- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
SLE is undoubtedly a disease in which health disparities, as defined by the NIH (1), are clearly present because it affects primarily one sex (women), young persons (reproductive age), and less-privileged individuals (ethnic minorities) in the US and around the world. Any of these areas could be elaborated further, but we have chosen to emphasize primarily health disparities in lupus in relation to ethnicity. Given that LUMINA is a multiethnic cohort we had the opportunity to compare and contrast data from patients of the 3 main US ethnic groups: Caucasians, African Americans, and Hispanics; in addition, we provide data for 2 Hispanic subgroups, those inhabiting the island of Puerto Rico and those of Mexican origin (the most frequent country of origin for all US Hispanics) recruited primarily in Texas. Inclusion of Hispanics when examining health disparities is quite relevant because they constitute the nation's largest (14% of the total population not including the 3.9 million residents of Puerto Rico) and fastest growing ethnic minority. In fact, by July 2004 there were more than 41 million Hispanics; by the year 2020 this figure is expected to reach 60 million (24).
As the data from the literature (25–28) and from the LUMINA cohort illustrate (9, 10, 13, 19, 21), there are substantial differences in disease onset, features, course, and outcome among patients with SLE from the major US ethnic groups, with Hispanic patients (particularly of Mexican ancestry [residents of Texas], but not of Puerto Rican ancestry) and African American patients exhibiting, overall, more serious disease at a younger age and with worse intermediate and final outcomes. Given that these 2 groups are also more socially disadvantaged, a clear picture as to what the underlying causes for these disparities are is difficult to draw. We attempted, based on the data presented, to build an explanatory model for the discrepancies observed (Figure 2); this model could be regarded as a template in which additional factors or variables are identified as further research is conducted and in which strategies that can modify these factors are built.
Figure 2. Disease course and outcome in systemic lupus erythematosus (SLE): genetic and nongenetic factors account for differences observed between ethnic groups. * Nongenetic factors (and to a lesser extent genetic factors) are also operative during the course of the disease (see text).
Download figure to PowerPoint
In its most simplistic manner, the natural course of SLE can be regarded as a continuum in which as the disease begins, the patient will experience different clinical manifestations; as time goes on, the patient will undergo periods of disease activity that may or may not be followed by damage in different organ systems (due to either the disease or treatments). Ultimately, the patient may succumb earlier than if lupus had not supervened.
For those that regard race as a purely biologic construct, the basis for the disparate outcomes observed are due to the genetic differences between ethnic groups. However, as pointed out by Lander et al (29), we now know that there is marked genetic homogeneity within humans; in fact, 99.9% of DNA is identical among all humans with the remaining 0.01% accounting for their differences. In contrast, ethnicity is not only a biologic construct, but also a social construct. An ethnic group is not defined by its anthropomorphic features (included in the now discredited notion of race), but rather by its common geography, history, language, culture, and values (30–34); furthermore, the ethnic groups inhabiting the US are not entirely homogenous in terms of their genetic features as our admixture data clearly show (17, 20). Therefore, the variance that is explained by ethnicity in multivariable models of outcome has a clear socioeconomic (nongenetic) component and a biologic (genetic) component, which influence each other, as shown in Figure 2. The tight relationship between genetic and nongenetic factors occurs throughout the course of the disease, although Figure 2 depicts their impact as occurring only at disease onset. Early in the disease, purely genetic factors appear quite important, whereas as time goes on that is not the case; socioeconomic factors, on their broadest sense, achieve prominence. We have consistently shown, for example, that disease activity, whether at disease onset, at enrollment into the cohort, or over the disease course, is of greater magnitude in Texan Hispanics and African Americans. Early in the disease, a purely genetic component explains to a certain extent the greater levels of disease activity among these ethnic groups (13). As time passes, the purely genetic factors initially identified are no longer singled out; instead, maladaptive coping strategies, lack of health insurance, and inadequate social support emerge as important contributors of this intermediate disease outcome (18).
African Americans and Texan Hispanics also tend to experience renal disease more frequently than Caucasians and Puerto Rican Hispanics (19). Although environmental factors can trigger the onset of renal involvement, the fact that once it occurs these 2 groups also tend to progress to permanent renal damage more frequently than the other 2 groups supports the biologic (genetic) basis for such progression (35–37). It is, however, increasingly recognized that the progression to renal damage may be accelerated by purely socioeconomic factors (inequalities in access and adherence to care) (19, 38, 39), which may result from the social environment in which patients experience their disease, as well as from psychosocial factors that may lead some patients to inadequate coping strategies and pernicious health behaviors.
