lupus Flashcards
the 4 autoimmune connective tissue disorder/multisystem autoimmune rheumatic diseases
systemic lupus erythematosus
sjogren’s syndrome
systemic sclerosis (scleroderma)
autoimmune inflammatory muscle disease
SLE where does it cause inflammation
multi-site inflammation- joints, kidney, skin
autoimmune connective tissue disorders general points
Erosive, non-erosive?
What is typically seen in serum?
Common symptom/sign?
1)typically non-erosive (unlike Rheumatoid)
2)serum autoantibodies are characteristic
3) raynaud’s phenomenon
intermittent vasospasm of digits. triggered by cold exposures=triphasic colour change
Typical triphasic colour changes in Raynaud’s phenomenon
WHITE -> Vasospasm leads to blanching of digit
BLUE -> Cyanosis as static venous blood deoxygenates
RED -> Reactive hyperaemia
SLE clinical features
swan neck deformity/malar rash
raynaud’s
arthralgia
thrombocytopenia/haemolytic anaemia
Anti-nuclear antibodies (ANA) how to use results
Negative ANA effectively rules out SLE
However, ANA is not specific for lupus
1)+ve ANA
2)report strength (- max dilution which ab can still be detected) and pattern (autoantigen the ab are reacting to)
3) specific autoAb test to identify what ANA are reacting to:
Anti-ds-DNA ab
Anti-Ro
Anti-La
Anti-smith
Anti-RNP
which is stronger and by how much in dilution: ANA 1:320 and ANA 1:80
ANA 1:320 is three times stronger than ANA 1:80
Antiphospholipid (APL) antibodies- where do they target
antibodies directed to phospholipids on cell membrane
Antiphospholipid (APL) antibodies are associated with ↑ risk of:
1) Thrombosis
arterial (e.g. stroke)
venous (e.g. deep vein thrombosis, DVT)
2) Pregnancy loss (miscarriage)
antiphospholipid antibody how to measure in lab
measure in clinical lab: anticardiolipin antibodies, anti-beta2glycoprotein 1 antibodies
Persistent presence of APL + a clinical event
“anti-phospholipid antibody syndrome”
primary anti-phospholipid antibody syndrome is:
Anti-phospholipid antibody syndrome in absence of SLE
what is anti-double stranded DNA antibodies (anti-dsDNA) significant in
specific for SLE
Serum level of ab correlates with disease activity
anti-Sm ab significance
specific for SLE
serum level of ab does NOT correlate with disease activity
anti-Ro ab
anti-La ab
significance
secondary to sjogren’s syndrome
neonatal lupus syndrome
what is seen in neonatal lupus syndrome
transient rash in neonate
permanent heart block
Rheumatoid arthritis auto-antibody
RF
Anti-cyclic citrullinated peptide antibody
(Anti-CCP is a type of ACPA)
SLE - immunopathogenesis
which are innate and which adaptive
innate immunity:
overactivity of type 1 interferon (ie.IFN-a) pathway/
complement pathway abnormalities
adaptive immunity:
autoreactive B+T cells
Gene expression studies compared lupus patients to healthy controls found overexpression of genes activated downstream of the type 1 interferon receptor binding-> “interferon gene signature.” what is a high interferon gene signature associated with
worsen disease
what does (not available in UK yet) can block type 1 interferon receptor to treat SLE
anifrolumab
SLE- waste disposal hypothesis. how is the immune system generating a response to nuclear antigens? (should be hidden inside the cell)
- apoptosis leads to translocation of nuclear antigen to membrane surface
- impaired clearance of apoptotic cells= enhance nuclear antigen presentation to immune cells
- B cell autoimmunity
4.- complement activation and Fc receptor engagement
SLE investigations
high ESR
normal CRP
measure urine protein (uPCR)
creatinine
albumin
kidney biopsy if proteinuria
ANA
Anti dsDNA ab
complement consumption- low C3/C4
Antiphospholipid AB
SLE-measuring disease activity
what is shown in unwell pt with active lupus
-what is their C3/C4/ anti-dsDNA ab levels
low complement C3/C4
High anti-dsDNA antibodies
SLE management: for all pt? mild/serious disease? renal disease?
