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Autoimmune Dis
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Autoimmune Diseases
2090-0422
2090-0430
Wiley

10.1155/2024/5593302
Research Article
Clinical Characteristics of Systemic Lupus Erythematosus in Caucasians and Latin American Hispanics: Data from a Single Tertiary Center
https://orcid.org/0000-0003-0614-2950
Marri Luca 1 2
Vassallo Chiara 2
https://orcid.org/0000-0002-0834-5586
Esposito Pasquale 1 3
Bottaro Luca 1
https://orcid.org/0000-0001-9070-8878
De Palma Raffaele 1 2
https://orcid.org/0000-0003-1267-4320
Negrini Simone negrini@unige.it
1 2
1 Department of Internal Medicine University of Genova, Genova 16132, Italy
2 Internal Medicine Clinical Immunology and Translational Medicine Unit IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy
3 Nephrology Dialysis and Transplantation Unit IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy
Academic Editor: Rizgar Mageed

2024
27 8 2024
2024 559330225 3 2024
20 5 2024
8 8 2024
Copyright © 2024 Luca Marri et al.
2024
https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background

Different studies report that systemic lupus erythematosus (SLE) tends to have a more aggressive course in Hispanic patients. In this study, we analysed epidemiologic, clinical, and laboratory characteristics in a cohort of Hispanic and Caucasian lupus patients in the context of Italian health service, which provides free access to care to all citizens, thus mitigating the impact of socioeconomic factors that negatively influence the course of the disease in ethnic minorities.

Methods

This single-center retrospective study was conducted at the San Martino Hospital “Lupus Clinic” in Genoa, Italy. Patients ≥18 years with a confirmed diagnosis of SLE and definite ethnicity (Hispanic or Caucasian) were recruited.

Results

A total of 126 patients (90 Caucasians and 36 Hispanics) were enrolled. We compared epidemiologic characteristics, clinical features, autoantibodies profile, and treatment options without evidencing any statistically significant difference between the two groups, except for disease duration, which was higher in the Caucasian group (20.4 years versus 14.2 years in the Hispanic group, P=0.002) and SLICC damage index, which was greater in Caucasian patients (2.11 versus 1.88 in Hispanics, P=0.037), but this difference was no longer significant after correction for disease duration (P=0.096).

Conclusions

In our cohort, Hispanic ethnicity is not associated with worse disease features and outcomes. Therefore, we speculated that socioeconomic factors, in particular, free access to healthcare, might be more relevant in influencing the course of the disease than genetic background.
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pmc1. Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease resulting from a complex interaction of genetic, epigenetic, and environmental favouring factors. The natural history of SLE is typically relapsing-remitting with pleomorphic clinical manifestations potentially involving every organ or tissue [1].

Several studies have shown that some sociodemographic predictors such as ethnicity, gender, age, income, education, and access to healthcare are important variables associated with the epidemiology and the outcome of SLE [2, 3]. In reference to ethnicity, incidence and prevalence rates are consistently higher among those of African, Hispanic, or Asian descent across studies from different countries. Notably, in these same ethnic groups, SLE seems to be more severe with higher disease activity and more damage accrual than in Caucasians [4–6].

Immigration can be considered a relatively new phenomenon in Italy, a country historically characterized by emigration. In the last decades, Genoa, similar to other Italian cities, has experienced a significant increase in immigration, especially from Latin America. According to the Italian National Institute of Statistics (ISTAT), foreign citizens (about 75000) account for 9.1% of the total population of the metropolitan area of Genoa [7]. The most represented foreign community in Genoa are Ecuadorians (around 20% of foreigners), and also other Latin American populations are present in the territory. Globally, Latin American/Hispanic is the most represented non-White ethnicity in our territory [7].

Several studies have pointed out that Hispanics seem to present a higher incidence of SLE, a more severe course of the disease, and poorer outcomes as compared to Caucasians. The LUMINA study was based on a prospective cohort specifically established to analyse minority SLE patients in the United States [8–10]. In this cohort, Texas Hispanics showed greater disease activity, accelerated damage accrual, increased frequency and severity of renal disease, and diminished survival than Caucasians and Puerto Rican Hispanics. Interestingly, Hispanics from Puerto Rico not only have a lesser proportion of ancestral Native American genes but also benefit from better socioeconomic conditions than Texas Hispanics [9, 11–13]. In the GLADEL study, Afro-Latin Americans and Mestizos had more severe SLE and develop renal disease at a higher proportion than Whites [14, 15]. Analysing disease features and outcomes in US SLE patients of Hispanic origin and their Mestizo counterparts in Latin America from the LUMINA and GLADEL cohorts, it emerged that US Hispanics seemed to have a poorer prognosis, despite a comparable genetic background, thus suggesting that socioeconomic factors may account for these discrepancies [16]. Similarly, Mexican patients living in Mexico had lower levels of disease activity and damage with respect to Texan Hispanics from the LUMINA cohort, of whom 95% are of Mexican descent [17]. Calvo-Alén et al. reported that Hispanics with a strong Amerindian background (US Hispano-Americans) have a more serious disease than that observed in Hispanics from Northern Spain, suggesting that the genetic pool and also socioeconomic differences between these two Hispanic subgroups probably explain for these findings [10]. Data from the RELESSER registry confirm this observation indicating that Latin-American Hispanic patients have an increased frequency of lupus nephritis and display higher disease severity than European Caucasians Hispanics [18, 19]. The multiethnic study profile showed that renal involvement is more frequent among non-Caucasian patients, and, within them, Hispanic patients seem to be at a higher risk of renal damage [20, 21]. The CDC, through five different US cohorts, reports that Hispanics have a higher incidence and prevalence of lupus and are at an increased risk of severe manifestations and early development of lupus nephritis, thrombocytopenia, and antiphospholipid syndrome [22].

