Original Research5 December 2017
A Nationwide Population-Based Study
    Author, Article and Disclosure Information
    Background:

    No large population-based studies have been done on systemic lupus erythematosus (SLE) mortality trends in the United States.

    Objective:

    To identify secular trends and population characteristics associated with SLE mortality.

    Design:

    Population-based study using a national mortality database and census data.

    Setting:

    United States.

    Participants:

    All U.S. residents, 1968 through 2013.

    Measurements:

    Joinpoint trend analysis of annual age-standardized mortality rates (ASMRs) for SLE and non-SLE causes by sex, race/ethnicity, and geographic region; multiple logistic regression analysis to determine independent associations of demographic variables and period with SLE mortality.

    Results:

    There were 50 249 SLE deaths and 100 851 288 non-SLE deaths from 1968 through 2013. Over this period, the SLE ASMR decreased less than the non-SLE ASMR, with a 34.6% cumulative increase in the ratio of the former to the latter. The non-SLE ASMR decreased every year starting in 1968, whereas the SLE ASMR decreased between 1968 and 1975, increased between 1975 and 1999, and decreased thereafter. Similar patterns were seen in both sexes, among black persons, and in the South. However, statistically significant increases in the SLE ASMR did not occur among white persons over the 46-year period. Females, black persons, and residents of the South had higher SLE ASMRs and larger cumulative increases in the ratio of the SLE to the non-SLE ASMR (31.4%, 62.5%, and 58.6%, respectively) than males, other racial/ethnic groups, and residents of other regions, respectively. Multiple logistic regression showed independent associations of sex, race, and region with SLE mortality risk and revealed significant racial/ethnic differences in associations of SLE mortality with sex and region.

    Limitations:

    Underreporting of SLE on death certificates may have resulted in underestimates of SLE ASMRs. Accuracy of coding on death certificates is difficult to ascertain.

    Conclusion:

    Rates of SLE mortality have decreased since 1968 but remain high relative to non-SLE mortality, and significant sex, racial, and regional disparities persist.

    Primary Funding Source:

    None.

