Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus

Main Article Content

Putu Ayunda Trisnia
Ketut Dewi KUmara Wati
Komang Ayu Witarini
Ida Bagus Ramajaya Sutawan
Hendra Santoso

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Untreated SLE often become progressive and lead to increased risk of mortality. Corticosteroid and cyclophosphamide remain the treatment of choice for severe SLE. Disease activity assessed with SLE Daily Activity Index (SLEDAI).


Objective To compare the disease activity of childhood-onset severe SLE at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide by using  SLEDAI.


Methods This study was conducted in the Division of Pediatric Allergy and Immunology, Department of Child Health, Udayana University/Sanglah Hospital, Denpasar, Bali. Subjects were SLE patient aged 0-18 years who had severe clinical manifestations. Subject received therapy combination of high dose methylprednisolone and cyclophosphamide every 2 weeks for six doses. SLEDAI score was assessed at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide.


Results During the study period, 51 children were diagnosed as SLE. Twenty-one subjects were included for analysis. Median SLEDAI score at the time of diagnosis was 23 (range 13-39). SLEDAI score after three months of cyclophosphamide was decreased to 2 (range 0-14). Post hoc analysis with Wilcoxon signed-rank test showed the improvement of SLEDAI score at the time of diagnosis and after three months of cyclophosphamide was statistically significant  (Z=-4.016, P<0.0001).


Conclusion SLEDAI score reduced after completion of high-dose methylprednisolone and three month of cyclophosphamide therapy.

Article Details

How to Cite
1.
Trisnia P, KUmara Wati KD, Witarini KA, Sutawan IB, Santoso H. Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus. PI [Internet]. 28Apr.2020 [cited 20Sep.2020];60(3):117-4. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2313
Section
Pediatric Allergy Immunology
Received 2019-09-17
Accepted 2020-04-28
Published 2020-04-28

