Systemic Lupus Erythematosus Flashcards
(17 cards)
What is SLE?
- Systemic autoimmune disease
- Chronic relapsing and remitting
- Unknown aetiology –multi-factorial genetic (HLA-DR3) and enviromental
- Multi-systems pathology- CNS, kidney, heart, foetus, blood, skin, joints, lungs.
Who is at increased risk of SLE? What is the prevalence?
- Females mostly (10:1 ratio)
- Age of onset 15-47
- Increased risk in afro-caribbean/asians
Describe the interplay of genetic and environmental factors in the pathogenesis of SLE.
Summarise the key steps involved in SLE pathogenesis.
- Loss of self-tolerance
- Production of auto-antibody
- Deposition of immune complexes
- Immune complex-associated inflammation
- Tissue fibrosis and damage
What are the steps that lead to autoantibody formation in SLE?
AUTOANTIBODY FORMATION:
abnormal clearance of apoptotic cell material
–>dendritic cell uptake of autoantigens and activation of B cells
–> B cell Ig class switching
–> IgG autoantibodies
–> immune complexes
–> complement activation, cytokine generation etc.
List the clinical features of SLE.
Presentation: (systemic)
- Malaise, fatigue, fever, wt loss
- Lymphadenopathy
Specific features: (organ specific)
- Butterfly rash, alopecia
- Arthralgia
- Raynaud’s phenomenon
Other features:
- Inflammation kidney, CNS, heart, lungs
- Accelerated atherosclerosis
- Vasculitis
Name some of the symptoms included in the SLEE -ACR Criteria. How many have to be fulfilled for SLE diagnosis?
Mnemonic for ACR criteria:
- S-Serositis
- O-oral ulcers
- A-arthritis
- P-Photosensitivity
- B-Blood (all low)
- Renal-proteinuria
- Immunological- ANA, anti-dsDNA
- N-neurological-seizures/psychosis
- M-Malar rash
- D- discoid rash
What are the clinical and laboratory signs of SLE disease activity?
Clinical features
- Weight loss, fatigue, malaise, hair loss
- Alopecia
- Rash
Laboratory markers
- ESR
- Increased complement consumption
- Increased anti-dsDNA
- Other Abs e.g. ANA and CRP poor indicators
List some drugs that can falsely induce Lupus.
- Drug induced Lupus- procanamide, hydrazine, quinidine, isonizaide
What do different patterns of ANAs indicate in a laboratory test?
- homogenous - SLE - Abs to DNA
- speckled -SLE overlap syndromes - Abs to Ro, La, Sm, RNP
- nucleolar - Scl (scleroderma) - topoisomerase
- fine speckled - CREST - limited cutaneous scleroderma
ANA is relatively non-specific but pattern is important.
What laboratory tests can be done to determine if a patient has SLE?
Antinuclear antibodies: ANA relatively non-specific, pattern important - see previous slide
Anti-dsDNA and Sm
- More specific but less sensitive
Anti-Ro and/or La
- Common in subacute cutaneous LE
- Neonatal lupus syndrome & Sjögren’s
Other tests
- Increased complement consumption
- Anti-cardiolipin antibodies
- Lupus anticoagulant
- ß1 glycoprotein
How do you assess disease severity in SLE?
1. Identify pattern of organ involvement
2. Monitor function of affected organs
- Renal - BP, U & E, urine sediment + 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
How do we divide SLE patients into treatment groups?
Dependsing on the severity of their disease.
Mild = joint and/or skin involvement.
Moderate = inflammation of other organs (pleuritis, pericarditis, mild nephritis)
Severe = inflammation in vital organs is severe e.g. severe nephritis, CNS disease, pulmonary disease, cardiac involvement, AIHA, thrombocytopaenia, TTP.
Describe the treatment of mild SLE.
A. Paracetamol +/- NSAID
- Monitor renal function
B. Hydroxychloroquine
- arthropathy
- cutaneous manifestations
- mild disease activity
C. Topical corticosteroids
Describe the treatment of moderate to severe SLE.
- Oral corticoseroids or IV methylprednisolone (0.5-1.0g OVER 3 DAYS)
- Add immunosupressants in severe organ disease
- Cyclophosphamide
- Mycofenalate Mofitil (MMF)
- Rituximab (anti-CD20 monoclonal Ab) for Lupus Nephritis
- Maintenance treatment = low dose oral steroids 9<5mg/day) and immunosupressants (methotrexate, azathioprine or MMF)
What lifestyle factors need to be managed in patients with SLE?
- Need to have regular follow-ups, monitoring of BP and urine and screening for CVD risk factors
- Use of hydroxychloroquine for skin and joint disease
- Use of high dose steroids plus immunosupression in major organ involvement
- Using sun block as lupus is very photosensitive
- Monitoring for Anti-Ro abs in pregnancy due to risk of congenital heart block
State the bimodal pattern of SLE.
Early = ACTIVE LUPUS - renal failure - CNS disease - infection
Late = MYOCARDIAL INFARCTION
