connective tissue disorders Flashcards
what is ankylosing spondylitis
seronegative
chronic spinal inflammation that can result in spinal fusion and deformity
site of inflammation includes enthesis
no autoantibodies = seronegative.
what is systemic lupus erythematosus
chronic tissue inflammation in presence of autoantibodies directed against self antigens
- multi site inflammation - particularly joints,skin and kidney
- associated with autoantibodes; anas,anti dsDNA antibodies and antiphospholipid antibodies.
connective tissue disorders key points
- arthralgia and arthritis (typically non erosive) may be present
- serum antibodies are characteristic and may aid diagnosis, correlate with disease activity and may be diretly pathogenic
- raynauds phenomenon common with these conditions
what is raynauds phenomenon
intermittent vasospasms of digits on exposure to cold
typical colour changes = white -> blue -> red
vasospasm leads to blanching of digit, cyanosis as static venous blood deoxygenates
reactive hyperaemia
* raynauds phenomenon is most comonly isolated and benign condition
what group does sle usually affects
female aged between 15-45 yrs
what are some of the wide ranging clinical manifestations of sle
malar rash - erythema that spares nasolabial fold
photosensitive rash
mouth ulcers
hair loss
raynauds phenomenon
arthalgia and sometimes arthritis
serositis( pericarditis, pleuritis, less commonly peritonitis)
renal disease - glomerulonephritis
cerebral disease - cerbral lupus e.g psychosis
pathogenesis of sle
*dont need to know
apoptosis leads to translocation of nuclear antigens to membrane surface -> impaired clearance of apoptotic results in enhanced presentation of nuclear antigens to immune cells -> b cell autoimmunity -> tissue damage by antibody effector mechanism e.g complement activation and fc receptor engagement
why are antiphospholipid antibodies serious in sle
associated with risk of arterial and venous thrombosis
*may occur in absence of sle in what is termed ‘primary antiphospholipid antibody syndrome’
what are some investigations and findings for sle
inflammation - high esr but crp is typically normal unless infection/serotitis/arthritis
haematology - haemolytic anaemia, lymphopenia, thrombocytopenia
renal - measure urine protein and urine protein: creatinine ratio, look at albumin too
immunological - anas,adsDNA, complement consumption
clotting - antiphospholipid antibodies
disease activity in sle….
unwell lupus patient has low complement c3 and c4 levels and high levels of anti-ds DNA antibodies
= serologically active lupus
how does lupus nephritis present
low serum albumin(leaking into urine)
egfr normal
what are the treatment aims in sle
aims at remission
or low disease activity and prevention of flares
management for sle
hydroxychloroquine is recommended in all patients
maintenance treatment glucocorticoid should be minimised and when possible withdrawn
appropriate initiation of immunomodulatory agents e.g methotrexate, azathioprine, mycophenonite can expedite discontinuation of glucocorticoids
what can be given to patients with persistently active/severe sle disease
cyclophosphamide targeted therapy and
b cell targeted therapies - belimumab and rituxumab
what should be assessed when sorting management for sle patients
antiphospholipid antibody status
should be assessed for their infectious and cardiovascular diseases risk profile
pregnancy planning
what is sjogrens syndrome
autoimmune exocrinopathy - lymphocytic infiltration of expecially exocrine gland and sometimes of other organs - extra glandular involvement
what symptoms does exocrine pathology in sjogrens lead to
dry eyes - xeropthalmia
dry mouth - xerostomia
parotid gland enlargement
what are the commonest extra glandular manifestations of sjogrens
non erosive arthritis
raynauds phenomenon
when is term secondary sjogrens syndrome used
if sjogrens syndrome occurs in context of another connective tissue disorder e.g sle
what is inflammatory muscle disease
proximal muscle weakness due to autoimmune mediated inflammation either with rash (dermatomyositis) or without polymyositis
what are some skin changes in dermatomyositis
- lilac coloured (heliotrope) rash on eyelids, malar region and nasolabial folds
- red/purple flat or raised lesions on knuckles = gottrons papules
- subcutaneous calcinosis
- mechanics hands (fissuring and crackling of skin over finger pads)
what findings would you expect in inflammatory muscle disease
elevated cpk,
abnormal electromyography, abnormal muscle biopsy (polymyositis = cd8 t cells, dermamyo.. = cd4 t cells and b cells)
associated with malignancy (10-15) and pulmonary fibrosis
what is systemic sclerosis/scleroderma
thickened skin with raynauds phenomenon
dermal fibrosis, cutaneous calcinosis and telangiectasia
what are the skin changes in diffuse systemic sclerosis
- fibrotic skin proximal to elbows/knees
- anti topoisomerase antibodies
- pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
- short history of raynauds phenomenon
skin changes in limited systemic sclerosis
fibrotic skin on hands, forearms, feet,neck and face
anti centromere antibodies
pulmonary hypertension
long history of raynauds phenomenon
what does crest the subtype stand for in limited systemic sclerosis
calcinosis raynauds phen eosophageal dysmobility sclerodactyl telangiactasia
what is overlap syndrome
features of more than 1 connective tissue disorder are present
what is mixed connective tissue disease
patients with features of sle, scleroderma, ra and polymyostitis
identified by presence of atiu1rnp antibody
autoantibodies in diffuse systemic sclerosis
anti sci70 antibody
autoantibodies in limited systemic sclerosis
anticentromere antibodies
key autoantibody in derma/ploymyositis
anti trna transferase antibodies aka antijo1
key auto antibodies in sjogrens
no unique abs
but typically see anti ro, anti la
rhematoid factor
