Miescher's cheilitis: Surgical management and long term outcome of an extremely severe case.

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InternationalJournalofSurgeryCaseReports31(2017)241–244

ContentslistsavailableatScienceDirect

International

Journal

of

Surgery

Case

Reports

j o u r n al ho m e p a g e :w w w . c a s e r e p o r t s . c o m

Miescher’s

cheilitis:

Surgical

management

and

long

term

outcome

of

an

extremely

severe

case

Alessandro

Innocenti

a,∗

_,

_Marco

_Innocenti

a

_,

_Cecilia

_Taverna

c

_,

_Dario

_Melita

a

_,

Francesco

Mori

a

_,

_Francesco

_Ciancio

d

_,

_Vincenzo

_De

_Giorgi

b

_,

_Paola

_Parronchi

e

_,

Alessandra

Vultaggio

f

_,

_Andrea

_Matucci

f

a_Plastic_and_{Reconstructive}_{Microsurgery,}_Department_of_Surgery_and_{Translational}_Medicine,_Careggi_University_Hospital,_Florence,_Italy b_Section_of_Dermatology,_Department_of_Surgery_and_{Translational}_Medicine,_University_of_Florence,_Florence,_Italy

c_Section_of_Anatomic_Pathology,_Department_of_Surgery_and_{Translational}_Medicine,_Careggi_University_Hospital,_Florence,_Italy d_Department_of_Plastic_and_{Reconstructive}_Surgery,_University_of_Bari,_Italy

e_Department_of_Medical_{Geriatric—Immunology}_and_Cellular_Therapies_Unit,_Careggi_University_Hospital,_Florence,_Italy f_Department_of_Medical_{Geriatric—Immunoallergology}_Unit,_Careggi_University_Hospital,_Florence,_Italy

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received3November2016

Receivedinrevisedform23January2017 Accepted25January2017

Availableonline30January2017

Keywords:

Cheilitisgranulomatosa Miescher’scheilitis Lip

Swellingofthelips Cheiloplasty Casereport

a

b

s

t

r

a

c

t

INTRODUCTION:Miescher’scheilitisisclinicallycharacterizedbypersistentswellingofthelip(s).Its

pathogenesisisstillunknown.Histopathologicallyischaracterizedbysub-epithelialedema,increased

numberofdilatedlymphaticvesselsandaninﬂammatoryinﬁltrateand/ornon-caseating/non-necrotic

granulomas.Evenifthedisordermustbecontrolledbymedicaltherapy,surgerymayberequiredtotreat

mostseverecases.

PRESENTATIONOFTHECASE:Wereporta30-year-oldmanwhopresentedapersistentswellingofboth

lipssince8years,previouslytreatedwithintralesionalsteroidandimmunosuppressivetherapy.Clinical

examinationdidnotshowfacialnervepalsyorotherassociatedconditions.Onthebaseofclinicaland

histopathologicalﬁndings,adiagnosisofMiescher’ssyndromewasmade.PatientunderwentConway’s

reductioncheilopastyrepairedwithlocalﬂaps.Atone-yearfollow-up,thepatientdoesnotshowlocal

recurrenceofthedeformity;bothoralcontinenceandlipsensationarepreserved.

DISCUSSION:Becauseofitsextremerarityandunknownetiopathogenesis,Miescher’scheilitisreceives

poorattentionandmayoftenremainmisdiagnosed.Severalmedicaltherapiesareproposed,inparticular

steroidsandimmunosuppression.Evenifmedicaltherapyremainsthemaintreatment,surgerymaybe

required.

CONCLUSION:Satisfactoryresultshavebeenobtainedcombiningmedicaltherapyandsurgicalapproach.

accessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Miescher’scheilitisisachronicdisﬁguringconditionclinically characterizedbypersistentswellingofthelips,consistingina gran-ulomatouscheilitis[1].TheetiologyofCG isstillunknown,but ageneticpredispositionmaybepossible[2].Itpresentsaseries ofclosely relateddisease,characterizedbylipswelling, suchas sarcoidosis,Crohn’sdisease,foreignbodyreaction,mycobacterial infections(tubercolosis,leprosyandatypicalmycobacteria infec-tion),deepfungalinfection,contactallergyanddentalinfections. Therefore,diagnosisofCGisadiagnosisofexclusionandallmajor pathologiesthatcanmimic thisconditionshouldberuleoutto startthetherapy, avoidingtheexacerbationofthediseaseitself

∗ Correspondingauthorat:VialeGiacomoMatteotti42,50132,Firenze,Italy. E-mailaddress:innocentialessandro@alice.it(A.Innocenti).

