Annular epidermolytic ichthyosis: a case report and literature review,

(1)

Dermatologia

www.anaisdedermatologia.org.br

CASE

REPORT

Annular

epidermolytic

ichthyosis:

a

case

report

and

literature

review

夽,夽夽

Emanuella

Stella

Mikilita

,

Irina

Paipilla

Hernandez

,

Ana

Letícia

Boff

,

Ana

Elisa

Kiszewski

∗

DermatologyService,SantaCasadeMisericórdiadePortoAlegre,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre, PortoAlegre,RS,Brazil

Received3April2019;accepted25September2019 Availableonline5May2020

KEYWORDS

Hyperkeratosis, epidermolyitic; Ichthyosis; Ichthyosiform erythroderma

Abstract Annularepidermolyticichthyosisisararesubtypeofepidermolyticichthyosisthat is characterized by erythematous,polycyclic, and migratory scaly plaquesaccompanied by palmoplantar keratoderma. This report presents the case ofan 8-year-old girl who devel-opedmigratory,erythematous,scalyplaquesassociatedwithpalmoplantarkeratoderma.The initial hypothesiswaserythrokeratodermia variabilis etprogressiva;however, theﬁndingof epidermolytichyperkeratosisinhistopathologicalexaminationledtothediagnosisofannular epidermolyticichthyosis.

Introduction

Annularepidermolyticichthyosis(AEI)isararephenotypic variantofepidermolyticichthyosis(EI),alsoknownas con-genitalbullousichthyosiform erythroderma,an autosomal

夽 _How _to _cite _this _article: _Mikilita _ES, _Hernandez _IP, _Boff _AL,

KiszewskiAE.Annularepidermolyticichthyosis:acasereportand literaturereview.AnBrasDermatol.2020;95:484---9.

夽夽_Study_conducted_at_the_Dermatology_Service,_Hospital_Santa

CasadeMisericórdiadePortoAlegre,UniversidadeFederalde Ciên-ciasdaSaúdedePortoAlegre,PortoAlegre,RS,Brazil.

∗_{Corresponding}_author.

E-mail:[email protected](A.E.Kiszewski).

dominantdisordercharacterizedbyextensiveerythroderma and formationof blisters inearly life.1---3 _Unlike _EI,_in _AEI

theclinicalsymptomsimproveintheﬁrstyearsoflife,and patients develop annular polycyclic, hyperkeratotic, and erythematousplaqueswithmigratoryfeatures,inthetrunk andextremitiesalongwithpalmoplantarkeratoderma.1,4

Case

report

An 8-year-old female patient was attended at the pedi-atric dermatology outpatient clinic of the Hospital Santa Casa of Porto Alegre with a report of diffuse dermatosis that began in theﬁrst monthsof life. Upon examination, thepatientpresentederythematous,scaly,hyperkeratotic https://doi.org/10.1016/j.abd.2019.09.030

(2)

Figure1 Hyperkeratosisinpalms.

plaques with prominent borders, affecting the mesogas-trium, cubital fossae, popliteal fossae, and inguinal and cervicalregions,aswellaspalmoplantarhyperkeratosisand yellowish hyperkeratotic plaques on the scalp and nasal introitus(Figs.1,2and3A).Noassociatedchangesinhair, nails,ormucosawereobserved.

Thepatientdeniedanysymptomsandtherewasno back-groundoffamilyhistoryofsimilarcasesandconsanguinity. Afterone month, shewasreassessed andthe appearance of the plaques changed, increasing the extension of the affectedareas;however,thepolycyclicaspectdisappeared (Fig.3B).

Skinbiopsyintheextensorportionoftheforearmshowed acanthosis,papillomatosis,andhyperkeratosiswithmarked epidermolysisinthegranularlayer(Fig.4).

