Rev. Bras. Reumatol. vol.57 número6

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w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Original

article

Initial

digital

vasculitis

in

a

large

multicenter

cohort

of

childhood-onset

systemic

lupus

erythematosus

Ana

Paula

Sakamoto

a

_,

_Clovis

_Artur

_Silva

b,c

,

Marco

Felipe

Castro

da

Silva

b

,

Anandreia

Simões

Lopes

a

_,

_Gleice

_Clemente

_Souza

_Russo

a

_,

_Adriana

_Maluf

_Elias

_Sallum

b

_,

Katia

Kozu

b

_,

_Eloisa

_Bonfá

c

_,

_Claudia

_{Saad-Magalhães}

d

_,

_Rosa

_Maria

_Rodrigues

_Pereira

c

_,

Claudio

Arnaldo

Len

a

_,

_Maria

_Teresa

_Terreri

a,∗

a_Universidade_Federal_de_São_Paulo_(UNIFESP),_Unidade_de_Reumatologia_Pediátrica,_São_Paulo,_SP,_Brazil

b_Universidade_de_São_Paulo_(USP),_Faculdade_de_Medicina,_Unidade_de_Reumatologia_Pediátrica,_São_Paulo,_SP,_Brazil c_Universidade_de_São_Paulo_(USP),_Faculdade_de_Medicina,_Divisão_de_{Reumatologia,}_São_Paulo,_SP,_Brazil

d_Universidade_Estadual_Paulista_(UNESP),_Faculdade_de_Medicina_de_Botucatu,_Hospital_das_Clínicas_de_Botucatu,_Botucatu,_SP,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received26September2016

Accepted10May2017

Availableonline16October2017

Keywords:

Digitalvasculitis

Childhood-onsetsystemiclupus

erythematosus Vasculitis Sledai-2K

a

b

s

t

r

a

c

t

Objectives: Toassessclinicaldigitalvasculitis(DV)asaninitialmanifestationof

childhood-onsetsystemiclupuserythematosus(cSLE)withinalargepopulation.

Methods:Multicentercross-sectionalstudyincluding852cSLEpatients(ACRcriteria)

fol-lowedintenPediatricRheumatologycentersinSãoPauloState,Brazil.

Results:DVwasobservedin25/852(3%)cSLEpatients.Periungualhemorrhagewas

diag-nosedin12(48%),periungualinfarctionin7(28%),tipfingerulcerationin4(16%),painful

nodulesin1(4%)andgangrenein1(4%).Apooroutcome,withdigitalresorption,occurred

in5(20%).ComparisonofpatientswithandwithoutDVrevealedhigherfrequencyofmalar

rash(80%vs.53%,p=0.008),discoidrash(16%vs.4%,p=0.017),photosensitivity(76%vs.

45%,p=0.002)andothercutaneousvasculitides(80%vs.19%,p<0.0001),whereasthe

fre-quencyofoverallconstitutionalfeatures(32%vs.61%,p=0.003),fever(32%vs.56%,p=0.020)

andhepatomegaly(4%vs.23%,p=0.026)werelowerinthesepatients.Frequencyoffemale

gender,severemulti-organinvolvement,autoantibodiesprofileandlowcomplementwere

alikeinbothgroups(p>0.05).SLEDAI-2Kmedian,DVdescriptorexcluded,wassignificantly

lowerinpatientswithDVcomparedtothosewithoutthismanifestation[10(0–28)vs.14

(0–58),p=0.004].VisceralvasculitisordeathwerenotobservedinthiscSLEcohort.The

fre-quencyofcyclophosphamideuse(0%vs.18%,p=0.014)wassignificantlylowerintheDV

group.

∗ _{Corresponding}_author_.

E-mail:teterreri@terra.com.br(M.T.Terreri).

https://doi.org/10.1016/j.rbre.2017.09.002

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Conclusion: OurlargemulticenterstudyidentifiedclinicalDVasoneoftherareinitial

man-ifestationofactivecSLEassociatedwithamildmultisystemicdisease,inspiteofdigital

resorptioninsomeofthesepatients.

BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Vasculite

digital

inicial

em

uma

grande

coorte

multicêntrica

de

pacientes

com

lúpus

eritematoso

sistêmico

de

início

na

infância

Palavras-chave:

Vasculitedigital

Lúpuseritematososistêmicode

inícionainfância

Vasculite Sledai-2K

r

e

s

u

m

o

Objetivos: Avaliaravasculitedigital(VD)clínicacomoumamanifestac¸ãoinicialdolúpus

eritematososistêmicodeinícionainfância(LESi)emumagrandepopulac¸ão.

