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Epidemiology of juvenile idiopathic arthritis in a multiethnic cohortEthnicity as a risk factor.

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ARTHRITIS & RHEUMATISM
Vol. 56, No. 6, June 2007, pp 1974–1984
DOI 10.1002/art.22709
© 2007, American College of Rheumatology
Epidemiology of Juvenile Idiopathic Arthritis in a
Multiethnic Cohort
Ethnicity as a Risk Factor
R. K. Saurenmann,1 J. B. Rose,2 P. Tyrrell,2 B. M. Feldman,2 R. M. Laxer,2
R. Schneider,2 and E. D. Silverman2
types. A higher frequency of enthesitis-related JIA was
observed among patients of Asian origin, while those of
black origin or native North American origin were more
likely to develop polyarticular RF-positive JIA.
Conclusion. In this multiethnic cohort, European
descent was associated with a significantly increased
risk of developing JIA, and the distribution of JIA
subtypes differed significantly across ethnic groups.
Objective. To study the influence of ethnicity on
the risk of developing juvenile idiopathic arthritis (JIA)
in a multiethnic community of patients with unrestricted access to health care.
Methods. A questionnaire on ethnicity was distributed to all patients with JIA being followed up at the
Hospital for Sick Children in Toronto, Ontario, Canada. Of 1,082 patients, 859 (79.4%) responded to the
questionnaire. To calculate the relative risk (RR) of
developing JIA in this study cohort, the results were
compared with data from the age-matched general
population of the Toronto metropolitan area (TMA) as
provided in the 2001 census from Statistics Canada.
Results. European descent was reported by 69.7%
of the patients with JIA compared with a frequency of
54.7% in the TMA general population, whereas a statistically significantly lower than expected percentage of
the patients with JIA reported having black, Asian, or
Indian subcontinent origin. Children of European origin had a higher RR for developing any of the JIA
subtypes except polyarticular rheumatoid factor (RF)–
positive JIA, and were particularly more likely to develop the extended oligoarticular and psoriatic sub-
Juvenile idiopathic arthritis (JIA) is the most
common rheumatic disease occurring in childhood in the
Western world. It is characterized by persistent inflammation of the joints, with onset prior to age 16 years.
Although there have been multiple names associated
with this illness, including juvenile rheumatoid arthritis
(JRA), juvenile chronic arthritis, and juvenile arthritis,
the currently agreed-upon classification is the International League of Associations for Rheumatology
(ILAR) revised classification, which refers to the illness
as JIA (1). The major subtypes of JIA are oligoarticular
JIA (up to 4 affected joints), which may be persistent or
extended (involving more than 4 joints after the first 6
months of disease), polyarticular (more than 4 affected
joints) rheumatoid factor (RF)–negative JIA, polyarticular RF-positive JIA, systemic JIA, enthesitis-related
arthritis (ERA), psoriatic JIA, or a classfication of
“other JIA” when the criteria for more than 1 subtype of
JIA or none of the criteria were met.
The first epidemiologic studies of JIA performed
in populations from Western Europe and North America showed an incidence of JIA between 1.3 and 22.6 per
100,000 person-years (2–8) and a prevalence of JIA
between 7 and 148 per 100,000 person-years (4,7–10).
However, comparison of these studies is difficult, because different diagnostic criteria and different study
designs were used. The few studies that were
Supported by grants from the Swiss Arthritis Society
(Rheumaliga Schweiz) and Stiftung Sanitas, Switzerland. Dr. Feldman
holds a Canada Research Chair in Childhood Arthritis.
1
R. K. Saurenmann, MD: Zurich University Children’s Hospital, Zurich, Switzerland, and The Hospital for Sick Children and
University of Toronto, Toronto, Ontario, Canada; 2J. B. Rose, HBSc,
P. Tyrrell, MSc, B. M. Feldman, MD, MSc, FRCPC, R. M. Laxer, MD,
FRCPC, R. Schneider, MBBCh, FRCPC, E. D. Silverman, MD,
FRCPC: The Hospital for Sick Children and University of Toronto,
Toronto, Ontario, Canada.
Address correspondence and reprint requests to R. K. Saurenmann, MD, Zurich University Children’s Hospital, Steinwiesstrasse
75, 8032 Zurich, Switzerland. E-mail: traudel.saurenmann@
kispi.unizh.ch.
Submitted for publication November 24, 2006; accepted in
revised form March 7, 2007.
1974
ETHNICITY IN JIA
population-based showed a higher prevalence of JIA,
between 167 and 400 per 100,000 person-years; this
difference is likely due to undiagnosed cases being
identified in “healthy” children when they underwent
examination by trained pediatric rheumatologists
(11,12).