Discussion

AEI wasﬁrstdescribed in 1992 by Sahn etal.5 _and _is _the

resultofdominantmutationsinthekeratin1andkeratin10 genes.1---7_Individuals_with_this_variant_may_present_with

bul-lous ichthyosis at birth and hyperkeratoticlichen plaques on the areas of ﬂexion and extensor surfaces in the ﬁrst yearsof life.1 _{Characteristically,} _they_also _develop

recur-Figure2 Erythematous,hyperkeratoticplaque,with promi-nentandgeographicalborderinthecervicalregion.Yellowish keratoticplaquesattheangleofthemouthandchin.

rent outbreaks of annular, polycyclic, erythematous, and scalyplaquesonthetrunkandproximalextremities.1,4_The

presentauthors have reviewedtheliterature publishedin English,Portuguese, andSpanish sinceitsdescription and found 19cases in 10 publications thatare summarized in

table1.1---10

Inthehistopathology, thehyperkeratoticlesionsofthe AEI revealed hyperkeratosis, acanthosis, and a thickened granularlayer.Keratinocytesinthespinouslayersand supe-riorgranulosa ofthe epidermisdemonstrated cytoplasmic vacuolization and prominent keratohyaline granules.1,2,4,6

Basal keratinocytes appeared normal, but there was an increaseinthenumberofmitoses.Regardingﬁndingsfrom electronmicroscopy,therewereabnormalkeratinﬁlaments inthesuprabasalkeratinocytes,increaseofkerato-hyaline

Figure3 (A)Erythematous,keratoticplaqueswithprominentandgeographicalbordersonthearms,forearms,cervical,armpits, lateralregionofthetrunk,andumbilicalandsupra-umbilicalregions.(B)Thesamepatientamonthlater,presentingerythematous andhyperkeratoticplaquesalongtheentirearm,forearm,andanteriorchest,sparingtheumbilicalandsupra-umbilicalregions.

(3)

Sahnetal.,1992 1 30years/F At8monthsofage,she presentedsevereand intermittentscalylesions associatedwithblisters.In adolescence,shepresented hyperkeratoticplaquesinthe ﬂexuresandjoints.Attheage of27,shehadintermittent annularhyperkeratotic, erythematous,polycyclic plaquesonthetrunkand proximalregionofthelimbs, associatedwithmild palmoplantarkeratoderma withﬁssures.

Topicaluseof60% propyleneglycoland6% salicylicacid.Partial responsetotreatment.

2 2years/M(son) At6monthsofage,he developedpapulesthat developedintoboliandcrusts. At2yearsofage,hehad keratoticplaquesonhisneck andarmpits,inadditionto multipleerythematouspapules onthetrunk,extremities,and ear.Noreportofpalmoplantar keratoderma.

Johetal.,1997 3(father) 33years/M Blistersdisseminatedfrom birth.Fromthe1styearoflife, intermittenthyperkeratotic anderythematousplaques associatedwithblistersand itchingupto16yearsofage. Attheageof31,heagain presentedintermittentblisters andhyperkeratoticplaquesin theﬂexures,ankles,andback ofthehandsassociatedwith annularmigratory,polycyclic, scaly,anderythematous plaquesinthetrunkand proximalregionofthelimbs. Palmoplantarkeratodermawas notreported.

Oralacitretin20mgperday topicallyassociatedwith ointmentcontaining propyleneglycoland5% urea.Goodresponseto treatment.

4(daughterof case3)

2nddayoflife/F Generalizedbullouslesionsand moderateerythemasincethe 2nddayafterbirth.At8weeks ofage,shehaderosionsinthe groinandinnerthighs

associatedwithmild desquamationonthedorsum ofthefeet.Noreportof palmoplantarkeratoderma.

(4)

Table1 (Continued)

Authors Casenumber Diagnosisage/sex Ageofonsetandclinical presentation

Treatmentperformed

Sugaetal.,1998 5 11years/M Nohistoryofblisters.Sincethe ageof7months,xeroticplates intheﬂexuresandextensor regions.Intermittentepisodes ofannular,erythematous, scaly,andserpiginousplaques onthetrunkandﬂexuresat11 yearsofage.Noreportof palmoplantarkeratoderma.

