Of all patients with systemic lupus erythematosus (SLE), 15–20% are diagnosed during childhood (1), with disease onset prior to the age of 16 years. Previous studies using nonstandardized disease measures suggest that immunologic, serologic, and clinical abnormalities of children with SLE are more pronounced than those of adults. In recent years, disease indices have been developed that allow for a standardized comparison of pediatric and adult SLE cohorts (2–5). Using these standardized disease measures, reports from several large prospective cohorts of adults and some pediatric cohorts suggest that SLE in adults is less active and is associated with less permanent damage than is childhood-onset SLE (6–14).
Because disease expression in SLE is influenced by environmental factors and differs between racial and ethnic groups, it is important to use cohorts of adults and children with SLE from similar backgrounds (6, 7, 15–19). The objectives of our study were as follows: to compare adult-onset SLE patients and childhood-onset SLE patients who received followup care in the same academic center and had similar social and environmental backgrounds for differences in overall and renal disease activity, and to compare the 2 groups for differences in the type and amount of disease damage according to standardized disease indices.
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
The results of our study support the concept that SLE in children is more active and is associated with more rapid accrual of damage than is SLE in adults. In our study, the racial distribution in the pediatric group as compared with that in the adult group was similar, unlike in previous studies (14). Our patients were drawn from the same geographic area, using prospective longitudinal data with standardized disease measures, which decreases the reliability and validity of the comparisons made. A comparable racial distribution of childhood-onset SLE and adult-onset SLE patients living in the same geographic area has previously been reported from Brazil (12). Similar to the findings of previous studies, our study was inconclusive as to whether anticardiolipin antibody positivity is more common in childhood-onset SLE than in adult-onset SLE (12–14).
A higher frequency of renal disease and a concomitantly lower frequency of cardiopulmonary involvement have been reported in other studies that compared childhood-onset SLE and adult-onset SLE (12, 14). In our study, a higher percentage of pediatric patients had biopsy-proven renal disease, and there was a trend toward significantly more proliferative nephritis in this group. This increased frequency and severity of renal disease was associated with increased disease activity, which was primarily observed in the renal domain rather than in other organ systems, in pediatric patients, confirming previous observations that renal disease is more common and more severe in childhood-onset SLE than in adult-onset SLE. This also supports the findings of an earlier study from Thailand, which compared 51 children and 308 adults with SLE and showed that there was a higher percentage of patients with renal disease in the childhood-onset SLE group as compared with the adult-onset SLE group (80% versus 53%) (13). Despite the more frequent use of immunosuppressive agents, the renal AMS score was more than twice as high among the children as the adults with SLE. In addition, global disease activity was higher in patients with childhood-onset SLE as manifested by a higher AMS score. Significant differences in the activity of renal disease (AMSrenal score) and overall disease activity (AMS score) between adult-onset SLE and childhood-onset SLE were also noted among patients of similar racial groups (Caucasian and non-Caucasian). These results suggest that current medications and therapeutic regimens tested mostly in adults may not be sufficient to achieve comparable control of overall disease activity and renal disease activity in patients with childhood-onset SLE.
Our results suggest that, compared with adult SLE patients, children with childhood-onset SLE had more active disease at diagnosis and developed damage over time more rapidly. These findings support the notion that high levels of disease activity at diagnosis, whether in childhood or adult SLE, are a risk factor for poor outcome (11, 32, 35).
Although a number of items in the SDI may reflect aging (cataracts, myocardial infarction, diabetes mellitus, malignancy), patients with childhood-onset SLE still developed significantly more disease damage than did the adult patients. This is likely related to increased disease activity and higher levels of corticosteroids and immunosuppressive agents required for disease control in the children as compared with the adults. Of note, most of the difference in the accrual of damage between children and adults with SLE was due to steroid-related damage features. In other pediatric cohorts, such as the one studied by Ravelli et al (36), both the overall damage and the steroid-related damage were less than that in our childhood-onset SLE patients. However, that study was a retrospective analysis, and a higher percentage of the patients were Caucasians, who are known to have less active disease and to accrue less disease damage over time than non-Caucasian patients (9, 37). The mortality rate in our cohort of children was lower than that reported in earlier childhood-onset SLE cohorts and was lower than that seen in our adult cohort or in other reports of adults with SLE (12, 14, 38).
Reasons for greater disease activity and more damage in childhood-onset SLE remain to be elucidated. Hormonal changes observed during puberty might add to the imbalance of the immune system in children with SLE. We did not see any difference in damage scores between prepubertal and postpubertal children (data not shown); therefore, we cannot address this issue in our study.
Limitations of our study include the fact that it is unlikely all adult SLE patients who were diagnosed in the Greater Toronto area during 1990 through 1998 were captured in the study. Because the Lupus Clinic at the Toronto Western Hospital is a well-known primary, secondary, and tertiary center for patients with SLE, we likely missed some of the less severely affected adult SLE patients. Based on the Canadian health system, we are very confident that almost all pediatric patients were included in the study. Thus, the finding of the study that childhood-onset SLE is more aggressive than adult-onset SLE would probably have been even more pronounced if all adults with SLE had been included.
Another limitation is that premature gonadal failure might have been missed in some of the childhood-onset SLE patients. In the SDI, premature gonadal failure is defined by the presence of secondary amenorrhea for at least 6 months. However, many of the childhood-onset SLE patients had not yet had regular menses, making the reliable assessment of this SDI item difficult. However, none of the postpubertal female adolescents had any evidence of secondary amenorrhea.
Study information on all of the adult SLE patients was recorded in a prospective database, whereas study information on the childhood-onset SLE patients was extracted retrospectively from the medical charts. However, all pediatric patient visit information was based on the use of standardized clinic forms, which had been developed to accurately record all of the information required to determine both the SLEDAI and the SDI scores. In addition, all childhood-onset and adult-onset SLE patients had regular standard laboratory testing. Therefore, our data are equivalent to high-quality prospectively collected data.
In summary, this is the first prospective study comparing adults and children with SLE from the same ethnic and environmental backgrounds using standardized disease measures, allowing for a valid comparison of adult-onset SLE with childhood-onset SLE. Compared with adult SLE patients, children with SLE have more active disease at diagnosis and over time. They acquire renal disease at a higher frequency and develop damage more rapidly, but the mortality rates in our cohorts were similarly low. The exact mechanisms of the more aggressive SLE in children than in adults remain to be elucidated.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Dr. Brunner, Dr. Gladman, and Ms Ibañez had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study design. Brunner, Gladman, Urowitz, Silverman.
Acquisition of data. Brunner, Gladman, Urowitz, Silverman.
Analysis and interpretation of data. Brunner, Gladman, Ibañez, Urowitz, Silverman.
Manuscript preparation. Brunner, Gladman, Urowitz, Silverman.
Statistical analysis. Ibañez.