Ethnicity also impacts drug response. In the short-term induction therapy for lupus nephritis, mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) have a similar overall efficacy; however, a significantly higher response to MMF with respect to CYC was observed in patients of Mestizo descent and individuals of Hispanic origin [23]. In the EXPLORER trial on rituximab in nonrenal lupus, Hispanic patients achieved significantly higher major clinical responses compared with other groups [24]. Unfortunately, limited access to these drugs in several Latin American countries, due primarily to cost issues, or in developed countries, owing to disparities in healthcare access often experienced by racial and ethnic minorities, hinders these patients from accessing the most effective medical care. This aspect is clearly exemplified by the recent GLADEL—Pan-American League of Associations of Rheumatology (PANLAR) recommendations, where not only the efficacy but also the costs and availability of a given medication strongly influence its usage in clinical practice of specific geographical context [25].

Overall, the abovementioned investigations indicate that Hispanics tend to have an increased prevalence, disease severity, risk of complications, and a worse outcome compared to Caucasian patients. Despite the consistent literature on the subject, the explanation of these disparities has not been univocally established, and differences in biologic/genetic background (e.g., higher proportion of ancestral Native American genes) and socioeconomic factors (e.g., unfavourable economic status, education, or access to healthcare) might contribute in a nonmutually exclusive manner.

The purpose of this study was to analyse epidemiological characteristics, clinical and laboratory features, and treatment options in an Italian cohort of SLE patients of Hispanic and Caucasian ethnicity. This study was conducted in the context of the Italian health system which provides universal coverage to all citizens, allowing to mitigate, at least in part, the bias due to socioeconomic disparities in healthcare access that typically impact racial/ethnic minorities.

2. Materials and Methods

2.1. Study Design

This is a retrospective and cross-sectional single-center study. The study was conducted in compliance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study was approved on October 17, 2022, by the local medical ethical committee (Liguria Regional Ethical Committee registry number 485/2022-DB id 12602), and all patients provided informed consent before the inclusion in the study.

2.2. Patients

Patients ≥18 years old with SLE, defined according to the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) 2019 classification criteria (2019 EULAR/ACR) [26], and definite ethnicity (see below) were recruited at San Martino Hospital Lupus Clinic, a dedicated SLE clinic located in Genoa, Italy, between October 2022 and March 2023. Caucasian patients were defined as those born in Italy with a Caucasian phenotype and without known non-Caucasian ancestors. Hispanic patients were defined as those immigrated from Latin American countries with an American-Indian phenotype with Latin American parents and without known African or European ancestors [18]. All Hispanic patients had universal health coverage, as is the case with all Caucasian subjects.

Data were extrapolated from medical records and transferred to a fully deidentified database for statistical analysis. Collected variables included sociodemographic and clinical characteristics, as well as laboratory characteristics.

Clinical manifestations have been defined according to the EULAR/ACR 2019 definition system and organized in various clinical domains (hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, and renal) [26]. The EULAR/ACR 2019 score has been assessed at disease onset and at the time of enrolment in the study [26]. The 2023 EULAR/ACR Classification Criteria have been adopted in order to define the presence of antiphospholipid syndrome (APS) [27].

Disease activity has been calculated by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [28]. Low Disease Activity State (LLDAS) was defined as SLEDAI-2K ≤ 4 without activity in major organ systems or new disease activity, Physician Global Assessment (PGA) ≤1, prednisone dose ≤7.5 mg/day, and/or immunosuppressive-biologic-antimalarial drugs on maintenance dose [29]. Accumulation of damage has been ascertained through the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SDI), a score system that records irreversible damage that has occurred since the onset of lupus in 12 different systems [30].

Immunological laboratory tests included antinuclear antibody (assessed on Hep-2 cells by indirect immunofluorescence), double-stranded DNA antibodies (assessed on Crithidia luciliae by indirect immunofluorescence), anti-Sm antibodies (by immunoenzymatic assay), antiphospholipid antibodies (i.e., anti-cardiolipin and anti-β2-glycoprotein antibodies by immunoenzymatic assay), presence of lupus anticoagulant (LAC), and complement levels.

Current treatment (at last visit) and previous therapeutic regimens were obtained from medical records.

