Lupus Flashcards
Systemic lupus erythematosus?
Autoimmune disease involving innate and adaptive immune system disturbance
Has autoantibodies - antibodies to nuclear components
Antibody-antigen (immune complexes) -> chronic tissue inflammation (particularly joints, skin and kidney)
SLE rash example?
Malar rash
Autoimmune connective tissue disorder? General points
- Arthralgia and arthritis typically non-erosive (unlike RA)
- Serum autoantibodies characteristic
- Raynaud’s phenomenon common
Raynaud’s phenomenon?
Intermittent vasospasm of digits, usually triggered by cold exposure
Triphasic colour changes
Typical Raynaud’s colours?
White - vasospasm leading to blanching of digit
Blue - cyanosis as static venous blood deoxygenates
Red - reactive hyperaemia
Severe Raynaud’s - tissue ischaemia, ulcers and necrosis
SLE epidemiology?
15-45
F:M - 9:1
Africa > Asian > white European
Clinical features? Skin
Malar rash - erythema that spares nasolabial fold
Photosensitive rash
Mouth ulcers
Hair loss
Clinical features? Vascular
Raynaud’s
Clinical features? MSK
Arthralgia and arthritis (non-erosive)
Clinical features? Internal organs
Serositis (pericarditis, pleuritis, rarely peritonitis)
Renal disease - glomerulonephritis
Cerebral disease
Myocarditis
Clinical features? Haematological
Autoimmune thrombocytopenia
Haemolytic anaemia
Lymphopenia
Clinical features? Other
Lymphadenopathy
Fever in absence of infection
Anti-nuclear antibodies?
Hallmark of SLE, in all patients
Examples of other autoantibodies:
Anti-ds-DNA antibody
Anti-Ro
Anti-La
Anti-Smith
Anti-RNP
Anti-phospholipid antibodies?
Directed to phospholipids on cell membrane
Associated with increased risk of thrombosis and pregnancy loss
persistent APL + clinical event = anti-phospholipid antibody syndrome
Main autoantibodies in SLE?
Antinuclear antibodies - in all SLE, non-specific
Anti-double stranded DNA antibodies - specific for SLE, serum level DO correlate with disease activity
Anti-phospholipid antibodies - can occur in absence of SLE (primary anti-phospholipid antibody syndrome)
Anti-Sm antibodies - specific for SLE, serum levels DON’T correlate with disease activity
SLE immunopathogenesis?
Overactivity of type 1 interferon pathway
Complement pathway abnormalities
Overactive B and T cells
Waste disposal hypothesis
- Apoptosis -> translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells = enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms
SLE investigations? Inflammation
High ESR, usually normal CRP
SLE investigations? Renal
Measure urine protein, creatinine, albumin
Kidney biopsy if persistent proteinuria
SLE investigations? Immunological
ANA
Anti-ds-DNA antibodies
Complement consumption (low C3 + C4)
Antiphospholipid antibodies
SLE complement and antibodies in unwell patient?
Low C3 + C4
High anti-dsDNA antibodies
SLE management aims?
- Treat SLE and prevent flares
- Prevent ionotropic harm of steroids (infection, osteoporosis, avascular necrosis)
- Specific treatment
SLE management? Pharmacology
Hydroxychloroquine recommended for all lupus patients
steroids for flare
Serious disease - immunomodulatory (mycophenolate, methotrexate, Azathioprine)
SLE renal disease treatment?
Mycophenolate +/- rituximab
Severe or life threatening SLE treatment?
IV steroids + IV cyclophosphamide
SLE + antiphospholipid antibody syndrome treatment?
Anticoag (warfarin)
SLE and pregnancy considerations?
- Antiphospholipid antibodies associated with miscarriage (give aspirin or heparin)
- Pregnancy increased Haemodynamic demands so will worsen renal dysfunction
- Ro antibodies - can cause fetal heartblock
- Drugs
Drug considerations? SLE and pregnancy, unsafe and safe
Unsafe - MMF, cyclophosphamide, methotrexate and warfarin are teratogenic
Safe - Hydroxychloroquine, Azathioprine and low weight molecular heparin
Ionotopic steroid side effects?
Infection, osteoporosis, avascular necrosis
