4: Systemic Lupus Erythematosus Flashcards
Summarise the epidemiology of systemic Lupus erythematosus (SLE)
- Rare disease
- Females more commonl than males (9:1)
- Normally onset between 15-40years
- increased prevalence in afro-carribean and asian population
- • Prevalence varies - 4 - 280/100,000
What is the role of genes in the development of systemic Lupus eryththematosus
- Associated with a genetic predisposition, multiple genes involved but
- rare can by monogenic origin:
- C1q+C3 deletion
- rare can by monogenic origin:
- Other: Fc receptors, IRF5, CTLA4, MHC class II HLAgenes
What are the general presenting features of someone with SLE?
1: very general presentation
- malaise, fecer, weight loss, fatigue –> patients are unwell!
- Lymphadenopathy (swollen lymph nodes)
- If this is chronic, not improving –> might suspect Lupus
What are specific signs and symptoms of Lupus?
What is their limitation in the digansis of the disease?
They are specific and make it easy to diagnose, but are not present in most people presenting with Lupus
- Butterfly rash –> sparing of nasal area, around cheeks and chin
- alopecia (hair loss)
- Arthralgia (joint pain)
- Raynaud’s phenomenon (spasm of arteries cause reduced blood flow to extremities)
Other features:
- Inflammation kidney, CNS, heart, lungs
- Accelerated atherosclerosis
- Vasculitis
Explain the characteristics of the SLE associated Butterfly rash
- no pus
- Present at cheeks and chins
- Sparing of nasal wings /area around nose
Can be
- epidermal
- or in severe cases: deep dermal with loss of pigmentation and peramnent scaring
Which facots play a role in the pathogenesis of systemic lupus erythematosus ?
It is a complicated disease caused by
- genetic predisposition in combination with
- several envirnmantal triggers –> activate the
- inate immune system
- adaptive immune system
- Immune complexes (can repeat until:)
- –> immune complex activation sets off dowonstream disease with permanent tissue damage
Explain the formation of auto-antibodies in SLE
- Abnormal clearance of apoptotic cell material (expsed foreign nuclear substances)
- Dendritic cell uptake of autoantigens and activation of B cells
- B cell Ig class switching and affinity mutation
- IgG autoantibodies
- immune complexes
- complement activation, cytokine generation etc
What are the diagnositic immune/antibody test that are done to diganose SLE?
-
Antinuclear Antibodies (ANA)
- non-specific but can be good indicator to do further:
-
Anti-Double-Strand DNA (Anti-DsDNA) and Smith Antigen (SM)
- highly specific but less sensitive (not everyone with Lupus has it
- Anti-Ro and/or La
- more antigen tests
What is an ANA?
How would it look in SLE?
Anti-nuclear Antibody test, in systemic Lupus Erythematosus
- would give homogenous pattern in SLE –> Antibodies to DNA are formed
Which other laboratory test (other than antibodies) cna be done to diagnose SLE?
Other general tests:
- Decreased complement levels (due to increased consumption)
- Lupus anti-coagulant (might be pro thrombotic)
- ß1-glycoprotien
Renal tests:
- Proteinuria, haematuria
- Active urinary sediment
Haematological
- Lymphopaenia, normochromic anaemia (due to haemolytic)
- Leukopaenia, AIHA, thrombocytopaenia
How could a blood film look like with someone with SLE?
Might have
- thrombocytopaenia (??? antobodies???)
- Leukopaenia/Lymphopaenia
- Autoimmune-haemolytic anaemia (normocytic)
How would you establish the severity of someone with SLE?
- Identify pattern of organ involvement
- Monitor function of affected organs
- Renal - BP, U & E, urine sediment + Prot:Crea ratio
- Lungs/CVS - lung function, echocardiography
- Skin, haematology, eyes
- Identify pattern of autoantibodies expressed
- Anti-dsDNA, anti-Sm (poorer prognosis if anti-SM+) - renal disease
- Anti-cardiolipin antibodies
What is the aim for the clinical management of SLE?
Aim: pre-empt an actue attackand prevent severe attach
How do you monitor someone with SLE?
Try to pick up an attach early via
Via the
- Clinical Features
- weight loss, fatigue, malaise, hair loss
- Alopecia (spot baldness)
- Rash
- Labortatory features
- ESR
- Increased complement consumption
- Increased anti-dsDNA
- Other Abs e.g ANA and CRP poor indicators
*
- Other Abs e.g ANA and CRP poor indicators
How would you classify a SLE as mild, moderate or severe?
Look at the involvement of different systems and how severe they are affected
What are the characteristics of a mild SLE?
- joint
+/- skin involvement
What are the characterisitcs of a moderate SLE?
Next to skin and joint invovement (mild) also
- inflammation of other organs
- pleuritis, pericarditis, mild nephritis
What are the characteristics of severe SLE?
severe inflammation in vital organs
- severe nephritis
- CNS disease –> depression, psychosis
- • pulmonary disease*
- • cardiac involvement –> rarew but possible*
• AIHA (auto-immune haemolytic anaemia) , Thrombocytopaenia, TTP (coagulation disorder)
How do you treat mild SLE?
- Paracetamol +/- NSAID
- Monitor renal function
-
Hydroxychloroquine
- arthropathy
- cutaneous manifestations
- mild disease activity
- Topical corticosteroids
How would you treat moderate SLE?
If NSAIDs fail/ and or there is a life-threatening disesae
Corticosterioids
- high initial dose to suppress disease activity (0.5-1.5mg/kg/day)
- iv methylprednisolone 3 x 0.5-1g per 24h
- initial oral dose for 4 weeks
- reduce slowly over 2-3 mths to 10 mg/d
- reduce slowly at 1mg per month
Additional to cortocosteriords, how would you treat severe SLE?
- Azathioprine
- effective, steroid sparing drug
- 20% neutropenia (3/1000 severe BM suppression)
- regular FBC & biochemistry monitoring
- Cyclophosphamide
- severe organ involvement, iv pulsed or oral Rx
- –> has severe side-effects but should still be used to prevent dangerous attack
- Mycophenolate mofetil
- supresses lmyphocyte (by blocking de novo purine synthesis)
- Anitbodies (Retuximab)
- Anti CD20 (B-cell)
What is the prognosis and survival of someone with SLE?
Dependant on the severity
15 year survival is
- 85% without renal involvement
- 60% with nepritis
–> highly dependant on and worse when black, male, low socio-economic status
Why and when do people die from SLE?
They can either die early from direct complcations or later due to bad atherosclerosis
- Early
- Acitve lupus
- Renal Failure
- CNS disease
- Infections (Immune supression)
- Acitve lupus
- Late
- MI/ Stroke –> because of bad atherosclerosis
What are biomarkers of active disease in SLE?
- ESR (increased)
- Anti-DsDNA/Sm
- Decreased C3, C4 complement
No CRP
