Lupus in Hispanics: A matter of serious concern

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Lupus in Hispanics: A matter of serious concern
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Guillermo J. Pons-Estel, MD, PhD
Graciela S. Alarcón, MD, MPH

Some diseases are either more serious or more frequent in US Hispanics, and systemic lupus erythematosus is one of them. This fact has not yet diffused to all providers, many of whom will be the ones dealing with these individuals when the disease first emerges.

In order to raise physicians’ awareness of this situation, we will briefly review here the salient features of lupus in US Hispanics and its short-term and long-term impact.

HISPANICS ARE THE LARGEST MINORITY IN THE UNITED STATES

Over the last 30 years, the Hispanic population in the United States has increased to the point that it is now the largest US minority group, and the fastest-growing. In the 2010 US census, Hispanics surpassed the 50 million mark.1 Physicians and health care providers are becoming familiar with this growing population and its ailments, but more needs to be done to familiarize them with specific conditions that are more frequent and more serious in US Hispanics.

No population-based study has yet defined the prevalence and incidence of lupus in US Hispanics. However, on the basis of hospital and outpatient visits in regions in which Hispanics make up a large part of the population, it has been inferred that this group has a higher frequency of lupus, probably as high as in African Americans.

Likewise, clinicians taking care of these patients have suspected that lupus is more severe in US Hispanics than in non-Hispanic Caucasians, but this was documented and brought to general attention only with the publication of reports from the Lupus in Minorities: Nature versus Nurture (LUMINA) study.2

LUMINA, a longitudinal study

LUMINA is a longitudinal study of 640 patients with lupus from four populations: Hispanic from Texas, Hispanic from Puerto Rico, African American, and Caucasian non-Hispanic (Table 1). At the time of recruitment, patients were at least 16 years old and had had lupus for 5 years or less. They come in for periodic visits to the University of Alabama at Birmingham, the University of Texas Health Science Center at Houston, and the University of Puerto Rico Medical Sciences Campus. Recruitment began in 1994 and finished in 2007. Follow-up ranges from 1 to 14 years, with a mean of 4.5 years.

LUMINA is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institutes of Health General Clinical Research Centers program, the National Center for Research Resources Clinical Research Infrastructure Initiative, the Mary Kirkland Center for Lupus Research Scholars Program, and Rheuminations Inc (New York, NY).

The purpose of the study is to shed light on the interplay of genetics and environment in this disease and, in the process, to raise awareness about the problem of lupus in Hispanics. In fact, much of the information in the following sections is from the LUMINA study.

HISPANICS ARE NOT A HOMOGENEOUS GROUP

In the United States, the term Hispanic describes anyone whose origin goes back to a Spanish-speaking country. However, US Hispanics are not a homogeneous racial group: they differ in genetics, culture, and problems.

The largest US Hispanic subgroup and the one more likely to be seen by US physicians is Hispanics of Mexican origin, who account for 66% of all US Hispanics. This group has a higher percentage of Amerindian genes than those of Puerto Rican ancestry.3 LUMINA researchers analyzed the DNA of 492 patients and found the following mixtures of genes3:

  • Hispanics in Texas (mostly of Mexican origin): 48% Amerindian, 18% African, 34% European
  • Hispanics from Puerto Rico: 20% Amerindian, 45% African, 35% European
  • African Americans: 0% Amerindian, 79% African, 21% European
  • Non-Hispanic Caucasians: 10% Amerindian, 18% African, 72% European.

Latin Americans of mixed European and Amerindian ancestry (which includes Aztec, Mayan, Quechuan, Aymaran, and other Central and South American groups) are called mestizos. Not all people in Latin America are mestizos: some are of European, African, or Asian ancestry, but in the United States they are all called Hispanics.

LUPUS DIFFERS AMONG SUBGROUPS

LUMINA research has revealed that lupus is heterogeneous also among US Hispanic subgroups. When people from Puerto Rico get lupus, it is generally less serious and devastating than in those from Mexico or Central America. Since US Hispanics of Mexican or Central American origin possess more Amerindian genes, this observation supports the notion that these genes are important contributors to the occurrence and expression of the disease.

Amerindian genes contribute to a greater susceptibility to lupus,4,5 although there is an interplay between genetic and nongenetic factors in the etiology and expression.6 Lupus starts at a younger age in Hispanics of predominantly Amerindian ancestry than in non-Hispanic Caucasians, and the onset is more likely to be acute.7

Renal involvement in these patients8 and mestizos from Latin America is rather common, probably as common as it is in US African Americans, and it tends to develop earlier than in non-Hispanic Caucasians.9 Amerindian ancestral genes, like African genes, contribute to the occurrence of renal disease in lupus patients.4 Furthermore, once nephritis ensues, end-stage renal disease occurs more often in US Hispanic and African American than in non-Hispanic Caucasian children, as demonstrated by Hiraki et al10 using national databases, and the same is true in adults, as shown in the LUMINA cohort.11

Other potentially serious manifestations of the disease are also more common, including hematologic and central nervous system manifestations. Not surprisingly, then, these patients show a higher degree of disease activity, both early in the course of the disease12,13 and over time.14

Table 1 compares the demographic and clinical features of LUMINA patients according to ethnicity. By and large, Hispanics from Texas have lower levels of education and income (comparable with levels in African Americans), and this can adversely affect the disease course by limiting these patients’ access to adequate care.15

DISEASE ACTIVITY AND ORGAN DAMAGE ARE GREATER IN HISPANICS

Disease activity in lupus reflects the ongoing immune-mediated inflammatory process. In LUMINA patients, regardless of the time at which disease activity was ascertained, it was higher in Hispanics from Texas and in African Americans than in non-Hispanic Caucasians and in Hispanics from Puerto Rico.7,12,16–18 Similar findings were seen in the Grupo Latinoamericano de Estudio de Lupus (GLADEL) cohort,13 in which mestizos and Hispanics of mixed African and European ancestry had higher maximum disease activity scores than non-Hispanic Caucasians.13

In addition, organ damage in lupus—the irreversible changes that occur in organ systems as a consequence of the disease or its treatments (eg, glucocorticoids, immunosuppressive drugs)—is more severe and develops sooner in Hispanics from Texas than in other groups.6,18,19 Using multivariate analysis, LUMINA investigators19 estimated the hazard ratio for the time until organ damage appeared for various risk factors, with values of 1 or greater indicating a shorter time and lower values indicating a longer time. Being a Hispanic from Texas carried a hazard ratio of 2.11 (95% confidence interval 1.15–3.88).

