r e v b r a s r e u m a t o l . 2016;56(1):82–85
w w w . r e u m a t o l o g i a . c o m . b r
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
Case
report
Generalized
morphea
in
a
child
with
harlequin
ichthyosis:
a
rare
association
Maria
F.A.
Giacomin
a,
Camila
M.P.
Franc¸a
a,
Zilda
N.P.
Oliveira
b,
Maria
C.R.
Machado
b,
Adriana
M.E.
Sallum
c,
Clovis
A.
Silva
a,c,∗aPediatricRheumatologyUnit,Children’sHospital,FaculdadedeMedicina,UniversidadeSãoPaulo,SãoPaulo,SP,Brazil
bPediatricDermatologyUnit,FaculdadedeMedicina,UniversidadeSãoPaulo,SãoPaulo,SP,Brazil
cDivisionofRheumatology,FaculdadedeMedicina,UniversidadeSãoPaulo,SãoPaulo,SP,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received24October2013 Accepted21May2014
Availableonline26November2014
Keywords:
Harlequinichthyosis Children
Morphea Scleroderma
a
b
s
t
r
a
c
t
Introduction:Harlequinichthyosis(HI)isasevereandrarehereditarycongenitalskindisorder
characterizedbyexcessivedryness,ectropionandeclabion.Theassociationofichthyosis withsystemicsclerosishasbeendescribedinonlythreechildren.Nopatientwith general-izedmorphea(GM)associatedwithharlequinichthyosiswasdescribed.
Casereport:A4-yearsand6-monthsgirl,diagnosedwithharlequinichthyosisbasedon
dif-fusecutaneousthickening,scaling,erythema,ectropionandeclabiumsincethefirsthoursof birthwasdescribed.Shewastreatedwithacitretin(1.0mg/kg/day)andemollientcream.At 3 years and 9 months, she developed musclecontractures with pain on motion and limitation in elbows and knees, and diffuse sclerodermic plaques on the abdomen, back,suprapubicareaandlowerlimbs.Skinbiopsyshowedrectifiedepidermisandmild hyperorthokeratosis,reticulardermiswithperivascularandperiadnexalinfiltratesof lym-phocytesandmononuclearcells,andreticulardermisandsweatglandsclerosissurrounded byadensecollagentissue,compatiblewithscleroderma.ThepatientfulfilledtheGM sub-typecriteria.Methotrexateandprednisonewereintroduced.At4yearsand3months,new sclerodermalesionsoccurredandazathioprinewasassociatedwithprevioustherapy,with noapparentchangesaftertwomonths.
Discussion:AcaseofharlequinichthyosisassociatedwithaGMwasreported.Thetreatment
ofthesetwoconditionsisachallengeandrequiresamultidisciplinaryteam.
©2014ElsevierEditoraLtda.Allrightsreserved.
Morfeia
generalizada
em
uma
crianc¸a
com
ictiose
arlequim,
uma
associac¸ão
rara
Palavras-chave:
Ictiosearlequim
r
e
s
u
m
o
Introduc¸ão:Ictiosearlequiméumadoenc¸acutâneacongênitagrave,autossômicaerara,
caracterizadaporressecamentoexcessivodapeleehiperqueratose.Aassociac¸ãodeictiose
∗ Correspondingauthor.
E-mailaddresses:clovis.silva@icr.usp.br,clovisaasilva@gmail.com(C.A.Silva). http://dx.doi.org/10.1016/j.rbre.2014.05.004
rev bras reumatol.2016;56(1):82–85
83
Crianc¸as Morfeia Esclerodermia
comesclerosesistêmicafoidescritaemapenastrêscrianc¸as.Aindanãofoidescritonenhum pacientecommorfeiageneralizada(MG)associadaàictiosearlequim.
