Paeds · rheumatology-musculoskeletal-and-sports
Systemic lupus erythematosus
Also known as Systemic lupus erythematosus · Childhood-onset SLE · Juvenile systemic lupus erythematosus · Lupus · cSLE
Fellowship guide to childhood-onset systemic lupus erythematosus: the SLICC 2012 and EULAR/ACR 2019 weighted classification criteria, the type I interferon and immune-complex pathophysiology behind low complement and anti-dsDNA, the multisystem clinical presentation dominated by adolescent girls, the hydroxychloroquine backbone for every patient with retinopathy screening, and the stepwise escalation from glucocorticoids through mycophenolate and azathioprine to belimumab and anifrolumab for refractory disease.
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Red flags
- Adolescent girl with new malar rash sparing the nasolabial folds, oral ulcers, photosensitivity, and arthralgia
- Unexplained cytopenias, particularly autoimmune haemolytic anaemia or thrombocytopenia, alongside alopecia and fatigue
- Falling complement C3 and C4 with a rising anti-dsDNA titre signalling a disease flare, often with renal involvement
- New hypertension, oedema, and active urinary sediment indicating lupus nephritis demanding urgent biopsy
- Acute neuropsychiatric presentation with seizures, psychosis, or cognitive change in a child with a malar rash
- Adolescent with chest pain and a rub suggesting serositis, or painless oral ulcers with Raynaud phenomenon
- Pregnant woman or neonate with rash and congenital heart block raising the possibility of neonatal lupus from anti-Ro antibodies
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- Recognises that childhood-onset SLE is a multisystem autoimmune disease most common in adolescent girls
- Initiates antinuclear antibody, anti-dsDNA, and complement in any child with a malar rash, oral ulcers, unexplained cytopenias, or arthralgia
- Identifies hydroxychloroquine as the foundation therapy for every patient and the need for retinopathy screening
- Applies the SLICC 2012 and EULAR/ACR 2019 weighted classification criteria and distinguishes them from the older ACR 1997 criteria
- Designs stepwise therapy from hydroxychloroquine and glucocorticoids through mycophenolate, azathioprine, and methotrexate to belimumab and anifrolumab
- Manages nephritis, neuropsychiatric lupus, and macrophage activation syndrome and coordinates long-term transitional and reproductive care
- SLICC 2012 and EULAR/ACR 2019 classification criteria and the additive weighted score threshold of 10
- Type I interferon overactivity, immune-complex deposition, and complement consumption in pathophysiology
- Hydroxychloroquine for all patients, retinopathy screening, and the escalation to biologics for refractory disease
- Recognises a deteriorating adolescent with a lupus flare and escalates immunosuppression
- Communicates the chronic relapsing-remitting nature, adherence, and steroid-sparing strategy to family and young person
- Counsels on sun protection, vaccination, contraception, and transition to adult care
- Level 1: Recognition that lupus is a multisystem disease and that a positive ANA with low complement warrants referral
- Level 2: Application of classification criteria, initiation of hydroxychloroquine, and appropriate referral for organ-threatening disease
- Level 3: Management of refractory disease, treatment toxicity, macrophage activation syndrome, and coordination of transitional care
- EULAR/ACR 2019 weighted classification criteria with the entry criterion of a positive ANA and a threshold of 10 points
- Type I interferon signature, anti-dsDNA and anti-Smith antibodies, and low complement in pathogenesis
- Hydroxychloroquine backbone, glucocorticoid-sparing immunosuppression, and biologic therapy
- Assessment and initial management of an adolescent girl with malar rash, oral ulcers, arthritis, and cytopenias
- Interpretation of autoantibody and complement profiles and recognition of a serological flare
- Structured explanation of the treatment ladder and counselling on hydroxychloroquine retinopathy and sun protection
- Recognition and initial evaluation of paediatric systemic lupus erythematosus including renal screening
- Classification criteria and the rationale for hydroxychloroquine in all patients
- Stepwise immunosuppression and biologic therapy with monitoring for treatment toxicity
- Recognition of childhood-onset SLE as a chronic multisystem disease and a major cause of morbidity in adolescents
- Initiation of appropriate serology and urgent rheumatology and nephrology referral
- Family communication on diagnosis, adherence, sun protection, and long-term surveillance
- Canadian approach to SLE classification and stepwise management aligned with EULAR and ACR guidance
- Use of mycophenolate, calcineurin inhibitors, and biologic agents in organ-threatening and refractory disease
- Long-term cardiovascular, bone, and reproductive follow-up after chronic immunosuppression
Overview & Definition
A 13-year-old girl presents with three months of fatigue, joint pains in her wrists and fingers, painful mouth ulcers, and a red rash across her cheeks that worsens in sunlight. Her haemoglobin is low, her platelets are borderline, and bloods reveal a strongly positive antinuclear antibody, a high-titre anti-dsDNA, and low complement C3 and C4. This is childhood-onset systemic lupus erythematosus, a chronic multisystem autoimmune disease in which loss of tolerance to nuclear antigens generates pathogenic autoantibodies and immune complexes that deposit in tissues and drive inflammation across virtually every organ. In children the disease is more aggressive than in adults, with a higher burden of organ involvement, particularly renal, haematological, and neuropsychiatric disease. [4]
Systemic lupus erythematosus is fundamentally a disease of disordered immune regulation. The body loses self-tolerance, produces autoantibodies directed against nuclear material (most characteristically anti-double-stranded DNA and anti-Smith), and forms immune complexes that circulate and deposit in skin, joints, glomeruli, serosa, and the central nervous system. Complement is consumed in the process, which is why low C3 and C4 are the serological hallmark of active disease. A persistent type I interferon signature amplifies the immune response and sustains the loss of tolerance, linking the genetic susceptibility, the environmental triggers of ultraviolet light and infection, and the clinical phenotype. [5]
The distinction between childhood-onset and adult-onset disease matters for the exam. Children more often present with organ-threatening disease at or soon after diagnosis, accumulate damage faster, and require more aggressive and sustained immunosuppression. Lupus nephritis affects roughly 50 to 80 percent of children compared with 30 to 40 percent of adults, and haematological and neuropsychiatric involvement are likewise over-represented. Because the kidney, brain, and blood can be the presenting organ, any child with an unexplained multisystem illness, cytopenia, or nephritis needs lupus excluded with a focused autoantibody and complement screen. [4]
References12ShowHide
- [1]Aringer M, Costenbader K, Daikh D, et al 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol, 2019.PMID 31385462
- [2]Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum, 2012.PMID 22553077
- [3]Hochberg MC Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1997.PMID 9324032
- [4]Kamphuis S, Silverman ED Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nat Rev Rheumatol, 2010.PMID 20683438
- [5]Groot N, de Graeff N, Avcin T, et al European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis, 2017.PMID 28877866
- [6]Fanouriakis A, Kostopoulou M, Alunno A, et al 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis, 2019.PMID 30926722
- [7]Marmor MF, Kellner U, Lai TY, et al Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology, 2016.PMID 26992838
- [8]Fanouriakis A, Kostopoulou M, Cheema K, et al 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis, 2020.PMID 32220834
- [9]Sammaritano LR, Askanase A, Bermas BL, et al 2024 American College of Rheumatism (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis Rheumatol, 2025.PMID 40331662
- [10]Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial (BLISS-52). Lancet, 2011.PMID 21296403
- [11]Brunner HI, Antón J, Calvo-Penadés I, et al. Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Belimumab in Pediatric Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken), 2026.PMID 41261055
- [12]Morand EF, Furie R, Tanaka Y, et al Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med, 2020.PMID 31851795