SLE (05.02.2020) Flashcards
What disease family is SLE in? What other diseases are in that family?
Family of chronic overlapping AI diseases
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Systemic sclerosis
- Polymyositis
- Dermatomyositis
- Sjögren’s syndrome
SLE - general info
- rare (3 in 10,000)
- mainly affects women (9:1)
- generally presents at 15-40 years of age
- increased in afro-carribean and asian population, prevalence varies
- genetic predisposition and environmental factors
- Principally affects joints and skin but also lungs, kidneys, haematology
- Severity from mild joint pain to fulminant & life threatening
- Clinical features depend on organ affected
Where does SLE sit on a spectrum of connected AI diseases?
- RA (mainly joints)
- SLE
- Sjorgen Syndrome
- Dermatomyositis (mainly muscular)
- Polymyositis (mainly muscular)
- scleroderma / systemic sclerosis (features of muscle, skin and joint involvement as well as lung disease)
Genetic associations of SLE
- multiple GWAS studies show that it is a polygenic disease with multiple susceptibility genes (e.g. Fc receptors, IRF5, CTLA4, MHC class II HLA genes)
- There are some genes, that if you are deficient you will have SLE (C1q and C3) -> complement deficiency
How does SLE clinically present?
- Malaise, fatigue, fever, wt loss
- Lymphadenopathy
Specific features:
• Butterfly rash, alopecia
• Arthralgia
• Raynaud’s phenomenon
Other features:
• Inflammation kidney, CNS, heart, lungs
• Accelerated atherosclerosis
• Vasculitis
Severe presentations are possible e.g. with myocarditis!
SLE ACR criteria
- Malar rash
- Discoid rash (sparing of nasal folds)
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis: (a) pleuritis or (b) pericarditis
- Renal disorder e.g. proteinuria > 0.5g/24h
- Neurological disorder e.g. seizures/ pyschosis
- Haematological disorder
- Immunologic disorder e.g anti-dsDNA Abs
- Antinuclear antibody in raised titre
- > 4 out of 11
- > a spectrum of tissues is affected!
Rash in SLE
- not everyone presents with it
- butterfly shape
- sparing of nasal folds (distinguishes it from rosacea)
- some patients may have scarring
- no pus in the rash
- there may be areas of erythema around the rash
- you may have scarring alopecia (this can be traced with local corticosteroid injections)
Pathogenesis of SLE
- genetic predisposition
- environmental triggers (e.g. virus and TLR but not understood yet; minor infections e.g. UTI can kick off a disease flare; perhaps bacterium) -> this probably happens a number of times
- then you get b-cell hyperactivity (critical point) chronically activated innate immune system -> witch from innate to adaptive immune response with antibodies and immune complex
- this goes through cycles but eventually there is irreversible (typically completement induced) tissue injury.
- Type 3 hypersensitivity
- also: clearance of apoptotic cells is deficient in SLE
- nuclear antigens come onto surface - we clear them fast but people with lupus can’t clear them and develop antibodies and immune complexes against them.
- ABs and immune complexes settle in the skin or kidneys and activate complement - complement mediated tissue damage causes rash and nephritis
What is the genetic haplotype with predisposition to SLE?
HLA-DR
What type of hypersensitivity is SLE?
Type 3
- immune complex driven
Pathophysiology of SLE (quick)
- abnormal clearance of apoptotic cell material
- dendritic cell uptake of auto antigens and activation of B-cells
- B cell Ig-Class switching and affinity maturation
- IgG autoantibodies
- immune complexes
- complement activation, cytokine generation etc.
ANA
- anti nuclear antibody (aABs against apoptotic cells)
- lab test that may point towards lupus if positive
- not diagnostic, but an indicator
- pattern important e.g. speckled or homogenous (indirect immunofluorescence shows where the attachments on the cells are)
Which laboratory tests are used in the diagnosis process of SLE?
- ANA
- anti-dsDNA and Sm (more specific but less sensitive)
- Anti-Ro and/or La
What do different patterns in the ANA test indicate?
- Homogenous - Abs to DNA
- Speckled - Abs to Ro, La, Sm, RNP
- Nucleolar - topoisomerase - scleroderma
- Centromere - limited cutaneous scleroderma
anti-dsDNA and Sm
- (more specific but less sensitive) than ANA
- absence does not exclude lupus (only 30% people with lupus have it)
- Sm = anti-Smith
- 20% people with lupus have it; rarely found in healthy individuals or other rheumatoid diseases
- can be used to confirm lupus