Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: Prevalence, incidence, clinical features, and mortality

Authors


Abstract

Objective

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a wide spectrum of manifestations, shows considerable variation across the globe, although there is little evidence to indicate its relative prevalence in Asia. This review describes its prevalence, severity, and outcome across countries in the Asia-Pacific region.

Methods

We conducted a systematic literature search using 3 groups of terms (SLE, epidemiology, and Asia-Pacific countries) of EMBase and PubMed databases and non–English language resources, including Chinese Wanfang, Korean KMbase, Korean College of Rheumatology, Japana Centra Revuo Medicina, Taiwan National Digital Library of Theses and Dissertations, and Taiwanese, Thai, and Vietnamese journals.

Results

The review showed considerable variation in SLE burden and survival rates across Asia-Pacific countries. Overall crude incidence rates (per 100,000 per year) ranged from 0.9–3.1, while crude prevalence rates ranged from 4.3–45.3 (per 100,000). Higher rates of renal involvement, one of the main systems involved at death, were observed for Asians (21–65% at diagnosis and 40–82% over time) than for whites. While infections and active SLE were leading causes of death, a substantial proportion (6–40%) of deaths was due to cardiovascular involvement. The correlation between the Human Development Index and 5-year survival was 0.83.

Conclusion

This review highlights the need to closely monitor Asian SLE patients in Asian countries for renal and cardiovascular involvement, especially those who may not receive proper treatment and are therefore at greater risk of severe disease. We hope this will encourage further research specific to this region and lead to improved clinical management.

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease with a wide spectrum of manifestations ranging from minor cutaneous involvement to severe major organ damage. While the prevalence, severity, and outcome of the disease show considerable variation across the globe, there is little evidence to indicate its relative prevalence in Asia (1, 2). However, clinical manifestations of the disease as observed in one study were of greater severity in Asia, with greater renal involvement in particular (3). Probability of long-term survival appears to be generally lower in Asia compared to America and Europe (4–6).

Differences in the causes of mortality have also been reported among SLE patients in different geographic regions. A bimodal distribution of the cause of death has been reported in the US, Denmark, and other European countries (7, 8), i.e., mortality late in the course of SLE is more often due to cardiovascular disease, and mortality early in the course of SLE is more frequently due to active disease or infection. In Asia, infections and active SLE remain the major causes of death both early and late in the course of the disease (9–11). However, the typical cohort followup periods in Asia may be too short to draw conclusions on the latter.

The epidemiology of SLE has been described worldwide, and there is a suggestion that differences between Asia and the other parts of the world exist, with Asia generally showing a poorer prognosis. However, a comprehensive review of the available SLE epidemiologic data in the Asia-Pacific region has not been performed thus far. This review intends to provide a better understanding of the patient population in that region and encourage more efficient clinical management for this population. The objectives of this review article are the following: 1) to provide an overview of SLE prevalence and incidence, as well as the clinical manifestations, long-term outcome, and causes of mortality among adult SLE patients in the Asia-Pacific region and 2) to describe any difference in the disease epidemiology across the countries in the region.

Significance & Innovations

  • This is the first review article that summarizes published data from English and non–English language resources on systemic lupus erythematosus (SLE) prevalence and incidence as well as the clinical manifestations, long-term outcome, and causes of mortality among adult SLE patients in the Asia-Pacific region.

  • Higher rates of renal involvement were observed for Asians (21–65% at diagnosis and 40–82% over time) than for whites, making it one of the main organs involved at death. While infections and active SLE were the leading causes of death, a substantial proportion (6–40%) of deaths was due to cardiovascular involvement.

  • Using the Human Development Index (HDI) as a proxy for standards of health care and the medical system, we found a strong correlation (0.83, P < 0.0005) between the HDI and the 5-year survival rates of SLE patients.

MATERIALS AND METHODS

Literature search.