Relatodecaso: Meninadequatroanoseseismesesdeidadecomdiagnósticodeictiose
arlequimbaseadoemespessamentocutâneodifuso,comfissuras,descamac¸ão,eritemae sangramentodalesãodesdeasprimeirashorasdevida.Apacientefoitratadacomacitretina (1,0mg/kg/dia)ecremeemoliente.Aostrêsanosenovemeses,desenvolveucontraturas muscularescomdoràmovimentac¸ãoelimitac¸ãonoscotovelosejoelhoseplacas escle-rodérmicasdifusasnoabdômen,nascostas,naregiãosuprapúbicaenasextremidades inferiores.A biópsiade pelemostrouepiderme retificadae hiperqueratoseleve,derme reticularcomlinfócitos,infiltradomononuclearperivasculareperianexialeescleroseda dermereticulareglândulasudorípararodeadaporumtecidocolágenodenso,compatível comesclerodermia.ApacientepreencheuoscritériosparaosubtipoMG.Metotrexatoe prednisonaforamintroduzidos.Aosquatroanosetrêsmeses,apresentounovaslesões esclerodérmicas,associando-seazatioprinaàterapêuticaanterior,semrespostaapósdois meses.
Discussão: UmcasodeictiosearlequimassociadaàMGfoidescrito.Otratamentodessas
duascondic¸õeséumdesafioerequerumaequipemultidisciplinar.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Juvenilecutaneoussclerodermaisarareconditionin pedi-atricpatientscharacterizedbytheinvolvementofthe skin and/orsubcutaneoustissue.1,2 Generalizedmorphea(GM)is anuncommonsubtypeoflocalizedsclerodermaandoccurs in7%ofthepatients.2TheassociationofGMwithother cuta-neousdiseaseswasrarelyreportedintheliterature,especially withichthyosiformdiseases.
Ofnote,ichthyosiscomprehendsaheterogeneousgroupof skindiseasescharacterizedbycutaneoushyperkeratinization andmaybecongenitaloracquired.3Harlequinichthyosisisa congenitalform,transmittedinanautosomalrecessivemode. Itisthemostsevereandoftenfatalformofichthyosis.4
Theassociationofichthyosiswithsclerodermahasbeen describedinonlyfourpatients.Threeofthemhadjuvenile systemic sclerosis, and one of them had localized sclero-derma.Twoofthejuvenilesystemicsclerosispatientswere associated with ichthyotic-appearing lesions,5 and one of them withacquired ichthyosis.6 Thelocalized scleroderma patient was associated with ichthyotic-appearing lesions.5 However,toourknowledge,nopatientwithGMscleroderma associated with the harlequim subtype of ichthyosis was reported.Thiscaseisdescribedherein.
Case
report
A4-yearsand6-monthsgirl wasdiagnosedwithharlequin ichthyosis at neonatal period, based on diffusecutaneous thickening,diffuseplate-likescales,erythema,fissures, bleed-inglesions,bilateral ectropionand eclabiumsincethefirst hours of life. No history of parental consanguinity and harlequin ichthyosis were observed. She was a term new-born after cesarean delivery. Her birth weight and height were2.650gmand43cm,respectively.Microcephaly,auricular pinna and nasal abnormalities, alopecia and flexion con-tracturewerenotevidenced.Shewastreatedwithacitretin
84
rev bras reumatol.2016;56(1):82–85Fig.1–Hyperkeratosisparaketatotic,agranulose,regular
epidermalacanthosisandthickeningofthedermiswith
proliferationofvesselswithmildlymphocytic inflammatoryinfiltrateandpsoriasiformdermatitis.
lesionsinabdomen(Fig.2),lowerlimbs,backandsupra-pubic areasandazathioprine(3.0mg/kg/day)wasintroducedalong withprednisoneandmethotrexatewithnoimprovementafter twomonthsoftherapy.Topicalcorticosteroidwasnotused. Atpresent,herfollow-upiscomposedofamultidisciplinary teamwitharheumatologist,dermatologist,ophthalmologist, geneticist,physiotherapistandoccupationaltherapist.
Fig.2–Diffusecutaneousthickening,cracking,scaling, erythema,bleedingandichthyosiformlesions,anddiffuse
sclerodermplaques(arrow)ontheabdomen.
