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We investigated nationwide prevalence, incidence, and sociodemographics of SLE and lupus nephritis among Medicaid-enrolled children.
Children aged 3 to <18 years with SLE (≥3 International Classification of Diseases, 9th Revision, codes of 710.0, all >30 days apart) were identified from Medicaid Analytic eXtract data (2000–2004), containing all inpatient and outpatient Medicaid claims for 47 U. S states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes >30 days apart for glomerulonephritis, proteinuria or renal failure. We calculated prevalence and incidence of SLE and lupus nephritis among Medicaid-enrolled children overall and within sociodemographic groups.
Of 30,420,597 Medicaid-enrolled children during these years, 2,959 with SLE were identified. SLE prevalence was 9.73 (95% CI 9.38 – 10.08) per 100,000. Of these, 84% were female, 40% African-American, 25% Hispanic and 21% White; 42% resided in the South. 1,106 (37%) of children with SLE had lupus nephritis: prevalence 3.64 (95% CI 3.43 – 3.86) per 100,000. The average annual incidence of SLE was 2.22 (95% CI 2.05–2.40) and that of lupus nephritis was 0.72 (95%CI 0.63– 0.83) cases per 100,000 Medicaid enrollees per year. Prevalence and incidence rates of lupus and lupus nephritis increased with age, were higher in girls than boys, and in all non-White than White racial/ethnic groups.
SLE prevalence and incidence rates among Medicaid-enrolled children in the U.S. are high compared to studies in other populations. These represent the first population-based estimates of lupus nephritis prevalence and incidence in the U.S. to date.
Systemic lupus erythematosus (SLE) presents throughout the age spectrum and one of its most severe manifestations, lupus nephritis, may have devastating consequences at any age(1–6). SLE presenting in childhood accounts for 15 to 20% of all cases and nephritis affects 20 to 75% of pediatric SLE patients(7–9).
Children are among the poorest and most vulnerable populations in the American healthcare system, facing some of the highest barriers to obtaining appropriate healthcare(10, 11). Comparisons of relatively small pediatric and adult cohorts of SLE patients have shown that children and adolescents have more active lupus, in particular lupus nephritis, at presentation and over time than adults(2, 12). Compared to adults with lupus, children receive more intensive drug therapy and accrue more end-organ damage, often related to steroid toxicity(2). In the LUpus in MInorities: NAture vs. nurture (LUMINA) multiethnic cohort, young age was an important independent predictor of new or worsening proteinuria on routine screening, and adolescent onset of SLE resulted in more aggressive disease and worse outcomes(12, 13). The high morbidity and mortality observed from lupus nephritis in past studies of SLE in children may be due to delays in diagnosis and treatment(1, 3, 4).
To date, only a small number of studies have examined the prevalence or incidence of SLE among children. Reported SLE prevalence rates among North American children have ranged from 3.3 to 24.0 per 100,000(6, 14–17). The incidence of new SLE presenting in children has been studied very infrequently, and reported as 0.28 and 0.48 per 100,000 children per year in the two past studies we identified(6, 14–17). Prevalence and incidence rates of lupus nephritis among children have not been determined for large populations of children nationwide.
Medicaid is a federal-state entitlement program for low-income children and parents, the aged or disabled poor. Little is known about the prevalence, incidence, or sociodemographic characteristics of SLE or lupus nephritis among children on Medicaid. We aimed to determine recent prevalence and incidence rates for SLE and lupus nephritis among US children receiving Medicaid health insurance. Determining the recent nationwide prevalence rates is an important first step to understanding public health impact, and how poverty and healthcare access may influence outcomes for children with SLE. We also aimed to compare incidence rates among girls and boys, according to age and racial/ethnic groups. Having a better understanding of the sex ratio in pediatric SLE presenting at different ages could provide insight into the underlying biology.
The Medicaid Analytic eXtract (MAX) data system contains demographic information and all billing claims for Medicaid enrollees from 47 states and the District of Columbia. (Arizona, Tennessee and Maine do not provide state-wide data and were thus excluded from these analyses.) Within MAX data for January 1, 2000 to December 31, 2004, we identified all individuals between 3 and < 18 years of age with SLE, defined as having ≥3 International Classification of Diseases, Ninth revision (ICD-9) codes for SLE (710.0), each at least 30 days apart, from hospital discharge or physician visit claims. From among the SLE cases, we then identified those with lupus nephritis, defined as having two or more physician and/or inpatient claims for nephritis, proteinuria and/or renal failure occurring on or after the SLE billing diagnoses and each at least 30 days apart (ICD-9 codes 580 to 588; 791.0; 630 to 640). We have previously demonstrated that this algorithm has a positive predictive value of 80% for the identification of lupus nephritis among adults in a Medicaid population(18).