    References

    • 1. Singh RR Systemic lupus erythematosus. In: Madhok R, Luthra H, eds. The Year in Rheumatic Disorders. Oxford, United Kingdom: Atlas Medical Publishing; 2007:171-90. Google Scholar
    • 2. Cervera R Khamashta MA Font J Sebastiani GD Gil A Lavilla P et alEuropean Working Party on Systemic Lupus ErythematosusMorbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore)2003;82:299-308. [PMID: 14530779] CrossrefMedlineGoogle Scholar
    • 3. Bernatsky S Boivin JF Joseph L Manzi S Ginzler E Gladman DD et alMortality in systemic lupus erythematosus. Arthritis Rheum2006;54:2550-7. [PMID: 16868977] CrossrefMedlineGoogle Scholar
    • 4. Urowitz MB Gladman DD Tom BD Ibañez D Farewell VT Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol2008;35:2152-8. [PMID: 18793004] CrossrefMedlineGoogle Scholar
    • 5. Yurkovich M Vostretsova K Chen W Aviña-Zubieta JA Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies. Arthritis Care Res (Hoboken)2014;66:608-16. [PMID: 24106157] doi:10.1002/acr.22173 CrossrefMedlineGoogle Scholar
    • 6. Lee YH Choi SJ Ji JD Song GG Overall and cause-specific mortality in systemic lupus erythematosus: an updated meta-analysis. Lupus2016;25:727-34. [PMID: 26811368] doi:10.1177/0961203315627202 CrossrefMedlineGoogle Scholar
    • 7. Uramoto KM Michet CJ Jr Thumboo J Sunku J O'Fallon WM Gabriel SE Trends in the incidence and mortality of systemic lupus erythematosus, 1950–1992. Arthritis Rheum1999;42:46-50. [PMID: 9920013] CrossrefMedlineGoogle Scholar
    • 8. Gudmundsson S Steinsson K Systemic lupus erythematosus in Iceland 1975 through 1984. A nationwide epidemiological study in an unselected population. J Rheumatol1990;17:1162-7. [PMID: 2290155] MedlineGoogle Scholar
    • 9. Ståhl-Hallengren C Jönsen A Nived O Sturfelt G Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis. J Rheumatol2000;27:685-91. [PMID: 10743809] MedlineGoogle Scholar
    • 10. Björnådal L Yin L Granath F Klareskog L Ekbom A Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964–95. J Rheumatol2004;31:713-9. [PMID: 15088296] MedlineGoogle Scholar
    • 11. Centers for Disease Control and Prevention. CDC WONDER. Updated 27 June 2017. Accessed at https://wonder.cdc.gov on 1 October 2015. Google Scholar
    • 12. Centers for Disease Control and Prevention edsInstructions for classifying the underlying cause of death. In: Centers for Disease Control and Prevention, eds. ICD-10 Mortality Manual 2a. Hyattsville, MD: Centers for Disease Control and Prevention; 2015. Google Scholar
    • 13. Centers for Disease Control and Prevention. Technical Appendix from Vital Statistics of United States 1999: Mortality. 2004. Accessed at www.cdc.gov/nchs/data/statab/techap99.pdf on 1 October 2015. Google Scholar
    • 14. Clegg LX Hankey BF Tiwari R Feuer EJ Edwards BK Estimating average annual per cent change in trend analysis. Stat Med2009;28:3670-82. [PMID: 19856324] doi:10.1002/sim.3733 CrossrefMedlineGoogle Scholar
    • 15. Lerman PM Fitting segmented regression models by grid search. Appl Stat1980;29:77-84. CrossrefGoogle Scholar
    • 16. Kim HJ Fay MP Feuer EJ Midthune DN Permutation tests for joinpoint regression with applications to cancer rates. Stat Med2000;19:335-51. [PMID: 10649300] CrossrefMedlineGoogle Scholar
    • 17. Alonso MD Llorca J Martinez-Vazquez F Miranda-Filloy JA Diazde Teran T Dierssen T et alSystemic lupus erythematosus in northwestern Spain: a 20-year epidemiologic study. Medicine (Baltimore)2011;90:350-8. [PMID: 21857367] doi:10.1097/MD.0b013e31822edf7f CrossrefMedlineGoogle Scholar
    • 18. Steinberg AD Kaltreider HB Staples PJ Goetzl EJ Talal N Decker JL Cyclophosphamide in lupus nephritis: a controlled trial. Ann Intern Med1971;75:165-71. [PMID: 4104337] LinkGoogle Scholar
    • 19. Sessoms SL Kovarsky J Monthly intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus. Clin Exp Rheumatol1984;2:247-51. [PMID: 6529878] MedlineGoogle Scholar
    • 20. Malaviya AN Singh RR Sindhwani R Singh YN Ahujà RK Bhuyan UN et alIntermittent intravenous pulse cyclophosphamide treatment in systemic lupus erythematosus. Indian J Med Res1992;96:101-8. [PMID: 1428048] MedlineGoogle Scholar
    • 21. Glicklich D Acharya A Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am J Kidney Dis1998;32:318-22. [PMID: 9708620] CrossrefMedlineGoogle Scholar
