Childhood-onset systemic lupus erythematosus: A descriptive and comparative study of clinical,laboratory,and treatment characteristics in two populations
Restricted accessResearch articleFirst published online September, 2024
Childhood-onset systemic lupus erythematosus: A descriptive and comparative study of clinical,laboratory,and treatment characteristics in two populations
The aim of this study was to characterize childhood-onset systemic lupus erythematosus (SLE) in two large cohorts from Turkey and the United States.
Methods
Patients diagnosed with childhood-onset SLE who fulfilled the 1997 American College of Rheumatology classification criteria for SLE from four reference centers in Turkey and the University of Pittsburgh School of Medicine in the United States were included in this study. A comparative analysis was conducted to evaluate the similarities and differences in clinical and laboratory features, damage accrual, and treatment experiences between the two populations.
Results
A total of 174 patients with childhood-onset SLE were included in this study (108 patients from Turkey and 66 patients from the United States). The female-to-male ratio was similar between the two cohorts (∼3:1, p = .73). The median age at diagnosis was 11.67 years (2.19-17.93) in the Turkish cohort and 13.68 years (2.74-17.93) in the U.S. cohort (p < .001). Photosensitivity (45.4% and 21.2%; p = .007) and renal involvement (41.7% and 36.4%; p = .045) were higher in the Turkish cohort. Anti-Ro/SSA (34.8% and 15.7%; p < .001), anti-Sm (59.1% and 19.4%; p < .001), and anti-RNP (47.0% and 14.8%; p < .001) positivity was more frequent in the U.S. cohort. Current use of rituximab (37.9% and 1.9%; p < .001) and belimumab (19.7% and 0%; p < .001) was more prevalent in the U.S. cohort, while the use of cyclophosphamide (often according to the low dose Euro-Lupus protocol) throughout the disease course (24.1% and 4.5%; p < .001) was more frequent in the Turkish cohort. SLICC/ACR Damage Index scores were not different between the two cohorts.
Conclusion
This study provides detailed clinical and laboratory features of childhood-onset SLE in two independent and geographically divergent cohorts. Our findings suggest an earlier age of disease onset and a higher prevalence of kidney involvement in Turkish patients. Differences in treatment approaches were also noted. However, damage accrual related to SLE does not appear to be different between the two patient populations.
CharrasASmithEHedrichCM. Systemic lupus erythematosus in children and young people. Curr Rheumatol Rep2021; 23: 20. DOI: 10.1007/s11926-021-00985-0.
2.
AlexanderTHedrichCM. Systemic lupus erythematosus - are children miniature adults?Clin Immunol2022; 234: 108907. DOI: 10.1016/j.clim.2021.108907.
3.
Valenzuela-AlmadaMOHocaogluMDabitJY, et al.Epidemiology of childhood-onset systemic lupus erythematosus: a population-based study. Arthritis Care Res2022; 74: 728–732. DOI: 10.1002/acr.24827.
4.
BrunnerHIGladmanDDIbanezD, et al.Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum2008; 58: 556–562. DOI: 10.1002/art.23204.
5.
TuckerLBUribeAGFernandezM, et al.Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus2008; 17: 314–322. DOI: 10.1177/0961203307087875.
6.
TsokosGCLoMSCosta ReisP, et al.New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol2016; 12: 716–730. DOI: 10.1038/nrrheum.2016.186.
7.
MassiasJSSmithEMAl-AbadiE, et al.Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK. Lupus2021; 30: 597–607. DOI: 10.1177/0961203320984251.
8.
HirakiLTBenselerSMTyrrellPN, et al.Ethnic differences in pediatric systemic lupus erythematosus. J Rheumatol2009; 36: 2539–2546. DOI: 10.3899/jrheum.081141.
9.
CooperGSParksCGTreadwellEL, et al.Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States. Lupus2002; 11: 161–167. DOI: 10.1191/0961203302lu161oa.
10.
GhaussyNOSibbittWJr.BankhurstAD, et al.The effect of race on disease activity in systemic lupus erythematosus. J Rheumatol2004; 31: 915–919.
11.
