Faktor- faktor yang Berhubungan dengan Kadar 25 Hidroksi Vitamin D Serum pada Anak dengan Lupus Eritematosus Sistemik

Valerie viola wibawa; Raynald O Takumansang; Jose M Mandei; Fima Lanra Fredrik Gerarld Langi

doi:10.36452/jkdoktmeditek.v31i4.3708

Authors

Valerie Viola Wibawa Departemen Ilmu Kesehatan Anak, Universitas Sam Ratulangi, Manado, Indonesia
Raynald O. Takumansang Departemen Ilmu Kesehatan Anak, Universitas Sam Ratulangi, Manado, Indonesia
Jose M. Mandei Departemen Ilmu Kesehatan Anak, Universitas Sam Ratulangi, Manado, Indonesia
Fima Lanra Fredrik Gerarld Langi Departemen Ilmu Kesehatan Anak, Universitas Sam Ratulangi, Manado, Indonesia

DOI:

https://doi.org/10.36452/jkdoktmeditek.v31i4.3708

Keywords:

lupus erythematosus, systemic, vitamin D deficiency

Abstract

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organ systems. Pediatric-onset SLE (pSLE) often presents with more severe organ involvement and a more aggressive course than adult-onset cases. Vitamin D, known for its immunomodulatory effects, has been implicated in SLE pathogenesis, yet data on serum 25-hydroxy vitamin D [25(OH)D] levels in pediatric patients remain limited. Objective: This study aimed to assess serum 25(OH)D levels in children with SLE and identify related factors. Methods: A cross-sectional observational study was conducted on 22 pediatric SLE patients aged 5–18 years treated at Prof. Dr. R. D. Kandou General Hospital, Manado. Patients with chronic kidney disease, nephrotic syndrome, chronic liver disease, congenital skeletal disorders, or parathyroid dysfunction were excluded. Serum 25(OH)D levels were measured via ELISA, along with other laboratory parameters. Results: Results showed all patients had vitamin D deficiency, with a mean level of 11.93 ± 5.25 ng/mL. Multivariate regression analysis revealed significant associations between vitamin D levels and complement C3, disease duration, SLEDAI scores, and dsDNA levels. Conclusion: Vitamin D deficiency is prominent among pSLE patients and is linked to disease activity and severity, suggesting its potential role in disease management and the need for further research

References

Valenzuela-Almada MO, Hocaoglu M, Dabit JY, Osei-Onomah SA, Basiaga ML, OrandiAB, et al. Epidemiology of childhood-onset systemic lupus erythematosus: a population-based study. Arthritis Car [Internet].2022 [Cited 2024 Jan 5] ;74(5):728–32.Available from https://pubmed.ncbi.nlm.nih.gov/34825516/

Kamphuis S, Silverman ED. Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nat Rev Rheumatol [Internet]. 2010 [Cited 2024 Jan 5];6(9):538–46. Available from: http://dx.doi.org/10.1038/nrrheum.2010.121

Tang SP, Lim SC, Arkachaisri T. Childhood-onset systemic lupus erythematosus: Southeast asian perspectives. J Clin Med [Internet]. 2021 [Cited 2024 Jan 5];10(4):559. Available from: https://pubmed.ncbi.nlm.nih.gov/33546120

Ashournia P, Sadeghi P, Rezaei N, Moradinejad MH, Ziaee V. Prevalence of family history of autoimmune disorders in juvenile systemic lupus erythematosus. Maedica– Journal of Clinical Medicine [Internet].2018 [Cited 2024 Jan 5];13(1):21–4. Available from: http://dx.doi.org/10.26574/maedica.2018.13.1.21

Ahmed S, Rehan Ali S, Karim F, Ishaq S, Qaiser I, Nayani K, et al. Childhood-onset systemic lupus erythematosus: a cohort study. Journal of the College of Physicians and Surgeons Pakistan [Internet]. 2018 [Cited 2024 Jan 5];28(5):365–9. Available from: http://dx.doi.org/10.29271/jcpsp.2018.05.365

Touma Z, Cervera R, Brinks R, Lorenzoni V, Tani C, Hoyer BF, et al. Associations between classification criteria items in systemic lupus erythematosus. Arthritis Care &amp [Internet]. 2020 [Cited 2024 Jan 5];72(12):1820–6. Available from: http://dx.doi.org/10.1002/acr.24078

Wright TB, Shults J, Leonard MB, Zemel BS, Burnham JM. Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus.J Pediatr [Internet].2009 [Cited 2024 Jan 5];155(2):260–5. Available from: http://dx.doi.org/10.1016/j.jpeds.2009.02.033

