Connective Tissue Disease Flashcards
What are connective tissue disease characterized by?
the presence of spontaneous over-activity of thewh immune system
what type of hypersensitivity is SLE?
type III
immune complexes
who is affected more by lupus- males or females?
females
what are the 3 main environmental factors which could contribute to the development of SLE?
- virus (eg eptein-barr virus)
- UV light
- silica dust (found in cigarette smoke)
why might defective apoptosis lead to the production of auto-antibodies?
cell death happens less efficiently so remnants are not cleared away quickly. This allows extended exposure to nuclear and intracellular antigens which might trigger the production of auto-antibodies.
where do the immune complexes get deposited in SLE?
in the wall of blood vessels
what is serositis?
inflammation of a lining ie pericarditis, peritonitis, pleuritis
what are the 5 main constitutional symptoms of SLE? (vague/non specific- most common symptoms)
fever malaise poor appetite weight loss fatigue
what are the 7 main mucocutaneous features of SLE?
- photosensitivity
- malar rash
- discoid lupus erythematosus
- subacute cutaneous lupus
- apthous ulcers
- alopecia
what is typically spared in an SLE malar rash?
nasolabial folds
what is different about discoid lupus?
can be solely cutaneous symptoms
what are the 4 main musculoskeletal features of SLE?
- non-deforming polyarthritis/polyarthralgia
- deforming arthropathy (Jaccoud’s arthritis)
- erosive arthritis
- myopathy
how is non-deforming polyarthritis of SLE differentiated from rheumatoid arthritis even though they have the same distribution?
SLE polyarthritis has no sign of erosion on radiological investigation
What is Jaccoud’s arthritis?
a reversibly deforming arthropathy (not erosive)
what are the 5 main pulmonary features of SLE?
- pleurisy (causing pleural effusion)
- infections
- diffuse lung infiltrate and fibrosis
- pulmonary hypertension
- pulmonary infarct (causing haemoptysis)
is a patient with SLE more likely to get a transudate or exudate pleural effusion?
exudate (due to inflammation, transudate more due to leakage)
what are the 4 main cardiac features of SLE?
- pericarditis
- cardimyopathy
- pulmonary hypertension
- Libman-Sachs endocarditis
what is Libman-Sachs endocarditis?
sterile (nonbacterial) endocarditis, valve vegetation but no microbes on lood cultuees
How do you detect glomerulonephritis in a patient with SLE?
urinalysis
what are the 5 main neurological features of SLE?
- depression/psychosis
- migraine
- cerebral ischamie (TIA or CVA)
- cranial or peripheral neuropathy
- cerebellar ataxia
what are the 4 main haematological features?
- lymphadenopathy
- leukopaenia
- anaemia
- thrombocytopaenia
why do patients with SLE have a susceptibility to infection?
- intrinsic factors (impaired immunity)
- extrinsic factors (ie immunosuppressive treatments)
what are the main immune tests to do in suspected SLE?
- anti-nuclear antibody
- anti-double stranded DNA antibody
- anti-extractable nuclear antigens (eg anti-Ro, anti-La, anti-Sm and anti-RNP)
- complement levels
which is more specific for lupus: anti-ds DNA or ANA
anti-ds DNA
rarely get false positives
which is antibody is present in more SLE patients- anti-ds DNA or ANA?
ANA
what antibody is important in pregnant patients with SLE because of pathogenic effects on foetus?
anti-Ro
anti-ENA
what can anti-Ro cause in a neonate?
congenital heart block (in utero)
neonatal lupus
what happens to anti-ds DNA titre and complement titre when SLE starts to become active again?
anti-ds DNA titre increase
complement titre decreases
why do complement levels decrease in the body during active SLE?
complement is being used up
what is the drug treatment of SLE?
- NSAIDs and simple analgesia
- anti-malarials (hyroxychloroquine)
- steroids
- immunosuppressives
- biologics (rituximab)
when are steroids used in SLE?
for acute flare up, never used long term
what is the function of rituximab (a biologic)?
B cell depletion therapy
what autoantibodies can be present in anti-phospholipid syndrome?
anti-cardiolipin antibodies
lupus anticoagulant
anti-beta2-glycoprotein
how do you diagnose anti-phospholipid syndrome?
1 laboratory sign AND 1 clinical sign
Lab sign: -positive anti-cardiolipin -lupus anticoagulant -anti-beta2-glycoprotein [on 2 occasions, 12 weeks apart]
Clinical sign:
- arterial or venous thrombosis
- pregnancy loss with no other explanation from 10 weeks +
- 3 pregnancy losses with no other explanation below 10 weeks
- pregnancy loss due to eclampsia, severe pre-eclampsia or placental insufficiency
why do patients with anti-phospholipid syndrome get blood clots when many have lupus anti-coagulant factor?
lupus anti-coagulant factor actually is a pro-coagulation factor in vivo
it only inhibits coagulation in vitro
who tends to get anti-phospholipid syndrome?
young women
what type of skin rash can be a feature of anti-phospholipid syndrome?
livedo reticularis (a vascularitic skin rash with a marbling appearance)
what is the the platelet count like in patients with anti-phospholipid syndrome usually?
low
still risk of thrombosis
what is the pharmacological treatment of anti-phospholipid syndrome?
for patients with prev episode of thrombosis- lifelong anti-coagulation (with heparin)
for patients with recurrent pregnancy loss- aspirin + heparin during future pregnancy
What is Sjogren’s syndrome?
an autoimmune condition which causes a lymphocytic infiltration of exocrine glands leading to xerostomia and keratoconjuctivitis sicca
(+ potentially other areas of dryness)
what are the 2 main autoantibodies associated with Sjogren’s syndrome?
anti-Ro
anti-La
what test is useful for testing xerostomia in suspected sjogren’s sundrome?
schirmer test
why can anti-Ro cause teratogenic effects?
anti-Ro can cross the placenta
who tends to get primary sjogren’s syndrome?
middle-ages women
what is the pharmacologicaly treatment of Sjogren’s syndrome?
