Rheumatoid arthritis Flashcards
Is articular disease of RA more likely seen in women or men?
Women
Is extra-articular disease more likely seen in men or women?
men
If a patient has manifestations of extra-articular disease, what does this tell you?
Pt must be seropositive. Seronegative RA never has extra-articular disease
What is the best serologic marker for RA?
ACPA: Arginine Citrullinated Protein Antibody
Describe the pathophysiology of RA
Tolerance is broken
ACPA are developed
5-10 years later, ACPA immune complexes form and deposit in the joint
Why is the joint targeted in RA?
The joint is proinflammatory and macrophages of the synovium are very reactive
What is the shared epitope?
HLA-DR and ACPA have a similar epitope. Thus, there is a specific 5 AA sequence within HLA-DR that predisposes to APCA antigen sensitivity.
What HLA type indicates increased risk for RA?
HLA-DR
What does it mean to be seropositive/negative in RA?
Seropositive pts have increased morbidity and mortality and are refractory to Tx. (i.e. seropositive for ACPA)
What percentage of patients are seropositive/negative early on in the disease?
Around 50/50 split
What happens to seronegatives over time?
Seronegatives drop out and remit, never occurring again. Once RA has become refractory, 80-85% are seropositive and 15-20% are seronegative
What is the 5 AA sequence that results in increased likelihood of seropositive HLA-DR?
QKRAA or QRRAA
These allow binding of citrullinated proteins. ONLY seropositive RA has a genetic association
What immune cell is RA mediated by?
CD4+ cells
What are the risk factors for RA?
Smoking
Females more likely
obesity: fat is inflammatory
HLA-DR positive
What are the Sx or RA?
- POLYarticular and bilateral onset, with symmetry
- Protrome sxs: fatigue for several years
- Better with exercise, worse with rest
- Morning is the worst time
- Shows up in the HANDS first, wrist/CMC joint/PIP/MTP
- Swelling
- Palmar sublexation and ulnar deviation
- Atrophy of the interosseous muscles
- MCP tender and soggy
Note that RA AVOIDS the DIP joint, while OA starts in the DIP and will have bony prominences with little swelling
What kind of onset does RA have?
abrupt
OR insidious
What would you see in the synovium or someone with RA?
Synovium will be hypercellular.
Loss of fat
Lots of lymphocytes and macrophages
Pannus: Granulation tissue forming in the cartilage
Which has more of a genetic predisposition, OA or RA?
OA. Twin studies only show 10-30% concordance in RA.
What specially named deformities would you see in RA?
Swan neck deformity: DIP joint
Boutiner deformity: Flexion of the PIP joint
What would you need to do on physical exam of someone with RA?
- Pain when shaking hands
- Inability to do the claw
- Lateral MCP/MTP squeeze
Why is ACPA a better marker of RA than rheumatoid factor?
ACPA has equal sensitivity but more specificity
Do you need diagnostic testing to make the diagnosis of RA?
No. History and physical are enough.
Where in the hospital would you see 100% of pts with positive RF?
Birthing pavilion. Rheumatoid factor works by potentiating the activity of IgG. IN RA, rheumatoid factor is made AGAINST ACPA, as a response to chronic inflammation
In RA, you would see high levels of which cytokines?
TNF-alpha
IL-6