Couture J, Silverman ED. Update on the pathogenesis and treatment of childhood-onset systemic lupus erythematosus. Curr Opin Rheumatol [Internet]. 2016 [Cited 2024 Jan 5];28(5):488–96. Available from: http://dx.doi.org/10.1097/bor.0000000000000317

Tesser A, de Carvalho LM, Sandrin-Garcia P, Pin A, Pastore S, Taddio A, et al. Higher interferon score and normal complement levels may identify a distinct clinical subset in children with systemic lupus erythematosus. Arthritis Res Ther [Internet]. 2020 [Cited 2024 Jan 5] ;22(1):91. Available from: https://pubmed.ncbi.nlm.nih.gov/32334613

Bakr A. Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. Pediatric Nephrology [Internet]. 2005 [Cited 2024 Jan 5];20(8):1081–6. Available from: http://dx.doi.org/10.1007/s00467-005-1900-2

Charras A, Smith E, Hedrich CM. Systemic lupus erythematosus in children and young people. Curr Rheumatol Rep [Internet]. 2021 [Cited 2024 Jan 5];23(3):20. Available from: https://pubmed.ncbi.nlm.nih.gov/33569643

Massias JS, Smith EMD, Al-Abadi E, Armon K, Bailey K, Ciurtin C, et al. Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups. 2020/03/31. 2020 [Cited 2024 Jan 5];29(5):474–81. Available from: https://pubmed.ncbi.nlm.nih.gov/32233733

Singh A, Kamen DL. Potential benefits of vitamin D for patients with systemic lupus erythematosus. Dermatoendocrinol [Internet]. 2012 [Cited 2024 Jan 5];4(2):146–51. Available from: https://pubmed.ncbi.nlm.nih.gov/22928070

Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol [Internet]. 2008 [Cited 2024 Jan 5];68(3):261–9. Available from: http://dx.doi.org/10.1111/j.1365-3083.2008.02127.x

Ritterhouse LL, Crowe SR, Niewold TB, Kamen DL, Macwana SR, Roberts VC, et al. Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheum Dis [Internet]. 2011 [Cited 2024 Jan 5];70(9):1569–74. Available from: https://pubmed.ncbi.nlm.nih.gov/21586442

Azab SF, Ali YF, Farghaly MAA, Hamed ME, Allah MAN, Emam AA, et al. Vitamin D receptor gene BsmI polymorphisms in Egyptian children and adolescents with systemic lupus erythematosus: a case-control study. [Internet]. 2016 [Cited 2024 Sept 17];95(46):e5233–e5233. Available from: https://pubmed.ncbi.nlm.nih.gov/27861345

Peroni DG, Trambusti I, Di Cicco ME, Nuzzi G. Vitamin D in pediatric health and disease. Pediatric Allergy and Immunology [Internet]. 2020 [Cited 2024 Sept 17];31(S24):54–7. Available from: http://dx.doi.org/10.1111/pai.13154

Robinson AB, Thierry-Palmer M, Gibson KL, Rabinovich CE. Disease activity, proteinuria, and vitamin D status in children with systemic lupus erythematosus and juvenile dermatomyositis. J Pediatr [Internet]. 2012 [Cited 2024 Sept 17];160(2):297–302. Available from: https://pubmed.ncbi.nlm.nih.gov/21924736

Brustad N, Yousef S, Stokholm J, Bønnelykke K, Bisgaard H, Chawes BL. Safety of high-dose vitamin D supplementation among children aged 0 to 6 Years: A Systematic Review and Meta-analysis. JAMA Netw Open [Internet]. 2022 [Cited 2024 Sept 17] ;5(4):e227410–e227410. Available from: https://pubmed.ncbi.nlm.nih.gov/35420658

Eloi M, Horvath DV, Ortega JC, Prado MS, Andrade LEC, Szejnfeld VL, et al. 25-hydroxivitamin D serum concentration, not free and bioavailable vitamin D, Is associated with disease activity in systemic lupus erythematosus patients. PLoS One [Internet]. 2017 [Cited 2024 Sept 17];12(1):e0170323–e0170323. Available from: https://pubmed.ncbi.nlm.nih.gov/28085957

Sudewi NP, Kurniati N, Suyoko EMD, Munasir Z, Akib AAP. Karakteristik klinis lupus eritematosus sistemik pada anak. Sari Pediatri [Internet]. 2016 [Cited 2024 Sept 17];11(2):108. Available from: http://dx.doi.org/10.14238/sp11.2.2009.108-12

