus  14(100%),  and  in  pem-­‐ phigoid  2(12.5%)  (Figure  5)     Initial  site  involvement  of  skin  versus   oral  mucosa  in  pemphigus  and  pemphi-­‐ goid   A  to-­‐ tal  of  60%   (18  out  of   30)  patients   has  skin  as  a   initial  site  of   manifesta-­‐ tion,  and   40%  (12  out   of  30)  as   oral  mucosa   as  a  initial   site  of  manifestation  of  diseases.  A   higher  frequency  of  oral  mucosa   as  a  initial  site  of  manifestation   was  observed  in  pemphigus  pa-­‐ tients  11(78.57%);  and  pemphi-­‐ goid  1(6.25%)  (Figure  6)     Oral  mucosal  site  geography  in  pemphi-­‐ gus  and  pemphigoid   Buccal  mucosa  was  the   most  common  site  for  pemphigus   13(92.85%),  and  hard  palate  was   most  common  site  among  patients   with  pemphigoid  2  (12.5%).  Most   of  the  patients  had  presented  the   oral  lesions  with  more  than  one   site.  (Figure  7)   Immunofluorescence  characterization  in   pemphigus  and  Pemphigoid   In  pemphigus,  direct  Im-­‐ munofluores-­‐ cence  method   demonstrated   the  presence  of   IgG  and  C3   components.  All   the  patients   (100%)  showed   the  positivity  for   IgG  autoanti-­‐ body,  and  8  out   of  13  (61.53%)   patients  showed   C3  component  positivity.  Whereas   in  Pemphigoid,  direct  immunoflu-­‐ orescent  method  demonstrated   the  positivity  for  IgG  and  C3  com-­‐ ponents  in  basement  membrane   zones  of  two  oral  tissue  speci-­‐ mens.  (Figure  8)     Mortality  in  pemphigus  and  pemphigoid     Mortality  rate  of  the  pem-­‐ phigus  in  the  present  study  is  be   14.28%  (2  out  of  14),  a  patient   with  pemphigus  foliaceus  and  an-­‐ other  patient  with  pemphigus   vegetans.  No  death  observed  in   pemphigoid  patients  during  study   period.     Discussion   Pemphigus  and  pemphi-­‐ goid  are  considered  to  be  a  pre-­‐ dominantly  a  dermatological  con-­‐ dition.  Oral  manifestations  of  the-­‐ se  diseases  provides  a  great   chance  to  dental  surgeons  to  iden-­‐ tify  the  disease  at  earlier  stage,   and  help  in  early  intervention  and   eventually  for  a  better  prognosis.6   The  present  study  showed  a  high-­‐ er  prevalence  of  pemphigus  and   pemphigoid  in  females.  Similar   report  was  published  in  a  study   from  Mexico.7  The  present  study   Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   5   showed  a  higher  prevalence   among  farmers  and  laborers,  and   our  results  were  consistent  with   previously  published  study  from   kerala  population  of  India.8  The   peak  age  of  pemphigus  and  pem-­‐ phigoid  disease  in  the  present   study  has  fall  between  the  31-­‐40   years,  with  the  mean  age  of  42   years  for  pemphigus  and  48  years   for  pemphigoid.  Ajith  Kumar  etal.,   in  their  study  reported  that  inci-­‐ dence  of  pemphigus  is  higher  in   the  age  group  between  40-­‐50   years  from  Thrissur  district  of  Ker-­‐ ala,  India.9           The  prevalence  of  pemphi-­‐ gus  in  the  present  study  is  46.66%,   with  higher  prevalence  of  pemphi-­‐ gus  vulgaris  (71.42%)  among  the   various  clinical  subtypes  of  pem-­‐ phigus,  which  is  followed  by  Pem-­‐ phigus  vegetans  (14.28%)  and   Pemphigus  foliaceus  (14.28%).   However,  the  present  study  had   not  reported  any  paraneoplastic   pemphigus.  Mortality  rate  of  the   pemphigus  in  the  present  study  is   considered  to  be  14.28%  (2  out  of   13),  a  patient  with  pemphigus  foli-­‐ aceus  and  another  patient  with   pemphigus  vegetans  had  died  due   to  the  severity  of  the  disease.  