Rheumoid arthritis Flashcards
(44 cards)
Define rehumatoid arthritis
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
THE SYNOVIUM IS THE SYNOVIAL MEMBRANE
SYNOVITIS IS INFLAMMATION OF THE SYNOVIAL MEMBRANE
T/f rheumatoid arthritis can result in problems with the lumbar spine
F… there is no synovium here… the only axial synovial joint is the atlanto-axial joint, the pivot joint for yes and no (but mostly peripheral joints)
Outline chronic arthristis assocciated with rheumatoid arthritis
CHRONIC arthritis:
Polyarthritis - swelling of the small joints of the hand and wrists is common
Symmetrical
Early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs
What disease outside of joints could be seen in RA
Rheumatoid nodules
Others rare e.g. vasculitis, episcleritis
(watch osmosis)
What kind of antibodies does rheumatoid factor involve?
IgM autoantibody against IgG
What is the genetic component of RA
Disease concordance rates for twins are 15-30% (monzygotic) and 5% (dizygotic) and heritability estimates of up to 60%
Specific HLA-DRB gene variants mapping to amino acids 70-74 of the DRb-chains are strongly associated with rheumatoid arthritis
Region encodes conserved amino acid sequence in the HLA-DR antigen-binding groove which is common to rheumatoid arthritis-associated DR alleles – termed ‘shared epitope’
What is the important environmental component associated with RA
Smoking – contributes 25% of population-attributable risk and interacts with shared epitope to increase risk
What are the most commonly affected joints in RA
Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
Examples of the joint damage and destruction present in RA
Swan-neck deformity affecting the ring finger – there is hyper-extension at the PIP joint and hyper-flexion at the DIP joint
Boutonnière (‘button-like’) deformity affecting little finger – there is hyper-flexion at the PIP joint
What is the primary site of damage in RA
Synovium
What structures does the synovium include (so are involved in RA)
The synovial joint
The tenosynovium (surrounding tendons)
The bursa
Outline disease relating to the synovial joint in RA
e.g. proximal inter-phalangeal joint synovitis
Outline disease relating to the tenosynovium in RA
Extensor tenosynovitis – note swelling is not above either the wrist or MCP joints
(incomplete extension of little and ring finger)
Outline disease relating to the bursa in RA
Olecranon bursitis
What is rheumatoid factor
IgM antibodies (pentameric) binding to Fc portion of IgG
So IgM anti-IgG antibody
Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
Aside from Rheumatoid factor, which other auto antibody is presnet in RA
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
How are proteins citrullinated
By peptidyl arginine deiminases (PADs)
Convert arginine –> citrulline
This process is enhanced by smoking in the lungs
Why do ACPAs develop in rheumatoid arthritis
Inflamed synovium means lots of neutrophils and monocytes. These have high levels of PADs
More citrulliation
Shared epitope of HLA-DRb chain (found in some HLA-DR4 and also other HLA types) preferentially binds non-polar AAs (such as citrulline, but the original arginine is polar, so this wouldn’t be presented) and presents them
Anti citrullinated protein antibodies (ACPA) more likely to develop because of increased presentation of the antigen
Smoking – increases ACPA-positive rheumatoid arthritis risk. ? Smoking enhances citrullination in lungs
T/f all patient swith the HLA-DR4 show the ‘shared epitope’, but no other HLA type does
F…
shared epitope= shared sequence in amino acids 70-74 of the HLA-DRβ chain
this is why multiple different HLA serotypes were associated with disease (HLA-DR4, -DR1, -DR6, DR10) – all contained the shared epitope and some individuals with HLA-DR4 not at risk – these HLA-DR4 did not contain shared epitope
What might cause inflammation and citrullination in RA
smoking, changes in microbiota, chronic infections (gingivitis)
might increase citrullination which might then increase shared epitope binding and thus presentation
Outline common adn uncommon extra-articular features in RA
Common:
Fever, weight loss, FATIGUE (due to cytokines)
Subcutaneous nodules
Uncommon:
vasculitis
Ocular inflammation e.g. episcleritis
Neuropathies
Amyloidosis
Lung disease – nodules, fibrosis, pleuritis
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
Outlien the radiographic abnormalities seen in RA
Radiographic abnormalities
Early
Juxta-articular osteopenia (reduced bone density near joints)
Later
Joint erosions at margins of the joint
Later still
Joint deformity and destruction
Outline the pathology seen within the joint in RA (diagram)
Bone erosion, pannus, cartilage degradation (joint space narrowing), synovitis
Outline the synovium component of a synovial joint
SYNOVIUM= SYNOVIAL MEMBRANE NOT SYNOVIAL FLUID
1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte)
and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
Type I collagen
NB: the synovium has type I and the articular cartilate has type II collagen
