Oral submucous fibrosis

ORAL SUBMUCOUS FIBROSIS

1. ORAL SUBMUCOUS
FIBROSIS
Dr Chandra Bhan
Assistant professor
MRAMC

2. (J.JPindborgandSirsat1966)
Itisaninsidiouschronicdiseaseaffectinganypartof
theoralcavityandsometimesthepharynx.
Althoughoccasionallyprecededbyand/orassociated
withvesicleformation,itisalwaysassociatedwith
juxta-epithelialinflammatoryreactionfollowedbya
fibro-elasticchangesofthelaminapropriawith
epithelialatrophyleadingtostiffnessoftheoral
mucosaandcausingtrismusandinabilitytoeat.
DEFINITION

3. HISTORY
Theconditionoforo-pharyngealOSMFoforal
cavitywasprevalenteveninthedaysof
Shushrutha(600B.C).
Shushrutha,thegreatestpractitionerofancient
medicinestatedinhisbook"ShushruthaSamhita'
aconditioncalled'VIDARI'inhisclassificationof
diseasesofmouthandthroat.
Thefeaturesofwhichsuitthesymptomatologyof
OSMF.

4. FirstdescribedamongfiveEastAfricanwomenof
IndianoriginunderthetermAtrophiaidiopathica
(tropica)MucosaeOrisbySchwartz1952.
Joshiin1953iscreditedtobethefirstpersonwho
describeditandgavethepresentterm“Oralsub-
mucousfibrosis”.
Intheyear1954,Su.1.P.fromTaiwandescribed
similarcondition,whichhecalled"Idiopathic
Sclerodermaofmouth"

5. Paymaster(1956)describedthepre-cancerous
natureofthecondition.
Othernamesthathavebeensuggestedare:
•Diffuseoralsub-mucousfibrosis(LalD.1953)
•Sclerosingstomatitis(Behl1962)
•Idiopathicpalatalfibrosis(Rao1962)

6. EPIDEMIOLOGY
OSMFisacripplingfibroticdisorderseencommonly
inIndiaandIndiansubcontinent.Sporadiccasesare
seeninMalaysia,Nepal,ThailandandSouthVietnam.
IncidenceofOSMFinIndiais0.2-0.5%ofpopulation.
Personsbetween20and40yearsofagearemost
commonlyaffected,butageshaverangedfrom2to89
yearsofage
Nocastorreligiouscommunityisespeciallyaffected.

7. Casereportsalsoincludeoccurrenceofthis
conditionina4yrsoldIndianimmigrantgirlin
Canada,whohadbeenchewingarecanutsincethe
ageof2yrs.
PrevalencerateinIndiarangesfrom0.2to1.2%.

8. ETIOLOGY

9. Exact etiology is unknown. The suggested factors are,
1. Chronic Irritation
-Chilies
-Lime
-Betel nut
-Tobacco Chewing
2.Deficiency disease.
3.Defective iron metabolism
4.Bacterial Infection
5.Collagen disorder
6.Immunological disorders
7.Genetic disorder.

10. Chronicirritation:
PathogenesisofOSMFliesinthecontinuous
actionofmildirritants.
Chilies:
"Capsaicin"aactiveextractfromcapsicum.
Theactiveprincipleirritantofchillies(Capsicum
annumandCapsicumfrutescence).

11. Thesuspicionthatchilliisanetiologicalagentarise
onthebasisofecologicalobservationsandwas
strengthenedbytheclinicalandhistological
characteristicsofthiscondition,i.e.
Bloodeosinophilia,
Tissueeosinophilsinthebiopsyspecimenand
presenceofsubepithelialvesiclessuggestedan
allergicnatureofthisdiseasepossiblyduetochilli
intake.

12. Lime:
Betelnut&limemixtureisusedforchewing.This
alsocontainsarecoline,limeandtannicacid,These
causelocalirritationanddamagetothemucosawith
vesicleandulcerationonsusceptibleindividual.
Limeinbetelquidcausesconstantaberrationoforal
mucosa,allowingdirectaccesstothecarcinogens.