Lan-­‐ gan  et  al  in  2008,  mentioned  that   mortality  rate  of  pemphigus  may   range  as  4.8%  and  54%.10  Oral  mu-­‐ cosal  manifestation  (fluid  filled   blisters  or  bullous,  erosions)  was   observed  in  all  the  patients,  and   most  prevalent  oral  site  was  buc-­‐ cal  mucosa  (92.85%),  which  is  fol-­‐ lowed  by  Soft  palate  (71.42%),   lower  lip  (42.85%),  tongue   (35.71%),  labial  mucosa  (28.57%),   floor  of  mouth  (21.42%),  upper  lip   (14.28%),  gingival  (14.28%),  and   hard  palate  (7.14%).  78.57%  (11   out  of  14)    patients  had  reported   that,  oral  mucosal  manifestation   as  a  primary  site  of  disease  pro-­‐ cess.  In  the  published  reports  of   Thorakkal  Shamim  et  al.,  revealed   that  pemphigus  vulgaris  is  the   most  common  subtype,  with  the   primary  site  of  oral  mucosa  in   53.52%  of  cases.  The  most  com-­‐ monly  affected  site  was  buccal   mucosa,  followed  by  palate,  lips,   tongue,  floor  of  mouth  and  gingi-­‐ val.11     The  histopathological  ex-­‐ amination  of  the  pemphigus  tissue   was  characterized  by  the  presence   of  acantholytic  epithelial  cells  with   resultant  cleft  formation  within   the  oral  epithelium.  Direct  Immu-­‐ nofluorescence  method  demon-­‐ strated  the  presence  of  IgG  and  C3   components.  All  the  patients   (100%)  showed  the  positivity  for   IgG  autoantibody,  and  8  out  of  13   (61.53%)  patients  showed  C3   component  positivity.  Anuradha  et   al.,  in  2011  stated  that  direct  Im-­‐ munofluorescence  of  pemphgius   showed  deposition  of  IgG  was  ob-­‐ served  in  80%  and  14%  of  cases   showed  C3  positivity.12     The  frequency  of  pemphi-­‐ goid  in  the  present  study  is   53.33%,  with  higher  prevalence  of   bullous  pemphigoid  87.5%  among   the  clinical  subtypes  of  pemphi-­‐ goid.  The  study  results  suggested  a   Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   6   female  predilection  in  pemphigoid   disease.  Fadia  et  al  in  2011,  sug-­‐ gested  that  pemphigoid  is  more   common  in  females  of  fifth  or   sixth  decade  of  life.  Majority  of   the  patients  (6  out  of  16,  37.5%)   fall  between  age  group  of  31-­‐40   years.13  The  median  age  of  pem-­‐ phigoid  disease  in  the  present   study  is  48  years.  Oral  mucosal   manifestation  (fluid  filled  blisters   or  bullous)  in  pemphigoid  in  the   present  study  is  12.50%  (2  out  of   16  patients)  which  is  considered  to   be  relatively  low,  and  only  one  pa-­‐ tient  (6.25%)  had  reported  oral   mucosa  as  an  initial  site  of  disease   manifestation.  The  most  common-­‐ ly  affected  site  in  oral  cavity  is   hard  palate  (12.5%),  which  is  fol-­‐ lowed  by  gingiva  (6.25%),  and  soft   palate  (6.25%).    Sunil  dogra  et  al  in   2003,  reported  that  palate  and   gingival  as  most  common  area  for   pemphigoid  disease.14  The  histo-­‐ pathological  examination  of  pem-­‐ phigoid  tissue  was  characterized   by  the  presence  of  sub  basilar  cleft   formation  in  the  oral  biopsied   specimens.  Direct  immunofluores-­‐ cent  method  demonstrated  the   positivity  for  IgG  and  C3  compo-­‐ nents  in  basement  membrane   zones  of  two  oral  tissue  speci-­‐ mens.  Stephen  et  al  in  2001,  stat-­‐ ed  the  direct  Immunofluorescence   of  pemphigoid  tissues  shows  a  lin-­‐ ear  deposition  of  IgG  and  C3  at   basement  membrane  zone.15     Conclusion   Identification  of  oral  mani-­‐ festations  in  pemphigus  and  pem-­‐ phigoid  are  important  in  both  den-­‐ tal  and  dermatology  practice.  Early   detection  of  oral  lesions  in  dental   practice,  and  referral  to  expert   dermatologist  may  help  in  early   intervention.  The  collaborative   approach  will  eventually  alter  the   prognosis,  and  provides  a  scope  to   reduce  morbidity  and/or  mortality   rate.     References   1. Oral  lesions  in  patients   with  pemphigus  vulgaris   and  bullous  pemphigoid.   