SLE in children and adolescents

Childhood-onset systemic lupus erythematosus (cSLE), also called paediatric SLE or juvenile SLE, presents before the age of 18 years and accounts for approximately 15–20% of all SLE cases. cSLE is characterised by a more severe disease phenotype than adult-onset SLE — with higher rates of lupus nephritis, neuropsychiatric involvement, haematological disease, and more frequent disease flares. The female predominance is less marked in prepubertal children (female:male ~4:1) but increases after puberty to ~9:1. Early and accurate diagnosis is critical as delayed treatment leads to disproportionate organ damage during critical developmental years.

The pathophysiology of cSLE mirrors adult SLE — dysregulated innate and adaptive immunity, type I interferon pathway activation, loss of self-tolerance to nuclear antigens, and immune complex-mediated tissue injury. However, monogenic causes of SLE-like disease are more prevalent in young children and should be considered, particularly in children presenting under 5 years of age.

Shared Mechanisms with Adult SLE

• Type I interferon pathway — plasmacytoid dendritic cells and neutrophil extracellular traps (NETs) drive IFN-α/β production; the interferon signature is prominent in cSLE and correlates with disease activity
• Autoantibody production — anti-dsDNA, anti-Sm, anti-Ro/SSA, antiphospholipid antibodies; identical to adult SLE
• Complement consumption — low C3/C4 during active nephritis; C4A null allele contributes to predisposition
• T and B cell dysregulation — loss of peripheral tolerance; autoreactive B cell survival; Th17/Treg imbalance

Monogenic and Early-Onset SLE

• Children presenting before age 5 years — consider monogenic interferonopathies (TREX1 mutations, STING-associated vasculopathy, RNASEH2 mutations) and complement deficiency syndromes (C1q, C2, C4 deficiency)
• TREX1 mutations — most common monogenic cause of childhood-onset lupus; impaired clearance of cytosolic DNA; constitutive type I IFN activation
• C1q deficiency — >90% develop SLE-like disease; impaired apoptotic clearance; very low C3/C4/CH50
• Genetics referral recommended for cSLE presenting <5 years, consanguinity, or unusual severity

Hormonal and Environmental Factors

• Prepubertal equal sex ratio increases post-puberty with oestrogen influence on B cell activity
• EBV infection — molecular mimicry with Sm antigen; strong epidemiological association with SLE onset
• UV light — activates keratinocyte apoptosis and NETosis; triggers flares as in adults

cSLE typically presents with a combination of constitutional symptoms and multi-organ involvement. The threshold for investigation should be low in any child with unexplained multisystem illness, cytopenias, or nephritis. Diagnosis may be delayed due to atypical presentations and low clinical suspicion.

Common Clinical Features in cSLE

Macrophage Activation Syndrome (MAS)

• MAS/haemophagocytic lymphohistiocytosis (HLH) is a life-threatening complication of cSLE — more common than in adults
• Features: paradoxically falling FBC despite disease activity; hyperferritinaemia (>500 μg/L; often >10,000); high LDH; coagulopathy; hepatosplenomegaly; high triglycerides
• Urgent paediatric rheumatology and haematology consultation; high-dose IV methylprednisolone ± ciclosporin; consider anakinra for refractory MAS

Investigation of suspected cSLE follows the same principles as adult SLE. Renal biopsy is indicated for lupus nephritis classification. Genetic testing is indicated for early-onset or atypical cases.

• Essential
  ANA (HEp-2 IIF)

  Entry criterion for 2019 EULAR/ACR criteria. Positive in >95% of cSLE. Titre ≥1:80 required. ANA positive in healthy children (~5–15%) — must be interpreted in clinical context. Homogeneous pattern suggests anti-dsDNA; speckled suggests anti-ENA.
• Essential
  Anti-dsDNA + ENA panel (anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-U1 RNP)

  Anti-dsDNA highly specific; correlates with nephritis risk. Anti-Sm highly specific for SLE. Anti-Ro/SSA in context of photosensitivity and neonatal lupus considerations for future pregnancies.
• Essential
  Complement C3, C4, CH50

  Low C3/C4 in active nephritis. Very low CH50 (<10%) suggests complement component deficiency (C1q, C2, C4) — consider genetics referral. Serial monitoring with anti-dsDNA.
• Essential
  FBC, UEC, LFTs, CRP, ESR, LDH, ferritin

