Systemic Lupus Erythematosus Flashcards
SLE clinical features
General features -Malaise -Fatigue -Fever -Weight loss -Lymphadenopathy Specific features -Butterfly rash -Alopecia -Arthralgia -Raynaud's phenomenon Other features -Inflammation of the kidney, CNS, heart or lungs -Accelerated atherosclerosis -Vasculitis
SLE treatment (mild disease)
Mild disease (joint +/- skin involvement)
- Paracetamol +/- NSAIDs
- Hydroxychloroquine
- Topical corticosteroids
SLE treatment (moderate disease)
Moderate disease (inflammation of other organs eg: pleuritis, pericarditis, mild nephritis)
SLE treatment (severe disease)
Severe disease (severe inflammation in vital organs eg: severe nephritis, CNS disease, pulmonary disease, cardiac involvement, AIHA, thrombocytopaenia, TTP)
SLE epidemiology
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ACR criteria for SLE
4 or more of:
- malar rash
- discoid rash
- photosensitivity
- oral ulcers
- arthritis
- serositis (pleuritis or pericarditis)
- renal disorder (eg: proteinuria >0.5g/24h)
- neurological disorder (eg: seizures/psychosis)
- haematological disorder
- immunologic disorder (eg: anti-dsDNA Abs)
- antinuclear antibody in raised titre
SLE pathogenesis: autoantibody formation
- abnormal clearance of apoptotic cell material
- dendritic cell uptake of autoantigens and B cell activation
- B cell Ig class switch and affinity mutation
- IgG autoantibodies
- immune complexes
- complement activation and cytokine generation
SLE pathophysiology: autoantibody formation
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Assessing SLE disease severity
- identify pattern of organ involvement
- monitor function of affected organs
- identify pattern of autoantibodies expressed
SLE laboratory tests
- Antinuclear antibodies
- Anti-dsDNA and Sm
- Anti-Ro and/or La
SLE prognosis and survival
15 year survival:
- no nephritis=85%
- nephritis=60%
-prognosis worse if black, male and of low socio-economic status
SLE genetic associations
- multiple genes implicated=Fc receptors, IRF5, CTLA4, MHC class II HLA genes
- complement deficiency=C1q and C3
SLE lab tests
ANTINUCLEAR ANTIBODIES IN SERUM
-ANAs relatively non-specific, pattern important
Antinuclear antibodies
Homogenous=Abs to DNA
- Speckled=Abs to Ro, La, Sm, RNP
- Nucleolar= topoisomerase-scleroderma
- Centromere=limited cutaneous scleroderma
Lab test of anti-dsDNA and Sm
-more specific but less sensitive
Lab test of anti-Ro and/or La
- common in subacute cutaneous LE
- neonatal lupus syndrome and Sjogren’s syndrome
SLE lab tests
- increased complement consumption
- anti-cardiolipin antibodies
- lupus anticoagulant
- beta1 glycoprotein
Haematology of SLE
- lymphopenia
- normochromic anaemia
- leukopenia
- AIHA (acquired autoimmune haemolytic anaemia)
- thrombocytopenia
Renal tests of SLE
- proteinuria, haematuria
- active urinary sediment
Assessing SLE disease severity
1) identify pattern of organ involvement
2) Monitor function of affected organs
- renal=BP, U and E, urine sediment and prot:crea ratio
- lungs/CVS=lung function, echocardiography
- skin, haematology, eyes
3) Identify pattern of autoantibodies expressed
- anti-dsDNA, anti-Sm=renal disease
- anti-cardiolipin antibodies
Try and pre-empt severe attacks
CLINICAL FEATURES -weight loss, fatigue, malaise, hair loss -alopecia -rash LABORATORY MARKERS -ESR -increased complement consumption -increased anti-dsDNA -other Abs eg: ANA and CRP poor indicators
Azathioprine
- effective steroid-sparing agent
- moderate to severe disease give 2.5mg/kg/day
- 20% of patients get neutropenia (3/1000 severe bone marrow suppression)
- regular FBC and biochemistry monitoring=negative effect on liver
- favoured as safe during pregnancy=SLE affects young women during window of fertilisation
Cyclophosphamide
- used in severe organ involvement (iv pulsed or oral prescription)
- side effects=BM suppression, infertility, cystitis (acrolein), risk of infection
Mycophenolate mofetil
- reversible inhibitor of inosine monophosphate dehydrogenase
- rate-limiting enzyme in de novo purine synthesis
- lymphocytes=dependent upon de novo purine synthesis
Rituximab
- anti-CD20 mAb therapy
- leads to depletion of B cells
- effective in lupus nephritis
