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r e v b r a s r e u m a t o l . 2 0 1 7;5 7(6):583–589

www.reumato logia .com.br

REVISTA BRASILEIRA DE
REUMATOLOGIA

riginal article

nitial  digital  vasculitis  in  a large  multicenter
ohort of  childhood-onset  systemic  lupus
rythematosus

na Paula Sakamotoa, Clovis Artur Silvab,c, Marco Felipe Castro da Silvab,
nandreia  Simões Lopesa, Gleice Clemente Souza Russoa, Adriana Maluf Elias Sallumb,
atia  Kozub, Eloisa Bonfác, Claudia Saad-Magalhãesd, Rosa Maria Rodrigues Pereirac,
laudio  Arnaldo Lena, Maria Teresa Terreria,∗

Universidade Federal de São Paulo (UNIFESP), Unidade de Reumatologia Pediátrica, São Paulo, SP, Brazil
Universidade de São Paulo (USP), Faculdade de Medicina, Unidade de Reumatologia Pediátrica, São Paulo, SP, Brazil
Universidade de São Paulo (USP), Faculdade de Medicina, Divisão de Reumatologia, São Paulo, SP, Brazil
Universidade Estadual Paulista (UNESP), Faculdade de Medicina de Botucatu, Hospital das Clínicas de Botucatu, Botucatu, SP, Brazil

 r  t  i  c  l  e  i  n  f  o

rticle history:

eceived 26 September 2016

ccepted 10 May 2017

vailable online 16 October 2017

eywords:

igital vasculitis

hildhood-onset systemic lupus

rythematosus

asculitis

ledai-2K

a  b  s  t  r  a  c  t

Objectives: To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-

onset  systemic lupus erythematosus (cSLE) within a large population.

Methods: Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) fol-

lowed in ten Pediatric Rheumatology centers in São Paulo State, Brazil.

Results: DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diag-

nosed  in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful

nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred

in  5 (20%). Comparison of patients with and without DV revealed higher frequency of malar

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

45%, p = 0.002) and other cutaneous vasculitides (80% vs. 19%, p < 0.0001), whereas the fre-

quency of overall constitutional features (32% vs. 61%, p = 0.003), fever (32% vs. 56%, p = 0.020)

and  hepatomegaly (4% vs. 23%, p = 0.026) were lower in these patients. Frequency of female

gender, severe multi-organ involvement, autoantibodies profile and low complement were

alike in both groups (p > 0.05). SLEDAI-2K median, DV descriptor excluded, was significantly
lower in patients with DV compared to those without this manifestation [10 (0–28) vs. 14

(0–58), p = 0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The fre-

quency of cyclophosphamide use (0% vs. 18%, p = 0.014) was significantly lower in the DV

group.

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

ttps://doi.org/10.1016/j.rbre.2017.09.002
255-5021/© 2017 Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://
reativecommons.org/licenses/by-nc-nd/4.0/).

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584  r e v b r a s r e u m a t o l . 2 0 1 7;5 7(6):583–589

Conclusion: Our large multicenter study identified clinical DV as one of the rare initial man-

ifestation of active cSLE associated with a mild multisystemic disease, in spite of digital

resorption in some of these patients.

© 2017 Published by Elsevier Editora Ltda. This is an open access article under the CC

BY-NC-ND license (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:

Vasculite digital

Lúpus eritematoso sistêmico de

início na infância

Vasculite

Sledai-2K

r  e  s  u  m  o

Objetivos: Avaliar a vasculite digital (VD) clínica como uma manifestação inicial do lúpus

eritematoso sistêmico de início na infância (LESi) em uma grande população.

Métodos: Estudo transversal multicêntrico que incluiu 852 pacientes com LESi (critérios do

ACR),  acompanhados em dez centros de reumatologia pediátrica do Estado de São Paulo.