    • 22. Hahn BH McMahon MA Wilkinson A Wallace WD Daikh DI Fitzgerald JD et alAmerican College of RheumatologyAmerican College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken)2012;64:797-808. [PMID: 22556106] doi:10.1002/acr.21664 CrossrefMedlineGoogle Scholar
    • 23. Manzi S Meilahn EN Rairie JE Conte CG Medsger TA Jr Jansen-McWilliams L et alAge-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol1997;145:408-15. [PMID: 9048514] CrossrefMedlineGoogle Scholar
    • 24. Lu LJ Wallace DJ Ishimori ML Scofield RH Weisman MH Review: male systemic lupus erythematosus: a review of sex disparities in this disease. Lupus2010;19:119-29. [PMID: 19946032] doi:10.1177/0961203309350755 CrossrefMedlineGoogle Scholar
    • 25. Reveille JD Moulds JM Ahn C Friedman AW Baethge B Roseman J et alSystemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum1998;41:1161-72. [PMID: 9663471] CrossrefMedlineGoogle Scholar
    • 26. Austin HA 3rd Boumpas DT Vaughan EM Balow JE High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients. Nephrol Dial Transplant1995;10:1620-8. [PMID: 8559480] MedlineGoogle Scholar
    • 27. Gómez-Puerta JA Barbhaiya M Guan H Feldman CH Alarcón GS Costenbader KH Racial/ethnic variation in all-cause mortality among United States Medicaid recipients with systemic lupus erythematosus: a Hispanic and Asian paradox. Arthritis Rheumatol2015;67:752-60. [PMID: 25590668] doi:10.1002/art.38981 CrossrefMedlineGoogle Scholar
    • 28. Walsh SJ DeChello LM Geographical variation in mortality from systemic lupus erythematosus in the United States. Lupus2001;10:637-46. [PMID: 11678453] CrossrefMedlineGoogle Scholar
    • 29. Durán S Apte M Alarcón GS LUMINA Study GroupPoverty, not ethnicity, accounts for the differential mortality rates among lupus patients of various ethnic groups [Editorial]. J Natl Med Assoc2007;99:1196-8. [PMID: 17987925] MedlineGoogle Scholar
    • 30. Yazdany J Feldman CH Liu J Ward MM Fischer MA Costenbader KH Quality of care for incident lupus nephritis among Medicaid beneficiaries in the United States. Arthritis Care Res (Hoboken)2014;66:617-24. [PMID: 24124011] doi:10.1002/acr.22182 CrossrefMedlineGoogle Scholar
    • 31. Schoenbach VJ Rosamond WD Understanding the Fundamentals of Epidemiology: An Evolving Text. Chapel Hill, NC: Univ North Carolina at Chapel Hill; 2000:129-51. Google Scholar
    • 32. Calvo-Alén J Alarcón GS Campbell R Jr Fernández M Reveille JD Cooper GS Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients. Rheumatology (Oxford)2005;44:1186-9. [PMID: 15956088] CrossrefMedlineGoogle Scholar
    • 33. Ward MM Education level and mortality in systemic lupus erythematosus (SLE): evidence of underascertainment of deaths due to SLE in ethnic minorities with low education levels. Arthritis Rheum2004;51:616-24. [PMID: 15334436] CrossrefMedlineGoogle Scholar
    • 34. Anderson RN Miniño AM Hoyert DL Rosenberg HM Comparability of cause of death between ICD-9 and ICD-10: preliminary estimates. Natl Vital Stat Rep2001;49:1-32. [PMID: 11381674] MedlineGoogle Scholar
    • 35. Klebba A Scott J Estimates of Selected Comparability Ratios Based on Dual Coding of 1976 Death Certificates by the Eighth and Ninth Revisions of the International Classification of Diseases. Hyattsville, MD: National Center for Health Statistics; 1980:1-19. Google Scholar
    • 36. Mullins JF Watts FL Wilson CJ Plaquenil in the treatment of lupus erythematosus. J Am Med Assoc1956;161:879-81. [PMID: 13319032] CrossrefMedlineGoogle Scholar
    • 37. Johnson SA Meyer OO The treatment of lupus erythematosus disseminatus with cortisone. Am J Med Sci1952;223:9-15. [PMID: 14902783] CrossrefMedlineGoogle Scholar
    • 38. Sztejnbok M Stewart A Diamond H Kaplan D Azathioprine in the treatment of systemic lupus erythematosus. A controlled study. Arthritis Rheum1971;14:639-45. [PMID: 4106177] CrossrefMedlineGoogle Scholar
    • 39. Felson DT Anderson J Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med1984;311:1528-33. [PMID: 6390198] CrossrefMedlineGoogle Scholar
    • 40. National Cancer Institute. Joinpoint Help Manual 4.5.0.1. Bethesda: National Cancer Institute. Accessed at https://surveillance.cancer.gov/joinpoint/Joinpoint_Help_4.5.0.1.pdf on 3 October 2017. Google Scholar