Métodos: Estudotransversalmulticêntricoqueincluiu852pacientescomLESi(critériosdo

ACR),acompanhadosemdezcentrosdereumatologiapediátricadoEstadodeSãoPaulo.

Resultados:Observou-seVDem25/852(3%)pacientescomLESi.Diagnosticaram-se

hemorra-giaperiunguealem12(48%),infartoperiunguealemsete(28%),úlceradepontadedígitoem

quatro(16%),nódulosdolorososemum(4%)egangrenaemum(4%).Umdesfechoruim,com

reabsorc¸ãodigital,ocorreuemcinco(20%)pacientes.Acomparac¸ãoentrepacientescome

semVDreveloumaiorfrequênciadeerupc¸ãomalar(80%vs.53%,p=0,008),erupc¸ãodiscoide

(16%vs.4%,p=0,017),fotossensibilidade(76%vs.45%p=0,002)eoutrasvasculitescutâneas

(80%vs.19%,p<0,0001),enquantoafrequênciadecaracterísticasconstitucionaistotais

(32%vs.61%,p=0,003),febre(32%vs.56%p=0,020)ehepatomegalia(4%vs.23%,p=0,026)

forammenoresnessespacientes.Afrequênciadogênerofeminino,oenvolvimentograve

demúltiplosórgãos,perfildeautoanticorposebaixocomplementoforamsemelhantesnos

doisgrupos(p>0,05).AmediananoSledai-2K,exclusiveodescritordeVD,foi

significativa-mentemenornospacientescomVDemcomparac¸ãocomaquelessemessamanifestac¸ão

[10(0a28)vs.14(0a58),p=0,004].Nãoforamobservadasvasculitevisceralnemmorte

nessacoortedepacientescomLESi.Afrequênciadeusodeciclofosfamida(0%vs.18%,

p=0,014)foisignificativamentemenornogrupoVD.

Conclusão: Este grande estudo multicêntrico identificou a VD clínica como uma rara

manifestac¸ão inicialdoLESi ativo,associadaa doenc¸amultissistêmicaleve, apesarda

ocorrênciadereabsorc¸ãodigitalemalgunsdessespacientes.

licenc¸aCCBY-NC-ND(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Systemic lupus erythematosus (SLE) is a multisystemic

autoimmunechronicdiseasemorecommoninadults(aSLE),

with only 10–20% of cases beginning during childhood or

adolescence.1–3_{Childhood-onset}_SLE_(cSLE)_is_{characterized}_by

moresevereandcumulativeacuteorganandsystem

involve-mentcomparingtoaSLE.Mucocutaneousinvolvementisone

ofthemostcommonmanifestationsandhasbeenreported

in up to 80% of children and adolescents at the time of

diagnosis.1,2

Vascularinflammatoryprocessisanimportantfeatureof

SLEandaffectsalargesubsetofpatientswithskin

manifes-tationsatany timeofdiseasecourse.4–7 _SLE_clinical_digital

vasculitis(DV)includespainfululcerationandnodulesmay

resultinsplinterhemorrhagesanddigitalinfarcts1,8,9_and_it

maybepresentin16–45%ofaSLEpatients.5,7,8,10

DataoncSLEpatientsarelimitedtocasereportsandsmall

series.1,9,11_There_are_no_published_data_{characterizing}_DV_in

alargepopulationofchildhoodlupuspatients.

Therefore,theobjectiveofthisstudywastoassessDVas

aninitialmanifestationinalargemulticenterstudy,

evalu-atingthepossibleassociationwithdemographicandclinical

features,laboratorialexams,treatmentandoutcomesincSLE

onset.

Methods

Studydesignandpatients

Thisisaretrospectivemulticenterstudyincluding1017cSLE

patientsfollowedintenPediatricRheumatologytertiary

refer-ral centers in São Paulo state, Brazil. One hundred and

sixty-five patientswere excludeddueto: incomplete

medi-calcharts(n=96),undifferentiatedconnectivetissuedisorder

with3orfewerAmericanCollegeofRheumatology(ACR)

crite-riaforSLE12₍_n₌_43),_isolated_cutaneous_lupus_{erythematosus}

(n=11), neonatal lupus erythematosus(n=8), drug-induced

lupus(n=5)andotherautoimmunediseases(n=2).Thus,the

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criteria12_and _presented_disease_onset_before₁₈_years_old13

withacurrentage upto25years.CommitteeforResearch

Ethicsofeachcenterapprovedthestudy.

