Systemic Lupus Erythematosus (SLE) is an enigmatic disorder aptly called “disease of thousand faces “. It has varied clinical and laboratory manifestations with plethora of autoantibodies. Genetic susceptibility studies have linked this disorder to MHC and HLA alleles though exact elucidation is still far from complete. As in all autoimmune disorders, environmental factors do play important role in initiation as well as propagation of aberrant immune responses though exact mechanisms for causation are not known. SLE has marked individual, ethnic and geographical variations in presentation and involvement of various organ systems. Outcomes also vary according to ethnicity and socioeconomic status. Epidemiology as the study of distribution and determinants of disease frequency in human populations is considered a basic science in medicine. Indeed, epidemiological principles and methods (including methods of statistical analysis) form the basis of any medical research, from case reports and other descriptive studies to cohort studies and experimental clinical trials. The advancement of medical knowledge follows a process resulting in a “spectrum of evidence”. Medical hypotheses are generated at the lowest level of evidence, where either clinical observation is made in a case-series or associations are observed in ecologic studies.

In addition to the important roles of descriptive epidemiological studies in the generation of etiological hypothesis, they also provide for the description of the frequency and/or patterns of disease occurrence at the individual or societal levels. Population-based surveys are crucial for quantifying the disease burden, contributing to evidence-based healthcare planning, and evaluating effectiveness and relative contribution of various primary and secondary/tertiary preventative measures for reducing burden of the disease/condition. In addition, analytic nonexperimental epidemiological studies often offer the only feasible alternatives to address specific hypotheses,such as the critically important role of case-control studies to test etiologic hypotheses in rare diseases. Susceptibility to SLE has a strong genetic component, and trans-ancestral genetic studies have revealed a substantial commonality of shared genetic risk variants across different genetic ancestries that predispose to the development of SLE. The geoepidemiology of this disease demonstrates ethnic variance, which might be explained by genetic susceptibility as well as environ­mental factors, including exposure to infectious agents (protective or pathogenic), ultraviolet radiation and environmental pollution. The highest increased risk of developing SLE is observed in black individuals (incidence 5- to 9-fold increased, prevalence 2- to 3-fold increased), with an increased risk also observed in South Asians, East Asians and other non-white groups, compared with white individuals. Black, East Asian, South Asian and Hispanic individuals with SLE tend to develop more severe disease with a greater number of manifestations and accumulate damage from lupus more rapidly. Increased genetic risk burden in these populations, associated with increased autoantibody reactivity in non-white individuals with SLE, may explain the more severe lupus phenotype. Even after taking into account socio-economic factors, race/ethnicity remains a key determinant of poor outcome, such as end-stage renal failure and mortality, in SLE. Community measures to expedite diagnosis through increased awareness in at-risk racial/ethnic populations and ethnically personalized treatment algorithms may help in future to improve long-term outcomes in SLE [1].

Ethnogenetic variation in the risk of SLE can be observed between distinct ethnic groups that live in the same geo­ graphical region. Ethnic background determines not only the risk of developing SLE, but also the clinical course and outcome of the disease. Findings from the ongoing LUMINA (Lupus in minorities: Nature versus Nurture) study, which is conducted by the NIH, reveal that African American and Hispanic American patients with SLE tend to develop the disease earlier in life, present with more ­severe symptoms at the time of diagnosis, and have more­ severe disease overall than white patients.2 Another environmental factor that might explain the reduced resistance of people from Africa who live in Europe or the USA is their reduced exposure to sunlight compared with those who live closer to the Equator. The decreased penetration of ultraviolet rays through the skin in these individuals could result in critically reduced levels of vitamin D, a hormone that is known to have an important immunomodulatory role.3 Smoking, which has been associated with an increased risk of SLE as well as of RA in genetically susceptible individuals, offers another possibility of a risk factor related to Western culture. Taken together, Africans who migrate far away from their native environmental and cultural conditions seem to have an increased susceptibility to SLE, which might be attributable to gene–environment interactions [3,4].