Resultados: Observou-se VD em 25/852 (3%) pacientes com LESi. Diagnosticaram-se hemorra-

gia  periungueal em 12 (48%), infarto periungueal em sete (28%), úlcera de ponta de dígito em

quatro (16%), nódulos dolorosos em um (4%) e gangrena em um (4%). Um desfecho ruim, com

reabsorção  digital, ocorreu em cinco (20%) pacientes. A comparação entre pacientes com e

sem  VD revelou maior frequência de erupção malar (80% vs. 53%, p = 0,008), erupção discoide

(16%  vs. 4%, p = 0,017), fotossensibilidade (76% vs. 45% p = 0,002) e outras vasculites cutâneas

(80%  vs. 19%, p < 0,0001), enquanto a frequência de características constitucionais totais

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

foram menores nesses pacientes. A frequência do gênero feminino, o envolvimento grave

de  múltiplos órgãos, perfil de autoanticorpos e baixo complemento foram semelhantes nos

dois grupos (p > 0,05). A mediana no Sledai-2 K, exclusive o descritor de VD, foi significativa-

mente menor nos pacientes com VD em comparação com aqueles sem essa manifestação

[10  (0 a 28) vs. 14 (0 a 58), p = 0,004]. Não foram observadas vasculite visceral nem morte

nessa coorte de pacientes com LESi. A frequência de uso de ciclofosfamida (0% vs. 18%,

p  = 0,014) foi significativamente menor no grupo VD.

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

manifestação inicial do LESi ativo, associada a doença multissistêmica leve, apesar da

ocorrência de reabsorção digital em alguns desses pacientes.

© 2017 Publicado por Elsevier Editora Ltda. Este é um artigo Open Access sob uma

ça  C

ria for SLE (n = 43), isolated cutaneous lupus erythematosus
(n = 11), neonatal lupus erythematosus (n = 8), drug-induced
licen

Introduction

Systemic lupus erythematosus (SLE) is a multisystemic
autoimmune chronic disease more  common in adults (aSLE),
with only 10–20% of cases beginning during childhood or
adolescence.1–3 Childhood-onset SLE (cSLE) is characterized by
more severe and cumulative acute organ and system involve-
ment comparing to aSLE. Mucocutaneous involvement is one
of the most common manifestations and has been reported
in up to 80% of children and adolescents at the time of
diagnosis.1,2

Vascular inflammatory process is an important feature of
SLE and affects a large subset of patients with skin manifes-
tations at any time of disease course.4–7 SLE clinical digital
vasculitis (DV) includes painful ulceration and nodules may
result in splinter hemorrhages and digital infarcts1,8,9 and it
may be present in 16–45% of aSLE patients.5,7,8,10

Data on cSLE patients are limited to case reports and small

series.1,9,11 There are no published data characterizing DV in
a large population of childhood lupus patients.
C BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Therefore, the objective of this study was to assess DV as
an initial manifestation in a large multicenter study, evalu-
ating the possible association with demographic and clinical
features, laboratorial exams, treatment and outcomes in cSLE
onset.

Methods

Study  design  and  patients

This is a retrospective multicenter study including 1017 cSLE
patients followed in ten Pediatric Rheumatology tertiary refer-
ral centers in São Paulo state, Brazil. One hundred and
sixty-five patients were excluded due to: incomplete medi-
cal charts (n = 96), undifferentiated connective tissue disorder
with 3 or fewer American College of Rheumatology (ACR) crite-

12
lupus (n = 5) and other autoimmune diseases (n = 2). Thus, the
study group comprised 852 cSLE patients; all fulfilled the ACR

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 . 2 0 1 7;5 7(6):583–589 585

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Table 1 – Clinical characteristics and outcome of digital
vasculitis (DV) in 852 cSLE patients at diagnosis.

DV characteristics cSLE
n = 25 (%)

DV duration, days 56  (10–933)

Number of affected fingers or toes 5 (1–20)
Periungual hemorrhage 12 (48)
Periungual infarct 7 (28)
Ulceration 4 (16)
Gangrene 1 (4)
Painful nodules 1 (4)

Outcome
Digital resorption 5 (20)
Visceral vasculitis 0 (0)
r e v b r a s r e u m a t o l

riteria12 and presented disease onset before 18 years old13

ith a current age up to 25 years. Committee for Research
thics of each center approved the study.

An investigator meeting was held for this study to define
he protocol, including definitions of clinical, laboratory and
reatment parameters and disease activity and damage score.
ll investigators used the same specific database.