13. TobaccoChewing
Itisaknownirritantandacausativefactorin
oralmalignancies
N’-nitrosonornicotineisproducedbybacterial
andenzymaticnitrosationofnicotineandcan
befoundbyreactionofsalivarynitrateswith
nornicotine.
N’-nitrosonornicotinelevelsincreased44%
whentobaccowasmixedwithsaliva.
N’-nitrosonornicotineextractedfromchewing
tobaccowithsalivaisapproximately1000
timesthatfoundincigarettesmoke.

14. Betelnut:
Consideredtobeoneofimportantetiological
factorforOSMF.
InIndiaarecanutischewedbyitselforinthe
formofvariousarecanutpreparationssuchas
supari,mawa,manipuri,panmasalaandinbetel
quideitherwithorwithouttobacco.

15. Thefactorsthatcontributetothepathogenesisin
habitualbetelnutchewers.
1.Theamountoftannicacid(14-18%)containedin
thebetelnut.
2.Theinfluenceofmixedcalciumpowder.
3.Actionofarecolinecontainedinthebetelnut
affectingthevascularnerveoforalmucosaand
causingneurotropicdisorder

16. Arecanutcontaindifferenttypeofalkaloids-
arecoline,arecadine,guvacoline,guvacineand
isoguvacine.
Nitrosationofarecolineleadstotheformationof
arecanutspecificnitrasamine.
Allarecanutspecificnitrosaminesarefoundtobe
powerfulcarcinogensandalkylateDNA.

17. KHANNAANDANDHARAsuggestedthat,Arecoline,
stimulatefibroblasticproliferationandcollagensynthesis.
Theflavonoidscatechinandtanninsstabilizethecollagen
fibrilsrenderingthemresistanttodegradationby
collagenase.
Theattendenttrismusisaresultofjuxtaepithelial
hyalinizationandsecondarymuscleinvolvement(i.e.
musculardegradationandfibrosis)
Thehabitofchewingarecanutleadstomusclefatigue

18. Deficiency disease
VitaminB12andIrondeficiencyareassociated
withOSMF.
Thedeficiencycouldbeduetothefactthat
defectivenutritionduetoimpairedfoodintakein
advancedcasesofOSMF,maybetheeffectrather
thanthecauseofthedisease

19. Defective iron metabolism
Impairedcellularutilizationofironexplainsthe
presenceofhypochromicmicrocyticanemia.
Thereisnodefiniteprooftosupportthehypothesis
thatdefectiveironutilizationbyoralmucosaand
sub-mucosaisthecauseofOSMF.

20. INFECTIONS
MukherjeeandBiswas(1972)suggestedthatthere
is:
Riseinmucoproteinandmucopolysaccharidelevel
Riseinanti-streptolysin-OtitreinOSMFpatients.
(Buttheseworksarenotconfirmed)

21. Collagendisorder:
Rao(1962)suggestedthatOSMFisalocalized
conditionofcollagendisease.
Helinkedittoscleroderma,rheumatoidarthritis,
duputreyenscontractureandintestinalfibrosis.
Histologicalfeatureswerefoundtobesimilarin
OSMFandscleroderma.

22. HARMONAL FACTORS
There would appear to be predisposition in female
with a ratio of women to men of 3:1
(Pillai R et al “pathogenesis of Oral submucous
fibrosis”, cancer 1992 ;69:2011-2017)

23. IMMUNOLOGICAL DISORDER:
OralSubmucousfibrosisisahighriskpre-cancerous
condition.RaisedESRandglobulinlevelsarefound,
indicativeofimmuneinflammatorydisorder.
SerumimmunoglobulinlevelsIgA,IgGandIgM
levelsareraised.Thesesuggestanantigenicstimulus
inabsenceofanyinfection.
IncreasedcirculatingimmunecomplexinOSMF

24. Geneticpredispositiontothedisease,involvingthe
HLAantigens,A10,DR3,DR7andprobablyB7and
thehaplotypicpairsA10/DR3andA10/B8hasbeen
demonstrated.
TheincreasedevidenceofCD4andHLA-DR-
positivecellsandhighratioofCD4toCD8inOSF
tissuesuggestanongoingcellularimmuneresponse
leadingtoimbalanceofimmunoregulationand
alterationinlocaltissuearchitecture.

