1B CTD Flashcards
What CTD related to rheum are there?
- Systemic Lupus Erythematosus (SLE)
- Sjogren’s syndrome
- Autoimmune Inflammatory Muscle Disease
- Systemic sclerosis (scleroderma)
What is overlap syndrome and who can it occur in more?
When features of >1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease.
They can occur, especially in children.
What is rheumatoid arthritis?
Chronic joint inflammation that can result in joint damage
Where is the main site of inflammation in RA?
Synovium
What is RA associated with?
Autoantibodies:
- Rheumatoid factor
- Anti-cyclic citrullinated peptide (CCP) antibodies
What is Ankylosing Spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity
Where is the site of inflammation for AS?
Includes the enthesis
What are some seronegative inflammatory arthritis conditions?
- Ankylosing spondylitis
- Reactive arthritis
- Psoriatic arthritis
- Enteropathic arthritis
What is Systemic Lupus Erythematosus?
- Autoimmune disease involving disturbance of both innate and adaptive immune systems
- Autoantibodies (antibodies directed against self antigens)
- Antibodies to nuclear components
- Antibody-antigen (immune complexes) & other mechanisms -> chronic tissue inflammation:
Multi-site inflammation but particularly the joints, skin and kidney
How are arthralgia (joint stiffness) and arthritis different between RA and SLE?
- Arthralgia and arthritis are present in both but in SLE they are typically non-erosive
- This is because there is no underlying synovitis in SLE but there is in RA
- There’s no obvious bedside inflammation of joints in SLE but there is in RA
How are serum autoantibodies important in diagnosing connective tissue disorders?
- May aid diagnosis
- Correlate with disease activity
- May be directly pathogenic
Raynaud’s phenomenon is common in these connective tissue conditions. What is it?
- Intermittent vasospasm of digits on exposure to cold
- Usually triggered by cold exposure
- Raynaud’s is the most commonly isolated and benign condition
What is the typical colour change in Raynaud’s phenomenon?
- White: Vasospasm leads to blanching of digit
- Blue: Cyanosis as static venous blood deoxygenates causing blue
- Red: Reactive hyperaemia
What clinical features related to the skin and mucosa are there for SLE?
- Malar rash: erythema that spares the nasolabial fold
- Photosensitive rash
- Mouth ulcers
- Hair loss
What vascular clinical features are there for SLE?
Raynaud’s
What MSK clinical features are there for SLE?
Arthralgia and sometimes arthritis (non-erosive)
What internal organ clinical features are there for SLE?
- Serositis (pericarditis, pleuritis, less commonly peritonitis)
- Renal disease: glomerulonephritis
- Cerebral disease
- Myocarditis
What haematological clinical features are there for SLE?
- Autoimmune thrombocytopenia (low platelets)
- Haemolytic anaemia
- Lymphopenia
What is a hallmark of SLE?
- Anti-nuclear antibodies (ANA)
- Found in all SLE patients
- Negative ANA = rules out SLE
However, it’s not specific for lupus: may be seen in other autoimmune diseases, infection or even healthy people
Aside from ANA, what other antibodies can SLE patients have?
- APL
- Anti-dsDNA
- Anti-Sm
What are APL associated with increased risk of?
1) Thrombosis
- arterial (e.g. stroke)
- venous (e.g. DVT)
2) Pregnancy loss (miscarriage)
Describe the immunopathogenesis of SLE
Innate immunity
- Overactivity of type 1 interferon pathway
- Complement pathway abnormalities
Adaptive immunity
- Autoreactive B and T cells
How is the immune system generating a response to nuclear antigens?
‘Waste disposal hypothesis’
- Apoptosis leads to translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What different types of investigations are there for SLE?
- Inflammation
- Haematology
- Renal
- Immunological
- Imaging
What do we look for when investigating inflammation in SLE?
- High ESR
- CRP is typically normal unless infection or serositis/arthritis
What do we look for in haematology?
- Haemolytic anaemia
- Lymphopenia
- Thrombocytopenia
What do we look for in renal investigations of SLE?
- Very important to measure urine protein (most commonly urine protein:creatinine ratio)
- Look at albumin
- Kidney biopsy if persistent proteinuria
What is important to keep in mind about eGFR and urine:creatinine?
It could be entirely normal in SLE patients so we need to check for albumin in urine even if patient feels well
Renal biopsy would be good too since type of lupus nephritis is important and influences management
What do we look for in immunological investigations for SLE?
- Antinuclear antibodies
- Anti-double stranded DNA antibodies- highly specific and correlate with disease activity
- Complement consumption e.g. low C4 and C3
- APL ABs
What imaging is done on specific organs for SLE investigations?
- CT thorax
- echocardiogram
- cardiac MRI for heart
dictated by symptoms
What does an unwell patient with active lupus typically have?
Low complement C3 and C4 levels and high anti-ds-DNA antibody levels
What is the aim of SLE treatment?
- Remission or low disease activity and prevention of flares
- Balance of controlling disease vs avoiding iatrogenic harm (esp. steroids)
- Specific choice of treatment will depend on disease severity and organ manifestations
What drug do we recommend for all lupus patients?
Hydroxychloroquine
What drug types in SLE management do we have to minimise/withdraw and what can help with this?
- Maintenance treatment glucocorticoids
- Appropriate initiation of immunomodulatory agents (e.g. methotrexate, azathioprine, mycophenolate) can expedite this
What do we use in persistent or severe lupus?
Cyclophosphamide and B cell targeted therapies e.g. rituximab and belimumab
What do we use when we want to acutely manage lupus?
Steroids
Explain the relationship between SLE and pregnancy
- SLE typically affects women during reproductive years
- Consider both risk of disease and drugs to both mother and foetus
- Best outcomes with pre-pregnancy planning and getting SLE into remission first
Which drugs are teratogenic?
- MMF
- Cyclophosphamide
- Methotrexate
- Warfarin
Which drugs are safe?
- Hydroxychloroquine
- Azathioprine
- Low molecular weight (LMWH) safe
What are some extra considerations for SLE in pregnant women?
- APL ABs associated with miscarriage
- Can reduce risk with aspirin or heparin
- Pregnancy increases haemodynamic demands: will worsen renal dysfunction
- Ro antibodies: can cause foetal heartblock