The role of the environment in determining the epi­demiology of SLE is further attested by the observation that lack of access to piped water during childhood is a risk factor for this disease in some ethnic groups. This observation suggests that poor hygiene and possibly the exposure to certain infectious agents (particularly viruses and bacteria) in early life could lead to suscep­tibility to, rather than protection against, SLE, as was suggested in the case of parasitic infections in African populations. The contrasting roles of infections revealed by geo-epidemiological studies of SLE is also supported by clinical findings.5 Industrial pollution was also associated with SLE in two US hot spots, namely Nogales, AZ, and Gainesville, GA, where the highest disease prevalence (up to 1,000 per 100,000 people) have ever been documented. The results of both studies, however, should be interpreted with caution. The Gainesville study’s extraordinary prevalence rates were based on a modest sized survey (that is, data from 300 individuals), and in Nogales, an investigation led by the Centre for Disease Control and Prevention failed to detect a difference in the presence of environmental pollutants in patients with SLE com­ pared with control individuals who resided in the same community. Nonetheless, findings of animal and in vitro studies, and several reports that linked occupational exposures, such as silica dust, mercury, pesticides and solvents metals, to an increased risk of SLE, also indicate industrial pollution as a potential risk factor [5].

Over recent years, our understanding of SLE has advanced at the level of its epidemiology, genetic susceptibility and depth of understanding of molecular mechanisms underlying its pathogenesis. These advances have been achieved through national and international collaboration between SLE researchers and clinicians, in conjunction with the harnessing of post-genome era technology. The overall message from an extensive body of literature is consistent; ancestry, race and ethnicity together have a major effect on the way in which SLE manifests. Black, Asian and Hispanic individuals with SLE tend to develop more severe disease, exhibit a greater number of manifestations and accumulate damage from lupus more rapidly.1,6 Even after taking into account socio-economic factors, race/ethnicity remains a key determinant of poor outcome, such as ESRD and mortality, in SLE.7,8 Ongoing genetic studies suggest an increased genetic risk burden in these populations associated with increased autoantibody reactivity in non-European SLE, which may partly explain the more severe lupus phenotype. Subgroup analyses from randomized controlled trials have shown that different ethnic groups respond differentially to therapeutic interventions. Community measures to improve early diagnosis through increased awareness in at-risk racial/ethnic communities, together with more ethnically personalized treatment algorithms, may be required in future to reduce the severity of SLE in high-risk populations and thus improve long-term outcome.

SLE in India was first reported in 1955 [11]. Only few case series have been published since than reporting clinical and immunological profiles of SLE patients from different regions of India. Only one case series has been published highlighting differences in presentation from various part of India. Prevalence was reported to be 3.2/100000 of population that was calculated way back in 1993 [12]. Indeed, this prevalence is quite low if compared to the Indian migrants settled in other countries. Epidemiological studies done in Asia have shown that SLE is fairly common in Asians, with an overall crude incidence rate (per 100 000 population per year) ranging from 0.9 to 3.1 and crude prevalence rates ranging from 4.3 to 45.3 (per 100 000) in the Asia-Pacific countries.1 SLE is at least two to three times more prevalent in Asia than in the Caucasian countries. As the population in Asia is huge, the burden of SLE disease in the Asian Pacific region is considerable [3]. Given the variation in available information about the epidemiology of lupus in Asia, a concerted effort using standardized methods will be useful in providing clinically useful and relevant information about how the disease impacts in the region. A common methodology, emphasizing uniform sampling and case identification, should be emphasized. Formation and adequate follow-up of longitudinal cohorts will aid in obtaining valid information about incidence, disease presentation, and disease course. This has been well demonstrated by invaluable information obtained about lupus outcomes from the Lupus in Minority populations: Nature vs. nurture (LUMINA) and Grupo Latinoamericano de Estudio del Lupus (GLADEL) [13] cohorts.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of clinical manifestations and a wide profile of autoantibodies. The clinical and serological heterogeneity makes it a great challenge for diagnosis, especially at the very early stage, when an inadequate number of features required to meet the criteria may be present. The most widely used classification criteria for SLE are those proposed by the American College of Rheumatology (ACR). The first version of the criteria was published in 1971 and revised in 1982 and 1997. The preliminary criteria including 14 items were effective in excluding normal patients in the population from which it was derived. However, it performed less well in patients during the early stage of their disease. Moreover, LE-cell test was often unavailable for these patients, thus high titres of anti-nuclear antibodies were also utilized as a criterion for validation. In 1982, a set of revised criteria was published. Compared with the 1971 criteria, this revision excluded certain cutaneous items such as Raynaud’s phenomenon and alopecia, and the ANA test was separated out as a new item. In addition, the criterion for proteinuria was reduced from >3.5g/day to >0.5g/day and two renal items were consolidated into one. The arthritis criterion had an additional description of non-erosive arthritis involving two or more joints. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.14 Piette et al. suggested that the ACR criteria be revised in light of the improved understanding of the association between antiphospholipid antibodies (aPLs) and SLE [15]. The 1997 updated classification criteria for SLE added these antibodies to their criteria list. The Systemic Lupus International Collaborating Clinics (SLICC), an international group focused on SLE clinical research, revised the SLE classification criteria to address various concerns that have arisen since the 1982 criteria were developed. The SLICC criteria improved on the revised ACR classification criteria in several critical ways. The cutaneous criteria, including both acute and subacute cutaneous lupus, are closer to the frequently used classification for CLE (the Gilliam and Sontheimer’s classification). Non-scarring alopecia was included because it performed well statistically and met the standards of clinical consensus. The changes in immunologic criteria reflect new understanding of serologic tests in SLE. Anti-dsDNA antibodies, anti-Sm antibodies, lupus anticoagulant, false-positive tests for syphilis, and anticardiolipin antibodies are split into separate items, so that each may contribute to classification. The new criterion for ANA requires a stricter cut-off for ELISA assays. “Newly-added” items such as anti-b2 glycoprotein 1 and low complement reflect a role of these biomarkers in the pathogenesis of SLE.