Because organ damage is an important and independent predictor of further damage20 and death,21 physicians need to take this disease quite seriously and try to prevent damage early in people at risk. To achieve that, the need to control disease activity must be balanced against the risk of overtreatment, as the important contribution of glucocorticoids to organ damage is well recognized.22

 

 

HISPANICS HAVE MORE COMORBIDITIES

Obesity, hypertension, diabetes, and metabolic syndrome are more common in US Hispanics, particularly those of Amerindian ancestry, than in the majority population of non-Hispanic Caucasians.23,24 The potential deleterious effects of glucocorticoids in patients already predisposed to these conditions need to be considered, balancing adequate disease control against the potential adverse effects.22

QUALITY OF LIFE IS WORSE WITH LUPUS

Whether it is measured with a generic instrument such as the Short Form 36 (SF-36), as it was in LUMINA,25 or with a disease-specific tool such as the Lupus-Pro, quality of life is significantly worsened by lupus. Furthermore, Fernandez et al26 found that a low level of health-related quality of life, as measured by the SF-6D version of the SF-36, was predictive of poor outcomes in LUMINA patients.

POVERTY, NOT ETHNICITY, ACCOUNTS FOR HIGHER MORTALITY RATE

As yet, we have no population-based data comparing survival in US Hispanic patients with lupus vs that of other population groups.

Figure 1. Kaplan-Meier survival curves for LUMINA patients as a function of ethnic group. African Americans and Texas Hispanics had a lower probability of survival than non-Hispanic Caucasians and and Puerto Rico Hispanics (log rank = 9.687; P = .021).

At first inspection, data from LUMINA indicate that Hispanics of primarily Amerindian ancestry have a lower survival rate than patients in other ethnic groups (Figure 1).6 However, when all other factors are taken into consideration, poverty, not ethnicity, is the major contributing factor (Table 2).6,27

This finding illustrates the important interplay between genetic and nongenetic factors in the course and final outcome of lupus, as already alluded to, although the exact relationship between them is not clear. It remains to be determined whether poverty is only a proxy for other population characteristics such as illiteracy, limited access to specialized care, limited access to medications, or cultural beliefs that may interfere with proper care.

ANTIMALARIAL DRUGS INCREASE SURVIVAL

Figure 2. Kaplan-Meier survival curve as a function of hydroxychloroquine use.

Using statistical analysis that adjusts for confounding by indication, we and others28–30 have shown that antimalarial drugs exert an independent and important protective effect on survival in lupus (Figure 2).

Important also is the protective effect of antimalarials on organ damage and the possibility of using them from disease outset in Hispanic patients at risk of early and rapid damage accrual,11 renal damage, and even lupus nephritis.31,32 This has very practical implications for the adequate and prompt management of these Hispanic patients.

PRACTICAL IMPLICATIONS

Lupus in US Hispanics is a serious disease with devastating consequences. Prompt diagnosis is paramount to prevent early organ damage and to prolong survival.

The disease may present in many different and unexpected ways, but joint pain, sun-sensitive rashes, renal involvement, cytopenias, and other manifestations should prompt the clinician to consider lupus in the differential diagnosis. Patients are often dismissed as having “arthritis” without being asked about other manifestations that may suggest a systemic connective tissue disease such as lupus. The same goes for skin rashes or unusual central nervous system manifestations.

The diagnosis of lupus is clinical, but some laboratory studies are essential to rule in or rule out renal or hematologic abnormalities and determine the level of disease activity. Tests usually ordered in patients suspected of having lupus include antinuclear antibody, complement levels, a complete blood cell count and differential, and a urinalysis. The need for additional tests depends on the results of the tests listed.

Once the disease is diagnosed, treatment should be tailored to the severity and type of clinical manifestations present. In general, glucocorticoids should be used at the smallest possible dose, antimalarials should be prescribed from the outset to all patients (following current guidelines in order to avoid ocular toxicity),33 and immunosuppressants and other treatments should be considered in certain instances. In parallel, consideration should be given to sun protection, adequate exercise, tobacco avoidance, osteoporosis and atherosclerosis prevention, planned conception, and compliance.

The goal in these people at risk is to control their lupus manifestations without causing undue damage, to preserve their quality of life, and to prevent an early demise.

