Concise report
Juvenile-onset systemic lupus erythematosus:
1
Centre for Paediatric
Rheumatology, Ghent University
Hospital, Ghent, Belgium;
2
Department of Rheumatology,
Université Catholique de
Louvain, Louvain, Belgium;
3
Department of Rheumatology,
Ghent University Hospital,
Ghent, Belgium; 4 Leids
Universitair Medisch Centrum,
Leiden, Netherlands; 5 University
College London, London, UK;
6
Research Institute for
Rheumatic Diseases, Piestany,
Slovakia; 7 Centre for Paediatric
Rheumatology, University of
Brussels, Brussels, Belgium
Correspondence to:
Dr D Elewaut, Ghent University
Hospital, Department of
Rheumatology, 185 De
Pintelaan, B-9000 Ghent,
Belgium; Dirk.Elewaut@
UGent.be
Accepted 30 September 2008
Published Online First
17 October 2008
412
different clinical and serological pattern than adult-
onset systemic lupus erythematosus
I E A Hoffman,1 B R Lauwerys,2 F De Keyser,3 T W J Huizinga,4 D Isenberg,5
L Cebecauer,6 J Dehoorne,1 R Joos,1 G Hendrickx,7 F Houssiau,2 D Elewaut1
ABSTRACT
Objective: To investigate differences in clinical signs and
symptoms, and in antinuclear antibodies (ANA), between
patients with juvenile-onset and adult-onset systemic
lupus erythematosus (SLE).
Methods: Clinical and serological data of 56 patients
with juvenile-onset SLE were compared with data of 194
patients with adult-onset SLE. ANA were determined by
line immunoassay and by indirect immunofluorescence on
Crithidia luciliae.
Results: Renal involvement, encephalopathy and hae-
molytic anaemia were seen, and anti-dsDNA, anti-
ribosomal P and antihistone antibodies found, significantly
more often in juvenile-onset SLE. Anti-dsDNA antibodies
were directly associated, and anti-ribosomal P antibodies
inversely associated, with renal involvement in juvenile-
onset SLE. In juvenile patients with SLE and anti-dsDNA
and without anti-ribosomal P antibodies the odds ratio for
glomerulonephritis was 9.00; no patients with anti-
ribosomal P but without anti-dsDNA had renal involve-
ment.
Conclusion: Patients with juvenile-onset SLE more often
have renal involvement and encephalopathy than patients
with adult-onset SLE. Anti-ribosomal P, anti-dsDNA and
antihistone antibodies are more often found in patients
with juvenile-onset SLE.
Many studies have been published highlighting the
clinical and serological characteristics of systemic
lupus erythematosus (SLE) in adults.
Autoantibodies, notably antinuclear antibodies
(ANA), are important both in the diagnosis and
pathophysiology of SLE. Some antibodies are
highly specific for SLE and some are associated
with clinical symptoms.1 2 The incidence of juve-
nile SLE is very low (less than 1/100 000), which
makes it hard to gather a substantial study group.
Several studies have demonstrated that renal
disease is more common in children.2–5 In contrast,
for other symptoms and autoantibodies few
differences have been found and confirmed. One
study reported the higher prevalence of anti-
ribosomal P antibodies in juvenile-onset SLE
compared with adult-onset SLE.6 Other studies
found a higher prevalence of anti-dsDNA,5 7 anti-
RNP7 and anti-Sm antibodies7 in juvenile-onset
SLE.
We report the prevalence of different signs,
symptoms and antibodies in juvenile-onset SLE,
compared with an adult-onset population.
Associations between antibodies and clinical fea-
tures were assessed.
