Arthritis Care & Research Vol. 64, No. 2, February 2012, pp 159 168 DOI 10.1002/acr.

20683 2012, American College of Rheumatology

ORIGINAL ARTICLE

Systematic Review of the Epidemiology of Systemic Lupus Erythematosus in the Asia-Pacic Region: Prevalence, Incidence, Clinical Features, and Mortality
RUPERT W. JAKES,1 SANG-CHEOL BAE,2 WORAWIT LOUTHRENOO,3 CHI-CHIU MOK,4 SANDRA V. NAVARRA,5 AND NAMHEE KWON1

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-Pacic region. Methods. We conducted a systematic literature search using 3 groups of terms (SLE, epidemiology, and Asia-Pacic countries) of EMBase and PubMed databases and nonEnglish 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-Pacic 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 specic 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 variaSupported by GlaxoSmithKline. Dr. Baes work was supported by the Korea Healthcare Technology R&D Project and the Ministry for Health and Welfare, Republic of Korea (A080588). 1 Rupert W. Jakes, PhD, Namhee Kwon, MD, PhD: GlaxoSmithKline, Singapore; 2Sang-Cheol Bae, MD, PhD, MPH: Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea; 3Worawit Louthrenoo, MD: Chiang Mai University, Chiang Mai, Thailand; 4Chi-Chiu Mok, MD, FRCP: Tuen Mun Hospital, Hong Kong, China; 5Sandra V. Navarra, MD: University of Santo Tomas, Manila, Philippines. Dr. Jakes owns stock in GlaxoSmithKline. Dr. Lou-

tion 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).

threnoo has received consultant fees, speaking fees, and/or investigator fees (less than $10,000 each) from Roche, Merck Sharp and Dohme, American Taiwan Biopharm, Actelion, Pzer, and TRB Chemedica. Dr. Navarra has received speaking fees (less than $10,000 each) from GlaxoSmithKline, Roche, and Human Genome Sciences. Dr. Kwon owns stock in GlaxoSmithKline. Address correspondence to Rupert W. Jakes, PhD, GlaxoSmithKline, 150 Beach Road, #22-00 Gateway West, Singapore 189720. E-mail: rupert.2.jakes@gsk.com. Submitted for publication December 20, 2010; accepted in revised form October 17, 2011.

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Jakes et al 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 are; 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 nonEnglish 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 identication 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 prespecied; 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 specic 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 denition 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. 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 nonEnglish language search and 2 articles found from hand searching references from selected articles were included. Therefore, this review is based on 38 articles that fullled 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 fullled at least 4 of the American College of Rheumatology (ACR) criteria for SLE (12,13). We extracted data

Signicance & Innovations

This is the rst review article that summarizes published data from English and nonEnglish 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-Pacic 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.

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-Pacic 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 efcient 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 AsiaPacic region and 2) to describe any difference in the disease epidemiology across the countries in the region.

MATERIALS AND METHODS

Literature search. In this review article, the term AsiaPacic 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

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Figure 1. Study selection ow chart. SLE systemic lupus erythematosus.

on prevalence, incidence, demographic prole, 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-specic 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 stratied, data on

demographic prole, clinical manifestations, laboratory features, or causes of death were combined and summarized as weighted mean, median, or percentage accordingly. Data on demographic prole, 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

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Table 1. Incidence and prevalence of SLE in the Asia-Pacic region* Incidence (per 100,000 per year) Source, ref. Iseki et al, 17 Kameda, 18 Country Period Cases, no. 35466 108 272442 108 26 14 6 13 Ethnicity NS NS Chinese All Aborigines Aborigines Whites Aborigines Overall Female Male Prevalence (per 100,000) Overall Female Male

Japan, Okinawa 19731991 Japan, 19751977 Fukuoka City Mok et al, 19 Hong Kong 20002006 Bossingham, 20 Australia, 1998 Queensland Segosothy and Phillips, 21 Australia, Central 19961997

0.92.8 1.44.7 0.40.8 4.337.7 7.768.4 0.87.0 1.03 ND ND 10.8 ND ND 3.1 ND ND ND ND 11 5.4 ND ND ND ND ND 0.8 ND ND ND ND ND ND 45.3 92.8 73.5 19.3 52.6 ND ND ND ND ND ND ND ND ND ND ND ND

Anstey et al, 22 Australia, Northern Territory

19861990

* Crude rates, not age adjusted. SLE systemic lupus erythematosus; NS not specied; ND not done. Prevalent cases if not otherwise indicated. Derived from reported estimates. Where only sex-specic 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.