- punctal plugs + eye drops
- saliva replacement
- pro-salivation agents
- hydroxychloroquine
- steroids + immunosuppression (only for severe case)
what is the function of pilocarpine?
stimulates salivation
what type of patients is pilocarpine contra-indicated in?
asthmatic patients
What is scleroderma/systemic sclerosis?
an autoimmune condition which causes fibrosis of the skin and internal organs
why does fibrosis of the skin and internal organs occur in scleroderma/systemic sclerosis?
due to excess deposition of colllagen
what vasculopathy of the hands occurs in almost every patient with scleroderma?
raynaud’s syndrome
What are the 2 classifications of scleroderma/systemic sclerosis?
- localised scleroderma
2. systemic scleroderma
what is the difference between localised and systemic scleroderma?
in localised scleroderma it is isolated to the skin, systemic scleroderma has systemic involvement
what are the 2 types of localised scleroderma?
morphoea
linea scleroderma
what are the 3 types of systemic scleroderma?
limited systemic sclerosis
diffuse systemic sclerosis
systemic sclerosis sine scleroderma
What are the features of limited systemic sclerosis?
CREST syndrome C- calcinosis R- raynauds E- esophageal dysmotility S- sclerodactyly T- telangiectasia \+ pulmonary hypertension
what is calcinosis?
depositions of calcium nodules in the sin
what is raynauds?
an exaggerated vasoconstrictive process in the hands in the cold
what is sclerodactyly?
skin thickening on the fingers
what is telangiectasia?
dilated capillaries on the hands, face and mucous membranes
blanche
what antibodies are associated with limited systemic sclerosis?
anti-centromere antibodies
What is diffuse systemic sclerosis?
systemic sclerosis with early significant organ involvement and skin changes
what antibodies are associated with diffuse systemic sclerosis?
anti-Scl-70 antibodies
what is systemic sclerosis sine scleroderma?
systemic sclerosis with organ involvement but no skin changes
who is more likely to get scleroderma- M or F?
F
what are the treatments for scleroderma?
target manifestations-
pulmonary hypertension: calcium channel blockers, bosentan, sildenafil, iloprost
interstitial lung disease: immunosuppression
reflux disease: PPI
others:
ACE inhibitors
prednisolone
what is the main con of using steroids in the treatment of scleroderma?
may provoke a hypertensive crisis
What is the autoantibody associated with mixed connective tissue disease?
anti-RNP
what is the autoantibody associated with polymyositis?
anti-Jo-1
for all connective tissue disease, what does the treatment hugely depend on? (what is the one exception to this)
depends on patients manifestations (which are very variable)
hydroxychloroquine in SLE is the one exception- ALWAYS used if possible
in connective tissue disease, what are the main risk factors to try and reduce?
cardiovascular risk factors
what connective tissue disease is associated with increased lymphoma risk?
Sjogren’s syndrome
what are the 3 phases of cutaneous involvement of scleroderma and what does this lead to?
- oedematous
- indurative
- atrophic
skin becomes thickened and tight
compare limited and diffuse systemic sclerosis in terms of location of skin changes?
limited- skin involvement confined to face, hands, forearms and feet
diffuse- can involve trunk (devlops more rapidly)
compare limited and diffuse systemic sclerosis in terms of development of organ involvement?
limited- organ involvement occurs late
diffuse- early organ involvement
compare limited and diffuse systemic sclerosis in terms of antibody association?
limited- anti-centromere antibody
diffuse- anti-Scl-70 antibody
what is the treatment for raynauds/digital ulcers in scleroderma?
calcium channel blockers
iloprost
bosentan
what is the treatment for renal involvement in scleroderma?
ACE inhibitors
what is the treatment for acid reflux in scleroderma?
proton pump inhibitos
what is the treatment for interstitial lung disease in scleroderma?
immunosupprssion
usually with cyclophosphamide
What is catastrophic anti-phospholipid syndrome?
a rare, serious and often fatal manifestation of APS characterised by multiorgan infarcations over a period of days-weeks
how can you distinguish between a malar rash and acne rosacea?
malar rash- sparing of the nasolabial folds
malar rash forms where sun has fallen on the face- photosensitivity
what treatments are used for mild SLE disease?
hydroxychloroquine
NSAIDs
topical steroids
what treatments are used for moderate SLE disease?
oral steroids
axathioprine
methotrexate
what treatments are used for severe SLE disease?
cyclophosphamide
IV Ig
Rituximab
what are the 2 reasons a patient with diffuse scleroderma might have shortness of breath?
-pulmonary fibrosis
or
-pulmonary hypertension
what investigations tests for pulmonary hypertension?
echocardiogram
