3. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
by multisystem inflammation and the presence of circulating autoantibodies
directed against self-antigens .
Nearly every organ may be affected, most commonly involved are the skin, joints,
kidneys, blood-forming cells, blood vessels, and the central nervous system
children and adolescents with SLE have more severe disease and more widespread
organ involvement.
4. EPIDEMIOLOGY
Pediatric SLE (pSLE) represents approximately 15-20% of all SLE patients
It is more common in females than in males, with a female to male ratio varying
from 2.3:1 to 9:1.
incidence of SLE with onset before age of 19 years is between 6 and 18.9 cases
per 100,000 .
Diagnosis of SLE is rare before the age of 10, and the average age at
presentation is 12.1 years6-11.
The survival rate for SLE has improved dramatically over the past 50 years, with a
5-year survival rate increasing from 50% in 1955 to more than 90% in 20048
5. ETIOPATHOGENESIS
Genetic factors
1. congenital deficiencies of C1q , C2 and C4
2. HLA B 8, HLA DR 2, HLA DR3
Immune alterations :
1. The ability to produce pathogenic autoantibodies;
2. lack of T-and B-lymphocyte regulation.
3. Defective clearance of autoantigens and immune complexes by the immune system.
Hormonal factors
Environmental factors
6.
7. CLINICAL FEATURES
Clinical characteristics and organ involvement very depending on age of onset,
gender and race .
Constitutional Fatigue, anorexia, weight loss, fever, lymphadenopathy.
8. MUSCULOSKELETAL
Arthritis, myositis, tendonitis, arthralgias, myalgias, avascular necrosis, osteoporosis
Arthritis occurs in more than ¾ of pediatric patients with SLE - symmetric non erosive,very
painful polyarthritis.
Arthritis can be only presenting manifestation of SLE
Treatment-induced musculoskeletal complications include avascular necrosis, osteoporosis and
growth failure.
12. RENAL MANIFESTATIONS
Renal involvement represent the first clinical manifestation of the disease in 60-80%
of children with SLE
About 80% of children and adolescents develop renal abnormalities generally in
the first year after diagnosis
Renal Hypertension, proteinuria, hematuria, edema, nephrotic syndrome, renal
failure
13. WHO CLASSIFICATION OF LUPUS NEPHRITIS
I.Minimal mesangial LN : No renal findings
II. Mesangial proliferative LN : Mild clinical renal disease; minimally active urinary
sediment; mild to moderate proteinuria (never nephrotic) but may have active
serology
III. Focal proliferative LN <50% glomeruli involved
A. Active
A/C. Active and chronic
C. Chronic
More active sediment changes; often active serology; increased proteinuria
(approximately 25% nephrotic); hypertension may be present; some evolve into class
IV pattern; active lesions require treatment, chronic do not
14. IV. Diffuse proliferative LN : (>50% glomeruli involved); all may be with segmental
or global involvement (S or G)
A. Active
A/C. Active and chronic
C. Chronic
Most severe renal involvement with active sediment, hypertension, heavy proteinuria
(frequent nephrotic syndrome), often reduced glomerular filtration rate; serology very
active. Active lesions require treatment
V. Membranous LN glomerulonephritis : Significant proteinuria (often nephrotic)
with less active lupus serology
VI. Advanced sclerosing LN : More than 90% glomerulosclerosis; no treatment
prevents renal failure
15.
16. CARDIOVASCULAR
Pericarditis ( most common form of cardiac involvement )
Myocarditis,
Conduction system abnormalities
Libman-Sacks endocarditis
Identified risk factors for premature atherosclerosis in pSLE include: Dyslipidemia,
high levels of homocystein, presence of aPL, LAC, hypertension, hyperinsulinemia,
nephritic range proteinuria, upregulated CD40-CD40 ligand interactions and
steroid-induced obesity.
17. LIBAMAN - SACKS ENDOCARDITIS
Small ( 1-4 mm)
Single or multiple
Pink warty ( verrucous ) vegetations
sterile
Located on undersurface of AV
valves , chords , mural endocardium.
18. NEUROLOGIC
Neuropsyciatric SLE occuring in 20-45% of children and adolescents, is the third most
common cause for mortality in Psle
CNS involvement occurs within the first year of disease in approximately 75% to 80% of
patients.
Seizures
Psychosis
Cerebritis
Stroke, transverse myelitis, depression, cognitive impairment
Headaches, migraines, pseudotumor,
Peripheral neuropathy (mononeuritis multiplex) , chorea, optic neuritis,
Cranial nerve palsies, acute confusional states, dural sinus thrombosis
19. PULMONARY
Pleuritis ( most common )
Interstitial lung disease
pulmonary hemorrhage
pulmonary hypertension
pulmonary embolism
Pulmonary function abnormalities were found in up to 40% of pSLE patients with no
evidence of clinical symptoms or radiographic changes .
