To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients.
Methods
We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients’ medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan–Meier plots.
Results
A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4–13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5–5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48–4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33–4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively.
Conclusions
This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.
SilvaCAAvcinTBrunnerHI. Taxonomy for systemic lupus erythematosus with onset before adulthood. Arthritis Care Res (Hoboken)2012; 64: 1787–1793.
2.
LevyDMKamphuisS. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am2012; 59: 345–364.
3.
TarrTDérfalviBGyőriN, et al.Similarities and differences between pediatric and adult patients with systemic lupus erythematosus. Lupus2015; 24(8): 796–803.
4.
MalattiaCMartiniA. Paediatric-onset systemic lupus erythematosus. Best Pract Res Clin Rheumatol2013; 27(3): 351–362.
5.
MinaRBrunnerHI. Pediatric lupus – are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus?Rheum Dis Clin N Am2010; 36: 53–80.
6.
SilvaCA. Childhood-onset systemic lupus erythematosus: early disease manifestations that the paediatrician must know. Expert Rev Clin Immunol2016; 12: 907–910.
7.
UrowitzMBGladmanDDTomBD, et al.Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol2008; 35: 2152–2158.
8.
TektonidouMGLewandowskiLBHuJ, et al.Survival in adults and children with systemic lupus erythematosus: a systematic review and Bayesian meta-analysis of studies from 1950 to 2016. Ann Rheum Dis2017; 76: 2009–2016.
9.
KamphuisSSilvermanED. Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nat Rev Rheumatol2010; 6: 538–546.
10.
RubinsteinTBKnightAM. Disparities in childhood-onset lupus. Rheum Dis Clin North Am2020; 46(4): 661–672.
11.
KhandelwalPGovindarajanSBaggaA. Management and outcomes in children with lupus nephritis in the developing countries. Pediatr Nephrol2023; 38: 987–1000.
12.
AbujamBGuptaASuriD, et al.Trends and predictors of mortality in childhood onset lupus in a single North-Indian centre over 23 years: a retrospective study. Clin Exp Rheumatol2016; 34(3): 554–559.
13.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725.
14.
PetriMOrbaiAMAlarcónGS, et al.Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012; 64: 2677–2686.
15.
GomesRCSilvaMFKozuK, et al.Features of 847 childhood-onset systemic lupus erythematosus patients in three age groups at diagnosis: a Brazilian multicenter study. Arthritis Care Res (Hoboken)2016; 68(11): 1736–1741.
16.
NovakGVMolinariBCFerreiraJCBrazilian Childhood-onset Systemic Lupus Erythematosus Group. , et al.Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study. Lupus2018; 27: 1712–1717.
17.
American College of Rheumatology Ad Hoc committee on neuropsychiatric Lupus Syndromes. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum1999; 42: 599–608.
GladmanDGinzlerEGoldsmithC, 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 Rheum1996; 39: 363–369.
20.
Brasil. Ministerio da Saude. Conselho Federal de Medicina. Centro Brasileiro de Classificacao de Doencas. A declaração de obito: documento necessario e importante [Death certificate: a necessary and important document]. 2nd ed.Brasilia: Ministerio da Saude; 2007.
21.
FacoMMLeoneCCamposLM, et al.Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus. Braz J Med Biol Res2007; 40: 993–1002.
22.
GoldmanLSaysonRRobbinsS, et al.The value of the autopsy in three medical eras. N Engl J Med1983; 308: 1000–1005.
23.
RamosGFRibeiroVPMercadanteMP, et al.Mortality in adolescents and young adults with chronic diseases during 16 years: a study in a Latin American tertiary hospital. J Pediatr (Rio J)2019; 95(6): 667-673.
24.
MahmoudGAShahinAAZayedHS, et al.Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience. Lupus2018; 27(9): 1562–1569.
25.
AggarwalAPhatakSSrivastavaP, et al.Outcomes in juvenile onset lupus: single center cohort from a developing country. Lupus2018; 27(11): 1867–1875.
26.
Tavangar-RadFZiaeeVMoradinejadMH, et al.Morbidity and mortality in Iranian children with juvenile systemic lupus erythematosus. Iran J Pediatr2014; 24(4): 365–370.
