24/8/2016

ParacetamolinducedStevenJohnsonsyndrome:Ararecasereport

ContempClinDent.2015Sep6(Suppl1):S278S281.

PMCID:PMC4632237

doi:10.4103/0976237X.166838

ParacetamolinducedStevenJohnsonsyndrome:Ararecasereport
RajanRajput,ShitalkumarSagari, 1AsthaDurgavanshi, 2andAlpanaKanwar3
DepartmentofOralMedicineandRadiology,JodhpurDentalCollegeGeneralHospital,Jodhpur,Rajasthan,India
1
DepartmentofOralandMaxillofacialPathology,JodhpurDentalCollegeGeneralHospital,Jodhpur,Rajasthan,India
2
DepartmentofOralMedicineandRadiology,IDSDentalcollegeandHospital,Bareilly,UttarPradesh,India
3
DepartmentofOralandMaxillofacialPathology,NIMSDentalCollegeGeneralHospital,Jaipur,Rajasthan,India
Correspondence:Dr.RajanRajput,DepartmentofOralmedicineandRadiology,JodhpurDentalCollegeandHospital,Jodhpur342001,
Rajasthan,India.Email:rajan099@gmail.com
Copyright:ContemporaryClinicalDentistry
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNonCommercialShareAlike3.0License,which
allowsotherstoremix,tweak,andbuildupontheworknoncommercially,aslongastheauthoriscreditedandthenewcreationsarelicensed
undertheidenticalterms.

Abstract
Inthecontemporaryera,useofdrugsisthedominantparadigmofhealthcare.Themostquotidiandrugused
forfeverandpainisparacetamol.AlthoughadversereactionstoparacetamolinIndiaarerare,attimesthey
cancauselifethreateningsituations.StevensJohnsonsyndrome(SJS)isonesuchpotentiallylethaladverse
drugreaction.ThemostreportedcasesofanalgesicinducedSJSwereduetooxicamsorpropionicacid
derivatives.ThereareveryfewdetailedreportsofSJSduetotheuseofparacetamol.Wereportacaseof
SJS,whichoccurredduetotheuseofparacetamol.Theclinicalfeaturesofthisconditionand
multidisciplinarymanagementofthepatientaredescribedinbrief.
Keywords:Adversedrugreaction,paracetamol,StevensJohnsonsyndrome

Introduction
StevenJohnsonsyndrome(SJS)isaninfrequentandasevereformoferythemamultiforme(EM).Itcan
occurduetoanadversehypersensitivityreactiontodrugswhichresultsinskinandmucosaleruptionsthat
canbepotentiallyfatal.Itisconsideredtobealesssevereformoftoxicepidermalnecrolysis(TEN).The
onlydifferencebeingtheextentofepidermaldetachmentthatis,30%ofthetotalbodysurfaceareawhile
1030%isknownasSJSTENoverlap.[1]
AneweruptivefeverwithstomatitisandophthalmiawasdescribedasaseverevariantofEMandwas
termedbyStevenandJohnsonin1922.[2]
SJSmaypresentasanonspecificfebrileillnessleadingtomalaise,headache,cough,rhinorrheawith
polymorphiclesionsoftheskinandmucousmembranecharacterizedbyacuteblistersanderosions.
TheincidenceofSJShasbeenestimatedtobearound16/1,000,000personsperyearwithamortalityrate
of15%whichrisesupto30%inTEN.MultipledrugshavebeenidentifiedtocauseSJSandTEN,
antibiotics(sulfonamides)beingthemostcommon.[3]
ThedrugsthatcauseSJScommonlyareantibacterials(sulfonamides),anticonvulsants(phenytoin,
phenobarbital,andcarbamazepine),nonsteroidalantiinflammatorydrugs(oxicamderivatives),andoxide
inhibitors(allopurinol).[4]
Paracetamolisamongthemostextensivelyusedanalgesicandantipyreticbecauseofeasyavailabilityand
costeffectiveness.Despitebeingconsideredrelativelysafe,adversereactionsincludingcutaneous
hypersensitivityreactionshavebeenreported.[5]

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VeryfewcasesofEMorSJShavebeenreportedwiththeingestionofparacetamol.Publicationsfrom1995
to2011describingSJSandTENinIndianpopulationweresearchedbyPateletal.inPubMed,Medline,
Embase,andUKPubMedCentralElectronicDatabasesshowed6.17%ofcasesofSJSandTENweredue
totheingestionofparacetamol.Hence,wepresentararecaseofSJSoccurredduetotheingestionof
paracetamol.[6]