PATIENTS AND METHODS
Patients
All the patients met four or more of the revised
American College of Rheumatology (ACR) classi-
fication criteria for SLE.8 9 Juvenile onset was
defined as diagnosis at the age of 18 or younger
according to the Paediatric Rheumatology
International Trials Organization (PRINTO).10
Fifty-six patients with juvenile-onset SLE and 194
patients with adult-onset SLE were studied. Several
centres participated: University Hospital Ghent,
Belgium; University Hospital Leiden, the
Netherlands; Research Institute of Rheumatic
Diseases Piestany, Slovakia; University College
London, UK; Université Catholique de Louvain,
Belgium; and University Hospital Brussels,
Belgium. All centres are tertiary referral centres.
Clinical data
A questionnaire covering clinical data was com-
pleted by the treating doctor, based on history
taking and on the patient’s medical chart (table 1).
Symptoms occurring during the entire disease
course were considered.
The study was conducted after approval by the
local ethics committees. Informed consent was
obtained from all patients.
Determination of autoantibodies
Serum samples were analysed by line immunoas-
say (INNO-LIA ANA update, K1090, Innogenetics,
Zwijnaarde, Belgium) as described previously.11
This multiparameter assay contains the following
antigens: SmB, SmD, RNP-A, RNP-C, RNP-70k,
Ro52, Ro60, La/SSB, Cenp-B, Topo-I, Jo-1, riboso-
mal P and histones.11
Anti-dsDNA antibodies were detected by indir-
ect immunofluorescence (IIF) on Crithidiae luciliae.
Statistical analysis
Statistical analysis was performed using SPSS,
version 15.0.
To determine associations a x2 test or the Fisher
exact test was used. We computed odds ratios (ORs)
and their 95% confidence interval (95% CI). No
correction for multiple testing was made. For compar-
ing medians, the Mann–Whitney U test was used.
RESULTS
Demography
In the adult group, 23 (11.9%) of the patients were
male, versus nine (16.1%) in the juvenile group
Ann Rheum Dis 2009;68:412–415. doi:10.1136/ard.2008.094813
 Concise report

Table 1 Incidence of signs and symptoms in juvenile-onset systemic Table 2 Prevalence of autoantibodies
lupus erythematosus (SLE) compared with adult-onset SLE Juvenile-onset Adult-onset
Incidence in Incidence in Autoantibodies SLE (%) SLE (%) p Value
juvenile-onset adult-onset
SLE SLE Sm 17.9 12.4 NS
Symptoms (%) (%) p Value RNP 14.3 17.5 NS
SSA/Ro 23.2 33.5 NS
Cutaneous symptoms
SSB/La 7.1 17.0 NS
Butterfly rash 69.6 58.6 NS
Ribosomal P 25.0 11.3 (0.01
Photosensitivity 44.6 53.2 NS
Histones 39.3 25.8 (0.05
Alopecia 41.1 45.1 NS
DNA 60.7 24.9 (0.001
Oral ulcers 28.6 23.5 NS
Localised discoid rash 13.2 19.1 NS
Disseminated discoid rash 5.7 9.5 NS 5.39), subacute cutaneous lupus, OR = 4.65 (1.20 to 18.02) and
Generalised erythema 20.0 9.5 (0.05
chilblains OR = 9.22 (1.73 to 49.00), which were all seen more
Genital ulcers 3.6 4.3 NS
often in juvenile patients. Fever occurred significantly more
Subacute cutaneous LE 9.6 2.2 (0.05
often in juvenile SLE, OR = 1.97 (1.05 to 3.70), whereas sicca
Chilblains 9.4 1.1 (0.01
symptoms and arthralgia were less common. Renal signs
General symptoms
occurred markedly more often in juvenile patients (proteinuria:
Xerostomia 7.5 21.4 (0.05
OR = 2.30 (1.23 to 4.28); glomerulonephritis: OR = 2.96 (1.60 to
Xerophthalmia 3.8 18.7 (0.01 5.49); urinary cellular casts, OR = 2.83 (1.48 to 5.40)). This was
Fatigue 78.6 83.5 NS also the case for encephalopathy (OR = 4.55 (1.82 to 11.41)) and
Raynaud’s disease 39.3 41.1 NS haemolytic anaemia (OR = 4.19 (2.07 to 8.48)).