of health care and the medical system, we calculated the correlation coefcient for the association between the HDI and 5-year survival rates of the studies identied 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-Pacic countries, with a trend toward higher prevalence of SLE in Australia compared to the cited Asian countries (45.3 versus 4.337.7). 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-Pacic countries who were mainly of Chinese (3.1 for incidence) or Japanese (0.9 2.8 for incidence and 4.337.7 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). Demographic and clinical features of SLE. The demographic prole of adult SLE patients in the Asia-Pacic region is summarized in Table 2. A preponderance of female patients was consistently observed across the cited countries, ranging from 8397% (excluding studies that recruited only female or male patients). The mean age at SLE onset ranged from 25.734.5 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). The main clinical manifestations and laboratory ndings 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 ndings at diagnosis and over the course of the disease were positive antinuclear antibodies, ranging from 93100% and 55100%, respectively, antiDNA ranging from 51 86% and 41 83%, respectively, and hematologic disorder ranging from 19 61% and 67 87%, respectively. The clinical and laboratory prole appeared broadly similar across the populations in the Asia-Pacic 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-Pacic region are summarized in Table 3. Survival rates ranged from 9398% at 1 year, 60 97% at 5 years, and 70 94% at 10 years (excluding survival data specied 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-Pacic region, prognosis of SLE appeared to be better in China (Shanghai; 98% at 5 years), Hong Kong (97% at 5

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Table 2. Demographic prole of adult SLE patients in the Asia-Pacic region* Country, ref. China 24 23 Korea 25 26 Japan 27 18 Taiwan 28 29 Hong Kong 32 30 19 15 33 31 Vietnam 34 Philippines 35 36 Thailand 37 16 Malaysia 38 39 40 Singapore 3 41 42 Australia 21 20 22 New Zealand 43 Study period Cases, no. Age, years 31.7 2010 19591993 19972007 19922005 19752004 19751977 19881998 19831996 2007 20062007 20002006 19912003 19821991 19851989 19962000 2005 1993 19862000 19901992 19992000 19971998 19761990 19951996 19801992 1988 19901999 19961998 19841991 20002005 1,682 566 32.3 11.3 914 588 NS 306 108 NS 194 72 41 11 1,082 306 442 235 137 156 438 1,070 75 349 335 32.1 82 134 494 NS 472 175 94 NS 24 108 22 NS 170 93 83 86 95 NS 34.1 13.8 NS 92 94 91 32.9 31.1 7.6 89 91 93 29.6 (1363) 31.2 (16.075.0) 5.48 (0.130.6) NS NS NS 32.1 11.7 90 96 91 92 94 96 94 96 97 30.1 97 90 25.7 10 27 10 2.5 3.9 31.6 10.7 2.0 (0.0216.3) NS 26.7 NS 28.5 11.5 NS 1.4 83 0 29.8 12.8 33.1 12.1 9.3 6.6 90 95 34.5 11.6 34.9 11.3 3.2 3.0 100 94 NS NS NS 68 90 28.9 10.9 NS 4.1 (0.522.3) Female, % Age at SLE onset, years 30.9 9.6 Age at SLE diagnosis, years NS Duration of SLE, years 5.3 3.9

* SLE systemic lupus erythematosus; NS not specied. 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.

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%). The main causes of death in SLE in the Asia-Pacic 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-Pacic region, and cardiovascular (6 40%) and renal involvement (736%) were the main systems involved at death. 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 rst review article that summarizes published data from English and nonEnglish language resources on SLE prevalence and incidence, as well as the clinical manifestations, long-term outcome, and causes of mortality

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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-Pacic region. ACA anticardiolipin antibodies; LAC lupus anticoagulant; STS serologic test for syphilis; ANA antinuclear antibodies.

among adult SLE patients in the Asia-Pacic 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-Pacic 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

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Table 3. SLE survival rates in the Asia-Pacic region* Survival rates (%) Source, ref. Chen et al, 9 Xie et al, 23 Kim et al, 44 Iseki et al, 17 Kameda, 18 Funauchi et al, 27 Pu et al, 28 Country China, Shanghai China, Shanghai Korea Japan, Okinawa Japan, Fukuoka City Japan, Osaka Taiwan Study period 19801998 19591993 19931997 19721993 19751977 19752004 19881998 Cases, no. 50 566 544 566 103 (females) 306 152 21 21 72 519 213 22 156 75 102 349 102 22 NS NS Korean NS NS NS NS, onset age 50 years NS, onset age 5064 years NS, onset age 65 years Chinese, male Chinese, female Chinese, adult onset Chinese, late onset Chinese Filipinos Filipinos Thai All (Chinese 47%, Malays 46%, Indians 7%) Aborigines Ethnicity 1-year 98 98 93 98 97 ND ND 97 76 74 85 89 ND ND ND 93** 94 ND 93 91 5-year 98 86 73 94 89 89 ND 88 66 55 76 81 94 66 97 88** 75 84 86 60 10-year 84 76 60 ND 78 64 89 82 54 55 75 78 87 44 94 ND ND 75 70 ND

Chang et al, 29 Mok et al, 15 Wong, 31 Amante, 36 Victorio et al, 45 Kasitanon et al, 37 Paton et al, 11 Anstey et al, 22

Taiwan Hong Kong Hong Kong Philippines Philippines Thailand Malaysia Australia, Northern Territory

19831996 19912003 19851989 1993# 19821988 19862000 19781993 19841991

* Time zero for calculation of survival rates were not specied unless otherwise stated. SLE systemic lupus erythematosus; NS not specied; 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.

