Ch. 41-Lupus Flashcards
What is the strongest risk factor for SLE?
Gender-Women6:1 ratio for sLE3:1 for cutaneous only
Name risk factors for sLE
female sexethnicity-africana American
Prevalence lupus in caucasian women? Africa-american women?
4 in 1000 AA1 in 1000 caucasian
How does lupus differ in African Americans compared to caucasians
-younger age-more severe disease-more internal organ involvement-higher mortality
What are some environmental factors contributing to lupus
UVRsmokingmedicationsviruses maybe-EBV*may be initial trigger in genetically susceptible host to cause damage and expose nuclear proteins to body
Name the genes most strongly associated with SLE
HLA-DR4PTPN22STAT4IRF5TREX1C1q
What genes are DLE associated with?
HLA-B8-DR3C2/C4 deficiency
What genes is associated with familial chilblain lupus?
TREX1=dysfunction of the exonuclease leads to an accumulation of IFN-stimulatory nucleic acids
What forms of lupus do autoantibodies play the strongest role?
SCLE
Neonatal lupus
Which antibodies are associated with SCLE?
Anti-ro (anti-SSA)
Anti-la (anti-SSB)
What are the 2 Anti-ro antibodies
anti-SSA/Ro60 and anti-SSA/Ro52
Which autoantibodies are associated with neonatal lupus
Anti-ro and anti-la
What role does SSA/Ro60 play in the body?
role in cell survival following UVR, possibly via binding to misfolded non-coding RNAs and targeting them for degradation
Deficiency/antibodies agains SSA thus may prevent this function
What role does SSA/Ro52 play?
SSA/Ro52 has a known regulatory role in inflammation, targeting both interferon regulatory factor 3 (IRF3) and IRF8 for degradationThus: deficiency in this is pro inflammatory
How does UVR cause lupus flare?
-UVR induces apoptosis, which leads to translocation of cellular and nuclear antigens -autoantiboides are thus exposed to the nuclear antigens and cause cascade inflammation
Which cell types make up the infiltrate seen in lupus?
CXCR3-positive CD4+ and cD8+ T cells (lymphocytic) immature plasmacytoid dendritic cells
Describe pathogenesis SLE
- nuclear antigens to be exposed due to lack of clearance of dead cells (e.g. complement factors help macrophages clear these dead cells via opsonization)
- Loss of self tolerance and sensitization to antigens–> causes immature APC to pick up antigen via TLR3. APC presents antigen to naive T helper cells4. IL-4 secreted promotes Th2 maturation
- Th2 promotes B-cell maturation and production
- Plasma cells produce auto-antibodies
How do autoantibodies produce damage in SLE
-Ag-Ab complex binds to Fc receptors of immune cells–> pro inflammatory cytokines like IFN and TNF-Ag-Ab complexes can bind directly to cells and cause complement activation and damage
Most important inflammatory cytokine in SLE?
IFN-alpha
What are the 3 specific cutaneous lesions of lupus? Others?
ACLE-acute cutaneous lupus
SCLE-Subacute cutaneous lupus
CCLE-Chronic cutaneous lupus: DLE, tumid lupus, lupus panniculitis, chilblains
Others:Rowells Syndrome, Bullous SLE
Which lupus forms have interface dermatitis
ACLE, SCLE, CCLE (only DLE, less likely other forms
Where does DLE typically occur on the body?
Head and neck–> face, scalp, ears.
Can be widespread, but unlikely to occur on the body without also lesions on head/neck
Can occur on muscosal surface
What level of the skin does DLE affect?
Superficial and deep dermis
What are the clinical features of DLE?
Erythema, scaly, round/annular plaques often with hypo pigmentation in centre with hyperpigmentation at border scarring, alopecia, atrophy, follicular plugging
Can be photo-distributed (head/neck) but no clear association between sun exposure and their development
firm/indurated
What % DLE develop SLE
10-20% (mostly first 5 yrs)Mostly by mucocutaneous involvementCan have arthralgia in DLEHigher risk if disseminated lesions
Variant of DLE?
Hypertrophic DLE with significant hyperkeratosis, often on extensor arms
Clinical features SCLE?
Photosensitive
Mostly photo exposed areas, mid face often spared, often involves lateral face, extensor arms, shoulders, chest, back
2 types: Annular: raised pink scaly borders with central clearing, or papular bordersPapulosquamous: chronic psoraisiform or eczematous
Minimally palpable
Can get hypo pigmentation or depigmentation but no scarring
What % SCLE are linked to medications?
20-30%
Medications associated with SCLE
“PTHIN DRAGS”
PPI/PUVA
Terbinafine/TNF-alpha inhibitors/Taxanes
HCTZ (#1)
IFN
NSAIDS
Diltirazem + other CCBS/BBs
Ranitidine
Acei, anti-epileptics
Griseofulvin
Statins
What % patients SCLE fulfills SLE criteria
30-50%
What antibody is most associated iwht SCLE? What % have it?
SSA/Anti-Ro
Ranges 60-100%, on avg 70%