Epidemiology

The ascertainment of SLE incidence and prevalence faces several difficulties. Many of the studies are based on small source populations and cases are ascertained in the absence of standardized diagnostic criteria. Some of the more recent studies are based on self- report or on health system databases. Both approaches have shown poor reliability and yield only rough estimates. In addition, the relapsing– remitting course of the disease in individual patients and the long duration of remission make it essential to carefully distinguish incident from prevalent cases with reactivated disease. Epidemiological studies on SLE show marked gender, age, racial, temporal and regional variations, indicating hormonal, genetic and environmental disease triggers. There are striking gender disparities in SLE burden, with higher disease prevalence in women compared to men. Based on clinical experiences alone, it was established that the disease generally affected females in 80–90% of the cases. By the end of 20th century, the female-to-male ratio in the childbearing years was reported to be about 12:1 [15]. These observations suggest that hormonal factors play important role in SLE pathogenesis.

Age distribution of SLE cases is usually broad, ranging from children as young as two years old to adults 80 years of age and older. However, in females, incidence of the disease is usually highest at 15–44 years of age, while its prevalence maximal at 45–64 years [14] Females’ highest risk for SLE during childbearing age also suggests a key role of hormones in SLE ethology. Studies of racial tendencies showed that SLE more frequently affected non-Caucasian individuals. For instance, in the USA, SLE is more frequent in African- Americans, Hispanics and Asians than in Caucasians. SLE occurrence is three to four times higher among African-American women compared to Caucasian women [15] This suggests an importance of genetic pre-disposition to SLE, although differences in exposure to environmental factors may also explain excess morbidity from SLE in non-Caucasians. Temporal increase in SLE burden has been reported by a number of researchers. For instance, only for a period from 1955 to 1974, the incidence of SLE in the USA increased from 1.0 to 7.6 [16] Temporal increase in SLE burden may be associated with changes in environmental factors, although increased recognition of the disease and improved diagnostic methods may cause artefactual changes in SLE frequency. Regional variations, and in particular, differences in SLE incidence and prevalence in similar racial groups living in different parts of the world, could further shed the light on role of genetic, environmental and other causative factors in ethology and natural history of the disease. However, the differences in SLE burden across the countries and continents are not fully described. Although some published studies included findings on various countries, the available data concerning the incidence and prevalence of SLE are limited and conflicting, partially due to differences in study methodology.

Asia is the world’s largest continent, covering 8.6% of the earth’s total surface area or 29.9% of its land area. It is home to approximately four billion people, comprising 60% of the world’s current human population [17] Prevalence data is available for 15 countries from Eastern, South eastern, and Western Asia obtained from three distinct sources, namely:

• Population-based surveys conducted as part of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD)

• Non-COPCORD surveys; and 

• Hospital-based inception cohorts

There is both wide disparity and a clustering of prevalence rates of lupus among the different Asian countries included in this review. While most studies showed a clustering of prevalence values between 30 and 50 per 100,000, some studies showed values higher and lower than these. For instance, the survey done in Shanghai gave a rate of 70/100,000, compared with three other surveys conducted in China which gave values ranging between 30 and 50.30 This may have been an overestimation as the survey was done among textile factory workers who were predominantly female and exposed to environmental risk factors different from the other populations. In contrast, prevalence rates in India [12], Japan [45] and Saudi Arabia [17] were remarkably lower. It is difficult to ascertain whether this was an underestimation or truly low disease prevalence in these countries. For instance, the survey in India obtained low prevalence of the disease, despite the use of a combination of two sensitive screening methods, and diagnosis was confirmed by a rheumatologist.