25. Mastcells
Mastcellsarecharacterizedbynumerouscytoplasmic
granules. Its cytoplasm contains
mucopolysaccharides,histamineandheparin.
ManypatientswithearlystageofOSMFgivehistory
offeelingofitchingsensationwhichcouldbedueto
releaseofhistamineexactroleofmastcellsin
inflammationisnotknown.

26. ARECANUT TOBACCO LIME VOLATILE OILSVOLATILE LIQUIDS
TANNIN&
AFLOTOXIN
ARECOLINE
DEGRADATION
OF COLLAGEN
INCREASED SYNTHESIS
OF COLLAGEN
MECHANICAL
TRAUMA
CHEMICAL BURN
HYPERSENSITIVITY
ALTERED IMMUNITY
GENETIC
REDISPOSITION
FIBROBLAST
FORMATION
IRREVERSIBLE FIBROSIS
CACINOMAEXPOSURE CONTINOUS

27. Malignant transformation rate is 7.6%
(JIAOM, vol-iv;no.3& 4 July-Dec.1993, p 12-15)

28. CLINICAL FINDINGS
Thedataregardingthesexpredilectionis
conflicting.Earlieritwasthoughttobecommon
infemales.
Butatpresent,studyratioshows2.3:1=M:F
Agegroupcommonis2to3rddecadeoflife
Butcaseshavebeenreportedfrom4yearto86yrs.

29. Prodromal symptoms :
Onset is insidious. The most common initial
symptoms are:
Burning sensation on eating spicy food
Blisters on the palate
Ulceration or recurrent stomatitis
Excessive salivation
Defective gustatory sensation
Dryness of mouth.

30. Later
Difficulty in opening mouth
Inability to whistle, blow
Difficulty in swallowing
When fibrosis involves pharynx-referred pain to the ear.
Changes in tone of the voice due to vocal cord involvement
Some times deafness due to occlusion of eustachian tubes

31. COMMON SITESINVOLVED
Buccalmucosa,faucialpillars,softpalate,lipsand
hardpalate.
Thefibrousbandsinthebuccalmucosarunina
verticaldirection,sometimessomarkedthatthe
cheeksarealmostimmovable.
Inthesoftpalatethefibrousbandsradiatefromthe
pterygomandibularrapheorthefaucialpillarsand
haveasearlikeappearance

32. Theuvulaismarkedlyinvolved,shrinksandappearsas
asmallfibrousbud.
Thefaucialpillarsbecomethick,short,andextremely
hard.
Thetonsilsmaybepressedbetweenthefibrosedpillars
Thelipsareoftenaffectedanduponpalpation,a
circularbandcanbefeltaroundtheentirerimaoris
Whengingivaisaffected,itisfibrotic,blanched.

33. BLANCHING LOWER LABIAL MUCOSA AND
FLOOR OF MOUTH

34. INVOLVING LOWER LABIAL MUCOSA

35. UVULA SHRUNKEN GIVING HOCKEY STICK APPEARANCE

36. PALE AND BALD TONGUE

37. SOFT PALATE

38. TRISMUS

39. INTERINCISAL OPENING MEASUREMENT

40. CLASSIFICATION
Kerr et al. 2011, the proposed grading system for OSMF
Grade 1 –Mild: Any features of the disease triad for OSMF
(burning, depapillation, blanching, or leathery mucosa) may be
reported –and inter-incisal opening > 35 mm.
Grade 2 –Moderate: Above features of OSMF + inter-incisal
limitation of opening 20-35 mm.
Grade 3 –Severe: Above features of OSMF + inter-incisal
opening < 20 mm.
Grade 4A –OSMF + other potentially malignant disorder on
clinical examination.
Grade 4B –OSMF with any grade of oral epithelial dysplasia
on biopsy.
Grade 5 –OSMF + oral squamous cell carcinoma.

