Successful therapeutic approach in a patient with elephantiasic pretibial myxedema,

AnBrasDermatol.2020;95(4):469---472

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

Successful

therapeutic

approach

in

a

patient

with

elephantiasic

pretibial

myxedema

夽,夽夽

Marina

Ferreira

_,

_Luciana

_Helena

_Zacaron

_,

_Annair

_Freitas

_do

_Valle

_,

Aloisio

Carlos

Couri

Gamonal

a_{UniversityHospital,UniversidadeFederaldeJuizdeFora,JuizdeFora,MG,Brazil}

b_{GraduateandPost-GraduatePrograminDermatology,FaculdadeSuprema,JuizdeFora,MG,Brazil}

Received15September2018;accepted11February2019

Availableonline25November2019

KEYWORDS Evaluationofresults oftherapeutic interventions; Myxedema; Steroids; Therapeutics

Abstract Localizedpretibialmyxedemaisadermopathywhosetreatmentisachallengein

dermatology, occurring in 0.5---4% of patients with Graves’ disease. This autoimmune

thy-roid conditionstimulatestheproductionofhyaluronicacidandglycosaminoglycansthatare

deposited particularlyin thepretibial region. Clinically, itpresents asa localized,

circum-scribed, and non-depressibleinfiltrate inplaques. Several treatment modalities have been

proposed,andtheir resultsvary,withworse responseobservedinseverecases.This report

presentsthecaseofapatientwithelephantiasicpretibialmyxedemawhowas subjectedto

intralesionalcorticosteroidapplications,resultinginanexcellentandencouragingtherapeutic

responsethatwasmaintained.

©2019SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan

openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

夽 _{How to cite this article: Ferreira M, Zacaron LH, Valle AF,}

Gamonal ACC. Successful therapeutic approach in a patient with elephantiasic pretibial myxedema. An Bras Dermatol. 2020;95:469---72.

夽夽_{StudyconductedattheUniversityHospital,Universidade}

Fed-eraldeJuizdeFora,JuizdeFora,MG,Brazil.

∗_{Correspondingauthor.}

E-mail:marinaferreirajf@yahoo.com.br(M.Ferreira).

Introduction

Localizedpretibialmyxedema isan infrequent manifesta-tion of autoimmune thyroid diseases, especially Graves’ disease.1,2 _{Itsprevalencevaries between0.5% and4%and}

itismorefrequent inthosewithsevereophthalmopathy.3

Commonly, it appears as localized infiltrated plaques, circumscribing the pretibial region.4 _{Its management is}

challenging in dermatology.2 _{Several treatments have}

been proposed, ranging from compression stockings to

https://doi.org/10.1016/j.abd.2019.02.007

0365-0596/©2019SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

470 FerreiraMetal.

Figure1 Clinicalaspectoftherightfootandankle:confluent

brownishnodulesonwaxyplaque.Hypertrichosisand

hyperpig-mentationarenoted.Firstsessionofintralesionalapplication

ofcorticosteroid.

intravenousimmunoglobulin, generating a mild to moder-ate response, with unpleasant results in severe cases.1,4

Thecurrentarticledescribestheauthors’experiencewith intralesionalcorticotherapyinpatientwhopresentwiththe elephantiasicform, noting a satisfactory andencouraging clinicalresponseduringthefollow-upofover11months.

Case

report

A47-year-oldfemalepatienthashadGraves’diseasesince 2005. Four years ago, she presented with elephantiasic-like myxedema on the lower right limb, with a similar condition, toa lesserextent, onthe lower left limb one year ago. The patient developed bilateral exophthalmos andsevereretro-orbitalimpairment.Shewassubjectedto orbitaldecompressionandiodinetherapyin2012, develop-inghypothyroidismwhilemaintainingclinicalstabilitywith levothyroxineuse.

