Lupus around the World

Lupus
2022, Vol. 31(6) 759–764
Comparison of clinical presentation and © The Author(s) 2022
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DOI: 10.1177/09612033221093482
journals.sagepub.com/home/lup
adulthood-onset of systemic lupus
erythematosus among Indonesian patients

Laniyati Hamijoyo1,2 , Gartika Sapartini3, Andri R Rahmadi1, Rachmat G Wachjudi1,

Sumartini Dewi1, Reni Ghrahani3, Suhendra Praptama2, Nisa R Rainy2,
Stefanie Y Usman2, Bernard S Suryajaya2, Sasfia Candrianita2, Endang Sutedja4 and
Budi Setiabudiawan3

Abstract
Introduction: The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to
differ from that of adult-onset SLE.
Objective: We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset
SLE in a cohort of Indonesian patients at tertiary care centers.
Methods: This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017.
The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old)
(Group 1) and adult-onset SLE (≥18 years old) (Group 2).
Results: Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20%
(174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical
manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients:
hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001)
were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in
childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in
childhood-onset group (11.5% vs 7.0%, p = 0.208).
Conclusion: Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared
to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the
need for more aggressive management approach to childhood-onset patients with SLE.

Keywords
Systemic lupus erythematosus (SLE), childhood-onset SLE, adult-onset SLE
Date received: 6 February 2022; accepted: 24 March 2022
Introduction
Systemic lupus erythematosus (SLE) is a chronic autoim-
mune disease with unknown etiology which affects both
children and adults.1 However, the incidence of SLE in
childhood was relatively rare and diagnosis prior to the age
of 16 years is around 15–20%.2,3 Age of onset modifies
expression of the disease by organ involvement and sero-
logical findings in SLE; hence, the clinical presentation in
children is generally considered to be different from adults.4
Childhood-onset SLE has a more aggressive disease course
1
Rheumatology Division, Faculty of Medicine, Department of Internal
Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital,
Bandung, Indonesia
2
Lupus Study Group, Immunology Study Center, Faculty of Medicine,
Universitas Padjadjaran, Bandung, Indonesia
3
Allergy and Immunology Division, Faculty of Medicine, Department of
Child Health, Universitas Padjadjaran/Hasan Sadikin General Hospital,
Bandung, Indonesia
4
Immunodermatology Division, Faculty of Medicine, Department of
Dermato Venereology, Universitas Padjadjaran/Hasan Sadikin General
Hospital, Bandung, Indonesia
Corresponding author:
Laniyati Hamijoyo, Rheumatology Division, Internal Medicine Department,
Faculty of Medicine Universitas Padjadjaran/Hasan Sadikin General
Hospital, Pasteur 38, Bandung, West Java 40161, Indonesia.
Email: hamijoyo@yahoo.com
760
and also greater morbidity and mortality than adult-onset
SLE. Therefore, early recognition of disease and diagnosis
which lead to optimal management are keys to a better
outcome of disease.1
Previous study presented distinctive clinical features of
SLE in different age classes in childhood-onset SLE.4
Another study also demonstrated genetic and ethnicity
could influence clinical features of childhood SLE.5 A
multiracial cohort study in the USA found higher genetic
risk for lupus was associated with more severe clinical
features in SLE. They also presented that proteinuria, malar
rash, anti-dsDNA antibody, hemolytic anemia, arthritis, and
leucopenia were found to be more common in childhood-
onset SLE.6 A study from the United Kingdom (UK)
showed that Black African/Caribbean juvenile-SLE (jSLE)
patients were presented by more “classical” laboratory and
clinical features in comparison to White Caucasian or Asian
patients at the time of diagnosis; they frequently had renal
involvement.7 A study in Korean population found fever,
