INTRODUCTION
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease that primarily affects women in their reproductive years. Globally, an estimated 3.41 million individuals are affected by SLE, with approximately 90% of cases occurring in women [1]. In Korea, SLE affects more than 14,000 adults, including over 12,000 women [2].
The incidence and prevalence of SLE exhibit considerable variation across age groups, time periods, and geographic regions, reflecting the influence of both genetic predispositions and environmental exposures [3-5]. Although incidence and prevalence estimates vary across populations, several studies have reported a decline in SLE incidence alongside rising prevalence in general population. In Korea, temporal trends between 2005 and 2014 demonstrated a modest decrease in annual incidence coupled with a gradual rise in annual prevalence [2].
A similar trend of declining incidence and increasing prevalence was observed in UK between 1999 and 2012 [6], and a decline in SLE incidence was also reported in Norway between 1999 and 2017 [7]. These trends have been suggested to reflect improvement in survival and disease management, in addition to changes in environmental and social factors such as postmenopausal hormonal use, evolving classification criteria, enhanced healthcare access, and healthcare policy changes [2,6,7].
SLE poses a significant public health challenge for women of childbearing age due to its profound effects on fertility, pregnancy outcomes, and long-term maternal and fetal health [8-10]. The highest incidence (8.18 per 100,000 person-years [PYs]) and prevalence (77.07 per 100,000 PYs) have been reported among women of 20~44 years of age [11]. As this group represents a particularly vulnerable population, understanding temporal changes in the epidemiology of SLE is essential for healthcare planning and targeted resource allocation.
However, there is a paucity of data addressing this issue. Our previous study demonstrated that among Korean women of childbearing age (20~44 years), no significant temporal change in incidence or prevalence was observed between in 2011 and 2015, suggesting that this population may not have been substantially influenced by social or environmental factors during that period [11]. As both incidence and prevalence evolve over time, updated estimates are required.
Therefore, the present study aimed to examine recent temporal trends (2011~2020) in the incidence and prevalence of SLE among Korean women of childbearing age, using a nationwide health information database encompassing over 50 million individuals. In this study, childbearing age was defined as 20~49 years, based on reports indicating that while the mean age at natural menopause among Korean women is 49.3 years, it increased to 50.5 years in those born between 1945 to 1949 [12]. We also compared patterns of incidence and prevalence between the periods 2011~2015 and 2016~2020.
MATERIALS AND METHODS
Study design and study population
We conducted a nationwide retrospective study utilizing data from the Korean National Health Insurance Service-National Health Information Database (NHIS-NHID) from 2009 to 2020. Korea operates a single-payer national health insurance system, the NHIS, which provides coverage for nearly the entire population [13]. To support research, the NHIS established the NHID, a comprehensive resource that includes data on health care utilization, health behaviors, bio-clinical risk factors and socio-demographics for the entire Korean population [14].
The target population in this study was women of childbearing age (defined as women between the ages of 20~49 years) between January 1, 2011 to December 31, 2020. This age range was selected based on the reported mean age at natural menopause in Korean women (49.3 years) and its upward secular trend reaching 50.5 years among those born between 1945 and 1949 [12]. The study protocol was reviewed and approved by the Institutional Review Board of the National Health Insurance Service Ilsan Hospital, South Korea (NHIMC 2024-01-018), and was conducted according to the principles of the Declaration of Helsinki.
Since the NHIS-NHID provides anonymized data for research purposes, informed consent was not required for this study.
Identification of cases
We identified all SLE cases using the diagnostic code M32 based on ICD-10 (International Classification of Disease, 10th revision) codes in the NHIS-NHID during the period from January 1, 2011 to December 31, 2020. Data from January 1, 2011 was used with the assumption that all patients with SLE were accurately coded under registration program for rare and intractable disease in the Individual Copayment Beneficiaries Program (ICBP). In 2009, the Korean government implemented the ICBP to alleviate medical expenses for patients with rare and intractable diseases, including SLE.