References
  1. Humes KR, Jones NA, Ramirez RR. Overview of race and Hispanic origin: 2010. 2010 Census briefs; 2011. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed October 20, 2012.
  2. Reveille JD, Moulds JM, Ahn C, et al; for the LUMINA study Group. Systemic lupus erythematosus in three ethnic groups. I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity and disease onset. Arthritis Rheum 1998; 41:1161–1172.
  3. Alarcón GS, Beasley TM, Roseman JM, et al; LUMINA Study Group. Ethnic disparities in health and disease: the need to account for ancestral admixture when estimating the genetic contribution to both (LUMINA XXVI) (Letter). Lupus 2005; 14:867–868.
  4. Alarcón GS, Bastian HM, Beasley TM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 2006; 15:26–31.
  5. Sanchez E, Webb RD, Rasmussen A, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum 2010; 62:3722–3729.
  6. Fernández M, Alarcón GS, Calvo-Alén J, et al; LUMINA Study Group. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum 2007; 57:576–584.
  7. Alarcón GS, Friedman AW, Straaton KV, et al. Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs Nurture. Lupus 1999; 8:197–209.
  8. Bastian HM, Alarcón GS, Roseman JM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XL II: factors predictive of new or worsening proteinuria. Rheumatology (Oxford) 2007; 46:683–689.
  9. Burgos PI, McGwin G, Pons-Estel GJ, Reveille JD, Alarcón GS, Vilá LM. US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011; 70:393–394.
  10. Hiraki LT, Lu B, Alexander SR, et al. End-stage renal disease due to lupus nephritis among children in the US, 1995–2006. Arthritis Rheum 2011; 63:1988–1997.
  11. Pons-Estel GJ, Alarcón GS, McGwin G, et al. Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 2009; 61:830–839.
  12. Alarcón GS, Roseman J, Bartolucci AA, et al. Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 1998; 41:1173–1180.
  13. Pons-Estel BA, Catoggio LJ, Cardiel MH, et al; Grupo Latinoamericano de Estudio del Lupus. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics.” Medicine (Baltimore) 2004; 83:1–17.
  14. Alarcón GS, Calvo-Alén J, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time. Ann Rheum Dis 2006; 65:1168–1174.
  15. Vilá LM, Alarcón GS, McGwin G, Bastian HM, Fessler BJ, Reveille JD; Lumina Study Group. Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity, and damage accrual. Arthritis Rheum 2006; 55:799–806.
  16. Zhang J, González LA, Roseman JM, Vilá LM, Reveille JD, Alárcon GS. Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX. Lupus 2010; 19:727–733.
  17. Vilá LM, Alarcón GS, McGwin G, et al; LUMINA Study Group. Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations. Rheumatology (Oxford) 2004; 43:358–363.
  18. Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39:363–369.
  19. Toloza SM, Roseman JM, Alarcón GS, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage. Arthritis Rheum 2004; 50:3177–3186.
  20. Alarcón GS, Roseman JM, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage. Rheumatology (Oxford) 2004; 43:202–205.
  21. Alarcón GS, McGwin G, Bastian HM, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum 2001; 45:191–202.
  22. Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 2012 E-pub ahead of print.
  23. Jordan HT, Tabaei BP, Nash D, Angell SY, Chamany S, Kerker B. Metabolic syndrome among adults in New York City, 2004 New York City Health and Nutrition Examination Survey. Prev Chronic Dis 2012; 9:E04.
  24. Matthews KA, Sowers MF, Derby CA, et al. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women’s Health Across the Nation (SWAN). Am Heart J 2005; 149:1066–1073.
  25. Alarcón GS, McGwin G, Uribe A, et al. Systemic lupus erythematosus in a multiethnic lupus cohort (LUMINA). XVII. Predictors of selfreported health-related quality of life early in the disease course. Arthritis Rheum 2004; 51:465–474.
  26. Fernández M, Alarcón GS, McGwin G, et al; LUMINA Study Group. Using the Short Form 6D, as an overall measure of health, to predict damage accrual and mortality in patients with systemic lupus erythematosus: XLVII, results from a multiethnic US cohort. Arthritis Rheum 2007; 57:986–992.
  27. Durán S, Apte M, Alarcón GSLUMINA Study Group. Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups. J Natl Med Assoc 2007; 99:1196–1198.
  28. Ruiz-Irastorza G, Egurbide MV, Pijoan JI, et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006; 15:577–583.
  29. Alarcón GS, McGwin G, Bertoli AM, et al; LUMINA Study Group. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 2007; 66:1168–1172.
  30. Shinjo SK, Bonfá E, Wojdyla D, et al; Grupo Latino Americano de Estudio del Lupus Eritematoso (Gladel). Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum 2010; 62:855–862.
  31. Fessler BJ, Alarcón GS, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum 2005; 52:1473–1480.
  32. Pons-Estel GJ, Alarcón GS, Hachuel L, et al. Antimalarials have a protective effect against the development of renal disease in Latin American SLE patients. The 9th International Congress on SLE June 24–27, 2010, Vancouver, Canada. Lupus 2010; 19(suppl 1):31–32.
  33. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69:20–28.
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Guillermo J. Pons-Estel, MD, PhD
Internal Medicine, Hospital Clinic Barcelona, Spain; Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Graciela S. Alarcón, MD, MPH
Jane Knight Lowe Chair of Medicine in Rheumatology, Emeritus, The University of Alabama at Birmingham; Principal Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Address: Graciela S. Alarcón, MD, MPH, The University of Alabama at Birmingham, 510 20 Street S, FOT 830, Birmingham, AL 35294; e-mail [email protected]

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Addressing Disparities in Health Care
Author(s)
Guillermo J. Pons-Estel, MD, PhD
Graciela S. Alarcón, MD, MPH
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Graciela S. Alarcón, MD, MPH
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Guillermo J. Pons-Estel, MD, PhD
Internal Medicine, Hospital Clinic Barcelona, Spain; Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Graciela S. Alarcón, MD, MPH
Jane Knight Lowe Chair of Medicine in Rheumatology, Emeritus, The University of Alabama at Birmingham; Principal Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Address: Graciela S. Alarcón, MD, MPH, The University of Alabama at Birmingham, 510 20 Street S, FOT 830, Birmingham, AL 35294; e-mail [email protected]

Author and Disclosure Information

Guillermo J. Pons-Estel, MD, PhD
Internal Medicine, Hospital Clinic Barcelona, Spain; Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Graciela S. Alarcón, MD, MPH
Jane Knight Lowe Chair of Medicine in Rheumatology, Emeritus, The University of Alabama at Birmingham; Principal Investigator, Lupus in Minorities, Nature Versus Nurture (LUMINA) study

Address: Graciela S. Alarcón, MD, MPH, The University of Alabama at Birmingham, 510 20 Street S, FOT 830, Birmingham, AL 35294; e-mail [email protected]

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Some diseases are either more serious or more frequent in US Hispanics, and systemic lupus erythematosus is one of them. This fact has not yet diffused to all providers, many of whom will be the ones dealing with these individuals when the disease first emerges.

In order to raise physicians’ awareness of this situation, we will briefly review here the salient features of lupus in US Hispanics and its short-term and long-term impact.

HISPANICS ARE THE LARGEST MINORITY IN THE UNITED STATES

Over the last 30 years, the Hispanic population in the United States has increased to the point that it is now the largest US minority group, and the fastest-growing. In the 2010 US census, Hispanics surpassed the 50 million mark.1 Physicians and health care providers are becoming familiar with this growing population and its ailments, but more needs to be done to familiarize them with specific conditions that are more frequent and more serious in US Hispanics.

No population-based study has yet defined the prevalence and incidence of lupus in US Hispanics. However, on the basis of hospital and outpatient visits in regions in which Hispanics make up a large part of the population, it has been inferred that this group has a higher frequency of lupus, probably as high as in African Americans.