oral ulcers, nephritis, anemia, and thrombocytopenia were
more common in juvenile-onset SLE (<18 years old) pa-
tients in comparison to adult (18–50 years old) or late-onset
SLE (>50 years old); however the frequency of malar rash,
discoid rash, alopecia, arthritis, arthralgia, pleuritis, peri-
carditis, CNS involvement, and Raynaud’s phenomenon
was similar among the groups.8 Disease onset was generally
more severe in childhood-onset SLE, but the prognosis of
childhood-onset SLE was reported comparable to adult
SLE.9
To date, there is no epidemiological study presenting the
comparison of demographic, clinical manifestation, and
outcomes both in childhood- and adult-onset SLE among
Indonesian patients. Hence, our study addressed to compare
these based on SLE cohort study of Indonesian patients
conducted in a tertiary care center.
Method
Population
This retrospective study included patients enrolled in the
Hasan Sadikin Lupus Registry (HSLR), which was initiated
in 2016. HSLR database included retrospectively the data of
SLE outpatients and inpatients who came to Department of
Pediatrics and Rheumatology Clinic, Hasan Sadikin Hos-
pital, Indonesia from 2008 to 2017.
Case definition and inclusion criteria
All patients were Indonesians who met American College of
Rheumatology revised criteria for the classification of
SLE.10,11 The childhood-onset SLE was defined as diag-
nosed SLE at 18 years old or younger (Group 1), and the
Lupus 31(6)
adult-onset was older than 18 years when diagnosed with
SLE (Group 2) as number of sample based on group 174 vs
696 patients, respectively.
Variables construction
The database form included patient’s gender, age of onset,
disease duration, and the clinical manifestations at diagnosis.
Autoantibody profiles were based on the available data,
performed in local laboratory, when they were diagnosed. The
result was defined as negative or positive based on the ref-
erenced value given by the laboratory. Mortality of any causes
of the patients related or not related to SLE was documented.
Statistical analysis
We used proportions and percentages for demographic,
clinical, and serological variables, while mean and median
were for continuous data. For statistical analyses, we used
Chi-square and Fisher’s exact tests to determine any sig-
nificant differences in all categorical data and Mann–
Whitney U test for continuous data. p-value of 0.05 or
less was considered as significant. Statistical analysis was
performed by using SPSS 22.0 version.
Study approval
This study was approved by the Ethical Committee of
Faculty of Medicine, University of Padjadjaran with reg-
istration number 407/UN6.KEP/EC/2018.
Result
Basic demographic data
The proportion of childhood-onset SLE was 20% (174 out
of 870), with 35 (20%) diagnosed at ≤ 10 years old. The
mean age of group 1 was 13.56 ± 3.04 years (range 1–18)
and group 2 was 30.41 ± 8.54 years (range 19–58). There
were 163 (93.7%) females in childhood-onset SLE group
and 632 (90.8%) in adult-onset groups, p = 0.146. The ratio
of female to male was 14:1 in group 1 and 17:1 in group 2.
The median duration of disease was 4 (range 1–44) months
in group 1 and 5 (range 1–25) months in group 2 (p = 0.129)
(Table 1).
Clinical manifestations
The following clinical manifestations at diagnosis were
more common in childhood-onset SLE (Group 1) than in
adult-onset SLE (Group 2) patients: arthritis (69.5% vs
68%, p = 0.006) and hematological involvement (77.6% vs
57.3%, p = 0.033). While following manifestations were
Hamijoyo et al. 761

Table 1. Demographic profile of childhood-onset and adult-onset of systemic lupus erythematosus.

Characteristic Childhood-onset (N = 174) Adult-onset (N = 696) p-value

Mean age of SLE diagnosed ±SD (years) 13.56 ± 3.04 30.41 ± 8.54 <0.001
Median age of SLE diagnosed, years (min-max) 14 (4–17) 29 (18–70)
Female sex (%) 163 (93.7) 632 (90.8) 0.146
Mean disease duration ±SD (months) 5.17 ± 4.84 5.92 ± 4.16 0.129
Median disease duration, months (min–max) 4 (1–44) 5 (1–25)

Table 2. Clinical manifestation and autoantibody at systemic lupus erythematosus diagnosed of childhood-onset and adult-onset lupus
patients.