Fever 67.3 51.0 (0.05
Arthralgia 75.0 98.7 (0.005
Prevalence of autoantibodies
Arthritis 59.3 66.8 NS
Table 2 shows the prevalence of autoantibodies. Anti-ribosomal
Myalgia 42.4 35.2 NS
P (p(0,01), anti-dsDNA (p(0.001) and antihistone antibodies
Pleuritis 18.5 32.1 NS
(p(0.05) were found significantly more often in the juvenile
Pericarditis 16.7 18.2 NS
patients. When we computed the total number of reactivities
Renal signs for each patient we found a higher number of reactivities in the
Proteinuria 63.6 43.2 (0.01 patients with juvenile-onset SLE than in adult-onset SLE (mean
Glomerulonephritis 62.5 36.0 (0.001 1.9 vs 1.4; p(0.05).
Urinary cellular casts 57.1 32.0 (0.001
Associations of autoantibodies with clinical signs
Neurological signs/symptoms
The most striking findings are the association of anti-dsDNA
Headache 25.5 30.9 NS
antibodies with renal signs and the inverse association of anti-
Concentration disorder 20.4 17.8 NS
ribosomal P with renal signs in juvenile SLE. Anti-dsDNA
Depression 12.7 15.8 NS
antibodies were significantly associated with glomerulonephritis,
Encephalopathy 20.4 5.3 (0.005
Seizures 14.5 6.9 NS
p(0.01; OR = 2.41 (1.25 to 4.64) and with urinary cellular casts
Cerebrovascular accident 5.6 6.9 NS p(0.05; OR = 3.33 (1.01 to 10.97). The association of anti-
Psychosis 9.3 5.9 NS dsDNA and proteinuria was not significant p = 0.086; OR = 2.67
(0.86 to 8.29). In contrast, anti-ribosomal P antibodies were
Haematological signs inversely associated with glomerulonephritis, p(0.05; OR = 0.22
Leucopenia 63.6 56.8 NS (0.06 to 0.80), with urinary cellular casts p(0.01; OR = 0.61 (0.04
Lymphopenia 67.9 64.1 NS to 0.70) and with proteinuria, p(0.05; OR = 0.20 (0.07 to 0.74).
Thrombocytopenia 31.5 25.0 NS We divided the patients according to their anti-dsDNA and
Haemolytic anaemia 38.5 13.0 (0.001 anti-ribosomal P status in order to clarify these results. The
Thrombosis 11.5 10.0 NS presence or absence of both antibodies in the same patient was
not associated with renal signs. However, if anti-dsDNA
antibodies were present and anti-ribosomal P antibodies were
(NS). Median age at diagnosis was 32 years for adults (range 19– absent (n = 23) a strong association with renal involvement was
73) and 15 years for juvenile patients (range 9–18). Median age found: OR for glomerulonephritis = 9.00 (2.23 to 36.33),
at sampling was 41 years (range 20–77) in adults and 20 years p(0.001; for urinary cellular casts OR = 6.57 (1.74 to 24.77),
(range 12–49) in juvenile patients. Median symptom duration at
p(0.005; and for proteinuria OR = 4.75 (1.32 to 17.11). In four
sampling was 5 years for adults and 5.5 years for juvenile
patients anti-ribosomal P antibodies were present and anti-
patients (NS). In the juvenile group 44/55 (80.0%) were
dsDNA antibodies were absent, none of them had renal
Caucasian (data missing for one patient), compared with 161/
involvement (all p,0.05).