41. ClinicallysignsofOSMFcanbegroupedas:
Stage1(S1)–Stomatitisand/orblanchingoforal
mucosa.
Stage2(S2)–Presenceofpalpablefibrousbandsin
buccalmucosaand/ororopharynx,with/without
stomatitis.
Stage3(S3)–Presenceofpalpablefibrousbandsin
buccalmucosaand/ororopharynx,andinanyotherparts
oforalcavity,with/withoutstomatitis.
Stage4(S4)(a)–Anyoneoftheabovestagealongwith
otherpotentiallymalignantdisorderse.g.,oral
leukoplakia,oralerythroplakia,etc.
Stage4(S4)(b)–Anyoneoftheabovestagealong
withoralcarcinoma.

42. StageIofstomatitis&vesiculation
Itisearlieststageandcharacterizedbyrecurrent
stomatitisandvesiculation.Patientcomplaintsof
burningsensationinthemouth&inabilitytoeat
spicyfood.
Onexaminationvesiclesonpalateareseen.
Theyruptureandformsuperficialulcers.
Someamountoffibrosisisalsopresent.

43. StageII:Stageoffibrosis
Thereisinabilitytoopenmouthcompletelyand
stiffnessinmastication.
Asdiseaseadvancesthereisdifficultyinblowingout
cheek&protrudingtongue.Sometimespaininear
andspeechismuffled.
Onexaminationthereinincreasingamountof
fibrosisinthesubmucosa.Thiscausesblanchingof
mucosa.

44. Lips&checksbecomestiff&loosetheirnormal
resistance.Shortening&disappearanceofuvula
inadvancedcases.
Dorsumoftongueshowsatrophyofpapillae.
Mucosaoffloorofmouthshowblanching&
stiffness

45. Stageofsequelae&Complication
Patientpresentswithallthecomplaintsasinstage
II.Alsotheremaybeevidenceofleukoplakia.
Changesinmucosaarewhitishorbrownishblack-
Pindborgetal(1967)foundtheOSMFwasfound
in40%casesoforalcancerthaningeneral
population1.2%.

46. CLINICAL GRADING OF SEVERITY OF OSMF
GRADE-I
Incipient
(very early stage)
GRADE-II
Mild
(early stage)
GRADE-III
Moderate
Moderately advanced
stage
GRADE-IV
severe
advanced
stage
1.Burning
sensation,
dryness of mouth,
vesicles or
ulceration
1.Burning
sensation,
dryness of
mouth
1.Burning sensation,
dryness of mouth
1.Burning
sensation,
dryness of
mouth
2.Irritation with
spicy food
2.Irritation
with
spicy food
2.Irritation with
spicy food
2.Irritation
with
spicy food

47. 3.Nochangein
mucosalcolour
3.Oralmucosa
isblanchedand
loses its
elasticity
3.Blanched
,opaque,leather
likemucosa
3.Blanched
,opaque,leather
likemucosa
4.No fibrous
bands
4.Noclearcut
fibroticbands
4. Vertical
fibroticbands
on buccal
mucosamaking
itstiff
4.Thickfibrous
bandsoccurring
onbothbuccal
mucosa, in
retromolararea
and at
ptrygomandibul
arraphe
5.Mouthopening
normal
5. Slight
restrictionof
mouthopening
5.Considerable
restrictionof
mouthopening
5.Verylittle
mouthopening

48. 6.Tongue
protrussion
normal
6.Tongue
protrussion
normal
6. Tongue
protrussionnot
muchaffected
6.Restricted
tongue
protrussion
7.Difficulty in
eating and
speaking
7.Speechand
eating very
muchimpaired
8.Oral hygiene
poor
8.Oralhygiene
verypoor

49. DIAGNOSISISBASEDON:
Clinicallydiscernibleblanchingandpallor.
Palpablebandsandrestriction-ofmouthopening.
Severeburningsensationofmouth,aggravatedby
useofevenmoderatespicyfood.

50. Biopsyreportcharacteristicallyshowing
histopathologically.
AtrophicOralepithelium.
Lossofretepegs.
Epithelialatypiamaybeobserved.
Hyalinizationofcollagenbundles.
Fibroblastsdecreasedandbloodvesselsobliterated.