CaseReport
A14yearoldmalepatientreportedtoDepartmentofOralMedicineandRadiologywithachiefcomplaint
ofpainfululcerationoflipsandoralcavityleadingtodifficultyinopeningmouthandeatingfoodsince5
days.Historyofpresentillnessrevealedthattherewasburningsensationfollowedbyulcerswhichappeared
firstinoralcavity,lips,andotherpartsofbodyincludingchest,arms,legsandthighs,andgenitalorgans
[Figure1aandb].Therednessofeyewasevident,andtherewasahistoryofwaterydischarge.Numerous
healedlesionswerealsoseenonthechest,axillawhichgavethetypicalappearanceoftargetlesionsor
bull'seyeappearance[Figure1c].
Thepastmedicalhistoryrevealedthatthepatientwassufferingfromfeverandpainsince2weeks.The
patientwasprescribedtabletcrocinforfeverandpainfor7daysbyalocalmedicalpractitioner.Thepatient
wasrelievedfromfeverandpainbutlaterhehadburningsensationfollowedbyulcersintheoralcavityand
extraoralsurface.
Intraoralexaminationrevealedasolitarymixedredandwhitelesionpresentonbothrightandleftbuccal
mucosa.Onleftbuccalmucosaitmeasured10mm8mmindiameterandrightsideabout16mm9mm
approximately.
Thelesionshavewelldefinedbordersandonpalpationitwasnonscrapableandnontenderwitharough
texture.Theupperandlowerlipswereswollen,andhemorrhagiccrustswerepresentalongwithprofuse
bleeding.Laboratoryinvestigationsrevealedleukocytosis(whitebloodcells,15101/l,referencevalue,
400011,000/l)andraisedCreactiveprotein59.87g/mlreferencerange,05g/Ml.Wehadsubjectedthe
patienttoonlythehematologicalinvestigationasthelesionbeingacute,andthepatientwasundersevere
discomfort.Basedonclinicalexamination,medicalhistory,andphysicalexaminationourdiagnosiswasSJS.
Thepatientwastreatedunderanexpertguidanceofdermatologistwithsystemicsteroidstabletprednisolone
30mgtwicedailydailyfor7days.Furtherreducedto20mgtwicedailyfornext7days.Gradually,10mg
and5mgforconsecutive7dayswereadministered.Gentianvioletapplication3timesdailyforlipsandskin
lesionswasadvocated.
ApplicationofKenacort(triamcinolone)ointmentthriceadaywasadvisedforulcersintheoralcavity.The
patientwasreviewedafteraweek.Lesionshadhealedsignificantlyintheoralcavityandontheskin.Recall
after2weeksrevealedalmostresolvedlesionsonallthesurfacesandcompletelyrecoveredapproximatelyin
40days[Figure2aandb].

