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ACETAMINOPHENINDUCEDCELLULITISLIKEFIXEDDRUGERUPTION

Performingyouroriginalsearch,cellulitisjournal,inPMCwillretrieve7347records.
IndianJDermatol.2011MarApr56(2):206208.

PMCID:PMC3108524

doi:10.4103/00195154.80419

ACETAMINOPHENINDUCEDCELLULITISLIKEFIXEDDRUGERUPTION
NeilaFathallah,ChakerBenSalem,RaoudhaSlim,LobnaBoussofara, 1NajetGhariani, 1andKamelBouraoui1
DepartmentofClinicalPharmacology,FacultyofMedicineofSousse,Sousse,Tunisia
1
DepartmentofDermatology,FarhatHachedUniversityHospital,Sousse,Tunisia
Addressforcorrespondence:NeilaFathallah,AveMohamedKaroui,4002Sousse,Tunisia.Email:neilafathallah@gmail.com
Received2009AugAccepted2010Jul.
CopyrightIndianJournalofDermatology
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,whichpermits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract

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Acetaminophenisawidelyusedanalgesicdrug.Itsadversereactionsarerarebutsevere.An89yearoldman
developedaninduratededematousanderythematousplaqueonhisleftarm1dayafteracetaminopheningestion.
Cellulitiswassuspectedandantibiotictherapywasstartedbuttherewasnoimprovementoftherashtherewasa
spectacularextensionofthelesionwithoccurrenceofflaccidvesiclesandblistersintheaffectedsites.The
diagnosisofgeneralizedbullousfixeddrugeruptioninducedbyacetaminophenwasconsideredespeciallywitha
reportedhistoryofapreviousmilderreactionoccurringinthesamesite.Acetaminophenwaswithdrawnandthe
rashimprovedsignificantly.AccordingtotheNaranjoprobabilityscale,theeruptionexperiencedbythepatient
wasprobablyduetoacetaminophen.Cliniciansshouldbeawareoftheabilityofacetaminophentoinducefixed
drugeruptionthatmayclinicallytakeseveralaspectsandmaybemisdiagnosed.
Keywords:Acetaminophen,generalizedbullousfixeddrugeruption,cellulitis
Introduction

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Acetaminophenisamongthemostcommonlyprescribedmedications.[1]Itscutaneousadverseeffectsarerare,
varyingfromtransientpruritisormaculopapularrashtoStevensJohnsonsyndromeandevenfataltoxicepidermal
necrolysis.[2,3]Onlyfewcasesofacetaminopheninducedgeneralizedbullousfixeddrugeruptionhavebeen
reportedinliterature.[4,5]Wereportacaseofgeneralizedbullousfixeddrugeruptioninducedbyacetaminophen
andpresentinginitiallylikecellulitis.
CaseReport

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An89yearoldmanpresentedwithaonedayhistoryofpainfulerythematousandedematouseruptionaffectinghis
leftarm.
Thepatient'smedicalhistorywassignificantforhypertensiontreatedwithfurosemide(40mg/day).Moreover,there
wasanotionofselfmedicationbyacetaminophenforrecentarthralgiainthelatest48h.
Onphysicalexamination,thepatientwasfebrilewithanaxillartemperatureof39C.Hehadalsoawetcoughwith
expectorationsofthickyellowishsputum.Vitalsignswerewithinnormalrange.Hisleftarmwasred,glossy,and
warmtothetouch.Theplaquewastenderandinduratedwithdefiniteborders,coveringtheleftforearmand
extendingtotheupperarm[Figure1].Clinically,thelesion'saspectmimickedacellulites,andthepatientwas
initiallytreatedwithintravenouscefapirine(4g/day).

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Figure1
Ontheleftthigh,twosuperficialblistersandarupturedbullaroofareseenonanerythematous
basewithepidermaldetachment:generalizedbullousfixeddrugeruption
Laboratoryinvestigationsshowedthefollowingvalues:whitebloodcellcountof8.3109/L(normalrange,4.5
11109/l)hemoglobin16g/dl(normalrange,1216g/dl)bloodureanitrogen9.6mg/dl(normalrange,621
mg/dl)andacreatininelevelof1.6mg/dl(normalrange,0.51.3mg/dl).
Twodayslater,superficialflaccidblistersappearedattheaffectedsiteandavaryingsizeofmultiplewell
circumscribederythematousandhyperpigmentedpatcheswereobservedontherightarm,theabdomen,andboth
legs.Someofthemwerestuddedwithflaccidvesiclesandblisters[Figure2].Themucousmembranesandtheface
werenotinvolved.
Figure2
Alargeerythematous,edematous,andshinyplaquewithdeterminate
borderscoveringtheleftarm:Cellulitislikefixeddrugeruption
Inviewofthisskindisorder,thediagnosisofgeneralizedbullousfixeddrugeruptionandStevensJohnson
syndromewereconsidered.
Meanwhile,thepatientgavehistoryofsimilarbutamorelocalizedreactionfollowingacetaminopheningestion
occurring2yearsearlier.Askinbiopsywascarriedout.Histopathologicalexaminationofthelesionalbiopsy
specimentakenfromaflaccidblisteroverlyingapurplishlividpatchontheleftarmrevealedathinepidermiswith
necrosisofepidermalkeratinocytes.Thedermiswasedematouswithamixedinflammatoryinfiltrateconsistingof
mononuclearcellsandfeweosinophils.DirectimmunofluorescencerevealednoIgG,IgE,orIgAandC3
depositionatthebasementmembranezone.
Thediagnosisofacetaminopheninducedgeneralizedbullousfixeddrugeruptionwasconfirmedbasedonthe
clinicalandhistologicalfindings.Acetaminophenwasthenwithdrawn.Theblistersandvesiclesdisappearedfew
dayslater.
Discussion