Ghrahani R, Ganesan PD, Ningrat RFS. Clinical Manifestations of Systemic Lupus Erythematous in Children at Dr. Hasan Sadikin General Hospital Bandung, Indonesia. Althea Medical Journal [Internet]. 2018 [Cited 2024 Sept 17] ;5(4):187–91. Available from: http://dx.doi.org/10.15850/amj.v5n4.664

Black SM, Walocko F, Li X, Chong BF. Development of systemic lupus in patients with cutaneous lupus using the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for systemic lupus erythematosus. J Am Acad Dermatol [Internet]. 2021 [Cited 2024 Sept 17];85(1):200–2. Available from: https://pubmed.ncbi.nlm.nih.gov/33421477

Aringer M, Petri M. New classification criteria for systemic lupus erythematosus. Curr Opin Rheumatol [Internet]. 2020 [Cited 2024 Sept 17];32(6):590–6. Available from: https://pubmed.ncbi.nlm.nih.gov/32925250

Octavius GS, Daleni VA, Angeline G, Virliani C. A systematic review and meta-analysis of prevalence of vitamin D deficiency among Indonesian pregnant women: a public health emergency. AJOG global reports [Internet]. 2023 [Cited 2024 Sept 17];3(2):100189. Available from: https://pubmed.ncbi.nlm.nih.gov/37234813

Adel Y, Elgamal M, Adel Abdelsalam S. Impact of vitamin D level and supplementation on systemic lupus erythematosus patients during COVID-19 pandemic. Arch Rheumatol [Internet]. 2022 [Cited 2024 Sept 17];37(2):288–99. Available from: https://pubmed.ncbi.nlm.nih.gov/36017215

Attar SM, Siddiqui AM. Vitamin d deficiency in patients with systemic lupus erythematosus. Oman Med J [Internet]. 2013 [Cited 2024 Sept 17];28(1):42–7. Available from: https://pubmed.ncbi.nlm.nih.gov/23386945

Thomas PE, Jensen BW, Sørensen KK, Jacobsen S, Aarestrup J, Baker JL. Early life body size, growth and risks of systemic lupus erythematosus – a large Danish observational cohort study. Semin Arthritis Rheum [Internet]. 2020 [Cited 2024 Sept 17];50(6):1507–12. Available from: http://dx.doi.org/10.1016/j.semarthrit.2020.01.011

Zou Y, Huang LC, Zhao D, He MJ, Su D, Zhang RH. Assessment of serum Vit A, D and zinc nutritional status and related dietary and exercise behaviors of children and adolescents in rural and urban area. Front Nutr [Internet]. 2023 [Cited 2024 Sept 17];9:1088155. Available from: https://pubmed.ncbi.nlm.nih.gov/36712499

Tobias DK, Luttmann-Gibson H, Mora S, Danik J, Bubes V, Copeland T, et al. Association of body weight with response to vitamin D supplementation and metabolism. JAMA Netw Open [Internet]. 2023 J[Cited 2024 Sept 17];6(1):e2250681–e2250681. Available from: https://pubmed.ncbi.nlm.nih.gov/36648947

Shamim R, Farman S, Batool S, Khan SEA, Raja MKH. Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus. Pak J Med Sci [Internet]. 2020 [Cited 2024 Sept 17];36(3):467–72. Available from: https://pubmed.ncbi.nlm.nih.gov/32292454

Athanassiou L, Kostoglou-Athanassiou I, Koutsilieris M, Shoenfeld Y. Vitamin D and autoimmune rheumatic diseases. Biomolecules [Internet]. 2023 [Cited 2024 Sept 17];13(4):709. Available from: https://pubmed.ncbi.nlm.nih.gov/37189455

Ao T, Kikuta J, Ishii M. The effects of Vitamin D on immune system and inflammatory diseases. Biomolecules [Internet]. 2021 [Cited 2025 March 3];11(11):1624. Available from: https://pubmed.ncbi.nlm.nih.gov/34827621

Asif S, Khan A, Zahoor S, Lashari N, Haroon M, Khanum A. Correlation between quantitative anti-dsDNA levels with severity of proteinuria in systemic lupus erythematosus patients. Reumatol Clin [Internet]. 2022 [Cited 2025 March 3];18(8):464–8. Available from: http://dx.doi.org/10.1016/j.reuma.2021.06.002

Zheng R, Gonzalez A, Yue J, Wu X, Qiu M, Gui L, et al. Efficacy and safety of vitamin D supplementation in patients with systemic lupus erythematosus: a meta-analysis of randomized controlled Trials. Am J Med Sci [Internet]. 2019 [Cited 2025 March 3];358(2):104–14. Available from: http://dx.doi.org/10.1016/j.amjms.2019.04.020