BorgiaREGurkaMJFilippSL, et al.Race, ethnicity and patient-reported outcomes in childhood-onset systemic lupus erythematosus. Clin Exp Rheumatol2023; 41: 186–194. DOI: 10.55563/clinexprheumatol/tn0x4k.
12.
LauCSYinGMokMY. Ethnic and geographical differences in systemic lupus erythematosus: an overview. Lupus2006; 15: 715–719. DOI: 10.1177/0961203306072311.
13.
CarterEEBarrSGClarkeAE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol2016; 12: 605–620. DOI: 10.1038/nrrheum.2016.137.
14.
YazdanyJMarafinoBJDeanML, et al.Thirty-day hospital readmissions in systemic lupus erythematosus: predictors and hospital- and state-level variation. Arthritis Rheumatol2014; 66: 2828–2836. DOI: 10.1002/art.38768.
15.
BrunnerHIKlein-GitelmanMSYingJ, et al.Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers. Clin Exp Rheumatol2009; 27: 155–162.
16.
SmithermanEAChahineRABeukelmanT, et al.Childhood-onset lupus nephritis in the childhood arthritis and rheumatology Research alliance registry: short-term kidney status and variation in care. Arthritis Care Res2023; 75: 1553–1562. DOI: 10.1002/acr.25002.
17.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725. DOI: 10.1002/art.1780400928.
18.
WeeningJJD'AgatiVDSchwartzMM, et al.The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol2004; 15: 241–250. DOI: 10.1097/01.asn.0000108969.21691.5d.
19.
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. DOI: 10.1002/art.1780390303.
20.
KarsMEBasakANOnatOE, et al.The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc Natl Acad Sci U S A2021; 118: e2026076118. DOI: 10.1073/pnas.2026076118.
21.
LythgoeHSmithEMDKilleenOG, et al.Prospective epidemiological study of juvenile-onset systemic lupus erythematosus in the UK and Republic of Ireland. Rheumatology2022; 61: 4097–4106. DOI: 10.1093/rheumatology/keac064.
22.
AmbroseNMorganTAGallowayJ, et al.Differences in disease phenotype and severity in SLE across age groups. Lupus2016; 25: 1542–1550. DOI: 10.1177/0961203316644333.
23.
HoffmanIELauwerysBRDe KeyserF, et al.Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis2009; 68: 412–415. DOI: 10.1136/ard.2008.094813.
24.
Ramirez GomezLAUribe UribeOOsioUO, et al.Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children. Lupus2008; 17: 596–604. DOI: 10.1177/0961203307088006.
25.
SalahSLotfyHMSabrySM, et al.Systemic lupus erythematosus in Egyptian children. Rheumatol Int2009; 29: 1463–1468. DOI: 10.1007/s00296-009-0888-5.
26.
BalciSEkinciRMKBayazitAK, et al.Juvenile systemic lupus erythematosus: a single-center experience from southern Turkey. Clin Rheumatol2019; 38: 1459–1468. DOI: 10.1007/s10067-019-04433-4.
27.
MassiasJSSmithEMDAl-AbadiE, et al.Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups. Lupus2020; 29: 474–481. DOI: 10.1177/0961203320909156.
28.
DesclouxEDurieuICochatP, et al.Influence of age at disease onset in the outcome of paediatric systemic lupus erythematosus. Rheumatology2009; 48: 779–784. DOI: 10.1093/rheumatology/kep067.
29.
Artim-EsenBSahinSCeneE, et al.Comparison of disease characteristics, organ damage, and survival in patients with juvenile-onset and adult-onset systemic lupus erythematosus in a combined cohort from 2 tertiary centers in Turkey. J Rheumatol2017; 44: 619–625. DOI: 10.3899/jrheum.160340.
30.
SahinSAdrovicABarutK, et al.Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome. Lupus2018; 27: 514–519. DOI: 10.1177/0961203317747717.
31.
SousaSGoncalvesMJInesLS, et al.Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register. Rheumatol Int2016; 36: 955–960. DOI: 10.1007/s00296-016-3450-2.
32.
WatsonLLeoneVPilkingtonC, et al.Disease activity, severity, and damage in the UK juvenile-onset systemic lupus erythematosus cohort. Arthritis Rheum2012; 64: 2356–2365. DOI: 10.1002/art.34410.