Likewise, clinicians taking care of these patients have suspected that lupus is more severe in US Hispanics than in non-Hispanic Caucasians, but this was documented and brought to general attention only with the publication of reports from the Lupus in Minorities: Nature versus Nurture (LUMINA) study.2

LUMINA, a longitudinal study

LUMINA is a longitudinal study of 640 patients with lupus from four populations: Hispanic from Texas, Hispanic from Puerto Rico, African American, and Caucasian non-Hispanic (Table 1). At the time of recruitment, patients were at least 16 years old and had had lupus for 5 years or less. They come in for periodic visits to the University of Alabama at Birmingham, the University of Texas Health Science Center at Houston, and the University of Puerto Rico Medical Sciences Campus. Recruitment began in 1994 and finished in 2007. Follow-up ranges from 1 to 14 years, with a mean of 4.5 years.

LUMINA is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institutes of Health General Clinical Research Centers program, the National Center for Research Resources Clinical Research Infrastructure Initiative, the Mary Kirkland Center for Lupus Research Scholars Program, and Rheuminations Inc (New York, NY).

The purpose of the study is to shed light on the interplay of genetics and environment in this disease and, in the process, to raise awareness about the problem of lupus in Hispanics. In fact, much of the information in the following sections is from the LUMINA study.

HISPANICS ARE NOT A HOMOGENEOUS GROUP

In the United States, the term Hispanic describes anyone whose origin goes back to a Spanish-speaking country. However, US Hispanics are not a homogeneous racial group: they differ in genetics, culture, and problems.

The largest US Hispanic subgroup and the one more likely to be seen by US physicians is Hispanics of Mexican origin, who account for 66% of all US Hispanics. This group has a higher percentage of Amerindian genes than those of Puerto Rican ancestry.3 LUMINA researchers analyzed the DNA of 492 patients and found the following mixtures of genes3:

  • Hispanics in Texas (mostly of Mexican origin): 48% Amerindian, 18% African, 34% European
  • Hispanics from Puerto Rico: 20% Amerindian, 45% African, 35% European
  • African Americans: 0% Amerindian, 79% African, 21% European
  • Non-Hispanic Caucasians: 10% Amerindian, 18% African, 72% European.

Latin Americans of mixed European and Amerindian ancestry (which includes Aztec, Mayan, Quechuan, Aymaran, and other Central and South American groups) are called mestizos. Not all people in Latin America are mestizos: some are of European, African, or Asian ancestry, but in the United States they are all called Hispanics.

LUPUS DIFFERS AMONG SUBGROUPS

LUMINA research has revealed that lupus is heterogeneous also among US Hispanic subgroups. When people from Puerto Rico get lupus, it is generally less serious and devastating than in those from Mexico or Central America. Since US Hispanics of Mexican or Central American origin possess more Amerindian genes, this observation supports the notion that these genes are important contributors to the occurrence and expression of the disease.

Amerindian genes contribute to a greater susceptibility to lupus,4,5 although there is an interplay between genetic and nongenetic factors in the etiology and expression.6 Lupus starts at a younger age in Hispanics of predominantly Amerindian ancestry than in non-Hispanic Caucasians, and the onset is more likely to be acute.7

Renal involvement in these patients8 and mestizos from Latin America is rather common, probably as common as it is in US African Americans, and it tends to develop earlier than in non-Hispanic Caucasians.9 Amerindian ancestral genes, like African genes, contribute to the occurrence of renal disease in lupus patients.4 Furthermore, once nephritis ensues, end-stage renal disease occurs more often in US Hispanic and African American than in non-Hispanic Caucasian children, as demonstrated by Hiraki et al10 using national databases, and the same is true in adults, as shown in the LUMINA cohort.11

Other potentially serious manifestations of the disease are also more common, including hematologic and central nervous system manifestations. Not surprisingly, then, these patients show a higher degree of disease activity, both early in the course of the disease12,13 and over time.14

Table 1 compares the demographic and clinical features of LUMINA patients according to ethnicity. By and large, Hispanics from Texas have lower levels of education and income (comparable with levels in African Americans), and this can adversely affect the disease course by limiting these patients’ access to adequate care.15

DISEASE ACTIVITY AND ORGAN DAMAGE ARE GREATER IN HISPANICS

Disease activity in lupus reflects the ongoing immune-mediated inflammatory process. In LUMINA patients, regardless of the time at which disease activity was ascertained, it was higher in Hispanics from Texas and in African Americans than in non-Hispanic Caucasians and in Hispanics from Puerto Rico.7,12,16–18 Similar findings were seen in the Grupo Latinoamericano de Estudio de Lupus (GLADEL) cohort,13 in which mestizos and Hispanics of mixed African and European ancestry had higher maximum disease activity scores than non-Hispanic Caucasians.13

In addition, organ damage in lupus—the irreversible changes that occur in organ systems as a consequence of the disease or its treatments (eg, glucocorticoids, immunosuppressive drugs)—is more severe and develops sooner in Hispanics from Texas than in other groups.6,18,19 Using multivariate analysis, LUMINA investigators19 estimated the hazard ratio for the time until organ damage appeared for various risk factors, with values of 1 or greater indicating a shorter time and lower values indicating a longer time. Being a Hispanic from Texas carried a hazard ratio of 2.11 (95% confidence interval 1.15–3.88).

Because organ damage is an important and independent predictor of further damage20 and death,21 physicians need to take this disease quite seriously and try to prevent damage early in people at risk. To achieve that, the need to control disease activity must be balanced against the risk of overtreatment, as the important contribution of glucocorticoids to organ damage is well recognized.22

 

 

HISPANICS HAVE MORE COMORBIDITIES

Obesity, hypertension, diabetes, and metabolic syndrome are more common in US Hispanics, particularly those of Amerindian ancestry, than in the majority population of non-Hispanic Caucasians.23,24 The potential deleterious effects of glucocorticoids in patients already predisposed to these conditions need to be considered, balancing adequate disease control against the potential adverse effects.22

QUALITY OF LIFE IS WORSE WITH LUPUS

Whether it is measured with a generic instrument such as the Short Form 36 (SF-36), as it was in LUMINA,25 or with a disease-specific tool such as the Lupus-Pro, quality of life is significantly worsened by lupus. Furthermore, Fernandez et al26 found that a low level of health-related quality of life, as measured by the SF-6D version of the SF-36, was predictive of poor outcomes in LUMINA patients.