188 (85.6%) in the adult group (NS) (data missing for six
In the adult population we could not find any significant
patients).
associations for patients positive for both antibodies or negative
for both antibodies. Moreover, no significant associations were
Distribution of symptoms found for the anti-dsDNA positive and anti-ribosomal P
The prevalence of symptoms in both groups was calculated negative group (n = 41). Fifteen adult patients had anti-
(table 1). Among cutaneous symptoms, significant differences ribosomal P antibodies without anti-dsDNA antibodies, only
were found for generalised erythema, OR = 2.38 (95% CI 1.05 to one of these had proteinuria and glomerulonephritis, none had

Ann Rheum Dis 2009;68:412–415. doi:10.1136/ard.2008.094813 413

 Concise report
Figure 1 Prevalence of glomerulonephritis in (A) juvenile-onset and (B)
adult-onset systemic lupus erythematosus (SLE), according to anti-
ribosomal P or anti-dsDNA antibody status.
cellular casts (all p,0.05). Figure 1 shows the occurrence of
glomerulonephritis according to antibody status.
DISCUSSION
We studied the occurrence of signs and symptoms of SLE and
ANA in patients with a diagnosis before the age of 18 as
compared with patients with adult-onset SLE. We searched for
associations between autoantibodies and clinical symptoms in
juvenile SLE. It has been suggested that juvenile SLE has a more
serious disease course than adult SLE.12 13 A higher occurrence of
renal disease, resulting in more renal damage has, notably, been
reported.14 We confirm the more frequent occurrence of renal
disease in juvenile SLE that has been described previously.2–5
Furthermore, we found a higher frequency of fever, generalised
erythema, chilblains, subacute cutaneous lupus, encephalopathy
and haemolytic anaemia in juvenile SLE. The higher prevalence
of renal, neurological and haematological symptoms points to a
more severe disease in juvenile SLE than in adult SLE.
Techniques for detecting ANA have changed markedly over
the past 10 years, making it hard to interpret earlier results
about the prevalence of antibodies. For detecting antibodies
towards Sm, RNP, Ro/SSA, La/SSB, ribosomal P and histones,
we used the sensitive and specific line immunoassay techni-
que.11 For detecting anti-dsDNA antibodies we used IIF on
Crithidia luciliae, which is very specific for SLE. It was previously
reported that anti-ribosomal P6 and anti-dsDNA antibodies5 7
are more common in juvenile SLE. We confirmed this and also
found a higher occurrence of antihistone antibodies. Reichlin et
al stated that both anti-dsDNA and anti-ribosomal P antibodies
were associated with a higher prevalence of renal involvement
in juvenile SLE.6 Since these antibodies are more common in
juvenile SLE this may explain the higher prevalence of renal
414
disease. However, this was not found in an earlier study
focusing on ribosomal P antibodies in juvenile SLE.15 Moreover,
our results indicate an inverse association between anti-
ribosomal P antibodies and renal disease in juvenile SLE,
whereas anti-dsDNA antibodies are associated with a higher
occurrence of renal disease. We investigated this in more detail,
looking at the different possible combinations of these
antibodies. This has not yet been done before. Surprisingly,
we found very strong associations between renal involvement
and some combinations of antibodies. Patients with anti-
dsDNA antibodies who did not have anti-ribosomal P antibodies
had a high OR for renal involvement, whereas none of the
patients with anti-ribosomal P antibodies without anti-dsDNA
antibodies had renal disease. Even though the patient numbers
are small, the results are statistically significant and the size of
the odds ratio points to their clinical relevance.
To confirm these findings, the associations between these
antibody combinations and renal symptoms should be investi-
gated in different cohorts. Ideally, prospective cohort studies
should be performed, which would also allow the timing of the
appearance of antibodies and of renal disease to be investigated.
In addition as our cohort is mainly of Caucasian origin, these
results need to be confirmed in patients with different ethnic
backgrounds. So far, the emphasis has been put on individual
antibodies rather than on combinations of autoantibodies as
reported here, which underlines the novelty of our findings.
Moreover, the age at onset of SLE seems to have an influence on
the occurrence of symptoms and autoantibodies as well as on
the associations between antibodies and clinical symptoms.
In conclusion, we confirm that juvenile SLE may have a more
severe disease course than adult SLE. We show a higher prevalence
of anti-dsDNA, anti-ribosomal P and antihistone antibodies in
juvenile SLE. In juvenile SLE we find a differential effect of anti-
ribosomal P and anti-dsDNA antibodies on renal involvement.
