Clustering of systemic lupus erythematosus mortality in southwestern Spain

Abstract

Objective

To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001–2020).

Methods

We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001–2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff’s spatial scan statistic were used to identify clusters.

Results

Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest).

Conclusions

We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.

Keywords

systemic lupus erythematosus autoimmune disease rheumatic disease Spain

Get full access to this article

View all access options for this article.

References

Kiriakidou

Ching

. Systemic lupus erythematosus. Ann Intern Med 2020; 172(11): ITC81–ITC96. DOI: 10.7326/AITC202006020.

Yen

Shaheen

Woo

JMP

, et al. 46-year trends in systemic lupus erythematosus mortality in the United States, 1968 to 2013. Ann Intern Med 2017; 167(11): 777–785. DOI: 10.7326/M17-0102.

Tian

Zhang

Yao

, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis 2022; 82: 351–356. DOI: 10.1136/ard-2022-223035.

Duarte-García

Hocaoglu

Valenzuela-Almada

, et al. Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades. Ann Rheum Dis 2022; 81: 1260–1266. DOI: 10.1136/annrheumdis-2022-222276. annrheumdis-2022-222276.

Rees

Doherty

Grainge

, et al. The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology 2017; 56(11): 1945–1961. DOI: 10.1093/rheumatology/kex260.

Reppe Moe

Haukeland

Molberg

, et al. Long-term outcome in systemic lupus erythematosus; knowledge from population-based cohorts. J Clin Med 2021; 10(19): 4306. DOI: 10.3390/jcm10194306.

Rúa-Figueroa

López-Longo

Calvo-Alén

, et al. Registro nacional de pacientes con lupus eritematoso sistémico de la sociedad española de reumatología: objetivos y metodología. Reumatol Clínica 2014; 10(1): 17–24. DOI: 10.1016/j.reuma.2013.04.013. English, Spanish.

Danchenko

Satia

Anthony

. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006; 15: 308–318.

Carter

Barr

Clarke

. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016; 12(10): 605–620. DOI: 10.1038/nrrheum.2016.137.

10.

Ruiz

Ramalle-Gómara

Elena

Spain RDR Working Group , et al. Trends in systemic lupus erythematosus mortality in Spain from 1981 to 2010. Lupus 2014; 23(4): 431–435. DOI: 10.1177/0961203313517015.

11.

Hernández-Rodríguez

Durán-Romero

Muñoz-Jiménez

, et al. Trends in mortality from lupus in Spain from 1980 to 2018. Lupus 2020; 29(13): 1719–1726. DOI: 10.1177/0961203320952864.

12.

Gómez-Rubio

López-Quílez

. Statistical methods for the geographical analysis of rare diseases. Rare Diseases Epidemiology 2010; 686: 151–171. DOI: 10.1007/978-90-481-9485-8_10.

13.

Instituto Nacional de Estadística. https://www.ine.es/index.htm (last accessed 10 January 2023).

14.

Eurostat . Revision of the European standard population. Report of Eurostat’s task force. Available at: https://ec.europa.eu/eurostat/en/web/products-manuals-and-guidelines/-/ks-ra-13-028 (2013, last accessed 10 January 2023).

15.

Joinpoint Regression Program, Version 4.9.1.0 - April 2022; Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute.

16.

GeoDa 1.20 for 64-bit windows. Available at: http://geodacenter.github.io/download.html last accessed 10 January 2023.

17.

Kulldorff

Nagarwalla

. Spatial disease clusters: detection and inference. Stat Med 1995; 14: 799–810.

18.

Besag

York

Mollié

. Bayesian image restoration, with two applications in spatial statistics. Ann Inst Stat Math 1991; 43: 1–20.

19.

Rue

Martino

Chopin

. Approximate Bayesian inference for latent Gaussian models by using integrated nested laplace approximations. J Roy Stat Soc B Stat Methodol 2009; 71: 319–392.

20.

R Development Core Team . R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. Available at: http://www.R-project.org/

21.

Scherlinger

Mertz

Sagez

, et al. Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014. Autoimmun Rev 2020; 19(6): 102531. DOI: 10.1016/j.autrev.2020.102531.

22.

Alonso

Martínez-Vázquez

Riancho-Zarrabeitia

, et al. Sex differences in patients with systemic lupus erythematosus from Northwest Spain. Rheumatol Int 2014; 34(1): 11–24. DOI: 10.1007/s00296-013-2798-9.

23.