Clinical manifestation Childhood onset (N = 174), n (%) Adult onset (N = 696), n (%) p-value

Malar rash 119 (68.4) 429 (61.6) 0.289

Photosensitivity 84 (48.3) 416 (59.8) <0.001
Discoid rash 53 (30.5) 232 (33.3) 0.036
Oral ulcers 93 (53.4) 363 (52.1) 0.068
Arthritis 121 (69.5) 477 (68.5) 0.006
Serositis 53 (30.5) 176 (25.3) 0.910
Nephritis 87 (50.0) 263 (37.8) 0.445
Neuropsychiatric involvement 39 (22.4) 140 (20.1) 0.981
Hematological involvement 135 (77.6) 399 (57.3) 0.033
ANA 170 (97.7%) 696 (100%) 0.891
Anti-dsDNA 98/103 (95.14%) 87/183 (47.5%) 0.670
ANA: anti-nuclear antibody, Anti-dsDNA: double stranded DNA.

found more common in adult: photosensitivity (59.8% vs Discussion

48.3.0%, p <0.001) and discoid rash (33.3% vs 30.5%, p =
0.036).
Antibody profiles
Anti-nuclear antibody (ANA) was more prominent in adult
patients compared to childhood-onset patient (100% vs
96.1%, p = 0.670), but not significantly (Table 2).
Treatment and mortality
Steroid, azathioprine, and antimalarial were used in both
groups (96% vs 98%, p = 0.661), (17.8% vs 36.5%,
p = <0.001), and (30.5% vs 58.4%, p < 0.001), respectively.
Other medications such as cyclophosphamide pulse therapy
and mycophenolate mofetil were more commonly used in
childhood-onset lupus (38.5% vs 21.0%, p < 0.001) and
(9.2% vs 2.3%, p = 0.065). While the other immunosup-
pressive drugs such as methotrexate did not show statistical
difference between the two groups (1.1% vs 3.2%, p =
0.399) (Table 3).
Mortality from any causes was 20 (11.5%) in group 1 and
49 (7.0%) in group 2, and the difference was not significant
(p = 0.208). The most causes of death were infection
(Table 4).
The true prevalence of childhood lupus is still unknown due
to the differences in the cutoff age; however, the prevalence
rates of 1.89–25.7/100,000 per year have been recorded,
with greater prevalence in Asian, Latin, African-American,
and Native American children.12 In our lupus cohort da-
tabase, we found 20% (174 out of 870) of SLE patients were
diagnosed at 18 years old or younger, higher than in the
previous studies.13–15 Among them, 20 (20%) patients were
diagnosed with SLE at 10 years old or younger, and the
youngest patient was 1 year old. Diagnosis of SLE prior to
10 years old was uncommon.16 Benseler et al. reported 6 to
618.9 cases per 100,000 children less than 10 years old of
same sex, age, and ethnic were diagnosed with lupus.17
The ratio of female to male in childhood-onset SLE is
various. In our cohort, it was 14:1. The proportion of
childhood-onset male to female SLE patients was lower
than adult-onset patients. This result was similar as reported
in several studies.18–20
Previous studies that have compared childhood-versus
adult-onset SLE showed varying results in terms of clinical
manifestations,1,4,18–22 but numerous studies have dem-
onstrated that disease activity was generally more severe in
childhood-onset SLE.9,15,19,23,24 Most studies supported
our finding that renal involvement, and hematological
762 Lupus 31(6)

Table 3. Medications of childhood-onset and adult onset patients with systemic lupus erythematosus.

Characteristic Childhood onset (N = 174) Adult onset (N = 696) p-value

Steroid 167 (96.0%) 682 (98%) 0.661

Cyclophosphamide 67 (38.5%) 146 (21.0%) <0.001
Hydroxychloroquine/Chloroquine 53 (30.5%) 406 (58.4%) <0.001
Azathioprine 31 (17.8%) 395 (56.8%) <0.001
Methotrexate 2 (1.1%) 22 (3.2%) 0.399
Mycophenolate mofetil 16 (9.2%) 15 (2.3%) 0.065

Table 4. Cause of mortality of lupus patients.