  Cytopenias; renal function; LDH and ferritin screen for MAS. CRP typically low-normal in SLE flare. Very high ferritin (>500) → exclude MAS.
• Essential
  Urinalysis and urine protein:creatinine ratio

  At every clinical visit in cSLE. Haematuria, proteinuria, red cell casts = nephritis. Urine PCR >100 mg/mmol = significant proteinuria in children.
• Essential
  Antiphospholipid antibody (aPL) panel

  Lupus anticoagulant, anti-cardiolipin IgG/IgM, anti-β2GP-I IgG/IgM. aPL present in ~25–40% cSLE; thrombosis risk assessment essential. Confirm positivity ≥12 weeks apart.
• Recommended
  Renal biopsy

  Indicated for suspected lupus nephritis (haematuria + proteinuria or renal impairment). Necessary for ISN/RPS class — guides induction therapy. Paediatric nephrology should be involved.
• Recommended
  Bone age X-ray and growth parameters

  Document height, weight, and pubertal status at diagnosis. Monitor growth velocity — chronic disease and corticosteroids impair linear growth. Bone age if growth faltering.
• Recommended
  Genetic testing (monogenic SLE panel)

  Indicated if onset <5 years, consanguinity, severe or refractory disease, or family history suggesting monogenic immunodeficiency. Referral to paediatric immunology/genetics.

cSLE is generally more severe than adult SLE. Disease activity is measured using the SLEDAI-2K (same as adults). Damage accrual during childhood significantly impacts adult quality of life and organ function. Risk stratification guides treatment intensity.

Pharmacological management of cSLE follows the same principles as adult SLE. Hydroxychloroquine is prescribed for all children with SLE. Dosing must be weight-based. Growth and pubertal development must be considered in treatment decisions. Specialist paediatric rheumatology guidance is essential.

Directed therapy addresses organ-specific manifestations in cSLE that require targeted approaches beyond standard immunosuppression.

Lupus Nephritis in Children

• Renal biopsy required to classify nephritis before induction — same ISN/RPS classification as adults
• Class III/IV induction: IV methylprednisolone pulses (10–30 mg/kg/day × 3) + MMF 600 mg/m² twice daily + oral prednisolone taper; or Euro-Lupus cyclophosphamide IV
• Class V induction: MMF + prednisolone; add calcineurin inhibitor for persistent nephrotic proteinuria
• Maintenance: MMF (600 mg/m² twice daily) for minimum 3–5 years; azathioprine as alternative
• ACE inhibitor (ramipril) — renoprotective regardless of blood pressure; reduces proteinuria
• Target: complete renal response at 12 months (proteinuria <200 mg/mmol PCR, stable creatinine)
• Blood pressure target: <90th percentile for age/sex/height; ACE inhibitor first-line

Neuropsychiatric cSLE

• MRI brain and CSF — exclude infection, metabolic causes before attributing to NPSLE
• Chorea — characteristically seen with aPL; treat with aspirin ± valproate for symptom control; immunosuppression escalation
• Seizures: anti-epileptic therapy + immunosuppression escalation; neurology co-management
• Cognitive dysfunction — neuropsychological assessment; school support plans; liaise with educational psychologist

Growth and Pubertal Support

• Growth velocity monitoring — plot on paediatric growth chart every 3–6 months
• Minimise steroid dose to preserve growth; alternate-day dosing where possible
• Delayed puberty — assess bone age; endocrinology referral if pubertal delay or short stature
• Bone density — DXA at diagnosis and yearly on steroids; calcium + vitamin D supplementation

Reproductive Health in Adolescents

• Reproductive counselling — MMF and MTX are absolutely contraindicated in pregnancy; discuss contraception with all adolescent females on teratogenic medications
• Combined oral contraceptive pill — generally safe in aPL-negative, low-disease-activity cSLE; avoid in aPL-positive (thrombosis risk)
• Fertility preservation — consider oocyte/ovarian tissue cryopreservation before cyclophosphamide in adolescent females

Non-pharmacological management in cSLE addresses sun protection, bone health, school and psychosocial support, and transition planning — all particularly important in the paediatric context.

