Paediatrics chapters
Systemic lupus erythematosus in children
Childhood lupus: who gets it, how autoantibodies cause damage, the 11 classification criteria, the key antibody and complement tests, lupus nephritis, treatment with hydroxychloroquine, steroids and immunosuppressants, lifelong monitoring and neonatal lupus.
- SLE is a chronic multisystem autoimmune disease driven by autoantibodies and immune complexes; in children it mostly begins around puberty, mainly in adolescent girls, and is rare under 9 years.
- Diagnosis needs 4 of 11 criteria (skin, mouth, joints, serosa, kidney, brain, blood, immunology, ANA); ANA is almost always positive, anti-dsDNA and anti-Sm are specific, and C3 and C4 are low in active disease.
- Lupus nephritis is the main cause of illness and death; treat with hydroxychloroquine, corticosteroids and, for severe renal or CNS disease, cyclophosphamide or other immunosuppressants, plus sun protection and lifelong monitoring.
On this page
Overview
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the body makes large amounts of autoantibodies against its own antigens, especially nuclear antigens such as DNA. These form immune complexes that inflame skin, joints, serosa, kidneys, brain and blood cells.
In children, kidney involvement is common and serious. Exams test the typical patient, the 11 criteria, the antibody and complement tests, lupus nephritis, treatment and neonatal lupus.
Definition
A multisystem inflammatory disease marked by circulating autoantibodies to self-antigens. It may begin suddenly with severe illness or slowly with vague symptoms.
Epidemiology
- About 5% of all SLE starts in childhood, mainly around puberty; it is rare under 9 years.
- Most affected children are adolescent girls.
- Sex ratio: Akbar gives about 2.5 girls to 1 boy before puberty and 9 to 1 in the reproductive years; Nelson notes a more even ratio in young children with female predominance from adolescence.
- Prevalence: the books differ (Akbar about 1-6, Nelson about 10-25 per 100,000 children). Exams usually test the age and sex pattern rather than the exact rate.
Aetiology and triggers
The cause is unknown; genetic, hormonal, immunological and environmental factors all play a part.
- Genetic: inherited deficiency of early complement components predisposes to SLE.
- Hormonal: female predominance after puberty.
- Ultraviolet light: damages skin cells, exposing nuclear material; sun exposure triggers flares.
- Drugs: drug-induced lupus (for example some anticonvulsants) causes fever, rash and pleuropericarditis that settle when the drug is stopped; it is linked with anti-histone (DNA-histone) antibodies.
Pathophysiology
- Loss of T-cell control of B cells (fewer and weaker regulatory T cells) leads to B-cell overactivity.
- B cells make autoantibodies against DNA and other nuclear antigens; a type I interferon signature promotes this.
- Damaged and dying cells (for example after UV light) release nuclear material that sustains the response.
- Autoantibodies and antigens form immune complexes that lodge in small vessels, especially glomeruli.
- These activate complement (so C3 and C4 fall), causing inflammation and ischaemia.
- Some antibodies act directly: against red cells, white cells and platelets (cytopenias) and against phospholipids (thrombosis).
Clinical features
| System | Features |
|---|---|
| Constitutional | Fever, fatigue, malaise, anorexia, weight loss |
| Skin (up to 95%) | Malar (butterfly) rash over cheeks and nose, sparing the nasolabial folds; photosensitivity; discoid lupus (scarring, loss of pigment, permanent alopecia on the scalp); vasculitic or purpuric lesions; Raynaud phenomenon; livedo reticularis |
| Mucosa | Oral and nasal ulcers, sometimes perforating the nasal septum |
| Musculoskeletal | Arthralgia or arthritis, often the commonest presenting feature; non-erosive, mainly small joints of the hands; myalgia or myositis |
| Kidney (50-80%) | Haematuria, proteinuria, nephrotic or nephritic syndrome, hypertension, renal failure |
| Serosa | Pleuritis, pericarditis, peritonitis |
| Heart and lungs | Pericarditis, myocarditis, Libman-Sacks endocarditis; pneumonitis, pulmonary haemorrhage |
| Nervous system | Seizures, psychosis, headache, stroke, chorea, transverse myelitis, poor school performance |
| Blood | Haemolytic anaemia, leucopenia and lymphopenia, thrombocytopenia |
| Reticuloendothelial | Lymphadenopathy (axillary nodes track activity), hepatosplenomegaly |
| Gut and eye | Mesenteric arteritis, pancreatitis, hepatitis; retinitis (cytoid bodies), episcleritis |
Lupus arthritis is non-erosive and rarely deforming; erosions on X-ray point instead to JIA (especially RF-positive polyarticular disease).