POVERTY, NOT ETHNICITY, ACCOUNTS FOR HIGHER MORTALITY RATE

As yet, we have no population-based data comparing survival in US Hispanic patients with lupus vs that of other population groups.

Figure 1. Kaplan-Meier survival curves for LUMINA patients as a function of ethnic group. African Americans and Texas Hispanics had a lower probability of survival than non-Hispanic Caucasians and and Puerto Rico Hispanics (log rank = 9.687; P = .021).

At first inspection, data from LUMINA indicate that Hispanics of primarily Amerindian ancestry have a lower survival rate than patients in other ethnic groups (Figure 1).6 However, when all other factors are taken into consideration, poverty, not ethnicity, is the major contributing factor (Table 2).6,27

This finding illustrates the important interplay between genetic and nongenetic factors in the course and final outcome of lupus, as already alluded to, although the exact relationship between them is not clear. It remains to be determined whether poverty is only a proxy for other population characteristics such as illiteracy, limited access to specialized care, limited access to medications, or cultural beliefs that may interfere with proper care.

ANTIMALARIAL DRUGS INCREASE SURVIVAL

Figure 2. Kaplan-Meier survival curve as a function of hydroxychloroquine use.

Using statistical analysis that adjusts for confounding by indication, we and others28–30 have shown that antimalarial drugs exert an independent and important protective effect on survival in lupus (Figure 2).

Important also is the protective effect of antimalarials on organ damage and the possibility of using them from disease outset in Hispanic patients at risk of early and rapid damage accrual,11 renal damage, and even lupus nephritis.31,32 This has very practical implications for the adequate and prompt management of these Hispanic patients.

PRACTICAL IMPLICATIONS

Lupus in US Hispanics is a serious disease with devastating consequences. Prompt diagnosis is paramount to prevent early organ damage and to prolong survival.

The disease may present in many different and unexpected ways, but joint pain, sun-sensitive rashes, renal involvement, cytopenias, and other manifestations should prompt the clinician to consider lupus in the differential diagnosis. Patients are often dismissed as having “arthritis” without being asked about other manifestations that may suggest a systemic connective tissue disease such as lupus. The same goes for skin rashes or unusual central nervous system manifestations.

The diagnosis of lupus is clinical, but some laboratory studies are essential to rule in or rule out renal or hematologic abnormalities and determine the level of disease activity. Tests usually ordered in patients suspected of having lupus include antinuclear antibody, complement levels, a complete blood cell count and differential, and a urinalysis. The need for additional tests depends on the results of the tests listed.

Once the disease is diagnosed, treatment should be tailored to the severity and type of clinical manifestations present. In general, glucocorticoids should be used at the smallest possible dose, antimalarials should be prescribed from the outset to all patients (following current guidelines in order to avoid ocular toxicity),33 and immunosuppressants and other treatments should be considered in certain instances. In parallel, consideration should be given to sun protection, adequate exercise, tobacco avoidance, osteoporosis and atherosclerosis prevention, planned conception, and compliance.

The goal in these people at risk is to control their lupus manifestations without causing undue damage, to preserve their quality of life, and to prevent an early demise.

Some diseases are either more serious or more frequent in US Hispanics, and systemic lupus erythematosus is one of them. This fact has not yet diffused to all providers, many of whom will be the ones dealing with these individuals when the disease first emerges.

In order to raise physicians’ awareness of this situation, we will briefly review here the salient features of lupus in US Hispanics and its short-term and long-term impact.

HISPANICS ARE THE LARGEST MINORITY IN THE UNITED STATES

Over the last 30 years, the Hispanic population in the United States has increased to the point that it is now the largest US minority group, and the fastest-growing. In the 2010 US census, Hispanics surpassed the 50 million mark.1 Physicians and health care providers are becoming familiar with this growing population and its ailments, but more needs to be done to familiarize them with specific conditions that are more frequent and more serious in US Hispanics.

No population-based study has yet defined the prevalence and incidence of lupus in US Hispanics. However, on the basis of hospital and outpatient visits in regions in which Hispanics make up a large part of the population, it has been inferred that this group has a higher frequency of lupus, probably as high as in African Americans.

Likewise, clinicians taking care of these patients have suspected that lupus is more severe in US Hispanics than in non-Hispanic Caucasians, but this was documented and brought to general attention only with the publication of reports from the Lupus in Minorities: Nature versus Nurture (LUMINA) study.2

LUMINA, a longitudinal study

LUMINA is a longitudinal study of 640 patients with lupus from four populations: Hispanic from Texas, Hispanic from Puerto Rico, African American, and Caucasian non-Hispanic (Table 1). At the time of recruitment, patients were at least 16 years old and had had lupus for 5 years or less. They come in for periodic visits to the University of Alabama at Birmingham, the University of Texas Health Science Center at Houston, and the University of Puerto Rico Medical Sciences Campus. Recruitment began in 1994 and finished in 2007. Follow-up ranges from 1 to 14 years, with a mean of 4.5 years.

LUMINA is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institutes of Health General Clinical Research Centers program, the National Center for Research Resources Clinical Research Infrastructure Initiative, the Mary Kirkland Center for Lupus Research Scholars Program, and Rheuminations Inc (New York, NY).

The purpose of the study is to shed light on the interplay of genetics and environment in this disease and, in the process, to raise awareness about the problem of lupus in Hispanics. In fact, much of the information in the following sections is from the LUMINA study.

HISPANICS ARE NOT A HOMOGENEOUS GROUP

In the United States, the term Hispanic describes anyone whose origin goes back to a Spanish-speaking country. However, US Hispanics are not a homogeneous racial group: they differ in genetics, culture, and problems.

The largest US Hispanic subgroup and the one more likely to be seen by US physicians is Hispanics of Mexican origin, who account for 66% of all US Hispanics. This group has a higher percentage of Amerindian genes than those of Puerto Rican ancestry.3 LUMINA researchers analyzed the DNA of 492 patients and found the following mixtures of genes3:

  • Hispanics in Texas (mostly of Mexican origin): 48% Amerindian, 18% African, 34% European
  • Hispanics from Puerto Rico: 20% Amerindian, 45% African, 35% European
  • African Americans: 0% Amerindian, 79% African, 21% European
  • Non-Hispanic Caucasians: 10% Amerindian, 18% African, 72% European.