52. INVESTIGATIONS

53. Labfindingsreflectthenatureoftissuechangesin
thisconditionratherthananydiagnosticimportance.
IncreasedESR
Anemia
Higheosinophilcount
Hypergammaglobulinaemia
LowerserumvitaminAlevels

54. MANAGEMENT

55. MANAGEMENT
Variousmodalitiesoftreatmenthavebeentried.
1.Restrictionofhabits/Behavioraltherapy
2.Medicinaltherapy
3.Surgicaltherapy.
4.OralPhysiotherapy

56. Restrictionofhabits/behavioraltherapy
Theconsumptionofpan,betelnut,chillies,spices,
&commerciallyavailable,panmasalas,guthkas
withorwithouttobaccoisincreasinginIndia.So
peopleshouldbeencouragedtostopthesehabits
Affectedpatientsshouldbeexplainedaboutthe
diseaseandpossiblemalignantpotentialofOSMF.
Possibleirritantsshouldberemoved.
Nutritionalsupplements.

57. MEDICINALTHERAPY
Antioxidants
Intralesionalinjectionsofhyaluronidase.
UseofPlacentrix2mlsolutionatintervalof3
daysinfivedividedregion.
Topicalapplicationof4%Aceticacid(variable)3
timesdaily.

58. Topicalapplicationofimmunomodulators:
5Fluorouracil
Systemicadministrationofimmunomodulators
Levamisole150mgfor3weeks
Dapsone75mgO.Dfor90days
Thesteroidsactbyinhibitinggenerationof
inflammatoryfactorsandincreasingtheapoptosisof
inflammatorycells.Althoughsteroidsareoneofthe
mostoftenuseddrugsfor.

59. SURGICAL TREATMENT
Fibrotomy
Cryosurgery
Laser treatment

60. Tongue flap
Preoperativelyinsomepatients,whohavemildtrismus,
extractsthelastupperandlowermolarstopreventthe
tongueflapgettinginthewayofocclusion,divisionof
whichmayresultinprofusebleedingduringmastication.
Patientisplacedinsupinepositionwiththeheadelevatedto
30°withthemouthwideopenwithaDoyen’sgag.The
tongueisanchoreddownwitha00silksutureatthetip.

61. Togivegoodinter-dentalworkingspace,theanteriorpillar
andretromolarfibroticbandsareincisedwithaknife.
Onthedorsolateralaspectoftongue,usingindeliblemarking
in,amarkismadestartinghalfofaninchfromtheanterior
pillarofthepalate,paralleltothemidlineofthetongueupto
1cmbehindthetipofthetongue.
Themarkingistakendowninferiorlytothesublingual
surfaceuptothelastmolar,whichincludesthelateralmargin
ofthetongue.

62. Anotherellipticalmarkingismadeonthecheek
startingfromthepalatoglossalfoldto2cmbehind
theangleofthemouth.
Thetongueisinfiltratedwithsalineandepinephrine
injection.
Thenadeepellipticaltongueflapisraiseduptothe
palatoglassalfoldwithinthemarkingsonthetongue,
whichincludesthetongueepitheliumandmuscle,
usingknifeandscissorsandcuttingcautery.

63. Tongueflapisraisedandrotatedoutwardlaterallytothe
rawareaafterexcisionofthelesioninthecheek.
Adeepsutureisplacedinthebedoftheflap,whichis
firmlyanchoredtotherawareainthecheek.
Themarginsofthetongueflapandedgesofthecheek
woundarefirmlyanchoredwithinterruptedsutures.
Thesameprocedureisadoptedonthecontralateralside.
Theoralcavityisflushedwithbetadineandmetrogyl
solution.

66. Coronoidectomyand Buccal Fat Pad
Replacement
Undergeneralanaesthesianasoendotrachealintubationwasdone
usingafibreopticbronchoscope.
LAwithadrenaline(1:200,000epinephrine)wasadministeredat
thesurgicalsite.
Bilaterallyincisionswereplacedonthebuccalmucosafromthe
cornerofthemouthanteriorlyextendingposteriorlyuptothe
pterygomandibularrapheoranteriorfauscialpillar.
ToavoidinjurytoStenson’sductincisionswereplacedatthelevel
ofoccusalplane.