Patient’s medical charts were meticulously revised accord-
ng to a standardized protocol for demographic data, DV
haracteristics, other clinical features, laboratorial findings,
herapeutic data and DV outcome (digital resorption, visceral
asculitis and death). Clinical DV was defined as ulcera-
ion, gangrene, tender finger nodules, periungual infarction
r splinter hemorrhages of the digits according to SLE Disease
ctivity Index 2000 score (SLEDAI-2K).14

emographic  data,  clinical  evaluation,  disease  activity,
isease  damage  and  drug  therapy

emographic data included gender, ethnicity and age at cSLE
nset. Descriptors and definitions of SLEDAI-2K were used
o score disease activity.14 Other SLE clinical manifestations
ncluded: fever (axillary temperature higher than 37.8 ◦C),
eight loss > 2 kg, lymphadenopathy (peripheral lymph node

nlargement > 1.0 cm), hepatomegaly [based on physical exam
ith liver edge ≥2 cm below the right costal margin or imag-

ng (ultrasound or computer tomography when available)]
nd splenomegaly [based on physical exam with palpable
pleen or imaging (ultrasound or computer tomography when
vailable)].15 Neuropsychiatric lupus included 19 syndromes
ccording to ACR classification criteria.16 Antiphospholipid
yndrome was diagnosed according to the preliminary cri-
eria for the classification of pediatric antiphospholipid
yndrome.17 High blood pressure was defined as systolic
nd/or diastolic blood pressures ≥95th percentile for gender,
ge and height on ≥3 occasions.18 Acute kidney injury was
etermined by sudden increase in serum creatinine above

 mg/dl19 or by modified RIFLE (Risk, Injury, Failure, Loss
f kidney function and End-stage kidney disease) criteria.20

hronic renal disease was defined as structural or functional
bnormalities of the kidney for ≥3 months (with or without
ecreased glomerular filtration rate) or glomerular filtration
ate < 60 ml/min/1.73 m2 for ≥3 months.21

Laboratorial assessment was comprised of retrospec-
ive analysis of erythrocyte sedimentation rate (ESR), C-
eactive protein (CRP), complete blood cell count, serum
rea and creatinine, urinalysis and 24-h urine protein
xcretion. Complement levels (CH50, C3 and C4) were
ssessed by immunodiffusion, turbidimetric immunoassay
r immunonephelometry. Antinuclear antibodies (ANA) were
ested by indirect immunofluorescence; anti-double-stranded
NA (anti-dsDNA) by indirect immunofluorescence or Enzyme
inked Immuno Sorbent Assay (ELISA) and anticardiolipin
aCL) IgG and IgM by ELISA were carried out at each center.

he cutoff values given by the kit manufacturer were used

o define normal or abnormal findings. Lupus anticoagulant
as detected according to the guidelines of the International
ociety on Thrombosis and Hemostasis.22
cSLE, childhood-onset systemic lupus erythematosus.
Results are presented as median (range) and n (%).

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

Patients were divided in two groups at the cSLE diagnosis
for the assessment of cSLE manifestations, laboratory exams
and treatment: patients with DV and without DV.

Statistical  analysis

All statistical analyses were performed with the Statistical
Package for the Social Sciences (SPSS), version 13.0. Results
were given as numbers (percentage) for categorical variables,
median (range) or mean ± standard deviation (SD) for con-
tinuous variables. Comparisons between categorical variables
were assessed by Pearson �-square or Fisher’s exact test
and continuous variables comparisons were compared by
Mann–Whitney test or t test. The significance levels of the
independent variable were set at 5% (p < 0.05).

Results

DV was observed in 25/852 (2.9%) cSLE patients at diagnosis.
Periungual hemorrhage on the fingers was found in 12 (48%)
cSLE patients, periungual infarct in 7 (28%), digital ulceration
in 4 (16%), digital gangrene in 1 (4%) and digital painful nodules
in 1 (4%) patient. The median of affected fingers or toes was
five (1–20). The features of DV and its outcome in 25/852 cSLE
are shown in Table 1.

Further comparisons of demographic data and current
clinical manifestations in 852 cSLE patients with and without
DV at diagnosis are illustrated in Table 2. The frequency of
constitutional features (32% vs. 61%, p = 0.003), fever (32%
vs. 56%, p = 0.020), hepatomegaly (4% vs. 23%, p = 0.026) and
arterial hypertension (0% vs. 25%, p = 0.001) were significantly

lower in cSLE patients with DV compared to those without this
manifestation. On the other hand, mucocutaneous involve-
ment (100% vs. 79%, p = 0.005), rash (80% vs. 53%, p = 0.008),
discoid lupus (16% vs. 4%, p = 0.017), photosensitivity (76% vs.



586  r e v b r a s r e u m a t o l . 2 0 1 7;5 7(6):583–589

Table 2 – Demographic data and current clinical manifestations in 852 childhood-onset systemic lupus erythematosus
(cSLE) patients grouped according to digital vasculitis (DV) at the diagnosis.