Aninvestigatormeetingwasheldforthisstudytodefine

theprotocol,includingdefinitionsofclinical,laboratoryand

treatmentparametersanddiseaseactivityanddamagescore.

Allinvestigatorsusedthesamespecificdatabase.

Patient’smedicalchartsweremeticulouslyrevised

accord-ing to a standardized protocol for demographic data, DV

characteristics,other clinicalfeatures, laboratorialfindings,

therapeuticdataandDVoutcome(digitalresorption,visceral

vasculitis and death). Clinical DV was defined as

ulcera-tion,gangrene,tenderfingernodules,periungualinfarction

orsplinterhemorrhagesofthedigitsaccordingtoSLEDisease

ActivityIndex2000score(SLEDAI-2K).14

Demographicdata,clinicalevaluation,diseaseactivity, diseasedamageanddrugtherapy

Demographicdataincludedgender,ethnicityandageatcSLE

onset.Descriptors and definitions of SLEDAI-2Kwere used

toscorediseaseactivity.14_Other_SLE_clinical_{manifestations}

included: fever (axillary temperature higher than 37.8◦_C),

weightloss>2kg,lymphadenopathy(peripherallymphnode

enlargement>1.0cm),hepatomegaly[basedonphysicalexam

withliveredge≥2cmbelowtherightcostalmarginor

imag-ing (ultrasound or computer tomography when available)]

and splenomegaly [based on physical exam with palpable

spleenorimaging(ultrasoundorcomputertomographywhen

available)].15_{Neuropsychiatric}_lupus_included₁₉_syndromes

according to ACR classification criteria.16 _{Antiphospholipid}

syndromewas diagnosed accordingto the preliminary

cri-teria for the classification of pediatric antiphospholipid

syndrome.17 _High _blood _pressure _was _defined _as _systolic

and/ordiastolicbloodpressures≥95thpercentileforgender,

ageandheighton≥3occasions.18 _Acute_kidney_injury_was

determined by sudden increase in serum creatinine above

2mg/dl19 _or _by _modified _RIFLE _(Risk, _Injury, _Failure, _Loss

ofkidney functionand End-stagekidneydisease)criteria.20

Chronicrenaldiseasewasdefinedasstructuralorfunctional

abnormalitiesofthekidneyfor≥3months(withorwithout

decreasedglomerularfiltrationrate)orglomerularfiltration

rate<60ml/min/1.73m2_for_≥₃_months.21

Laboratorial assessment was comprised of

retrospec-tive analysis of erythrocyte sedimentation rate (ESR),

C-reactive protein (CRP), complete blood cell count, serum

urea and creatinine, urinalysis and 24-h urine protein

excretion. Complement levels (CH50, C3 and C4) were

assessed by immunodiffusion, turbidimetric immunoassay

orimmunonephelometry.Antinuclearantibodies(ANA)were

testedbyindirectimmunofluorescence;anti-double-stranded

DNA(anti-dsDNA)byindirectimmunofluorescenceorEnzyme

Linked Immuno Sorbent Assay (ELISA) and anticardiolipin

(aCL)IgGand IgMbyELISAwerecarriedoutateachcenter.

Thecutoffvaluesgivenbythekit manufacturerwereused

todefinenormalorabnormalfindings.Lupusanticoagulant

wasdetectedaccordingtotheguidelinesoftheInternational

SocietyonThrombosisandHemostasis.22

Table1–Clinicalcharacteristicsandoutcomeofdigital vasculitis(DV)in852cSLEpatientsatdiagnosis.

DVcharacteristics cSLE

n=25(%)

DVduration,days 56(10–933)

Numberofaffectedfingersortoes 5(1–20) Periungualhemorrhage 12(48) Periungualinfarct 7(28)

Ulceration 4(16)

Gangrene 1(4)

Painfulnodules 1(4)

Outcome

Digitalresorption 5(20) Visceralvasculitis 0(0)

cSLE,childhood-onsetsystemiclupuserythematosus. Resultsarepresentedasmedian(range)andn(%).

