Abstract
Objective
To evaluate the influence of ethnicity on self-reported health related quality of life (HRQOL) in the Canadian childhood-onset systemic lupus Erythematosus (cSLE) population.
Methods
Patients with cSLE at 4 pediatric centers were consecutively enrolled. Sociodemographics and multiple disease activity measures were collected. The Child Health Questionnaire (CHQ) was administered and analysed by ethnicity.
Results
We enrolled 213 cSLE patients, and complete data from 196 patients with these ethnicities were analysed: White (33%), Asian (32%), South Asian (16%), Black (11%), Latino/Hispanic (5%), and Aboriginal (4%). Compared to healthy children, cSLE patients rated their HRQOL significantly more poorly in 9 of 10 individual domains, and in 4 of 10 domains when compared to a cohort of juvenile arthritis. Within the cSLE cohort, CHQ scores were lower in 5 of 10 domains in white patients versus nonwhite ethnicities (p<0.05 for each). Physical summary scores (PhS) were lower for white patients compared to the other ethnicities aggregated together (46.0 ± 11.9 vs. 50.4 ± 10.1, p = 0.009); however, psychosocial summary scores (PsS) were similar among the groups (40.5 ± 14.6 vs. 42.8 ± 12.7, p = 0.26). Disease activity measures, including Systemic Lupus Disease Activity Index, Systemic Lupus Activity Measure and physician global visual analogue scale were similar across ethnicities. However, patient reported Systemic Lupus Activity Questionnaire symptom scores were greater in patients of white ethnicity compared to those of Asian ethnicity (8.2 ± 5.8 vs. 4.5 ± 4.7, p=0.004).
Conclusion
The self- and parent-reported health status of Canadian cSLE patients differed across ethnicities, with white patients reporting lower HRQOL, despite similar and overall low disease activity.
Keywords: child, adolescent, pediatric, health status, spydergram, autoimmune disease, chronic illness, systemic lupus erythematosus, child health questionnaire
Introduction
Systemic Lupus Erythematosus (SLE) is diagnosed in childhood and adolescence in up to 20% of cases. A chronic multisystem autoimmune disease that frequently requires complicated treatment regimens, childhood-onset SLE (cSLE) affects educational success, social and emotional interactions, and participation in physical and other extracurricular activities during these important developmental periods. Health related quality of life (HRQOL) is a multi-dimensional construct that encompasses the physical and mental domains that can affect health, and should be examined in addition to disease activity and accumulated damage in evaluating the prognosis of SLE.1 Studies of patients with cSLE have demonstrated impaired HRQOL as compared to healthy children, and compared to children with juvenile arthritis, another chronic autoimmune disease.2–4
Ethnicity plays an important role in the expression of cSLE disease activity, disease expression and clinical phenotype, with nonwhite ethnicities generally accepted as having more severe disease with more rapid accrual of damage.5–9 However, it is not clear if HRQOL in SLE differs by ethnicity. The Lupus in Minority Populations, Nature versus Nurture (LUMINA) study of adult-onset SLE demonstrated better baseline mental health in Caucasians than African Americans and Hispanics, but no differences in the other HRQOL domains.10 Others have observed no influence of ethnicity on HRQOL,11 and instead suggest that factors such as depression are important determinants of HRQOL irrespective of ethnicity.12 In multinational studies of patients with cSLE HRQOL has been studied only in the context of tool validation and not compared across ethnicities.13
The 1000 Faces of Canadian Lupus is a nationwide prospective observational cohort of adult and cSLE that seeks to determine the influence of ethnicity and socioeconomic factors on disease characteristics and outcomes.14 We have previously reported that the clinical phenotype of cSLE differed by ethnicity in this cohort; in particular a greater proportion of patients of nonwhite ethnicity developed renal disease and other organ manifestations. However, the overall prevalence of neurologic disease (seizures and/or psychosis) was low, and did not differ among the ethnicity groups.15 In the current report our objective was to evaluate the influence of ethnicity on HRQOL in this cSLE cohort.
