Familial “benign” pemphigus? Erythroderma and fatal outcome,

AnBrasDermatol.2020;95(1):75---77

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

Familial

‘‘benign’’

pemphigus?

Erythroderma

and

fatal

outcome

夽,夽夽

Paula

Baldissera

Tansini

_,

_Ana

_Letícia

_Boff

_,

_Magda

_Blessmann

_Weber

_,

Renan

Rangel

Bonamigo

a_{PublicHealthDermatologyService,SecretariaEstadualdeSaúde,PortoAlegre,RS,Brazil}

b_{InstitutodeDermatologiaProf.RubemDavidAzulay,RiodeJaneiro,RJ,Brazil}

c_{DermatologyService,SantaCasadeMisericórdiadePortoAlegre,PortoAlegre,RS,Brazil}

d_{DermatologyService,UniversidadeFederaldeCiênciasdaSaúde,PortoAlegre,RS,Brazil}

e_{SchoolofMedicine,UniversidadeFederaldoRioGrandedoSul,PortoAlegre,RS,Brazil}

Received3September2018;accepted19February2019 Availableonline25November2019

KEYWORDS Pemphigus,benign familial; Dermatitis, exfoliative; Skindiseases, vesiculobullous

Abstract Hailey---Haileydisease,orfamilialbenignpemphigus,isararebullous genodermato-sis that usually presents with flaccidblisters, erosions, andmaceration limitedto flexural areas,resultinginincreasedmorbidityandreducedqualityoflifeforaffectedpatients.The authors reportanunusualcaseofgeneralizedHailey---Haileydiseasewith erythrodermaand fataloutcome.

©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

夽 _{Howtocitethisarticle:TansiniPB,BoffAL,WeberMB,Bonamigo}

RR. Familial ‘‘benign’’ pemphigus? Erythroderma and fatal out-come.AnBrasDermatol.2019;95:75---7.

夽夽_{Study conductedat the PublicHealth Dermatology Service,}

SecretariaEstadualdeSaúde,PortoAlegre,RS,Brazil.

∗_{Correspondingauthor.}

E-mail:[email protected](P.B.Tansini).

Introduction

Hailey---Haileydiseaseisararecutaneousdisorder,featuring dominantautosomalinheritancewithcompletepenetrance andvariableexpressivity, affecting adhesionbetween the epidermal keratinocytes. It is caused by a mutation in theATP2C1gene,whichencodestheintracellularcalcium pump, altering the homeostasis of this ion. Calcium is involved in cellular differentiation, skin barrier repair, cellularadhesion,and keratinocyte motility.Itsincreased levels lead to the alteration of desmosomes and cellular adhesionto theepidermal junction, causing acantholysis. Characterizedbypainful blistering,erosions, and

macera-https://doi.org/10.1016/j.abd.2019.02.006

0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

76 TansiniPBetal. tion,itprimarilyinvolvestheflexuralareasinasymmetric

fashion.1

Case

report

A64-year-oldwomanpresentedwitherythematousplaques with peripheral detachment and multiple erosions in the inframammary, axillary, inguinal, dorsal, and cubital and popliteal fossa regions. Mucous membranes were unaf-fected. She reporteda family history of mother,siblings, and maternal aunts with similar lesions, and previ-ous medical history of systemic hypertension, coronary arterydisease,congestiveheartfailure,dyslipidemia,and hypothyroidism. Histopathological examination revealed acantholysis with intra-epidermal cleavage involving the entire epidermal thickness, demonstrating absence of dermal villi and eosinophils (Fig. 1). The patient was diagnosed with Hailey---Hailey disease based on clin-ical, familial, and histopathological data. Given the multiple comorbidities of the patient, treatment was limitedtotetracycline,prednisone,dapsone, sulfamethox-azole+trimethoprim, cephalexin, and methotrexate, with little or no response. After one year of follow-up, the patientdevelopederythroderma(Figs.2and3)andsystemic symptoms,and was hospitalized. She died due to venous catheter-relatedinfectiouscomplications onemonthafter hospitalization.

