Abstract
Systemic lupus erythematosus (SLE) results from complex abnormalities of the innate and acquired immune systems. For reasons that are currently not well understood, the disease course and phenotype associated with SLE, although quite variable, are generally more severe when the diagnosis is made during childhood. Active disease, infections, lupus nephritis, and neuropsychiatric SLE manifestations are associated with higher morbidity and mortality. Unlike in adult-onset SLE, systemic glucocorticoid therapy and immunosuppressive medications are needed for the treatment of the majority of children and adolescents with SLE. The complex nature of childhood-onset SLE demands a comprehensive, multidisciplinary management approach that considers the patients' growth and development, their educational needs, and the unpredictable course of SLE and its complications.
Key Points
-
Disease severity and issues of growth, development, educational and psychosocial needs are some of the features that distinguish pediatric SLE (pSLE) from adult-onset SLE (aSLE)
-
Disease indices used to measure disease activity and damage in aSLE have been validated and are used in pSLE
-
Patients with pSLE require monitoring for adherence and response to treatment, occurrence of disease flares and damage, as well as health-maintenance issues such as immunizations, bone density and premature atherosclerotic disease
-
Patients with pSLE are at a high risk of tissue damage, and require prompt, often aggressive, management
-
Research is ongoing to improve the available tests for assessing disease activity in pSLE, especially lupus nephritis
-
Treatments for pSLE currently have similar limitations as those for aSLE; however, improvement in our understanding of the B-cell biology of SLE may result in more therapeutic options for pSLE
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lo, J. T. et al. Sex differences in pediatric systemic lupus erythematosus: a retrospective analysis of 135 cases. J. Microbiol. Immunol. Infect. 32, 173–178 (1999).
Hochberg, M. C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40, 1725 (1997).
Ferraz, M. B. et al. Evaluation of the 1982 ARA lupus criteria data set in pediatric patients. Committees of Pediatric Rheumatology of the Brazilian Society of Pediatrics and the Brazilian Society of Rheumatology. Clin. Exp. Rheumatol. 12, 83–87 (1994).
Tucker, L. B. & Fernandez, M. Clinical differences between juvenile and adult onset patients with systemic lupus erythematosus: results from a multiethnic longitudinal cohort. Arthritis Rheum. 54, S162 (2006).
Brunner, H. I., Gladman, D. D., Ibañez, D., Urowitz, M. D. & Silverman, E. D. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 58, 556–562 (2008).
Mina, R. & Brunner, H. I. Pediatric lupus—are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus? Rheum. Dis. Clin. North Am. 36, 53–80 (2010).
Cook, C. D., Wedgwood, R. J., Craig, J. M., Hartmann, J. R. & Janeway, C. A. Systemic lupus erythematosus. Description of 37 cases in children and a discussion of endocrine therapy in 32 of the cases. Pediatrics 26, 570–585 (1960).
Tucker, L. B. 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). Lupus 17, 314–322 (2008).
Brunner, H. I., Sherrard, T. M. & Klein-Gitelman, M. S. Cost of treatment of childhood-onset systemic lupus erythematosus. Arthritis Rheum. 55, 184–188 (2006).
Cervera, R. et al. Lessons from the “Euro-Lupus Cohort”. Ann. Med. Interne (Paris) 153, 530–536 (2002).
Glidden, R. S., Mantzouranis, E. C. & Borel, Y. Systemic lupus erythematosus in childhood: clinical manifestations and improved survival in fifty-five patients. Clin. Immunol. Immunopathol. 29, 196–210 (1983).
Gonzalez, B. et al. Changes in the survival of patients with systemic lupus erythematosus in childhood: 30 years experience in Chile. Lupus 14, 918–923 (2005).
Hersh, A. O. et al. Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus. Arthritis Care Res. (Hoboken) 62, 1152–1159 (2010).
Gutiérrez-Suárez, R. et al. A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum. 54, 2989–2996 (2006).
Hurley, R. M., Steinberg, R. H., Patriquin, H. & Drummond, K. N. A vascular necrosis of the femoral head in childhood systemic lupus erythematosus. Can. Med. Assoc. J. 111, 781–784 (1974).
Ibanez, D., Gladman, D. D. & Urowitz, M. B. Adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2K is a predictor of outcome in SLE. J. Rheumatol. 32, 824–827 (2005).
Nakamura, J. et al. Age at time of corticosteroid administration is a risk factor for osteonecrosis in pediatric patients with systemic lupus erythematosus: a prospective magnetic resonance imaging study. Arthritis Rheum. 62, 609–615 (2010).
Powell, C., Chang, C., Naguwa, S. M., Cheema, G. & Gershwin, M. E. Steroid induced osteonecrosis: an analysis of steroid dosing risk. Autoimmun. Rev. 9, 721–743 (2010).