In this review article, the term “Asia-Pacific” refers to the following countries with available data: China, Korea, Japan, Taiwan, Hong Kong, Vietnam, Philippines, Thailand, Malaysia, Singapore, Indonesia, Australia, and New Zealand. We searched EMBase and PubMed from January 1985 to July 2010 and the inclusion criteria were according to the following search terms: 1) systemic lupus erythematosus or lupus erythematosus or lupus or lupus nephritis or CNS lupus; 2) epidemiology or incidence or prevalence or morbidity or mortality or survival or severity or hospitalis(z)ation or flare; and 3) Asia(n) or Australia(n) or Japan(ese) or China or Chinese or Taiwan(ese) or Hong Kong or Korea(n) or Thai(land) or Philippines or Filipino(s) or Singapore(an) or Malaysia(n) or Vietnam(ese) or Indonesia(n) or New Zealand. Additionally, the search was extended to identify potential articles from the following non–English language resources: Wanfang Database (Chinese), Korean KMbase, Korean College of Rheumatology, Japana Centra Revuo Medicina (Japanese), National Digital Library of Theses and Dissertations in Taiwan, Index to Taiwan Periodical Literature System, relevant local Vietnamese journals, and the local journal of the Thai Rheumatology Association. Following the identification of articles meeting the objectives of the review, the references were hand searched for articles missed by the EMBase and PubMed searches.

Study selection.

Based on the title and abstract, articles that met the following criteria were excluded (Figure 1): 1) commentaries, editorials, conference abstracts, review articles, meta-analyses, or studies undertaken in countries outside those prespecified; 2) animal, autopsy, genetic, laboratory, pathology, or renal biopsy studies; 3) therapeutic intervention studies, quality of life, or disease cost studies; 4) case reports or case series; 5) selected patient groups (pregnancy, pediatric, inpatients, patients with specific comorbidity, lupus nephritis); 6) association studies (e.g., smoking and risk of SLE); and 7) studies of the validation of questionnaires. Full manuscripts of the resulting articles were retrieved and carefully reviewed for inclusion by applying the above criteria; 48 articles were excluded as a result. In addition, 1 study was excluded as it based the definition of SLE upon insurance claims codes rather than standard criteria, 7 studies were excluded as the population described was a subset of those reported in selected articles, and 7 studies where there was no relevant data to extract were also excluded.

Figure 1.

Study selection flow chart. SLE = systemic lupus erythematosus.

Our literature search yielded 3,650 articles from EMBase and 2,341 articles from PubMed. After reviewing these articles and applying the above exclusion criteria, 35 articles remained that met our criteria for inclusion. In addition, 1 article from the non–English language search and 2 articles found from hand searching references from selected articles were included. Therefore, this review is based on 38 articles that fulfilled our criteria and reported data on prevalence, incidence, clinical manifestations, survival, or causes of mortality among adult SLE patients in the countries of interest. Of the 38 selected studies, 3 were conducted in China, 4 in Korea, 4 in Japan, 2 in Taiwan, 6 in Hong Kong, 1 in Vietnam, 4 in the Philippines, 2 in Thailand, 4 in Malaysia, 4 in Singapore, 3 in Australia, and 1 in New Zealand.

Data extraction.

All selected articles included patients who fulfilled at least 4 of the American College of Rheumatology (ACR) criteria for SLE (12, 13). We extracted data on prevalence, incidence, demographic profile, clinical manifestations, laboratory features, survival, and causes of death from the selected articles where available and organized them into tables or graphs, which were sorted by countries according to their geographic location and ordered from north to south. Where data in an article included patients with childhood onset of SLE (14–16), we excluded these patients during the data extraction.

We reported incidence as the number of new cases per 100,000 of population per year and prevalence as the number of cases per 100,000. In articles where only sex-specific incidence or prevalence rates were provided, we calculated the overall rate as an average of the male and female rates. In articles where results were stratified, data on demographic profile, clinical manifestations, laboratory features, or causes of death were combined and summarized as weighted mean, median, or percentage accordingly. Data on demographic profile, clinical manifestations, or laboratory features, if available from more than 1 article for the same country, were combined and summarized accordingly.

