Connective Tissue Disease Flashcards
who is lupus most common in?
mostly women
afro-caribbeans
afro-americans
Asians uncommon in black africans
what are the contributing factors
genetic predisposition
environmental factors
immunological factors
humoral factors
what genetic factors affect lupus?
high concordance in monozygotic twins
and relatives
what hormonal factors can influence lupus?
increased incidence in people with higher oestrogen exposure - early menarche, on oestrogen containing contraceptives and HRT
pathogenesis of lupus?
defective apoptosis = dead cells aren’t cleared properly and their material which is released floats around the body for too long (acts as auto-antigens)
immune system activates T and B cells and develops antibodies against these
antibodies attack dead cell material as well as healthy cells
how does lupus cause renal disease?
deposition of immune complexes in mesangium/walls of blood vessels and activate complement which attracts leukocytes (e.g neutrophils) which release cytokines
cytokines perpetuate inflammation which cause necrosis and scarring
results in non functioning kidney
what drives lupus disease?
immune complex formation
= hypersensitivity type 3
is B cell function normal?
no
producing auto-antibodies
common clinical features of lupus?
skin involvement mucosal involvement alopecia joint involvement serositis (pleura, pericardium involvement) renal involvement neurological (brain fog > seizures) haemolytic anaemia leukopenia (low WCC) thrombocytopenia (low platelets)
what parts of FBC may be altered in lupus?
all of them
what are some common constitutional symptoms of lupus?
fever malaise poor appetite weight loss fatigue
name some mucocutaneous features of lupus?
photosensitivity - malar rash discoid lupus erythematous subacute cutaneous lupus mouth ulcers alopecia (hair on the pillow)
how do lupus rashes appear?
hours-days after sun exposure and last for weeks
sparing of fold between face and nose
what is discoid lupus?
rash with coin shaped lesions
can often be a separate disease - not systemic lupus
MSK features of lupus?
joint pain or inflammation (often in smaller joints)
muscle pain, weakness or inflammation
deforming and non-deforming arthropathy
what is Jaccoud’s arthritis?
type of deforming arthropathy
normal X ray
looks like rheumatoid deformity from outside but has normal joints
due to laxity of ligaments
what is serositis?
inflammation of the pericardium or pleura
what can occur in serositis?
pleural effusion
pericardial effusion
pericarditis
pleurisy
renal features of lupus?
tends to cause no symptoms
clinical signs of renal disease?
proteinuria (>500mg)
haematuria sometimes
red cell casts
what is red cell cast a sign of?
glomerulonephritis
- renal disease
next step if high protein found in urine?
renal biopsy
neurological features of lupus?
depression/psychosis migranes seizures cranial or peripheral neuropathy mononeuritis multiplex (inflammation of blood supply to a long nerve causing a palsy)
MRI features of naeurological disease?
white spots
haematological features of lupus?
lymphadenopathy leucopenia lymphopenia haemolytic anaemia thrombocytopenia often not that low so don't really cause much of a problem
what is anti-phospholipid syndrome?
causes blood clots in veins and arteries
can cause recurrent miscarriage
associated with lupus
what does anti-phospholipid syndrome look like?
mottling of skin
= livido reticularis
are lupus patients more pron to infection?
yes
due partly to features of disease but a lot to do with immunosuppressive treatment
what intrinsic factors cause susceptibility to infection in lupus?
low complement
impaired cell mediated immunity
defective phagocytosis
poor antibody response to certain antigens
aims of lupus investigation?
confirm diagnosis
determine degree of organ involvement
how good an indicator of lupus is ANA (anti-nuclear antibodies)?
present in low levels in 20% of population
present in high levels in 98% of lupus
sensitive but not specific
when should an ANA positive result be taken seriously?
if others are present
if the patient has clinical features and symptoms
what antibodies are associated with lupus?
anti- dsDNA (most important)
anti - Sm
anti - Ro
anti - RNP
how does anti- dsDNA present?
in 60% of lupus patients
highly specific
can go up and down with activity of disease
can be associated with renal disease
how does anti-Ro present?
60% of lupus patients
associated with cutaneous problems and congenital heart block
what are the 2 anti ENA antibodies?
Anti Sm - neurological involvement
ANti RNP - overlap features
3 antibodies of anti-phospholipid syndrome?
anti-cardiolipin antibody
lupus anticoagulant
anti-beta 2 glycoprotein
must be positive on 2 occasions 12 weeks apart for diagnosis
what is the most sensitive auto antibody for lupus?
anti - double stranded DNA (dsDNA) antibody
how do anti dsDNA levels change?
titre rises when disease is active or flaring
first test after lupus diagnosis?
urinalysis (must test for renal involvement first!)
what other tests are used in lupus?
depend on symptoms
i.e - chest involvement = CXR
what would indicate that someone is experiencing a flare of their lupus?
fall in complement levels as its being consumed
what inflammatory markers vary in lupus?
ESR
plasma viscosity
does ANA levels correlate to disease activity?
no
how can activity of SLE be monitored?
clinical assessment anti dsDNA C3/4 levels urine examination FBC blood biochemistry
general management of lupus?
counselling
regular monitoring
avoid excessive sun exposure
pregnancy issues
SLE drug treatment?
hydroxychloroquine = MAIN
NSAIDs and simple analgesia
steroids (only for short periods of time)
Immunosuppressives if anything more than mild
how do steroids work in SLE?
dose related to the severity of the disease
only used short term (few weeks) usually for flare up
what other drugs can be used?
biologics
- anti CD20 rituximab
- anti Blys (belimumab)
treatment for mild SLE?
HCQ
topical steroids
NSAIDs
treatment for moderate SLE?
oral steroids
azathioprine
methotrexate
treatment for severe SLE?
IV steroids
cyclophosphamide
rituximab
belimumab
what goes down when anti dsDNA levels go up?
complement
first line tests for suspected SLE?
urinalysis
anti dsDNA
complement
FBC
pain in one side of chest in lupus patients?
possible PE due to anti- phospholipid syndrome
PE X ray?
normal
lupus anticoagulant indicates what?
anti-phospholipid syndrome
what is cyclophosphamide?
potent immunosuppressive
what are connective tissue diseases?
not diseases of connective tissue
spontaneous over activity of the immune system with specific auto antibodies
evolve over years and lead to organ failure/death
what is lupus?
systemic autoimmune disease that can affect any part of the body
immune system attacks body cells and tissue causing inflammation and tissue damage