Tektonidou, M. G., Malagari, K., Vlachoyiannopoulos, P. G., Kelekis, D. A. & Moutsopoulos, H. M. Asymptomatic avascular necrosis in patients with primary antiphospholipid syndrome in the absence of corticosteroid use: a prospective study by magnetic resonance imaging. Arthritis Rheum. 48, 732–736 (2003).
Nakamura, J. et al. Development of new osteonecrosis in systemic lupus erythematosus patients in association with long-term corticosteroid therapy after disease recurrence. Clin. Exp. Rheumatol. 28, 13–18 (2010).
Nakamura, J. et al. Spontaneous repair of asymptomatic osteonecrosis associated with corticosteroid therapy in systemic lupus erythematosus: 10-year minimum follow-up with MRI. Lupus 19, 1307–1314 (2010).
Brunner, H. I. et al. Health-related quality of life and its relationship to patient disease course in childhood-onset systemic lupus erythematosus. J. Rheumatol. 36, 1536–1545 (2009).
Brunner, H. I., Feldman, B. M., Bombardier, C. & Silverman, E. D. 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 Rheum. 42, 1354–1360 (1999).
Brunner, H. I., Silverman, E. D., Bombardier, C. & Feldman, B. M. European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood-onset systemic lupus erythematosus. Arthritis Rheum. 49, 335–341 (2003).
Brunner, H. I. et al. Minimal clinically important differences of the childhood health assessment questionnaire. J. Rheumatol. 32, 150–161 (2005).
Ruperto, N. et al. The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement. Arthritis Rheum. 55, 355–363 (2006).
Mina, R. et al. Defining and measuring global flares in juvenile systemic lupus erythematosus. Presented at the 9th International Congress on Systemic Lupus Erythematosus, Vancouver, Canada, June 2010.
Meiorin, S. et al. Validation of the Childhood Health Assessment Questionnaire in active juvenile systemic lupus erythematosus. Arthritis Rheum. 59, 1112–1119 (2008).
Moorthy, L. N. et al. Multicenter validation of a new quality of life measure in pediatric lupus. Arthritis Rheum. 57, 1165–1173 (2007).
Ho, A., Barr, S. G., Magder, L. S. & Petri, M. A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum. 44, 2350–2357 (2001).
Ho, A., Magder, L. S., Barr, S. G. & Petri, M. Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum. 44, 2342–2349 (2001).
Rovin, B. H., Birmingham, D. J., Nagaraja, H. N., Yu, C. Y. & Hebert, L. A. Biomarker discovery in human SLE nephritis. Bull. NYU Hosp. Jt Dis. 65, 187–193 (2007).
Calano, S. J. et al. Cell-bound complement activation products (CB-CAPs) as a source of lupus biomarkers. Adv. Exp. Med. Biol. 586, 381–390 (2006).
Manzi, S. et al. Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus. Arthritis Rheum. 50, 3596–3604 (2004).
Hinze, C. H. et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum. 60, 2772–2781 (2009).
Suzuki, M. et al. Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis. Pediatr. Res. 65, 530–536 (2009).
Zhang, X. et al. Biomarkers of lupus nephritis determined by serial urine proteomics. Kidney Int. 74, 799–807 (2008).
Kazderova, M., Jancova, E., Rysava, R., Merta, M. & Tesar, V. Mycophenolate mofetil in low doses stabilizes and improves antineutrophil cytoplasmic antibody-associated vasculitis and lupus nephritis. Arch. Med. Res. 39, 115–119 (2008).
Chaussabel, D. et al. A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29, 150–164 (2008).
Costedoat-Chalumeau, N. et al. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 54, 3284–3290 (2006).
Brunner, H. I., Klein-Gitelman, M. S., Ying, J., Tucker, L. B. & Silverman, E. D. Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers. Clin. Exp. Rheumatol. 27, 155–162 (2009).
Schanberg, L. E. et al. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima–media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. Arthritis Rheum. 60, 1496–1507 (2009).
Guiducci, C. et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465, 937–941 (2010).
Touma, Z. et al. Mycophenolate mofetil for induction treatment of lupus nephritis: a systematic review and metaanalysis. J. Rheumatol. 38, 69–78 (2011).
Molino, D. et al. Childhood lupus nephritis (LN): mycophenolate mofetil (MMF) as induction and maintenance therapy. Pediat. Nephrol. 25, 1878 (2010).
Sundel, R. P., Lisk, L. & Grp, A. Mycophenolate mofetil compared with intravenous cyclophosphamide as induction treatment for pediatric lupus nephritis: a randomized trial. Arthritis Rheum. 58, S632–S633 (2008).