Human Development Index (HDI) analysis.

The HDI is a composite statistic that can be used to rank countries in terms of their economic and social development; its components include national income, educational attainment, and life expectancy. Using the HDI as a proxy for standards of health care and the medical system, we calculated the correlation coefficient for the association between the HDI and 5-year survival rates of the studies identified in our systematic review. The HDI values for the calendar year corresponding to the year of survival estimates were used (http://hdr.undp.org/en/data/explorer).

RESULTS

Incidence and prevalence in frequency of SLE.

The incidence and prevalence of SLE are summarized in Table 1. Overall crude incidence rates (per 100,000 per year) ranged from 0.9–3.1, while crude prevalence rates ranged from 4.3–45.3 (per 100,000) in the cited Asia-Pacific countries, with a trend toward higher prevalence of SLE in Australia compared to the cited Asian countries (45.3 versus 4.3–37.7). SLE was more common in Aborigines (11 for incidence and 52.6–92.8 for prevalence) compared to whites (19.3 for prevalence) in Australia and Asians in the cited Asia-Pacific countries who were mainly of Chinese (3.1 for incidence) or Japanese (0.9–2.8 for incidence and 4.3–37.7 for prevalence) ethnicity. It also affected women much more frequently than men (1.4–5.4 versus 0.4–0.8 for incidence and 7.7–68.4 versus 0.8–7.0 for prevalence).

Table 1. Incidence and prevalence of SLE in the Asia-Pacific region*
Source, ref.CountryPeriodCases, no.EthnicityIncidence (per 100,000 per year)Prevalence (per 100,000)
OverallFemaleMaleOverallFemaleMale
  • *

    Crude rates, not age adjusted. SLE = systemic lupus erythematosus; NS = not specified; ND = not done.

  • Prevalent cases if not otherwise indicated.

  • Derived from reported estimates. Where only sex-specific incidence or prevalence rates were provided, the overall rate was calculated as an average between male and female rates.

  • §

    Includes 78 patients of European or mixed descent (72%), 26 Aborigines (24%), 2 Sikhs (2%), 1 Filipino (0.9%), and 1 Indonesian (0.9%).

  • Incident cases.

Iseki et al,17Japan, Okinawa1973–199135–466NS0.9–2.81.4–4.70.4–0.84.3–37.77.7–68.40.8–7.0
Kameda,18Japan, Fukuoka City1975–1977108NS1.03NDND10.8NDND
Mok et al,19Hong Kong2000–2006272–442Chinese3.15.40.8NDNDND
Bossingham,20Australia, Queensland1998108All§NDNDND45.3NDND
   26AboriginesNDNDND92.8NDND
Segosothy and Phillips,21Australia, Central1996–199714AboriginesNDNDND73.5NDND
   6WhitesNDNDND19.3NDND
Anstey et al,22Australia, Northern Territory1986–199013Aborigines11NDND52.6NDND

Demographic and clinical features of SLE.

The demographic profile of adult SLE patients in the Asia-Pacific region is summarized in Table 2. A preponderance of female patients was consistently observed across the cited countries, ranging from 83–97% (excluding studies that recruited only female or male patients). The mean age at SLE onset ranged from 25.7–34.5 years, with patients in Malaysia (25.7 years) and Philippines (26.7 years) demonstrating earlier onset compared to patients in the other countries. SLE duration (since diagnosis of SLE) ranged from 1.4–9.3 years, with longer disease duration observed among patients in Australia (7.6 years) and Hong Kong (9.3 years).

Table 2. Demographic profile of adult SLE patients in the Asia-Pacific region*
Country, ref.Study periodCases, no.Age, yearsFemale, %Age at SLE onset, yearsAge at SLE diagnosis, yearsDuration of SLE, years
  • *

    SLE = systemic lupus erythematosus; NS = not specified.

  • Studies were sorted according to the last year of the study period.

  • Values are the mean ± SD or the median (range).

  • §

    Indicates publication year.

