Connective Tissue Disorders Flashcards
list key connective tissue disorders
systemic lupus erythematous Sjorgen's syndrome autoimmune inflammatory muscle disease systemic sclerosis (scleroderma) overlap syndromes
what is rheumatoid arthritis?
chronic joint inflammation that can result in joint damage
site of inflammation of rheumatoid arthritis
synovium
rheumatoid arthritis is associated with?
autoantibodies
what is ankylosing spondylitis?
chronic spinal inflammation that can result in spinal fusion and deformity
site of inflammation of ankylosing spondylitis
includes the enthesis
is ankylosing spondylitis associated with autoantibodies?
no
‘seronegative’
list seronegative spondyloarthropathies
ankylosing spondylitis
reactive arthritis (Reiter’s syndrome)
Psoriatic arthritis
arthritis associated with GI inflammation (enteropathic synovitis)
what is systemic lupus erythematosus?
chronic tissue inflammation in the presence of antibodies directed against self antigens
site of inflammation of SLE?
multi site
particularly the joints, skin, kidney
is systemic lupus erythematosus associated with autoantibodies?
yes
anti nuclear antibodies
anti-double stranded DNA antibodies
anti-phospholipid antibodies
list connective tissue diseases
SLE Sjogren's syndrome autoimmune inflammatory muscle disease systemic sclerosis overlap syndrome
what phenomenon is common in connective tissue disorders?
Raynaud’s phenomenon
what is Raynaud’s phenomenon?
intermittent vasospasm of digits on exposure to cold
colour change: blanching of digits, cyanosis, reactive hyperaemia
typical demographic for SLE
female
15-45
clinical manifestations of SLE include
malar rash photosensitive rash mouth ulcers hair loss Raynaud's phenomenon arthralgia/arthritis serositis e.g. pericarditis, pleuritis renal disease e.g. glomerulonephritis cerebral disease e.g. psychosis
current paradigm for pathogenesis of systemic lupus erythematosus
apoptosis > translocation of nuclear antigens to membrane surface > impaired clearance of apoptotic cells > enhanced presentation of nuclear antigens to immune cell > B cell autoimmunity > tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
what autoantibodies are involved in systemic vasculitis?
antinuclear cytoplasmic antibodies
antinuclear antibody screening includes?
Anti-Ro Anti-La Anti-centromere Anti-Sm Anti-RNP Anti-ds-DNA antibodies Anti-Scl-70
cytoplasmic autoantibodies include?
Anti-tRNA synthetase antibodies
Anti-ribosomal P antibodies
which autoantibodies are specific for SLE?
anti dsDNA
anti Sm
antiphospholipid antibodies are associated with the risk of what in SLE?
arterial and venous thrombosis
serum level of anti-dsDNA antibody correlates with?
disease activity
treatment for SLE aims for?
remission or low disease activity and prevention of flares
drug treatments for SLE patients
hydroxychloroquine recommended
maintenance treatment glucocorticoids minimised (can be helped by methotrexate, azathioprine)
in persistently active/severe disease use cyclophosphamide and B cell targeted therapies e.g. rituximab/belimumab
patients with SLE should be assessed for?
antiphospholipid antibody status
infectious and cardiovascular diseases risk profile
pregnancy planning
disease activity in SLE
low complement C3/C4 high anti-dsDNA antibodies low platelet count low albumin low Hb, lymphocyte high reticulocyte
what is sjogren’s syndrome?
chronic autoimmune disease affecting salivary glands and tear glands, autoimmune exocrinopathy
exocrine gland pathology results in?
dry eyes (xerophthalmia) dry mouth (xerostomia) parotid gland enlargement
Commonest extra-glandular manifestations in Sjogren’s syndrome are?
non-erosive arthritis
Raynaud’s phenomenon
salivary gland biopsy of patient with Sjogren’s syndrome will show?
lymphocytic infiltration predominantly CD4 helper T cells and to lesser extent B lymphocytes
what is Schirmer’s test?
a test to assess tear production. Filter paper is placed under lower eyelid and extent of wetness measured after 5 minutes
abnormal result of Schirmer’s test is?
<5mm after 5 minutes
Sjogren’s syndrome typical demographic
females
35-50
inflammatory muscle disease
Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
skin changes in dermatomyositis
Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
Red or purple flat or raised lesions on knuckles (Gottron’s papules)
Subcutaneous calcinosis
Mechanic’s hands (fissuring and cracking of skin over finger pads)
inflammatory muscle disease is associated with?
malignancy
pulmonary fibrosis
inflammatory muscle disease will have what abnormal test results?
elevated CPK
abnormal electromyography
abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells in addition to B cells)
what is systemic sclerosis?
group of diseases causing hardening and tightening of skin and connective tissues.
manifestations of systemic sclerosis
dermal fibrosis
cutaneous calcinosis telangiectasia
skin changes in systemic sclerosis may be ________ or ______
diffuse
limited
diffuse systemic sclerosis
Fibrotic skin proximal to elbows or knees (excluding face and neck)
Anti-topoisomerase-1 (anti-Scl-70) antibodies
Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
Short history of Raynaud’s phenomenon
limited systemic sclerosis
Fibrotic skin hands, forearms, feet, neck and face
Anti-centromere antibodies
Pulmonary hypertension
Long history of Raynaud’s phenomenon
CREST describes a sub-type of limited systemic sclerosis, it stands for?
Calcinosis Raynaud's phenomenon Esophageal dysmotility Sclerodactyly Telangietasia
what is overlap syndrome?
features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease
what is undifferentiated connective tissue disease?
When incomplete features of a connective tissue disease are present
what is mixed connective tissue disease?
In one instance a group of patients with features of seen in SLE, scleroderma, rheumatoid arthritis, and polymyositis were identified by the presence of an autoantibody:
Anti-U1-RNP antibody
key autoantibodies in diffuse systemic sclerosis
anti-Scl-70 antibody
key autoantibodies in limited systemic sclerosis
anti-centromere antibodies
key autoantibodies in dermato-/polymyositis
anti-tRNA transferase antibodies
key autoantibodies in Sjogren’s syndrome
no unique antibodies but typically see
antinuclear antibodies (anti-Ro and anti-La)
rheumatoid factor
key autoantibodies in mixed connective tissue disorders
anti-U1-RNP antibodies