More recently, epidemiologic studies from countries other than in Europe and North America showed a
different pattern of prevalence of the JIA subtypes as
well as a different rate of development of uveitis (a
common complication of JIA) (13–23) as compared with
the results obtained in the North American and European studies. A study from Japan showed a very low
overall disease prevalence (18), and studies from India
and Kuwait showed a much lower than expected rate of
antinuclear antibody (ANA) positivity and uveitis
(13,17). Studies of African American patients and black
South African patients showed a higher rate of RFpositive polyarticular JIA and a lower rate of uveitis in
these ethnic groups (14,19). Moreover, in studies of
native North American patients, higher rates of the
polyarticular subtypes, both RF positive and RF negative, were found (9,16,24,25). Possible reasons for the
differences observed between ethnic groups include
environmental and genetic factors but also underrepresentation of the milder forms of JIA, such as oligoarticular JIA, because of the potential for underdiagnosis
in children, which could be attributed to restrictions in
their access to health care facilities.
The Canadian Health Care System provides unrestricted and universal access to health care facilities
for all of its residents. Toronto is a city with a predominant immigrant component and high ethnic diversity
within the population. Pediatric rheumatology clinical
services in Toronto are provided by a single tertiary care
center, which serves the population of 4.7 million inhabitants of the Toronto metropolitan area (TMA). In the
present study, we used this background population to
define the influence of ethnicity on the prevalence and
presentation of JIA and the risk of developing JIArelated uveitis.
PATIENTS AND METHODS
Patients. A search of the database of the Division of
Rheumatology at The Hospital for Sick Children in Toronto
revealed that arthritis had been diagnosed in 1,605 patients
between July 1, 1984 and June 30, 2002. Following a review of
the charts of all 1,605 patients, we identified a total of 1,082
patients who had a confirmed diagnosis of JIA and whose
minimum followup time was 1 month. The following data were
collected: sex, date of birth, date of diagnosis of JIA, type of
JIA, ANA status, RF status, HLA–B27 status, and date of
1975
diagnosis of uveitis. The study was approved by the Research
Ethics Board of The Hospital for Sick Children.
In autumn 2003, a questionnaire was either mailed or
handed out at clinic visits to the cohort of 1,082 patients. The
questionnaire required patients, or their parents, to provide
information about their ancestry/country of origin. In addition,
patients were contacted by telephone and asked to provide the
same information verbally, after they had given their informed
consent to participate in the study. The questionnaire contained a list of countries of origin (Figure 1), grouped by ethnic
regions in accordance with the list of countries and ethnic
regions used in the 2001 census by Statistics Canada. Patients
were asked to provide a response for as many categories as
applied. Questionnaires from 859 patients (79.4%) were returned. The answers from 101 patients were not useful in our
study, because 6 patients had not given any answer, 36 had
indicated Canadian as their ethnic group, and 59 had indicated
more than 1 ethnicity. Therefore, our study cohort consisted of
758 patients with JIA.
Diagnosis of JIA. The diagnosis of JIA and identification of subtypes of JIA were based on the ILAR 1997 revised
criteria (26). Patients whose diagnosis was made prior to the
use of the ILAR criteria were subsequently diagnosed as
having JIA according to the ILAR criteria from a review of the
medical records. If only 1 test of RF was performed, as was the
case in many patients, then the results of this test were used to
assign a JIA subtype rather than apply the subtype category of
“other JIA.” ANAs were considered positive if a titer of ⱖ1:20
was obtained on at least 1 clinic visit during the disease course.
This cutoff point for ANA positivity is in accordance with the
normal values used in our laboratory. In the context of the
present study, we chose to apply this cutoff value to identify
patients with ANA-positive JIA, because we do not know of
any evidence suggesting that a different cutoff level would be
better to recognize the JIA subtype associated with ANAs.
Ethnicity. According to the answers obtained from the
questionnaire, the patients were categorized into 1 of the
following ethnic groups: 1) European, comprising patients of
European or west Asian origin; 2) black, comprising patients of
black African, African American, or Caribbean origin; 3)
native North American origin; 4) Latin American, comprising
patients of Central or South American origin; 5) Asian,
comprising patients of southeast Asian, Chinese, Japanese, or
Pacific Islands origin; 6) Indian subcontinent origin; and 7)
Arab, comprising patients of north African or Arabic origin.
For some analyses, the patients were categorized into 1 of 2
groups, those of European origin and those of non-European
origin.
TMA general population data on ethnicity. Data from
the 2001 census provided by Statistics Canada were used for
comparison of the distribution of ethnicities found in our JIA
study cohort with that in the general age-matched population
of the TMA. Statistics Canada provided data for the percentage of children ages 0–14 years and those ages 15–24 years,
rather than the desired single grouping of 0–18 years. In
addition, the age distribution within each ethnic group was
available for only the total Canadian population, and not
specifically for the population of Toronto. Therefore, to account for these differences, the number of children/adolescents
in each ethnic group within the TMA population was derived
as follows: total TMA population of any ethnic group ⫻
(percentage of that ethnic group within the 0–14-year age
1976
SAURENMANN ET AL
Figure 1. Ethnicity questionnaire administered to 1,082 patients with juvenile idiopathic arthritis.
group [for all Canada] ⫹ 30% of the percentage of that ethnic
group for ages 15–24 years [for all Canada]); the latter
proportion of 30% was used because children ages 15–18 years
account for 30% of the 15–24-year-olds in the total Canadian
population.