Methods
Study Design and Setting
This cross-sectional study enrolled incident and prevalent cases of cSLE at the four largest Canadian pediatric rheumatology centres at the time of the study, in Halifax, Montreal, Toronto and Vancouver. Eligible patients were consecutively recruited at routine clinic visits starting in November 2005. Patients completed a baseline visit and yearly follow-up visits; this report presents the HRQOL data from the baseline visit only. An interview with the patient and his or her parent was conducted, in addition to a physical examination and laboratory tests. Approval from local Research Ethics Boards were obtained at each participating site. Further details of the study methods are as previously described.14,15
Participants
All patients with a diagnosis of SLE prior to their 18th birthday and followed at one of the participating centers were eligible to enroll. The clinical diagnosis of cSLE was made by an experienced pediatric rheumatologist, and the majority of subjects (89%) fulfilled at least 4 of the American College of Rheumatology (ACR) classification criteria for SLE.16
Study variables
We collected detailed disease characteristics and sociodemographic data using a comprehensive standardized clinical record form.15 Self-selected ethnicity used the format and categories of Statistics Canada.17 For the current analysis, patients were categorized according to the primary self-selected ethnic category. Study investigators reviewed medical records at the baseline visit and clinical data were abstracted. Disease activity was measured using the SLE Disease Activity Index 2000 (SLEDAI-2K) and revised Systemic Lupus Activity Measure (SLAM-R).18,19 Parents completed the Systemic Lupus Activity Questionnaire (SLAQ), a self-assessment questionnaire containing 24 items in 9 organs/systems, rating disease activity (mild/moderate/severe/no problem) over the past 3 months for each symptom item. Additional items completed from the SLAQ included a global assessment (0–10), an assessment of fatigue (0–10), and an assessment of flare (none/mild/moderate/severe flare), each item evaluated for the past 3 months.20
The parent report Childhood Health Questionnaire (CHQ-PF50), a generic health status measure, was completed by parents. The CHQ is a pediatric adaptation of the Short Form 36 (SF-36), and is one of several measures frequently used to examine HRQOL. The CHQ is a profile measure of 50 questions that measures ten mental and physical domains, or subscales: physical functioning (PF), bodily pain (BP), general health perceptions (GH), role/social limitations – physical (RP), role/social limitations – emotional /behavioral (REB), parent impact – time (PT) and parent impact – emotions (PE), self-esteem (SE), mental health (MH), and general behavior (BE). Each subscale score ranges from 0 to 100, with higher scores representing better health status. Two summary scores, physical summary (PhS) and psychosocial summary (PsS) are calculated by aggregation of the subscales. Summary scores are standardized to a mean of 50 with a standard deviation of 10; higher scores reflect better health status.21 We used the available normative data for healthy children and children with juvenile arthritis as published by the developers of the CHQ. The healthy children sample includes 391 non-institutionalized children from the general United States (U.S.) population, ages 5 – 18, and predominantly of white ethnicity (83%). The sample of children with juvenile arthritis includes 74 U.S. children, predominantly female (82%), white ethnicity (94%) and with a mean age of 10 years.21
Statistical analyses
We summarized baseline characteristics using descriptive statistics with categorical data presented as percentages and continuous data presented as means, standard deviations and medians. Comparisons between subgroups used chi-square, Fisher’s exact test, or the nonparametric Wilcoxon test. We assessed for differences in CHQ domain and summary scores between the ethnicities using ANOVA with pairwise comparisons using a Bonferroni correction for multiple testing. Relationships between disease activity scores and CHQ scores were analysed using Pearson’s correlation coefficients. Correlations coefficients of 0.3 – 0.49, 0.5 – 0.69, and 0.7 – 1.0 indicated low, moderate, and high correlations, respectively. Spydergrams were created for presentation of the CHQ HRQOL data, as has been similarly done for the SF-36.22 For consistency, the order of domains proceeds clockwise with the four physical domains (PF, RP, GH, BP) followed by the six mental domains (PT, PE, REB, SE, MH, BE). Domain scores were plotted from 0 (worst) at the centre to 100 (best) at the outside. Statistical analyses were considered significant if p values were <0.05. Statistical analyses were performed using STATA 12 statistical software (College Station, TX).
