lupus in the developing world – is it any different?
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4evident. While the poorer outcome in developing countries is partly related to inherent geneticdifferences, better outcomes can be achieved if new initiatives are undertaken to define the bur-
1521-6942/$ - see front matter 2008 Elsevier Ltd. All rights reserved.
Best Practice & Research Clinical RheumatologyVol. 22, No. 4, pp. 643655, 2008
doi:10.1016/j.berh.2008.05.003available online at http://www.sciencedirect.com* Corresponding author. Tel./Fax: 27 11 938 8738.E-mail address: firstname.lastname@example.org (M. Tikly).den of disease, increase public awareness, and establish algorithms for diagnosis and treatmentbased on the available resources and local health-care delivery systems.
Key words: lupus; epidemiology; Africa; Asia; Latin America.in the developing world and is a major cause of morbidity and mortality. Discoid lupus and lym-phopenia are frequent clinical features of SLE in patients of African extraction. Thrombotic com-plications and associated anti-phospholipid antibodies are less common in the Chinese and BlackAfrican SLE patients than in Caucasian patients. High frequencies of antibodies to extractablenuclear antigens, especially anti-Sm and anti-U1RNP, have been reported in SLE patients inmany developing countries. Infections, including tuberculosis, are among the most importantcauses of comorbidity and mortality in SLE across all regions of the developing world. Witha few exceptions, survival rates for SLE patients in developing countries are substantially lowerthan those reported in industrialized countries, with early death from infection and active dis-ease. The bimodal pattern of mortality observed in many industrialized countries, is also lessLupus in the developing world is it any
Mohammed Tikly* FRCP, PhDProfessor and Head
Division of Rheumatology, Department of Medicine, Chris Hani Baragwanath Hospital and
University of the Witwatersrand, P.O. Bertsham 2013, South Africa
Sandra V. Navarra MD, FPCP, FPRAProfessor and Head
Section of Rheumatology, Clinical Immunology and Osteoporosis, University of Santo Tomas, Manila, Philippines
Systemic lupus erythematosus (SLE) is known to occur in all populations across the globe. Inmany respects SLE is similar across regions in its spectrum of clinical features, but the severityof the disease and comorbidity are appreciably different in the developing and industrializedworlds. Although data on the prevalence of SLE among Africans and Asians living in the tropicsare limited, SLE is reportedly more common and more severe in people of African and Asianextraction living in industrialized countries. Renal disease is especially common in SLE patients
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease withprotean manifestations, ranging from relatively minor skin and joint symptoms to se-
644 M. Tikly and S. V. Navarravere life-threatening major organ involvement such nephritis and neuropsychiatriccomplications. The disease occurs in all populations, but the prevalence, spectrumand severity of the disease varies across the globe.1
In this paper we review the published literature of SLE in the developing world,highlighting the reported differences in epidemiology, clinico-serological features, co-morbidity, and outcome compared to the industrialized Western world. Two obviousbut very important caveats to this discussion need to be emphasized. Firstly, thedeveloping world does not constitute a homogeneous population with respect togeography, ethnicity, environmental factors, or socio-economic conditions. What isperhaps common to all of the developing world which includes Africa, Latin Americaand most of Asia is that majority of people are non-Caucasian, reside mainly inwarmer tropical or subtropical regions of the southern hemisphere, and live underpoor socioeconomic conditions. Secondly, SLE has not been researched to anywherenear the same extent in developing countries as in the industrialized world. Hence,while many of the reported differences probably reflect true biological differencesdue to a combination of genetic, environmental and socioeconomic factors, at leastsome of the apparent differences are simply a reflection of lack of good researchdata on SLE in the developing world.