The most frequent pattern observed was lung restrictive disease.
20. HEMATOLOGIC
Immune-mediated cytopenias (hemolytic anemia, thrombocytopenia or
leukopenia)
Autoimmune thrombocytopenia is the initial manifestation in up to 15% of the
pediatric cases
Anemia of chronic inflammation
Hypercoagulability
Thrombocytopenic thrombotic microangiopathy
Antiphospholipid antibodies (aPL) are present in 75% of pSLE patients
patients with SLE and aPL, specifically lupus anticoagulant (LAC), are at high risk of
developing thromboembolic events.
22. ACR REVISED CLASSIFICATION CRITERIA
PRESENCE OF 4 OUT OF FOLLOWING 11 CRITERIA :
Malar rash
Discoid rash
Photosensitivity
Oral or nasal ulcers
Arthritis Nonerosive, ≥2 joints
Serositis Pleuritis, pericarditis or peritonitis
Renal manifestations : Consistent renal biopsy
Persistent proteinuria or renal casts
Seizure or psychosis
Hematologic manifestations : Hemolytic anemia ,Leukopenia (<4,000 leukocytes/mm3)
Lymphopenia (<1,500 leukocytes/mm3) , Thrombocytopenia (<100,000 thrombocytes/mm3)
Immunologic abnormalities : Positive anti–double-stranded or anti-Smith antibody False-
positive rapid plasma regain test result
positive lupus anticoagulant test result, or elevated anticardiolipin immunoglobulin (Ig) G or IgM
antibody
Positive antinuclear antibody test result
23. SLICC CRITERIA
CLINCAL CRITERIA :
The presence of 4 criteria ( including atleast 1 clinical and 1 immunological crieteria )
Acute cutaneous lupus : Malar rash, bullous lupus, toxic epidermal necrolysis variant of
SLE, maculopapular lupus rash, photosensitive lupus rash, or subacute cutaneous lupus
Chronic cutaneous lupus : Classic discoid rash, lupus panniculitis, mucosal lupus, lupus
erythematous tumidus, chilblains lupus, discoid lupus/lichen planus overlap
Oral or nasal ulcers
Nonscarring alopecia
Synovitis (≥2 joints)
Serositis : Pleurisy or pericardial pain ≥1 day, pleural effusion or rub, pericardial
effusion or rub, ECG evidence of pericarditis
24. Renal : Presence of red blood cell casts or urine protein/creatinine ratio representing >500
mg protein/24 hours
Neurologic : Seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or cranial
neuropathy, or acute confusional state
Hemolytic anemia
Leukopenia (<4,000/mm3) or lymphopenia (<1,000/mm3)
Thrombocytopenia (<100,000/mm3
25. IMMUNOLOGIC CRITERIA
Positive antinuclear antibody
Positive double-stranded DNA antibody
Positive anti-Smith antibody
Antiphospholipid antibody positivity
Positive lupus anticoagulant
false-positive test for rapid plasma regain
medium to high titer anticardiolipin antibody level (IgA, IgG, IgM)
or positive anti–B2-glycoprotein I antibody (IgA, IgG, IgM)
Low complement Low C3, C4, or Ch50 level
Positive direct Coombs test (in the absence of hemolytic anemia
26. DIFFERENTIAL DIAGNOSIS
Infections ( sepsis, EBV , parvovirus B 19 , endocarditis )
Malignancies ( leukemia and lymphoma )
Post streptococcal glomerulonephritis
Systemic onset juvenile idiopathic arthritis
Drug induced lupus.
28. PROBABLE ASSOCIATION
Phenytoin, ethosuximide, carbamazepine
Sulfasalazine, amiodarone, quinidine, rifampin
Nitrofurantoin, beta blockers, lithium, captopril, interferon-γ
Hydrochlorothiazide, glyburide, docetaxel, penicillin, tetracycline
Statins, gold, valproate, griseofulvin, gemfibrozil, propylthiouracil
Drug-induced lupus affects males and females equally.
A genetic predisposition toward slow drug acetylation may increase the risk of drug-
induced lupus
Hepatitis, which is rare in SLE, is more common in drug-induced lupus.