Results
Participants
Between November 2005 and February 2009, 213 patients with cSLE were enrolled into the study cohort. The CHQ was not completed by 7 participants; therefore, data from 206 subjects were available for these analyses. The number of patients enrolled at each site was representative of the size of the clinical centre. At the Hospital for Sick Children in Toronto, 133 (65%) patients were enrolled, 48 (23%) from British Columbia (B.C.) Children’s Hospital in Vancouver, 18 (9%) from Montreal Children’s Hospital, and 7 (3%) from Halifax IWK Hospital. Demographic data were similar between the ethnicities, as described in Table 1 for the 196 patients analyzed who completed the CHQ and declared their ethnicity. Self-selected ethnicity data were available for 197 subjects; in addition to ethnicities shown in Table 1, one patient identified as Arab/Middle Eastern, and was not included in further analyses. We defined Asian as those from East and Southeast Asia primarily China, Korea, Taiwan, Philippines and Vietnam, and South Asian as those primarily from India, Pakistan, Sri Lanka and Bangladesh. As a contributing factor to HRQOL, we measured missed school days, which did not differ by ethnic group although 14% of the entire cohort reported missing school, on average, at least one day per week due to their SLE. More detailed disease characteristics of the cohort have been previously described.15
Table 1.
Demographics and disease activity measures by ethnicity
| Total* (N=196) |
Aboriginal (n=8) |
Asian (n=62) |
South Asian (n=31) |
Latino/Hispanic (n=9) |
Black (n=22) |
White (n=64) |
P- value |
||
|---|---|---|---|---|---|---|---|---|---|
| Age (years) (mean ± SD) | 14.9 ± 3.0 | 16.6 ± 1.5 | 15.2 ± 2.9 | 14.6 ± 3.6 | 13.2 ± 4.0 | 15.1 ± 2.8 | 14.7 ± 2.7 | 0.22 | |
| Disease Duration (years) | 2.3 ± 2.5 | 4.3 ± 4.6 | 2.7 ± 2.4 | 2.1 ± 2.4 | 2.6 ± 3.6 | 2.7 ± 2.5 | 1.7 ± 2.1 | 0.06 | |
| SLEDAI-2K score | 3.1 ± 4.1 | 3.8 ± 4.2 | 3.6 ± 5.1 | 2.1 ± 1.9 | 3.0 ± 2.5 | 3.6 ± 5.0 | 2.9 ± 3.7 | 0.62 | |
| SLAM-R score | 3.4 ± 3.6 | 4.5 ± 3.9 | 3.0 ± 2.9 | 2.8 ± 2.2 | 4.1 ± 2.7 | 4.7 ± 5.8 | 3.5 ± 4.0 | 0.37 | |
| SLAQ symptom score | 6.4 ± 5.8 | 7.5 ± 5.9 | 4.5 ± 4.7 | 5.8 ± 5.7 | 10 ± 5.7 | 5.6 ± 6.9 | 8.2 ± 5.8 | 0.003* | |
|
Physician global (VAS) (0 – 100) |
(N=184) 15.2 ± 22.6 |
(n=7) 11.4 ± 16.5 |
(n=59) 14.9 ± 23.9 |
14.7 ± 25.2 |
10.7 ± 9.3 |
(n=20) 13.1 ± 17.7 |
(n=58) 17.5 ± 23.8 |
0.93 |
|
|
Parent Global Assessment (0 – 10) |
(N=191) 3.0 ± 3.0 |
4.3 ± 3.5 |
2.2 ± 2.5 |
2.6 ± 3.0 |
4.8 ± 3.8 |
(n=21) 3.0 ± 3.6 |
(n=60) 3.5 ± 3.1 |
0.06 |
|
|
Fatigue Assessment (0 – 10) |
(n=194) 3.5 ± 3.4 |
3.3 ± 2.4 |
2.6 ± 3.3 |
3.9 ± 3.6 |
6.2 ± 2.6 |
(n=21) 2.7 ± 3.1 |
(n=63) 4.0 ± 3.4 |
0.02* |
|
| Missed School Days (#, %) | (N=187) | (n=8) | (n=61) | (n=27) | (n=8) | (n=61) | |||
| ≥1 day per week | 26 (14) | 3 (38) | 4 (7) | 3 (11) | 2 (25) | 1 (5) | 13 (21) | 0.19 | |
| Twice a month | 12 (6) | 1 (13) | 3 (5) | 0 | 1 (13) | 0 | 7 (11) | ||
| Once a month | 36 (19) | 0 | 11 (18) | 6 (22) | 1 (13) | 6 (27) | 12 (20) | ||
| <1 day per month | 101 (54) | 4 (50) | 40 (66) | 16 (59) | 4 (50) | 13 (59) | 28 (46) | ||
| other | 8 (4) | 0 | 3 (5) | 2 (7) | 0 | 2 (9) | 1 (2) | ||
| Household Income (#, %) | (N=172) | (n=7) | (n=52) | (n=28) | (n=7) | (n=18) | (n=60) | 0.06 | |