2.3. Statistical Analysis

Overall comparisons of the clinical and immunologic categorical variables among the two ethnic groups were performed using cross tabulations, and their significance was assessed by means of the chi-square/Fisher's exact test. Regarding continuous variables, the comparison among the two groups was assessed using parametric (Student's t-test) or nonparametric (Mann–Whitney U test) test according to the distribution of the analysed variables and the sample size. For some relevant variables, a multivariate analysis was performed using a logistic regression model in order to estimate the adjusted odds ratio of each variable. Spearman's rho coefficient was used to assess correlations. All statistical analyses were performed with Jamovi [31].

3. Results

3.1. Demographic Factors

Overall, 126 SLE patients were enrolled; 90 of them were Caucasians (71%) and 36 were Hispanics (29%). Among Hispanics, most of them were from Ecuador (64%) and Peru (19%). The remaining percentage of Hispanic patients (17%) were from other geographical areas of Latin America. All Hispanics enrolled in this study were first-generation immigrants. As expected, the majority of patients in both ethnic groups were female, and the mean age at the enrolment was 51.6 and 47.8 years in Caucasians and Hispanics, respectively. Among Hispanic patients, 89% received their SLE diagnosis in Italy, while the remaining percentage were diagnosed in their countries of origin. The comparison of the two ethnic groups showed no significant differences in the univariate analysis for gender and age. The demographic variables are detailed in Table 1.

3.2. Clinical and Laboratory Variables

Mean age at disease onset, defined as age of onset of first SLE-related manifestation(s), was similar in Caucasians (31.1 years) and in Hispanic patients (33.6 years). Disease duration was significantly higher in Caucasians (20.4 years) than in the Hispanic group (14.2 years). Among Hispanic patients, 89% (32 out of 36) were diagnosed in Italy. Compared to those diagnosed in their countries of birth (11%), no significant differences in age or disease duration were observed (48.6 ± 9.6 vs. 48.3 ± 20.1 years, P=0.894; 13.47 ± 8.5 vs. 20.0 ± 15.9 years, P=0.413, respectively).

At onset, overt disease (fulfilling SLE classification criteria) was present in 38.9% and 52.7% of Caucasians and Hispanics, respectively (P=0.154), whereas the remaining patients of both groups presented initially as undifferentiated connective tissue disease and later developed additional clinical/laboratory manifestations of complete SLE. The mean ACR/EULAR 2019 score assessed at the time of enrolment (last visit) was similar in the two ethnicities, independently from disease duration.

As shown in Table 2, the cumulative prevalence of clinical manifestations (articular, hematologic, renal, mucocutaneous, neuropsychiatric, and serositis) was comparable among the two ethnic groups. These results were maintained after adjustment for disease duration. The detailed analysis of the hematologic domain showed no significant differences between Caucasians and Hispanics in the prevalence of autoimmune hemolytic anaemia (17.8 vs. 19.4%, P=0.804), autoimmune thrombocytopenia (32.2% vs. 19.4%, P=0.192), and leukopenia (44.4% vs. 55.6%, P=0.259). Similarly, the prevalence of specific lupus skin manifestations showed no significant differences in acute (25.6% vs. 33.3%, P=0.379), subacute (6.7% vs. 0%, P=0.182), and chronic cutaneous lupus (15.6% vs. 5.6%, P=0.151) as well as photosensitivity (24.4% vs. 27.8%, P=0.698) in the two ethnicities.

The percentage of patients with renal involvement was not significantly different in Caucasians and Hispanics (62.2% vs. 50.0%, respectively). A kidney biopsy was performed in 54 of the 74 patients who developed renal manifestations (relevant proteinuria and/or increase in the serum creatinine), and histologic LN was confirmed in all samples. The percentage of eligible patients who underwent renal biopsy was similar in the two ethnic groups (71.4% Caucasians vs. 77.8% Hispanics, P=0.764). The most common forms of LN observed in our cohort were focal and diffuse proliferative glomerulonephritis (classes III and IV) with no significant differences between the two ethnic groups (77.5% Caucasians vs. 64.3% Hispanics, P=0.479).

As concern immunological markers of disease, no significant differences in the prevalence of anti-dsDNA and anti-Sm antibodies were found across the two ethnic groups (Table 2). Complement reduction (C3 and/or C4 decreased below the lower laboratory limit) was found in the majority of patients in both populations (Table 2) and associated with a higher prevalence of hematologic manifestations (OR, 5.51, 95% CI, 2.16–14.1, P < 0.001). Caucasians and Hispanics tested positive for antiphospholipid antibodies in at least two determinations in about one-third of patients of each group. Of those, 42.9% Caucasians and 46.2% Hispanics developed clinical manifestations (thrombotic and/or obstetric events), thus fulfilling the criteria for APS with no difference among the two ethnicities (Table 2).

As concern disease activity, LLDAS was assessed at the last clinical evaluation, with no significant differences between Caucasians and Hispanics (respectively, 88.9% vs. 80.6%, P=0.252). The SDI scores, calculated at the time of enrolment, were significantly higher in Caucasian than in Hispanic patients (2.11 ± 1.91 and 1.23 ± 1.31, respectively; P=0.037) in the univariate analysis. As expected, we found a correlation between disease duration and SDI score (rho = 0.227, P=0.023). Accordingly, the difference in the SDI score between Caucasians and Hispanics lost statistical significance after adjustment for disease duration (P=0.096 in the multivariate analysis).