On clinical examination, she presented with non-depressibleedema,associatedwithnodulesand yellowish-brownplaquesthatformedanelephantiasiformpatternon thelowerrightlimb,ontheankleandfootregions,in addi-tiontohyperpigmentation andfissureswithhypertrichosis onthedorsum ofthe footandphalanges, andtoa lesser extent,non-depressibleedemainthelowerleftlimb(LLL) (Figs.1and2).

Thehistopathologicalexaminationshowed hyperortoker-atosisintheepidermis,anintensedepositofmucinbetween collagenbundlesinthereticulardermis, viewedin redon alcianbluecoloration,thatwascompatiblewithmyxedema cutaneous(Fig.3).

Inlightofconfirmationoftheclinicalconditionandthe patient’s desire to improve her appearance, a therapeu-ticprogramwasestablishedwiththeuse oftriamcinolone acetate20mg/mLwithoutdilution,appliedover50points, 0.1mL per point deposited through a 26G 1/2 needle intothe reticulardermis, withthe distance between two application points standardized at 1.0cm. The following areasweretreated:dorsumandlateralregionoftheright foot,proximalphalanx of theright firsttoe,and the left ankle.Theinitialfrequencyoftheprocedurewasmonthly. Afterfourmonthsandbasedonaverysatisfactoryclinical response,theintervalbetweenapplicationswasincreased tobimonthly,withareduction ofthe compoundthat was administered by 50%, maintaining a satisfactory clinical response.

Figure2 Clinicalappearanceoftherightfootandankleatthe

firstsessionofintralesionalapplicationofcorticosteroid.

Non-depressibleedemaassociatedwithhyperpigmentationreaching

thelowerthirdoftherightlimb,includinglateralandposterior

portions.

Figure 3 Importantspacing ofthecollagenbundles ofthe

upperreticulardermis,slightincreaseinthenumberof

fibrob-lasts.Abundantdepositofmucin(arrow)(Hematoxylin&eosin,

Successfultherapeuticapproachinapatientwithelephantiasicpretibialmyxedema 471

Figure4 Clinicalappearanceoftherightfootandankleafter

11monthsofintralesionalcorticosteroidtherapy.Almosttotal

reductionofnodulesandedema,makingtheappearance

resem-blethecontralateralfoot.

Acleardecreaseofnon-depressibleedemaandnodules wasobserved,improvingthecolorationoftheaffectedskin, allowingthepatienttowearshoesthatshewaspreviously unabletoduetohercondition(Figs.4and5).

Discussion

Graves’diseaseistriggered bytheemergence of antibod-ies againstTSH receptors. Exophthalmia,acropathia, and

Figure5 Clinicalappearanceoftherightfootandankleafter

11monthsoftreatmentwithintralesionalcorticosteroid

ther-apy.Animportantreductionofnodulesandcutaneoustexture

isobserved.

pretibialmyxedemaareassociatedconditionsandrepresent latemanifestations,affecting15---50per100,000peopleper year,primarily women.Exophthalmiais usuallypresent in patientswithmyxedema,inapproximately15%ofcases.3---5

The etiology of myxedema is unknown, but it is spec-ulatedthat stimulation of anti-TSH receptorleads tothe proliferationoffibroblasts,causinganincreaseinhyaluronic acidandglycosaminoglycansandtheconsequent accumula-tionoffluidsandcompressionofthesmalllocallymphatics. Other proposedcausalfactors arevenous stasis andlocal trauma.4

Clinically, the lesions are light-colored, but may also appear as yellowish-brown to reddish-brown. Hyper-pigmentation, hyperkeratosis, fissures, hiperhidrosis and hypertrichosisarealsopresent. Lesionsmayhave adense aspect,withtheprominenceofhairfollicles,generatingthe peaud’orangesign.Thisdermopathymaybeclassifiedinto fourtypes:non-depressibleedemathatisaccompaniedby changesincolor,plaques,nodules,andelephantiasiform.1,5

Themost commonlyaffected locationisthe anterolateral regionofthelowerlimbextremities,possiblyextendingto theposteriorfaceandfeet.Thecondition maypersistfor monthstoyears,andtherearerarecasesof spontaneous regression,especiallyinlocalizedconditions.Elephantiasic formsarerare,typicallyprogressiveandrefractoryto treat-ments,leadingtoseverefunctionalandemotionaldamage,6

aspresentedinthisreport.