Sun Protection and School

• SPF 50+ broad-spectrum sunscreen daily — applied before school; reapply at lunch if outdoor activity
• UV-protective clothing, wide-brim hat; inform school staff about photosensitivity needs
• School plan letter — communicate physical limitations, medication needs, fatigue, and sun protection requirements to school
• Physical education — adapt to capacity; avoid prolonged outdoor activity in peak UV

Bone Health

• Calcium 1000–1300 mg/day + vitamin D 1000–2000 IU/day — all children on corticosteroids
• Bisphosphonate (pamidronate IV or zoledronate IV) — for significant bone density loss on prolonged steroids; specialist endocrinology input
• Weight-bearing exercise — promotes bone mineralisation; physiotherapy guidance
• DXA bone density — baseline; Z-score used in children (not T-score); annually on prolonged steroids

Vaccination

• Annual influenza vaccine — all cSLE patients; strongly recommended for immunosuppressed children
• Pneumococcal vaccine (13-valent + 23-valent) — all immunosuppressed children
• Meningococcal ACWY and B — recommended on immunosuppression
• HPV vaccine (Gardasil 9) — complete before immunosuppression if possible; recommended for all children
• Live vaccines (MMR, varicella, rotavirus) — contraindicated on significant immunosuppression; ensure up to date before starting
• COVID-19 vaccine — recommended for all cSLE patients; discuss timing with rheumatologist if on rituximab

Psychosocial Support

• Chronic illness in childhood — significant impact on identity, peer relationships, school performance, and mental health
• Psychology referral — anxiety and depression are common in cSLE; CBT effective for chronic pain and fatigue
• Lupus Australia and Arthritis Australia — paediatric resources and peer support networks
• Parent/carer education — disease understanding, medication recognition, flare recognition, emergency plan

Monitoring in cSLE is more intensive than in adults due to higher disease activity, growth parameters, and developmental considerations. All monitoring should be coordinated by paediatric rheumatology in collaboration with GP and paediatric subspecialties.

Transition to Adult Care

• Planned transition at 16–18 years — not a single handover but a structured process over 1–2 years
• Transition preparation — develop self-management skills; ensure adolescent understands their diagnosis, medications, and monitoring needs
• Joint clinic visits — paediatric and adult rheumatologist together; facilitates relationship building
• Transfer summary — comprehensive handover document including disease history, renal biopsy results, immunosuppression history, damage accrual, aPL status, vaccination record
• Flare risk at transition — adolescence and early adulthood associated with poor adherence; psychological support during transition

Specific subgroups within the cSLE population require additional consideration.

Very Early Onset SLE (<5 Years)

• Consider monogenic causes — TREX1, RNASEH2, STING, C1q/C2/C4 deficiency; genetics referral mandatory
• JAK inhibitors (baricitinib) may be beneficial in STING-associated vasculopathy and TREX1-associated interferonopathy — specialist paediatric rheumatology/immunology
• Family screening for complement deficiency and monogenic SLE

Male Children with cSLE

• More likely to have complement deficiency — check CH50 and individual complement components
• Often more severe disease — nephritis and neuropsychiatric involvement at higher rates than female children
• Do not overlook diagnosis because of male sex — SLE in boys is often diagnosed late

Neonatal Lupus (Maternal Anti-Ro/SSA)

• Neonatal lupus is caused by transplacental passage of maternal anti-Ro/SSA (and anti-La/SSB) antibodies — not cSLE
• Features: congenital complete heart block (CHB; permanent, may require pacing), transient rash, cytopenias, hepatitis — resolves as maternal antibodies clear (~6 months)
• CHB screening — fetal echocardiography weekly 16–26 weeks in anti-Ro/SSA positive mothers
• Preventive treatment for CHB — hydroxychloroquine during pregnancy reduces CHB recurrence risk

Adherence in Adolescents

• Medication non-adherence is a major cause of flares and damage accrual in cSLE — especially hydroxychloroquine
• Address denial, body image concerns (steroid weight gain, alopecia, rashes), peer pressure, and transition-related disruption
• Motivational interviewing and age-appropriate education; pharmacist medication counselling

Stewardship in cSLE focuses on minimising corticosteroid toxicity, ensuring HCQ adherence, age-appropriate dosing, and safe reproductive management in adolescents.

GP and Paediatrician Role

• Urinalysis at every visit — the single most important screen for lupus nephritis recurrence
• Growth monitoring — plot on chart at every visit; signal to rheumatologist if growth faltering
• Blood pressure monitoring — use paediatric norms; hypertension = nephritis signal
• Vaccination review — update annually before immunosuppression escalation
• School letter support — assist family with school accommodation letters for physical limitations
• HCQ adherence support — reinforce importance at every visit; address barriers

Lifelong rheumatologist-led follow-up is required. The critical paediatric period — from diagnosis through adolescence to transition — requires structured, developmental-stage-appropriate care.

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