Walsh

Gilchrist

. Geographical clustering of mortality from systemic lupus erythematosus in the United States: contributions of poverty, Hispanic ethnicity and solar radiation. Lupus 2006; 15(10): 662–670. DOI: 10.1191/0961203306071455.

24.

Grant

. Letter to the editor. Lupus 2004; 13: 281–282.

25.

Walsh

Dechello

. Geographical variation in mortality from systemic lupus erythematosus in the United States. Lupus 2001; 10(9): 637–646. DOI: 10.1191/096120301682430230.

26.

Canney

Induruwage

McCandless

, et al. Disease-specific incident glomerulonephritis displays geographic clustering in under-serviced rural areas of British Columbia, Canada. Kidney Int 2019; 96(2): 421–428. DOI: 10.1016/j.kint.2019.02.032.

27.

Alamanos

Voulgari

Siozos

, et al. Epidemiology of systemic lupus erythematosus in northwest Greece 1982–2001. J Rheumatol 2003; 30(4): 731–735.

28.

Tan

Long

, et al. Frequency of systemic lupus erythematosus was decreasing among hospitalized patients from 2013 to 2017 in a national database in China. Front Med 2021; 8: 648727. DOI: 10.3389/fmed.2021.648727.

29.

Llano

Alguacil

Ariza

. XII informe: el estado de la pobreza en España. Seguimiento de los indicadores de la Agenda UE 2030. 2015–2021. Available at: https://www.eapn.es/estadodepobreza/ARCHIVO/documentos/informe-AROPE-2022-resumen-ejecutivo.pdf last accessed January 2023.

30.

Atlas de radiación solar en España. Available at: https://www.aemet.es/es/serviciosclimaticos/datosclimatologicos/atlas_radiacion_solar last accessed January 2023.

31.

Concannon

Rudge

Yan

, et al. The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the starship experience (2000−2010). Lupus 2013; 22(11): 1156–1161. DOI: 10.1177/0961203313503051.

32.

Hernández-Cruz

Alonso

Calvo Alén

, et al. AB0436 all the “Hispanics” are not equal. The severity and activity of patients with SLE Is higher in Mestizos Latin American vs. European Caucasian. Lessons from relesser. Ann Rheum Dis 2016; 75: 1056.

33.

Estadísticas del Padrón Continuo . Provincias. Población extranjera por nacionalidad (1998–2020). Available at: https://www.ine.es/jaxi/Datos.htm?path=/t20/e245/p08/l0/&file=03005.px last accessed January 2023.

34.

Ramal

De Pablo

Guadix

, et al. HLA class II allele distribution in the Gypsy community of Andalusia, southern Spain. Tissue Antigens 2001; 57: 138–143.

35.

Manzano-Gamero

Pardo-Cabello

Vargas-Hitos

, et al. Effect of ethnicity on clinical presentation and risk of antiphospholipid syndrome in Roma and Caucasian patients with systemic lupus erythematosus: a multicenter cross-sectional study. International Journal of Rheumatic Diseases 2018; 21(11): 2028–2035. DOI: 10.1111/1756-185X.13117.

36.

Ramal

López-Nevot

Sabio

, et al. Systemic lupus erythematosus in southern Spain: a comparative clinical and genetic study between Caucasian and gypsy patients. Lupus 2004; 13(12): 934–940. DOI: 10.1191/0961203304lu2036oa.

37.

Estudio-mapa sobre vivienda y población gitana, 2015. Available at: https://www.gitanos.org/upload/29/29/informecompletoe-mobreviviendaypg.pdf last accessed January 2023.

38.

Calvo-Alén

Alarcón

Campbell

Jr , et al. Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients. Rheumatology 2005; 44(9): 1186–1189. DOI: 10.1093/rheumatology/keh717.

39.

Falasinnu

Rossides

Chaichian

, et al. Do death certificates underestimate the burden of rare diseases? The example of systemic lupus erythematosus mortality, Sweden, 2001–2013. Publ Health Rep 2018;133(4):481-488.

40.

Thomas

Griffiths

Smeeth

, et al. Burden of mortality associated with autoimmune diseases among females in the United Kingdom. Am J Publ Health 2010; 100(11): 2279–2287.

41.

Sedgwick

. Understanding the ecological fallacy. BMJ 2015; 351: h4773.

42.

Bermudi

PMM

Pellini

ACG

Diniz

CSG

, et al. Clusters of high-risk, low-risk, and temporal trends of breast and cervical cancer-related mortality in São Paulo, Brazil, during 2000–2016. Ann Epidemiol 2023; 78: 61–67. DOI: 10.1016/j.annepidem.2022.12.009.