3.3. Therapy

During the course of the disease, all patients received different treatment associations including corticosteroids (CCs) and/or hydroxychloroquine (HCQ) and/or disease-modifying antirheumatic agents (conventional synthetic and/or biologic DMARDs). A comparison of the two ethnic groups showed no significant differences in treatment strategies employed (Table 3). Regarding treatments evaluated during the last visit, most of the patients were taking low dose of CCs, defined as an equivalent dose of prednisone ≤7.5 mg/day, with no difference in the two ethnicities. Similarly, the percentage of Caucasian and Hispanic patients on antimalarials and/or DMARDs was comparable in the two groups (Table 3).

4. Discussion

In this study, we analysed demographics, clinical, and laboratory features of a cohort of patients affected by SLE, comparing data from Caucasians and Hispanics.

Regarding demographic factors, the two groups were homogeneous in terms of gender and age. As expected, the majority of Hispanic patients were from Ecuador, the most represented foreign community in Genoa [7]. In the current literature, Hispanic patients originate from many different countries (e.g., multicentric studies) or from a single specific country (nation-based single-center studies) or country of origin is simply not reported. Since it is now clear that not all “Hispanics” are the same, our data, derived mainly from Ecuadorian patients, might not be directly compared with other studies [32]. Importantly, Ecuador's population shows high degrees of Native American genetic ancestry [33], a genetic background evoked as an independent factor in SLE onset and severity [2, 34–36]; thus, it might be considered highly representative of the Hispanic patient population.

With regard to clinical characteristics, disease duration was significantly longer in Caucasian than in Hispanic patients (21 vs. 14 years, respectively). This observation may be explained by the fact that immigration is a recent phenomenon in our region and, consequently, our cohort of Hispanic patients includes subjects with a more recent diagnosis of SLE compared to the Caucasian cohort.

The cumulative incidence of clinical manifestations related to SLE, including articular, hematologic, renal, and neuropsychiatric disorders, and serositis as well as mucocutaneous lupus, was evaluated in Hispanic and Caucasian patients without evidencing significant differences in the two ethnicities, even after adjustment for disease duration.

Different studies report a higher prevalence and severity of renal disease in non-Caucasian patients, including Hispanics [9, 11, 12, 14, 15, 18–22]. In our cohort, we did not find significant differences in terms of prevalence of LN, percentage of biopsies performed, and histological classes among the two groups.

Serositis and cytopenias (in particular, thrombocytopenia and leukopenia) are reported in the literature as more frequent in Hispanics than in Caucasians, although to a lesser extent than renal damage [6, 12, 20]. In our study, both populations exhibit a similar prevalence of serosal and hematologic complications, with the latter encompassing single manifestations such as leukopenia, thrombocytopenia, or autoimmune hemolytic anaemia.

In relation to immunologic laboratory features, such as anti-dsDNA antibodies, anti-Sm antibodies, and complement reduction, no differences emerged comparing the two ethnicities. In agreement with what was reported in the literature, complement reduction was correlated with a higher prevalence of hematologic manifestations [37, 38].

Antiphospholipid syndrome (APS) is characterized by vascular thrombosis, gestational morbidity, and/or nonthrombotic manifestations in the presence of antiphospholipid antibodies [39]. According to the literature, antiphospholipid antibodies can be detected in up to 40% of SLE patients, but only one-third of them will develop clinical manifestations with no clear differences among various races/ethnicities [40]. Consistently, in our cohort, we find a comparable prevalence of aPL positivity and APS, with no differences between Caucasian and Hispanic SLE patients.

Several authors have reported that Hispanics with SLE experience higher disease activity and disease-related damage than Caucasians [9, 11, 12, 18, 19, 41]. Regarding disease activity, we assessed LLDAS at the last clinical evaluation, finding no significant differences between the two ethnic groups. Overall, we found that a large proportion of patients in both groups achieved LLDAS at the time of this study. This observation may be explained, at least partially, by the long disease duration characterizing our cohort (globally 19.5 years) compared to patients' populations analysed in other studies. Indeed, it is well known that SLE tends to be more active in the first years after disease onset, while patients with long disease duration show a higher prevalence of low disease activity and remission [42–44]. Damage accrual related to SLE, assessed by the SDI score, was higher in Caucasians, but this difference disappeared after adjustment for disease duration. This observation is not surprising since the damage is correlated to disease duration which, in our cohort, was significantly higher in Caucasians [45].

Both Hispanics and Caucasians received comparable therapeutic options during the course of the disease. As widely recommended, the majority of patients were treated with hydroxychloroquine, a drug characterized by multiple positive effects in SLE with an optimal safety profile [46]. In our cohort, a substantial proportion of patients either discontinued or were on low-dose steroid therapy, to achieve and maintain this result, and the use of steroid-sparing agents, such as immunomodulating-immunosuppressive drugs, is essential [46]. In many countries, the primary constraint in prescribing certain immunosuppressants is related to their cost. In our cohort, due to the policy of the Italian healthcare system, the use of immunosuppressive drugs relies primarily on medical judgement, independent of patients' economic conditions, thus granting the optimal treatment strategy for all patients.