In a teenage girl with fever, joint pains, malar rash and abnormal urine, think of SLE first.
Diagnostic criteria (1997 revised criteria quoted in both books)
Four or more of these 11 criteria, present together or at different times, classify a patient as having SLE (about 98% sensitive and 97% specific).
| No. | Criterion | Detail |
|---|---|---|
| 1 | Malar rash | Fixed redness over the cheeks |
| 2 | Discoid rash | Scarring plaques |
| 3 | Photosensitivity | Rash after sunlight |
| 4 | Oral or nasal ulcers | Mouth or nose |
| 5 | Arthritis | Non-erosive, two or more joints with tenderness or effusion |
| 6 | Serositis | Pleuritis or pericarditis |
| 7 | Renal disorder | Persistent proteinuria (over 500 mg/24 hours) or cellular casts |
| 8 | Neurological disorder | Seizures or psychosis with no other cause |
| 9 | Haematological disorder | Haemolytic anaemia with reticulocytosis, leucopenia under 4,000/mm3, lymphopenia under 1,500/mm3 (on two occasions), or thrombocytopenia under 100,000/mm3 |
| 10 | Immunological disorder | Anti-dsDNA, anti-Sm, or antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, or false-positive syphilis serology) |
| 11 | Positive ANA | Without drugs known to cause lupus |
"SOAP BRAIN MD": Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood, Renal, ANA, Immunological, Neurological, Malar, Discoid.
Investigations
Baseline
- Full blood count: anaemia (chronic disease or Coombs-positive haemolysis), lymphopenia, thrombocytopenia.
- ESR: raised.
- Urinalysis: red cells, white cells, red cell casts, proteinuria; urine protein quantified.
- Urea, creatinine, albumin; blood pressure.
- Serum globulins: polyclonal hypergammaglobulinaemia.
- Coagulation (a prolonged APTT suggests lupus anticoagulant).
Confirmatory
| Test | Key points |
|---|---|
| ANA | Positive in over 97%, usually at high titre; most sensitive; a negative ANA effectively excludes SLE, but a positive ANA alone is not specific |
| Anti-double-stranded DNA | Found in most patients (Akbar: about two-thirds), almost only in SLE; titre rises with activity and with renal disease |
| Anti-Smith (Sm) | Highly specific, but present in only about 30% |
| Anti-Ro (SSA), anti-La (SSB) | Also in Sjogren syndrome; cause neonatal lupus |
| Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant) | Increase the risk of arterial and venous thrombosis; false-positive VDRL |
| C3, C4, CH50 | Low in active disease (complement consumed); normalise with effective treatment, so used to monitor |
| Anti-histone | Drug-induced lupus |
| Rheumatoid factor | Sometimes positive |
| Renal biopsy | Gold standard for lupus nephritis; done to classify it and choose treatment |
| CSF and MRI brain | For suspected CNS lupus: raised CSF protein and IgG index; MRI may show infarcts, vasculitis or atrophy |
ANA = most sensitive; anti-dsDNA and anti-Sm = most specific; anti-dsDNA and complement = follow disease activity.
Lupus nephritis
- Kidney involvement is present in up to 80% of children at presentation (Nelson 50-70%) and is the most important cause of morbidity and death.