| <$15 000 | 11 (6) | 0 | 5 (10) | 2 (7) | 1 (14) | 2 (11) | 1 (2) | ||
| $15 000 – $29 999 | 13 (8) | 0 | 6 (12) | 3 (11) | 2 (29) | 1 (6) | 1 (2) | ||
| $30 000 – $49 999 | 34 (20) | 0 | 13 (25) | 5 (18) | 1 (14) | 6 (33) | 9 (15) | ||
| >$50 000 | 114 (66) | 7 (100) | 28 (54) | 18 (65) | 3 (43) | 9 (50) | 49 (82) | ||
p-values are from ANOVA. Subsequent pairwise testing with Bonferroni correction for multiple testing: For SLAQ Symptom score the comparison of Asian versus White groups was significant, and for the Fatigue Assessment only the comparison of Asian versus Hispanic groups was significant.
SLEDAI-2K = systemic lupus erythematosus disease activity index 2000; SLAM-R = systemic lupus erythematosus activity measure, revised; SLAQ = systemic lupus assessment questionnaire; VAS = visual analog scale
Health Related Quality of Life (HRQOL) in cSLE
Figure 1 depicts the differences in CHQ subscale scores of the total cSLE cohort compared to healthy children and to children with juvenile arthritis. Compared to the healthy children cohort, cSLE patients rated their HRQOL significantly more poorly for 9 of the 10 domains, with the 10th domain (the mental domain general behavior, BE) rated higher by the cSLE patients compared to a healthy children cohort (78.9 versus 75.6, p=0.02). Compared to the juvenile arthritis cohort, the cSLE cohort reported lower scores for the physical subscale of general health perceptions (GH; mean score 50.7 versus 59.5, p<.001), and mental subscales parent impact – time (PT; 78.9 versus 86.5, p=0.03), parent impact – emotion (PE; 59.3 versus 72.0, p=0.001) and role/social limitations – emotional/behavioral (REB, 83.8 versus 92, p=0.02). Conversely, the cSLE cohort reported higher scores than the juvenile arthritis cohort for the physical subscale reflecting bodily pain (BP; 73.0 versus 62.7, p=0.003). For the summary scores, the mean psychosocial summary score (PsS) was lower for the cSLE cohort compared to both the juvenile arthritis cohort (49.1 versus 53.4, p=0.003) and to healthy children (49.1 versus 51.2, p=0.01). Although the mean physical summary Score (PhS) was nearly identical for the SLE and juvenile arthritis cohorts (42.1 versus 42.3, p=0.9), the cSLE cohort scored significantly lower than healthy children (42.1 versus 53.0, p<.001).
Figure 1. Child Health Questionnaire Domain Scores in Children and Adolescents.
Domain scores for each cohort are plotted, from 0 (poorest) at the center to 100 (best) at the outside of the spydergram, with domains scores connected to form a 2 dimensional shape. Overall, the figure demonstrates that cSLE patients scored more poorly than the healthy children and children with juvenile arthritis in almost all domains. Significant differences between the cSLE and juvenile arthritis cohorts are noted by *(p<0.05) and ** (p<0.001). Significant differences between the cSLE cohort and healthy children are noted by # (p<0.05) and ## (p<0.001).
cSLE = childhood-onset Systemic Lupus Erythematosus; PF = physical functioning; RP = role/social limitations – physical; GH= general health perceptions; BP = bodily pain; PT = parent impact – time; PE = parent impact – emotions; REB = role/social limitations – emotional/behavioral; SE = self esteem; MH = mental health; BE = general behavior.