Statistical analysis. Statistical analyses were performed using the JMP IN 5.1 program (SAS Institute, Cary,
NC). The chi-square test, one-way analysis of variance
(ANOVA), Kaplan-Meier survival analysis, and Cox proportional hazards regression analyses were used to assess the
79 (10.4)
87.3
79.5
3.9
(0.6–13.8)
223 (29.4)
76.2
71.2
5.1
(1.1–16.4)
302 (39.8)
79.1
73.4
4.8
(0.6–16.4)
417 (38.6)
77.5
72.5
4.8
(0.6–16.4)
All
167 (22.0)
78.4
51.9
6.2
(0.5–17.8)
223 (20.6)
79.8
50
6.3
(0.5–17.8)
Polyarticular
RF negative
27 (3.6)
88.9
56
11.4
(3.4–16.1)
34 (3.1)
88.2
56.3
11.1
(3.4–16.1)
Polyarticular
RF positive
* JIA ⫽ juvenile idiopathic arthritis; RF ⫽ rheumatoid factor; ANA ⫽ antinuclear antibody.
99 (9.2)
88.9
80.6
3.8
(0.6–13.8)
Extended
318 (29.4)
73.9
69.9
5.1
(0.6–16.4)
Persistent
Oligoarticular JIA
Characteristics of the patients with JIA in the total hospital cohort and the study cohort*
Total hospital cohort
No. (%) of patients
% female
% ANA positive
Age at diagnosis,
mean (range) years
Study cohort
No. (%) of patients
% female
% ANA positive
Age at diagnosis,
mean (range) years
Table 1.
103 (13.6)
51.5
19.3
7.4
(1.1–17.0)
157 (14.5)
47.8
19
7.0
(0.9–17.0)
Systemic
JIA
82 (10.8)
51.2
50.7
9.0
(1.1–17.2)
122 (11.3)
56.6
50
8.9
(0.8–17.2)
Psoriatic
JIA
67 (8.8)
25.4
32.5
11.4
(2.8–16.9)
115 (10.6)
22.6
30.8
11.7
(2.8–17.6)
Enthesitisrelated JIA
10 (1.3)
50
10
7.4
(2.8–10.8)
14 (1.3)
64.3
8.3
8.3
(2.8–12.6)
Other
JIA
758
67.4
56.9
6.74
(0.5–17.8)
1,082
65.6
55.7
6.9
(0.5–17.8)
Total
ETHNICITY IN JIA
1977
1978
SAURENMANN ET AL
differences between ethnic groups. The chi-square test was
used to compare the distribution of ethnicities in our JIA
cohort with the distribution of ethnicities in the age-matched
TMA general population. In addition, the chi-square test was
used to calculate the relative risk (RR) of developing JIA
among the different ethnic groups in our study cohort (see the
VassarStats Web site for Statistical Computation, at http://
faculty.vassar.edu/lowry/VassarStats.html).
RESULTS
Ethnic differences between the JIA study cohort
and the TMA general population. We did not find any
statistically significant differences in the characteristics
of the patients in our JIA study cohort of 758 patients as
compared with The Hospital for Sick Children total JIA
cohort of 1,082 patients (Table 1). Using the responses
from the questionnaire, we determined the distribution
of ethnicities among our JIA study cohort and compared
it with the data provided by Statistics Canada on the
general population of children in the TMA. We found
that there was an overrepresentation of patients of
European origin and native North American origin and
an underrepresentation of patients of black, Asian, or
Indian subcontinent origin in our JIA cohort as compared with the TMA general population (Figures 2A
and B). European descent was reported by 69.7% of the
patients with JIA compared with a frequency of 54.7% in
the TMA general population.
The difference in the distribution of children
according to European versus non-European ancestry in
our JIA study cohort as compared with that in the TMA
population of children was statistically significant (P ⫽
0.005 by chi-square test). Overall, children of European
ancestry had an increased RR for developing JIA (RR
1.26), whereas children of non-European ancestry had a
decreased RR for developing JIA (RR 0.43); both of
these risk values were statistically significant when compared with the predicted values (P ⬍ 0.0001). When we
directly compared the risk of developing JIA in the
group of children of European descent with that in the
group of children of non-European descent, we found
that those of European descent had a significantly
increased risk of developing JIA (RR 3.12) as compared
with those of non-European descent (P ⬍ 0.0001).
