Lupus Flashcards
What are the autoimmune connective tissue disorders?
- systemic lupus erythmatosus
- autoimmue inflammatory muscle disease
- systemic sclerosis (scleroderma)
- Sjorgen’s syndrome
When are overlap syndromes of autoimmune connective tissue disorders most likely to occur?
In childhood
What is SLE?
- autoimmune disorder affecting both innate and adaptive immune systems
- involves autoantibodies to nuclear components of cells
- immune complexes and other mechanisms cause chronic tissue inflammation
Where is inflammation most likely to manifest in SLE?
Joints, skin and kidney
How is arthirits and artharlagia different in SLE than in RA?
Non-erosive
What is a common feature of autoimmune connective tissue disorders?
Raynaud’s phenomenon
What is Raynaud’s phenomenon?
- intermittent vasospasm of digits
- usually triggered by cold exposure
What is the triphasic colour change which happens in Raynaud’s phenomenon?
- White - vasospasm causes digits to blanch
- Blue - cyanosis due to static venous blood becoming deoxygenated
- Red - reactive hyperaemia
What are the features of severe Raynaud’s?
Tissue ischaemia, ulcers and necrosis
What are the common clinical features of SLE?
- malar (butterfly) rash
- photosensitive rash
- mouth ulcers
- hair loss
- Raynaud’s
- arthralgia
- serositis
- renal disease
- cerebral disease
- myocarditis
- autoimmune thrombocytopenia
- haemolytic anaemia
- lymphopenia
- lymhodenopathy
- fever with no infection
What is the hallmark feature of SLE?
- Anti-nuclear antibodies (ANA)
- found in all SLE patients
Why can ANA be used to rule out lupus but not diagnose it?
ANA is not specific for lupus and can be seen in other diseases, infections and even in healthy people
What will the clinical laboratory report if ANA is positive?
- strength (maxiumum dilution at which antibody can still be detected)
- pattern of staining (suggests which autoantigen the antibodies are reacting to)
Which further tests indicate that a patient is positive for SLE?
- anti-ds-DNA antibodies
- anti-Ro
- anti-La
- anti-Smith
- anti-RNP
Which other antibodies do some patients with SLE present with?
Antiphospholipid antibodies (APL)
What is the presence of APL associated with?
- arterial thrombosis (stroke)
- venous thrombosis (DVT)
- pregnancy loss
What is anti-phospholipid antibody syndrome?
- presistent presence of APL + clinical event
- cann occur in absence of SLE (primary APL syndrome)
Which antibodies are specific for SLE?
- anti-double stranded DNA antibodies
- anti-Smith antibodies
Which antibody specific to SLE has serum levels which indicate the severity of the diesease?
Anti-ds DNA antibodies
What is the immunopathogenesis of SLE?
- Interference with innate immunity
- overactivity of type 1 interferon pathway
- complement pathway abnormalities - Interference with adaptive immunity
- autoreactive B and T cells
How does the immune system generate a repsone to nuclear antigens?
Waste disposal hypothesis
What is the waste disposal hypothesis?
- apoptosis translocates nuclear antigens to the membrane surface
- impaired clearance of apoptotic cells means more nuclear antibodies are presented to immune cells
- causes B cell autoimmunity
- leads to tissue damage by antibodies activating complement and Fc receptor engagement
Why are the manifestations of SLE so varied?
Autoimmunity is systemic so almost any organ can be involved
Which investigations are done for SLE?
- ESR (high)
- CRP (usually normal)
- FBC (anaemia, lymphopenia, thrombocytopenia)
- urinalysis to measure urine protein
- creatinine
- U&E
- albumin
- kidney biopsy is persistent proteinuria
- ANA
- anti-ds DNA
- compelement (low C3 and C4)
- ALP
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What should be measured in patients who are on medication for SLE and why?
- FBC and LFT
- may have adverse reactions to the medication
How do you measure disease activity in SLE?
- clinical symptoms and signs
- low C3 and C4 levels
- high anti-ds DNA antibodies
What are the general principals of managing SLE?
- aim for remission or low disease activity and preventing flare ups
- balance controlling disease with avoiding iatrogenic harm from steroids
- choose treatment depending on the disease severity and organ manifestations
What are the steroid side effects seen in SLE?
- infection
- osteoporosis
- avascular necrosis (necrosis of bone, often affecting hips) especially in patients with ALP
Which medications are recommended for all patients with SLE?
Hydroxychloroquine
When can steroids be used for SLE?
In acute flare ups
What medications are used in more serious SLE?
Immunomodulatory agents (mycophenolate, methotrexate, azithioprine)
Which medications are used for kindey disease in SLE?
Mycophenolate +/- rituximab
Which medications are used in persistently active SLE?
- B cell targeted therapies
- rituximab (depeltes B cells, anti-CD20)
- belimumab (anti-BAFF, cytokine needed for B cell survival)
How do you treat life-threatening disease e.g myocarditis?
- IV steroids
- IV cyclophosphamide
- +/- rituximab
What should patients with SLE and antiphospholipid antibody syndrome be given?
Warfarin for anticoagulation
What are the emerging therapies for SLE?
Interferon receptor blockade e.g anifrolumab
Who does SLE usually affect?
Women during their reproductive years
What needs to be taken into consideration when treating patients with SLE who are of child bearing age?
- risk of disease and drugs to both mother and fetus
- better outcomes with pre-pregnancy planning and getting SLE into remission first
What is the effect of ALP on pregnancy?
- associated with miscarriage
- can reduce risk with aspirin or heparin
How does pregnancy affect renal function?
Increases haemodynamic demands which worsens renal function
What can Ro antibodies cause in pregnancy?
Fetal heartblock
Which medications for SLE are teratogenic?
- MMF
- cyclophosphamide
- methotrexate
- warfarin
Which medication for SLE are safe for pregnancy?
- hydroxychloroquine
- azathioprine
- low molecular weight heparin