In multivariable models of damage, poverty emerges as an important added factor to ethnicity; having more severe lupus (for example, in terms of more disease activity) places minority individuals in a precarious position from the outset. Their overall poor socioeconomic status including less structured families, fewer years of formal education, higher levels of poverty, and inadequate health insurance may act not in an additive manner but in a synergistic manner over the years to account for the negative intermediate and final disease outcomes we observe among these patients. The Puerto Rican Hispanics offer an interesting experience that distinguishes them from the Texan Hispanics. Despite their high proportions of Amerindian and African ancestries and their high levels of exposure to ultraviolet B light (40), Puerto Rican Hispanics tend to have a less serious disease; they also have a higher socioeconomic status than the Texan Hispanics, with nearly universal federally mandated access to health care and more years of formal education than the Caucasian majority in the continental US. Moreover, even though Puerto Rico is a US commonwealth, it is also a country in its own right. Many of the Texan Hispanics are recent immigrants (and probably many of them also illegal), which is not the case for the Puerto Ricans; having an illegal immigrant status is, with all probability, an additional factor negatively affecting the outcome of lupus among the Texan Hispanics. Unfortunately, we have not been able to explore this construct. However, low levels of acculturation per se, as would be the case with illegal immigrants, was not found to be associated with higher levels of disease activity (41). Furthermore, given that Puerto Ricans are residing in their place of origin and are not immigrants, they are probably less likely to feel discriminated against than the Texan Hispanics, particularly when dealing with the health care system. Overall, the odds are in favor of the Puerto Rican Hispanics to experience better intermediate and long-term outcomes; in fact, with their inclusion in LUMINA they have become, in many cases, the reference group in different multivariable exploratory analyses because they distinguish themselves from all other groups, Caucasians included. Finally, it goes without saying that the data generated from our LUMINA Hispanic patients cannot be generalized to all other Hispanic subgroups within or outside the US because their characteristics, both genetic and nongenetic, may substantially differ from the groups we have studied.
Further supporting the important role of environmental, socioeconomic/demographic, and psychosocial factors as determinants of the ethnic differences in SLE outcome is our mortality data. As noted in Figure 1, the difference between survival curves as a function of ethnicity is statistically significant. However, in multivariable models, poverty (and not ethnicity) consistently emerges as an independent contributor of this ultimate outcome. Of course, it is possible that in some patients the biologic component of ethnicity, rather than its socioeconomic component, may be the most important. All things considered, poverty and, to a lesser extent, inadequate coping strategies, damage accrued, disease activity, and age drive the mortality outcome. Furthermore, the biologic and nonbiologic basis of poverty including chronic stress, associated depression, and access and adherence to health care should be considered and explored (42–45).
As valuable as we believe the LUMINA cohort is, it is by no means perfect. First, some of the LUMINA patients have been recruited from tertiary referral centers; therefore, the data generated may not be fully applicable to community lupus patients. It should be pointed out, however, that at least for the African American and Caucasian patients, the LUMINA data are consistent with data reported in the literature (6, 46, 47). Second, the retention rate of LUMINA cohort members has not been uniform across the different ethnic groups, with African Americans having the highest rate of being lost to followup, which may differentially compromise the assumptions made about the longitudinal data (48). Finally, because the LUMINA protocol has evolved over a number of years, some constructs that had not been initially explored have been added (self-efficacy for example) (49); however, because data on these constructs are not available in all patients from the outset, they have been of limited use in multivariable models of outcome, because a significant number of patients are excluded when these constructs are part of the analyses. Measures to include a higher proportion of community-based patients and to improve the retention rates of those at risk of being lost to followup are now being implemented.
In the explanatory model depicted in Figure 2, are there specific points for the development of effective interventions aimed at modifying these disparities? Primary prevention is not yet possible in SLE, given its poorly understood etiology. Once the disease begins, however, where can we intervene to substantially alter the poor outcomes observed among ethnic minority patients? From a clinical viewpoint, African American and Hispanic patients, particularly those in the continental US, with an overall poor socioeconomic status should be considered at very high risk of having poor outcomes. As important as genetic factors are throughout the course of the disease, no interventions are yet available to modify them. Improving a patient's income or improving health care access in the current sociopolitical environment is not possible. Therefore, efforts should be directed at intervening on modifiable socioeconomic/demographic and psychosocial factors (50). The primary focus should be on educating these high-risk patients about the nature of their disease and the importance of adequately controlling the disease, while at the same time attempting to improve the patient's social network and his or her coping strategies. The charge should not be for the patients alone, but rather a team effort in which physicians, patients, and patients' families work together to maintain the disease in remission, so that premature death or undesirable organ system damage that may ultimately affect the patients' quality of life do not supervene.
As to which is the best method to deliver these educational and psychosocial interventions is not settled. In fact, regardless of whether such interventions have been delivered via telephone, the Internet, or other method, the intervention group has always exhibited a better outcome than the control group (51–55). Printed materials available from different sources may also be used, but they may not be tailored to the targeted population (language, literary level) (56), limiting their usefulness. Although the World Wide Web has information that is readily accessible, it is of varying quality and, often times, misleading; moreover, high-risk patients may have limited access to the World Wide Web or limited abilities to comprehend what they may find there. Therefore, improving outcomes among these patients with lupus has to be achieved one patient at a time; this can only be done in the context of the physician-patient encounter. Of course, these measures may be insufficient to achieve the desired outcome, unless simultaneous actions aimed at closing the gap between the rich and the poor are also implemented. As clinicians, however, we cannot wait for changes to occur at the societal or political levels, but those preventive and educational activities are certainly within our reach. Taking these actions, we would assist our patients at risk of losing years of life and/or important organ function.
Further research into the interplay of genetic and nongenetic factors is a priority if the basis for the disparities observed among patients with lupus is to be understood. To further examine the biologic component of ethnicity, admixture should be considered in multivariable models of outcome; furthermore, admixture can now be ascertained in a more accurate manner than in the past, given the strides made in both genotyping (many more ancestral markers can now be examined) and in computational genetics. LUMINA investigators are committed to pursuing these studies searching for the logical explanations and the proper solutions for the health disparities observed.