Latin Americans of mixed European and Amerindian ancestry (which includes Aztec, Mayan, Quechuan, Aymaran, and other Central and South American groups) are called mestizos. Not all people in Latin America are mestizos: some are of European, African, or Asian ancestry, but in the United States they are all called Hispanics.

LUPUS DIFFERS AMONG SUBGROUPS

LUMINA research has revealed that lupus is heterogeneous also among US Hispanic subgroups. When people from Puerto Rico get lupus, it is generally less serious and devastating than in those from Mexico or Central America. Since US Hispanics of Mexican or Central American origin possess more Amerindian genes, this observation supports the notion that these genes are important contributors to the occurrence and expression of the disease.

Amerindian genes contribute to a greater susceptibility to lupus,4,5 although there is an interplay between genetic and nongenetic factors in the etiology and expression.6 Lupus starts at a younger age in Hispanics of predominantly Amerindian ancestry than in non-Hispanic Caucasians, and the onset is more likely to be acute.7

Renal involvement in these patients8 and mestizos from Latin America is rather common, probably as common as it is in US African Americans, and it tends to develop earlier than in non-Hispanic Caucasians.9 Amerindian ancestral genes, like African genes, contribute to the occurrence of renal disease in lupus patients.4 Furthermore, once nephritis ensues, end-stage renal disease occurs more often in US Hispanic and African American than in non-Hispanic Caucasian children, as demonstrated by Hiraki et al10 using national databases, and the same is true in adults, as shown in the LUMINA cohort.11

Other potentially serious manifestations of the disease are also more common, including hematologic and central nervous system manifestations. Not surprisingly, then, these patients show a higher degree of disease activity, both early in the course of the disease12,13 and over time.14

Table 1 compares the demographic and clinical features of LUMINA patients according to ethnicity. By and large, Hispanics from Texas have lower levels of education and income (comparable with levels in African Americans), and this can adversely affect the disease course by limiting these patients’ access to adequate care.15

DISEASE ACTIVITY AND ORGAN DAMAGE ARE GREATER IN HISPANICS

Disease activity in lupus reflects the ongoing immune-mediated inflammatory process. In LUMINA patients, regardless of the time at which disease activity was ascertained, it was higher in Hispanics from Texas and in African Americans than in non-Hispanic Caucasians and in Hispanics from Puerto Rico.7,12,16–18 Similar findings were seen in the Grupo Latinoamericano de Estudio de Lupus (GLADEL) cohort,13 in which mestizos and Hispanics of mixed African and European ancestry had higher maximum disease activity scores than non-Hispanic Caucasians.13

In addition, organ damage in lupus—the irreversible changes that occur in organ systems as a consequence of the disease or its treatments (eg, glucocorticoids, immunosuppressive drugs)—is more severe and develops sooner in Hispanics from Texas than in other groups.6,18,19 Using multivariate analysis, LUMINA investigators19 estimated the hazard ratio for the time until organ damage appeared for various risk factors, with values of 1 or greater indicating a shorter time and lower values indicating a longer time. Being a Hispanic from Texas carried a hazard ratio of 2.11 (95% confidence interval 1.15–3.88).

Because organ damage is an important and independent predictor of further damage20 and death,21 physicians need to take this disease quite seriously and try to prevent damage early in people at risk. To achieve that, the need to control disease activity must be balanced against the risk of overtreatment, as the important contribution of glucocorticoids to organ damage is well recognized.22

 

 

HISPANICS HAVE MORE COMORBIDITIES

Obesity, hypertension, diabetes, and metabolic syndrome are more common in US Hispanics, particularly those of Amerindian ancestry, than in the majority population of non-Hispanic Caucasians.23,24 The potential deleterious effects of glucocorticoids in patients already predisposed to these conditions need to be considered, balancing adequate disease control against the potential adverse effects.22

QUALITY OF LIFE IS WORSE WITH LUPUS

Whether it is measured with a generic instrument such as the Short Form 36 (SF-36), as it was in LUMINA,25 or with a disease-specific tool such as the Lupus-Pro, quality of life is significantly worsened by lupus. Furthermore, Fernandez et al26 found that a low level of health-related quality of life, as measured by the SF-6D version of the SF-36, was predictive of poor outcomes in LUMINA patients.

POVERTY, NOT ETHNICITY, ACCOUNTS FOR HIGHER MORTALITY RATE

As yet, we have no population-based data comparing survival in US Hispanic patients with lupus vs that of other population groups.

Figure 1. Kaplan-Meier survival curves for LUMINA patients as a function of ethnic group. African Americans and Texas Hispanics had a lower probability of survival than non-Hispanic Caucasians and and Puerto Rico Hispanics (log rank = 9.687; P = .021).

At first inspection, data from LUMINA indicate that Hispanics of primarily Amerindian ancestry have a lower survival rate than patients in other ethnic groups (Figure 1).6 However, when all other factors are taken into consideration, poverty, not ethnicity, is the major contributing factor (Table 2).6,27

This finding illustrates the important interplay between genetic and nongenetic factors in the course and final outcome of lupus, as already alluded to, although the exact relationship between them is not clear. It remains to be determined whether poverty is only a proxy for other population characteristics such as illiteracy, limited access to specialized care, limited access to medications, or cultural beliefs that may interfere with proper care.

ANTIMALARIAL DRUGS INCREASE SURVIVAL

Figure 2. Kaplan-Meier survival curve as a function of hydroxychloroquine use.

Using statistical analysis that adjusts for confounding by indication, we and others28–30 have shown that antimalarial drugs exert an independent and important protective effect on survival in lupus (Figure 2).

Important also is the protective effect of antimalarials on organ damage and the possibility of using them from disease outset in Hispanic patients at risk of early and rapid damage accrual,11 renal damage, and even lupus nephritis.31,32 This has very practical implications for the adequate and prompt management of these Hispanic patients.

PRACTICAL IMPLICATIONS

Lupus in US Hispanics is a serious disease with devastating consequences. Prompt diagnosis is paramount to prevent early organ damage and to prolong survival.

The disease may present in many different and unexpected ways, but joint pain, sun-sensitive rashes, renal involvement, cytopenias, and other manifestations should prompt the clinician to consider lupus in the differential diagnosis. Patients are often dismissed as having “arthritis” without being asked about other manifestations that may suggest a systemic connective tissue disease such as lupus. The same goes for skin rashes or unusual central nervous system manifestations.