  • Study selected only female or male patients.

China  31.7 30.9 ± 9.6NS5.3 ± 3.9
 242010§1,682 68   
 231959–1993566 90   
Korea  32.3 ± 11.3 28.9 ± 10.9NS4.1 (0.5–22.3)
 251997–2007914 100   
 261992–2005588 94   
Japan  NS NSNSNS
 271975–2004306 90   
 181975–1977108 95   
Taiwan  NS 34.5 ± 11.634.9 ± 11.33.2 ± 3.0
 281988–1998194 83   
 291983–199672 0   
Hong Kong  41 ± 11 29.8 ± 12.833.1 ± 12.19.3 ± 6.6
 3220071,082 90   
 302006–2007306 96   
 192000–2006442 91   
 151991–2003235 92   
 331982–1991137 94   
 311985–1989156 96   
Vietnam       
 341996–2000438NS94NSNSNS
Philippines    26.728.5 ± 11.51.4
 3520051,070NS96   
 361993§75NS97   
Thailand  32.1 ± 11.7 30.131.6 ± 10.72.0 (0.02–16.3)
 371986–2000349 97   
 161990–1992335 90   
Malaysia  32.1 25.7 ± 1027 ± 102.5 ± 3.9
 381999–200082 89   
 391997–1998134 91   
 401976–1990494 93   
Singapore  NS 29.6 (13–63)31.2 (16.0–75.0)5.48 (0.1–30.6)
 31995–1996472 92   
 411980–1992175 94   
 421988§94 91   
Australia  NS 32.931.17.6
 211990–199924 83   
 201996–1998108 86   
 221984–199122 95   
New Zealand  NS NS34.1 ± 13.8NS
 432000–2005170 93   

The main clinical manifestations and laboratory findings at diagnosis and during the course of SLE of the adult patients described in Table 2 are illustrated in Figure 2. Nonerosive arthritis, malar rash, and renal disorder were the most common clinical manifestations observed at diagnosis (ranging from 31–80%, 48–63%, and 14–65%, respectively) and over time (ranging from 48–83%, 41–84%, and 30–82%, respectively). The most frequently observed laboratory findings at diagnosis and over the course of the disease were positive antinuclear antibodies, ranging from 93–100% and 55–100%, respectively, anti-DNA ranging from 51–86% and 41–83%, respectively, and hematologic disorder ranging from 19–61% and 67–87%, respectively.

Figure 2.

Frequency of key clinical features at diagnosis (A), cumulative frequency of clinical features during disease course (B), frequency of laboratory features at diagnosis (C), and cumulative frequency of laboratory features during the disease course (D) of systemic lupus erythematosus in the Asia-Pacific region. ACA = anticardiolipin antibodies; LAC = lupus anticoagulant; STS = serologic test for syphilis; ANA = antinuclear antibodies.

The clinical and laboratory profile appeared broadly similar across the populations in the Asia-Pacific region except for strikingly lower rates of renal involvement observed in New Zealand (14% at diagnosis) and Australia (30% over time) compared to the Asian countries (21–65% at diagnosis and 40–82% over time).

Survival and main causes of death in SLE.

Survival rates in the Asia-Pacific region are summarized in Table 3. Survival rates ranged from 93–98% at 1 year, 60–97% at 5 years, and 70–94% at 10 years (excluding survival data specified as calculated from SLE onset) across the cited countries, with a general trend of improvement in survival for more recent studies. Among the cited countries in the Asia-Pacific region, prognosis of SLE appeared to be better in China (Shanghai; 98% at 5 years), Hong Kong (97% at 5 years and 94% at 10 years), and South Korea (94% at 5 years), while the Aborigines in Australia showed poor prognosis at 5 years (60%).

Table 3. SLE survival rates in the Asia-Pacific region*
Source, ref.CountryStudy periodCases, no.EthnicitySurvival rates (%)
1-year5-year10-year
  • *

    Time zero for calculation of survival rates were not specified unless otherwise stated. SLE = systemic lupus erythematosus; NS = not specified; ND = not done.