To qualify for this program, patients must meet established classification criteria for SLE, and be officially registered as having a rare disease. The registration system records diagnostic codes (based on the Korean Standard Classification of Diseases [KCD]-7, aligned with ICD-10), the date of confirmed diagnosis, and relevant clinical test results.
Outcome measures and analysis
To calculate annual incidence, the numerator for each year was the number of individuals identified as incident cases within that specific calendar year, while the denominator was the total mid-year population at risk reported by the Korean National Statistical Office for the corresponding year. Incidence calculations covered the period from January 1, 2011 to December 31, 2020 with a 2-year washout period before 2011 to minimize the misclassification of prevalent cases as incident cases. For annual prevalence, the numerator for each year was the total number of prevalent cases during that calendar year, and the denominator was the total mid-year population reported by the Korean National Statistical Office for the corresponding year.
Prevalence rates were determined for the period from 2011 to 2020. Crude rates, age-specific rates, and 95% confidence intervals (CIs) were calculated for incidence and prevalence. CIs were calculated using the Wald method based on binomial distribution.
Comparison of age-standardized incidence and prevalence rates between time periods were conducted using the χ² test. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA).
RESULTS
Incidence and prevalence
Table 1 presents the incidence and prevalence of SLE among women of childbearing age (20~49 years) during the decade from 2011 to 2020. Out of 111,597,601 women in this age group, 9,187 women were newly diagnosed with SLE. The overall incidence of SLE during this period was 8.2 cases per 100,000 PYs.
The highest incidence was observed in the 20~24-year age group with 14.8 cases per 100,000 PYs, while the lowest was in the 45~49-year age group with 6.4 cases per 100,000 PYs. The incidence rates in the 25~29, 30~34, 35~39, 40~44-year age groups were fairly consistent, ranging from 7.2 to 7.5 cases per 100,000 PYs.
During the same period, among 111,597,601 women of childbearing age, 101,139 were identified as having SLE, yielding a prevalence rate of 90.6 cases per 100,000 PYs. The prevalence increased progressively with age, starting at 52.6 cases per 100,000 PYs in the 20~24-year age group and peaking at 109.2 cases per 100,000 PYs in the 40~44-year age group. A slight decline was observed in the 45~49-year age group, with a prevalence of 101.1 cases per 100,000 PYs.
Temporal trend in incidence
Figure 1 illustrates yearly trends in the incidence of SLE among women of childbearing age. Overall, the incidence remained relatively stable throughout the study period, peaking in 2016 at 8.8 cases per 100,000 PYs and a low in 2020 at 7.4 cases per 100,000 PYs (Figure 1A). Similarly, no chronological changes were observed in incidence rates during the study period for each age group (Figure 1B and Supplementary Table 1).
Age-stratified incidence by the year showed right-skewed reverse J-shaped distribution, with the highest incidence observed in the 20~24-year age group, followed by a sharp decline in the 25~29-year age group and a plateau across the 30~34, 35~39, 40~44, 45~49 age groups. This pattern was consistent across all analyzed years (Figure 1C).
A comparison of SLE incidence in women of childbearing age between the periods 2011~2015 and 2016~2020 showed no statistically significant differences overall (8.2 vs. 8.3/100,000 PYs, p=0.403). Similarly, no significant differences were observed when comparing incidence rates across various age groups between the two periods.
However, in the 25~29-year age group, there was a trend toward an increase in incidence during 2016~2020 compared to 2011~2015 (p=0.053) (Table 2).
Temporal trend in prevalence
Figure 2 illustrates the annual trends in SLE prevalence among women of childbearing age. Overall, prevalence steadily increased throughout the study period, rising from 77.1 cases per 100,000 PYs in 2011 to 101.0 cases per 100,000 PYs in 2019. However, a slight decrease was noted in 2020, with prevalence dropping to 99.9 cases per 100,000 PYs compared to 2019 (Figure 2A).
