Rheumatoid arthritis

Question 1

Is articular disease of RA more likely seen in women or men?

Answer 1

Women

Question 2

Is extra-articular disease more likely seen in men or women?

Answer 2

men

Question 3

If a patient has manifestations of extra-articular disease, what does this tell you?

Answer 3

Pt must be seropositive. Seronegative RA never has extra-articular disease

Question 4

What is the best serologic marker for RA?

Answer 4

ACPA: Arginine Citrullinated Protein Antibody

Question 5

Describe the pathophysiology of RA

Answer 5

Tolerance is broken
ACPA are developed
5-10 years later, ACPA immune complexes form and deposit in the joint

Question 6

Why is the joint targeted in RA?

Answer 6

The joint is proinflammatory and macrophages of the synovium are very reactive

Question 7

What is the shared epitope?

Answer 7

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.

Question 8

What HLA type indicates increased risk for RA?

Answer 8

HLA-DR

Question 9

What does it mean to be seropositive/negative in RA?

Answer 9

Seropositive pts have increased morbidity and mortality and are refractory to Tx. (i.e. seropositive for ACPA)

Question 10

What percentage of patients are seropositive/negative early on in the disease?

Answer 10

Around 50/50 split

Question 11

What happens to seronegatives over time?

Answer 11

Seronegatives drop out and remit, never occurring again. Once RA has become refractory, 80-85% are seropositive and 15-20% are seronegative

Question 12

What is the 5 AA sequence that results in increased likelihood of seropositive HLA-DR?

Answer 12

QKRAA or QRRAA

These allow binding of citrullinated proteins. ONLY seropositive RA has a genetic association

Question 13

What immune cell is RA mediated by?

Answer 13

CD4+ cells

Question 14

What are the risk factors for RA?

Answer 14

Smoking
Females more likely
obesity: fat is inflammatory
HLA-DR positive

Question 15

What are the Sx or RA?

Answer 15

1. POLYarticular and bilateral onset, with symmetry
2. Protrome sxs: fatigue for several years
3. Better with exercise, worse with rest
4. Morning is the worst time
5. Shows up in the HANDS first, wrist/CMC joint/PIP/MTP
6. Swelling
7. Palmar sublexation and ulnar deviation
8. Atrophy of the interosseous muscles
9. 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

Question 16

What kind of onset does RA have?

Answer 16

abrupt

OR insidious

Question 17

What would you see in the synovium or someone with RA?

Answer 17

Synovium will be hypercellular.
Loss of fat
Lots of lymphocytes and macrophages
Pannus: Granulation tissue forming in the cartilage

Question 18

Which has more of a genetic predisposition, OA or RA?

Answer 18

OA. Twin studies only show 10-30% concordance in RA.

Question 19

What specially named deformities would you see in RA?

Answer 19

Swan neck deformity: DIP joint

Boutiner deformity: Flexion of the PIP joint

Question 20

What would you need to do on physical exam of someone with RA?

Answer 20

1. Pain when shaking hands
2. Inability to do the claw
3. Lateral MCP/MTP squeeze

Question 21

Why is ACPA a better marker of RA than rheumatoid factor?

Answer 21

ACPA has equal sensitivity but more specificity

Question 22

Do you need diagnostic testing to make the diagnosis of RA?

Answer 22

No. History and physical are enough.

Question 23

Where in the hospital would you see 100% of pts with positive RF?

Answer 23

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

Question 24

In RA, you would see high levels of which cytokines?

Answer 24

TNF-alpha

IL-6

Question 25

How do you treat RA?

Answer 25

Use a DMARD like Methotrexate within the first year!
Use early therapy because damage is most extensive in that first year. And a lot of the damage may occur subclinically–>serious concern. So when pts present, they’ve already had significant destruction of their joints.

This is why we treat early and aggressively, REGARDLESS of the clinically severity of the diisease as assessed by ADL.

Question 26

What are contraindications for methotrexate?

Answer 26

Drinker

Pregnancy

Question 27

What lifestyle changes are important in RA?

Answer 27

weight loss and smoking cessation

Question 28

What are manifestations of extraarticular RA?

Answer 28

1. rheumatoid nodules
2. Vasculitis
3. Episcleritis
4. Lung nodules/interstitial lung disease
5. Carpal tunnel
6. Peripheral neuropathy

Question 29

Synovial compression from RA results in what complications

Answer 29

1. carpal tunnel syndrome
2. tarsal tunnel syndrome
3. Atlantoaxial subluxation disconnects C1 and C2

Question 30

Why should you always get Xrays of the head before surgery in someone with RA?

Answer 30

Atlantoaxial subluxation: With intubation (head extension), can result in spinal cord damage

Question 31

What are poor prognostic factors in RA?

Answer 31

High-titer rheumatoid factor, ACPA antibody
Expression of rheumatoid nodules (a marker for high titer RF) Progressive disease for at least 1 year (remission unlikely)
Poor function
HLA-DR haplotypes-homozygosity for HLA-DR4 + shared epitope

Question 32

What other therapies are available aside from MTX?

Answer 32

Sulfazalazine. Unknown MOA
Leflunomide: Inhibits pyrimidine synthesis
Hydroxychloroquine

Question 33

Describe what rheumatoid nodules feel like

Answer 33

Hard and immobile

Question 34

Why do patients with RA develop anemia?

Answer 34

Anemia of chronic disease

Question 35

What biologics are available for RA?

Answer 35

1. TNF-alpha antibodies
2. Rituximab
3. Abatacept (CTLA4 IgG)
4. Tocilizumab (Anti-IL6)

These agents have remarkable activity the prevent erosive disease. But they are expensive!!