Among the individual non-European ethnic
groups of children, those of black origin (RR 0.33),
Indian subcontinent origin (RR 0.38), and Asian origin
(RR 0.41) each had a statistically significantly lower
likelihood of developing JIA as compared with the
predicted values in the total at-risk population of children in the TMA (each P ⬍ 0.0001 versus TMA
population). Similarly, children of Latin American ori-
Figure 2. Distribution of ethnicities among the population of children
and adolescents in the Toronto metropolitan area as provided by
Statistics Canada in the 2001 census (A) and in the study cohort of 758
patients with juvenile idiopathic arthritis (B).
gin and those of Arab origin had a decreased RR for
developing JIA (RRs of 0.72 and 0.72, respectively), but
these estimates were not statistically significant when
compared with the predicted values (P ⫽ 0.40 and P ⫽
0.54, respectively). The only non-European ethnic group
in whom the RR of developing JIA was increased was
the children of native North American descent (RR
1.72), but this was not statistically significant when
compared with the predicted values (P ⫽ 0.075). Of
note, only 10 patients with JIA in our cohort were of
native North American descent.
Characteristics of the study patients with JIA.
The mean age at diagnosis of JIA was significantly
ETHNICITY IN JIA
younger among patients of European origin, whose
mean age at diagnosis was 6.5 years (95% confidence
interval [95% CI] 6.1–6.8 years), as compared with those
of non-European origin, whose mean age at diagnosis
was 7.8 years (95% CI 7.1–8.4 years) (P ⫽ 0.005 by
one-way ANOVA). Patients of European origin had a
higher female:male ratio, at 7:3, as compared with a
female:male ratio of 3:2 for those of non-European
origin (P ⫽ 0.047). Patients of native North American
origin and those of Latin American origin had the
highest female:male ratios, both at 9:1, while patients of
black origin and those of Indian subcontinent origin
each had female:male ratios of 2:1. Patients of Asian
origin and those of Arab origin had the lowest female:
male ratios, at 1:1 and 2:3, respectively. The sex distributions were statistically significantly different among
the ethnic groups (P ⫽ 0.002 by chi-square test).
The frequency of RF positivity was 3.4% among
patients of European origin (13 of 384 patients tested),
which was much lower than the frequency of 14.4% (16
of 111 patients tested) among patients of non-European
origin (P ⫽ 0.0003 by chi-square test). There was no
statistically significant difference in the frequency of
ANA positivity between children of European ancestry
and those of non-European ancestry (P ⫽ 0.12). There
was also no significant difference in the overall rate of
uveitis between patients of European ancestry and those
of non-European ancestry (14.4% and 12.8%, respectively, P ⫽ 0.6). HLA–B27 was positive in 28.1% of the
patients of European descent (46 of 164 patients tested)
and in 40.5% of the patients of non-European descent
(17 of 42 patients tested); this difference in frequency of
HLA–B27 between groups was not significant (P ⫽
0.13), which may be attributable to the low number of
patients tested.
Distribution of JIA subtypes in the study cohort.
Within the European and non-European ethnic groups,
subtypes of JIA were not equally distributed (Table 2).
As compared with the distribution of disease subtypes
among the patients in the total JIA study cohort, children of European ancestry were overrepresented among
patients with the subtypes of extended oligoarticular JIA
and psoriatic JIA, whereas children of non-European
ancestry were overrepresented among those with the
subtypes of RF-positive polyarticular JIA, ERA, and
systemic JIA (P ⫽ 0.001 versus total JIA study cohort, by
chi-square test).
We then subdivided the patients of nonEuropean ancestry into specific ethnic groups and examined the distribution of JIA subtypes by ethnicity. We
found that RF-positive polyarticular JIA was overrepresented among children of native North American, black,
1979
Table 2. Distribution of JIA subtypes in children of European
descent compared with those of non-European descent*
Ethnic group
JIA subtype
All subtypes
Systemic
Oligoarticular
Persistent
Extended
RF-negative polyarticular
RF-positive polyarticular
Enthesitis-related
Psoriatic
Young-onset ANA positive†
European
(n ⫽ 599)
Non-European
(n ⫽ 159)
79
75.7
21
24.3
80.3
88.6
82
48.1
67.2
87.8
83.3
19.7
11.4
18
51.9
32.8
12.2
16.7
* Values are the percent of patients within the European or nonEuropean group. See Table 1 for definitions.
† Subset of patients with onset of ANA-positive arthritis at a younger
age.
Latin American, or Indian subcontinent ethnicity. ERA
was overrepresented in children of Asian origin, whereas
persistent oligoarticular JIA was underrepresented in
native North American children. Extended oligoarticular JIA was not seen in any patient of Arab or Latin
American origin, and psoriatic JIA was underrepresented in the Indian subcontinent, Latin American, and
native North American ethnic groups (Table 3). The
difference in the distribution of the JIA subtypes between the specific non-European ethnic groups was
significant (P ⫽ 0.0005 by chi-square test).