Variables With DV (n = 25) Without DV (n = 827) p

Demographic data
Female gender, n = 852 22/25  (88) 710/827 (86) 1.000
Caucasian, n = 830 8/24 (33) 230/806 (29) 0.609
Age at cSLE onset, years, n = 852/852 13 (4.25–17) 11.8 (0.25–17.8) 0.067

Clinical manifestations
Constitutional features, n = 843 8/25 (32) 501/818 (61) 0.003

Fever, n = 837 8/25 (32) 451/812 (56) 0.020
Weight loss > 2 kg, n = 822 7/25 (28) 251/797 (32) 0.385

Reticuloendothelial system involvement, 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

Mucocutaneous involvement, n = 848 25/25 (100) 651/823 (79) 0.005
Rash, n = 842 20/25 (80) 434/817 (53) 0.008
Discoid lupus, n = 844 4/25 (16) 31/819 (4) 0.017
Photosensitivity, n = 844 19/25 (76) 367/819 (45) 0.002
Mucosal ulcer, n = 845 8/25 (32) 276/820 (34) 0.863
Alopecia, n = 843 11/25 (25) 251/818 (31) 0.156
Other skin vasculitis lesions, n = 844 20/25 (80) 152/819 (19) <0.0001

Musculoskeletal involvement, 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

Neuropsychiatric involvement, n = 847 2/25 (8) 202/822 (25) 0.059
Peripheral nervous system involvement, n = 847 0/25 (0) 7/818 (1) 1.000
Central nervous system involvement, 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
Urinary cast, n = 822 3/25 (12) 171/797 (22) 0.326
Proteinuria > 0.5 g/day, n = 804 7/25 (28) 368/779 (47) 0.058

Anti-phospholipid syndrome, n = 785 0/25 (0) 15/760 (2) 1.000
Ocular involvement, n = 841 1/25 (4) 13/816 (2) 0.347
Other

Arterial hypertension, n = 840 0/25 (0) 202/815 (25) 0.001
Acute renal failure, n = 839 1/25 (4) 98/814 (12) 0.346
Chronic renal failure, n = 835 0/25 (0) 18/810 (2) 1.000

Our large multicenter cohort was the first characterizing DV  as
Results are presented in n (%) and median (range).

45%, p = 0.002) and other skin vasculitis lesions (80% vs. 19%,
p < 0.0001) were significantly higher in cSLE patients with DV
compared to those without this cutaneous involvement. A ten-
dency of lower frequency of neuropsychiatric (p = 0.059) and
renal involvement (p = 0.075) was observed in patients with DV
(Table 2). None of the patients with DV had antiphospholipid
syndrome or thrombotic thrombocytopenic purpura.

Disease activity and laboratory tests of 852 cSLE patients
are shown in Table 3. The median of SLEDAI-2K including the
DV score item [20 (8–36) vs. 14 (0–58), p = 0.014] was significantly
higher in DV patients compared to patients without this com-
plication. On the other hand, when calculating the median
of SLEDAI-2K excluding DV descriptor [10 (0–28) vs. 14 (0–58),
p = 0.004], it was lower in the group with DV, scored mainly by
mucocutaneous involvement [rash (80%) and mucosal ulcers
(32%)]. In spite of that, all patients with DV had SLEDAI-2K > 8.

The laboratory tests comparison was similar in both groups
(p > 0.05, Table 3).
Therapy in cSLE patients with and without DV at the time
of diagnosis is shown in Table 4. The frequency of cyclophos-
phamide use (0% vs. 18%, p = 0.014) was significantly lower in
patients with DV compared to those without this manifesta-
tion. Frequency of other medications use was similar in both
groups (p > 0.05, Table 4). No cSLE patient was treated with
intravenous immunoglobulin, rituximab or plasmapheresis at
diagnosis.

Regarding outcome, digital resorption was evidenced in
5/25 (20%). Visceral vasculitis or death was not observed in
cSLE patients with DV, with no statistical significance com-
pared to the patients with no DV.

Discussion
one of the rare initial manifestations of cSLE patients, mainly
associated with other mucocutaneous involvement.



r e v b r a s r e u m a t o l . 2 0 1 7;5 7(6):583–589 587

Table 3 – Current disease activity and laboratory tests in 852 childhood-onset systemic lupus erythematosus (cSLE)
patients grouped according to digital vasculitis (DV) at diagnosis.

