The geoepidemiology of systemic lupus erythematosus
Introduction
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with a plethora of immunological and laboratory abnormalities, and clinical manifestations. There clearly is a genetic component to lupus susceptibility. It is generally accepted, however, that environmental or other factors are required as triggers of disease development. Lupus can affect almost every organ, most prominently and devastatingly the kidney and the central nervous system. Its severity in individual patients can range from mild cutaneous involvement to severe organ damage, its outcome from lasting remission to death. In addition, disease activity can fluctuate greatly, with most patients experiencing disease flares alternating with prolonged periods of remission. The clinical manifestations of SLE differ not only from patient to patient, but also show considerable geographic or ethnic variation between populations (see Table 1). Similar variation is obvious in disease activity and accrual of organ damage. Note that the comparison of disease activity between different cohorts has been greatly facilitated by the development of standardized and validated tools for assessing disease activity. These include the SLE Disease Activity Index (SLEDAI, SLEDAI-2K if the revised version is used), the European Consensus Lupus Activity Measure (ECLAM), and the Systemic Lupus Activity Measure (SLAM, SLAM-R, Bilag, if the revised version is used). Whereas no international consensus has yet been reached concerning the best tool for assessing disease activity, the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI) is in worldwide use for determining organ damage. It measures irreversible change attributable not only to lupus itself, but also to concomitant diseases or treatment, in 12 organs or systems.
This chapter will attempt to provide an overview of the genetic basis of SLE and the major geographical and ethnic differences in the frequency and severity of clinical manifestations. This will be followed by a discussion of the factors that are thought to play a role in these ethnic differences, focusing specifically on two of the major clinical manifestations of SLE, namely renal and neuropsychiatric involvement, and two commonly used outcome measures, disease activity and overall organ damage. Despite considerably improved survival probabilities in recent decades, the ultimate outcome measure in SLE remains mortality. Therefore, this chapter also includes a brief discussion of geographic and ethnic differences in survival probabilities and causes of death.
Several aspects of lupus are beyond the scope of this chapter. 1) The antiphospholipid syndrome is an important issue in SLE since it affects between 6% and 30% of patients in different cohorts and is associated with significant morbidity and mortality, but is addressed in a separate chapter and will not be a major focus here. 2) SLE most frequently affects adult women, but in about 15–20% of cases, disease onset occurs during childhood. The disease course in childhood onset lupus seems to differ from that seen in adult-onset disease, being more severe with faster and more severe damage accrual. Because of these differences, studies of childhood onset SLE will not be included here.
Section snippets
Incidence and prevalence and gender distribution of SLE
The ascertainment of SLE incidence and prevalence faces several difficulties. Many of the existing studies were based on small source populations and cases were 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
Genetics
Concordance rates of 24–58% in monozygotic twins compared to 2–5% in dizygotic twins indicate that there is a substantial genetic component to SLE susceptibility. This is further supported by the increased frequency of SLE – and other autoimmune diseases – in family members of SLE patients compared to the general population. The frequency of familial SLE overall appears to be in the range of 8–10%, the rates being similar in Europeans, Latin Americans, African Americans, Afro-Caribbeans, and
Clinical profiles of different populations
The frequencies of the individual clinical manifestations of SLE show substantial geographic or ethnic variation (see Table 2). Despite the considerable heterogeneity even within the major continental ethnic groups, certain patterns have emerged. Europeans and their descendants in other parts of the world generally show more frequent mucocutaneous manifestations, in particular photosensitivity, compared to most other ethnic groups [45], [46], [47]. However, SLE patients of African descent more
Survival probabilities and standardized mortality rates
There is overwhelming evidence that the probability of surviving 5 years after diagnosis of SLE increased from < 50% in the 1950s to ∼ 95% in the most recent studies [82], [83], [84], [85]. Nonetheless, the standardized mortality ratios (SMRs) for SLE patients remain 2–4-fold higher compared to the general population. In the Hopkins Lupus Cohort, survival probabilities were 95%, 91% 85% and 78% at 5, 10, 15 and 20 years after diagnosis, respectively [83]. Very similar survival rates have been
Concluding remarks
There are clear geographical and ethnic differences in the incidence, clinical course, and outcome of SLE. Numerous studies have investigated the confounding of the ethnicity effect by indicators of socioeconomic status. The results suggest that ethnicity is a more important determinant of renal and neuropsychiatric involvement and damage than socioeconomic factors. Both ethnicity and socioeconomic status are independently associated with disease activity and overall organ damage. However, the
Take-home messages
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SLE affects essentially all other ethnic groups more frequently than Europeans and their descendants
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SLE generally is less severe in Europeans compared to most other ethnic groups
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Genetic, environmental, sociodemographic and cultural factors all contribute to the different geographical/ethnic distribution and severity of clinical manifestations.
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