2. SLE has been classically described as a prototypic
autoimmune disease with a wide array of clinical
manifestations and characterized by the production
of auto-antibodies to components of the cell
nucleus.
Gilbert et al. Pediatric Rheumatology 2014, 12:16
Systemic Lupus Erythematosus
3. z
SLE - Historical
Classical
Neoclassical
Modern
First description of the cutaneous disorder;
term "lupus" was coined. "lupus" that means wolf in
Latin. 13th Century physician Rogerius
1872: Moriz Kaposi : description of the disease’s
systemic or disseminated manifestations,
two forms of the disease — what we know as systemic
lupus erythematosus and discoid lupus
Discovery of the LE cell in bone marrow in 1948 by
Malcolm Hargraves
1957 : first anti-DNA antibody
4. z
Female:Male = 9:1, but before puberty it is 3:15
pSLE makes 20% of all cases1
Incidence <15 yrs: 0.5-0.6 per 100,000 persons2
Prevalence 4 – 250 cases per 100, 000 persons3
More than 90% cases of SLE occur in women4
SLE - Epidemiology
7. z
SLE Pathology
The LE cell is a neutrophil that has
engulfed the antibody-coated nucleus of
another neutrophil.
LE cells may appear in rosettes where
there are several neutrophils vying for an
individual complement covered protein.
• Immune complexes within the dermal–
epidermal junction.
• “lupus band test” which is specific for SLE.
9. 1. Malar rash
2. Naso-oral ulcers
3. Photosensitive rash
4. Discoid rash
5. Arthritis
6. Pleuritis or pericarditis
7. Proteinuria (>500 mg/d) or evidence of nephritis in urinalysis
8. Hemolytic anemia, thrombocytopenia, leukopenia, or lymphopenia
9. Seizure or psychosis
10. Positive ANA finding
11. IMMUNOLOGIC ABNORMALITIES: Positive anti–dsDNA, anti-Smith, or
antiphospholipid antibody / lupus anticoagulant
The Systemic Lupus International Collaborative Clinics (SLICC) recently published a modification of
the ACR criteria.
Lupus patients meet 4 criteria with at least 1 clinical and 1 immunologic criterion or
with biopsy-proven nephritis in association with positive ANA and anti-dsDNA
The ACR’s ( American College of Rheumathology) diagnostic criteria for SLE :
20. z
SLE – Clinical
Neuropsychiatric Manifestations (20-40% )
• Second to nephritis as most common cause of
morbidity & mortality
• Can occur at any time; even at presentation
COMMON • Depression, organic brain
syndrome, functional psychosis,
headaches, seizures, cognitive
impairment, dementia, coma
OCCASIONAL • Cerebral vascular accidents,
aseptic meningitis, peripheral
neuropathy, cranial nerve palsies
RARE: • Paralysis, transverse myelopathy,
chore
21. z
SLE – Clinical
Hematologic Findings
• Leukopenia, especially lymphopenia
• Anemia
• mild to moderate, due to chronic disease and mild hemolysis
• severe, uncommon (5%), due to immune mediated hemolysis
(Coombs +)
• Thrombocytopenia
• Bone marrow suppression / arrest -- very rare
• Coagulopathy – prolonged PTT
22. z
SLE – Clinical
Renal Findings
Most common cause of morbidity & mortality
• Glomerulonephritis – at least 75%
• Microscopic or gross hematuria
• Proteinuria, including nephrotic syndrome
• Hypertension
• Decreased GFR
• Renal failure (up to 30-50% of children prior to 1980)
• Renal biopsy predictive of potential for renal damage
23. z
International Society of Nephrology 2003 Revised Classification of SLE Nephritis
Class Classification Features
Class I
Minimal mesangial Normal light microscopy findings; abnormal electron
microscopy findings
Class II
Mesangial
proliferative
Hypercellular on light microscopy
Class III Focal proliferative < 50% of glomeruli involved
Class IV Diffuse proliferative
=50% of glomeruli involved; classified segmental or
global;
to be treated aggressively
Class V Membranous
Predominantly nephrotic disease may occur with
class III or IV
Class VI Advanced
sclerosing
=90% of glomeruli involved without residual activity
Chronic lesions and sclerosis
25. z
NeonatalLupus
• Passive transplacental transfer of maternal
anti-Ro/SSA and anti-La/ SSB antibodies
causes the transient skin lesions
• Characteristic annular or macular rash typically
affecting the face, trunk & scalp – usually clear
by 6 mo age
• Ultraviolet light may exacerbate or initiate
cutaneous lesions.
• Cytopenias and
• Cholestatic liver disease
• Congenital heart block (30%)- most feared
complication
Annular plaque
27. z
Auto-antibodies
ANA - Sensitive but not specific, 95-98% pts positive
Against nuclear components of the cell
Other :
Anti dsDNA : high specificity for lupus (over 80%)
RNP assoc w/ MCTD (Mixed connective-tissue disease),
Anti Smith Abs : specific for SLE
Ro/ La (SS-a/ SS-b): neonatal lupus, Sjogren’s
Anti Histone Abs : drug induced lupus
29. z
SLE - Treatment
MODERATE DISEASE: MILD + OTHER SYSTEM
INVOLVEMENTS
Treatment:
Prednisone 1-2 mg/kg/day,
NSAIDS,
Antimalarials,
Azathioprine
30. z
SLE - Treatment
SEVERE DISEASE: Severe, life-threatening organ system
involvement (e.g. Class IV lupus nephritis, myocarditis,
encephalopathy)
High dose corticosteroids (2-3 mg/kg/day)
Immunosuppressives:
IV pulse methyl prednisolone / dexamethasone
OR
Monthly pulses of Cyclophosphamide),
Plasmapheresis,
Anticoagulation where appropriate
31. z
Management of Pediatric SLE
General Use high-SPF sunscreen throughout the year.
Encourage good sleep and nutritional patterns.
Address psychological aspects of disease/treatment.
Prescribe calcium and vitamin D supplements
Immunize against pneumococcus.
Anticoagulant if evidence of antiphospholipid antibody is
present
Perform annual ophthalmologic evaluations
Treat dyslipoproteinemia when present.
Maintain good blood pressure control in those with
hypertension