As mentioned, several studies have reported that SLE tends to present a more severe course in Hispanics compared to Caucasians. Unfortunately, the frequent association between non-Caucasian ethnicities and unfavourable socioeconomic status makes biologic and environmental contributions difficult to disentangle. The existing data in the literature predominantly stem from studies conducted in countries where migration is a long-standing phenomenon. Consequently, these findings may not readily translate to countries with a more recent history of immigration, such as Italy. In addition, the majority of these studies are from the American continent where the socioeconomic status of minorities, including access to healthcare, may significantly differ compared to European countries, especially Italy, where the healthcare system provides universal coverage and a largely free access to care to all citizens. To the best of our knowledge, our study is the first investigation conducted in Italy on this subject, and the second one in Europe alongside the Spanish registry RELESSER [18, 19].

There are limitations in this study, which necessarily inform the interpretation of our results. Firstly, the power of our study is limited by the retrospective design, monocentric nature, and the relatively small sample size. The low number of patients might have led to a type II statistical error, and data derived from a single center may limit their generalizability and external validity. Furthermore, the cross-sectional and retrospective design inherently limits our ability to establish causal relationships and introduces potential bias due to the heterogeneity of the studied populations, particularly regarding variations in disease duration. This variability may indeed influence the expression of time-related clinical manifestations and consequently affect the observed results. Nevertheless, the monocentric structure of our study might potentially provide more homogeneous and uniform data as compared to multicentric cohorts. As noted above, all Hispanic SLE patients enrolled in this study were first-generation immigrants. This may represent a limitation of this study related to a bias known as “healthy migrant effect,” a theory postulating that healthy people are more likely to migrate and consequently first-generation immigrants are healthier than the average person in both the home and host countries [47, 48]. The fact that the majority of Hispanic patients have been diagnosed in Italy may be attributed to this phenomenon. The healthy migrant effect could further account for the observation that our cohort of Hispanic patients have a milder-than-expected disease course, similar to that observed in Caucasians, implying that patients with early-onset SLE and/or more severe disease might have been unable to migrate. Interestingly, data from GLADEL have shown that older age at diagnosis is associated with a less severe course of disease [3, 49]. An additional limitation of our study is the omission of potentially relevant variables such as comorbidities or socioeconomical aspects (i.e., yearly income, years of education, home ownership, and home density). However, according to the literature, these elements tend to be unfavourable in Hispanic immigrants and are evoked as an explanation for ethnicity-related differences among SLE patients, differences that were not observed in our study [32, 50].

Hispanic ethnicity is considered an independent risk factor for severe disease and adverse outcomes in SLE, and many authors have emphasized the important, sometimes prominent, role of unfavourable socioeconomic factors to explain these observations [13, 16, 51–53]. In many studies, particularly those conducted in developed countries, Hispanic patients represent an ethnic minority that often suffers from poor socioeconomic conditions, which have a negative impact on access to healthcare. In contrast to these reports, our cohort of patients benefit from free access to a specialized care center that provides comprehensive care and all available treatment options for SLE, independently from their socioeconomic situations.

In conclusion, we observed similar disease features in Hispanics and Caucasians, suggesting that socioeconomic variables, specifically healthcare access, might be more influential on disease course than biologic and genetic background linked to ethnicity. Validation and replication of our findings in larger studies conducted in similar public health settings are crucial for improving our understanding of the role of ethnicity in SLE.

Acknowledgments

The authors gratefully acknowledge the National Lupus Patient Association “Gruppo LES italiano ODV” for its constant and unconditioned support of our Lupus clinic.

Data Availability

The datasets generated and/or analysed during the current study are not publicly available due to individual data privacy but may be available from the corresponding author on reasonable request, in compliance with ethical and legal standards.

Conflicts of Interest

The authors declare no conflicts of interest.

Table 1 Sample demographics.

 	Global	Caucasian	Hispanic	P value	
Population	126	90 (71.4%)	36 (28.6%)	 	
Country of birth	 	 	 	 	
 Italy	90	90 (100%)	—	 	
 Ecuador	23	—	23 (63.9%)	 	
 Peru	7	—	7 (19.4%)	 	
 Chile	1	—	1 (2.8%)	 	
 Argentina	1	—	1 (2.8%)	 	
 Colombia	1	—	1 (2.8%)	 	
 Cuba	1	—	1 (2.8%)	 	
 Dominican Republic	1	—	1 (2.8%)	 	
 Paraguay	1	—	1 (2.8%)	 	
Gender	 	 	 	 	
 Male	9 (7.1%)	8 (8.9%)	1 (2.8%)	0.444	
 Female	117 (92.9%)	82 (91.1%)	35 (97.2%)	0.444	
Age (years)	50.6 (±12.2)	51.6 (±12.6)	47.8 (±10.8)	0.113	
Categorical parameters are given as n (%). Continuous variables are given as mean ± SD.

Table 2 Clinical and laboratory characteristics.