Circulating anti histone antibodies
29. LABORATORY FINDINGS
Anti nuclear antibody – high sensitivity , poorly specific
Anti–double-stranded DNA - Correlates with disease activity, especially nephritis, in
some with SLE
Anti-Smith antibody -Specific for the diagnosis of SLE
Antiribonucleoprotein antibody -
Increased risk for Raynaud phenomenon and pulmonary hypertension
High titer may suggest diagnosis of mixed connective tissue disorder
Anti-Ro antibody (anti-SSA antibody)
Associated with sicca syndrome
May suggest diagnosis of Sjögren syndrome
30. Anti La antibody
Increased risk of neonatal lupus in offspring (congenital heart block)
May be associated with cutaneous and pulmonary manifestations of SLE
May be associated with isolated discoid lupus
Antiphospholipid antibodies (including anticardiolipin antibodies) Increased risk
for venous and arterial thrombotic events
Antihistone antibodies Present in a majority of patients with drug-induced
lupus
May be present in SLE
31. EACH CLINIC VISIT
CBC with differential count
ESR and CRP
Creatinine / albumin/ electrolytes
Urinalysis
Aldolase and CPK
Liver function
CH 50 / C3 /C4
Anti ds DNA antibody
Blood pressure
34. MANAGEMENT
Goals of treatment are to:
prevent flares
treat flares when they occur
minimize organ damage and complications
Corticosteroids (Mainstay of SLE treatment)
To rapidly suppress inflammation
Usually start with high-dose IV pulse and convert to PO steroids with goal of
tapering .
Commonly used: prednisone, hydrocortisone, methylprednisolone, and
dexamethasone
Steroid sparing immunosuppressive drugs - methotrexate , leflunomide
,azathioprine , mycophenolate mofetil ,cyclophosphamide , belimumab.
35. CONSERVATIVE MANAGEMENT
For those w/out major organ involvement.
NSAIDs: to control pain, swelling, and fever
Caution w/ NSAIDS though. SLE pts are at increased risk for aseptic meningitis
Antimalarials: Generally to treat fatigue joint pain, skin rashes, and inflammation of
the lungs
Commonly used: Hydroxycholorquine
Used alone or in combination with other drugs
Statins – for primary prevention of atherosclerotic disease in pubertal pts with
elevated CRP .
Routine immunization – annual influenza and pneumococcal vaccines .
36. Corticosteroids Disease flare, major organ involvement
Hydroxychloroquine Prevention of disease flares, skin and joint manifestations
Azathioprine Lupus nephritis,
Cyclophosphamide Life-threatening complications (nephritis, NP-SLE, pulmonary
hemorrhage)
Methotrexate Arthritis, lupus nephritis (in conjunction with CYC)
Aspirin Positive anti-antiphospholipid antibodies
NSAIDS Joint manifestations , pleuritis, pericarditis
Cyclosporin Lupus nephritis
Vitamin D , calcium Prevention of osteoporosis
Biphosphonates Osteoporosis
MMF Lupus nephritis
37. TREATMENT OF LUPUS NEPHRITIS
prednisone at a dose of 1-2 mg/kg/day in divided doses followed by a slow
steroid taper over 4-6 mo beginning 4-6 wk after achieving a serologic remission.
For severe forms of nephritis (WHO classes III and IV), induction therapy consists
of 6 consecutive monthly intravenous infusions of cyclophosphamide at a dose of
500-1,000 mg/m2
Pulse intravenous methylprednisolone (1000 mg/m2) is also used in addition to
oral corticosteroids.
Maintenance therapy of lupus nephritis – mycophenolate mofetil , every 3 mo IV
cyclophosphamide , or azathioprine for 12 months .
38. COMPLICATIONS AND PROGNOISIS
Most common cause of death in SLE include infections , lupus nephritis ,
neuropsychiatric disease .
Over long term ,most common causes of mortality include complications of
atherosclerosis and malignancy .
Severity of pediatric SLE is worse than adult onset SLE .
5 yr survival rate for pediatric SLE is 95 % with 10 yr survival rate 80 – 90 %.
39. NEONATAL LUPUS
Characteristic annular or macular rash typically affecting the face (especially the
periorbital area), trunk, and scalp.
The rash - 1st 6 wk of life after exposure to ultraviolet light
lasts 3-4 mo; however, it can be present at birth.
Infants may also have cytopenias and hepatitis
most feared complication is congenital heart block
Conduction system abnormalities range from prolongation of the PR interval to
complete heart block, with development of progressive cardiomyopathy in the most
severe cases.
The noncardiac manifestations of neonatal lupus are usually reversible, whereas
congenital heart block is permanent.
40.
41. With cardiac pacing, children with conduction system disease in the absence of
cardiomyopathy have an excellent prognosis.
If the conduction defect is not addressed, affected children are at risk for exercise
intolerance, arrhythmias, and death .
42. SUMMARY
Pediatric systemic lupus erythematosus (pSLE) is a chronic mutisystemic
autoimmune disease with complex clinical manifestations .
Pathogenesis of SLE involves a combination of environmental, hormonal and
genetic factors .
Malar rash is the hall mark of SLE.
Arthritis occur in more than ¾ th of patients with SLE .
Class 1V is the most common and most severe type of lupus nephritis .
Anti ds DNA Ab are more specific .
Corticosteroids are main stay of treatment. 5 yr survival rate for pediatric SLE is 95
% with 10 yr survival rate 80 – 90 %.
43. REFERENCES
NELSON TEXTBOOK OF PEDIATRICS SOUTH ASIAN 1ST EDITION
ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE 9 TH EDITION