HRQOL by ethnicity
Using ANOVA, we compared CHQ domain scores by ethnicity and observed differences in bodily pain, and in three mental domains (self-esteem, mental health and general behavior). Following omnibus testing, pairwise testing with bonferroni corrections demonstrated lower scores for the white ethnic group compared to the Asian and South Asian groups in the domains of bodily pain and self-esteem, respectively. Further, there was an overall difference in psychosocial summary scores across ethnicities; however, post hoc pairwise testing did not demonstrate differences among specific ethnicity groups, likely due to unbalanced and small sample sizes in the individual ethnicity groups (Table 2). When the five nonwhite ethnic groups were aggregated together, HRQOL ratings were lower for the white ethnic group than the nonwhite ethnicities for 5 of 10 individual domains (general health perceptions, bodily pain, role/social limitations – emotional/behavior, self-esteem, and mental health) (Figure 2). Physical summary scores were lower for white patients compared to the other ethnicities aggregated together (46.0 ± 11.9 versus 50.4 ± 10.1, p = 0.009), however, psychosocial summary scores were similar among the groups (40.5 ± 14.6 versus 42.8 ± 12.7, p = 0.26).
Table 2.
Child Health Questionnaire subscales by ethnicity
| Total (N=196) |
Aboriginal (N=8) |
Asian (N=62) |
South Asian (N=31) |
Black (N=22) |
Latino/Hispanic (N=9) |
White (N=64) |
p-value | |
|---|---|---|---|---|---|---|---|---|
| PF | 81.1 ± 24.1 | 84.7 ± 24.6 | 85.3 ± 21.3 | 78.1 ± 26.2 | 77.8 ± 30.2 | 69.8 ± 28.2 | 80.6 ± 22.8 | 0.42 |
| RP | 82.0 ± 29.7 | 72.9 ± 37.7 | 86.0 ± 24.0 | 81.2 ± 31.0 | 92.9 ± 22.7 | 74.1 ± 32.4 | 77.2 ± 33.9 | 0.22 |
| GH | 50.3 ± 17.7 | 52.9 ± 25.0 | 50.7 ± 14.3 | 51.2 ± 19.4 | 58.9 ± 22.3 | 52.0 ± 15.0 | 45.8 ± 16.8 | 0.09 |
| BP | 72.8 ± 25.0 | 55.0 ± 30.2 | 81.5 ± 22.7 | 75.8 ± 22.5 | 76.4 ± 23.8 | 66.7 ± 16.6 | 64.8 ± 26.0 | 0.001* |
| PT | 78.5 ± 28.6 | 87.3 ± 25.2 | 78.3 ± 28.4 | 81.7 ± 28.3 | 76.8 ± 34.4 | 72.8 ± 28.4 | 77.4 ± 27.7 | 0.91 |
| PE | 58.5 ± 31.3 | 69.0 ± 20.2 | 62.4 ± 33.5 | 62.1 ± 25.0 | 55.3 ± 41.4 | 42.6 ± 29.6 | 55.0 ± 28.7 | 0.36 |
| REB | 83.6 ± 27.4 | 83.3 ± 25.2 | 86.4 ± 25.8 | 88.5 ± 21.6 | 93.1 ± 22.6 | 65.4 ± 35.8 | 77.8 ± 30.2 | 0.05 |
| SE | 75.4 ± 21.1 | 80.0 ± 15.1 | 77.8 ± 20.2 | 82.9 ± 21.4 | 80.3 ± 19.3 | 75.0 ± 13.8 | 67.0 ± 22.0 | 0.006^ |
| MH | 75.5 ± 16.8 | 83.1 ± 11.3 | 77.5 ± 15.7 | 79.4 ± 18.0 | 79.1 ± 13.4 | 70.6 ± 19.3 | 70.1 ± 17.4 | 0.03 |
| BE | 78.6 ± 17.2 | 88.6 ± 10.4 | 79.1 ± 16.6 | 84.0 ± 14.8 | 80.0 ± 15.9 | 66.9 ± 26.9 | 75.5 ± 17.3 | 0.03 |
| PsS | 49.0 ± 10.9 | 54.9 ± 6.0 | 49.9 ± 10.2 | 52.7 ± 9.4 | 50.2 ± 10.8 | 43.3 ± 10.1 | 46.0 ± 12.0 | 0.02 |
| PhS | 42.1 ± 13.4 | 37.8 ± 13.2 | 44.7 ± 11.1 | 40.7 ± 14.6 | 44.3 ± 13.2 | 38.0 ± 14.2 | 40.5 ± 14.6 | 0.34 |
pairwise comparisons demonstrate p <0.05 for White versus Asian ethnic groups;
pairwise comparisons demonstrate p<0.05 for White versus South Asian ethnic groups
PF = physical functioning; RP = role/social limitations – physical; GH= general health perceptions; BP = bodily pain; PT = parent impact – time; PE = parent impact – emotions; REB = role/social limitations – emotional/behavioral; SE = self esteem; MH = mental health; BE = general behavior; PsS = psychosocial summary score; PhS = physical summary score
Figure 2. Child Health Questionnaire Domain Scores in cSLE: White versus Non-White Ethnicities.