Similar upward trends in prevalence were observed across different age groups, with more prominent increases observed in the 35~39, 40~44, and 45~49-year age group throughout the study period. Notably, the 45~49-year age group demonstrated the most significant rise after 2015, reaching the prevalence observed in the 40~44-year age group, showing the highest prevalence among the age groups analyzed (Figure 2B and Supplementary Table 2). Age-stratified prevalence by the year displayed a bell-shaped distribution, with the lowest prevalence in the 20~24-year age group, followed by an increase in the 25~29 and 30~34-year age groups, and a plateau across the 30~34, 35~39, and 40~44-year age groups, before declining in the 45~49-year age group.
Of note, between 2016~2020, the bell-shaped distribution skewed leftward compared to 2011~2015, with notable increase observed in the 45~49-year age group (Figure 2C).
The prevalence of SLE among women of childbearing age showed a statistical increase when comparing the periods 2011~2015 and 2016~2020 (83.5 vs. 98.0/100,000 PYs, p<0.001). This rise in prevalence was evident across all age groups with highest prevalence in the 45~49-year age group during both periods.
The most notable increase was observed in the 45~49-year age group, with a rise of 32.9 cases per 100,000 PYs during 2016~2020 compared to 2011~2015 (Table 3).
DISCUSSION
The epidemiology of SLE is continuously evolving. Our retrospective, population-based cohort study is the first to examine recent trends in the incidence and prevalence of SLE specifically among women of childbearing age, a population particularly vulnerable to the disease, during the recent decade from 2011 to 2020. The key findings of this study are that the prevalence of SLE in women of childbearing age significantly increased during 2016~2020 compared to 2011~2015, while the incidence remained relatively stable.
Only few studies have investigated temporal trends in the incidence and prevalence in SLE, and most have focused on the overall SLE population across all age groups. A population-based cohort study from Norway reported a decline in SLE incidence between 1999 and 2017, from 3.4 to 1.1/100,000 PYs, with the most pronounced decrease observed in women aged 50~59 years [7]. Similarly, a retrospective cohort study using a longitudinal database of UK general practice records documented a 1.8% annual decline in SLE incidence during 1999~2012 [6], and a Korean study reported a decrease in annual incidence from 5.4 to 3.6/100,000 PYs between 2005 and 2015 [2].
In contrast, our study found that the incidence among women aged 20~49 years remained relatively stable between 2011 and 2020, averaging 8.2 cases per 100,000 PYs, with no statistically significant difference between the periods 2011~2015 and 2016~2020 (8.2 vs. 8.3/100,000 PYs, p=0.403). The decline in SLE incidence reported in the general population in the Norwegian study has been suggested to be associated with environmental factors, most notably the reduced use of menopausal hormone therapy in Southeast Norway, which decreased from 8.3% in 1999 to 2.2% in 2017 [7], following global concerns about increased risk of breast cancer associated with menopausal hormone treatments [15].
This interpretation aligns with evidence from a large prospective study identifying postmenopausal hormones as one of the strongest epidemiologic risk factors for SLE development [16]. By contrast, the stable incidence of SLE among women aged 20~49 years may reflect relatively consistent estrogen exposure during the reproductive years, a well-established factor for SLE susceptibility and pathogenesis [11,17-19].
This study demonstrated a steady increase in the prevalence of SLE among women of childbearing age between 2011 and 2019, rising from 77.1 to 101.0/100,000 PYs. When comparing the two time periods, the average prevalence significantly increased from 83.5/100,000 PYs in 2011~2015 to 98.0/100,000 PYs in 2016~2020. A similar upward trend in SLE prevalence over the past two decades has been reported in the German, UK, and Korean population across all age groups [2,6,20].
The recent increase in prevalence may be attributed to improved disease management, driven by advances in immunosuppressive therapies, earlier diagnosis, and comprehensive multidisciplinary care, which likely contributed to reduced mortality and prolonged survival in patients with SLE [21-26]. Among women of childbearing age, the rising prevalence may similarly reflect better disease control during pregnancy and postpartum period, facilitated by coordinated, multidisciplinary care and enhanced healthcare access [27,28]. Government-supported maternal health programs may also have contributed to improved outcomes in this population [29,30].