Treatment withtopicalmedium-tohigh-potency corti-costeroidsunderocclusionhasbeen described,generating afavorableclinicalresponsebutwithahigherfailurerate withregard to long-term remission.1,4 _{Trials with}

intrale-sionaltriamcinolonehavereportedtherapeuticsuccessand ahigherpercentageofcompleteremissioninthreetofour years,includingdramaticresponses,withouttherecurrence oflesions,asobservedbyKumaranetal.in2015.4_Several

studieshavecombinedmedications,suchaspentoxifylline andtopicalororalcorticosteroid,withlesseffectiveresults inthecasesofsevereforms(elephantiasiformanddiffuse).4

In2015,Lanetal.comparedtheuseofintralesional tri-amcinoloneacetateinpatientswithseveralclinicalformsof localizedmyxedema,reportingsatisfactoryresponsesinall presentations,corroboratingthetherapeuticinitiativeand thetechniqueperformedinthepatient.2

472 FerreiraMetal. Theinjectiontechniquewithcorticosteroids,duetotheir

anti-inflammatoryandimmunosuppressiveproperties,7

gen-erates a significant and permanent reduction in pretibial dermalinfiltratesinthesepatients,withoutcausing degen-eration,atrophy,orhyperpigmentationafterapplication.In addition,it ispossible tomaintain theseresults,asin the caseofthepatientafter11months.

Thus,thepresentpatient’stherapeuticsuccessusingonly intralesional corticosteroid without other adjuvant treat-ments was associated with a rapid clinical response and theabsenceofsystemicsideeffects,producing apositive emotionalandsocialimpactandencouragingtheuseofthis techniqueinotherpatientswithsimilarcases.

Financial

support

Nonedeclared.

Authors’

contributions

MarinaFerreira:Compositionofthemanuscript;intellectual participationinthe propaedeuticand/ortherapeutic con-ductinthestudiedcases;criticalreviewoftheliterature.

LucianaHelenaZacaron:Approvalofthefinalversionof themanuscript;intellectualparticipationinthe propaedeu-ticand/ortherapeuticconductinthestudiedcases;critical reviewoftheliterature;criticalreviewofthemanuscript.

AnnairFreitasdoValle:Approvalofthefinalversionof themanuscript;intellectualparticipationinthe propaedeu-ticand/ortherapeuticconductinthestudiedcases;critical reviewoftheliterature;criticalreviewofthemanuscript.

AloisioCarlosCouriGamonal:approvalof thefinal ver-sion of the manuscript; conception and planning of the study; critical review of the literature; criticalreview of themanuscript.

Conflicts

of

interest

Nonedeclared.

References

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4.Sendhil Kumaran M, Dutta P, Sakia U, Dogra S. Long-term follow-upand epidemiologicaltrends in patientswith pretib-ialmyxedema:an11-yearstudyfromatertiarycarecenterin northernIndia.IntJDermatol.2015;54:e280---6.

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6.RapoportB,AlsabehR,AftergoodD,McLachlanSM. Elephantia-sicpretibialmyxedema:insightintoandahypothesisregarding thepathogenesisoftheextrathyroidalmanifestationsofGraves’ disease.Thyroid.2000;10:685---92.

7.VannucchiG, Campi I, Covelli D,Forzenigo L, Beck-Peccoz P, Salvi M. Treatment of pretibial myxedema with dexametha-zoneinjectedsubcutaneouslybymesotherapyneedles.Thyroid. 2013;23:626---32.