[3].Histopathologically,itischaracterizedbysub-epithelialedema, increasednumberofdilatedlymphaticvessels,inflammatory infil-trateandnonnecroticandnoncaseatinggranulomas,consisting oflymphocytesandepithelioidhistiocytes.Traditionally,medical therapiesrepresentthefirstchoiceoftreatment.Itincludes bio-logicagents,immunomodulatorsandintralesionalinfiltrationof steroids[4–7]Evenifreductioncheiloplastyremainstheonlyreal effectivesolutionforunresponsivecases,Miescher’schelitis gran-ulomatosaneedsmedicaltherapytostabilizethesurgicaloutcome andtopreventrecurrenceofthepathology.Wehereinreporta caseofMiescher’scheilitis,unusualforitsextremeseverity,forthe simultaneousinvolvementofboththelipscompletely unrespon-sivetothepreviousmedicaltreatments.

http://dx.doi.org/10.1016/j.ijscr.2017.01.062

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242 A.Innocentietal./InternationalJournalofSurgeryCaseReports31(2017)241–244

Fig1. Frontalpreoperativeviewshowingdiffusesevereenlargementofboththe lips,withﬁssuringinthemidlineofthelower.

2. Casereport

A30-year-oldman ofAfricandescent cametoourattention becauseofanextremelysevereswellinginvolvingbothlips(Fig.1). Suchconditionbeganin 2006withtheinvolvementfirstofthe upper,followedbythelowerlip.Thediseaseprogressivelyworsen up to the present. Both past medical and family history were unremarkable.Tuberculosis,sarcoidosisandCrohn’sdiseasewere excludedbyChestHigh-resolutioncomputedtomography(HRCT), colonoscopyandintestinalbiopsy.Neurologicexaminationdidnot showedperipheralfacialnervepalsy.Thepatienthadalready expe-riencedseveralmedicaltreatmentsincludingintra-lesionalsteroid injections (triamcinolone)and systemic steroids (prednisolone) withprogressionofthelipedemaandoff-labelanti-TNF-alfa ther-apy(infliximab5mg/kgevery8weeks)whichwasabletostabilize thedisease.Localphysicalexaminationreportedsevereswellingof bothlips.Thesuperficialmucosalookedtranslucent,dry,with para-medianbrownishdottingandfissuredchaps.Consistencyofthelips wasfirmlyelastic,thustolimitfacialmimic.Intraoralexamination showednoparticulartissueabnormalities,neitherfissuredtongue orlinguaplicata.Thepatientreferredloweredlocalsensation, func-tionallimitation,but, aboveall, dramaticsocial embarrassment withacompletelackofconfidence.

Anincisionalbiopsywastakenfromtheupperlip. Histopatho-logicalexaminationshowednumerousdilatedlymphaticvessels andamildinflammatoryinfiltrate,composedoflymphocytesand rarenoncaseatingepithelioidgranulomasinthesubepithelial con-nectivetissue (Fig.2), consistentwitha diagnosisofMiescher’s cheilitis.Invitrostudiesfromabiopsyfragmentrevealedamixed CD4+ andCD8+ T lymphocytepopulationable toproducehigh levelsofInterferon(IFN-)-gammaandTumornecrosisfactor (TNF-)-alfa,consistentwiththegranulomatousinflammation(datanot shown).

Afteraclinicallystablepreoperativeperiodoftwoyearswith nofurtherincreaseoflipdimensions,achievedwithanti-TNF-alfa

Fig.2. Histopathologicalexaminationofanincisionalbiopsytakenfromtheupper lipshowednumerousdilatedlymphaticvesselsandamildinﬂammatoryinﬁltrate composedoflymphocytesandrarenon-caseatinggranulomasinthesubepithelial connectivetissue(inset),consistentwithadiagnosisofMiescher’scheilitis.

therapy,thepatientunderwent a surgicalprocedure. Toreduce thepronouncedanteriorprojectionofthevermillion,thepatient underwentatransversesickle-shapedmucosaenblockremoval between1.2 and1.5cm dorsaltothe vermillionborder, basing onConway’stechnique[8](Fig.3).Intra-andextraoralmucosal ﬂapswereharvestedtoisolateandremovealltheedematous tis-sue,whichinvolvedpartoftheorbicularismuscle.Macroscopically inﬁltratedmusclewasalsoremoved.Oncetheareawascompletely remodeled,theexcessofmucosawasremovedandthedefectwas closedinadoublelayer.After12-monthsfollow-up,thepatientdid notshowlocalrecurrenceofthediseaseandtheoralcontinence waspreserved,withnormallipsensation(Fig.4).

3. Discussion

In 1945 Miescher [9] described a mono-symptomatic or oligo-symptomaticdiseaseconsistinginagranulomatous cheili-tis, actually regarded as the most common manifestation of Melkersson-Rosenthalsyndrome,whichincludesCG,facialpalsy andﬁssuredtongue[10].ItisestimatedthattheincidenceofCGis 0,08%inthepopulation[11].

