Transcript Who Gets Lupus?

Gender Differences in
Immune Response
Females resist a variety of infections
better than males ???
Females may reject transplanted organs
more rapidly
Females have a higher frequency of
autoimmune diseases
Evidence to Support Hormone Role
in Human Lupus
Female predominance
Disease  during pregnancy, menses
 Levels of androgen in women with lupus
 Frequency of lupus in Klinefelter (XXY)
men
 Disease with estrogen administration ?
Evidence to Support Hormone Role
in Murine Lupus
Mouse model lupus (NZB x NZW) disease
identical to human F > M
Female mice die earlier than males
Male castration and estrogen accelerates
disease
Male sex hormones delay onset of lupus in
female mice
Role of Hormones on Immune Function
Male hormones (androgen) suppress
Female hormones (estrogen) enhance
CRITERIA FOR THE DIAGNOSIS OF SLE
(As revised in 1997 by the American College of Rheumatology)
A person is said to have SLE if four of these criteria are
present at any time:
Skin criteria
• Butterfly rash (lupus rash over the cheeks and nose)
• Discoid rash (thick rash that scars, usually on sun-exposed
areas
• Sun sensitivity
• Oral ulcerations
Systemic criteria
• Arthritis
• Serositis
• Proteinuria or cellular urinary casts
• Seizures or psychosis with no other explanation
Diagnostic Challenges
Con
1. Interpretation of criteria
2. Manifestations not in criteria
3. Other diseases may mimick lupus
4. Evolving symptoms over time
5. Patients may present very differently
Disease Mimickers
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Sjogren’s syndrome
Fibromyalgia (+ ANA)
Early rheumatoid arthritis
ITP
Primary antiphospholipid syndrome
Drug-induced lupus
Natural History of SLE
• Disease flares/activity (reversible)
• Organ damage (irreversible)
disease
treatment
SLE
Damage
SLE
Activity
1
2
3
4
5
Time (years)
6
7
8
SLE Activity vs Damage
Activity
Nephritis
Damage
Renal failure/scar
Inflammation and
medications
Osteoporosis/Fx
Ovarian failure
Myocardial infarction
Autoantibody Determined Clinical
Subsets of SLE
RNP
SSA (Ro)
SSB (La)
phospholipids
Ribosomal-P
ANA (+)>95% patients
dsDNA
ANA + > 90%, nonspecific
CD40L-CD40 Interactions
TCR
T-cell
B
Cell
CD3
CD40
CD40L (gp39)
CD40: B-cells, endothelial cells,
macrophages, Ag-presenting cells,
renal parenchymal, tubular, etc cells
CD40L: T-cells,
platelets
Autoantibody Determined Clinical
Subsets of SLE
SSA/SSB (rash and neonatal lupus,
dry eyes and mouth)
RNP
(Raynauds)
Ribosomal-P
(CNS, psychosis)
Phospholipid
(clotting and
miscarriage)
dsDNA (kidney disease)
Pathogenesis of SLE
Current Standard Therapy
Mild to Moderate Disease
arthritis
fever
pleurisy
pericarditis
cutaneous
Therapy
photoprotection
NSAID
corticosteroids
methotrexate
antimalarials
topical agents
physical therapy
Current Standard Therapy
Moderate to Severe Disease
nephritis
vasculitis
cyclophosphamide
pneumonitis
CNS
hematologic
Therapy
corticosteroids
azathioprine
cyclosporine
IVIg
plasmapheresis ???
mycophenylate mofetil
Novel Therapies
Immunosuppressants
T cells
B cells
Complement
Cytokine
Hormonal
Immunoablation
Lupus Center of Excellence 2004
Lupus Center of Excellence 2003