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Fixeddrugeruptionisaspecificcutaneousadversereactioninducedbyaneverexpandinglistofdrugs.Itusually
consistsofsolitaryormultiplelesionsoccurringafterthedrugexposure.Thereactionsvaryinseverityfrom
localizedlesionstogeneralizederuptions.Acetaminopheninducedfixeddrugeruptionisreportedinliteraturein
lessthan1.5%ofallcasesoffixeddrugeruption.[6]Thisadversereactionrarelyprogressestoageneralized
bullousfixeddrugeruption.Itcanexceptionallyappearunderaclinicalshape,whichmimescellulitis.[7]Inour
reviewoftheliteratureandaccordingtodatafromaMEDLINEsearchforoverthepast40years,weidentified
onlyonepublicationregardingacaseofcellulitislikefixeddrugeruptioninducedbyacetaminophen.Inthiscase,
thefixeddrugeruption,whichwasdevelopedina65yearoldwomanclinicallyseemedlikecellulitis.Therewas
absenceofdevelopmentofblistersevenafterrechallengeofacetaminophen.[7]
Ourcaseisoriginalinthesensethattheeruptiontookseveralaspectsinthesamepatientandchangedfroma
cellulitislikeeruptiontoageneralizedbullousone.Infact,ourpatientdevelopedatfirstaneruptionclinically
mimickingcellulitisandinitiallytreatedassuch.However,theexacerbationofclinicalmanifestationunder
antibiotictherapyandwithcontinuedexposuretoacetaminophensuggestedthediagnosisoffixeddrugeruption
especiallywiththereportedhistoryofapreviousmilderreactionoccurringinthesamesite.Theclinicalaspectof
theeruptionwiththeflaccidvesiclesandblisterswasunusualinfixeddrugeruption.Afterarepeatedexposureto
theoffendingdrug,theseverityoffixeddrugeruptionmayincreaseandmayprogressrarelytoageneralized
bullousfixeddrugeruption,whichisanextensiveformoffixeddrugeruption.Itischaracterizedbymultiple,large,
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welldefined,purplishlividpatcheserodedbyflaccidblisters.[8]Theclinicalaspectmaybemisdiagnosedas
StevensJohnsonsyndrome,whichisanimportantdifferentialdiagnosisthatcanbeseparatedbyclinicalmeans,
butnotintermsofthehistopathology.Ingeneralizedbullousfixeddrugeruption,lesionsoccurquiteearlywithin
fewhoursofdrugintake.Itgenerallyinvolvesthesamesites,whichwereaffectedinthepreviousepisodes.By
contrast,recurrentlesionsinStevensJohnsonsyndromeshownopredilectionforpreviouslyaffectedsites.The
epidermalchangesingeneralizedbullousfixeddrugeruptionandStevensJohnsonsyndromevaryfromfew
scatterednecrotickeratinocytestofullthicknessepidermalnecrosisandthehistopathologicaldifferentiationcannot
beeasilydistinguishedinallconditions.Infixeddrugeruption,amixedinflammatoryinfiltrateisnotedaround
superficialanddeepplexuses,whichmainlycontainneutrophilisandeosinophilisinadditiontolymphocytesand
histocytes.Presenceofintraepidermalvesiculationwithkeratinocytenecrosismakesthediagnosisoffixeddrug
eruptionmorelikely.[9]
Inourcase,therearemanyargumentsinfavorofgeneralizedbullousfixeddrugeruptioninducedby
acetaminophen.Infact,thereisatemporalcorrelationbetweenthedrugintroductionandtherashappearance,
previoushistoryofmilderreaction,favorableevolutionandrapidrecoveryafteracetaminophenwithdrawal.Skin
biopsywasalsoconsistentwiththisdiagnosis.AccordingtotheobjectivecausalityassessmentbytheNaranjo
probabilityscale,[10]acetaminopheninducedbullousfixeddrugeruptionwasprobable.Thepatientwasfirmly
instructedtoavoidselfmedication,particularlywithacetaminophen.
Conclusions

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Physiciansshouldbeawareoftheriskoftheoccurrenceofcutaneousadversereactionsunderacetaminophen,
especiallyfixeddrugeruptionthatmayclinicallyappearwithvariableaspectsandmaybemisdiagnosed.
Footnotes

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SourceofSupport:Nil
ConflictofInterest:Nil.

References

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