Domain scores are plotted for the patients of white ethnicity, and for all non-white ethnicity patients aggregated together as one group. Significant differences between the White and Non-white ethnicity domain scores are indicated by * p<0.05 and **p<0.01 for each comparison
PF = physical functioning; RP = role/social limitations – physical; GH= general health perceptions; BP = bodily pain; PT = parent impact – time; PE = parent impact – emotions; REB = role/social limitations – emotional/behavioral; SE = self esteem; MH = mental health; BE = general behavior; PsS = psychosocial summary score; PhS = physical summary score
Disease Activity and HRQOL
Overall disease activity measured by SLEDAI-2K and SLAM-R were low in this cohort, with mean scores of 3.1 and 3.4, respectively. As previously described, these disease activity scores did not differ significantly by ethnicity15 and, therefore, we did not examine correlations with HRQOL and disease activity by ethnic group. However, SLAQ symptom scores, or parent-rated disease activity did differ overall by ethnicity (p=0.003), with subsequent pairwise testing demonstrating higher SLAQ symptom scores in white patients compared to Asians (8.2 versus 4.5, p=0.004). We found moderate to strong correlations between SLAQ symptom scores and all CHQ domain scores, and several weak to moderate negative correlations between physician-rated disease activity score (SLEDAI-2K and SLAM-R) and CHQ domain scores across both physical and mental domains (Table 3).
Table 3.
Correlations between Disease Activity and Health Related Quality of Life
| Domain | SLEDAI-2K (N=196) |
SLAM-R (N=195) |
SLAQ Symptom Score (N=196) |
|---|---|---|---|
| Physical Functioning (PF) | −0.146* | −0.292** | −0.518** |
| Role/Social Limitations – Physical (RP) | −0.183* | −0.297** | −0.502** |
| General Health Perceptions (GH) | −0.199* | −0.268** | −0.413** |
| Bodily Pain (BP) | −0.226* | −0.389** | −0.679** |
| Parent Impact – Time (PT) | −0.148* | −0.262** | −0.434** |
| Parent Impact – Emotions (PE) | −0.166* | −0.290** | −0.476** |
| Role/Social Limitations – Emotional/Behavioral (REB) | −0.220* | −0.324** | −0.471** |
| Self-Esteem (SE) | −0.209* | −0.326** | −0.494** |
| Mental Health (MH) | −0.131 | −0.203* | −0.503** |
| General Behavior (BE) | −0.014 | −0.075 | −0.260** |
| Psychosocial Summary (PsS) | −0.177* | −0.288** | −0.535** |
| Physical Summary (PhS) | −0.213* | −0.378** | −0.644** |
Pearson correlations between the disease activity scores and the individual domains of the Child Health Questionnaire are shown.
p<0.05;
p<0.001
Disease Severity and HRQOL
As HRQOL may differ not only by disease activity but by overall severity of disease manifestations, we further examined CHQ domain and summary scores among patients with and without renal disease and observed a significant difference only in the bodily pain domain which was higher in patients who (ever) had renal disease (BP; 70.0 ± 2.3 versus 77.6 ± 2.7, p=0.04). Examining the cohort by neurologic disease (defined by SLE classification criteria as a history of seizures and/or psychosis), the 26 patients with neurologic disease had significantly poorer HRQOL as measured in 8 of 10 CHQ domains and in both physical and psychosocial summary scores (data not shown). Of note, these few patients with neurologic disease were proportionally distributed among the ethnicity groups.