Unreported

Michaeletal.,1999 6---9(membersof samefamily)

NA Transientblistersfrombirth. Intermittenterythematous plaques,non-migratory polycyclichyperkeratotic plaquesonthetrunk associatedwithpalmoplantar keratoderma.

Topicaluseof corticosteroids,

calcipotriene,tazarotene. andsalicylicacid.Minimum responsetotreatment.

Sybertetal.,1999 10 5years/M Theﬁrsthoursoflifeshowed bullouslesionsanderosions. Sincethe1stmonth,hehad intermittentpalmoplantar thickeninganderythroderma. At3yearsofage,migratory andintermittent,

hyperkeratotic,erythematous plaquesonthechest,back, andﬂexures.

Unreported.

11(motherofcase 10)

18years/F Intermittentandmigratory erythematousplaques. Erythemaandskinerosions sincebirth.Intermittent palmoplantarhyperkeratosis. Intermittentepisodesof erythrodermaand palmoplantarkeratoderma. 12(auntofcase 10) NA/F Yonedaetal.,1999 13and14(mother

andson)

48years/F Blistersdisseminatedafter birthinbothcaseswith spontaneousimprovementin theﬁrstmonthsandworsening ataround4yearsofage,with annularhyperkeratoticand migratoryplaquesinthetrunk andextremities,maintaining thisconditionintermittently untiladulthood.Noreportof palmoplantarlesions. Etretinatewithout

improvement(did

notreportdose). 18years/M

Naiketal.,2003 15 21years/F Noreportsofcutaneouslesions atbirth.Sincethe1styearof life,therewereintermittent andmigratingpolycyclic erythematousplaquesonthe trunkandhyperkeratotic, verrucous,brownishplaqueson theknees,elbows,andankles. Intermittentpalmoplantar keratoderma.

Oralisotretinoin,topical glucocorticoids,and keratolytics.Topical tazarotenewithpartial response.

(5)

Jhaetal.,2015 16 26years/F Spreadingblisters,recurrent sincebirth.Intermittent hyperkeratoticplaquesonthe trunkfromthe1styearoflife to8yearsofage.Shehad hyperkeratoticplaquesinthe ﬂexuresfromchildhoodto adulthood.Aftertheageof23, shehadannular,intermittent, hyperkeratotic,scaly

erythematousplaquesonthe trunkandthighs.Noreportof palmoplantarkeratoderma.

Acitretin0.5mg/kg/day. Goodresponsefourweeks afterstartingtreatment.

17 2nddayoflife/F Erythrodermaatbirth.Inthe ﬁrstmonthsoflife,

hyperkeratotic,polycyclic, scalyplaquesonthetrunkand limbs.Noreportof

palmoplantarkeratoderma.

Useofemollients.

Abdul-Wahabetal.,2016 18 25years/F Nohistoryoflesionsatbirth. Historyofichthyosiformlesions intheknees,elbows,and ﬂexuresinchildhood.At25 yearsofage,erythematous, scaly,andmigratoryplaqueson thetrunkandlimbs.Noreport ofpalmoplantarlesions.

Lowdoseoralisotretinoin withgoodresponse.

Zakietal.,2018 19 5years/F Blistersdisseminatedafter birth.Migratoryand intermittenterythematous plaques,inadditionto hyperkeratoticplaquesonthe trunkandﬂexures.

Hyperkeratosisand

palmoplantarscalingsincethe ﬁrstmonthsoflife.

Unreported.

M,male;F,female.

granulesin granulelayercells, andperinuclear accumula-tionsofthickenedtonoﬁlamentthatformedaninterrupted perinuclearring.4,5