We then examined the RR values for the likelihood of developing any of the subtypes of JIA relative to
the total at-risk population in the TMA, i.e., the number
of children ages ⬍18 years in the ethnic groupings
defined by Statistics Canada. We found that children of
European origin had an increased RR for developing
any of the subtypes of JIA except RF-positive polyarticular JIA (Table 4). Among the specific non-European
ethnic categories, children of black origin and those of
Indian subcontinent origin were at a lower risk of
developing any of the JIA subtypes except RF-positive
polyarticular JIA, while children of Asian origin were at
a lower risk of developing any of the JIA subtypes except
ERA (Table 4). Although there were only small numbers of patients of Arab origin or Latin American origin
within each subtype, the distribution of risk of developing each subtype was similar to that seen in patients of
European descent. Patients of native North American
descent tended to develop polyarthritis, including both
RF-positive and RF-negative polyarticular JIA and extended oligoarticular JIA.
1980
SAURENMANN ET AL
Table 3. Distribution of JIA subtypes by specific non-European versus European ethnic group*
Non-European
JIA subtype
Oligoarticular
Persistent
Extended
RF-negative polyarticular
RF-positive polyarticular
Systemic
Psoriatic
Enthesitis-related
Native
P,
JIA study
Indian
Latin
North P, European between
cohort European
All
Asian subcontinent Black
Arab American American
vs. nonethnic
(n ⫽ 758) (n ⫽ 599) (n ⫽ 159) (n ⫽ 50) (n ⫽ 40) (n ⫽ 31) (n ⫽ 17) (n ⫽ 11) (n ⫽ 10) European
groups
29.8
9.3
22.2
3.3
13.7
11.4
9.3
30.1
11.8
23.1
2.2
13.1
12.1
7.6
29.6
6.3
18.9
8.8
16.3
6.3
13.8
26.0
2.0
20.0
4.0
12.0
8.0
24.0
35.0
10.0
12.5
7.5
17.5
0.0
12.5
19.4
9.7
19.4
16.1
12.9
12.9
9.7
35.3
0.0
17.7
0.0
23.5
11.8
11.8
36.4
0.0
18.2
18.2
27.3
0.0
0.0
10.0
10.0
40.0
20.0
10.0
0.0
0.0
0.79
0.029
0.2
0.0004
0.36
0.03
0.024
0.5
0.048
0.57
0.0013
0.74
0.012
0.013
* Values are the percent of the 758 patients in the JIA study cohort. The subtype of “other JIA” is not shown; 5 patients of European descent, 2
patients of Asian descent, 2 patients of Indian subcontinent descent, and 1 patient of native North American descent were classified in the “other
JIA” subtype. P values were calculated by chi-square test. See Table 1 for definitions.
Risk of young-onset ANA-positive arthritis. It has
been suggested that patients with onset of ANA-positive
arthritis at a younger age constitute a homogeneous
disease subset. We therefore examined whether this was
true across different ethnicities (27). We found that the
RR for developing young-onset ANA-positive arthritis
in children of European origin as compared with children of non-European origin was 4.21 (P ⬍ 0.0001)
(Table 4), and that patients in the young-onset ANApositive disease subset made up 31.6% of the patients of
European origin but only 23.6% of the patients of
non-European origin (P ⫽ 0.03 by chi-square test).
Among the different ethnic groups, patients of Asian
origin had the lowest rate of young-onset ANA-positive
arthritis (18%), and those of native North American
origin had the highest rate (40%), but these differences
between the individual ethnic groups were not significant (P ⫽ 0.095). Among the non-European ethnic
groups, the RR for young-onset ANA-positive arthritis
as compared with that among the total at-risk TMA
population of children ages ⬍18 years was 0.24 for
children of Asian origin (P ⬍ 0.0001), 0.26 for children
of black origin (P ⫽ 0.0003), 0.36 for children of Indian
subcontinent origin (P ⫽ 0.0001), 0.52 for children of
Latin American origin (in only 2 patients), and 0.75 for
children of Arab origin (in only 5 patients) (Table 4).
Risk of JIA-related uveitis. Within the JIA study
cohort, the rate of uveitis was the same regardless of
ethnicity. However, when compared with the total atrisk TMA population of children ages ⬍18 years, chil-
Table 4. Relative risk of developing JIA (by subtype) and JIA-related uveitis, according to ethnic group*
Non-European†
Arab
Indian
subcontinent
Native
North
American
European vs.
