Predictors of mortality in children with systemic lupus erythematosus
Abstract
Background Systemic lupus erythematosus (SLE) is a multisystem chronic disease with a relatively high mortality rate in children, despite improvements in prognosis and survival rate over the past decade. Studies on the predictors of mortality in children with SLE, especially in low- and middle-income countries, are limited.
Objective To determine the predictors of mortality of children with SLE.
Methods This was case-control study using data from medical records of children with SLE at Dr. Sardjito Hospital, Yogyakarta, Indonesia, between 2009 and 2017. Subjects were children aged <18 years diagnosed with SLE. Cases were those who died within one year of diagnosis; the controls were those who were discharged alive. From subjects’ medical records, we collected clinical data including age, sex, date of diagnosis, nutritional status, anti-dsDNA antibody, antinuclear antibody (ANA), hypertension, disease activity based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, proteinuria, thrombocytopenia, mortality/survival outcome, date of death, cause of death, and clinical data including fever, seizures, antibiotic used, microbial culture outcomes, and infection-related diagnoses. We performed bivariate analysis of the association between predictor variables (SLEDAI score, proteinuria, infection, hypertension, and seizures) and mortality outcome (survival or death), followed by logistic regression analysis.
Results Eighty-four patients with SLE were included, of which 72 were female. Median age at diagnosis was 14 (range 4-18) years. Twenty-three patients (27%) died within one year after diagnosis. The most common causes of death were infection and renal failure in 8/23 and 7/23 subjects, respectively. On bivariate analysis, the variables significantly associated with mortality were hypertension (OR 3.34, 95%CI 1.22 to 9.14) and infection (OR 3.71; 95%CI 1.36 to 10.12). Seizures, proteinuria, and SLEDAI score were not found to be significantly associated with mortality. On logistic regression analysis, infection was the only significant predictor of mortality (OR 3.22; 95%CI 1.15 to 9.05).
Conclusion Among the factors studied, infection is significantly associated with mortality in children with SLE.
References
Rad-Tavangar F, Ziaee V, Moradinejad M-H, Tahghighi F. Juvenile systemic lupus erythematous in Iranian children. Iran J Pediatr. 2014; 24: 365-70. https://doi.org/10.1186/1546-0096-12-S1-P330
Weiss JE. Pediatric systemic lupus erythematosus: More than a positive antinuclear antibody. Pediatr Rev 2012; 33: 62-74. https://doi.org/10.1542/pir.33-2-62 PMid:22301032
Pusat Data dan Informasi Kementrian Kesehatan Republik Indonesia. Situasi Lupus di Indonesia. Jakarta: Pusdatin Kemenkes RI; 2017. [cited 2017 July 24]. Available from: www.pusdatin.kemkes.go.id.
Mok CC, Lee KW, Ho CT, Lau CS, Wong RW. A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population. Rheumatology. 2000; 39: 399-406. https://doi.org/10.1093/rheumatology/39.4.399 PMid:10817773
Blancas-galicia L, Guevara-cruz M, Berrón-pérez R, Berrón-ruiz L. Survival of Mexican patients with paediatric-onset systemic lupus erythematosus and abnormal electroencephalogram. Allergol Immunopathol. 2013; 41: 108-13. https://doi.org/10.1016/j.aller.2011.11.007 PMid:22316551
Faco MMM, Leone C, Campos LM, Febrônio MV, Marques HHS, Silva CA. Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus. Brazilian J Med Biol Res. 2007; 40: 993-1002. https://doi.org/10.1590/S0100-879X2006005000110
