Association between three autoimmune diseases: vitiligo, primary biliary cirrhosis, and Sjögren's syndrome,

(1)

AnBrasDermatol.2019;94(6):710---712

Anais

Brasileiros

de

Dermatologia

www.anaisdedermatologia.org.br

CASE

REPORT

Association

between

three

autoimmune

diseases:

vitiligo,

primary

biliary

cirrhosis,

and

Sjögren’s

syndrome

夽,夽夽

Lara

Silveira

Abdo-Aguiar

a,∗

_,

_Caio

_César

_Silva

_de

_Castro

b

a_Dermatology_Service,_Hospital_Santa_Casa_de_{Misericórdia}_de_Curitiba,_Curitiba,_PR,_Brazil b_Discipline_of_Dermatology,_Pontifícia_Universidade_Católica_do_Paraná,_Curitiba,_PR,_Brazil

Received20March2018;accepted24July2018

Availableonline23October2019

KEYWORDS Autoimmunity; Livercirrhosis, biliary; Sjogren’ssyndrome; Vitiligo

Abstract Althoughtheassociationofmultipleautoimmunediseaseshasalreadybeenwidely

described,noreportsoftheassociationbetweenvitiligo,primarybiliarycirrhosisandSjogren’s

syndromewereretrievedintheSciELOandPubMeddatabases.Theauthorsdescribethecase

ofafemalepatientwhowasdiagnosedwithprimarybiliarycirrhosisandSjogren’ssyndrome

atage54.Atage58,shedevelopedvitiligorestrictedtotheface,associatedwithsigniﬁcant

impairmentofself-esteemandqualityoflife.Antinuclearantibodywasnegativeattheonset

ofthecondition,butbecamepositiveafterphototherapyinitiation.Ingeneral,theoccurrence

ofmultipleautoimmunediseasesinthesamepatientisknownasamosaicofautoimmunity.

However,speciﬁcmechanismsappeartointerconnectprimarybiliarycirrhosis andSjogren’s

syndrome,suchasPDC-E2-mediatedgeneralizedepithelitis.

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

夽 _How_to_cite_this_article: _Abdo-Aguiar_LS,_Castro_CCS.

Associa-tionbetweenthreeautoimmunediseases:vitiligo,primarybiliary cirrhosisandSjögren’ssyndrome.AnBrasDermatol.2019;94:710---2.

夽夽_Study_conducted_at_the_Hospital_Santa_Casa_de_{Misericórdia}_de

Curitiba,Curitiba,PR,Brazil.

∗_{Corresponding}_author.

E-mail:laraabdo@yahoo.com.br(L.S.Abdo-Aguiar).

Introduction

Vitiligo is a chronic autoimmune diseasecharacterized by

the appearance of hypochromic and achromic macules

and patches on the skin and mucous membranes, due to

the disappearance of melanocytes in the affected area.1

In turn, primary biliary cirrhosis (PBC) is a chronic

hep-aticautoimmune diseasecharacterizedbythedestruction

of the epithelial cell lining the intrahepatic bile ducts,

https://doi.org/10.1016/j.abd.2018.07.002

(2)

Associationbetweenthreeautoimmunediseases 711

Figure 1 Vitiligo on the face, front position (Wood’s light examination).

progressively evolving to ﬁbrosis and cirrhosis.2 _Sjogren’s

syndrome(SS)isachronicautoimmuneconditionaffecting

exocrineglands,especiallythelacrimalandsalivaryglands.