67. Bluntdissectionwascarriedouttorelievethefibrousbands
andmouthopeningwasincreasedusingaFergussonmouth
gag.
Incisionwasplacedonthelabialmucosaandthefibrousbands
wererelieved.
Thecoronoidprocesseswereapproachedfromthesame
incisionandbilateralcoronoidectomywasdone.
TheBuccalfatpadwasapproachedthroughtheposterio
superiorpartoftheexistingincisionandwasteasedoutgently
andcarefullyuntilasufficientamountwasobtainedtocover
thedefectwithouttension.

68. Thebuccalfatpadwassecuredtothewoundby
interruptedsuturesusing3-0vicryl.Copioussaline
irrigationwasdone.Restofthewoundclosurewasdone
using3-0vicryl.

69. Nasolabialflaps
Undergeneralanesthesiawithnasalintubation.After
openingthemouth,thebuccalmucosawasincised
transverselyfromjustbehindthecommissureoftheoral
cavityextending
posteriorlydepending
uponthelocationof
thefibroticbands.

70. Mouthopeningwaschecked&intraoperative
interincisaldistancewasmorethan35mminall
patientsimmediatelyafterreleaseofbands.
Themaxillaryandmandibularthirdmolarswere
extracted.
Nasolabialflapsfromthetipofnasolabialfoldto
cornerofmouthweremarked&bilaterallyraisedin
theplaneofthesuperficialmusculoaponeurotic
system.

72. Thearteryresidesinthedensefibroustissueattheoral
commissureandcontinuesalongthesuperiorborderofthe
upperliptothenasalala.Itthencontinuesinamedial
coursealongthenasofacialgroovetowardthemedial
canthusoftheeye.Arterialperfora-torsareespecially
concentratedintheinferiortwo-thirdsofthenasolabial
groove.

74. Averageflapdimensionsare2.5cminwidthand6cm
inlength.
Thesuperiorborderoftheflapisinferiortothe
medialcanthusalongthenasofacialjunction.
Theinferiorborderoftheflapshouldbeatthe
superiorborderofthemandible;
Forreconstructionofpalataldefectsandanttonsillar
pillarhowever,requirestheinferiorbordertobe
approximatelyattheleveloftheoralcommissure.

76. Theskinincisioniscarriedthroughthedermisand
subcutaneousfattotheleveloftheunderlyingmusculature.
Thearteryliesinaplanedeeptothefacialmimetic
musculatureandinamedialpositionalongthenasofacial
groove.
Theflapiselevatedinasuperior-to-inferiorfashionina
planedeeptothefacialmusculature,arteryandvein,with
thearteryidentifiedcarefullybybluntdissection.
Theparotidductisidentifiedandpreserved.Thesuperior
labialarterymayrequireligation.

78. Theflapwastransposedintraorallythrougha
smalltransbuccaltunnelnearthecommisureof
themouth,withnotensionandthecaudalbaseof
theinferiorlybasednasolabialflapwas
deepithelizedinatriangularfashion.

80. Theextraoraldefectwasclosedprimarilyinlayers
afterunderminingskininsubcutaneousplaneto
preventtensionacrossthemsutureline.
Physiotherapywasstartedfromthe5
th
postoperativeday&patientswereinstructedto
continuethephysiotherapythemselvesforupto6
monthstopreventrelapse.

81. Fullthicknessskingraftscanalsobeusedlike
Bilateralradialarteryforearmfreeflapsandthebi-
paddledradialforearmflap.
Theyneedmicrovascularexpertiseanddebulking
ofthegraftsina2ndsurgery.
Superficialtemporalfasciaflapwithsplitskingraft
hasbeenusedwithagoodsuccessratebutagain
debulkingprocedureisneededina2ndsurgery.

82. Palatalflapscanbeusedbutwideareaofraw
palateisexposedduringbilateralpalatalflapsand
2ndmolarsareneededtobeextractedtofixthe
flapwithbuccalmucosawithouttension.