The diagnosis of lupus is clinical, but some laboratory studies are essential to rule in or rule out renal or hematologic abnormalities and determine the level of disease activity. Tests usually ordered in patients suspected of having lupus include antinuclear antibody, complement levels, a complete blood cell count and differential, and a urinalysis. The need for additional tests depends on the results of the tests listed.

Once the disease is diagnosed, treatment should be tailored to the severity and type of clinical manifestations present. In general, glucocorticoids should be used at the smallest possible dose, antimalarials should be prescribed from the outset to all patients (following current guidelines in order to avoid ocular toxicity),33 and immunosuppressants and other treatments should be considered in certain instances. In parallel, consideration should be given to sun protection, adequate exercise, tobacco avoidance, osteoporosis and atherosclerosis prevention, planned conception, and compliance.

The goal in these people at risk is to control their lupus manifestations without causing undue damage, to preserve their quality of life, and to prevent an early demise.

References
  1. Humes KR, Jones NA, Ramirez RR. Overview of race and Hispanic origin: 2010. 2010 Census briefs; 2011. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed October 20, 2012.
  2. Reveille JD, Moulds JM, Ahn C, et al; for the LUMINA study Group. Systemic lupus erythematosus in three ethnic groups. I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity and disease onset. Arthritis Rheum 1998; 41:1161–1172.
  3. Alarcón GS, Beasley TM, Roseman JM, et al; LUMINA Study Group. Ethnic disparities in health and disease: the need to account for ancestral admixture when estimating the genetic contribution to both (LUMINA XXVI) (Letter). Lupus 2005; 14:867–868.
  4. Alarcón GS, Bastian HM, Beasley TM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 2006; 15:26–31.
  5. Sanchez E, Webb RD, Rasmussen A, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum 2010; 62:3722–3729.
  6. Fernández M, Alarcón GS, Calvo-Alén J, et al; LUMINA Study Group. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum 2007; 57:576–584.
  7. Alarcón GS, Friedman AW, Straaton KV, et al. Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs Nurture. Lupus 1999; 8:197–209.
  8. Bastian HM, Alarcón GS, Roseman JM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XL II: factors predictive of new or worsening proteinuria. Rheumatology (Oxford) 2007; 46:683–689.
  9. Burgos PI, McGwin G, Pons-Estel GJ, Reveille JD, Alarcón GS, Vilá LM. US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011; 70:393–394.
  10. Hiraki LT, Lu B, Alexander SR, et al. End-stage renal disease due to lupus nephritis among children in the US, 1995–2006. Arthritis Rheum 2011; 63:1988–1997.
  11. Pons-Estel GJ, Alarcón GS, McGwin G, et al. Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 2009; 61:830–839.
  12. Alarcón GS, Roseman J, Bartolucci AA, et al. Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 1998; 41:1173–1180.
  13. Pons-Estel BA, Catoggio LJ, Cardiel MH, et al; Grupo Latinoamericano de Estudio del Lupus. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics.” Medicine (Baltimore) 2004; 83:1–17.
  14. Alarcón GS, Calvo-Alén J, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time. Ann Rheum Dis 2006; 65:1168–1174.
  15. Vilá LM, Alarcón GS, McGwin G, Bastian HM, Fessler BJ, Reveille JD; Lumina Study Group. Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity, and damage accrual. Arthritis Rheum 2006; 55:799–806.
  16. Zhang J, González LA, Roseman JM, Vilá LM, Reveille JD, Alárcon GS. Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX. Lupus 2010; 19:727–733.
  17. Vilá LM, Alarcón GS, McGwin G, et al; LUMINA Study Group. Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations. Rheumatology (Oxford) 2004; 43:358–363.
  18. Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39:363–369.
  19. Toloza SM, Roseman JM, Alarcón GS, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage. Arthritis Rheum 2004; 50:3177–3186.
  20. Alarcón GS, Roseman JM, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage. Rheumatology (Oxford) 2004; 43:202–205.
  21. Alarcón GS, McGwin G, Bastian HM, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum 2001; 45:191–202.
  22. Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 2012 E-pub ahead of print.
  23. Jordan HT, Tabaei BP, Nash D, Angell SY, Chamany S, Kerker B. Metabolic syndrome among adults in New York City, 2004 New York City Health and Nutrition Examination Survey. Prev Chronic Dis 2012; 9:E04.
  24. Matthews KA, Sowers MF, Derby CA, et al. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women’s Health Across the Nation (SWAN). Am Heart J 2005; 149:1066–1073.
  25. Alarcón GS, McGwin G, Uribe A, et al. Systemic lupus erythematosus in a multiethnic lupus cohort (LUMINA). XVII. Predictors of selfreported health-related quality of life early in the disease course. Arthritis Rheum 2004; 51:465–474.
  26. Fernández M, Alarcón GS, McGwin G, et al; LUMINA Study Group. Using the Short Form 6D, as an overall measure of health, to predict damage accrual and mortality in patients with systemic lupus erythematosus: XLVII, results from a multiethnic US cohort. Arthritis Rheum 2007; 57:986–992.
  27. Durán S, Apte M, Alarcón GSLUMINA Study Group. Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups. J Natl Med Assoc 2007; 99:1196–1198.
  28. Ruiz-Irastorza G, Egurbide MV, Pijoan JI, et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006; 15:577–583.
  29. Alarcón GS, McGwin G, Bertoli AM, et al; LUMINA Study Group. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 2007; 66:1168–1172.
  30. Shinjo SK, Bonfá E, Wojdyla D, et al; Grupo Latino Americano de Estudio del Lupus Eritematoso (Gladel). Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum 2010; 62:855–862.
  31. Fessler BJ, Alarcón GS, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum 2005; 52:1473–1480.
  32. Pons-Estel GJ, Alarcón GS, Hachuel L, et al. Antimalarials have a protective effect against the development of renal disease in Latin American SLE patients. The 9th International Congress on SLE June 24–27, 2010, Vancouver, Canada. Lupus 2010; 19(suppl 1):31–32.
  33. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69:20–28.
References
  1. Humes KR, Jones NA, Ramirez RR. Overview of race and Hispanic origin: 2010. 2010 Census briefs; 2011. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed October 20, 2012.