Themainclinicalmanifestationsarexerostomiaand

xeroph-thalmia.Theprimaryformofthediseaseismoreprevalent

infemalesthanmales,inaratioof9:1,affecting

approxi-mately0.5%ofthepopulation,aprevalencesimilartothat

ofsystemiclupuserythematosusandsystemicsclerosis.3_It

iswellknownthattheoccurrenceofanautoimmunedisease

increasestheriskofotherautoimmunediseasesinthesame

patient,aphenomenonthathasbeenexploredinpreviously

publishedreportsandcaseseries;however,theassociation

betweencommonvitiligo,PBCandSShasnotbeenpublished

todate.4

Case

report

A female patient was diagnosed with PBC and SS at 54

yearsof age. She started treatment withursodeoxycholic

acid, deﬂazacort, hydroxychloroquine, and pilocarpine,

reachingsatisfactorydiseasecontrol.Subsequently,atage

58, she evolved with hypochromic and, later, achromic

lesionscharacteristicofvitiligorestrictedtothefacialarea

(Figs. 1 and 2), associated withsigniﬁcant impairmentin

self-esteemand quality of life.She had a positive family

historyofvitiligoinathird-degreerelative.Attheﬁrst

eval-uation,thepatienthadnegativeantinuclearantibody(ANA)

andanemiaduetochronic irondeﬁciency,requiringblood

transfusion.Forvitiligo,topicaltreatmentwithtacrolimus

and phototherapy with narrow band UVB were indicated,

whichstabilizedtheprogressionofthedisease,withoutnew

lesionsappearingonthefaceorotherareasoftheskin.After

startingphototherapy,laboratorytestsshowedpositiveANA

withmixedpattern---thickreticulatedspeckled1:320and

ﬁnespeckled1:640---withnootherchanges.

Figure2 Vitiligoonlefthemiface(Wood’slightexamination).

Discussion

Autoimmunediseasesarechronicconditionsthatresultfrom

thelossofimmunetolerancetoself-antigens.Theoriginof

autoimmunitymechanismsremains partiallyknown,anda

combinationofgenetic,immunological,environmental,and

hormonalfactorsislinkedtoitsdevelopment.Autoimmune

diseases can be classiﬁed as either organ-speciﬁc (e.g.,

myasthenia gravis, Graves’ disease, and polymyositis) or

multisystemdiseases(e.g.,systemiclupuserythematosus,

rheumatoidarthritis,andsystemicsclerosis).2

Vitiligo is a cutaneous disease of chronic and

autoim-munenaturethat,althoughoccurringsporadically,isknown

tohave a certain degree of heredity.Studies have

previ-ouslydemonstratedthe involvementof differentgenes in

itspathogenesis, but todate thereis no knownevidence

of avalidated serumor tissue markerassociated with its

occurrence.Casereportsandserieshaveassociatedvitiligo

withotherautoimmunediseases,andstudieshavereported

commongenesbetween thiscondition andsystemic lupus

erythematosusandHashimoto’sthyroiditis.1

PBC is considered a prototype of autoimmune disease

due to the characteristic antimitochondrial autoantibody,

itshomogeneousclinicalpresentation,andthespeciﬁcityof

theanatomopathologicalﬁndings.Geneticdeﬁcienciesand

mechanismsofimmuneregulation take partin the

patho-genesisofthedisease,whichresultsindamageexclusively

tothesmall-andmedium-caliberbileductcells;overtime,

consequentlyandprogressively,astate ofchronic

autoim-munecholangitisdevelops.4,5

In2012,Efeetal.carriedoutamulticenterstudyof71

patientswithPBCandautoimmunehepatitis(AIH)toanalyze

theassociation of thesewithother autoimmune diseases.

Thedataindicatedthat76.1%ofthepatientshadapositive

anti-nuclear factor, 74.6% had antimitochondrial

antibod-ies,and 52.1% had both markers. In 31 patients (43.6%),

(3)