non-European‡
JIA subtype
European†
All
Asian
Black
Latin
American
All JIA
Oligoarticular
Persistent
Extended
RF-negative polyarticular
RF-positive polyarticular
Psoriatic
Enthesitis-related
Systemic
Young-onset ANA positive
Uveitis
1.26§
0.43§
0.41§
0.33§
0.72
0.8
0.38§
1.72
3.12§
1.28§
1.43§
1.31§
0.8
1.46§
1.05
1.16
1.34§
1.27§
0.39§
0.25§
0.36§
1
0.23§
0.61§
0.46§
0.32§
0.36§
0.35§
0.07§
0.38§
0.39
0.32§
1.1
0.34§
0.24§
0.28§
0.22§
0.22
0.31§
1.5
0.42
0.38
0.27§
0.26§
0.36
0.82
0
0.93
3
0
0
1.32
0.52
1.08
0.95
0
0.67
0
0.92
0.98
1.2
0.75
0.26
0.44§
0.39§
0.21§
0.92
0
0.54
0.49§
0.36§
0.33§
0.45
1.79
3.2
8.4
0
0
0.91
2.4
2.98
3.3§
6.0§
3.9§
0.8
6.4§
1.74§
2.5§
4.21§
3.5§
* JIA ⫽ juvenile idiopathic arthritis; RF ⫽ rheumatoid factor; ANA ⫽ antinuclear antibody. See Figure 1 for definitions of ethnic groups.
† Values are the relative risk versus the total at-risk population (the number of children ages ⬍18 years in each ethnic group as defined by Statistics
Canada.
‡ Values are the relative risk in European versus non-European ethnic groups.
§ P ⬍ 0.05 versus other ethnic groups or between groups.
ETHNICITY IN JIA
dren of European ancestry had an RR of 1.27 for
developing JIA-related uveitis (P ⫽ 0.036), whereas
children of non-European ancestry had an RR of 0.36
for developing JIA-related uveitis (P ⬍ 0.0001) (Table
4); thus, those of European origin as compared with
those of non-European origin had an increased risk of
developing JIA-related uveitis (RR 3.5). The presence
of uveitis was statistically significantly associated with
ANA positivity among patients of European descent (72
of 86 patients tested; P ⬍ 0.0001) but not among patients
of non-European descent (13 of 18 patients tested; P ⫽
0.10). Among all specific ethnic groups of children of
non-European descent, the majority of patients with
uveitis were ANA positive, but the number of patients
with uveitis was very small, and there was no statistically
significant association between the presence of uveitis
and ANA positivity.
Each of the individual risk factors of ANA status,
sex, JIA subtype, and age at diagnosis has been associated with the development of uveitis in patients of
different ethnicities (28). However, our Cox regression
analysis, which incorporated all of the available variables
(ANA status, sex, JIA subtype, age at diagnosis, and
ethnicity), demonstrated that the combined profile of
young-onset ANA-positive arthritis was the only risk
factor associated with a significant risk of developing
JIA-related uveitis, with an RR of 1.7 (P ⬍ 0.00009).
We also performed Kaplan-Meier survival analyses in the different ethnic groups and found that youngonset ANA-positive arthritis was a significant risk factor
for the development of JIA-related uveitis both in
patients of European origin (P ⬍ 0.0001) and in patients
of non-European origin (P ⫽ 0.0023). However, among
the non-European ethnic groups, young-onset ANApositive arthritis was a significant risk factor only in
children of black origin (P ⫽ 0.027) and in those of Latin
American origin (P ⫽ 0.034), and there was a tendency
toward an association in those of native North American
origin (P ⫽ 0.07). In contrast, young-onset ANA-positive
arthritis was not a significant risk factor in children of
Arab origin (P ⫽ 0.12), Asian origin (P ⫽ 0.39), or
Indian subcontinent origin (P ⫽ 0.7). Because of the
small numbers of patients, it was not possible to perform
Cox proportional hazards regression analysis of multiple
risk factors by ethnicity.
DISCUSSION
Most large epidemiologic studies in which the
prevalence of subtypes of JIA has been examined were
based on populations of patients who were mainly of
European ancestry. In contrast, smaller studies from
Hawaii (20), Asia (22,23,29), and Central America
1981
(21,30) showed that there may be ethnic differences in
the prevalence of JIA subtypes. The rheumatology clinic
at The Hospital for Sick Children in Toronto is a large
clinic that serves a multiethnic population of more than
4 million people whose access to health care is universal
and unrestricted, making it an ideal center at which to
study the potential influence of ethnicity. In this study,
we demonstrated that there is a difference in the prevalence of JIA and in the subtype distribution of JIA
based on ethnic background.
Results of previous studies have suggested that
oligoarticular JIA, RF-positive polyarticular JIA, and
ERA have different prevalence rates in different ethnic
groups (14,19,31). Our results demonstrated that children of European ancestry, as compared with children of
non-European ancestry, had an increased risk of developing all of the subtypes of JIA except RF-positive
polyarticular JIA and systemic JIA. Children of black or
Indian subcontinent origin were at a lower risk of
developing any of the JIA subtypes except RF-positive
polyarticular JIA, while children of Asian origin were
less likely than children of European ancestry to develop
any of the subtypes of JIA except ERA. Patients of
native North American origin tended to have an increased risk of developing polyarthritis, including RFpositive and RF-negative polyarticular JIA and extended
oligoarticular JIA, as compared with the children of
European descent.