Miescher’scheilitisconsistsinaninﬂammatorydisorderwith non-infectiousandnon-necroticgranulomasanditappearsasa painless enlargementof thelips,withor withoutfacial edema,

Fig.3. (a)Preoperativefrontalview;(b)and(c)Transversesickle-shapedmucosaenblockremovalbetween1.2and1.5cmdorsaltothevermillionborder;(d)Removalof themucosalexcess;(e)Immediatepostoperativefrontalview.

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A.Innocentietal./InternationalJournalofSurgeryCaseReports31(2017)241–244 243

Fig.4.Oneyearpostopfollow-upfrontalview.

producing both aestheticand functionaldeformities. Usually,it appearsduringtheseconddecadeoflife,affectingmostlywomen, withnoracial or ethnicpredilection and it regresseswith age. Althoughdifferentmedicaltreatmentshavebeenproposed, includ-ingintra-lesioninjectionsofsteroidsorimmune-modulatordrugs

[4–7], surgicaltherapy oftenremains theonly solutiontotreat

unresponsive cases. Thiscondition limits the social life due to severe embarrassment, especially in the most dramatic forms. Cheiloplastyactsthemostefﬁcientmanagementof these unre-sponsive and disﬁguring conditions, providing good aesthetic resultsandfunctionalrecoveryevenifthemedicaltherapyneeds tobeadministered[12,13].

Due to its extreme rarity,Miescher’s cheilitis receives poor attentionandmayoftenremainmisdiagnosed.Evenifitisvery difﬁculttocorrelateMiescher’scheilitistospeciﬁcetiologicfactors, probablythedisorderisapoly-etiologicaldiseasebasedongenetic oracquiredpredisposition,associatedtofunctionaldisturbanceof autonomousnervoussystemresultinginagranulomatousreaction.

[14]Itmaymimicsangioedemabutitdoesnotrespondto antihis-taminesorsteroids.Althoughitmayresolvespontaneously,after severalrecurrencesitcouldbecomechronic,resultinginmultiple non-infectiveandnon-necroticgranulomas.

Granulomatous cheilitis usually affects only the upper lip

[15–17]lessfrequentlyonlythelowerlip,andonlyrarely,asinour

casereport,bothlips.Evenifsomepermanentfacialinvolvement hasbeenreportedfollowingmultipleattacks,facialnerveweakness usuallyresolves spontaneously.Sometimespatientsmayreport pain or burning sensation, especially in intraoral involvement. Rarely, it appears in associationwith systemic symptoms such asfever,regionallymphnodesenlargementandgeneralmalaise

[18,19].Miescher’scheilitismaypresentaloneorinconjunction

withotherchronicdiseases (likeDown’ssyndrome,sarcoidosis, Crohn’s disease,psoriasis,thyroiditis, kerathitis,diabetes melli-tus,ocularpalsies,leprosy and multiplesclerosis.) Inthe latest stagesofthedisorder,noncaseatinggranulomascanbepresent inthechorioneveniftheirabsencedoesnotexcludethecondition. Differentialdiagnosisshould includeeveryconditioncaused by granulomas,allthechronicformsofmacrocheliaandfacialedema.

4. Conclusion

The medical treatment of Miescher’s cheilitis often results inefﬁcient, requiring surgical treatmentfor satisfactory results. Reduction cheiloplasty is proven to bean effective method to correctthedeformity,recoveringbothfunctionalandsatisfactory aestheticappearance,whenprevioustherapiesfailed.Inanycase, medicaltherapyismandatoryinpost-surgicalperiodtomaintain thesurgicalresult.

Conﬂictofinterest

Allauthors disclose anyﬁnancial and personal relationships withotherpeopleororganisationsthatcouldinappropriately inﬂu-ence(bias)theirwork.

Financialdisclosure

None.

Authorcontribution

Allauthorshavecontributedtocreatethepaper.

Funding/Support

Nosourcesoffundingsponsoredthisstudy.

Ethicalapproval

Alltheprocedureperformedinstudiesinvolvinghuman par-ticipants werein accordance withthe ethical standards of the institutionalandnationalresearchcommitteeandwiththe1964 Helsinkideclarationanditslateramendmentsorcomparable eth-ical standards.The patient’s consentwas obtainedfor thecase report.

ThiscasereportiscompliantwiththeSCAREGuidelines[20].

Consent

Writteninformedconsentwasobtainedfromthepatientfor publicationofthiscasereportandaccompanyingimages.Acopy ofthewrittenconsentisavailableforreviewbytheEditor-in-Chief ofthisjournalonrequest.

Guarantor

Dott.AlessandroInnocenti.

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