Discussion
The 1000 Faces of Canadian Lupus project has documented the variable phenotype of SLE in Canada, across a multi-ethnic population of both children and adults. The current analysis demonstrated that the HRQOL of the cSLE cohort is poorer than that of healthy children, and of children with juvenile arthritis. Greater differences were noted on the physical scales than the psychosocial scales. Although we have demonstrated that HRQOL varied by ethnicity, importantly, the differences in HRQOL found between whites and nonwhites were independent of the observed differences in severity of organ involvement between these groups. Patients with renal disease did not report significantly different HRQOL than those without, although the small number of patients with severe neurologic symptoms who were proportionally distributed among the different ethnicity groups did report poorer HRQOL.
Prior studies in cSLE have demonstrated associations between higher disease activity and damage and significantly lower HRQOL or physical function.2–4,23 Studies of adults with SLE have also demonstrated that SLE leads to reduced HRQOL in all domains,24,25 with poorer HRQOL associated with greater disease activity and damage. However, the recent PATROL study demonstrated instead that depression, rather than disease activity or other sociodemographic factors, was the most significant predictor of HRQOL in this cohort of Hispanic and Caucasian patients with SLE.12 In the current study, we observed significant correlations between disease activity and HRQOL domains although correlations between parent-reported disease activity and HRQOL were stronger than those between physician-rated disease activity and (parent-reported) HRQOL. This would suggest that patients (and parents) evaluated their disease activity based on their physical and psychological sense of well-being, in contrast to the more objective measures used by the physician.
A multinational study that included patients from the United States, Italy, Mexico, Greece and Japan reported a trend towards poorer HRQOL scores by patients from Mexico than from other countries. The PhS and PsS scores of the overall cohort were lower than those observed in the current study (40.2 and 44.8, respectively); however, analyses by ethnicity were not done.4 Similar to the current study, overall PhS and PsS scores correlated with SLEDAI score,4 although patients in the current study had lower overall disease activity (mean SLEDAI score of 3.1 versus 7.2), so the lower CHQ scores may be explained by greater disease activity. An earlier small Canadian cSLE cohort (15 patients) found that disruption of family functioning was the only abnormally low CHQ domain.26 Again there were no analyses of scores by ethnicity.
Since SLE can affect all four domains of HRQOL – global health, physical health, psychosocial health and parents/family life, our results are not unexpected. Patients with SLE experience many physical symptoms including fatigue, headaches, joint pain and fevers and may require multiple medications. Add to this multiple appointments, missed school days, limited sun exposure and significant cosmetic side effects from medications including weight gain, Cushingoid facies, hair loss, and striae, and there is significant disruption of “normal adolescence”. Considering all of these issues, we might be surprised that the physical summary scores were lower than the psychosocial scores; however, by using the parent proxy measure, we may have omitted the child/adolescent’s subjective responses. The parents’ personal expectations and experiences may not reflect the totality of the child/adolescent’s psychosocial experience (e.g. self-esteem) of this chronic disease. Nevertheless, we did observe the largest differences between healthy children and SLE in the parent impact-emotional domain, evidence that having a child with SLE is a tremendous emotional strain for parents.
We found that the major difference across ethnicities in HRQOL were lower subscale scores in white patients as compared to other ethnic groups, despite similar socioeconomic status and disease activity scores. The most affected domains were bodily pain, self-esteem, mental health and the aggregated psychosocial summary score. Our recent cluster analysis of this same cohort suggested that white patients have a milder disease phenotype than Asians and Blacks;15 however, the current study demonstrating poorer HRQOL ratings suggests that patients may be influenced by their environment (family, friends, cultural environment) leading to different perceptions and intrusiveness of their disease manifestations. Our findings are similar to the findings of the adult LUMINA study,27 which noted that although African-Americans and Hispanics (from Texas) had lower socioeconomic status than whites, the whites demonstrated lower ratings on multiple HRQOL subscales and on the physical functioning summary score. As we were not able to measure how patient and parental expectations of disease intrusiveness and disease burden may differ by cultural, ethnic and other environmental influences, we believe this association between ethnicity and perception of HRQOL deserves further study.