Notably, the Korean national stillbirth rate has been significantly decreased from 2.8 per 1,000 births in 2015 to 2.5 per 1,000 births in 2020 [31]. In our study, the highest SLE prevalence was observed in women aged 40~44. Notably, during 2016~2020, the age distribution shifted slightly toward older ages, with a more pronounced increase in the 45~49-year group compared to 2011~2015.
This pattern aligns with previous Korean data demonstrating a shift in peak prevalence from women in their 30s in 2010 to those in their 40s in 2015 [2]. These findings suggest that more women with SLE are reaching the later reproductive years with fewer complications due to advances in treatment and care.
With the increasing prevalence of SLE among women of childbearing age, there is a growing need to reassess healthcare policies and resource allocation to better support this vulnerable population. While our findings suggest improvements in disease management during the reproductive years, further research is warranted, particularly clinical trials evaluating the impact of emerging therapies on pregnancy-related outcomes in women with SLE. The stable incidence of SLE observed in this group suggests that the primary prevention remains a challenge.
Encouragingly, a recent study demonstrated that certolizumab pegol may reduce adverse pregnancy outcomes in patients with antiphospholipid syndrome [32]. However, additional trials are required to determine the safety and efficacy of newer treatments in pregnant women with SLE to improve both maternal and fetal outcomes. Given the well-established benefits of multidisciplinary care in improving pregnancy and neonatal outcomes in this population [26], expanding access to integrated care models is critical.
Increased allocation of healthcare resources to support collaborative, multidisciplinary teams will be essential for delivering comprehensive and effective care to women with SLE during their reproductive years. Women of childbearing age with SLE are at higher risk of pregnancy related complications and comorbidities, often due to high disease activity and greater use of immunosuppressive therapies during this period [9,10,33]. Given the potential impact of these factors on long-term outcomes, it is essential to develop healthcare policies that focus on early detection, prevention, and effective management of these complications and comorbidities during the reproductive years.
Tailored care strategies and supportive frameworks are needed to proactively address these risks and improve the overall health and survival in this high-risk group.
A major strength of this study is that it is the first to examine long-term trends in the incidence and prevalence of SLE specifically among women of childbearing age, a population uniquely affected by the disease and often underrepresented in epidemiological research. The stable incidence of SLE observed in this group suggests that primary prevention remains a challenge. However, the increasing prevalence in recent years, particularly among women aged 45~49 years, indicates improved survival and long-term management.
These findings provide strong epidemiological evidence that advances in diagnosis, treatment, and multidisciplinary care are contributing to better outcomes for women with SLE during their reproductive years. Despite the strengths of this study, limitations should be noted. First, because the NHIS database includes only individuals who have accessed healthcare services, there is a possibility that the incidence and prevalence of SLE may be slightly underestimated.
However, given that the NHIS provides near-universal coverage of the Korean population, any such underestimation is likely minimal. Second, our case definition relied solely on the ICD-10 code M32 in patients registered in the ICBP, assuming diagnostic accuracy, which may introduce misclassification bias. Most cases were classified based on 1997 ACR criteria, and only small number of patients were classified based on the 2019 EULAR/ACR criteria.
Furthermore, the diagnostic validity of SLE cases registered in ICBP has not been formally validated. Future studies should assess the diagnostic accuracy of ICD-10-based SLE identification in the ICBP by comparing it with algorithmic case definitions that incorporate diagnostic codes with medication use or hospital visits.
CONCLUSION
This study revealed a significant increase in the prevalence of SLE among women of childbearing age during 2016~2020 compared to 2011~2015, while the incidence remained relatively stable over the same period. These findings may reflect advancements in the early diagnosis, treatment, and overall disease management during the reproductive years, leading to improved survival and quality of life in this vulnerable population. However, due to ongoing disease burden and the unique challenges faced by women of childbearing age with SLE, continued efforts are needed to optimize care strategies, promote multidisciplinary approaches, provide patient education, and inform health policy aimed at improving long-term outcomes.
SUPPLEMENTARY DATA
Supplementary data can be found with this article online at https://doi.org/10.4078/jrd.2025.0168