Competing interests: None.
Ethics approval: Approved by the local ethics committees.
REFERENCES
1. Hoffman IEA, Peene I, Meheus L, Huizinga TWJ, Cebecauer L, Isenberg D, et al.
Specific antinuclear antibodies are associated with clinical features in systemic lupus
erythematosus. Ann Rheum Dis 2004;63:1155–8.
2. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Systemic
lupus erythematosus: clinical and immunological patterns of disease expression in a
cohort of 1000 patients. Medicine (Baltimore) 1993;72:113–24.
3. Carreno L, Lopez-Longo FJ, Monteagudo I, Rodriguez-Mahou M, Bascones M,
Gonzalez CM, et al. Immunological and clinical differences between juvenile and adult
onset of systemic lupus erythematosus. Lupus 1999;8:287–92.
4. Barron KS, Silverman ED, Gonzales J, Reveille JD. Clinical, serological and
immunogenetic studies in childhood-onset systemic lupus erythematosus. Arthritis
Rheum 1993;3:348–54.
5. Pande IRA, Sekharan NG, Kailash S, Uppal SS, Singh RR, Kumar A, et al. Analysis of
clinical and laboratory profile in Indian childhood systemic lupus erythematosus and
its comparison with SLE in adults. Lupus 1993;2:83–7.
6. Reichlin M, Broyles TF, Hubscher O, James J, Lehman TA, Palermo R, et al.
Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus
erythematosus compared with the adult disease. Arthritis Rheum 1999;42:69–75.
7. Tucker LB, Menon S, Schaller JG, Isenberg D. Adult- and childhood onset systemic
lupus erythematosus: a comparison of onset, clinical features, serology, and
outcome. Br J Rheumatol 1995;34:866–72.
8. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982
revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum
1982;25:1271–7.
9. Hochberg MC. Updating the American College of Rheumatology revised criteria for the
classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.
10. Ruperto N, Bazso A, Ravelli A, Malattia C, Filocamo G, Pistorio A, et al. The Paediatric
Rheumatology International Trials Organization (PRINTO). Lupus 2007;16:670–6.
11. Meheus L, Van Venrooij WJ, Wiik A, Charles PJ, Tzioufas AG, Meyer O, et al.
Multicenter validation of recombinant, natural and synthetic antigens used in a single
multiparameter assay for the detection of specific anti-nuclear auto-antibodies in
connective tissue diseases. Clin Exp Rheumatol 1999;17:205–14.
Ann Rheum Dis 2009;68:412–415. doi:10.1136/ard.2008.094813
 Concise report

12. Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED.
Clinical and laboratory characteristics and long-term outcome of pediatric
systemic lupus erythematosus: a longitudinal study. J Pediatr
2008;152:550–6.
13. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease
features between childhood-onset and adult-onset systemic lupus erythematosus.
Arthritis Rheum 2008;58:556–62.
14. Tucker LB, Uribe AG, Fernandez M, Vila LM, McGwin G, Apte M, et al. Adolescent
onset of lupus results in more aggressive disease and worse outcomes: results of a
nested matched case control study within LUMINA, a multiethnic US cohort
(LUMINA LVII). Lupus 2008;17:314–23.
15. Press J, Palayex K, Laxer RM, Elkon K, Eddy A, Rakoff D, et al. Antirobosomal P
antibodies in pediatric patients with systemic lupus erythematosus and psychosis.
Arthritis Rheum 1996;39:671–6.

Save your favourite articles and useful searches

Use the ‘‘My folders’’ feature to save and organise articles you want to return to quickly—saving space
on your hard drive. You can also save searches, which will save you time. You will only need to register
once for this service, which can be used for this journal or all BMJ Journals, including the BMJ.

Ann Rheum Dis 2009;68:412–415. doi:10.1136/ard.2008.094813 415