From MAX administrative data, in addition to physician and hospital claims, we obtained the following demographic data for all Medicaid enrollees between ages 3 and 18 years: date of birth, sex, race (White, Black, Hispanic or Latino, Asian, Native Hawaiian or other Pacific Islander, American Indian or Alaskan Native, other or more than one race) and zip code of residence. Utilizing the age at the time of the first SLE or lupus nephritis claim, we categorized age in four categories (3 –<6 years, 6 – <9 years, 9 – <12 years, 12 – <15 years, 15 – <18 years), re-categorized racial/ethnic group in five categories (White, African American, Asian, Hispanic, Native American, and other), and categorized US region of residence based on zip code as Northeast, South, Midwest, and West.
Prevalence rates with 95% confidence intervals (CIs) for SLE and lupus nephritis per 100,000 Medicaid eligible children were calculated from all identified cases and all Medicaid enrollees between ages 3 and18 years in MAX between 2000 and 2004. Prevalence rates were calculated for the total cohort and stratified by sex, race, US region, age category, and by cross-classified sex and age category and sex and racial/ethnic group category.
The annual incidence rates (and 95% CIs) for SLE and lupus nephritis were calculated by identifying cases of newly diagnosed SLE and lupus nephritis, meeting the definitions above, with at least 24 months of Medicaid enrollment without any SLE (or lupus nephritis) claims. The time of SLE onset was defined as the date of the first SLE or lupus nephritis claim. Subjects contributed to the person-months denominator once they had 24 months of Medicaid enrollment and were censored at the time of their first SLE or lupus nephritis claim. Average annual incidence rates (per 12 months of enrollment) for these three years were calculated for the total cohort and stratified by sex, racial/ethnic group, US region, age category, and by sex and age category. Prevalence and incidence rate ratios with 95% CIs were calculated using Poisson techniques to demonstrate differences in incidence rates among different sociodemographic groups.
As Medicaid medical coverage was discontinuous for many children during the period of analyses, we conducted a sensitivity analysis for incidence rates by restricting the analysis to those with at least 24 months of continuous Medicaid enrolment without any SLE or lupus nephritis claims. All analyses were conducted in SAS, version 9.2 (Cary, NC). Data were obtained from the Center for Medicare and Medicaid Services (CMS) through an approved data use agreement. Our institution, Partners Healthcare, waived human subjects institutional review board approval for this study.
Of 30,420,597 children covered by Medicaid from 2000–2004, 2,959 with SLE were identified. Overall SLE prevalence was 9.73 (95% CI 9.38 – 10.08) per 100,000. Of those 2,959 children with SLE, 83.8% were female, 39.6% African American, 25.4% Hispanic and 20.6% White; 41.9% resided in the South and 23.0% in the West. The calculated prevalence rates for SLE overall and in specific demographic groups of children are shown in Table 1. The prevalence of SLE was more than 5 times higher among girls than boys. Prevalence rates were highest among girls aged 15–<18 (18.92, 95% CI 17.95 – 19.94). Prevalence of SLE among Asian children (23.79 per 100,000) exceeded that in other racial and ethnic groups, and was higher among African-Americans (14.08), Hispanics (11.51) and Native Americans (13.38), than among Whites (4.86). The SLE prevalence rates were lowest in the Midwest (8.03) compared to other regions of the country.
Prevalence rates for lupus nephritis (Table 1) showed similar sociodemographic variation. Among the 2,959 children with SLE, 1,106 (37%) were identified as having lupus nephritis. Overall, the prevalence of lupus nephritis was 3.64 cases per 100,000 children. It was 4.46 times higher among girls than boys, highest among girls ages 15– < 18, and highest among Asians, African-Americans, Hispanics and Native Americans. Again, prevalence rates for lupus nephritis were slightly lower in the Midwest than in other regions of the country. Figure 1 displays prevalence rate ratios for girls and boys for SLE and lupus nephritis in each racial/ethnic group compared to Whites (referent group=1.0). The prevalence rate ratios were highest for lupus nephritis among Asian girls and Asian and Native American boys (compared to White children of the same sex).
The average incidence rates of SLE and lupus nephritis per 100,000 Medicaid-enrolled children per year in the US, from 2002–2004 are displayed in Table 2. Overall, the average incidence rates were 2.22 for SLE and 0.72 for lupus nephritis per 100,000 children per year. Incidence rates increased dramatically with age and were again highest in all non-White racial and ethnic groups. The Midwest showed significantly lower incidence rates for SLE and lupus nephritis cases per 100,000 children in the population enrolled in Medicaid per year. Incidence rate ratios comparing rates among girls to boys (referent=1.0) were lowest among children 3 – < 6 years of age (3.68, 95% CI 0.76, 17.72) and highest among those 6 – < 9 years of age (8.45, 95% CI 2.54, 28.06). For girls aged 15 – < 18 compared to boys of same age, the incidence rate ratio was 5.99, (95% CI 4.27, 8.41). In comparison, our sensitivity analysis yielded an average incidence rate of 2.25 for SLE and 0.74 for lupus nephritis per 100,000 children per year, with an incidence rate ratio of girls compared with boys of 6.33 in the youngest age category and 6.70 in the oldest age category (Supplementary Table 1).
