Connective Tissue Diseases: SLE Flashcards
what are connective tissue diseases characterised by
spontaneous over activity of immune system
SLE
chronic autoimmune disease, the presentation and course can be highly varied
immune system attacks body’s cells and tissues, leading to inflammation and tissue damage
antiboidy immune complexes precipitate and cause a further immune response
epidemiology
onset usually after puberty, 20s and 30s
females>males
prevalence high in black persons in UK and US, although rarely in blacks in Africa
what happens when males get the disease
get a more severe form
genetic factors
genetic predisposition:
concordance in monozygotic twins, inc incidence among relatives
hormonal factors
higher oestrogen - early menarche and oestrogen containing contraceptives
environmental factors
- viruses eg EBV
- UV light may stimulate skin cells to secrete cytokines stimulating B cells eg UVA/B therapy
- silica dust may inc risk
- toxins eg cigarette smoke
development of autoantibodies
defect in apoptosis causes increased cell death and a disturbance in immune tolerance
defective clearance of apoptotic cell debris causes extended exposure to antigen and immune complex formation (autoantibodies)
what type of hypersensitivity reaction
III
what are many of the clinical manifestations of SLE due to
deposition of immune complexes that form with antigens in various tissues
form in the small blood vessels causing an inflammatory reaction
are desposited on BM of skin and kidneys
renal disease
asymptomatic and very severe - RENAL BIOPSY if urinalysis suggests appropriate
what may mild disese involve
only joint pain,alopecia and skin rash
name some constitutional symptoms
fever, malaise, poor appetite, weight loss and fatigue
muco cutaenous symptoms
malar rash
photosensitivity
discoid lupus
subacute cutaenous lupus
alopecia
oral/nasal ulceration
Rayndaus phenomemon
discoid lupus
- Benign variant of lupus in which only the skin is involved. The rash is characteristic and appears on the scalp, face and ears as well-defined erythematous plaques that progress to scarring and pigmentation
- There is often hair loss
- Most patients will just have skin involvement, up to 10% of people will eventually develop SLE
photosensitivity
prolonged exposure to sunlight can lead to exacerbations of the disease
what can non scarring alopecia lead to
irreversible bald patches
describe the rash that is seen
butterfly pattern
spares the naso-labial folds
what mucocutaneous feature can precede the development of other clinical signs by years
Raynaud’s phenomenon
MSK symptoms
polyarthralgia and poyarthritis
myopathy
inflammatory arthrits
arthropathy - rarely deforming or erosive
what deforming arthropathy can occur
- Jaccoud’s arthritis is a chronic non-reversible joint disorder that may occur after repeated bouts of arthritis
- Causes ulnar deviation through MCP subluxation
- Can occur in lots of rheumatology things
what is there an increased prevalence of in the femoral head
avascular nerosis - may relate to steroids use
what is the most common respiratory manifestation
- pleurisy (2/3 patients) with/out effusion - effusions are small and bilateral
- also PE, pumonary hypertension and ILD
what are some other respiratory manifestations
Basal pneumonitis is often present, perhaps as a result of poor movement of the diaphragm, or restriction of chest movements because of pleural pain.
Also, PE, pulmonary hypertension and interstitial lung disease.
renal symptoms
lupus nephritis - severe and often asymptomatic
- 1/3 patients will have evidence of renal damage
- the most frequently observed abnormality is proteinuria, causes nephrotic syndrome
- renal biopsy is required
- early treatment needed
- The most common and severe form is the diffuse proliferative GN (class IV), ‘wire-loop’ appearance
management of proteinuria
- Proteinuria >3mg treated with steroids
- Step up to steroids and cyclophosphamide ± immunosuppression
neurological symptoms
- Occurs in up to 60% cases and symptoms often fluctuate. There may be a mild depression, but occasionally more severe psychiatric disturbances.
- Depression/psychosis, migrainous headache, seizures, cranial or peripheral neuropathy, mononeuritis multiplex (individual peripheral nerves affected – foot or wrist drop).
what happens if mononeuritis multiplex onyl affects one nerve
foot or wrist drop
haematological symptoms
lymphadenopathy
leukopaenia
anaemia - haemolytic
thrombocytopaenia
what haematological symptom occurs in a quarter of patients
lymphadenopathy
cardiac symptoms
pericarditis, pericardial effusion, hypertension
which drugs can cause SLE, and what are the associated antibodies
associated with isoniazid, anti-histone antibodies
anti-phospholipid syndrome symptoms
thrombocytopaenia (low platelet count) causes venous AND arterial thrombosis
livido reticularis (skin)
late spontaenous, or reccurent early foetal loss
migraines common
what is the classic presentation of someone with APS
child bearing age, with recurrent miscarriage and eg DVT
recurrent PE and thrombosis can also lead to pulmonary hypertension
is APS primary or secondary
both
why are patinets with APS more susceptible to infection
intrinsic: low complement, imparied cell mediated immunity, defective phagocytosis etc
extrinsic: steroids, IS drugs, nephrotic syndrome
what are the anti-phospholipid antibodies
- anti-cardiolipin
- anti-beta 2 glycoprotein
- lupus anticoagulant
must be positive on 2 occasions less than 12 weeks apart
APS treatment
lifelong coagulation
hydroxychloroquine helps with systemic symptoms
anticoagulation for APS
- lifelong warfarin - however this is teratogenic
- in pregnancy - aspirin/heparin
diagnosis of APS
what are the aims of investigation
confirm/establish diagnosis and determine organ involvement
wide range of investigations that depend on symptoms
what investigations would always be done
immunology
FBC - may show thrombocytopaenia
urinalysis/renal biopsy
immunology
ANA
anti-dsDNA antibody
anti-Sm
C3/4 levels
ANA
- sensitive but not remotely specific
- good screening test
- can be positive in all autoimmune diseases, RA, HIV etc
- ≥1:160 in 90% of patients withbSLE
what ANA level is seen in the general population
1:160
anti-dsDNA antibody
- the most specific and varies with disease activity
- levels often relfect lupus nephritis activity
anti-SM
the most specific but low sensitivity
other immunology
Anti Ro, anti-La and anti-RNP – may be seen in SLE but also may be seen in other conditions.
C3/4 levels
negatively correlate with disease activity
what must be done once the diagnosis is established
- urinalysis to look fo evidence of GN
- screen for organ involvement - CT, MRI, ECHO
management - non pharmacological
counselling, regular monitoring and advice on pregnancy issues is essential
avoid sun exposure (photosensitivity)
what is given to all patients with SLE
hydroxychloroquine (anti-malarial)
may reduce systemic complications
side effects of hydroxychloroquine
- irreversible retinopathy - blindness
- corneal deposits
what drugs are commonly used
NSAIDs and analgesia
what are steroids used for
- Used in small doses for skin rashes, arthritis and serositis
- Moderate does for haematological abnormalities and persistent serosits
- High doses for severe haematological changes and major organ involvement
when is IS used
- used when there is inflammatory arthritis or some types or organ involvement
- (e.g. azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil)
what are the negative effects of IS drugs
possibly teratogenic
bone marrow suppression and inc suscpetibility to infection
treatment of severe organ disease eg lupus nephritis
IV steroids and cyclophosphamide
treatment of unresponsive cases
other therapies such as IV immunoglobulin and biologics may be necessary.
- Rituximab (anti-CD20)
- Belimumab (anti-byls)
monitoring
anti dsDNA antibodies are checked regularly, as these vary wtih disease activity
check urinalysis for blood or protein
subactue cutaneous lupus
raynaud’s phenomenon