Discussion
SJSisanuncommon,severe,mucocutaneousblisteringdisorderwithanacuteandunpredictableonset
causingconsiderablemorbidity.ItsmoresevereformiscalledTEN.Previously,SJSwasconsideredasEM
major,butnowisconsidereddistinctfromEMonthebasisofseverity,presenceofconstitutionalsigns,
atypicaltargetlesionswithtendencytoconfluence,positiveNikolsky'ssign,morethanonemucosalsite
involvement,andresidualsequelae.
Intheoralcavity,SJScauseswidespreadulcerativelesions.Prodromalsymptomsseeninabout30%ofcases
andmaypossiblyinitiatewithin13weeksofstartinganewdrug,andlastsfor12weeks,presentingwith
flulikesymptoms,sorethroat,headache,arthralgias,myalgias,fever,andotherrashes.
Ocularchangessuchasdryeyesthatresemblethoseofmucousmembranepemphigoidmaybenotedinfew
cases.Urethritisandvulvalulcersmayoccur.[7]Ourpatientdidnotreportanyprodrome,buttheeyeand
genitalulcerationswerepresent,alongwithskinandmouthulcers.
AlthoughmanyfactorshavebeenproposedasriskfactorsofSJS,includingdruginduced,infections,
malignantdisorders,andgraftrejection,mostofthemwereduetotheadverseeffectofdrugs.Themost
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commondrugsareanonsteroidalantiinflammatorydrug(NSAIDs),antipsychotics,antibiotics,allopurinol,
andanticonvulsants.[4]
SJScanbedifferentiatedfromotherskinconditionsonthreeclinicalcriteria,(i)thepatternofindividualskin
lesions,(ii)distributionoflesions,and(iii)extentofepidermaldetachment.
ThecharacteristicfindingsinSJSarewidespreaderythematousorpurpuricmaculeswhichformflatatypical
targetlesionsasthediseaseprogressestocausefullthicknessepithelialnecrosis.[3]
Ourcaseshowedulcerationoforalcavity,crustingoflipsandprofusebleeding,involvementofeyewith
rednessandwaterydischarge,ulcerationofgenitalregionalongwithnumeroushealedlesionsonchest,
axillawhichshowedtypicalappearanceoftargetlesionsorbull'seyeappearance.Thelesionswere
widespreadascomparedtoEM,whichislocalized.
Inastudydoneamongchildreninthehospital,itwasfoundthatanticonvulsantdrugswerereportedthe
highestriskforSJSandparacetamollestandvaccinespresentednoriskatall.AmongtheNSAIDs,
paracetamolandnimesulidearemostcommonreported.TheSeverecutaneousadversereactions(SCARs)
studyhasfoundanoverallriskofSJSwithoxicamderivatives.Itreportstheincreasedriskwithparacetamol
fromGermany,Italy,andPortugalexceptFrancebutveryfewcasesfromIndia.[6,8]
However,paracetamolisfoundtobeapotentialriskfactorinchildrenaccordingtosurveydatafrom
pediatricpatientsfromtheSCAR.[6]ThepresentcasewasdiagnosedasparacetamolinducedSJSbased
uponthefactthatasequentialrelationshipwiththedrugwasestablished,andcorrelationwithexposurewith
signsandsymptomswasmade.
Khawajaetal.[1]reportedacaseofAcetaminopheninducedSJSandTENwithwidespreadmaculapapular
rash,stingingintheeyes,oralmucosalulcerations,andhighgradefever.Similarfeatureswereseeninour
case,buttherewastheabsenceofhighgradefeverandepithelialdetachment.
Thefirststepinthemanagementwasanimmediatewithdrawaloftheoffendingagentfollowedby
supportivecare.GarciaDovaletal.,reportthatearlierthedrugiswithdrawn,bettertheprognosiswhile
exposuretodrugswithlongerhalflivesincreasestheriskofdeath.Supportivecaremustincludethe
managementoffluidandelectrolyterequirements.[9]
Routineantibioticsarenotindicatedunlessthereistheevidenceofinfectionasfevermaybepartofthe
diseaseprocess.Debridementofnecroticskinshouldnotbeperformedbeforediseaseactivityceases.
However,inourcase,therewerelesionsonaxilla,abdomen,thighsandtrunkregioninthehealingphase,so
debridementwasnotanecessarystep.
Topicalantiseptics(0.5%silvernitrateor0.05%chlorhexidine)areusedtopaint,bathe,ordressthepatients.
Dressingsmaybegauzeswithpetrolatum,silvernitrate,povidoneiodine,andhydrogels.Someauthorsuse
biologicskincoversafterepidermalstrippingcadavericallografts,culturedhumanallogeneicorautologous
epidermalsheets.Inourcase,gentianvioletapplicationforlipsandskinlesionswereadvocated.
DramaticimprovementinbothSJSTENhasbeenreportedwiththeuseofintravenousimmunoglobulin,
0.20.75g/kgbodyweight.AlternativesystemictreatmentmethodsfortheacutephaseofSJSTENinclude
hemodialysis,plasmapheresis,cyclophosphamide,andcyclosporine.[10]
UseofcorticosteroidinthemanagementofSJSiscontroversial.Accordingtosome,theirusecanleadto
delayedwoundhealing,increasedchancesofinfection,maskingofearlysignsofsepsis,gastrointestinal
bleeding,andincreasedmortality.Ifsteroidsaretobeused,itshouldbeinitiatedduringinitialstageand
rapidlytaperedoff.[11,12]Antibioticswithintravenouscorticosteroidshownaremarkableimprovementina
similarcase.[13]Hence,weprescribedtabletpredinsolone30mgthreetimesdailydailyfor7days.Further
taperedto20mgtwicedailyfornext7days.Gradually,10mgand5mgforconsecutive7days.His
conditionimprovednosequelaewerefoundduring3540daysoffollowup.

Conclusion
Thiscasereportreportsthefactthatseverehypersensitivityreactionscanoccurwithparacetamol,whichcan
bepossiblydangerousandlifethreatening.Therefore,cliniciansmustbemorecautiouswhileprescribing.
PatientsshouldalsobeeducatedregardingtheadverseeffectsofNSAIDs.
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Financialsupportandsponsorship
Nil.
Conflictsofinterest
Theauthorshaveobtainedthenecessarypatientconsentformswherethepatientshavegiventheirapproval
forparticipationintheinvestigation,followedbyrepresentationintheconcernedarticle.Thepatientsdo
understandthattheauthorswillensurethattheiridentitieswon'tberevealed,howeveranonymitycannotbe
guaranteed.

References
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casereport.IntJResMedSci.20153:4923.
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200511:2617.[PubMed:16120111]
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syndrome.IndianJMedRes.2012136:10513.[PMCID:PMC3612312][PubMed:23391805]
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2000136:3237.[PubMed:10724193]
10.RoujeauJC,KellyJP,NaldiL,RzanyB,SternRS,AndersonT,etal.Medicationuseandtheriskof
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phenytoin:Acasereport.IntJBasicClinPharmacol.20132:8435.
12.PattersonR,GrammerLC,GreenbergerPA,LawrenceID,ZeissCR,DetjenPF,etal.StevensJohnson
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FiguresandTables
Figure1

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ParacetamolinducedStevenJohnsonsyndrome:Ararecasereport

(a)Initialpresentationofthecaseshowingencrustedlesiononlipsandintraoralerythema.(b)Hemorrhagicerosionon
mucousmembraneofglanspenis,(c)targetoidrashesoverchest

Figure2

(a)Healingofcrustingoflipsandhealinglesionofbuccalmucosa,(b)Healedlesionofupperandlowerlips
ArticlesfromContemporaryClinicalDentistryareprovidedherecourtesyofMedknowPublications

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