27.
JongvilaikasemPMcNeilEBDissaneewateP, et al.Improvement of survival rates in the last decade in Thai childhood-onset systemic lupus erythematosus. Pediatr Rheumatol Online2018; 16(1): 62.
28.
FatemiAMatinfarMSmileyA. Childhood versus adult-onset systemic lupus erythematosus: long-term outcome and predictors of mortality. Clin Rheumatol2017; 36(2): 343–350.
29.
SahinSAdrovicABarutK, et al.Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome. Lupus2018; 27(3): 514-519.
30.
VachvanichsanongPDissaneewatePMc NeilE. Twenty-two years´ experience with childhood-onset SLE in a developing country: are outcomes similar to developed countries?Arch Dis Child2011; 96: 44–49.
KhajezadehMAZamaniGMoazzamoB, et al.Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus. Neurol Res Int2018; 2548142.
33.
Das Chagas MedeirosMMBezerraMCBragaFN, et al.Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE. Lupus2016; 25(4): 355-363.
34.
SakthiswaryRD'CruzD. Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis. Medicine (Baltimore)2014; 93(16): e86.
35.
Nieto-AristizábalIMartínezTUrbanoMA, et al.Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients. Lupus2019; 28(13): 1566-1570.
36.
PagnouxCKorachJMGuillevinL. Indications for plasma exchange in systemic lupus erythematosus in 2005. Lupus2005; 14(11): 871–877.
37.
Aguirre-ValenciaDNaranjo-EscobarJPosso-OsorioI, et al.Therapeutic plasma exchange as management of complicated systemic lupus erythematosus and other autoimmune diseases. Autoimmune Dis2019; 2019: 5350960.
38.
ChighizolaCBOngVHMeroniPL. The use of cyclosporine A in rheumatology: a 2016 comprehensive review. Clin Rev Aller Immunol2017; 52(3): 401–423.
39.
AytaçSBatuEDÜnalŞ, et al.Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus. Rheumatol Int2016; 36(10): 1421-1429.
40.
GrootNShaikhaniDTengYKO, et al.Long-term clinical outcomes in a cohort of adults with childhood-onset systemic lupus erythematosus. Arthritis Rheumatol2019; 71(2): 290-301.
41.
LimLSHPullenayegumELimL, et al.From childhood to adulthood: the trajectory of damage in patients with juvenile-onset systemic lupus erythematosus. Arthritis Care Res (Hoboken)2017; 69(11): 1627–1635.
42.
MokCCTseSMChanKL, et al.Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort. Lupus2018; 27(5): 722–727.
43.
TsakonasEJosephLEsdaileJM, et al.A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus. the Canadian Hydroxychloroquine Study Group. Lupus1998; 7(2): 80-85.
44.
Pons-EstelGJAlárconGSMcGwinGJr.Lumina Study Group, et al.Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum2009; 61(6): 830-839.
45.
ChiewthanakulPSawanyawisuthKFoocharoenC, et al.Clinical features, and predictive factors in neuropsychiatric lupus. Asian Pac J Allergy Immunol2012; 30(1): 55–60.
46.
VyasSHidalgoGBaqiN, et al.Outcome in African-American children of neuropsychiatric lupus and lupus nephritis. Pediatr Nephrol2002; 17: 45–49.
47.
LopesSRMGormezanoNWSGomesRCBrazilian Childhood-onset Systemic Lupus Erythematosus Group, et al.. Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups. Lupus2017; 26(9): 996-1001.
48.
Torrente-SegarraVSalman MonteTCRúa-FigueroaI, et al.Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Semin Arthritis Rheum2018; 0: 1–5.
49.
TektonidouMGWangZDasguptaA, et al.Burden of serious infections in adults with systemic lupus erythematosus: a National Population-Based Study, 1996-2011. Arthritis Care Res2015; 67(8): 1078–1085.
50.
SantosACEZLuglioMDelgadoAF, et al.Acute petrified myocardium associated with meningococcal sepsis in childhood-onset systemic lupus erythematous: a fatal case. Rev Inst Med Trop Sao Paulo2019; 61: e39.
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