Discussion
To our knowledge, we describe herein the first case of harlequinichthyosisassociatedtoGMdiagnosis.This congen-italdiseaseoccurredpreviouslytothesclerodermadiagnosis, notinagreementwiththerarecasesofacquiredichthyosis andsclerodermareportedintheliterature.5,6
Accordingtothenewclassificationcriteria,localized scle-roderma hasfour differentsubtypes:plaquemorphea, GM, linearsclerodermaanddeepmorphea.8–10TheGMisdefined by the presence of four or more plaques, with individual plaquesgreaterthan 3cmandinvolvingatleasttwooutof sevenanatomicsites,2 asevidencedinourpatientthat pre-sentedlesionsoccurringinupperandlowerlimbs,andtrunk. Furthermore,ichthyosis iscomposedofcutaneous kera-tinization diseases that can be inherited or acquired.3 Congenitalichthyosisisoftenassociatedwithavarietyof typi-calneonatalphenotypeswithscalinganderythema.Themain subtypesarecongenitalichthyosiformerythroderma,lamellar andharlequinichthyosis,includingoverlappingphenotypes. Themildsubtypeiscongenitalichthyosiformerythroderma withfineandwhitescaling,anddifferentdegreesoferythema. Coarse and brown/dark scaling are observed in lamellar ichthyosis,generallywithcollodionmembraneandectropion. Theharlequinichthyosisisamoreseveresubtypeassociated withveryscalingerythroderma,collodionmembraneand pro-nouncedectropion.5,11Ofnote,acollodionbabyisdefinedby erythroderma,shinyandtightskin,likeparchment,covering the entirebody atbirth.Itisaninitialpresentationof sev-eralgeneticconditions,includingcongenitalichthyosis,12as observedinourcase.
Thediseasecourseisgenerallyseverewithmultiplejoint contractures.13,14Ourpatientpresentedcontracturesmainly inelbowsandknees,possiblyduetoassociationwithGM.
One limitation of the present case was the absence of electronicmicroscopyintheskinbiopsyandgenetic evalua-tions,sincethisisanautosomalrecessivecongenitaldisease.5 ABCA12mutationanalysisshowedthat52%ofsurvivorshad heterozygousmutations,andalldeathswereassociatedwith homozygousmutations,whilemissensemutationsare usu-ally related with milder phenotypes.5,15,16 The association between harlequinichthyosis and scleroderma,an autoim-munedisease,isprobablycoincidental.
Ofnote, acquiredichthyosis withsystemic sclerosishas been described in four patients after this autoimmune diagnosis,6,7 however the rare subtype of harlequin had not been previously reported. Other associations between harlequinichthyosisandautoimmunechronicdisordershave beenrarelydescribedwithoutaclearrelationshipwith patho-genesis ofautoimmunity, such ashypothyroidism,13 celiac disease17andjuvenileidiopathicarthritis.13,14
rev bras reumatol.2016;56(1):82–85
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ofthetreatmentconcomitantlyofthesetwosevereandrare conditionsshouldhavecontributedtothepoorresponse ther-apyinourcase.
Theoutcomeofharlequinichthyosisisgenerallyrelated tostillbirth orfirst weeksoflifedeathduetoprematurity, renalfailure,respiratoryinsufficiencyandinfection.21Toour knowledge,onlyeightcaseswithisolatedharlequinichthyosis orassociatedwithjuvenilerheumatoidarthritissurvivedthe neonatal period, with a median of current age of 4 years (rangedfrom6monthsto14years).13
In conclusion, we reported the first case of harlequin ichthyosisassociatedwithararetypeofjuvenilescleroderma. Thetreatment ofthese two simultaneousillnesses isvery challengingindeedandrequiresamultidisciplinaryteam.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgments
ThisstudywassupportedbyFundac¸ãodeAmparoàPesquisa doEstadodeSãoPaulo–FAPESP(grant#08/58238-4toC.A.S.), Conselho Nacional de Desenvolvimento Científico e Tec-nológico–CNPq(302724/2011-7toC.A.S.),FedericoFoundation toC.A.S.andNúcleodeApoioàPesquisa“SaúdedaCrianc¸ae doAdolescente”daUSP(NAP-CriAd).
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