SLE (connective tissue disease) Flashcards
What causes inflammation and tissue damage in SLE?
The immune system attacking the body’s cells.
(autoimmune)
Antibody-immune complexes precipitate and cause a further immune response.
Is SLE more common in males or females?
Females (9:1)
Which races is SLE most common in IN THE UK/US?
Asians, Afro-Americans, Afro-Caribbeans, Hispanic Americans (more than americans of european decent)
What hormonal factors are thought to increase incidence of SLE?
Incidence increased in those with higher oestrogen exposure. (those who develop early, those on oestrogen containing contraceptive, those on HRT)
What environmental factors are thought to increase risk of SLE?
Viruses (e.g. epstein-barr virus)
UV light exposure (stimulating skin cells to secrete cytokines, stimulating B ells)
Silca dust (in cleaning powders, cigarette smoke and cement)
Outline some of the main points in the pathogenesis of SLE:
Loss of immune regulation
Increased and defective apoptosis
Necrotic cells release nuclear material (which act as potential auto-antigens) (autoimmunity probable results from the extended exposure to nuclear and intracellular auto-antigens)
B and T cells stimulated
Autoantibodies are produced
What constitutional symptoms can be present in SLE?
Fever Malaise Poor appetite Weight loss Fatigue
What mucocutaneous features can be present in SLE?
Photosensitivity Malar rash Discoid lupus erythematosus (may scar) Subacute cutaneous lupus Mouth ulcers (painless) Alopecia non-scarring)
What musculoskeletal features can be present in SLE?
Non-deforming polyarthritis/polyarthralgia
Deforming arthropathy 0 Jaccoud’s arthritis
Erosive arthritis (RARE)
Myoathy - weakness, myalgia and myositis
What type of distribution does non-deforming polyarthritis have?
Same distribution as Rheumatoid Arthritis but no radiological erosion
What renal features can be present in SLE?
Proteinuria of .500mg in 24 hours
Red cell casts
What is serositis?
Inflammation of the serous membrane
What can serositis in SLE cause?
4
Pericarditis
PLeurisy
Pleural effusion
Pericardial effusion
What neurological features can be present in SLE?
Depression, psychosis ( not always related to disease activity) Migrainous headache Seizures Cranial or peripheral neuropathy Mononeuritis multiplex
What is mononeuritis multiplex (seen in SLE)?
A form of damage to one or more peripheral nerves (nerves outside brain and spinal cord)
What haematological features can be present in SLE?
Lympadenopathy
Leucopenia (a reduction in the number of white cells in the blood)
Lymphopenia (low level of lymphocytes in blood)
Haemolytic anaemia
Thrombocytopenia (deficiency of platelets)
How many patients with SLE will have lymphadenopathy during their course of illness?
(%)
Approx. 25%
What is anti-phospholipid syndrome?
A disorder of the immune system that causes an increased risk of blood clot
What other name is used for anti-phospholipid syndrome?
Hughes Syndrome
What happens in anti-phospholipid syndrome?
Increased risk of blood clots. Venous and arterial thrombosis. Recurrent miscarriage. Livido reticularis (skin appearance) Thrombocytopenia Prolongued APTT (activated partial thromboplastin time)
Association with other autoimmune conditions, especially SLE)
What is livido reticularis?
A common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by swelling of the venules owing to obstruction of capillaries by small blood clots.
(Anti-phospholipid syndrome)
Why are people with SLE particularly susceptible to infection?
Intrinsic factors: Low complements Impaired cell mediated immunity Defective phagocytosis Poor antibody response to certain antigens
Extrinsic Factors:
Steroids
Other immunosuppressive drugs
Nephrotic syndrome (kidney disease)
In what titre is ANA positive in in almost all SLE patients (95%)?
Positive in titire of 1:160 or greater
titres less than 1:160 are present in up to 20% of healthy population
Other than SLE, what conditions is ANA found in?
RA, HIV, Hep C, other autoimmune conditions
How many patients with SLE does anti-double stranded DNA antibody occur in?
Approx. 60% of patients with SLE
Highly specific for SLE
(Titre correlates with disease activity)
(May be associated with lupus nephritis)
Is anti-double stranded DNA antibody highly specific for SLE?
Yes
Is ANA highly specific for SLE?
No
(in titres <1:160, present in about 20% of healthy population)
(Can also be found in other conditions such as Hep C, HIV, Rheumatoid Arthritis and other autoimmune conditions)
What is lupus nephritis?
Inflammation of the kidney caused by SLE
When should a positive ANA test be taken seriously (as an indicator of SLE?
If other antinuclear antibodies are positive (Anti-dsDNA, anti-Sm, anti-Ro, Anti-RNP)
When the patient presents with connective tissue disease features
What is Anti-Ro associatd with?
Associated with cutaneous manifestations
(usually associated with anti-La)
(60%)
Is Anti-Sm specific?
Yes, very.
(Probable association with neurological involvement)
(10-20%)
Is Anti-Sm sensitive?
No
specific but low sensitivity
(if positive - likely to be SLE)
(if negative, doesn’t rule out)
Are Anti-Ro, Anti-La and Anti-RNP specific?
No, may be seen in SLE but may also be seen in other conditions
What happens to C3/4 levels in SLE?
Levels are lower when SLE active, especially renal disease
Why is urinalysis does in SLE?
To look for evidence of glomerulonephritis
Which anti-phospholipid antibodies may be positive in SLE?
Anti-cardiolipin antibody
Lupus anticoagulant
Anti-beta 2 glycoprotein
(Must be positive on 2 occasions, 12 weeks apart)
What is monitored to monitor disease activity in a patient with SLE after diagnosis?
Anti-dsDNA (positivity correlates with activity)
(C3/4 levels negatively correlate with disease activity)
(clinical assessment (incl. BP), urine examination incl. protein, cells and casts, FBC, blood biochemistry)
What is the drug management of SLE?
NSAIDs and simple analgesia
Hydroxychloroquine (Anti-malarials) - (Useful for arthritis, cutaneous manifestations and constitutional symptoms)
(May reduce systemic complications)
Steroids (useful but associated wih numerous side-effects)
When (and in what doses) would you give steroids (prednisolone) for SLE?
Small doses - for skin rashes, arthritis, serositis
Moderate doses - for resistant serositis, haematologic abnormalities and class V glomerulonephritis
High doses - for severe/resisitant haematologic changes, diffuse glomerulonephritis and major organ involvement
Name 4 immunouppressives that are used in SLE:
Azathioprine
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
(all cause bone marrow suppression)
(all can cause increased succeptibility to infection
(ptentially teratogenic)
Which (2) Biologics may be used in SLE?
Anti-CD20 (Rituximab)
Anti-Blys (Belimumab)