Drug treatment data (prednisone, intravenous methyl-prednisolone,chloroquinediphosphate,hydroxychloroquine sulfate,methotrexate,azathioprine,cyclosporine, mycophe-nolate mofetil,intravenous cyclophosphamide,intravenous immunoglobulin, rituximab and plasmapheresis) were also recorded.

PatientsweredividedintwogroupsatthecSLEdiagnosis fortheassessmentofcSLEmanifestations,laboratoryexams andtreatment:patientswithDVandwithoutDV.

Statisticalanalysis

All statistical analyses were performedwith the Statistical Packageforthe SocialSciences (SPSS),version13.0.Results weregivenasnumbers(percentage)forcategoricalvariables, median (range)or mean±standard deviation (SD)for con-tinuousvariables.Comparisonsbetweencategoricalvariables were assessed by Pearson -square or Fisher’s exact test and continuous variables comparisons were compared by Mann–Whitney testor ttest. Thesignificancelevels ofthe independentvariableweresetat5%(p<0.05).

Results

DVwasobservedin25/852(2.9%)cSLEpatientsatdiagnosis. Periungualhemorrhageonthefingerswasfoundin12(48%) cSLEpatients,periungualinfarctin7(28%),digitalulceration in4(16%),digitalgangrenein1(4%)anddigitalpainfulnodules in1(4%)patient.Themedianofaffectedfingersortoeswas five(1–20).ThefeaturesofDVanditsoutcomein25/852cSLE areshowninTable1.

Further comparisons of demographic data and current

clinicalmanifestationsin852cSLEpatientswithandwithout

DVatdiagnosis areillustratedinTable2.Thefrequencyof

constitutional features (32% vs. 61%, p=0.003), fever (32%

vs. 56%,p=0.020),hepatomegaly(4% vs.23%,p=0.026)and

arterialhypertension(0%vs.25%,p=0.001)weresignificantly

lowerincSLEpatientswithDVcomparedtothosewithoutthis

manifestation.Onthe otherhand,mucocutaneous

involve-ment (100%vs. 79%,p=0.005),rash(80%vs.53%,p=0.008),

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Table2–Demographicdataandcurrentclinicalmanifestationsin852childhood-onsetsystemiclupuserythematosus (cSLE)patientsgroupedaccordingtodigitalvasculitis(DV)atthediagnosis.

Variables WithDV(n=25) WithoutDV(n=827) p

Demographicdata

Femalegender,n=852 22/25(88) 710/827(86) 1.000

Caucasian,n=830 8/24(33) 230/806(29) 0.609

AgeatcSLEonset,years,n=852/852 13(4.25–17) 11.8(0.25–17.8) 0.067

Clinicalmanifestations

Constitutionalfeatures,n=843 8/25(32) 501/818(61) 0.003

Fever,n=837 8/25(32) 451/812(56) 0.020

Weightloss>2kg,n=822 7/25(28) 251/797(32) 0.385

Reticuloendothelialsysteminvolvement,n=831 5/25(20) 267/806(33) 0.199

Lymphadenopathy,n=825 4/25(16) 164/800(21) 0.801

Hepatomegaly,n=831 1/25(4) 181/806(23) 0.026

Splenomegaly,n=830 0/25(0) 76/805(9) 0.157

Mucocutaneousinvolvement,n=848 25/25(100) 651/823(79) 0.005

Rash,n=842 20/25(80) 434/817(53) 0.008

Discoidlupus,n=844 4/25(16) 31/819(4) 0.017

Photosensitivity,n=844 19/25(76) 367/819(45) 0.002 Mucosalulcer,n=845 8/25(32) 276/820(34) 0.863

Alopecia,n=843 11/25(25) 251/818(31) 0.156

Otherskinvasculitislesions,n=844 20/25(80) 152/819(19) <0.0001

Musculoskeletalinvolvement,n=846 18/25(72) 561/821(68) 0.697

Myositis,n=843 2/25(8) 32/818(4) 0.267

Arthritis,n=850 17/25(68) 555/825(67) 0.939

Serositis,n=847 5/25(20) 233/822(28) 0.499

Pleuritis,n=846 1/25(4) 148/821(18) 0.104

Pericarditis,n=846 5/25(20) 163/821(20) 1.000

Neuropsychiatricinvolvement,n=847 2/25(8) 202/822(25) 0.059

Peripheralnervoussysteminvolvement,n=847 0/25(0) 7/818(1) 1.000 Centralnervoussysteminvolvement,n=843 2/25(8) 198/822(24) 0.090

