2: SLE Flashcards
What is SLE
Multi-system autoimmune disorder
In which gender is SLE more common
Females (10:1)
What is the peak incidence of SLE
20-40y
What is the typical demographic for SLE
Middle age females
What ethnicity is SLE more common in
Asians
African Americans
What is the aetiology of SLE
Genetic predisposition with genes:
HLA DR1
HLA DR3
What are two ‘groups’ of risk factors for SLE
High oestrogen
Enviromental
What are 3 causes of high oestrogen that predispose to SLE
COCP
HRT
Endometriosis
What are 4 environmental causes that predispose to SLE
Smoking
Epstein Barr Virus
Medications
UV
What infection predisposes to SLE
Epstein Barr Virus
What two medications predispose to SLE
- Procainamide
- Hydralazine
How is the progression of SLE characterised
Remission and relapse
What % if people with SLE present with skin symptoms
70%
What are 5 cutaneous symptoms of SLE
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Non-scarring alopecia
What is malar rash
Erythematous rash with sparing of the naso-labial folds
What is discoid rash
Erythematous patches with adherent keratotic scarring
What % of people with SLE have joint symptoms
80
What are 3 systemic symptoms of SLE
Lethargy
Weight loss
Low-grade fever
What are the main symptoms of SLE
- Arthalgia (90%)
- Lethargy (80%)
- Cutaneous (70%)
What are the 2 MSK symptoms of SLE
Myalgia
Lymphadenopathy
What are 2 serositis symptoms of SLE
Pericarditis
Pleuritis
What is the kidney symptom of SLE
Lupus nephritis
What are 3 GI symptoms of SLE
Oeseophagitis
Pancreatitis
Hepatitis
What are 3 vascular symptoms of SLE
Reynaud’s
Vasculitis
VTE
What are 5 neurological symptoms of SLE
Seizures Psychosis Personality change Aseptic meningitis Polyneuropathy Myasthenia Gravis
What are 3 haematological symptoms of SLE
Haemolytic anaemia
Thrombocytopenia
Leucopenia
Describe the criteria for SLE diagnose
Requires four or more of criteria list (at least one clinical and one lab), or biopsy proven lupus nephritis with positive ANA or anti-DNA
What are the 11 clinical criteria for lupus nephritis
- Acute cutaneous lupus
- Chronic cutaneous lupus
- Non-scarring alopecia
- Oral ulcers
- Synovitis
- Serositis
- Proteinuria or red cell casts
- Neurological features
- Haemolytic anaemia
- Leucopenia
- Thrombocytopenia
What are the 6 lab criteria of lupus nephritis
- ANA
- anti-dsDNA
- anti-smith
- anti-phospholipid
- low complement
- positive coombs test
What is a good mnemonic to remember features of SLE
SOAP BRAIN MD
What are the symptoms/features of SLE
Serositis Oral ulcers Arthritis Photosensitivity Blood disorders Renal involvement Anti-nuclear antibodies Immunological phenomenon Neurological disorders Malar rash Discoid rash
What are 3 sub-types of lupus
- Discoid lupus
- Sub-acute cutaneous lupus
- Drug-induced lupus
What is discoid lupus erythematosus
Triggered by UV - it is erythematous scaly plaques
What % of lupus is discoid lupus erythematosus
50-80%
What triggers discoid lupus
UV
What regions does discoid lupus affect
head, neck and face
How will discoid lupus present
erythematous scaly plaques that leave scar tissue
What is the risk of developing SLE with discoid lupus
10-15%
What % of lupus is subacute cutaneous lupus
10%
Which regions does subacute cutaneous lupus affect
Neck, shoulder and forearms but spares the face
Which region does subacute cutaneous lupus not affect
Face
How does subacute cutaneous lupus present
small erythematous rash
What is drug-induced lupus erythematosus
lupus like symptoms that resolve in days to months following cessation
What drugs trigger drug-induced lupus
Ms. Pip:
Methyldopa Sulfa-containing drugs Procainamide Isoniazid Phenytoin
Which 5 drugs may cause drug-induced lupus
- procainmide
- hydralazine
- isoniazid
- phenytoin
- methyldopa
Which age group is drug induced lupus more common
older individuals
How does drug induced lupus present
- fever
- serositis
- poly arthritis
- myalgia
- rash
What is present in drug-induced lupus on investigation
anti-histone antibodies
What type of hypersensitivity reaction is SLE
Type 3 hypersensitivity reaction
Explain the pathophysiology of SLE
- Individuals exposed to UV causes DNA damage and apoptosis. This produces apoptotic bodies and expose remaining body to the nucleus
- Susceptibility genes (HLADR2 + HLADR3) are more likely to recognise these antigens as foreign and generate an immune response
- Also reduce clearance of apoptotic bodies increasing nuclear antigens in circulation
- Anti-nuclear antibodies bind antigens to form complexes
- Complexes enter different tissues and adhere to walls in vessels
- When adhered they produce an inflammatory reaction that activates complement system causing damage
- This disrupts osmotic channels in cell membranes causing rupture
What investigations are used for SLE
- Anti-nuclear antibodies
- Anti dsDNA antibodies
- Anti smith antibodies
- Rheumatoid factor
- SS-A
- SS-B
What is the most specific antibody for SLE
Anti-smith
What is the most sensitive antibody for SLE
Anti-dsDNA (70%)
What 3 tests are used to monitor disease activity in SLE
ESR
Complement
Anti dsDNA
How will CRP present in SLE and therefore what does a raised CRP indicate
CRP will be normal - therefore a raised CRP indicates underlying infection.