References

1. Weiss JE. Pediatric systemic lupus erythematosus: more than a positive antinuclear antibody. Pediatrics in Review. 2012;33:62-74. DOI: 10.1542/pir.33-2-62.
2. Tan JHT, Hoh SF, Win MTM, Chan YH, Das L, Arkachaisri T. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles. Lupus. 2015;0:1-8. DOI: 10.1177/0961203315584413.
3. Fatemi A, Matinfar M, Saber M, Smiley A. The association between initial manifestations of childhood-onset systemic lupus erythematosus and the survival. International Journal of Rheumatic Diseases. 2015;1-7. DOI: 10.1111/1756-185X.12807.
4. Huang JL, Yeh KW, Yao TC, Huang YL, Chung HT, Ou LS, et al. Pediatric lupus in Asia. Lupus. 2010;19:1414-8. DOI: 10.1177/0961203310374339.
5. Saleh AM, Kurniati N, Syarif BH. Penilaian aktivitas penyakit lupus eritematosus sistemik dengan skor SLEDAI di Departemen Ilmu Kesehtan Anak RSCM. Sari Pediatri. 2014;16:292-8. DOI: 10.14238/sp16.4.2014.292-8.
6. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78:736-45. DOI: 10.1136/annrheumdis-2019-215089.
7. Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A. Diagnosis, monitoring, and treatment of systemic lupus erythematosus: a systematic review of clinical practice guidelines. Arthritis Care & Research. 2015;67:1440-52. DOI: 10.1002/acr.22591.
8. Nazri SKSM, Wong KK, Hamid WZWA. Retrospective analysis of clinic-laboratory parameters and their association with systemic lupus erythematosus disease activity index score. Saudi Med J. 2018;39:627-31. DOI: 10.15537/smj.2018.6.22112.
9. Zhang XW, Li C, Ma CC, Zhao JX, An Y, Liu S, et al. Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study. Clin Rheumatol. 2014;33:939-45. DOI: 10.1007/s10067-014-2590-6.
10. Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido ER, Danieli MG, et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis. Arthritis & Rheumatism. 2004;50:3934-40. DOI: 10.1002/art.20666.
11. Brunner HI, Feldman BM, Bombardier C, Silverman ED. Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis & Rheumatism 1999;42(7):1354-60. DOI: 10.1002/1529-0131(199907)42:7<1354::AID-ANR8>3.0.CO;2-4.
12. Griffiths B, Mosca M, Gordon C. Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices. Best Practice & Research Clinical Rheumatology 2005;19(5):685-708. DOI: 10.1016/j.berh.2005.03.010.
13. Salehi-Abari I. 2015 ACR/SLICC revised criteria for diagnosis of systemic lupus erythematosus. Autoimmune Dis Ther Approaches. Open Access 2015;2:1-4. DOI: 10.14437/ADTAOA-2-114.
14. Pusongchai T, Jungthirapanich J, Khositseth S. Pediatric systemic lupus erythematosus in Thammasat University Hospital. J Med Assoc Thai. 2010;93(Suppl.7):S283-93. PMID: 21294427.
15. Indonesia IDA. Rekomendasi ikatan dokter anak Indonesia: asuhan nutrisi pediatrik (pediatric nutrition care). Jakarta: Ikatan Dokter Anak Indonesia; 2011.
16. Rachmawati P, Murni IK, Nugroho S, Noormanto, Sumadiono. Factor associated with pericardial effusion in pediatric systemic lupus erythematosus. Pediatr Indones. 2018;58(5):227-32. DOI: 10.14238/pi58.5.2018.227-32.
17. Munasir Z, Mariana T, Suradi R. Clinical and laboratory features of childhood systemic lupus erythematosus and its course in Department of Child Health, Cipto Mangunkusumo Hospital, Jakarta. Pediatr Indones. 2001;41(7-8):214-24. DOI: 10.14238/pi41.4.2001.214-24.
18. Dung NTN, Loan HT, Nielsen S, Zak M, Petersen FK. Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatric Rheumatology. 2012;10:38. DOI: 10.1186/1546-0096-10-38.
19. Gulay CB, Dans LF. Clinical presentations and outcomes of Filipino juvenile systemic lupus erythematosus. Pediatric Rheumatology. 2011;9:7. DOI: 10.1186/1546-0096-9-7.
20. Faisal S, Akib A, Tambunan T. Clinical and laboratory manifestations of childhood and adult-onset systemic lupus erythematosus in Cipto Mangunkusumo Hospital. Paediatr Indones. 2003;43:199-204. DOI: 10.14238/pi43.6.2003.199-204.
21. Malleson PN, Mackinnon MJ, Sailer-Hoeck M, Spencer CH. Review for the generalist: the antinuclear antibody test in children – when to use it and what to do with the positive titer. Pediatric Rheumatology. 2010;8:27. DOI: 10.1186/1546-0096-8-27.
22. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol. 2000;53:424-32. DOI: 10.1136/jcp.53.6.424.
23. Chou IJ, Kuo CF, See LC, Hsia SH, Yu KH, Luo SF, et al. Antinuclear antibody status and risk of death in children and adolescents. Scand J Rheumatol. 2011;40:472-7. DOI: 10.3109/03009742.2011.593546.
24. Silva CA. Childhood-onset systemic lupus erythematosus: early disease manifestations that the paediatrician must know. Expert Review of Clinical Immunology. 2016;12:907-10. DOI: 10.1080/1744666X.2016.1195685.
25. Binder E, Edelbauer M. Use of biomarkers in the management of children with lupus. Curr Rheumatol Rep. 2013;15:312. DOI: 10.1007/s11926-012-0312-0.
26. Levy DM, Kamphuis S. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am. 2012;59:345-64. DOI: 10.1016/j.pcl.2012.03.007.
27. Hahn BH, McMahon M, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald J, et al. American College of Rheumatology Guidelines for screening, treatment and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64:797-808. DOI: 10.1002/acr.21664.
28. Thakral A, Klein-Gitelman MS. An update on treatment and management of pediatric systemic lupus erythematosus. Rheumatol Ther. 2016;3:209-19. DOI: 10.1007/s40744-016-0044-0.
29. Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr. 2008;152:550-6. DOI: 10.1016/j.jpeds.2007.09.019.