Rheumatoid Arthritis Flashcards
what is rheumatoid arthritis?
what 3 things characterise it?
chronic inflammatory condition characterised by:
-PAIN
- STIFFNESS
- SYMMETRICAL SYNOVITIS
(inflammation of synovial membrane) of synovial joints.
what are the key features of RA in terms of findings and presentation?
o Rheumatoid “factor” (Anti-IgG IgM-auto-antibody).
o Extra-articular disease
o Chronic arthritis.
what are the features of chronic (rheumatoid) arthritis?
Polyarthritis – swelling of small joints (hand/wrist).
Symmetrical.
Early morning stiffness.
May lead to joint damage & destruction (swan neck and boutonniere deformity )
which gender does RA affect most?
women (x3 more likely than men)
what are the predispositions to RA?
- genetic component accounts for upto 60%
- environmental component like smoking contributes 25% of population-attributable risk
what specific genetic component attributes to RA?
specific set of amino-acids in the beta-chain of the HLA-DR molecule
This specific set is then shared amongst all RA HLA sub-sets – termed “Shared epitope”.
what joints are most commonly affected?
o Metacarpophalangeal joints (MCP). o Proximal interphalangeal joints (PIP). o Wrists. o Knees. o Ankles. o Metatarsophalangeal joints (MTP).
what are the deformities seen in RA?
o Symmetrical polyarthritis
– SYMMETRICAL!
o Swan-neck deformities
– affects ring-finger with hyper-extension of PIP joint and hyper-flexion of DIP joint.
o Boutonnière deformity – affects little finger with hyper-flexion of PIP joint.
what are the primary sites of pathology in RA?
synovium located at: o Synovial joints – PIP joint synovitis. o Tenosynovium – extensor tenosynovitis (Tendons wrapped in Tenosynovium) o Bursa – olecranon bursa
what are subcutaneous nodules?
Made of a central area and peripheral area
c– fibrinoid necrosis surrounded by macrophages.
p– connective tissue
occur in about 30% of patients and associated with severe RA
what is rheumatoid factor?
IgM antibodies against IgG i.e. anti-IgG antibodies
- IgG antibodies are the self-antigens that have been altered therefore RF has been created against them
- present in 70% at disease onset
- further 15% tested positive after 2 years of diagnosis
what is the correlation with disease presentation and high RF?
o High RF proportionate with likelihood of joint damage.
o High RF proportionate with how ill the patient feels.
what happens to citrullinated peptides in RA?
antibodies against citrullinated peptides are created
ACPA= anti-cyclic citrullinated peptide antibodies
- citrullination is a change that occurs to self-antigens induced by environment
- this is sampled by immune cells who take it T helper cells who cause B cell activation to produce antibodies
how is citrullination of peptides done?
via peptidyl arginine deiminases (PADs)
arginine –> citrulline
PADs are more active at sites of inflammation when they are produced by neutrophils and monocytes.
what lifestyle are ACPAs associated with?
ACPA is strongly associated with smoking (more citrullination in lungs) and HLA “Shared epitope”.
what is the effect of having the shared epitope?
HLA-DR1, 4, 6, 10
epitope preferentially binds non-polar substances such as CITRULLINE
what is the effect of smoking on citrulline?
enhance levels of citrulline
what are the common extra-articular features of RA?
Pyrexia
weight loss.
SC nodules.
what are the uncommon extra-articular features of RA?
Vasculitis. Episcleritis – ocular inflammation. Neuropathies. Amyloidosis. Lung disease – fibrosis, nodules. Felty’s syndrome – (3) triad of – splenomegaly, leucopenia, RA.
what are the early radiographic findings in RA?
Juxta-articular osteopenia (low bone density juxta-articular bone).
what are the later radiographic findings in RA?
joint erosions at margins of joints.
what are the even later radiographic findings in RA?
Joint deformity and destruction.
what are the 3 things found in a synovial joint?
o Synovium
o Synovial fluid
o Articular cartilage
what is the structure of synovium?
1-3 cells thin.
Contains – type-A synoviocyte (phagocytic), type-B synoviocytes (produce hyaluronic acid) and T1 collagen.
what does synovial fluid contain?
Hyaluronic acid
GAG chains that are hydrophilic
what type of collagen does articular cartilage contain?
Type 2 collagen.
Proteoglycan – mainly aggrecan.
what substances are blockaded as part of biological therapy of RA?
pro-inflammatory cytokines:
TNF-a, IL-6 and IL-1
e.g. using infliximab, belumimab
how can B-cells be depleted as part of biological therapy of RA? what drug is used?
RA by IV anti-CD20 antibodies
namely Rituximab
what does the multidisciplinary approach to RA include?
physio, occupational therapy, hydrotherapy, surgery
what type of drugs are used in RA treatment?
DMARDs – Disease-Modifying Anti-Rheumatic Drugs
when should RA to treated?
as early as possible and aggressively to minimise joint destruction where inflammation happens over time
what type of drugs are safer to use than steroids?
DMARDs (“steroid-sparing agents”) e.g methotrexate are safer and more effective in the long term
better than steroids as it won’t have the long term side effects of steroids
what drug is used in glucocorticoid therapy of RA? how should usage be controlled?
prednisolone
avoid long term use due to its side effect but can be used short term to alleviate the symptoms
what effect do DMARDs have on RA treatment?
induce remission (not cure) and prevent joint damage by reducing inflammation in synovium and slowing/preventing structural joint damage
slow effect
example of DMARDs
methotrexate, sulphasalazine, hydroxychloroquine (commonly used)
Leflunomide, gold and penicillamine (rarely used).
regular blood monitoring needed due to significant side effects
which antibody drugs can be used in RA management?
Rituximab & Infliximab: chimeric antibodies (Fab mouse regions and human constant regions)
Adalimumab & Golimumab:
full human antibodies
used for severe RA
when is biological therapy used?
when methotrexate (non-biological) has failed. Biological therapy involved all the antibody treatments (expensive and restricted) which is used later
what is an increased risk with use of biological therapy?
increased risk of infection
how can RA treatments lead to infection?
o TNF-a inhibition:
increased susceptibility to mycobacterial infections (screen patients for TB).
o B-cell depletion (can) lead to hepatitis B re-activation (so screen patients for Hep B).
o B-cell depletion (can) lead to JC virus infection and progressive multi-focal leukoencephalopathy (PML).
examples of monoclonal antibody drugs?
belimumab
tocilizumab
denosumab
what does the drug abatacept do?
blocks co-stimulation of T cells and therefore their activation
what does the drug etanercept do?
inhibits TNF-alpha
what are the key antibodies in rheumatoid ?
- rheumatoid factor
- anti- cyclic citrullinated peptide antibodies
which HLA gene defect caused rheumatoid?
HLA DR4