Employing nationwide billing data from five recent years for children enrolled in Medicaid, the federal-state program that provides health insurance to the poor, we have estimated the overall prevalence of SLE to be approximately 10 per 100,00 children. The prevalence of SLE is 5.3 times higher in girls than boys. More than one third of the children (37%) had lupus nephritis. The prevalence of lupus nephritis was estimated to be 3.6 per 100,000 children and 4.5 times higher in girls than boys. As has been shown in several previous studies in other populations, there was a higher prevalence of both SLE and lupus nephritis among all non-White children compared to White children. Rates of SLE and lupus nephritis were significantly lower in the Midwest section of the country than in other regions, likely due to the racial and ethnic population composition there (lower proportions of non-Whites). We identified only two past studies of SLE incidence among children, one in Canada in 1991–1993(14) and one conducted in Austria in 1997–1998(17). In these studies, the incidence rates were estimated to be 0.28 and 0.48 per 100,000 children per year respectively, lower than our incidence estimates in U.S. Medicaid-enrolled children. As in the few past studies that have examined the female to male ratio in new onset pediatric SLE and lupus nephritis, we have found that the incidence rate ratios (girls to boys) were lowest in the 3– < 6 year age group. The same pattern was found in a nationwide French study involving 156 pediatric SLE cases(19).
The current rate estimates among Medicaid-enrolled children in the U.S. demonstrate the substantial demographic variation that exists in this disease (Table 1 and and2).2). This range may represent true differences across populations as has been observed in the past, with higher prevalence rates among African American, Hispanic, Native American and Asian population compared with non-Hispanic White populations. However, these differences may also be due to the challenges of determining prevalence including variation in case definition and case ascertainment between studies, as well as a lack of a consensus age definition for pediatric SLE (a range of age cutoffs in past studies from 16 to 21 years of age)(16, 20) (Table 3).
Variation in prevalence and incidence estimates may also reflect differences in the source populations. The vast majority of past studies have been hospital- or clinic-based, likely representing patients with more severe disease. When using such data, it is often difficult to calculate population-based prevalence estimates which require assumptions regarding referral patterns to define the population that gave rise to cases seen in hospitals and clinics. Administrative healthcare databases have been used for research purposes including surveillance, outcomes research and quality assessment. However, they too have their limitations. Complete case identification may be difficult to ensure particularly since validation of the case definition is not always feasible.
In this study, we investigated the prevalence, incidence and sociodemographic characteristics of SLE and lupus nephritis among children covered by Medicaid in the U.S., 2000–2004. The U.S. Medicaid population is distinct from the general population in socioeconomic terms by definition: to be eligible for Medicaid in most states individuals must be living in poverty according to the Federal annual income threshold(21). This socioeconomically disadvantaged population likely includes a higher proportion of and more severe cases of SLE than the more affluent remainder of the U.S. population. By most measures, individuals with lower socioeconomic status have been shown to have higher incidence, severity and mortality from lupus than do those of higher socioeconomic status (22–25). Significant predictors of poor outcomes and disease progression in the LUMINA cohort have included poverty, lack of education, and lack of social support (22, 26). Adult lupus patients in LUMINA with incomes below the federal poverty level were four times more likely to die than were those with higher incomes (27), and poverty was a stronger predictor of mortality than was ethnicity(28).
The identification of patients with SLE and lupus nephritis employing administrative billing has been previously applied in adult populations. Algorithms employing two separate SLE billing diagnoses separated in time had excellent performance in administrative billing data in Quebec (29). We increased this to three billing diagnoses for SLE as Medicaid does not uniformly code subspecialty (thus, we could not examine rheumatologists’ visits separately) and to exclude those who were seen for one “rule-out” SLE visit and follow-up. In a past study, we found that the range of renal disease billing codes employed had an 80% positive predictive value for lupus nephritis in an adult Medicaid population(18). However, neither of these methods of case identification has been validated for pediatric patients. Additionally, many children were not continuously covered in Medicaid during the period of study. For the calculations of incidence rates, we limited all observations to Medicaid-enrolled time periods only (denominator population as well as numerator case numbers). We also performed sensitivity analyses limited to the 80% of children who were continuously enrolled in Medicaid for a minimum of 24 months during these years and the results were very similar (Supplementary Table 1).
This is the largest and only nationwide study of pediatric SLE to date, with over 30 million Medicaid-enrolled children. We analyzed national data collected over five years in an administrative dataset that captures all claims to Medicaid medical insurance. Within this large population, we were able to investigate potential variation in SLE and lupus nephritis rates in children across the country and by age and sociodemographic group. The elevated numbers of identified pediatric SLE cases highlight the public health significance of the disease. They provide an important indication of burden of this disease by age, sex, race/ethnicity and region of the U.S., and underscore how disproportionately distributed within society it is. The implications of this unequal distribution are important at the individual, family and societal levels. These results should allow study of health care access and outcomes among pediatric SLE and lupus nephritis patients on Medicaid. The estimated prevalence and incidence rates and demographic descriptors may also provide guidance to clinicians and policy makers on strategies to reduce barriers and improve care for children with SLE.
Supported by grants from the National Institutes of Health (RO1 AR057327, Dr. Costenbader); and the Canadian Institute of Health Research (Health Professionals Fellowship Award, Dr. Hiraki)