Rheum - RA Flashcards
RA?
Rheumatoid Arthritis
Define RA
Chronic inflammatory condition characterised by
• PAIN
• STIFFNESS
&
• SYMMETRICAL SYNOVITIS (inflammation of synovial membrane) of synovial joints
Key features of RA?
o Chronic arthritis
• Polyarthritis – swelling of small joints (hand/wrist)
• Symmetrical
• Early morning stiffness
• May lead to joint damage & destruction
o Extra-articular disease (may occur)
• Rheumatoid nodules – SC swellings (immune complexes and RF)
o Rheumatoid “factor” (Anti-IgG IgM-auto-antibody)
• IgM auto-Ab against IgG
Epidemiology of RA?
1% of population affected
F:M = 3:1
Genetic component of RA?
Heritability estimates of up to 60%
The genetic component comes from a 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”
Environmental component of RA?
Smoking
• interacts with shared epitope to increase risk!
Most common affected joints of RA?
o Metacarpophalangeal joints (MCP). o Proximal interphalangeal joints (PIP). o Wrists. o Knees. o Ankles. o Metatarsophalangeal joints (MTP).
My Poor Willy Knows All Mothers.
Features of RA?
SYMMETRICAL POLYARTHRITIS
• symmetrical!!
Swan-neck deformities
• affects ring-finger with HYPER-extension of PIP join
AND
• HYPER-flexion of DIP joint
Boutonniere deformity
• affects little finger with HYPER-flexion of PIP joint
Where is the 1o site of pathology of RA?
In the SYNOVIUM, located at:
• Synovial joints - PIP joint synovitis
• Tenosynovium - extensor tenosynovitis
- tendons wrapped in Tenosynovium
• Bursa - olecranon bursa for e.g.
What then develops after the 1o site of pathology and explain this
Sub-cutaneous nodules!
Nodule structure:
• Central area – fibrinoid necrosis surrounded by macrophages
• Peripheral area – connective tissue
o Occur in ~30% patients.
o Associated with – severe RA, extra-articular manifestations, RF
Explain the influence RF has on RA
RF - rheumatoid factor
These are Abs that recognise the Fc portion of IgG as their target antigen!
• typically IgM Abs i.e. IgM anti-IgG Abs
RF is present in 70% at disease onset and a further 10-15% become positive over the first 2 years of diagnosis
Correlations:
o High RH alpha with likelihood of joint damage.
o High RH /alpha/ with how ill the patient feels.
Explain the influence of ACPA on RA
ACPA - anti-cyclic citrullinated peptide Ab
Abs to citrullinated peptides are HIGHLY SPECIFIC for RA
• mediated by PADs (enzymes)
• PADs are MORE active at sites of inflammation when they are produced by neutrophils & monocytes
ACPA is strongly associated with:
• smoking (more citrullination in lungs)
• HLA - ‘shared epitope’
Why might an individual be more susceptible to RA in regards to ACPA?
An individual may be susceptible if they carry the specific amino-acid sequence in their HLA-DR antigen-binding groove – “Shared epitope”
- Shared sequence in amino-acids 70-74 of the HLA-DRbeta- chain
- Hence, multiple serotypes of HLA are associated with RA (HLA-DR1, 4, 6, 10) – all have “Shared epitope”
This shared epitope preferentially binds non-polar substances such as CITRULLINE
Environmental factors can enhance levels of citrulline (e.g. smoking) so the cause of anti-CCP antibodies could be a combination of genetics and the environment.
Extra-articular features of RA - both common and uncommon?
Common:
Pyrexia, weight loss
SC nodules
Uncommon: Vasculitis Episcleritis – ocular inflammation Neuropathies Amyloidosis Lung disease – fibrosis, nodules Felty’s syndrome – (3) triad of – splenomegaly, leucopenia, RA
Radiographic abnormalities of RA?
Early
• juxta-articular osteopenia (low bone density juxta-articular bone)
Later
• joint erosions at margins of joints
Later still
• joint deformity and destruction
