Systemic Lupus Erythematosus in Pediatric Age
Introduction to Pediatric Systemic Lupus Erythematosus
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder characterized by multisystem inflammation and the production of autoantibodies. Pediatric-onset SLE, defined as disease onset before 18 years of age, accounts for approximately 20% of all SLE cases. It is generally more severe than adult-onset SLE, with higher rates of organ involvement and mortality.
Pediatric SLE presents unique challenges in diagnosis and management due to its more aggressive course, potential impact on growth and development, and long-term consequences of both the disease and its treatment. Understanding the nuances of pediatric SLE is crucial for early diagnosis and optimal management to improve long-term outcomes.
Epidemiology of Pediatric SLE
Incidence and Prevalence:
- The estimated incidence of pediatric SLE ranges from 0.3 to 0.9 per 100,000 children per year.
- Prevalence varies by region and ethnicity, ranging from 3.3 to 24 per 100,000 children.
Demographic Factors:
- Age: Peak onset is during adolescence, with a median age of 11-12 years. Rarely occurs before age 5.
- Gender: Female predominance, with a female to male ratio of 4:1 to 5:1 (less pronounced than in adult SLE).
- Ethnicity: Higher incidence and prevalence in non-Caucasian populations, particularly African American, Hispanic, and Asian children.
Genetic and Environmental Factors:
- Strong genetic component, with a concordance rate of 25-69% in monozygotic twins.
- Environmental triggers include UV radiation, infections (especially Epstein-Barr virus), and certain medications.
Pathophysiology of Pediatric SLE
The pathogenesis of pediatric SLE is multifactorial, involving complex interactions between genetic susceptibility, environmental triggers, and dysregulation of the immune system.
Key Components:
- Genetic Factors:
- Multiple susceptibility genes identified, including HLA-DR2 and HLA-DR3.
- Complement deficiencies (C1q, C2, C4) strongly associated with SLE.
- Immune Dysregulation:
- Impaired clearance of apoptotic cells and immune complexes.
- Hyperactive B cells producing autoantibodies.
- T cell abnormalities, including defective regulatory T cells.
- Increased production of pro-inflammatory cytokines (e.g., IFN-α, TNF-α, IL-6).
- Autoantibody Production:
- Anti-nuclear antibodies (ANA) - hallmark of SLE.
- Anti-double-stranded DNA (anti-dsDNA) antibodies.
- Anti-Smith (anti-Sm) antibodies.
- Antiphospholipid antibodies.
- Tissue Damage:
- Immune complex deposition in tissues.
- Complement activation.
- Direct cellular injury by autoantibodies.
Clinical Manifestations of Pediatric SLE
Pediatric SLE is characterized by a wide range of clinical manifestations, often more severe than in adult-onset disease. Common presentations include:
- Constitutional Symptoms:
- Fever, fatigue, weight loss, anorexia.
- Mucocutaneous Manifestations:
- Malar rash (butterfly rash) - 60-85% of cases.
- Photosensitivity - 50-60% of cases.
- Oral ulcers - 40-50% of cases.
- Alopecia - 30-40% of cases.
- Musculoskeletal Involvement:
- Arthritis or arthralgia - 80-95% of cases.
- Myositis - 20-30% of cases.
- Renal Involvement:
- Lupus nephritis - 50-75% of pediatric SLE cases.
- More common and severe in children compared to adults.
- Hematological Abnormalities:
- Anemia - 50-75% of cases.
- Leukopenia - 45-65% of cases.
- Thrombocytopenia - 15-45% of cases.
- Neuropsychiatric Manifestations:
- Headache, cognitive dysfunction, mood disorders.
- Seizures, psychosis, chorea (less common).
- Cardiovascular Involvement:
- Pericarditis - 15-25% of cases.
- Myocarditis, valvular disease (less common).
- Pulmonary Involvement:
- Pleuritis - 15-20% of cases.
- Interstitial lung disease, pulmonary hypertension (rare).
Diagnosis of Pediatric SLE
Diagnosis of pediatric SLE is based on a combination of clinical features and laboratory findings. The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria are commonly used:
- Entry Criterion: ANA titer ≥1:80
- Additive Criteria (need ≥10 points for classification):
- Clinical domains: Constitutional, Hematologic, Neuropsychiatric, Mucocutaneous, Serosal, Musculoskeletal, Renal
- Immunologic domains: Antiphospholipid antibodies, Complement proteins, SLE-specific antibodies
Key Laboratory Tests:
- Complete blood count (CBC)
- Urinalysis and urine protein-to-creatinine ratio
- Serum creatinine and estimated glomerular filtration rate (eGFR)
- Complement levels (C3, C4)
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- Autoantibodies: ANA, anti-dsDNA, anti-Sm, antiphospholipid antibodies
Additional Investigations:
- Renal biopsy (if nephritis suspected)
- Neuroimaging (if CNS involvement suspected)
- Echocardiogram (to assess cardiac involvement)
Treatment of Pediatric SLE
Management of pediatric SLE requires a multidisciplinary approach and is tailored to disease severity and organ involvement. The goals of treatment are to control disease activity, prevent organ damage, and minimize drug toxicity.