  2. Reveille JD, Moulds JM, Ahn C, et al; for the LUMINA study Group. Systemic lupus erythematosus in three ethnic groups. I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity and disease onset. Arthritis Rheum 1998; 41:1161–1172.
  3. Alarcón GS, Beasley TM, Roseman JM, et al; LUMINA Study Group. Ethnic disparities in health and disease: the need to account for ancestral admixture when estimating the genetic contribution to both (LUMINA XXVI) (Letter). Lupus 2005; 14:867–868.
  4. Alarcón GS, Bastian HM, Beasley TM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 2006; 15:26–31.
  5. Sanchez E, Webb RD, Rasmussen A, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum 2010; 62:3722–3729.
  6. Fernández M, Alarcón GS, Calvo-Alén J, et al; LUMINA Study Group. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum 2007; 57:576–584.
  7. Alarcón GS, Friedman AW, Straaton KV, et al. Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs Nurture. Lupus 1999; 8:197–209.
  8. Bastian HM, Alarcón GS, Roseman JM, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XL II: factors predictive of new or worsening proteinuria. Rheumatology (Oxford) 2007; 46:683–689.
  9. Burgos PI, McGwin G, Pons-Estel GJ, Reveille JD, Alarcón GS, Vilá LM. US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011; 70:393–394.
  10. Hiraki LT, Lu B, Alexander SR, et al. End-stage renal disease due to lupus nephritis among children in the US, 1995–2006. Arthritis Rheum 2011; 63:1988–1997.
  11. Pons-Estel GJ, Alarcón GS, McGwin G, et al. Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 2009; 61:830–839.
  12. Alarcón GS, Roseman J, Bartolucci AA, et al. Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 1998; 41:1173–1180.
  13. Pons-Estel BA, Catoggio LJ, Cardiel MH, et al; Grupo Latinoamericano de Estudio del Lupus. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics.” Medicine (Baltimore) 2004; 83:1–17.
  14. Alarcón GS, Calvo-Alén J, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time. Ann Rheum Dis 2006; 65:1168–1174.
  15. Vilá LM, Alarcón GS, McGwin G, Bastian HM, Fessler BJ, Reveille JD; Lumina Study Group. Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity, and damage accrual. Arthritis Rheum 2006; 55:799–806.
  16. Zhang J, González LA, Roseman JM, Vilá LM, Reveille JD, Alárcon GS. Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX. Lupus 2010; 19:727–733.
  17. Vilá LM, Alarcón GS, McGwin G, et al; LUMINA Study Group. Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations. Rheumatology (Oxford) 2004; 43:358–363.
  18. Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39:363–369.
  19. Toloza SM, Roseman JM, Alarcón GS, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage. Arthritis Rheum 2004; 50:3177–3186.
  20. Alarcón GS, Roseman JM, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage. Rheumatology (Oxford) 2004; 43:202–205.
  21. Alarcón GS, McGwin G, Bastian HM, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum 2001; 45:191–202.
  22. Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 2012 E-pub ahead of print.
  23. Jordan HT, Tabaei BP, Nash D, Angell SY, Chamany S, Kerker B. Metabolic syndrome among adults in New York City, 2004 New York City Health and Nutrition Examination Survey. Prev Chronic Dis 2012; 9:E04.
  24. Matthews KA, Sowers MF, Derby CA, et al. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women’s Health Across the Nation (SWAN). Am Heart J 2005; 149:1066–1073.
  25. Alarcón GS, McGwin G, Uribe A, et al. Systemic lupus erythematosus in a multiethnic lupus cohort (LUMINA). XVII. Predictors of selfreported health-related quality of life early in the disease course. Arthritis Rheum 2004; 51:465–474.
  26. Fernández M, Alarcón GS, McGwin G, et al; LUMINA Study Group. Using the Short Form 6D, as an overall measure of health, to predict damage accrual and mortality in patients with systemic lupus erythematosus: XLVII, results from a multiethnic US cohort. Arthritis Rheum 2007; 57:986–992.
  27. Durán S, Apte M, Alarcón GSLUMINA Study Group. Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups. J Natl Med Assoc 2007; 99:1196–1198.
  28. Ruiz-Irastorza G, Egurbide MV, Pijoan JI, et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006; 15:577–583.
  29. Alarcón GS, McGwin G, Bertoli AM, et al; LUMINA Study Group. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 2007; 66:1168–1172.
  30. Shinjo SK, Bonfá E, Wojdyla D, et al; Grupo Latino Americano de Estudio del Lupus Eritematoso (Gladel). Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum 2010; 62:855–862.
  31. Fessler BJ, Alarcón GS, McGwin G, et al; LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum 2005; 52:1473–1480.
  32. Pons-Estel GJ, Alarcón GS, Hachuel L, et al. Antimalarials have a protective effect against the development of renal disease in Latin American SLE patients. The 9th International Congress on SLE June 24–27, 2010, Vancouver, Canada. Lupus 2010; 19(suppl 1):31–32.
  33. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69:20–28.
Issue
Cleveland Clinic Journal of Medicine - 79(12)
Issue
Cleveland Clinic Journal of Medicine - 79(12)
Page Number
824-834
Page Number
824-834
Publications
Cleveland Clinic Journal of Medicine
Publications
Cleveland Clinic Journal of Medicine
Topics
Immunology
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Article
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Lupus in Hispanics: A matter of serious concern
Display Headline
Lupus in Hispanics: A matter of serious concern
Sections
Addressing Disparities in Health Care
Inside the Article

KEY POINTS

  • Amerindian genes contribute to a greater susceptibility to lupus, although there is an interplay between genetic and nongenetic factors in its etiology and expression.
  • In large studies, disease activity and organ damage were greater in African Americans and in Hispanics from Texas than in Caucasians and Hispanics from Puerto Rico.
  • Hispanics of primarily Amerindian ancestry (which includes Aztec, Mayan, Quechuan, Aymaran, and other Central and South American groups) have a lower survival rate than patients in other ethnic groups, but poverty is the responsible factor.
  • The need to control disease activity with corticosteroids must be balanced against the risk of overtreatment and organ damage.
  • Antimalarial drugs such as chloroquine and hydroxychloroquine should be prescribed from the outset to all patients with lupus, according to current guidelines designed to avoid ocular toxicity.
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