the US, Europe, Canada, and Australia, as reported by Danchenko et al (1), our ndings do not provide sufcient evidence to conclude whether SLE is more common in some countries or races in the Asia-Pacic 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 inuenced 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 denition 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 (25.734.5 years) or diagnosis (2734.9 years) in the cited Asia-Pacic 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 involve-

ment at diagnosis and over the course of SLE in the cited Asia-Pacic 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-Pacic region who may not be treated properly and are therefore at greater risk of severe disease. None of the selected studies specically studied comorbidities. Therefore, available data were scarce and did not present a good picture of the comorbidities related to the disease in the Asia-Pacic region. There was considerable variation in survival rates across the cited countries in the Asia-Pacic 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

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Table 4. Underlying causes of death in SLE in the Asia-Pacic region* Country, no. of deaths China, 16 Age at death, years 35.6 13.1 33.8 13.6 Duration of SLE, years 11.4 5.2 3.9 1.8 NS Ethnicity (%)

Source, ref. Chen et al, 9

Underlying causes of death (%) Infection (31), renal (31), cardiovascular (13), cerebrovascular (13), GI vasculitis (6), unknown (6) Infection (33), active SLE (25), cardiovascular (18), cerebrovascular (10), hematologic (8), pulmonary (3), GI (3), unknown (3) Active SLE (80), infection (10), suicide (10) Infection (35), active SLE (27), cardiovascular (7), cerebrovascular (10), GI (7), suicide (6), malignancy (3), hepatic (2), others (2), unknown (1) Infection (69), renal (17), pulmonary (14), cerebrovascular (6), CNS (6), malignancy (6), unknown (8) Infection (33), renal (20), CNS (20), pulmonary (13), cerebrovascular (7), malignancy (7) Infection (60), cerebrovascular (10), renal (7), cardiovascular (6), malignancy (3), suicide (3), unknown (10) Active SLE (60), infection (40) Cerebrovascular (45), renal (36), infection (23), cardiovascular (9), suicide (5), GI (5) Infection (50), infection and active SLE (30), active SLE (10), cardiovascular and renal (10), pancreatitis (10) Active SLE (56), infection (35), cardiovascular (16), cerebrovascular (10), malignancy (1), suicide (1) Infection (52), active SLE (35), cardiovascular (4), thromboembolism (2), malignancy (2), transfusion reaction (2), iatrogenic intraabdominal hemorrhage (2), unknown (2) Infection (52), active SLE (19), cerebrovascular (14), thromboembolism (5), GI and renal (5), unknown (5) Infection (30), renal (15), pulmonary (14), cardiovascular (7), CNS (5), malignancy (1), acuteanaphylaxis (1), unknown (27), SLE as a contributory factor of death (19) Active SLE (45), infection (40), thromboembolism (8), malignancy (6), cardiovascular (2)

Kim et al, 44

Korea, 40

Korean

Chun and Bae, 46 Ichikawa et al, 47

Korea, 10 Japan, 212

NS 33.3 11.3

NS NS

Korean NS

Pu et al, 28

Taiwan, 36

NS

NS

Chinese

Chang et al, 29 Mok et al, 19

Taiwan, 15 Hong Kong, 30 Hong Kong, 5 Hong Kong, 137 Philippines, 10 Philippines, 200 Thailand, 52

NS 43.8 17.4

NS 5.1 5.9

Chinese Chinese

Wong, 31 Lee et al, 33 Amante, 36

NS NS NS

NS NS NS

Chinese Chinese Filipinos

Lanzon and Navarra, 14 Kasitanon et al, 37

NS

NS

Filipinos

NS

NS

Thai

Paton et al, 11

Malaysia, 21 Malaysia, 100

28

3.3

NS

Yeap et al, 40

28.6 11.1

1.0 (0.114.1)

Chinese (73) Malays (18) Indians (9) Chinese (79) Malays (16) Indians (9) Others (2) Aborigines (67) European (22) Sikh (11) Aborigines Aborigines

Koh et al, 10

Singapore, 67

35.1 14

4.0 (0.120.8)

Bossingham, 20 Segasothy and Phillips, 21 Anstey et al, 22

Australia, 9

NS

9.2

Australia, 2 Australia, 9

36 30.0

1.2 2.9

Thromboembolism (56), active SLE or treatment complications (33), suspected thromboembolism (11) Infection (50), thromboembolism (50) Infection (67), cardiovascular (22), renal (11)

* Age and duration are shown as the mean SD or median (range) unless otherwise specied. SLE systemic lupus erythematosus; NS not specied; 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.

SLE in the Asia-Pacic Region 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 coefcient by plotting the HDI against 5-year survival rates of the studies identied 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 AsiaPacic region. Notably, however, there appeared to be a substantial proportion of deaths due to cardiovascular involvement (6 40%) in the Asia-Pacic 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-Pacic region. This may encourage further research on SLE to address issues specic to this region, which may eventually lead to more efcient clinical management of this population.

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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.

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ACKNOWLEDGMENTS
Medical writing support was provided by Hui-Hwa Choo and Sen-Kwan Tay. AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the nal 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.

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