712 Abdo-AguiarLS,CastroCCS

withpredominancefor thyroiddisordersin13participants

ofthestudy.Otherﬁndings includedSS insixparticipants

(8.4%)andpsoriasis,celiacdisease,andrheumatoid

arthri-tisin threepatients each (4.2%).Vitiligo wasobserved in

twopatients(2.8%);thesameproportionwasobservedfor

systemiclupuserythematosus.2

Theconcomitantoccurrenceofmultipleautoimmune

dis-easesinthesamepatientdrawsattentiontothepresence

ofcommonmechanisms.Theconceptofmosaicof

autoim-munityhas been proposed to describe this condition and

demonstratedinreportsandseriesofcases,asmentioned

above, although the speciﬁc immunological and genetic

mechanismshavenotyetbeenfullyelucidated.2

Patientswithautoimmunehepaticdiseases,suchasPBC

and AIH, may also present with other organ-speciﬁc or

multisystemic autoimmune conditions. In the

aforemen-tionedindividuals, SS wasthe most frequent multisystem

autoimmunecomorbidity.2_Two_previously_published_studies

analyzed34 SS patientswhohad a concomitantelevation

ofhepaticenzymes,amongwhichadiagnosisofPBCorAIH

wasmadein15andninepatients,respectively.6,7

A signiﬁcant portion of patients with PBC suffer from

the so-called sicca syndrome, and some of them present

classicalSS.BothPBCandSSarecharacterizedby

inﬂamma-tionandimmune-mediateddestructionofepithelialtissue;

moreover,thePDC-E2targetantigenhasbeenidentiﬁedin

bothbileductandsalivaryglandepithelium,whichstrongly

demonstratestheassociationbetweenbothconditions.2,5_In

addition,theﬁndingthatthesalivaryandlacrimalglands,as

wellastheurinarytractepithelium,mayalsobedamaged

inPBChasledtothehypothesis thatPBC,similarlytoSS,

canbeconsideredageneralizedepithelitis.8_To_date,_there

isnoevidencethatvitiligohasthesamepathophysiological

mechanism.

Finally,theassociationbetweenthispatient’s

comorbidi-tiesandtheirunderlyingpathophysiologicalmechanismwas

clariﬁed;thetripleassociationwasexplainedbythemosaic

ofautoimmunityandtheoccurrenceofepithelitis.

Financial

support

Nonedeclared.

Author’s

contributions

Lara Silveira Abdo Aguiar: Elaboration and writing of the

manuscript;obtaining,analyzingandinterpretingthedata;

intellectualparticipationinpropaedeuticand/or

therapeu-ticconductofthecasesstudied.

CaioCésarSilvade Castro:Conceptionandplanning of

the study; effective participationin research orientation;

intellectualparticipationinpropaedeuticand/or

therapeu-tic conduct of the cases studied; critical review of the

literature.

Conﬂicts

of

interest

Nonedeclared.

References

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2.Efe C,Wahlin S, Ozaslan E,Berlot AH, PurnakT, Muratori L, etal.Autoimmunehepatitis/primarybiliarycirrhosisoverlap syn-dromeandassociatedextrahepaticautoimmunediseases.EurJ GastroenterolHepatol.2012;24:531---4.

3.FoxRI.Sjögren’ssyndrome.Lancet.2005;366:321---31.

4.ShoenfeldY,BlankM,Abu-ShakraM,AmitalH,BarzilaiO,Berkun Y,etal.Themosaicofautoimmunity:prediction,autoantibodies, andtherapy inautoimmunediseases--- 2008.IsrMedAssoc J. 2008;10:13---9.

5.Selmi C, Meroni PL, Gershwin ME. Primary biliary cirrhosis andSjögren’ssyndrome:autoimmuneepithelitis.JAutoimmun. 2012;39:34---42.

6.Matsumoto T, Morizane T, Aoki Y, Yamasaki S, Nakajima M, EnomotoN, et al. Autoimmunehepatitisin primary Sjögren’s syndrome:pathological studyof the liversand labialsalivary glandsin17patientswithprimarySjögren’ssyndrome.Pathol Int.2005;55:70---6.

7.SkopouliFN,BarbatisC,MoutsopoulosHM.Liverinvolvementin primarySjögren’ssyndrome.BrJRheumatol.1994;33:745---8.

8.TanakaA,NalbandianG,LeungPS,BensonGD,MunozS,Findor JA, et al. Mucosal immunity and primary biliary cirrhosis: presenceofantimitochondrial antibodiesinurine.Hepatology. 2000;32:910---5.