 	Global (n = 126)	Caucasian (n = 90)	Hispanic (n = 36)	P value	
Age of onset (years)	31.8 (±13.2)	31.1 (±13.6)	33.6 (±12.1)	0.156	
Disease duration (years)	18.6 (±10.5)	20.4 (±10.4)	14.2 (±9.44)	0.002	
Clinical manifestations	
 Articular	88 (69.8%)	63 (70.0%)	25 (69.4%)	0.951	
 Hematologic	79 (62.7%)	56 (62.2%)	23 (63.9%)	0.861	
 Neuropsychiatric	11 (8.7%)	7 (7.8%)	4 (11.1%)	0.509	
 Mucocutaneous	55 (43.7%)	38 (42.2%)	17 (47.2%)	0.609	
 Renal	74 (58.7%)	56 (62.2%)	18 (50.0%)	0.208	
 Antiphospholipid syndrome	18 (14.3%)	12 (13.3%)	6 (16.7%)	0.779	
 Serositis	33 (26.2%)	20 (22.2%)	13 (36.1%)	0.109	
Laboratory data	
 Anti-dsDNA	78 (61.9%)	60 (66.7%)	18 (50%)	0.082	
 Anti-Sm	20 (15.9%)	12 (13.3%)	8 (22.2%)	0.280	
 Antiphospholipid positivity	41 (32.5%)	28 (31.1%)	13 (36.1%)	0.588	
 Low C3 and/or C4	103 (81.7%)	75 (83.3%)	28 (77.8%)	0.456	
Disease burden	
 ACR/EULAR Score 2019 at last visit	23.1 (±8.02)	23.8 (±7.81)	21.4 (±8.41)	0.128	
 LLDAS at last visit	109 (86.5%)	80 (88.9%)	29 (80.6%)	0.252	
 SLICC Damage Index (SDI) at last visit	1.88 (±1.81)	2.11 (±1.91)	1.23 (±1.31)	0.037	
Categorical parameters are given as n (%). Continuous variables are given as mean ± SD. P values < 0.05 in bold. ACR/EULAR, American College of Rheumatology-European Alliance of Associations for Rheumatology; dsDNA, double-stranded DNA; LLDAS, lupus low disease activity state; SLICC, Systemic Lupus Erythematosus International Collaborating Clinics. Antiphospholipid positivity was defined as the presence of any of the following: anti-cardiolipin (IgM and/or IgG) and/or anti-β2-glycoprotein (IgM and/or IgG) antibodies and/or presence of lupus anticoagulant (LAC).

Table 3 Previous and current treatments.

