Antibodies/ANA
What is an ANA? How do we test? What are we using? How do we interpret?
Do healthy people have positive ANAs?
Basically, what is going on with these tests...
ANA: autoantibody that targets various nuclear antigens
Can be detected via Elisa (newer cheaper) or IIF (older but more sensitive) Substrate is Hep2 cancer cell line
Titer: highest dilution of patients serum that still produces fluorescence
>1:40: 20-30% in healthy individuals, % decreases with dilution in healthy people
How do you differentiate on a basic level between the malar rash in LE v DM?
LE spares nasolabial folds. DM typically does not
Drug induced LE TYPICALLY lacks what?
BONUS: what are some exceptions?
Skin findings and renal/CNS abnormalities
Presents with arthritis/arthalgia (90%), myalgia (50%), serositis, fever, weight loss
**HCTZ/Terbinafine can induce SCLE but SCLE presents with cutaneous findings (papulosquamous v annular)
**Minocycline: often negative anti-histone, + ANCA
**TNFa: anti-dsDNA, malar rash, photosensitivity, SCLE, DLE lesions
CREST stands for what? Which subtype of SSc is this in reference to?
Calcinosis cutis/anti-Centromere, Raynauds phenomenon, Esophogeal dysmotility, Sclerodactyly, Telangiectasias
Limited SSc
Diffuse SSc: Raynauds and no cutaneous involvement
Name the categories and respective sub-types of cutaneous LE.
Acute CLE
SCLE: annular, papulosquamous, syndromic (Neonatal, drug, complement deficiency)
CCLE: Discoid (Localized, Disseminated), Hypertrophic, LE-LP overlap, Chilblain LE, Tumid, LE panniculitis (No overlying involvement, overlying DLE, systemic involvement)
What are the 3 ANA IIF patterns?
Homogenous/diffuse: dsDNA, histone (SLE and drug-induced)
Peripheral/rim: dsDNA (SLE)
Speckled/particulate: Ro, La, Smith, Scl-70, U1RNP (SCLE, SLE, SSclerosis)
IIF looks at the ANA pattern, ELISA identifies specific antigenic targets
Which type of CLE is most strongly a/w SLE and how does it present clinically?
ACLE
- malar erythema following sun exposure (spares nasolabial folds)
- can develop papules, erosions, poikiloderma (facial)
- Similar appearing rash may develop on v-neck (red poikiloderma v violaceous in DM), upper back and extremities
What antimalarial is the mainstay of tx for CLE? What should patients NOT do while on this medication?
Hydroxychloroquine
Smoking. Can decrease efficacy 2-fold and flare disease
Anti-topoisomerase II is found in 75% of what CTD?
Anti-topoisomerase I?
Morphea, 75% overall with 85-50% in generalized morphea
Topo I is Scl-70 and seen in diffuse SSc > limited SSc
Anti-centromere in SSc (limited)
Dermoscopic findings of nails that help support SLE v DM/SSC?
Periungual telangiectasis, erythema (red lunula) Dilated glomeruloid loops
DM: symmetric dilation of vessels w/ alternating dropout on proximal nail fold, RAGGED cuticles
SSc: giant capillary loops WITH sclerodactyly, can have drop out as well
What antibody is most strongly correlated to SCLE?
Anti-SSA/Ro is elevated 70% of the time
Anti-SSB/La about 50% of time
In bullous LE, what is the target and pattern seen on DIF?
Bonus: treatment? Response time
Collagen 7
Continuous granular to linear deposition of IgM, IgG, IgA, C3
Dapsone: 1-2 days
Add Quinacrine
Side effects?
What is the most common subtype of morphea in adults? Children?
Adults: Plaque
Children: Linear. En coupe de sabre and Perry Romberg are subtypes of linear morphea
TRUE or FALSE. Raynauds phenomenon is one of the cutaneous findings used to diagnoses SLE.
FALSE: 4 cutaneous findings are malar erythema, photosensitivity, oral ulcers and discoid rash
80% of lichen sclerosus patients have IgG antibodies to what?
BONUS: This antibody target is mutated in what other derm condition?
ECM-1
Lipoid protenosis
What are the classic anatomic locations seen in DLE?
What location has a stronger correlation w/ SLE?
- Face, scalp, CONCHAL BOWL
- Widespread DLE: lesions above AND below the neck
What causes neonatal lupus? Specific antibody
What is the risk of having a subsequent child with NLE after the first?
Transplacental passage of Anti-Ro/SSA
25%
Women with SLE or other CTD anti-Ro/SSA have 15% of NLE
Most common cause of mortality in systemic sclerosis?
ILD in diffuse SSC (topo 1)
Pulmonary hypertension in Limited SSc/CREST (centromere)
GI most common site of visceral involvment
What is a clinically distinct finding in relapsing polychondritits. What antibody test might you order?
Spares earlobes
Abs against collegen type 2
What percentage of patients with SLE have a positive ANA and which antibody is most specific for SLE?
ANA is roughly 97% positive in patients with SLE
Anti-dsDNA and Anti-Smith are more specific but less sensitive for SLE with Smith >specific than dsDNA
TRUE OR FALSE? There is vacuolar interface change seen in tumid lupus.
FALSE. Superficial/deep lymphocytic infiltrate with:
-NO EPIDERMAL ATROPHY
-No BMZ thickening
-No follicular plugging
Bolognia Table 41.7
Which complement deficiency is most commonly associated with SLE?
Which is most severe?
Primary C2: most common complement disorder, but less severe SLE
Primary C1q and C4 deficiency is associated with more severe SLE
Thought to be caused by incomplete clearance of antigen expressing (Ro) UV-damaged keratinocytes from lack of early complement (classic pathway), leading to autoantibody formation
Eosinophilic fasciitis is associated with what lab abnormality? Classically associated with what preceding event?
Peripheral eosinophilia. Strenuous exercise
- TIMP-1 (metalloproteinase inhibitor-1): new marker for disease activity
- Responds to systemic steroids
What is the lupus band test?
Granular continuous band of IgM>G>A deposits and complement at DEJ in lesional and non-lesional skin of exposed and protected sites in patients with SLE via DIF
3 types: lesional (highest sensitivity in SLE), non-lesional sun-exposed (70-80% +), non-lesional-sunprotected (30-35% +)