Nephritis,n=836 8/25(32) 406/811(50) 0.075

Hematuria,n=825 9/25(36) 358/800(45) 0.386

Pyuria,n=821 4/25(16) 269/796(34) 0.083

Urinarycast,n=822 3/25(12) 171/797(22) 0.326

Proteinuria>0.5g/day,n=804 7/25(28) 368/779(47) 0.058

Anti-phospholipidsyndrome,n=785 0/25(0) 15/760(2) 1.000

Ocularinvolvement,n=841 1/25(4) 13/816(2) 0.347

Other

Arterialhypertension,n=840 0/25(0) 202/815(25) 0.001 Acuterenalfailure,n=839 1/25(4) 98/814(12) 0.346 Chronicrenalfailure,n=835 0/25(0) 18/810(2) 1.000

Resultsarepresentedinn(%)andmedian(range).

45%,p=0.002)andotherskinvasculitislesions(80%vs.19%,

p<0.0001)weresignificantlyhigherincSLEpatientswithDV comparedtothosewithoutthiscutaneousinvolvement.A ten-dencyoflowerfrequencyofneuropsychiatric(p=0.059)and renalinvolvement(p=0.075)wasobservedinpatientswithDV (Table2).NoneofthepatientswithDVhadantiphospholipid

syndromeorthromboticthrombocytopenicpurpura.

Diseaseactivityandlaboratorytestsof852cSLEpatients

areshowninTable3.ThemedianofSLEDAI-2Kincludingthe

DVscoreitem[20(8–36)vs.14(0–58),p=0.014]wassignificantly

higherinDVpatientscomparedtopatientswithoutthis

com-plication.Ontheother hand,whencalculatingthe median

ofSLEDAI-2KexcludingDVdescriptor[10(0–28)vs.14(0–58),

p=0.004],itwaslowerinthegroupwithDV,scoredmainlyby

mucocutaneousinvolvement[rash(80%)andmucosalulcers

(32%)].Inspiteofthat,allpatientswithDVhadSLEDAI-2K>8.

Thelaboratorytestscomparisonwassimilarinbothgroups

(p>0.05,Table3).

TherapyincSLEpatientswithandwithoutDVatthetime

ofdiagnosisisshowninTable4.Thefrequencyof

cyclophos-phamideuse(0%vs.18%,p=0.014)wassignificantlylowerin

patientswithDVcomparedtothosewithoutthis

manifesta-tion.Frequencyofothermedicationsusewassimilarinboth

groups (p>0.05,Table 4). NocSLEpatientwas treatedwith

intravenousimmunoglobulin,rituximaborplasmapheresisat

diagnosis.

Regarding outcome,digital resorption was evidenced in

5/25 (20%).Visceralvasculitis ordeathwasnotobservedin

cSLEpatientswithDV,withnostatisticalsignificance

com-paredtothepatientswithnoDV.

Discussion

OurlargemulticentercohortwasthefirstcharacterizingDVas

oneoftherareinitialmanifestationsofcSLEpatients,mainly

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Table3–Currentdiseaseactivityandlaboratorytestsin852childhood-onsetsystemiclupuserythematosus(cSLE) patientsgroupedaccordingtodigitalvasculitis(DV)atdiagnosis.

Currentdiseaseactivity/damagescores

SLEDAI-2KwithDVscore,n=789/852 20(8–36) 14(0–58) 0.014 SLEDAI-2KwithoutDVscore,n=789/852 10(0–28) 14(0–58) 0.004

SLEDAI-2K≥8,n=789/852 25(100) 743(90) 0.062

Laboratorytests

ESRmm/1st/hour,n=717/852 44(10–130) 50(1–160) 0.601

CRPmg/dL,n=454/852 1.85(0–47) 3(0–413) 0.531

Autoimmunehemolyticanemia,n=830 3/25(12) 170/805(21) 0.328 Leucopenia<4000mm−3_,_n₌₈₃₆ _5/25₍₂₀₎ _222/811₍₂₇₎ _0.500 Lymphopenia<1500mm−3_,_n₌₈₃₄ _9/25₍₃₆₎ _349/809₍₄₃₎ _0.157 Thrombocytopenia,<100,000mm−3_,_n₌₈₃₄ _1/25₍₄₎ _128/809₍₁₆₎ _0.540 LowC3,C4and/orCH50,n=727 21/23(91) 511/704(73) 0.054 Anti-dsDNAantibody,n=801 15/25(60) 542/776(70) 0.292 Lupusanticoagulant,n=415 1/18(6) 64/397(16) 0.330 AnticardiolipinIgMantibody,n=498 1/19(5) 110/479(23) 0.090 AnticardiolipinIgGantibody,n=496 3/18(17) 130/478(27) 0.270

SLEDAI-2K,SystemicLupusErythematosusDiseaseActivityIndex2000;ESR,erythrocytesedimentationrate;CRP,C-reactiveprotein. Resultsarepresentedinn(%)andmedian(range).