How will complement present in disease activity and why
Complement will be low - due to use in reaction
What general treatment is used for SLE
- Avoid sun exposure
- High Factor Sun cream
- Hydroxychloroquine
- Topical steroids
what has hydroxychloroquine be shown to do
Reduce disease activity and improve survival
when are topical steroids recommended
Skin flares
what is used as maintenance therapy for SLE
NSAIDs
Hydroxychloroquine
if individuals have high antibody positive disease what else may be used
Belimumab
what defines a mild flare
No organ damage
what is used to treat a mild flare of SLE
Low dose oral steroids
Hydroxychloroquine
what defines a moderate flare
Evidence of organ involvement
what is used to manage a moderate flare of SLE
DMARDs
Mycophenolate
what defines a severe flare of SLE
Organ threatening: haemolytic anaemia, nephritis, pericarditis, CNS disease
how is a severe flare of SLE treated
IV steroids
Mycophenolate
Rituximab
Cyclophosphamide
What is survival of SLE at 15y
80%
What are two risks of SLE
increase risk of osteoporosis and CVD
What are two complications of SLE
Lupus nephritis
Antiphospholipid syndrome
What is lupus nephritis
Interstitial nephritis caused by deposition of complement in SLE
What % of individuals with SLE develop lupus nephritis
50%
How may lupus nephritis present
nephritic or nephrotic syndrome
What is WHO class I lupus nephritis
Normal kidney
What is WHO class II lupus nephritis
Mesangial Glomerulonephritis
What is WHO class 3 lupus nephritis
Focal (segmental glomerulonephritis)
What is WHO class 4 lupus nephritis
Diffuse proliferative glomerulonephritis
What is WHO class 5 lupus nephritis
Diffuse membraneous glomerulonephritis
What is WHO class 6 lupus nephritis
Sclerosing glomerulonephritis
What is the most common and severe form of lupus nephritis
Who Class 4: diffuse proliferative glomerulonephritis
What investigations may be done in lupus nephritis
- Urinalysis
- A:Cr ratio
- Kidney biopsy
When is a kidney biopsy considered
A:Cr >30
P:Cr >50
How will diffuse proliferative glomerulonephritis appear on kidney biopsy
- Endothelial and mesangial proliferation (wire-loop appearance)
- Thickened capillary wall
- Subendothelial immune deposits
What is the management of lupus nephritis
- Treat HTN
- Corticosteroids
- Immunosuppressants (azathioprine, cyclophosphamide)
How is lupus nephritis prevented
Patients with SLE should have regular urinalysis at check-ups to look for proteinuria
What is antiphospholipid syndrome
Autoimmune disease that increases risk of thrombosis due to pro-coagulators antibodies
What causes primary antiphospholipid syndrome
Associated with HLA DR7
What are 5 causes of secondary antiphospholipid syndrome
- SLE
- RA
- HIV
- Hep A,B and C
- Infection (TB, syphillis, lymes disease)
What % of individuals with SLE have antiphospholipid syndrome
20-30%
What is a mnemonic to remember symptoms of anti-phospholipid syndrome. What are the symptoms of antiphospholipid syndrome
CLOTS
Coagulation defect (arterial and venous) Livedo reticularis Obstetric complications Thrombocytopenia Splinter haemorrhages
What are 4 arterial thrombotic complications of antiphospholipid syndrome
TIA
Stroke
End-organ ischaemia (MI)
Occlusion of distal extremity
What are 4 venous thrombotic complications of antiphospholipid syndrome
PE
DVT
Livedo reticularis
Chronic venous ulcers
What are two obstetric complications of antiphospholipid syndrome
Recurrent miscarriage
Premature birth
Why do obstetric complications of antiphospholipid syndrome occur
Thrombosis of the placenta vessels causing infarction
Explain the pathophysiology of antiphospholipid syndrome
- Antiphospholipid antibodies form complexes with anti-coagulatory proteins (protein C, S, anti-thrombin 3)
- Antibodies activate platelets and vascular endothelium
- This induces a hyper-coagulable state
What prompts investigation for antiphospholipid syndrome
- history of recurrent miscarriages
- history of arterial/venous thrombosis
What investigation is performed in antiphospholipid syndrome
antiphospholipid antibody panel
What are the antiphospholipid antibodies
- lupus anticoagulant
- anticardiolipin antibody
How will lupus anticoagulant appear on coagulation screen
raised aPTT (partial thromboplastin time)
if patients have anti-cardiolipin antibodies what will they test falsely positive for and why
syphillis. As the test for syphillis uses cardiolipin
What is the acute management of antiphospholipid syndrome
LMWH
IV Unfractioned heparin
If severe, what is offered for antiphospholipid syndrome
High-dose corticosteroids or plasmapheresis
what prophylaxis is offered for low risk antiphospholipid syndrome
Aspirin
what prophylaxis is offered for high risk antiphospholipid syndrome with no desire to be pregnant
Warfarin
what prophylaxis is offered for high risk antiphospholipid syndrome with desire to be pregnant
LMWH and aspirin