Hernandez-Cruz B, Tapia N, Villa-Romero AR, Reyes E, Cardiel MH. Risk factors associated with mortality in systemic lupus erythematosus. A case-control study in a tertiary care center in Mexico City. Clin Exp Rheumatol. 2001; 19: 395-401. PMid:11491494
Ward MM, Pajevic S, Dreyfuss J, Malley JD. Short-term prediction of mortality in patients with systemic lupus erythematosus: classification of outcomes using random forests. Arthritis Rheum. 2006; 55: 74-80. https://doi.org/10.1002/art.21695 PMid:16463416
Farkhati MY, Hapsara S, Satria CD. Antibodi Anti DS-DNA Sebagai Faktor Prognosis Mortalitas pada Lupus Eritematosus Sistemik. Sari Pediatr. 2012; 14: 2-8. https://doi.org/10.14238/sp14.2.2012.90-6
Sinha R, Raut S. Pediatric lupus nephritis: Management update. World J Nephrol. 2014; 3: 16. https://doi.org/10.5527/wjn.v3.i2.16 PMid:24868499 PMCid:PMC4023399
Zhao H, Li S, Yang R. Thrombocytopenia in patients with systemic lupus erythematosus: significant in the clinical implication and prognosis. Platelets. 2010; 21: 380-5. https://doi.org/10.3109/09537101003735564 PMid:20433308
Iaccarino L, Larosa M, Doria A. Disease activity indices and prognosis of systemic lupus erythematosus. In: Roccatello D, Emmi L, eds. Connective tissue disease: A comprehensive guide. Cham: Springer International Publishing; 2016. p. 199-211. https://doi.org/10.1007/978-3-319-24535-5_15
Kamphuis S, Silverman ED. Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nat Rev Rheumatol. 2010; 6: 538-46. https://doi.org/10.1038/nrrheum.2010.121 PMid:20683438
Gulay CB, Dans LF. Clinical presentations and outcomes of Filipino juvenile systemic lupus erythematosus. Pediatr Rheumatol. 2011; 9: 7. https://doi.org/10.1186/1546-0096-9-7 PMid:21306603 PMCid:PMC3045886
Jakes RW, Bae S-C, Louthrenoo W, Mok C, Navarra S V, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res. (Hoboken). 2012; 64: 159-68. https://doi.org/10.1002/acr.20683 PMid:22052624
Teh CL, Ling GR. Causes and predictors of mortality in hospitalized lupus patient in Sarawak General Hospital, Malaysia. Lupus. 2013; 22: 106-11. https://doi.org/10.1177/0961203312465780 PMid:23112253
Feng X, Pan W, Liu L, Wu M, Ding F, Hu H, et al. Prognosis for hospitalized patients with systemic lupus erythematosus in China: 5-year update of the Jiangsu cohort. PLoS One. 2016; 11: 1-15. https://doi.org/10.1371/journal.pone.0168619 PMid:28030595 PMCid:PMC5193352
Baqi N, Moazami S, Singh A, Ahmad H, Balachandra S, Tejani A. Lupus nephritis in children: a longitudinal study of prognostic factors and therapy. J Am Soc Nephrol. 1996; 7: 924-9. PMid:8793802
Feng M, Lv J, Fu S, Liu B, Tang Y, Wan X, et al. Clinical features and mortality in Chinese with lupus nephritis and neuropsychiatric lupus: A 124-patient study. J Res Med Sci. 2014; 19: 414-9. PMid:25097623 PMCid:PMC4116572
Oktadianto L, Prasetyo RV, Soemyarso NA, Noer MS. Predictors of mortality in children with nephritis lupus. Paediatr Indones. 2014; 54: 338-43. https://doi.org/10.14238/pi54.6.2014.338-43
Ryan MJ. The pathophysiology of hypertension in systemic lupus erythematosus. Am J Physiol Regul Integr Comp Physio. 2009; 296: R1258-67. https://doi.org/10.1152/ajpregu.90864.2008 PMid:19158408 PMCid:PMC2698608
Taylor EB, Ryan MJ. Understanding mechanisms of hypertension in systemic lupus erythematosus. Ther Adv Cardiovasc. Dis. 2017; 11: 20-32. https://doi.org/10.1177/1753944716637807 PMid:26985016 PMCid:PMC5065379
Trager J, Ward MM. Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol. 2001; 13: 345-51. https://doi.org/10.1097/00002281-200109000-00002 PMid:11604587
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Accepted 2019-02-06
Published 2019-02-08