- Mechanism: immune complexes (including anti-dsDNA) deposit in glomeruli and activate complement.
- Presents as nephritic or nephrotic syndrome with hypertension and reduced renal function; rarely as rapidly progressive glomerulonephritis. Oedema or hypertension in a child with SLE suggests renal disease.
- The urine can underestimate the damage, so renal biopsy is used to stage the disease (WHO classes).
- Treatment by class (Akbar):
- Class I and II: no specific therapy.
- Class III and IV (moderate to severe): prednisolone 1-2 mg/kg/day for 4-6 weeks, tapered to a maintenance dose of 0.2-0.3 mg/kg/day for 2-3 years or more, with intravenous cyclophosphamide pulses at regular intervals; mycophenolate is an alternative to cyclophosphamide.
Post-streptococcal glomerulonephritis lowers C3 with a raised ASO and a normal ANA; lupus nephritis lowers both C3 and C4 with positive ANA and anti-dsDNA.
Differential diagnosis
- Systemic-onset JIA (fever, rash, serositis, but ANA negative and high platelets).
- Acute post-streptococcal glomerulonephritis.
- Acute rheumatic fever, infective endocarditis.
- Leukaemia, immune thrombocytopenic purpura, autoimmune haemolytic anaemia.
- Viral infections, drug-induced lupus, mixed connective tissue disease and other collagen-vascular diseases.
Management
Treatment is matched to the organs involved, to limit drug toxicity.
General
- Avoid sun and use sunscreen: sunlight triggers flares.
- Calcium and vitamin D to protect bone on long-term steroids.
- Treat hyperlipidaemia early, keep weight healthy and stay active (cardiovascular risk).
- Education of child and family; school support.
Drugs
| Drug | Use |
|---|---|
| Hydroxychloroquine (Akbar: 5-7 mg/kg/day orally) | Skin and joint disease, discoid lupus and maintenance; lengthens periods of wellness and reduces flares |
| NSAIDs | Arthritis and pleuritic pain |
| Corticosteroids (the mainstay) | Prednisone 1-2 mg/kg/day for systemic disease, tapered to the lowest effective dose once complement returns to normal |
| Pulse methylprednisolone | Severely ill patients: 30 mg/kg/dose (maximum 1 g) over 60 minutes for 3 days, then weekly pulses |
| Cyclophosphamide (Akbar: 0.5-1 g/m2 IV monthly) | Severe lupus nephritis, CNS lupus, vasculitis, pulmonary haemorrhage; reduces progression to renal failure |
| Azathioprine (Akbar: 2-3 mg/kg/day orally) | Steroid-sparing; helps prevent renal progression |
| Mycophenolate mofetil, methotrexate, ciclosporin | Steroid-sparing agents; mycophenolate is an alternative to cyclophosphamide in some nephritis |
| Rituximab (anti-CD20) and other biologics | Refractory disease |
| Anticoagulation | For thrombosis with antiphospholipid antibodies, at least until remission; low molecular weight heparin preferred, warfarin also used |
- Side effects of steroids: hypertension, gastritis, cataract, osteopenia, Cushingoid features, avascular necrosis.
- Side effects of cytotoxics: infection, gonadal damage, possible later malignancy; prepubertal children are at lower risk of gonadal damage.
Long-term monitoring
SLE is a lifelong illness and needs indefinite follow-up:
- Disease activity: symptoms, C3 and C4, anti-dsDNA titre, ESR, blood counts.
- Kidneys: blood pressure, urinalysis, urine protein, creatinine.
- Drug toxicity: growth, bone density, eyes, blood counts, infection.
- Cardiovascular risk: lipids, weight.
Complications
- Major causes of death: infection (including bacterial endocarditis), nephritis and renal failure, CNS disease, pulmonary haemorrhage, myocardial infarction and accelerated atherosclerosis, malignancy, pulmonary fibrosis.
- Others: avascular necrosis from steroids, persistent cytopenias, thrombosis, recurrent miscarriage in adult life (antiphospholipid antibodies).