  • From SLE onset.

  • From SLE diagnosis.

  • §

    Adult onset = age 16–50 years; late onset = age >50 years.

  • From SLE diagnosis; exact survival rates were not indicated in the cited article. Rates were extrapolated from the survival curve shown in the article.

  • #

    Indicates publication year.

  • **

    From SLE diagnosis; derived from reported cumulative mortality rate.

Chen et al,9China, Shanghai1980–199850NS989884
     988676
Xie et al,23China, Shanghai1959–1993566NS937360
Kim et al,44Korea1993–1997544Korean9894ND
Iseki et al,17Japan, Okinawa1972–1993566NS978978
Kameda,18Japan, Fukuoka City1975–1977103 (females)NSND8964
Funauchi et al,27Japan, Osaka1975–2004306NSNDND89
Pu et al,28Taiwan1988–1998152NS, onset age <50 years978882
   21NS, onset age 50–64 years766654
   21NS, onset age ≥65 years745555
Chang et al,29Taiwan1983–199672Chinese, male857675
   519Chinese, female898178
Mok et al,15Hong Kong1991–2003213Chinese, adult onset§ND9487
   22Chinese, late onset§ND6644
Wong,31Hong Kong1985–1989156ChineseND9794
Amante,36Philippines1993#75Filipinos93**88**ND
Victorio et al,45Philippines1982–1988102Filipinos9475ND
Kasitanon et al,37Thailand1986–2000349ThaiND8475
Paton et al,11Malaysia1978–1993102All (Chinese 47%, Malays 46%, Indians 7%)938670
Anstey et al,22Australia, Northern Territory1984–199122Aborigines9160ND

The main causes of death in SLE in the Asia-Pacific region are summarized in Table 4. Infections (30–80%) and active SLE disease (19–95%) were the leading causes of death among the cited countries in the Asia-Pacific region, and cardiovascular (6–40%) and renal involvement (7–36%) were the main systems involved at death.

Table 4. Underlying causes of death in SLE in the Asia-Pacific region*
Source, ref.Country, no. of deathsAge at death, yearsDuration of SLE, yearsEthnicity (%)Underlying causes of death (%)
  • *

    Age and duration are shown as the mean ± SD or median (range) unless otherwise specified. SLE = systemic lupus erythematosus; NS = not specified; GI = gastrointestinal; CNS = central nervous system.

  • CNS includes lupus, CNS involvement, and neurologic disease. Pulmonary includes pulmonary disease, respiratory disease, interstitial lung disease, pulmonary hemorrhage syndrome, pulmonary hemorrhage, acute respiratory distress syndrome, pulmonary edema, and pneumonitis. Cardiovascular includes pulmonary hypertension, rheumatic heart disease, myocarditis, cardiac death, and ruptured aortic aneurysm. Pulmonary embolism includes thromboembolism.

  • Percentages may not add up to 100% due to rounding or subjects in cited reference may have more than 1 cause of death.