hydroxychloroquine- All pts
steroids-acute flare
mild-hydroxychloroquine
serious-immunomodulatory agent (methotrexate)
renal disease-mycophenolate+/-rituximab
steroid side effects
infection
osteoporosis
AVN
SLE management: for persistently active disease, life-threatening, SLE+ Antiphospholipid antibody syndrome
for persistently active disease,
Bell target therapies- rituximab
life-threatening, (ie.myocarditis)
iv steroid+ IV cyclophosphamide
SLE+ Antiphospholipid antibody syndrome
anticoagulation (warfarin)
SLE and pregnancy what to do to get best outcome
pre-pregnancy planning and getting SLE into remission
SLE and pregnancy- APL ab, renal, Ro ab?
1) Antiphospholipid antibodies associated with miscarriage.
Can reduce risk with aspirin or heparin
2) Pregnancy increases haemodynamic demands – will worsen renal dysfunction
3) Ro antibodies: can cause fetal heartblock
SLE-pregnancy- Drug considerations: WHICH ARE teratogenic
MMF, cyclophosphamide, methotrexate, warfarin are teratogenic.
sjogren’s syndrome what it is and effects *IGNORE
Autoimmune-
lymphocytic infiltration of exocrine glands (lacrimal and salivary glands)
Exocrine gland pathology:
Dry eyes (xerophthalmia)
Dry mouth (xerostomia)
Parotid gland enlargement
sjogren’s syndrome (other manifestation) *IGNORE
non-erosive arthritis
Raynaud’s phenomenon
autoimmune hepatitis
autoantibodies present in sjogren’s syndrome *IGNORE
Autoantibodies: Ro+, La+. RF often + but CCP -.
what is it called Sjögren’s syndrome if occurs in context of another connective tissue disorder e.g. SLE *IGNORE
‘secondary’ Sjögren’s syndrome
what is the schirmer’s test *IGNORE
assess tear production- under 5mm after 5 mins is abnormal
inflammatory muscle disease 2 types *IGNORE
dermatomyositis
=muscle and skin inflammation
polymyositis
=muscle only, no rashes
skin changes in dermatomyositis *IGNORE
-lilac colour rash around eyelids, malar, naso-labial folds
-red/purple flat/raised lesions on knuckles (Gottron’s papules)
inflammatory muscle disease investigation *IGNORE
1) bloods: high CK
2) electromyography- electrical activities of muscle
3) muscle biopsy
polymyositis = CD8 T cell
dermatomyositis = CD4 T cells+ B cells
what is inflammatory muscle disease associated with *IGNORE
malignancy and pulmonary fibrosis
systemic sclerosis signs *IGNORE
Thickened skin with Raynaud’s phenomenon
-dermal fibrosis
-cutaneous calcinosis
-telangiectasia
systemic sclerosis the 2 different types and elaborate *IGNORE
Limited systemic sclerosis
-Fibrotic skin limited to hands, forearms, feet, neck and face
-Anti-centromere antibodies
-Pulmonary hypertension
-Long history of Raynaud’s phenomenon
Diffuse systemic sclerosis
-Fibrotic skin proximal to elbows or knees (excluding face and neck)
-Anti-Scl-70 antibodies
-Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
-Short history of Raynaud’s phenomenon
what does CREST describe and what it stands for
CREST describes a sub-type of limited systemic sclerosis.
Calcinosis,
Raynaud’s phenomenon,
Esophageal dysmotility,
Sclerodactyly,
Telangiectasia
SLE-pregnancy- Drug considerations: WHICH ARE safe for pregnancy
Hydroxychloroquine, azathioprine, low molecular weight heparin (LMWH) safe