33.
WebbRKellyJASomersEC, et al.Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients. Ann Rheum Dis2011; 70: 151–156. DOI: 10.1136/ard.2010.141697.
34.
ReidSAlexssonAFrodlundM, et al.High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Ann Rheum Dis2020; 79: 363–369. DOI: 10.1136/annrheumdis-2019-216227.
35.
DasdemirSYildizMCelebiD, et al.Genetic screening of early-onset patients with systemic lupus erythematosus by a targeted next-generation sequencing gene panel. Lupus2022; 31: 330–337. DOI: 10.1177/09612033221076733.
36.
BhattadSRawatAGuptaA, et al.Early complement component deficiency in a single-centre cohort of pediatric onset lupus. J Clin Immunol2015; 35: 777–785. DOI: 10.1007/s10875-015-0212-y.
37.
MokCC. Polygenic risk score: the potential role in the management of systemic lupus erythematosus. RMD Open2024; 10: e004156. DOI: 10.1136/rmdopen-2024-004156.
38.
ChenLWangYFLiuL, et al.Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity. Hum Mol Genet2020; 29: 1745–1756. DOI: 10.1093/hmg/ddaa030.
39.
ChiewchengcholDMurphyRMorganT, et al.Mucocutaneous manifestations in a UK national cohort of juvenile-onset systemic lupus erythematosus patients. Rheumatology2014; 53: 1504–1512, DOI: 10.1093/rheumatology/keu137.
40.
ChottawornsakNRodsawardPSuwannachoteS, et al.Skin signs in juvenile- and adult-onset systemic lupus erythematosus: clues to different systemic involvement. Lupus2018; 27: 2069–2075. DOI: 10.1177/0961203318805851.
41.
OzturkKCaglayanSTanatarA, et al.Low disease activity state in juvenile-onset systemic lupus erythematosus. Lupus2021; 30: 2144–2150. DOI: 10.1177/09612033211054399.
42.
ChighizolaCBPetacciaAGattinaraM, et al.Insights into the clinical presentation of juvenile systemic lupus erythematosus: the PRAGMA monocentric cohort of 177 patients. Clin Exp Rheumatol2023; 41: 1926–1933. DOI: 10.55563/clinexprheumatol/rp916a.
43.
PluchinottaFRSchiavoBVittadelloF, et al.Distinctive clinical features of pediatric systemic lupus erythematosus in three different age classes. Lupus2007; 16: 550–555. DOI: 10.1177/0961203307080636.
44.
NovakGVMarquesMBalbiV, et al.Anti-RO/SSA and anti-La/SSB antibodies: association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus. Autoimmun Rev2017; 16: 132–135. DOI: 10.1016/j.autrev.2016.12.004.
45.
MinaRvon SchevenEArdoinSP, et al.Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus. Arthritis Care Res2012; 64: 375–383. DOI: 10.1002/acr.21558.
46.
GrootNde GraeffNAvcinT, et al.European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis2017; 76: 1788–1796. DOI: 10.1136/annrheumdis-2016-210960.
47.
JiangYPZhaoXXChenRR, et al.Comparative efficacy and safety of mycophenolate mofetil and cyclophosphamide in the induction treatment of lupus nephritis: a systematic review and meta-analysis. Medicine (Baltim)2020; 99: e22328. DOI: 10.1097/MD.0000000000022328.
48.
SmithEAl-AbadiEArmonK, et al.Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis. Lupus2019; 28: 613–620. DOI: 10.1177/0961203319836712.
49.
SmithEMDEgbivwieNJorgensenAL, et al.Real world treatment of juvenile-onset systemic lupus erythematosus: data from the UK JSLE cohort study. Clin Immunol2022; 239: 109028. DOI: 10.1016/j.clim.2022.109028.
50.
RobertsJEBerbertLChangJ, et al.Association of race and ethnicity with medication use for pediatric lupus in the childhood arthritis and rheumatology Research alliance registry. ACR Open Rheumatol2022; 4: 954–963. DOI: 10.1002/acr2.11494.
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