Chen et al,9China, 1635.6 ± 13.111.4 ± 5.2NSInfection (31), renal (31), cardiovascular (13), cerebrovascular (13), GI vasculitis (6), unknown (6)
Kim et al,44Korea, 4033.8 ± 13.63.9 ± 1.8KoreanInfection (33), active SLE (25), cardiovascular (18), cerebrovascular (10), hematologic (8), pulmonary (3), GI (3), unknown (3)
Chun and Bae,46Korea, 10NSNSKoreanActive SLE (80), infection (10), suicide (10)
Ichikawa et al,47Japan, 21233.3 ± 11.3NSNSInfection (35), active SLE (27), cardiovascular (7), cerebrovascular (10), GI (7), suicide (6), malignancy (3), hepatic (2), others (2), unknown (1)
Pu et al,28Taiwan, 36NSNSChineseInfection (69), renal (17), pulmonary (14), cerebrovascular (6), CNS (6), malignancy (6), unknown (8)
Chang et al,29Taiwan, 15NSNSChineseInfection (33), renal (20), CNS (20), pulmonary (13), cerebrovascular (7), malignancy (7)
Mok et al,19Hong Kong, 3043.8 ± 17.45.1 ± 5.9ChineseInfection (60), cerebrovascular (10), renal (7), cardiovascular (6), malignancy (3), suicide (3), unknown (10)
Wong,31Hong Kong, 5NSNSChineseActive SLE (60), infection (40)
Lee et al,33Hong Kong, 137NSNSChineseCerebrovascular (45), renal (36), infection (23), cardiovascular (9), suicide (5), GI (5)
Amante,36Philippines, 10NSNSFilipinosInfection (50), infection and active SLE (30), active SLE (10), cardiovascular and renal (10), pancreatitis (10)
Lanzon and Navarra,14Philippines, 200NSNSFilipinosActive SLE (56), infection (35), cardiovascular (16), cerebrovascular (10), malignancy (1), suicide (1)
Kasitanon et al,37Thailand, 52NSNSThaiInfection (52), active SLE (35), cardiovascular (4), thromboembolism (2), malignancy (2), transfusion reaction (2), iatrogenic intraabdominal hemorrhage (2), unknown (2)
Paton et al,11Malaysia, 21283.3NSInfection (52), active SLE (19), cerebrovascular (14), thromboembolism (5), GI and renal (5), unknown (5)
Yeap et al,40Malaysia, 10028.6 ± 11.11.0 (0.1–14.1)Chinese (73) Malays (18) Indians (9)Infection (30), renal (15), pulmonary (14), cardiovascular (7), CNS (5), malignancy (1), acuteanaphylaxis (1), unknown (27), SLE as a contributory factor of death (19)
Koh et al,10Singapore, 6735.1 ± 144.0 (0.1–20.8)Chinese (79) Malays (16) Indians (9) Others (2)Active SLE (45), infection (40), thromboembolism (8), malignancy (6), cardiovascular (2)
Bossingham,20Australia, 9NS9.2Aborigines (67) European (22) Sikh (11)Thromboembolism (56), active SLE or treatment complications (33), suspected thromboembolism (11)
Segasothy and Phillips,21Australia, 2361.2AboriginesInfection (50), thromboembolism (50)
Anstey et al,22Australia, 930.02.9AboriginesInfection (67), cardiovascular (22), renal (11)

Analysis of HDI.

For the 13 studies where 5-year survival rates were available, the correlation between the HDI and 5-year survival was 0.83 (P < 0.0005). We excluded the Australian study (22) as its subjects were rural Aborigines, and we felt that the very high HDI for Australia did not represent the Aborigine population.

DISCUSSION

This is the first review article that summarizes published data from English and non–English language resources on SLE prevalence and incidence, as well as the clinical manifestations, long-term outcome, and causes of mortality among adult SLE patients in the Asia-Pacific region. It also describes differences in the disease epidemiology observed across the cited countries in that region.

We found considerable variation in SLE burden across the cited countries in the Asia-Pacific region. Most of our cited studies from Australia showed that Aborigines have higher SLE rates than local whites. While these studies concurred with an earlier review of white populations in the US, Europe, Canada, and Australia, as reported by Danchenko et al (1), our findings do not provide sufficient evidence to conclude whether SLE is more common in some countries or races in the Asia-Pacific region compared to others due to limited epidemiologic data from studies in this region. Further, it should be noted that while disease burden may be influenced by true differences across the countries or races, other differences between studies, such as year of study and whether incidence of a single year or over a period of time was reported, and methodologic issues such as study design, referral pattern, inconsistencies in definition of ACR criteria for SLE, and method of case ascertainment also contribute to variability in the reported rates.

It has been reported that age at SLE onset or diagnosis is higher among white populations (38–51.7 years) compared to nonwhite populations (20–32.3 years for Asian populations and 32.2 years for Aborigines) (48). Our review showed that the mean age at SLE onset (25.7–34.5 years) or diagnosis (27–34.9 years) in the cited Asia-Pacific countries was similar to that reported in nonwhite populations. This could be attributed to the high proportion of nonwhite populations in the cited studies from Australia (28–100% Aborigines) and New Zealand (59%) (20–22, 43).