Athanassiou L, Kostoglou-Athanassiou I, Tsakiridis P, Devetzi E, Mavroudi M, Fytas P, et al. Vitamin D levels in Greek patients with systemic lupus erythematosus. [Internet] 2022 [Cited 2025 March 3];31(1):125–32. Available from: http://dx.doi.org/10.1177/09612033211066462

Irfan SA, Ali AA, Shabbir N, Altaf H, Ahmed A, Thamara Kunnath J, et al.Effects of vitamin D on systemic lupus erythematosus disease activity and autoimmunity: a systematic review and meta-analysis. Cureus [Internet].2022 [Cited 2025 March 3]. Available from: https://pubmed.ncbi.nlm.nih.gov/35844337/

Pesqueda-Cendejas K, Parra-Rojas I, Mora-García PE, Montoya-Buelna M, Ruiz-Ballesteros AI, Meza-Meza MR, et al. CRP Serum levels are associated with high cardiometabolic risk and clinical disease activity in systemic lupus erythematosus patients. J Clin Med [Internet]. 2022 [Cited 2025 March 3];11(7):1849. Available from: https://pubmed.ncbi.nlm.nih.gov/35407457

Yamany A, Behiry ME, Ahmed SA. Hyponatremia as an inflammatory marker of lupus activity is a fact or fad: a cross-sectional study. Open Access Rheumatol [Internet]. 2020 [Cited 2025 March 3];12:29–34. Available from: https://pubmed.ncbi.nlm.nih.gov/32210647

Du X, Zhao D, Wang Y, Sun Z, Yu Q, Jiang H, et al. Low serum calcium concentration in patients with systemic lupus erythematosus accompanied by the enhanced peripheral cellular immunity. Front Immunol [Internet]. 2022 [Cited 2025 March 3];13:901854. Available from: https://pubmed.ncbi.nlm.nih.gov/35757710

Guan S, Cai H, Wang P, Lv T, Liu L, Mao Y, et al. Association between circulating 25‐hydroxyvitamin D and systemic lupus erythematosus: a systematic review and meta‐analysis. Int J Rheum Dis [Internet]. 2019 [Cited 2025 March 3];22(10):1803–13. Available from: http://dx.doi.org/10.1111/1756-185x.13676

Alch C, Njoroge J, Keiser P. Hematological abnormalities among patients with systemic lupus erythematosus at Kenyatta national hospital, Nairobi. Ann Glob Health [Internet]. 2016 [Cited 2025 March 3];82(3):398. Available from: http://dx.doi.org/10.1016/j.aogh.2016.04.120

Cyntia Ratnadi P, Suega K, Made Renny Anggraeni Rena N. Hubungan Antara Kadar Hemoglobin dengan Tingkat Keparahan Penyakit Pasien Systemic Lupus Erythematosus di RSUP Sanglah. [Internet]. 2014 [Cited 2025 March 3]. Available from: https://ojs.unud.ac.id/index.php/eum/article/download/20926/13716

Bonakdar ZS, Jahanshahifar L, Jahanshahifar F, Gholamrezaei A. Vitamin D deficiency and its association with disease activity in new cases of systemic lupus erythematosus. Lupus. [Internet]. 2011 [Cited 2025 March 3];20(11):1155–60. Available from: http://dx.doi.org/10.1177/0961203311405703

Imran S, Thabah MM, Azharudeen M, Ramesh A, Bobby Z, Negi VS. Liver Abnormalities in systemic lupus erythematosus: a prospective observational Study. Cureus [Internet]. 2021 [Cited 2025 March 3];13(6):e15691–e15691. A Available from: https://pubmed.ncbi.nlm.nih.gov/34277279

Wang H, Ren Y le, Chang J, Gu L, Sun LY. A Systematic review and meta-analysis of prevalence of biopsy-proven lupus nephritis. Arch Rheumatol [Internet]. 2017 [Cited 2025 March 3] 25;33(1):17–25. Available from: https://pubmed.ncbi.nlm.nih.gov/29900975

Putri EVA, Subandijah K, Tjahjono HA. Perbedaan kadar vitamin 25-Oh-D antara nefritis lupus dengan lupus eritematosus sistemik pada anak. Sari Pediatri [Internet]. 2024 [Cited 2025 March 3];25(5):305. Available from: http://dx.doi.org/10.14238/sp25.5.2024.305-9