Musc 8 - SLE Flashcards
Describe the features of SLE
- Systemic autoimmune disease
- Chronic relapse and remitting
- Unknown aetiology - multifactorial genetic (HLA-DR3) and environmental
Affects multiple systems - CNS, kidney, heart, skin and joints, etc
What type of patient is SLE most likely to affect
Female, onset = 15-47, increased risk in afro-caribbean/Asian
Quite rare
Explain the pathogenesis of lupus
- Innate susceptibility (HLA DR3, etc)
- Environmental stimuli (UV exposure, drugs, microbial response)
The above 2 contribute to autoimmune proliferation - hyperactive B/T cell proliferation —-> giving rise to autoantibody production —> immune complexes form and accumulate in organs (e.g. skin and kidneys) –> complement mediated inflammation
How does auto antibody formation occur in SLE
1, Abnormal clearance of apoptotic cell material
- Dendritic cell uptake of autoantigens and activatation of B cells
- B cell Ig class switching
- IgG antibodies
- Immune complexes
- Complement activation, cytokine generation, etc
Describe the clinical features of SLE
Presentation:
- Malaise, fatigue, fever, weight loss
- Lymphadenopathy
Specific features:
- Butterfly rash, alopecia
- Arthralgia
- Raynauds phenomenon
SLE ACR criteria, how many are needed?
At least 4/11.
Criterion:
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood (low)
Renal - proteinuria
Immunological - ANA, anti-dsDNA
Neurological - seizures/psychosis
Malar rash
Discoid rash
Which drugs can cause a lupus presentation (drug induced lupus)
It is also possible to just get cutaneous SLE without systemic involvement
Procanamide, hydrazine, quinidine, isonizaide
Explain the diagnosis of lupus
- Lab tests - Antinuclear antibodies (ANA) tests using ELISA, fluorescence. Pattern useful for diagnosing lupus.
- Other lab tests - e.g. increased complement consumption, anti-cardiolipin antibodies, lupus anticoagulant,
Haematology - lymphopaenia, normochromic anaemia, leukopenia, AIHA, thromocytopenia
Renal - proteinuria, haematuria, active urinary sediment
Why may it be better to use anti-dsDNA and Sm than ANAs to diagnose lupus?
Anti-dsDNA and SM more specific (but less sensitive)
How do we asses SLE disease severity
- Identify pattern of organ involvement
- Monitor function of affected organs (e.g. renal - BP, U & E, urine sediment and protein:creat ratio, lungs/cvs - lung function, echocardiography, skin, haematology, eyes)
- Identify pattern of autoantibodies expressed - anti-dsDNA, anti-SM (high anti-dsDNA could indicate impending flare up), anti-cardiolipin antibodies
How do we try and preempt severe attacks?
Clinical features - wt loss, fatigue, malaise, hair loss, alopecia, rash
Lab markers - ESR, increased complement consumption, increased anti-dsDNA
SLE treatment. How is it based
SLE divided into 3 groups:
Mild - joint + skin involvement
Moderate - inflammation of other organs, pleuritis, pericarditis, mild nephritis
Severe - severe inflammation in vital organs - severe nephritis, CNS disease, pulmonary disease, cardiac involvement, AIHA, thrombocytopenia, TTP
How is mild SLE treated
- Paracetamol (+/- NSAID)
- Hydroxychloroquine
- Topical corticosteroids
How is moderate SLE treated
- Oral steroids or IV methyprednisolone
- (depending on organ involvement - immunosuppressant, cyclophosphamide, mycofenalate mofitil (MMF), rituximab)
Thereafter need to be on long term immunosuppression maintenance therpay
What is rituximab?
Anti-CD20 monoclonal antibody