Childhood onset (N = 174) Adult onset (N = 696) p-value

Died in follow-up 20 (11.5) 49 (7.0) 0.208

Cause of death
Pulmonal (including infection) 3 (14.3) 13 (25.5)
Pulmonal (without infection) 0 (0) 8 (15.7)
Sepsis 1 (4.8) 4 (7.8)
Neuropsychiatric 1 (4.8) 1 (2.0)
Intracranial hemorrhage 0 (0) 3 (5.9)
Cardiac disease 1 (4.8) 6 (11.8)
Nephritis 1 (4.8) 1 (2.0)
Pregnancy-related embolism — 1 (2.0)
Unknown 14 (66.7) 14 (27.5)

involvement were more common in children with
SLE.15,19,22,25–27 However, the frequency of skin involve-
ment including malar rash was reported to be similar in both
groups.1 Our study found that arthritis and hematological
involvements were more common in childhood-onset than
in adult-onset SLE patients, while photosensitivity and
discoid rash were more common significantly in adult-onset
group. The frequency of mucocutaneous lupus without
systemic feature is very low in children.28 Neuropsychiatric
involvement has been reported common in adult patients
with SLE than childhood-onset of SLE.18 This was similar
to our finding which showed no significant difference in
neuropsychiatric manifestations between the two groups. It
is possible that neuropsychiatric symptoms are more
commonly manifested later on during the disease and not as
a presenting manifestation.29,30
Most of studies showed no difference in the prevalence
of ANA between childhood and adult-onset of SLE;
however Mina et al. reported a higher prevalence of anti-
dsDNA antibodies in childhood with SLE in comparison to
adult SLE patients (61–93% vs 25–78%).23 Our study found
lower anti-dsDNA result than several studies. Although
only small portion of our subjects tested for anti-dsDNA, the
test should be compared by other studies.18,19,25
Children and juvenile SLE have unique problems related
to growth and development that affect both the need for and
the impact of aggressive therapy, which was associated with
higher medication iatrogenic effects.31 Sinha et al. sug-
gested more aggressive therapy to the child lupus patients
with the high active index on renal biopsy for their better
outcome.32 Cyclophosphamide therapy significantly re-
duced proteinuria among childhood SLE patients and in-
creased creatinine clearance among those with decreased
function prior to therapy, as well as prevented progression of
renal scarring.33 In our setting, the involvement of renal in
SLE as well as the use of cyclophosphamide was more
common in childhood-onset SLE; however, there was no
complete data regarding the renal biopsy of those patients.
Younger age at onset of SLE has greater disease
severity,22,27 with the more severe prognosis than adult,9 as
they have longer duration of diseases from age of diag-
noses.10 We found that both childhood and adult-SLE pa-
tients had the similar median duration of disease; however,
the mortality was different in both groups, with higher
prevalence in childhood-onset SLE. This finding is similar
to several studies13,14,18,34; nevertheless, it may indicate
earlier diagnosis and treatment of SLE should be undergone
to reduce the worsening of disease outcome.32
The limitation of our study was the incomplete data of
antibody profiles of the patients as not all patients had
complete serologic tests due to financial limitations. Data on
renal biopsy was not collected, since only a few patients
underwent kidney biopsy in this center. The other limitation
was the unavailability of the exact cause of death of some
Hamijoyo et al.
patients. There was no autopsy done to confirm cause of
death on these patients. Furthermore, some patients died
outside of the hospital, without knowing the cause of death
to be recorded.
Conclusion
Arthritis and hematological involvements at diagnosis were
more prominent in childhood-onset compared to adult-onset
SLE. Mortality in childhood-onset is relatively higher than
in adult-onset. This data may suggest a need for more
aggressive management approach to childhood-onset pa-
tients with SLE.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with re-
spect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
project was supported by Internal Research Grant of University of
Padjadjaran.
ORCID iD
Laniyati Hamijoyo  https://orcid.org/0000-0002-1310-674X
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