Rheum - SLE Flashcards
(28 cards)
SLE?
Systemic Lupus Erythematosus
What is SLE?
It is a rare disease
• a part of a family of overlapping chronic AI diseases including - RA, SLE, systemic sclerosis, polymyositis
Background info surrounding SLE?
o M: F = 1: 9 and presents at 15-40 years of age.
o More prevalent in Afro-Caribbean’s, Asians and Chinese people – prevalence = 4-280/100,000
o Principally affects the joints and skin – also affects lungs, kidneys and has unique haematology
Genetic associations:
Multiple genes:
• Fc receptors, IRF5, CTLA4, MHC class 2 HLA genes.
Complement deficiency – C1q and C3.
How does SLE present?
Malaise Fatigue Fever Weight loss Lymphadenopathy (lymphomas excluded)
What is special features associated with SLE?
Butterfly rash! (on face!!)
Alopecia
Arthralgia
Raynaud’s phenomenon
Other features associated with SLE?
Inflammation of the kidney, CNS, heart, lungs
Accelerated atherosclerosis
Vasculitis
What is the ACR criteria for diagnosis of SLE?
4+ of the 11 criteria
Pathogenesis of SLE?
Pathogenesis NOT fully understood
• but tend to have OVERACTIVE IS - particularly their humoral immunity
What are the 2 things associated with the pathogenesis of SLE?
- Apoptotic defects
2. B-Cell hyperactivity
Explain the effect of apoptotic defects on SLE
There is impaired clearance associated with inflammation of apoptotic bodies in SLE
• the apoptotic bodies linger in the body
and
• expose nuclear antigens on their surface which generate auto-antibodies
Explain the effect of B-Cell Hyperactivity on SLE
Overactive b-cells are exposed to the auto-antigens and the plasma cells begin to produce auto-ABs which form immune complexes
• this deposits in tissues (mainly kidneys/skin) which then activates complement in the tissues
Describe the process of auto-Ab formation in SLE
- Abnormal clearance of apoptotic bodies
- Dendrites take up autoantigens –> b-cell activation
- B-cell Ig-class switch and affinity maturation
- IgG-autoantibodies
- Immune complexes
- Complement activation via classical pathway
How can SLE be diagnosed in the lab?
First, send a serum to check for anti-nuclear antibodies.
• This is NOT diagnostic of SLE
Serum is combined with cells and if ANAs are present, they will bind to the cells’ nuclear antigens
• a fluorescently labelled AB is added that binds to ANAs and you observe the pattern of attachment
What tests can be ordered in the lab to assess the activity of the disease?
- ANA
- Anti-dsDNA and Sm
- Anti-Ro and/or La
- Other tests
- Haematology
- Renal
(onenote!!)
Why will INCREASED complement consumption be diagnostic of SLE?
Patients with ACTIVE lupus will have
• more complement bound to immune complexes
and so the blood complement will be LOW in active lupus.
What else do SLE patients present with?
SLE patients will present with AI haemolytic anaemia
• ABs bind to RBC surfaces and they are extravascularly removed in the spleen
What is lupus correlated with?
LOW counts of everything!
• i.e. -paenia
How do you assess the severity of SLE?
- Identify pattern of organ involvement
- Monitor function of affected organs:
a. Renal – BP, U&E, urine sediment GFR
b. Lungs/CVS – lung function tests, echocardiography - Identify the patterns of auto-Abs expressed
a. Anti-dsDNA, anti-Sm – high levels of these ABs can predict renal disease
b. Anti-cardiolipin antibodies.
How can you try and pre-empty severe attacks associated with SLE?
Picking up on symptoms early can result in less damage to organ system
• Wt loss, fatigue, malaise, hair loss
• Alopecia
• Rash
ESR will RISE is the disease is becoming more severe! Other lab markers include • increased complement consumption • increased anti-dsDNA • other Abs e.g. ANA and CRP
How is SLE treated iniitally?
The disease is split into 3 groups based on severity:
• MILD - no sign of organ involvement
• MODERATE - inflammation of other organs
e.g. pleuritis, pericarditis, mild nephritis
• SEVERE - severe inflammation in vital organs
e.g. severe nephritis, CNS/pulmonary disease etc
How do you treat MILD SLE?
A. Paracetamol +/- NSAID
- monitor renal function
B. Hydroxychloroquine
- arthropathy
- cutaneous manifestations
- mild disease activity
C. Topical corticosteroids
What is an indicator that the SLE has now become MODERATE?
Hydroxychloroquine/NSAID STOP working
How do you treat MODERATE SLE?
Switch from topical –> ORAL glucocorticoids
• high dose initially to suppress disease activity AND THEN titrate down
• BUT very toxic so can give with steroid-sparing agents to lower dose required
How do you treat SEVERE SLE?
Azathioprine - a steroid-sparing drug
• comes with a risk of neutropenia & bone marrow suppression
• SO requires blood monitoring
Cyclophosphamide
• only used in SEVERE organ involvement
• side effect is INFERTILITY