Table4–Therapyin852childhood-onsetsystemiclupuserythematosus(cSLE)patientsgroupedaccordingtodigital vasculitis(DV)atdiagnosis.

Nonsteroidalanti-inflammatory,n=836 2/25(8) 115/811(14) 0.380

Glucocorticosteroids

Prednisone,n=836 24/25(96) 757/811(93) 1.000

Currentdose,mg/day,n=762/852 40(10–75) 40(3–180) 0.421 mg/kg/day,n=728/852 1.0(0.2–2) 1.0(0.1–4) 0.438 Intravenousmethylprednisolone,n=821 10/25(40) 348/796(44) 0.712

Antimalarialdrugs,n=838 18/25(72) 444/813(55) 0.085

Immunosuppressiveagents

Azathioprine,n=839 6/25(24) 100/814(12) 0.082

Cyclosporine,n=839 0/25(0) 8/814(1) 1.000

Methotrexate,n=840 3/25(12) 33/815(4) 0.087

Mycophenolatemofetil,n=838 1/25(4) 8/813(1) 0.240

Cyclophosphamide,n=841 0/25(0) 144/816(18) 0.014

Others

Intravenousimmunoglobulin,n=845 0/25(0) 28/820(3) 1.000

Rituximab,n=843 0/25(0) 0/818(0) –

Plasmapheresis,n=841 0/25(0) 11/816(1) 1.000

Resultsarepresentedinn(%).

TheadvantageofincludingalargecSLEpopulationselected intertiaryreferralcentersallowedabetterevaluationofthis rarevasculiticmanifestation.Theuseofastandardized com-bineddatabase,withproperDVdefinition,minimizedpossible bias.However,themainlimitationofthisstudywasthe ret-rospectivedesignand possiblemissing data, aswell asno biopsyor angiographic evidenceofvasculitis inany ofour patients.Itwasnotpossibletoexaminenailfoldcapillaroscopy becauseitwasnotaroutineprocedureinallparticipant Pedi-atricRheumatologycenters.Thisexamcouldbeusefulasa toolfordiseaseactivityassessmentrelatedtosmallvessels involvementincaseswithDV.23,24

VascularskininjuryisanimportantcharacteristicofSLE

andaffectsthemajorityofpatientsduringthewholedisease

courseanditwasreportedinassociationwithlupusflaresor

thrombosis.8–10 _We_confirmed_the_possible_association_with

activediseaseand lessprobableassociationwith

antiphos-pholipid syndromedue totheabsence ofantiphospholipid

antibodiesinDVcases.Ofnote,SLEDAI-2Kevaluationrevealed

a predominanceofmucocutaneous involvementandlower

frequencyofmajororganinvolvements(neuropsychiatricand

renal)reinforcingtheconceptthatDVisassociatedwithmild

systemic disease activity andmoreactive skindisease.DV

descriptorhasweightof8andconsequentlycontributeswith

highvaluesofSLEDAI-2Kscore,despiteofthemilddisease

thatthismanifestationrepresentedinourpatients.9

Despite the factthat skinvasculitis isacommon lupus

(6)

clin-icalDV wasrarelyreportedinadults11,25 _and _cSLE.1,8,9 _In_a

cross-sectional study with 168aSLE patients, DV appeared

in16%ofthepatientsassociatedwithconstitutional

symp-toms,mucocutaneousandhematologicalmanifestations.7_In

anotherstudyreporting670aSLEcases,11%presenteddigits

ulcerationand/orischemiclesions.25 _We_observed_from _our

resultsthatalthoughthefrequencyofDVatcSLEdiagnosisis

verylow,itisinfactassociatedwithpermanentdamagein1/5

ofthepatients.

DVwasnotassociatedwithany lupusspecificantibody.