 	Global (n = 126)	Caucasian (n = 90)	Hispanic (n = 36)	P value	
Previous therapies	
 Corticosteroids	121 (96.0%)	86 (95.6%)	35 (97.2%)	1.000	
 Hydroxychloroquine	106 (84.1%)	73 (81.1%)	33 (91.7%)	0.183	
 DMARDs	103 (81.7%)	73 (81.1%)	30 (83.3%)	1.000	
 Belimumab	18 (14.3%)	12 (13.3%)	6 (16.7%)	0.779	
Current therapy	
 Corticosteroids	 	 	 	 	
  PDN ≤7.5 mg/day	114 (90.5%)	83 (92.2%)	31 (86.1%)	0.321	
  PDN >7.5 mg/day	12 (9.5%)	7 (7.8%)	5 (13.9%)	0.321	
 Hydroxychloroquine	93 (73.8%)	63 (70.0%)	30 (83.3%)	0.178	
 DMARDs	63 (50.0%)	43 (47.8%)	20 (55.6%)	0.430	
 Belimumab	17 (13.5%)	12 (13.3%)	5 (13.9%)	1.000	
DMARDs, disease-modifying antirheumatic drug; PDN, prednisone.
==== Refs
1 Ameer M. A. Chaudhry H. Mushtaq J. An overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management Cureus 2022 14 10 10.7759/cureus.30330 e30330
2 Alarcon G. S. Calvo-Alen J. McGwin G. Jr. Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time Annals of the Rheumatic Diseases 2006 65 9 1168 1174 10.1136/ard.2005.046896 16905579
3 Catoggio L. J. Soriano E. R. Imamura P. M. Latino Americano De Estudio del, Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup? Lupus 2015 24 8 788 795 10.1177/0961203314563134 2-s2.0-84930921801 25504653
4 Lewis M. J. Jawad A. S. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus Rheumatology 2017 56 suppl_1 i67 i77 10.1093/rheumatology/kew399 2-s2.0-85021856383 27940583
5 Maningding E. Dall’Era M. Trupin L. Murphy L. B. Yazdany J. Racial and ethnic differences in the prevalence and time to onset of manifestations of systemic lupus erythematosus: the California lupus surveillance project Arthritis Care & Research 2020 72 5 622 629 10.1002/acr.23887 31115180
6 Gonzalez L. A. Toloza S. M. McGwin G. Jr. Alarcon G. S. Ethnicity in systemic lupus erythematosus (SLE): its influence on susceptibility and outcomes Lupus 2013 22 12 1214 1224 10.1177/0961203313502571 2-s2.0-84896717084 24097993
7 ISTAT (Italian National Institute of Statistics) 2023 https://www.istat.it/en/
8 Alarcon G. S. Roseman J. Bartolucci A. A. 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 & Rheumatism 1998 41 7 1173 1180 9663472
9 Reveille J. D. Moulds J. M. Ahn C. Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset Arthritis and Rheumatism 1998 41 7 1161 1172 10.1002/1529-0131(199807)41:7:1161::aid-art4>3.0.co;2-k 9663471
10 Calvo-Alen J. Reveille J. D. Rodriguez-Valverde V. Clinical, immunogenetic and outcome features of Hispanic systemic lupus erythematosus patients of different ethnic ancestry Lupus 2003 12 5 377 385 10.1191/0961203303lu372oa 2-s2.0-0038579721 12765301
11 Toloza S. M. Roseman J. M. Alarcon G. S. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage Arthritis and Rheumatism 2004 50 10 3177 3186 10.1002/art.20578 2-s2.0-5644256975 15476246
12 Gonzalez L. A. Pons-Estel G. J. Toloza S. M. A. Ugarte-Gil M. F. Alarcon G. S. Understanding risk factors for poor outcomes in a multiethnic longitudinal cohort: the LUMINA (lupus in minorities: nature vs. Nurture) experience (LUMINA LXXXII) Rheumatic Disease Clinics of North America 2021 47 1 55 64 10.1016/j.rdc.2020.09.002 34042054
13 Fernandez M. Alarcon G. S. Calvo-Alen J. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE Arthritis Care and Research 2007 57 4 576 584 10.1002/art.22672 2-s2.0-34248573475 17471524
14 Pons-Estel B. A. Catoggio L. J. Cardiel M. H. 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 1 17 10.1097/01.md.0000104742.42401.e2 2-s2.0-9144226796 14747764
15 Pons-Estel G. J. Alarcon G. S. Hachuel L. Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort Rheumatology 2012 51 7 1293 1298 10.1093/rheumatology/ker514 2-s2.0-84863820014 22389125
16 Ugarte-Gil M. F. Pons-Estel G. J. Molineros J. Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary Rheumatology 2016 55 3 436 440 10.1093/rheumatology/kev280 2-s2.0-84965082086 26412809
17 Uribe A. G. Romero-Diaz J. Apte M. Impact of immigration on the clinical expression of systemic lupus erythematosus: a comparative study of Hispanic patients residing in the USA and Mexico Rheumatology 2009 48 11 1392 1397 10.1093/rheumatology/kep266 2-s2.0-73349093416 19717548
18 Hernandez Cruz B. Alonso F. Calvo Alen J. Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry) Lupus 2020 29 1 27 36 10.1177/0961203319889667 31801040
19 Galindo-Izquierdo M. Rodriguez-Almaraz E. Pego-Reigosa J. M. Characterization of patients with lupus nephritis included in a large cohort from the Spanish society of Rheumatology registry of patients with systemic lupus erythematosus (RELESSER) Medicine (Baltimore) 2016 95 9 p. e2891 10.1097/md.0000000000002891 2-s2.0-84962486441 26945378
20 Alarcon G. S. McGwin Jr G. Petri M. Baseline characteristics of a multiethnic lupus cohort: profile Lupus 2002 11 2 95 101 10.1191/9612332lu155oa 11958584
21 Alarcon G. S. McGwin G. Jr. Petri M. Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort PLoS Medicine 2006 3 10 p. e396 10.1371/journal.pmed.0030396 2-s2.0-33750887728
22 Drenkard C. Lim S. S. Update on lupus epidemiology: advancing health disparities research through the study of minority populations Current Opinion in Rheumatology 2019 31 6 689 696 10.1097/bor.0000000000000646 2-s2.0-85071360186 31436582
23 Isenberg D. Appel G. B. Contreras G. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study Rheumatology 2010 49 1 128 140 10.1093/rheumatology/kep346 2-s2.0-77349120902 19933596