Variables With DV (n = 25) Without DV (n = 827) p

Current disease activity/damage scores
SLEDAI-2K with DV score, n = 789/852 20 (8–36) 14 (0–58) 0.014
SLEDAI-2K without DV score, n = 789/852 10 (0–28) 14 (0–58) 0.004
SLEDAI-2K ≥ 8, n = 789/852 25 (100) 743 (90) 0.062

Laboratory tests
ESR mm/1st/hour, n = 717/852 44 (10–130) 50 (1–160) 0.601
CRP mg/dL, n = 454/852 1.85 (0–47) 3 (0–413) 0.531
Autoimmune hemolytic anemia, n = 830 3/25 (12) 170/805 (21) 0.328
Leucopenia < 4000 mm−3, n = 836 5/25 (20) 222/811 (27) 0.500
Lymphopenia < 1500 mm−3, n = 834 9/25 (36) 349/809 (43) 0.157
Thrombocytopenia, <100,000 mm−3, n = 834 1/25 (4) 128/809 (16) 0.540
Low C3, C4 and/or CH50, n = 727 21/23 (91) 511/704 (73) 0.054
Anti-dsDNA antibody, n = 801 15/25 (60) 542/776 (70) 0.292
Lupus anticoagulant, n = 415 1/18 (6) 64/397 (16) 0.330
Anticardiolipin IgM antibody, n = 498 1/19 (5) 110/479 (23) 0.090
Anticardiolipin IgG antibody, n = 496 3/18 (17) 130/478 (27) 0.270

SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Results are presented in n (%) and median (range).

Table 4 – Therapy in 852 childhood-onset systemic lupus erythematosus (cSLE) patients grouped according to digital
vasculitis (DV) at diagnosis.

Variables With DV (n = 25) Without DV (n = 827) p

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

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

Current dose, 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

Intravenous methylprednisolone, n = 821 10/25 (40) 348/796 (44) 0.712

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

Immunosuppressive agents
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
Mycophenolate mofetil, n = 838 1/25 (4) 8/813 (1) 0.240
Cyclophosphamide, n = 841 0/25 (0) 144/816 (18) 0.014

Others
Intravenous immunoglobulin, 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

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Results are presented in n (%).

The advantage of including a large cSLE population selected
n tertiary referral centers allowed a better evaluation of this
are vasculitic manifestation. The use of a standardized com-
ined database, with proper DV definition, minimized possible
ias. However, the main limitation of this study was the ret-
ospective design and possible missing data, as well as no
iopsy or angiographic evidence of vasculitis in any of our
atients. It was not possible to examine nailfold capillaroscopy
ecause it was not a routine procedure in all participant Pedi-
tric Rheumatology centers. This exam could be useful as a

ool for disease activity assessment related to small vessels
nvolvement in cases with DV.23,24

Vascular skin injury is an important characteristic of SLE
nd affects the majority of patients during the whole disease
course and it was reported in association with lupus flares or
thrombosis.8–10 We  confirmed the possible association with
active disease and less probable association with antiphos-
pholipid syndrome due to the absence of antiphospholipid
antibodies in DV cases. Of note, SLEDAI-2K evaluation revealed
a predominance of mucocutaneous involvement and lower
frequency of major organ involvements (neuropsychiatric and
renal) reinforcing the concept that DV is associated with mild
systemic disease activity and more  active skin disease. DV
descriptor has weight of 8 and consequently contributes with

high values of SLEDAI-2K score, despite of the mild disease
that this manifestation represented in our patients.9

Despite the fact that skin vasculitis is a common lupus
manifestation at diagnosis of aSLE and cSLE patients, clin-



 o l . 2

r

588  r e v b r a s r e u m a t

ical DV was rarely reported in adults11,25 and cSLE.1,8,9 In a
cross-sectional study with 168 aSLE patients, DV appeared
in 16% of the patients associated with constitutional symp-
toms, mucocutaneous and hematological manifestations.7 In
another study reporting 670 aSLE cases, 11% presented digits
ulceration and/or ischemic lesions.25 We  observed from our
results that although the frequency of DV at cSLE diagnosis is
very low, it is in fact associated with permanent damage in 1/5
of the patients.