We recognize the limitations of our study methods and interpretation. We were unable to collect and analyze for differences in HRQOL by ethnicity at disease presentation, and track these potential differences through the disease course as this was a cross-sectional study design that recruited both incident and prevalent cases. We chose to use the primary ethnicity designation by the parent, and we were unable to take into account mixed parental heritage and heterogeneous background due to limitations in the cohort size. Additionally, we recognize that measurements of patient HRQOL in this study may have reflected parental HRQOL as younger patients were unable to complete these measures on their own. Moreover, the healthy children and juvenile arthritis normative samples were historical, from geographically different sites, and not matched for age, sex or ethnicity. The healthy children cohort included 66 non-Caucasian children (combining African-American, Hispanic and Asian), and this group demonstrated lower scores than the Caucasians (324 healthy children) on all domains except self-esteem, although the differences were not examined for statistical significance.21 Because this cohort was small, based on parental ethnicity, and did not specify the breakdown of the multiple ethnicities, we did not compare to these “normative” non-Caucasian data in the current analyses.
In conclusion, we observed lower HRQOL ratings in patients with cSLE compared to patients with juvenile arthritis and to healthy children across both physical and psychosocial domains. Disease activity as observed by the physician and reported by the patient/parent, correlated with almost all domains of the CHQ. Physician-rated disease activity was similar across ethnicities, however parent-reported disease activity differed. Despite similar physician-rated disease activity, patient-reported HRQOL was lower in white patients. In the future, a greater understanding of how ethnic, cultural and environmental influences affect patient disease expectations and HRQOL may improve our ability to provide culturally sensitive and individualized patient-centered care for our cSLE patients.
Significance and Innovation.
This study of health related quality of life reports on one of the largest multicenter, nationally acquired and ethnically diverse cohorts of patients with childhood-onset systemic lupus erythematosus (cSLE).
Children and adolescents with SLE endorsed poorer health related quality of life in multiple domains compared to healthy children and children with juvenile arthritis, confirming prior reports of studies from North America and Europe.
Despite similar socioeconomic status and overall low physician-rated disease activity, cSLE patients self-identified as white ethnicity reported poorer health related quality of life than patients of nonwhite ethnicity, suggesting an association between ethnicity and perception of the intrusiveness of disease manifestations.
Acknowledgement
The CaNIOS 1000 Faces Investigators, coordinators and research assistants, in addition to the authors are as follows:
BC Children’s Hospital: Ross Petty, MD, PhD, David Cabral, MB BS, Kristin Houghton, MD, MSc, Kimberly Morishita, MD, MHSc
Montreal Children’s Hospital: Sarah Campillo, MD, Karen Duffy, MD, and Rosie Scuccimarri, MD
IWK Health Centre: Bianca Lang, MD, Suzanne Ramsey, MD, and Aleasha Warner
Hospital for Sick Children: Lawrence Ng, BSc
Toronto Western Hospital, University Health Network: Paul Fortin, MD, PhD, Murray Urowitz, MD, Dafna Gladman, MD, Lori Albert, MD, Simon Carette, MPhil, MD, Rob Inman, MD, and Tamara McKenzie
Montreal General Hospital: Ann Clarke, MD, MSc, Christian Pineau, MD, Sasha Bernatsky, MD, PhD, Michele Tobaly and Tania Santopietro
Ottawa General Hospital: C. Douglas Smith, MD, Sherri Simpson and Katrin Smith
Hopital Maisonneuve-Rosemont: Michel Zummer, MD and Diane Ferland
Lethbridge Regional Health Centre: Hector Arbillaga, MD and Annella Wehlage
Jewish General Hospital: Marie Hudson, MD, Murray Baron, MD, and Laeora Berkson, MD and Jessica Bernstein
Halifax Queen Elizabeth II: John Hanly, MD
St. Joseph’s Health Sciences Centre: Sara Hewitt and Janine Ouimet
Health Sciences Centre, University of Manitoba: Carol Hitchon, MD, MSc, Andrea Craig (1000 Faces National Coordinator) and Mellissa Moyen
Financial Support: Supported by The Arthritis Society National Office (grant TAS04/0049). The Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus is supported in part by Lupus Canada, Lupus Ontario, BC Lupus, and the Arthritis and Autoimmune Research Centre Foundation. Dr. Levy’s work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Sin Diseases (grant K23-AR-053202).
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