Musculoskeletal and cutaneous involvements are the two most common features and leukopenia is the most common hematologic abnormality seen among Asian patients. Discoid rash, serositis, and neurologic features are less common. Renal involvement is common at onset and throughout the course of disease. Compared with Caucasian populations (Spanish, Puerto Rican, European, and American)59–62 wherein nephritis is found in 10–40%, almost two thirds of the included studies reported nephritis in 40–70% of their patients [7].

Table 1 The frequency of clinical and laboratory manifestations among Asian Countries are being summarized

Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune inflammatory disorder with varied manifestations ranging from benign skin manifestations to life threatening renal manifestations. Epidemiological data suggests geographical and ethnical differences pointing towards role of both genetic and environmental factors playing their role in phenotypic expression of disease. Various autoimmune markers in the form of autoantibodies have been discovered which correlate with phenotypic expression of disease

1. Lewis, Myles J., and Ali S. Jawad. "The Effect of Ethnicity and Genetic Ancestry on the Epidemiology, Clinical Features and Outcome of Systemic Lupus Erythematosus." Rheumatology, vol. 56, 2017, pp. 67–77.

2. Alarcon, G.S., J. Calvo-Alen, G. McGwin Jr., A.G. Uribe, S.M.A. Toloza, J.M. Roseman, and M. Fernandez. "Systemic Lupus Erythematosus in a Multiethnic Cohort: LUMINA XXXV. Predictive Factors of High Disease Activity Over Time." Annals of the Rheumatic Diseases, vol. 65, no. 9, Sept. 2006, pp. 1168–1174.

3. Lahita, Robert G., and George Tsokos. Systemic Lupus Erythematosus. 5th ed., Amsterdam: Academic Press, 2011, pp. 511–530.

4. Caroline, Gordon, and David Isenberg. Systemic Lupus Erythematosus. 1st ed., Oxford: Oxford University Press, 2016, pp. 321–346.

5. Kamen, Diane L. "Environmental Influences on Systemic Lupus Erythematosus Expression." Rheumatic Disease Clinics of North America, vol. 40, no. 3, Aug. 2014, pp. 401–vii.

6. Mok, Chi Chiu. "Special Issue on Systemic Lupus Erythematosus in Asia." International Journal of Rheumatic Diseases, vol. 18, 2015, p. 112.

7. Osio-Salido, E., and H. Manapat-Reyes. "Epidemiology of Systemic Lupus Erythematosus in Asia." Lupus, vol. 19, 2010, pp. 1365–1373.

8. Danchenko, N., J.A. Satia, and M.S. Anthony. "Epidemiology of Systemic Lupus Erythematosus: A Comparison of Worldwide Disease Burden." Lupus, vol. 15, 2006, pp. 308–318.

9. Desai, S.C., and S.D. Bhandarkar. "A Case Report of Acute Disseminated Lupus Erythematosus." Indian Journal of Dermatology and Venereology, vol. 21, 1955, pp. 131–134.

10. Malviya, A.N., et al. "Prevalence of Systemic Lupus Erythematosus in India." Lupus, vol. 2, no. 2, Apr. 1993, pp. 115–118.

11. Tan, E.M., A.S. Cohen, J.F. Fries, A.T. Masi, D.J. McShane, N.F. Rothfield, et al. "The 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus." Arthritis and Rheumatism, vol. 25, 1982, pp. 1271–1277.

12. Piette, J.C., B. Wechsler, C. Francis, and P. Godeau. "Systemic Lupus Erythematosus and the Antiphospholipid Syndrome: Reflections About the Relevance of ARA Criteria." Journal of Rheumatology, vol. 19, 1992, pp. 1835–1837.

13. Siegel, M., and S.L. Lee. "The Epidemiology of Systemic Lupus Erythematosus." Seminars in Arthritis and Rheumatism, vol. 3, 1973, pp. 1–54.

14. Ramsey-Goldman, R., and S. Manzi. "Systemic Lupus Erythematosis." Women and Health, Academic Press, 2000, p. 704.

15. Fessel, W.J. "Systemic Lupus Erythematosus in the Community: Incidence, Prevalence, Outcome, and First Symptoms; the High Prevalence in Black Women." Archives of Internal Medicine, vol. 134, 1974, pp. 1027–1035.

16. Fukase, M. The Epidemiology of Systemic Lupus Erythematosus in Japan. Baltimore, MD: University Park Press, 1980.

17. Al-Arfaj, A.S., S.R. Al-Balla, A.N. Al-Dalaan, et al. "Prevalence of Systemic Lupus Erythematosus in Central Saudi Arabia." Saudi Medical Journal, vol. 23, 2002, pp. 87–89.