Figure1 Extensivesuprabasalacantholysiswith intraepider-mal bullae and keratinocytes with ‘‘dilapidated brick wall’’ appearance(Hematoxylin&eosin,_×40).

Figure2 Exfoliativeerythroderma.Intertriginousareaswith extensiveerythemaandtendencytomaceration.

Figure3 Diffuseerythema,vesicular lesions,erosions,and crustsinlowerlimbsclosetoinguinalfolds.

Discussion

Hailey---Hailey disease was first described in 1939 by the Hailey brothers.1 _{Its prevalence remains unknown and}

its autosomal dominant inheritance pattern shows com-pletepenetranceandvariableexpressivity.Itspathogenesis involvesATP2C1 genemutation,leadingtochangesin cal-cium transport into the Golgi apparatus that result in desmosomaldysfunctionandkeratinocyteacantholysis.2

Disease progression is characterized by chronicity and periodsofexacerbation,withonsetusuallyoccurringinthe secondandthirddecadesoflife.Clinically,flaccidvesicles anderosionsarepresent,witherythematous,occasionally maceratedplaquesthatsymmetricallyinvolvetheflexural, axillary, inframammary, inguinal, and cervical regions. The segmentalformisusuallyunilateral andlinear (along the lines of Blaschko).3 _{The generalized form, as in the}

case reported here, is rare, and a common complication issecondaryinfectionbyfungiandbacteria.Otherfactors associated with worsening of symptoms include heat, sweating, friction, and ultraviolet radiation.4 _{The main}

differential diagnoses are pemphigus vulgaris, Darier’s disease,inversepsoriasis,seborrheicdermatitis,intertrigo, anderythrasma.5_{Thediagnosisisconfirmedby}

histopathol-ogy, which shows extensive suprabasal acantholysis with ‘‘dilapidatedbrickwall’’appearanceand,possibly, dysker-atotic keratinocytes. Immunofluorescence is classically negativeinHailey---Haileydisease,beingunnecessaryinthe presenceoftypicalclinicalandhistopathologicalfeatures.3

Treatment options are limited and depend on clinical severity. Theyincludeoral and topicalantibiotics,topical calcineurin inhibitors, oral and topical corticosteroids, dapsone, acitretin, methotrexate, and cyclosporine.6

Treatmentalternativesforrecalcitrantcasesarebotulinum toxin, surgicalresection,lasertherapy,andphotodynamic therapy.7,8_{Inmost cases,clinical symptomsarelimitedto}

flexural and intertriginous areas. Generalized manifesta-tionsareuncommon,anderythrodermawithfataloutcome isextremelyrare.Thefewcasesreportedintheliterature describe bacterial infection,9 _{cutaneous adverse drug}

reaction, and herpes10 _{as triggering factors for an acute}

disseminationofthedisease.However,thesefactorsdiffer from those of the case reported here, since the patient

Familial‘‘benign’’pemphigus? 77 presented with chronic generalized involvement,

regard-lessofthediagnosisofsecondaryinfectionsandantibiotic therapies,andnotriggersforerythrodermawereidentified. This was, therefore, an extremely severe case of Hailey---Hailey disease that was highly resistant to treat-ment,inapatientwithmultiplecomorbidities,resultingin thedeathofthepatient.

Financial

support

Authors’

contribution

PaulaBaldisseraTansini:Compositionofthemanuscript. Ana Letícia Boff: Intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases.

MagdaBlessmannWeber:Intellectualparticipationinthe propaedeutic and/or therapeutic conduct of the studied cases.

RenanRangelBonamigo:Approvalofthefinalversionof themanuscript;intellectualparticipationinthe propaedeu-ticand/ortherapeuticconductofthestudiedcases;critical reviewofthemanuscript.

Conflicts

of

interest

References

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