DV was not associated with any lupus specific antibody.
Only a few patients had antiphospholipid antibodies, char-
acterizing a distinct profile from those with more severe
organ involvement.26–28 Although it is not possible to exclude
antiphospholipid syndrome in these patients, the absence
of clinical criteria makes this diagnosis very unlikely. The
only clinical feature was the digital thrombotic vascular dam-
age that may have had a similar clinical aspect to lupus
vasculitis.4–7 Further studies regarding this association are
necessary.

The majority of SLE patients with small vessel lesions had
clinical DV characterized by erythematous punctuate lesions
on the fingers,7 as observed in our study. This feature is dif-
ferent from those cSLE patients with visceral medium vessel
vasculitis associated with increased morbidity and mortality
due to involvement of cerebrovascular, gastrointestinal, renal,
cardiovascular and pulmonary involvements.29–32 Intravenous
cyclophosphamide treatment was less frequent reinforcing
the concept of milder systemic activity of the cases. Further-
more, concomitant visceral and cutaneous vasculitis is rare
in aSLE (2%),33 emphasizing the importance of distinguishing
between these two subtypes of vasculitis.

In conclusion, our large multicenter study identified clini-
cal DV as a rare initial manifestation of active cSLE associated
with mild multisystemic disease in spite of accrued damage
with digital resorption in some of these patients.

Funding

This study was supported by grants from Conselho
Nacional de Desenvolvimento Científico e Tecnológico
(CNPq 303422/2015-7 to Clovis Artur Silva, 301805/2013-0 to
Rosa Maria Rodrigues Pereira, 305068/2014-8 to Eloisa Bonfá,
301479/2015 to Claudia Saad-Magalhães and 303752/2015-7
to Maria Teresa Terreri), Federico Foundation (to Clovis
Artur Silva, Rosa Maria Rodrigues Pereira and Eloisa Bonfá)
and by Núcleo de Apoio à Pesquisa “Saúde da Criança  e do
Adolescente” of USP (NAP-CriAd) to Clovis Artur Silva.

Conflicts  of  interest

The authors declare no conflicts of interest.

Acknowledgements
Our gratitude to Ulysses Doria-Filho for the statistical analy-
sis. The authors thank the following Pediatric Rheumatology
Divisions and colleagues for including their patients: Pedi-
atric Rheumatology Unit, FMUSP (Adriana Almeida de Jesus,

1

1

 0 1 7;5 7(6):583–589

Adriana Maluf Elias Sallum, Cristina Miuki Abe Jacob, Gabriela
Blay, Gabriela Nunes Leal, Gabriella Erlacher Lube de Almeida,
Heloisa Helena de Souza Marques, João Domingos Montoni
da Silva, Joaquim Carlos Rodrigues, Juliana Caíres de Oliveira
Achili Ferreira, Laila Pinto Coelho, Luciana dos Santos Hen-
riques, Maria Helena Vaisbich, Nadia Emi  Aikawa, Lucia Maria
Arruda Campos, Victor Marques, Werther Brunow de Car-
valho); Pediatric Rheumatology Unit, UNIFESP (Aline Nicácio
Alencar, Daniela Gerent Petry Piotto, Giampaolo Faquin, Gleice
Clemente Souza Russo, Luis Eduardo Coelho Andrade, Maria
Odete Esteves Hilário, Melissa Mariti Fraga, Octavio Augusto
Bedin Peracchi); Division of Rheumatology, FMUSP (Juliane A.
Paupitz, Glauce Leão Lima); UNESP (Priscila R. Aoki, Juliana
de Oliveira Sato, Silvana Paula Cardin, Taciana Albuquerque
Pedrosa Fernandes); Irmandade da Santa Casa de Misericór-
dia de São Paulo (Andressa Guariento, Eunice Okuda, Maria
Carolina dos Santos, Natali Weniger Spelling Gormenzano);
State University of Campinas (Maraísa Centeville, Renata Bar-
bosa, Simone Appenzeller); Ribeirão Preto Medical School –
University of São Paulo (Francisco Hugo Gomes, Gecilmara
Salviatto Pileggi, Paola Pontes Pinheiro, Virginia Paes Leme Fer-
riani); Hospital Infantil Darcy Vargas (Jonatas Libório, Luciana
Tudech Pedro Paulo); Hospital Municipal Infantil Menino Jesus
(Simone Lotufo, Tânia Caroline Monteiro de Castro) and Pon-
tifical Catholic University of Sorocaba (Valéria C. Ramos).

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