Our review showed that frequencies of renal involvement at diagnosis and over the course of SLE in the cited Asia-Pacific countries ranged from 14–65% and 30–82%, respectively, with higher rates of renal involvement observed among the cited Asian countries (21–65% at diagnosis and 40–82% over time) compared to New Zealand (14% at diagnosis) and Australia (30% over time). This concurs with reports of renal involvement being more common among Asian populations than white populations (2) and highlights the need to closely monitor the Asian populations in the Asia-Pacific region who may not be treated properly and are therefore at greater risk of severe disease. None of the selected studies specifically studied comorbidities. Therefore, available data were scarce and did not present a good picture of the comorbidities related to the disease in the Asia-Pacific region.

There was considerable variation in survival rates across the cited countries in the Asia-Pacific region. The 5-year survival rates ranged from 60% among the Aborigines in Australia to 94% in South Korea, 97% in Hong Kong, and 98% in China (Shanghai), while 10-year survival rates ranged from 70% in Malaysia to 94% in Hong Kong. Difference in survival might result from a delay in treatment and poor compliance of patients. These may vary across countries because of cultural differences, medical systems, educational background, and socioeconomic factors. Other reasons for this observation include differences in study methodology (such as those mentioned above) and other factors such as nonstandardization of “time zero” for calculation of survival rates.

Vasudevan and Krishnamurthy (49) undertook an analysis to describe the HDI against survival of SLE patients at 5 years and found a correlation of 0.56. Using the HDI as a proxy for standards of health care and the medical system, we calculated the correlation coefficient by plotting the HDI against 5-year survival rates of the studies identified in our systematic review. For the 13 studies where 5-year survival rates were available, we found a strong correlation (0.83, P < 0.0005). As countries achieve higher economic and social status, we might see improved outcome and survival in SLE patients.

We found, similar to reports on causes of death among SLE patients in Asia (50), that infections and active SLE disease remain the leading causes of death. The second peak of death due to cardiovascular disease was not observed as in the Western countries. This might be due to the short duration of followup in most cited articles. Renal involvement remains as one of the main organ systems involved at death among the SLE populations in the Asia-Pacific region. Notably, however, there appeared to be a substantial proportion of deaths due to cardiovascular involvement (6–40%) in the Asia-Pacific region. This highlights the importance of increasing the awareness of the risks of cardiovascular death for SLE patients whose susceptibility to the disease increases as they age and to implementing proactive measures to reduce the risk factors for cardiovascular disease in this population.

We recognize that regional differences in SLE epidemiology observed across the countries may be related to factors such as differences in environment, age at onset, sex, socioeconomic status, availability and accessibility to health care resources, availability of therapy, compliance to medical care, and methodologic issues across the studies. Some of these factors need to be considered when making comparisons across studies. Nonetheless, this article provides valuable information on the burden of SLE, in particular prevalence and incidence, as well as the clinical manifestations, long-term outcome, and causes of mortality among adult SLE in the Asia-Pacific region. This may encourage further research on SLE to address issues specific to this region, which may eventually lead to more efficient clinical management of this population.

AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Jakes 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 conception and design. Jakes, Bae, Louthrenoo, Mok, Navarra, Kwon.

Acquisition of data. Jakes, Bae, Louthrenoo, Mok, Navarra, Kwon.

Analysis and interpretation of data. Jakes, Bae, Louthrenoo, Mok, Kwon.

ROLE OF THE STUDY SPONSOR

GlaxoSmithKline oversaw the study design, data collection, data analysis, and writing of the manuscript, and approved the content of the submitted manuscript. Publication of this article was not contingent on the approval of GlaxoSmithKline.

Acknowledgements

Medical writing support was provided by Hui-Hwa Choo and Sen-Kwan Tay.

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