Prognosis and counselling
- The course is highly variable, with flares and remissions.
- Outlook depends on the extent and severity of organ involvement; worst with severe nephritis or cerebritis.
- With modern treatment and renal transplantation, most patients live well into adulthood; Akbar quotes 5-year survival of about 95%.
- Counsel about sun avoidance, adherence, infection risk on immunosuppression, and the need for lifelong review.
Neonatal lupus
- Caused by passive transfer of maternal IgG anti-Ro (SSA) and anti-La (SSB) antibodies across the placenta from about 16 weeks of gestation. The mother usually has SLE or carries these antibodies.
- Skin: annular or macular rash on the face (especially around the eyes), trunk and scalp; may be present at birth or appear within the first 6 weeks, often after UV light, and fades over about 3-4 months.
- Other transient features: cytopenias (thrombocytopenia), hepatitis, haemolysis.
- Congenital heart block: from a prolonged PR interval to complete heart block; affects about 2% of babies of antibody-positive mothers; it is permanent. Recurrence risk in a later pregnancy after an affected child is about 17% (Akbar). Nelson notes a mortality of about 20%; most survivors need pacing.
- Diagnosis: maternal anti-Ro or anti-La antibodies; fetal echocardiography from 16 weeks to detect conduction problems.
- Management: pacing for heart block; skin lesions with topical steroids; others resolve. Antenatal options include fluorinated steroids (dexamethasone, betamethasone), IVIG and maternal hydroxychloroquine, which may help prevent heart block.
- Neonatal lupus is not ongoing autoimmunity, but there is a higher risk of autoimmune disease later.
Neonatal lupus = maternal anti-Ro/anti-La; rash, cytopenias and hepatitis fade, but congenital heart block is permanent.
Expect: an adolescent girl with fever, arthritis, malar rash and haematuria; 4 of 11 criteria; ANA most sensitive (a negative ANA virtually excludes SLE); anti-dsDNA and anti-Sm most specific; low C3 and C4 in active disease and their use in monitoring; lupus nephritis as the main cause of death, renal biopsy for classification and steroids plus cyclophosphamide for severe classes; hydroxychloroquine for skin and joints; antiphospholipid antibodies and thrombosis; drug-induced lupus with anti-histone antibodies; neonatal lupus with anti-Ro and congenital heart block.
Quick revision
- Multisystem autoimmune disease with autoantibodies and immune complexes; low complement.
- Children: mostly adolescent girls; rare under 9 years.
- 4 of 11 criteria: malar, discoid, photosensitivity, ulcers, arthritis, serositis, renal, neuro, blood, immunology, ANA.
- ANA over 97% sensitive; anti-dsDNA and anti-Sm specific; anti-dsDNA tracks activity.
- Lupus nephritis is the main threat; biopsy to classify; steroids plus cyclophosphamide or mycophenolate for class III-IV.
- Hydroxychloroquine for skin, joints and fewer flares; NSAIDs for joints and pleurisy.
- Sun protection, calcium and vitamin D, lifelong monitoring.
- Neonatal lupus: anti-Ro/La; permanent congenital heart block needs pacing.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Does a positive ANA mean a child has lupus?
No. ANA is very sensitive but not specific and occurs in other conditions such as JIA. A negative ANA, however, makes SLE very unlikely; anti-dsDNA and anti-Sm are the specific tests.
Why are complement levels checked in SLE?
Immune complexes use up C3 and C4, so levels are low in active disease. They rise back to normal with effective treatment, which helps doctors judge response and taper steroids.
Why is a renal biopsy needed when the urine test is only mildly abnormal?
The urine can underestimate how much kidney damage is present. The biopsy class decides whether strong immunosuppression such as cyclophosphamide is needed and guides the prognosis.
Can a baby get lupus from the mother?
Yes, as neonatal lupus, caused by maternal anti-Ro and anti-La antibodies crossing the placenta. The rash and blood changes fade within months, but any congenital heart block is permanent.