24 Merrill J. T. Neuwelt C. M. Wallace D. J. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial Arthritis and Rheumatism 2010 62 1 222 233 10.1002/art.27233 2-s2.0-74849131972 20039413
25 Pons-Estel B. A. Bonfa E. Soriano E. R. First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR) Annals of the Rheumatic Diseases 2018 77 11 1549 1557 10.1136/annrheumdis-2018-213512 2-s2.0-85050598145 30045853
26 Aringer M. Costenbader K. Daikh D. 2019 European League against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus Annals of the Rheumatic Diseases 2019 78 9 1151 1159 10.1136/annrheumdis-2018-214819 2-s2.0-85070711882 31383717
27 Barbhaiya M. Zuily S. Naden R. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria Arthritis and Rheumatology 2023 75 10 1687 1702 10.1002/art.42624 37635643
28 Gladman D. D. Ibanez D. Urowitz M. B. Systemic lupus erythematosus disease activity index 2000 Journal of Rheumatology 2002 29 2 288 291 11838846
29 Franklyn K. Lau C. S. Navarra S. V. Definition and initial validation of a lupus low disease activity state (LLDAS) Annals of the Rheumatic Diseases 2016 75 9 1615 1621 10.1136/annrheumdis-2015-207726 2-s2.0-84951816992 26458737
30 Gladman D. Ginzler E. Goldsmith C. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus Arthritis and Rheumatism 1996 39 3 363 369 10.1002/art.1780390303 2-s2.0-13344270914 8607884
31 The jamovi project 2023 https://www.jamovi.org/
32 Pons-Estel G. J. Alarcon G. S. Lupus in Hispanics: a matter of serious concern Cleveland Clinic Journal of Medicine 2012 79 12 824 834 10.3949/ccjm.79a.12048 2-s2.0-84873718983 23208987
33 Nagar S. D. Conley A. B. Chande A. T. Genetic ancestry and ethnic identity in Ecuador Human Genetics and Genomics Advances 2021 2 4 10.1016/j.xhgg.2021.100050 100050
34 Sanchez E. Rasmussen A. Riba L. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations Arthritis and Rheumatism 2012 64 11 3687 3694 10.1002/art.34650 2-s2.0-84868092719 22886787
35 Seldin M. F. Qi L. Scherbarth H. R. Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus Genes and Immunity 2008 9 4 389 393 10.1038/gene.2008.25 2-s2.0-44849127667 18401351
36 Sanchez E. Webb R. D. Rasmussen A. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus Arthritis and Rheumatism 2010 62 12 3722 3729 10.1002/art.27753 2-s2.0-78650065026 20848568
37 Ho A. Barr S. G. Magder L. S. Petri M. A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus Arthritis and Rheumatism 2001 44 10 2350 2357 10.1002/1529-0131(200110)44:10:2350::aid-art398>3.0.co;2-a 11665976
38 Gandino I. J. Scolnik M. Bertiller E. Scaglioni V. Catoggio L. J. Soriano E. R. Complement levels and risk of organ involvement in patients with systemic lupus erythematosus Lupus Science & Medicine 2017 4 1 10.1136/lupus-2017-000209 2-s2.0-85059703520 e000209
39 Negrini S. Pappalardo F. Murdaca G. Indiveri F. Puppo F. The antiphospholipid syndrome: from pathophysiology to treatment Clinical and Experimental Medicine 2017 17 3 257 267 10.1007/s10238-016-0430-5 2-s2.0-84975470945 27334977
40 Ghembaza A. Saadoun D. Management of antiphospholipid syndrome Biomedicines 2020 8 11 p. 508 10.3390/biomedicines8110508
41 Kabani N. Ginzler E. M. Is ethnicity linked to the severity of SLE manifestations? Nature Reviews Rheumatology 2019 15 9 515 516 10.1038/s41584-019-0271-1 2-s2.0-85069513501
42 Bertsias G. K. Ioannidis J. P. Aringer M. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs Annals of the Rheumatic Diseases 2010 69 12 2074 2082 10.1136/ard.2010.130476 2-s2.0-78649742730 20724309
43 Mahajan A. Amelio J. Gairy K. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression Lupus 2020 29 9 1011 1020 10.1177/0961203320932219 32571142
44 Zen M. Doria A. Response to: Remission or low disease activity as a target in systemic lupus erythematosus by Ugarte-Gil Annals of the Rheumatic Diseases 2019 78 1 p. e4 10.1136/annrheumdis-2017-212911 2-s2.0-85049007873
45 Gladman D. D. Urowitz M. B. Rahman P. Ibanez D. Tam L. S. Accrual of organ damage over time in patients with systemic lupus erythematosus Journal of Rheumatology 2003 30 9 1955 1959 12966597
46 Fanouriakis A. Kostopoulou M. Alunno A. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus Annals of the Rheumatic Diseases 2019 78 6 736 745 10.1136/annrheumdis-2019-215089 2-s2.0-85063719926 30926722
47 Fennelly K. The healthy migrant effect Minnesota Medicine 2007 90 3 51 53 17432759
48 Akresh I. R. Frank R. Health selection among new immigrants American Journal of Public Health 2008 98 11 2058 2064 10.2105/ajph.2006.100974 2-s2.0-55249127534 18309141
49 Ugarte-Gil M. F. Wojdyla D. Pastor-Asurza C. A. Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort Lupus 2018 27 4 536 544 10.1177/0961203317728810 2-s2.0-85044409024 28857715
50 Hasan B. Fike A. Hasni S. Health disparities in systemic lupus erythematosus-a narrative review Clinical Rheumatology 2022 41 11 3299 3311 10.1007/s10067-022-06268-y 35907971
51 Vila L. M. Alarcon G. S. McGwin G. Jr. Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations Rheumatology 2004 43 3 358 363 10.1093/rheumatology/keh048 2-s2.0-1542299615 14623949
52 Duran S. Apte M. Alarcon G. S. Lumina Study Group Poverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups Journal of the National Medical Association 2007 99 10 1196 1198 17987925
53 DeQuattro K. Yelin E. Socioeconomic status, health care, and outcomes in systemic lupus erythematosus Rheumatic Disease Clinics of North America 2020 46 4 639 649 10.1016/j.rdc.2020.07.004 32981641
