Rheumatoid Arthritis

Question 1

Shared Epitope Hypothesis

Answer 1

Sequencing revealed that the different alleles shared a common sequence. Several HLA alleles have a conferred risk for RA. RA-associated HLA-DRB1 molecules all contain the conserved amino acids QKRAA, QRRAA, or RRRAA.

Question 2

ACPA with RA

Answer 2

ACPA is a/w protein antigens w/citrulline. It predates RA in 40% of patients.

Question 3

Extra-articular manifestations of RA

Answer 3

1. Rheumatoid nodules (common on extensor surfaces), 2.

Rheumatoid vasculitis, 3. Felty’s syndrome, 4. Eye manifestations

Question 4

Diagnositc Tests for RA

Answer 4

Rh factor and ACPA. They both have a sensitivity of 66% BUT ACPA is 95% specific as compared to Rh at 66% specificity. On X-rays we can see joint erosion, significant for RA.

Question 5

Criteria for Dx of RA

Answer 5

1. Morning stiffness, 2. Symmetric Arthritis, 3. Arthritis of 3 or more joints, 4. Arthritis in hand joints, 5. Rheumatoid nodules, 6. Serum rheumatoid factor, 7. Radiographic changes.

Question 6

Tx for RA

Answer 6

Methotrexate is the preferred DMARD of most rheumatologists. Methotrexate is dramatically effective in slowing radiographic progression. NSAIDS ( e.g., ibuprofen, naprosyn) are for symptomatic therapy; they are not DMARDS. If insufficient response to Methotrexate give Biologic Agents (IV or SQ).

Question 7

Patient-reported outcome measures

Answer 7

Patient reported outcome instruments can be used to guide therapy in a treat-to-target algorithm. It asks patient if they can preform certain tasks and asks them to assess their pain.

Question 8

Treat-to-target strategies

Answer 8

1. Target (identify therapeutic agent), 2. Timeline (assess patient regularly), 3. Treatment (modify treatment until target is met). Should reevaluate tx every 3 mo and change if needed.

Question 9

What is Rheumatoid Arthritis?

Answer 9

RA: A long-term (ongoing) immune response causing synovial proliferation that leads to inflammation of the joints and surrounding tissues and eventual joint destruction. It can also affect other organs.

Question 10

RA is strong associated with:

Answer 10

Smoking and gingivitis

Question 11

Clinical Features of RA (Where does it start?)

Answer 11

Most commonly, the disease starts in the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints. There are signs of synovitis joint-line tenderness, joint warmth, redness, and swelling (synovial hypertrophy, effusion)

Question 12

Cervical involvement of RA

Answer 12

Cervical involvement – anterior subluxation of C1 on C2 can compromise the spinal cord

Question 13

Rheumatoid vasculitis

Answer 13

ulcers are most common on the dorsum of foot and lateral aspect of the ankle

Question 14

Felty’s syndrome:

Answer 14

triad of: RA, neutropenia and splenomegaly; is associated with Large granular Lymphocyte leukemia.

Question 15

Extra-auricular eye manifestations of RA

Answer 15

Scleritis can progress to scleral thinning revealing deep pigmentation or to perforation of the orbit
(scleromalacia perforans).

Question 16

Cachexia:

Answer 16

TNF (also called TNF-alpha) was first called cachexin and is the central mediator of muscle wasting in rheumatoid arthritis

Question 17

Laboratory tests for RA

Answer 17

Rheumatoid factor: an IgM antibody that binds the Fc portion of immunoglobulin G as its antigen; ACPA: anti-citrullinated peptide antibody; binds protein antigens with citrulline. Marginal erosions on X-rays.

Question 18

Predictor of Outcome in early synovitis

Answer 18

The number of swollen joints may be a better predictor of outcome in early synovitis than the diagnosis of RA.

Question 19

Methotrexate Complications

Answer 19

1. teratogen - need 6 months off drug prior to pregnancy.
2. hepatitis – monitor every 2-3 months.
3. bone marrow suppression – monitor.
4. oral and GI ulcerations – give folate, 1 mg per day.

Question 20

Biological Agents in Tx RA

Answer 20

When there is insufficient response to methotrexate, biologic drugs are added. Biologics are molecules, usually proteins, that mimic naturally occurring molecules, including antibodies and receptors. They directly target the cytokines and cellular interactions responsible for RA.
Given IV or SQ. TNF antagonists are antibodies or soluble receptors that bind and remove TNF. Rituximab, Abatacept and Anticytokine Therapies.

Question 21

Age of Onset of RA

Answer 21

25-50

Question 22

Who is RA more common in?

Answer 22

2-3x more common in females

Question 23

RA in a/w Mortality

Answer 23

High mortality rate; shortens lifespan by 3-18 yrs.

Question 24

T/F: Shared Epitope hypothesis is a/w chromosome 3

Answer 24

True according to BOB. He said this was important to note.

Question 25

What are the key pathological agents in RA?

Answer 25

TNF and II-I Beta

Question 26

RA unlike OA common affects which joints?

Answer 26

shoulders, elbows, wrists and ankles

Question 27

___________ is the cell mediator of muscle wasting in RA

Answer 27

TNF (Cachexia)

Question 28

Rituximab

Answer 28

binds to CD20 and prompts immune system to selectively deplete CD20 positive B cells

Question 29

Abatacept

Answer 29

binds to CD80/86 on the APC and prevents stimulation of the T cells CD23 receptor.

Question 30

Anticytokine Therapies

Answer 30

(TNF and IL-1 blockers): interfere with work of cytokines

Question 31

Problem with patient reported outcomes:

Answer 31

A patient’s symptoms may reflect cumulative joint damage rather than disease activity. The goal is to treat disease activity; there is no treatment for joint damage other than joint replacement surgery.