Over the past 5060 years there has been a rise of more than ten-fold in the annualincidence of SLE in industrialized Western countries.1 This temporal increase in SLE isthought to be due to both a true increase in incidence, related to exposure to envi-ronmental factors, and increased recognition of the disease. The epidemiology of SLEin the developing world remains largely unknown. Where formal epidemiological stud-ies have been undertaken, the occurrence of SLE has been found to be within therange reported in industrialized countries or higher. The annual incidence has been es-timated to be as high 8.7/100 000 in a Brazilian study in the tropical urban area of NatalCity2, and prevalence rates (per 100 000) of 12. 2 in Black South Africans3, 19.3 in Sau-dis4, 60 in the southern Chinese of Hong Kong5, and as high as 159 in Puerto Ricans6
have been reported.One of the enigmas of the epidemiology of SLE is that it is rarely seen in rural tropical
areas of Africa and Asia710, yet people of African and Asian extraction living in indus-trialized countries have amongst highest prevalence rates of SLE in the world.1,11 Not-withstanding the fact that SLE is probably under-diagnosed in many parts of rural Africaand Asia, where facilities to do even the basic indirect immunofluorescence antinuclearantibody (ANA) test are often not available12, many experts hypothesize that there is anSLE prevalence gradient. Racial admixture, as in the case of African Americans13, andenvironmental factors such as smoking, viral infections and silica are thought toincrease the risk of SLE in people of African or Asian extraction living in industrializedcountries.14 By contrast, tropical infections, in particular malaria, appear to conferprotection against SLE.15
SLE primarily affects women in the child-bearing years, and is estimated to be 912times more common in women than in men.1 Paediatric SLE, although rare, has beenobserved in several developing countries.1618 The mean age of disease onset appearsto be lower in developing countries. As in the case of rheumatoid arthritis, this mightbe a reflection of the lower overall life expectancy in the developing world.19,20
Alternatively, elderly-onset SLEmight be underdiagnosed because of its less florid clinicaland serological expression.21 There is also a suggestion that female preponderance of
Lupus in the developing world 645SLE is greater in developing countries (Table 1), which may be due to factors extraneousto the biology of the disease, such as differences in accessibility to health-care services.
CLINICAL AND SEROLOGICAL FEATURES
Studies from Western industrialized countries consistently show that the severity andburden of SLE is greatest in non-Caucasian ethnic groups of African and Asian extrac-tion.1,22,23 The clinical spectrum (Table 1), autoantibody profile, and comorbidity ofSLE in the developing world are not dissimilar to those in non-Caucasian SLE patientsliving in industrialized countries.
Perhaps the most outstanding clinical feature of SLE in the developing world is the highprevalence and severity of lupus nephritis, which impacts directly on morbidity andmortality (see below). Most studies from developing countries report lupus nephritisin at least one third of patients, and studies from South East Asia have shown that asmuch as 6469.3% of patients have renal disease24,25 compared to 27.9% in a study ofa 1000 European SLE patients.26 Moreover, a large proportion of patients have renaldisease at presentation, frequently as the presenting feature of SLE.20,27,28 At biopsy,proliferative glomerulonephritis (WHO class III and IV) is a common histological find-ing20,29, which apart from increasing the risk of end-stage renal disease (ESRD), is as-sociated with proteinuria and nephrotic syndrome in some populations.2931 In a Thaistudy of 569 patients with lupus nephritis, 43.6% of patients had nephrotic-range pro-teinuria and 58.0% had a creatinine clearance
Table 1. Demographic characteristics and frequency of key clinical features of systemic lupus erythematosus in developing countries.
Region Africa Asia Latin America27
Country/ethnic group RSA20 Tunisia40 Saudia88 Pakistan89 India61 Malaysia90 Singapore91 Hong Kong5 Philippines92 White Mestizo ALA
Year of publication 2007 2004 2007 2004 1997 1997 1998 2003 2006 2004
Sample size 226 100 86 196 1366 539 472 709 115 507 537 152
Mean age of onset (years) 34 32 24 31 24 26 31 30 31 30 28 26
Female:male ratio 18:1 11.5:1 10:1 7.2:1 8:1 12.5:1 11.8:1 e 28:1 9:1
Clinical features (%)
Photosensitivity 39 53 22 6 48 26 25e31 35 45 60 52 59
Malar rash 58 63 37 29 58.5 61e76 45e60 56 70 63 59 63Discoid rash 41 18 7 6 7 3 5e10 12 49 11 10 20
Oral ulcers 39 e 17 20 55 24 25e31 11 49 41 43 40
Arthralgia/arthritis 70 78 68 38 85 36e50 51e61 84 64 94 93 94
Serositis 18 e 27 22 22 6e13 7e21 19 23 e e ePleurisy e 29 19 e e e e e e 24 21 21
Pericarditis e 18 18 e e e e e e 16 16 26
Nephritis 44 43 61 33 73 50e74 18e54 50 80 44 58 55
Neuropsychiatric 16 25 19 26 27 23 4e14 6 24 e e eSeizures _ 6 10 e e e e 3 e 8 9 7
Psychosis e 20 e e e e e 3 e 3 5 4
Haemolytic anaemia e 6 14 e 1 19 e 20 3 13 12 10Leukopenia e e 24 22 12 24e39 e 32 23 40 43 47
Lymphopenia e 50 62 e e e e e e 51 64 70
Thrombocytopenia 13 12 16 26 7.5 16e30 e 25 10 19 18 23
ANA positive 99 100 95 86 96 93 97 e e 99 96 99
RSA, Republic of South Africa; ALA, Afri