Lertdumrongluk, P. et al. Pharmacokinetics of mycophenolic acid in severe lupus nephritis. Kidney Int. 78, 389–395 (2010).
Roland, M. et al. Mycophenolate mofetil in patients with systemic lupus erythematosus: a prospective pharmacokinetic study. Lupus 18, 441–447 (2009).
Houssiau, F. A. et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum. 50, 3934–3940 (2004).
Somers, E. C., Marder, W., Christman, G. M., Ognenovski, V. & McCune, W. J. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum. 52, 2761–2767 (2005).
Silva, C. A. & Brunner, H. I. Gonadal functioning and preservation of reproductive fitness with juvenile systemic lupus erythematosus. Lupus 16, 593–599 (2007).
Sanz, I. & Lee, F. E. B cells as therapeutic targets in SLE. Nat. Rev. Rheumatol. 6, 326–337 (2010).
Marks, S. D. & Tullus, K. Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis. Acta Paediatr. 99, 967–974 (2010).
Merrill, J. T. et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62, 222–233 (2010).
Huggins, J. L. & Brunner, H. I. Targeting B cells in the treatment of childhood-onset systemic lupus erythematosus. J. Pediatr. 148, 571–573 (2006).
Birmingham, D. J. et al. Relationship between albuminuria and total proteinuria in systemic lupus erythematosus nephritis: diagnostic and therapeutic implications. Clin. J. Am. Soc. Nephrol. 3, 1028–1033 (2008).
Ross, A. C., Taylor, C. L., Yaktine, A. L. & Del Valle, H. B. Dietary Reference Intakes for Calcium and Vitamin D (The National Academies Press, Washington, D. C., (2011).
Bishop, N. et al. Dual-energy X-ray aborptiometry assessment in children and adolescents with diseases that may affect the skeleton: the 2007 ISCD Pediatric Official Positions. J. Clin. Densitom. 11, 29–42 (2008).
Ardoin, S. P. et al. Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort. Lupus 19, 1315–1325 (2010).
Metjian, A. & Lim, W. ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am. Soc. Hematol. Educ. Program 2009, 247–249 (2009).
Millet, A., Decaux, O., Perlat, A., Grosbois, B. & Jego, P. Systemic lupus erythematosus and vaccination. Eur. J. Intern. Med. 20, 236–241 (2009).
Lu, C. C. et al. A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: safety and immunity. Vaccine 29, 444–450 (2011).
Kuramochi, Y. et al. Cardiac tamponade due to systemic lupus erythematosus in patient with Prader–Willi syndrome after growth hormone therapy. Lupus 16, 447–449 (2007).
Yap, H. K., Loke, K. Y., Murugasu, B. & Lee, B. W. Subclinical activation of lupus nephritis by recombinant human growth hormone. Pediatr. Nephrol. 12, 133–135 (1998).
Yazdany, J. et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. 61, 370–377 (2009).
Duvdevany, I., Cohen, M., Minsker-Valtzer, A. & Lorber, M. Psychological correlates of adherence to self-care, disease activity and functioning in persons with systemic lupus erythematosus. Lupus 20, 14–22 (2011).
Koneru, S. et al. Adherence to medications in systemic lupus erythematosus. J. Clin. Rheumatol. 14, 195–201 (2008).
Acknowledgements
This work is supported by NIH grants 5U01-AR51868 and P60-AR047884.
C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
Author information
Authors and Affiliations
Contributions
H. I. Brunner and J. Huggins researched data for the article. H. I. Brunner and M. S. Klein-Gitelman made substantial contributions to discussing the content of the article. All authors took part in writing, reviewing and editing the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Brunner, H., Huggins, J. & Klein-Gitelman, M. Pediatric SLE—towards a comprehensive management plan. Nat Rev Rheumatol 7, 225–233 (2011). https://doi.org/10.1038/nrrheum.2011.15
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrrheum.2011.15
This article is cited by
-
Analysis of Meibomian Glands in Juvenile Systemic Lupus Erythematosus Patients without Dry Eye Symptoms and Signs
Japanese Journal of Ophthalmology (2023)
-
Systemic lupus of pediatric onset in Afro-Caribbean children: a cohort study in the French West Indies and French Guiana
Pediatric Rheumatology (2022)
-
IgM on the surface of T cells: a novel biomarker of pediatric-onset systemic lupus erythematosus
Pediatric Nephrology (2021)
-
Impact of the longitudinal quantitative assessment of juvenile systemic lupus erythematosus severity on the disease outcome
Clinical Rheumatology (2021)
-
Epidemiology and risk factors for avascular necrosis in childhood systemic lupus erythematosus in a Taiwanese population
Scientific Reports (2020)