It has been suggested in some studies, but not all
studies, that patients with JIA from the Indian subcontinent as well as those from Asia and Costa Rica have
lower rates of young-onset oligoarticular arthritis and
lower rates of uveitis as compared with European patients (13,21–23,31–33). Overall, we did not find any
differences in the percentage of patients with persistent
oligoarticular JIA between the European group of children and the non-European group of children, nor did
we find any differences in the percentage of patients
with oligoarthritis between those of Indian subcontinent
descent and either the total JIA cohort or the patients of
European descent. These results suggest that the apparent underrepresentation of patients with oligoarthritis
found in some studies from India may represent a
referral bias (31,32).
Consistent with previous findings, however, we
did observe that patients of native North American
origin, black origin, and Asian origin were less likely to
have oligoarticular JIA than were patients in other
ethnic groups (22,23,34,35). Our population of children
of Latin American origin, comprising 11 patients, was
too small to make meaningful comparisons with the
results in the study from Costa Rica (21,30). Overall,
1982
patients of European ancestry were more likely to
develop extended oligoarticular JIA than were patients
of non-European ancestry, with the lowest frequency of
extended disease seen in patients of Asian, Arab, or
Latin American descent.
Previous studies from Asia demonstrated that
patients with oligoarticular JRA were older at disease
onset and were less likely to be female than their
European counterparts, and that spondylarthropathy
was more frequent in Asian patients; however, ethnicityspecific prevalence or incidence rates of JRA were not
given (23). It is likely that such patients would have been
classified as having ERA in our study. If this assumption
is true, then our findings further confirm that patients of
non-European ancestry are more likely to have ERA
than are patients of European ancestry, and that this is
attributable to an overrepresentation of patients with
ERA among patients of Asian, Indian subcontinent, or
Arab ancestry. Although patients of Asian descent constituted a larger proportion of the total ERA population
than was predicted based on the percentage of Asians in
the total JIA cohort, these patients had the same risk of
developing ERA as did patients of European descent.
These findings are consistent with those reported in
studies from Singapore and Taiwan, in which it was
shown that the overall prevalence of JIA was lower in
Asian patients as compared with European patients, and
that ERA was the most common subtype (22,23).
It has previously been suggested that patients
with JRA who were of African American or native
North American descent were more likely to have
RF-positive polyarticular JRA (20% of African American patients and at least 50% of native North American
patients) than were patients of European origin (4%
with RF-positive polyarticular JRA) (9,14,24,34,36).
Consistent with those results, we found that 16% of
black patients and 20% of native North American
patients had RF-positive polyarticular JIA as compared
with 3% of the total JIA cohort and 2% of patients of
European descent. There was a trend toward an increased RR for the development of RF-positive polyarticular JIA in black children as compared with children
of European descent in the total cohort. There was also
a trend toward an increased RR in native North American children; however, our at-risk population may have
been too small to allow detection of the absolute increased risk reported in previous studies in larger populations of adult and pediatric native North American
patients (9,24,34,37).
In contrast to the results among patients with
RF-positive polyarticular JIA, we did not find any
statistically significant difference in the percentage of
SAURENMANN ET AL
European patients and percentage of non-European
patients with RF-negative polyarticular JIA, although
children/adolescents of European ancestry in the Toronto area had a higher risk of developing polyarticular
JIA than children of non-European ancestry. The only
exception was the native North American population,
whose RR for developing polyarticular RF-negative JIA
was the highest, at 3.2.
When we examined patients with extended oligoarticular JIA, we found that children of European
descent had a higher frequency of this JIA subtype than
did non-Europeans. Within the non-European group of
patients with JIA, those of black, Indian subcontinent, or
native North American origin had a frequency of extended oligoarticular JIA that was similar to that in
European patients. In addition, children of European
descent as compared with children of non-European
descent had a higher risk of developing this form of JIA.
Within the non-European group of children, those of
Asian, Arab, or Latin American origin had an exceptionally low risk of developing extended oligoarticular JIA.
Only native North American children had a risk of
developing this subtype that was comparable with that in
European children. To our knowledge, this is the first
study to examine whether the risk of extended arthritis
in patients with oligoarticular JIA differed according to
ethnicity.
There was a relative overrepresentation of Europeans as compared with non-Europeans among the
disease subtype of psoriatic JIA. This was true for
children in all non-European ethnic groups, except for
children of Asian descent, in whom the frequency of
psoriatic JIA was similar to that in European patients.
Of note, we did not find any cases of psoriatic arthritis
among the 38 patients of Indian subcontinent origin.
Previous studies in adults have shown that there is an
overall lower prevalence of psoriasis in India as compared with Europe and North America (38), but to our
knowledge, studies comparing the epidemiologic patterns of psoriatic arthritis among different ethnicities
have not been performed. Most studies of pediatric
patients have not differentiated psoriatic arthritis from
other forms of spondylarthropathy. Thus, our report
appears to be the first to comment on the prevalence of
juvenile psoriatic arthritis in different ethnicities.