Themaindifferentialdiagnosisofannularepidermolytic ichthyosisiswitherythrokeratodermiavariabiliset progres-siva(EKVP),1,2 _an _autosomal _dominant_cutaneous _disorder

characterized by erythrokeratodermia and migratory ery-thematous plaques.1,2,7 _EKVP _is _typically _associated _with

mutationsintheconnexins 30.3,31,and 43(GBJ4,GJB3, andGJA1),butrecentstudiessuggestgeneticheterogeneity. DistinctivefeaturesofEKVPincludeonsetduringchildhood, absenceof epidermal fragility, and histologywithout evi-denceofepidermolysis.1_The_major_{ultrastructural}_feature

ofEKVPisareductioninthenumberofkeratinosomesinthe granularlayer.2

Treatment options in the small number of patients reported included topical medications such as retinoids, topicalcorticosteroids,propyleneglycol,calcipotriene,and

keratolyticagents,andlittleresponsewasobserved.5,8,9,10

Threearticlesreportgoodresponsewithsystemicretinoids; twoarticlesciteacitretintreatmentwithgoodresponse6,8

and another reports good response with low doses of isotretinoin.7

Financial

support

Nonedeclared.

Authors’

contributions

Emanuella Stella Mikilita: Approval of ﬁnal version of the manuscript;conceptionandplanningofthestudy;drafting andeditingofthemanuscript.

IrinaPaipillaHernandez:Approvalofﬁnalversionofthe manuscript; conception and planning of the study;

(6)

draft-Figure4 Acanthosis,papillomatosis,andhyperkeratosiswith epidermolysis of the granular layer (Hematoxylin & eosin, ×400).

ingandeditingofthemanuscript;collection,analysis,and interpretationofdata;criticalreviewoftheliterature.

AnaLetíciaBoff:Draftingandeditingofthemanuscript; collection,analysis,andinterpretationofdata.

Ana Elisa Kiszewski: Approval of ﬁnal version of the manuscript; conception and planning of the study; draft-ing and editing of the manuscript; collection, analysis, andinterpretationofdata;intellectualparticipationinthe propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of themanuscript.

Conﬂicts

of

interest

Nonedeclared.

References

1.Zaki TD,Yoo KY,KassardjianM,ChoateKA. Ap.478I>T KRT1 mutationinacaseofannularepidermolyticichthyosis.Pediatr Dermatol.2018;35:e414---5.

2.SybertVP,FrancisJS,CordenLD,SmithLT,WeaverM,Stephens K,etal.Cyclicichthyosiswithepidermolytichyperkeratosis:a phenotypeconferredbymutationsinthe2Bdomainofkeratin k1.AmJHumGenet.1999;64:732---8.

3.SugaY,DuncanKO,HealdPW,RoopDR.Anovelhelix termina-tionmutationinkeratin10inannularepidermolyticichthyosis, avariantofbullouscongenitalichthyosiformerythroderma.J InvestDermatol.1998;111:1220---3.

4.Yoneda K, Morita E, Akiyama M†, Kusunoki T‡, Yamada S, YamamotoS.Annularepidermolyticichthyosis.Br.J.Dermatol. 1999;141:747---76.

5.Sahn EE, Weimer CE Jr, Garen PD. Annular epidermolytic ichthyosis:auniquephenotype.JAmAcadDermatol.1992;27 Pt2:348---55.

6.Jha A, Taneja J, Ramesh V, Singh A. Annular epidermolytic ichthyosis: a rare phenotypic variant of bullous congenital ichthyosiformerythroderma.IndianJDermatolVenereol Lep-rol.2015;81:194---7.

7.Abdul-Wahab A, Takeichi T, Liu L, Stephens C, Akiyama M, McGrathJA.Intrafamilialphenotypicheterogeneityof epider-molyticichthyosisassociatedwithanewmissensemutationin keratin10.ClinExpDermatol.2016;41:290---3.

8.JohGY,TraupeH,MetzeD,NashanD,HuberM,HohlD,etal. Anoveldinucleotidemutationinkeratin10intheannular epi-dermolyticichthyosisvariantofbullouscongenital ichthyosis erythroderma.JInvestDermatol.1997;108:357---61.

9.MichaelEJ,SchneidermanP,GrossmanME,ChristianoAM. Epi-dermolytichyperkeratosiswithpolycyclicpsoriasiformplaques resultingfrommutationinthekeratin1gene.ExpDermatol. 1999;8:501---3.

10.NaikNS.Annularepidermolyticichthyosis.DermatolOnlineJ. 2003;9:4.