Onlyafewpatients hadantiphospholipidantibodies,

char-acterizing a distinct profile from those with more severe

organinvolvement.26–28_Although_it_is_not_possible_to_exclude

antiphospholipid syndrome in these patients, the absence

ofclinical criteria makes this diagnosis very unlikely. The

onlyclinicalfeaturewasthedigitalthromboticvascular

dam-age that may have had a similar clinical aspect to lupus

vasculitis.4–7 _Further _studies _regarding_this _association _are

necessary.

ThemajorityofSLEpatientswithsmallvessellesionshad

clinicalDVcharacterizedbyerythematouspunctuatelesions

onthefingers,7_as_observed_in_our_study._This_feature_is

dif-ferentfromthosecSLEpatientswithvisceralmediumvessel

vasculitisassociatedwithincreasedmorbidityandmortality

duetoinvolvementofcerebrovascular,gastrointestinal,renal,

cardiovascularandpulmonaryinvolvements.29–32_Intravenous

cyclophosphamidetreatment was less frequentreinforcing

theconceptofmildersystemicactivityofthecases.

Further-more,concomitant visceraland cutaneousvasculitis israre

inaSLE(2%),33_emphasizing_the_importance_of_{distinguishing}

betweenthesetwosubtypesofvasculitis.

Inconclusion,ourlargemulticenterstudyidentified

clini-calDVasarareinitialmanifestationofactivecSLEassociated

withmildmultisystemicdiseaseinspiteofaccrueddamage

withdigitalresorptioninsomeofthesepatients.

Funding

This study was supported by grants from Conselho

Nacional de Desenvolvimento Científico e Tecnológico

(CNPq303422/2015-7toClovis ArturSilva,301805/2013-0 to

RosaMariaRodriguesPereira,305068/2014-8toEloisaBonfá,

301479/2015 to Claudia Saad-Magalhães and 303752/2015-7

to Maria Teresa Terreri), Federico Foundation (to Clovis

ArturSilva,RosaMariaRodriguesPereira andEloisa Bonfá)

andbyNúcleodeApoio àPesquisa“Saúdeda Crianc¸aedo

Adolescente”ofUSP(NAP-CriAd)toClovisArturSilva.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgements

OurgratitudetoUlyssesDoria-Filhoforthestatistical

analy-sis.TheauthorsthankthefollowingPediatricRheumatology

Divisions and colleagues forincluding their patients:

Pedi-atricRheumatologyUnit,FMUSP(AdrianaAlmeidadeJesus,

AdrianaMalufEliasSallum,CristinaMiukiAbeJacob,Gabriela

Blay,GabrielaNunesLeal,GabriellaErlacherLubedeAlmeida,

Heloisa Helenade SouzaMarques, JoãoDomingosMontoni

daSilva,JoaquimCarlosRodrigues,JulianaCaíresdeOliveira

AchiliFerreira, LailaPinto Coelho,LucianadosSantos

Hen-riques,MariaHelenaVaisbich,NadiaEmiAikawa,LuciaMaria

Arruda Campos, Victor Marques, Werther Brunow de

Car-valho);PediatricRheumatologyUnit,UNIFESP(AlineNicácio

Alencar,DanielaGerentPetryPiotto,GiampaoloFaquin,Gleice

ClementeSouzaRusso,LuisEduardoCoelhoAndrade,Maria

OdeteEstevesHilário,MelissaMaritiFraga,OctavioAugusto

BedinPeracchi);DivisionofRheumatology,FMUSP(JulianeA.

Paupitz,GlauceLeão Lima);UNESP (PriscilaR.Aoki, Juliana

deOliveiraSato,SilvanaPaulaCardin,TacianaAlbuquerque

PedrosaFernandes);IrmandadedaSantaCasade

Misericór-diadeSãoPaulo(AndressaGuariento,EuniceOkuda,Maria

Carolina dosSantos,Natali WenigerSpellingGormenzano);

StateUniversityofCampinas(MaraísaCenteville,Renata

Bar-bosa, SimoneAppenzeller);RibeirãoPreto MedicalSchool–

University ofSão Paulo (FranciscoHugo Gomes,Gecilmara

SalviattoPileggi,PaolaPontesPinheiro,VirginiaPaesLeme

Fer-riani);HospitalInfantilDarcyVargas(JonatasLibório,Luciana

TudechPedroPaulo);HospitalMunicipalInfantilMeninoJesus

(SimoneLotufo,TâniaCarolineMonteirodeCastro)and

Pon-tificalCatholicUniversityofSorocaba(ValériaC.Ramos).

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