Ravelli et al (27), in a study from Italy, suggested
that patients with early-onset (diagnosis before age 6
years) ANA-positive, RF-negative JIA constitute a distinct disease subset, irrespective of the ILAR classification. When we examined patients with young-onset
ANA-positive arthritis without regard to the number of
involved joints or the presence of psoriasis, we found
ETHNICITY IN JIA
that this group contained a significantly higher than
expected proportion of patients of European ancestry
compared with those of non-European ancestry, and
that the TMA pediatric population of patients of European ancestry had a higher RR of developing this
particular disease entity than did patients of nonEuropean ancestry. Within the non-European ethnic
groups of children, all groups had a decreased RR for
developing young-onset ANA-positive arthritis except
for children of native North American origin and children of Arab origin. These results suggest that a predisposing genetic factor is responsible for the development
of this combination of JIA characteristics in patients of
European ancestry. Further studies are required to
assess whether the involvement of the joints differs
among ethnicities in patients with young-onset ANApositive arthritis.
We found that the percentage of patients of
European ancestry who developed JIA-related uveitis
and the percentage of patients in this ethnic group who
were ANA positive were similar to the percentages of
patients of non-European ancestry who had these disease characteristics. These results appear to be in contrast to the findings in studies from India (17), Costa
Rica (21), South Africa (19), and Singapore (23). However, when we examined the RR values for developing
uveitis in the TMA general population, we found that
Europeans had a higher RR than did non-Europeans,
which is likely associated with the higher risk of developing JIA in those of European ancestry; nevertheless,
once JIA was established in either ethnic group, the risk
of developing uveitis was the same. These results are
consistent with the findings from Singapore and India,
but not with the findings from Costa Rica (17,21,23);
however, our number of Latin American patients was
smaller than that in the study from Costa Rica (21),
which may account for the discrepancy between studies.
Our results suggest that the risk factors for JIAassociated uveitis differ between ethnicities, and that the
commonly found risk factors, such as young age at onset
and ANA positivity, may not apply in patients of Asian,
Indian subcontinent, or Arab origin.
We are aware of the possible shortcomings of our
study, in particular the fact that the data on ethnicity
were self-reported. However, since the ethnicity assessment used by Statistics Canada for the 2001 census was
also self-reported and the same ethnic groups were used,
we believe that our results are valid. Furthermore, as we
have shown, our results are supported by a variety of
previous studies. Despite the large size of the JIA
cohort, our study was limited by the small number of
patients of non-European origin. Although most of our
1983
findings are supported by a number of other reports, our
study can, in many respects, only point out areas of
interest for further research.
In conclusion, our study was able to show, for the
first time, in a multiethnic community, that European
ancestry is an important predisposing factor for the development of JIA, but especially the disease subtypes of
extended oligoarticular JIA and psoriatic JIA. European
ancestry can also be a predisposing factor for a combination of JIA characteristics defined by young age at diagnosis and ANA positivity, and, in the presence of these
characteristics, the development of JIA-related uveitis.
Our study was further able to show that there
were significant differences in JIA subtype distribution
among the different ethnic groups, suggesting that predisposing genetic factors exist. We have shown that
despite these ethnic differences in the distribution of
JIA subtypes, children of European ancestry are at the
highest risk of developing all types of JIA except RFpositive polyarticular JIA. The only other exception, as
suggested by the findings of previous studies, may be
that native North American children are at a higher risk
than children of European descent of developing a
polyarticular course of disease, such as extended oligoarticular JIA, RF-negative polyarticular JIA, and RFpositive polyarticular JIA.
Finally, we were able to show that the known risk
factors for development of JIA-related uveitis may not be
sufficient to explain the development of uveitis in patients
of all ethnic backgrounds. Additional country-specific prevalence studies and other studies in large multiethnic populations are required to confirm our findings.
ACKNOWLEDGMENTS
Special thanks go to David N. Fisman, MD, MPH,
medical epidemiologist at The Hospital for Sick Children and
the University of Toronto, for reviewing the manuscript from
an epidemiologist’s perspective. This work would not have
been possible without the many hours of work and hundreds of
telephone calls performed by the rheumatology volunteers at
The Hospital for Sick Children. We particularly thank
Stephanie Silverman, Reto Saurenmann, and Max Silverman
for their support with the data collection.
AUTHOR CONTRIBUTIONS
Dr. Saurenmann had full access to all of the data in the study
and takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study design. Saurenmann, Feldman, Silverman.
Acquisition of data. Saurenmann, Rose, Tyrrell, Laxer, Schneider.
Analysis and interpretation of data. Saurenmann, Tyrrell, Feldman,
Laxer, Schneider, Silverman.
Manuscript preparation. Saurenmann, Feldman, Laxer, Schneider,
Silverman.
Statistical analysis. Saurenmann, Feldman.
1984
SAURENMANN ET AL
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