General Principles:
- Sun protection and education about lifestyle modifications
- Regular monitoring of disease activity and treatment side effects
- Vaccination against preventable infections (avoid live vaccines during immunosuppression)
- Psychosocial support and transition planning for adolescents
Pharmacological Treatment:
- Antimalarials:
- Hydroxychloroquine - cornerstone of SLE treatment
- Used in almost all patients, regardless of disease severity
- Glucocorticoids:
- Used for rapid control of disease activity
- Dose and duration based on severity of manifestations
- Long-term use associated with significant side effects
- Immunosuppressants:
- Mycophenolate mofetil - first-line for lupus nephritis
- Cyclophosphamide - severe organ involvement
- Azathioprine - maintenance therapy
- Methotrexate - predominantly cutaneous and musculoskeletal manifestations
- Biologics:
- Belimumab - FDA-approved for pediatric SLE (age ≥5 years)
- Rituximab - used off-label for refractory cases
Management of Specific Manifestations:
- Lupus nephritis: Aggressive immunosuppression with mycophenolate or cyclophosphamide
- Neuropsychiatric SLE: High-dose glucocorticoids, cyclophosphamide, or rituximab
- Hematologic involvement: Consider IVIG, rituximab for refractory cases
Prognosis of Pediatric SLE
The prognosis of pediatric SLE has significantly improved over the past decades due to earlier diagnosis and more effective treatments. However, it remains a chronic disease with potential for significant morbidity and mortality.
Survival Rates:
- 5-year survival rate: >95%
- 10-year survival rate: 80-90%
Prognostic Factors:
- Negative prognostic factors include:
- Severe organ involvement at onset (especially renal and CNS)
- Persistent disease activity
- Antiphospholipid antibody positivity
- Lower socioeconomic status
- Positive prognostic factors include:
- Early diagnosis and treatment
- Adherence to therapy
- Regular follow-up
Long-term Complications:
- Chronic organ damage (e.g., chronic kidney disease)
- Growth delay and pubertal delay
- Osteoporosis
- Cardiovascular disease
- Infections
- Malignancies (increased risk, particularly lymphomas)
Transition to Adult Care:
- Crucial for continuity of care and long-term outcomes
- Should be a gradual, planned process starting in early adolescence
- Focus on promoting self-management skills and health literacy
Systemic Lupus Erythematosus in Pediatric Age
- What is the typical age of onset for pediatric Systemic Lupus Erythematosus (SLE)?
Between 3 and 15 years, with a peak at 11-12 years - What is the female to male ratio in pediatric SLE?
4:1 to 5:1 - Which ethnic groups have a higher incidence of pediatric SLE?
African American, Hispanic, and Asian populations - What percentage of all SLE cases are diagnosed in childhood?
15-20% - Which organ system is more frequently and severely affected in pediatric SLE compared to adult SLE?
Renal system - What is the most common initial presenting symptom of pediatric SLE?
Fever - Which skin manifestation is considered the hallmark of SLE?
Malar (butterfly) rash - What percentage of pediatric SLE patients develop nephritis?
50-75% - Which autoantibody is highly specific for SLE?
Anti-double stranded DNA (anti-dsDNA) - What is the name of the diagnostic criteria used for SLE?
SLICC (Systemic Lupus International Collaborating Clinics) criteria or 2019 EULAR/ACR criteria - Which hematologic abnormality is common in pediatric SLE?
Leukopenia - What is the most common neuropsychiatric manifestation in pediatric SLE?
Headache - Which complement components are typically low in active SLE?
C3 and C4 - What is the gold standard for diagnosing lupus nephritis?
Renal biopsy - Which medication is considered the cornerstone of SLE treatment?
Hydroxychloroquine - What is the role of corticosteroids in pediatric SLE treatment?
Used for rapid control of disease activity, especially during flares - Which immunosuppressive agent is commonly used for severe lupus nephritis?
Cyclophosphamide - What is the name of the tool used to measure disease activity in pediatric SLE?
SLEDAI (SLE Disease Activity Index) - Which cardiovascular complication is more common in pediatric SLE compared to the general pediatric population?
Accelerated atherosclerosis - What is the most common endocrine abnormality in pediatric SLE?
Hypothyroidism - Which pulmonary complication is associated with poor prognosis in pediatric SLE?
Pulmonary hemorrhage - What is the role of B-cell depleting therapy (e.g., rituximab) in pediatric SLE?
Used in refractory cases or severe organ involvement - Which growth-related complication is associated with long-term corticosteroid use in pediatric SLE?
Growth retardation - What is the recommended frequency of ophthalmologic examinations for pediatric SLE patients on hydroxychloroquine?
Annually - Which vaccine is contraindicated in pediatric SLE patients on high-dose immunosuppression?
Live attenuated vaccines - What is the role of sunscreen in SLE management?
To prevent photosensitivity reactions and disease flares - Which autoantibody is associated with an increased risk of thrombosis in SLE?
Antiphospholipid antibodies - What is the name of the syndrome characterized by fever, cytopenia, and hyperferritinemia in SLE?
Macrophage Activation Syndrome (MAS) - Which medication is used for maintenance therapy in lupus nephritis?
Mycophenolate mofetil or azathioprine - What is the 10-year survival rate for pediatric SLE in developed countries?
Over 90%