Budimir  J1,  Mihić  LL,  Situm   M,  Bulat  V,  Persić  S,  Tom-­‐ ljanović-­‐Veselski  M.  Acta   Clin  Croat.  2008   Mar;47(1):13-­‐8.    PMID:   18714642   2. Oral  Manifestations  of   Pemphigus  Vulgaris:  Clini-­‐ cal  Presentation,  Differen-­‐ tial  Diagnosis  and  Man-­‐ agement.  Bascones-­‐ Martinez  A,  Munoz-­‐ Corcuera  M,  Bascones-­‐ Ilundain  C,  Esparza-­‐Gómez   G.  J  Clin  Exp  Dermatol  Res   2010  Dec;1:112.     3. Clinical  and  histological   characterization  of  oral   pemphigus  lesions  in  pa-­‐ tients  with  skin  diseases:  a   cross  sectional  study  from   Sudan.  Nada  M  Suliman,   Anne  N  Åstrøm,  Raouf  W   Ali,  Hussein  Salman  and   Anne  C  Johannessen.  BMC   Oral  Health.  2013  Nov   21;13:66.  PMCID:   PMC3871015   4. Mucous  membrane  pem-­‐ phigoid  affecting  the  oral   cavity:  short  review  on  eti-­‐ opathogenesis,  diagnosis   and  treatment.  Petruzzi  M.     Immunopharmacol  Immu-­‐ notoxicol.  2012   June;34(3):363-­‐7.  PMID:   22564172   5. Immunofluorescence  and   its  application  in  dermato-­‐ pathology  with  oral  mani-­‐ festations:  Revisited.   Arvind  Babu  RS,  P  Chan-­‐ drasekar,  K  Lalith  Prakash   Chandra,  G  Sridhar  Reddy,   K  Krian  Kumar,  BV  Ramana   Reddy.  J  Oro  Fac  Sci  2013   June;5(1):2-­‐8.   6. The  anti-­‐desmoglein  1  au-­‐ toantibodies  in  Pemphigus   vulgaris  sera  are  pathogen-­‐ ic.  Xiang  Ding,  Luis  A  Diaz,   Janet  A  Fairley,  George  J   Giudice,  Zhi  Liu.  J  Invest   Dermatol.  2005   May;124(5):939-­‐46.  PMID:   15854034   7. Frequency  of  oral  condi-­‐ tions  in  dermatology  clinic.   Velia  A  Ramrez  Amador,   Lilly  Esquirvel  Pedraza,  Ro-­‐ cio  Orozco  Topete.  Int  J   Dermatol.  2000   Jul;39(7):501-­‐5.  PMID:   10940113   8. Prevalence  and  socio-­‐ demographic  determinants   of  skin  disease  among  low-­‐ er  primary  school  children   in  Calcicut,  Kerala.  Libu  GK,   Thomas  Bina,  Lucy  Rapha-­‐ el,  SHyam  E  Balakrishnan,   Biju  George,  Joan  Felicita   Samson.  Kerala  Medical   Journal  2009  Octo-­‐ ber;5:185-­‐90.   Oral  mucosal  lesions  in  pa/ents  with  pemphigus  and  pemphigoid  skin  diseases:  a  cross  sec/onal  study  from  southern  India     Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.59    http://dentistry3000.pitt.edu   7   9. Incidence  of  pemphigus  in   Thrissur  district,  South  In-­‐ dia.  Kidangazhiyathmana   Ajith  Kumar.  Indian  J  Der-­‐ matol  Venereol  Leprol.   2008  Jul-­‐Aug;74(4):349-­‐ 51.PMID:  1879705.   10. Bullous  pemphigoid  and   pemphigus  vulgaris  –  inci-­‐ dence  and  mortality  in  the   UK  population  based  co-­‐ hort  study.  Langan  SM,   Smeeth  L,  Hubbard  R,   Flemming  KM,  Smith  CHP,   West  J.  BMJ.  2008  Jul   9;337:a180.  PMID:   18614511   11. Pemphigus  vulgaris  in  oral   cavity:  Clinical  analysis  of   71  cases.  Thorakkal   Shamim,  Vengal  Ipe  Var-­‐ ghese,  Pallikandi  Maliyek-­‐ kal  Shameena,  Sivasankar   Sudha.  Med  Oral  Patol  Oral   Cir  Bucal.  2008  Oct   1;13(10):E622-­‐6.  PMID:   18830168.   12. Current  concepts  of  Immu-­‐ nofluorescence  in  Oral  mu-­‐ cocutaneous  diseases.   Anuradha  CH,  Anandan,   Magesh  KT,  Malathi  N.  J   Oral  Maxillofac  Pathol.   2011  Sep;15(3):261-­‐6.   PMCID:  PMC3227250.   13. Pemphigus  vulgaris  and   mucous  membrane  pem-­‐ phigoid:  update  on  eti-­‐ opathogenesis,  oral  mani-­‐ festations  and  manage-­‐ ment.  Fadia  Ata  Ali,  Javier   Ata  Ali.  J  Clin  Exp  Dent   2011;3(3):  246-­‐50.     14. Mucous  membrane  pem-­‐ phigoid.  Sunil  Dogra,  Am-­‐ rinder  Jit  Kanwar.  Indian  J   Dermatol  2003   Dec;48(4):239-­‐40.     15. Immunodiagnosis  of  pem-­‐ phigus  and  Mucous  mem-­‐ brane  pemphigoid.  Ste-­‐ phen  J  Challacombe,  Jane   Setter  field,  Pepe  Shirlaw,   Karen  Harman,  Crispian   scully,  Martin  M  Black.  Ac-­‐ ta  Odontol  Scand.  2001   Aug;59(4):226-­‐34.  PMID:   11570526