Rheumatoid Arthritis

Question 1

what is rheumatoid arthritis?

Answer 1

Systemic autoimmune disease characterized by joint inflammation

Question 2

epidemiology of RA

Answer 2

most common systemic/inflammatory rheumatic disease
1% of adults
HLA-DR4 alleles for risk of disease
F>M

Question 3

define autoimmune diseases

Answer 3

own immune system stimulated to act against self, produce Ab to self antigens

Question 4

what is arthralgia

Answer 4

joint pain

Question 5

where does the inflammation occur

Answer 5

synovium

pain due to nerve endings on subchondral bone

Question 6

what are causes of RA

Answer 6

idiopathic

Question 7

role of synoviocytes in RA

Answer 7

synovial hyperplasia

produce proinflammatory cytokines

Question 8

role of macrophages in RA

Answer 8

APC
synoviocyte and tissue type macrophage
ingest and process antigens
present to HLA-DR matched T cells

Question 9

role of dendritic cells in RA

Answer 9

APC, activate naive T cells
self-antigen presentation to T cells
inappropriate DC activation could convert self-tolerance to overt autoimmunity

Question 10

role of T cells in RA

Answer 10

interact w APC through MHCI (HLA-A,B,C)) and MHCII (HLA-DR, DP, DQ)
produce cytokines (interleukins, IFN gamma, TNF-alpha and beta)

Question 11

3 critical roles of B cells in RA

Answer 11

antigen presentation and T cell activation
autoantibody production
cytokine production

Question 12

role of fibroblasts in RA

Answer 12

produce hyaluronan

inflammation - produce metalloproteinases

Question 13

role of complements in RA

Answer 13

immune complex activate cascade (rheumatoid factor is component of complex)
complement fragments attract neutrophils
degranulation –> enzymes damage cartilage

Question 14

what are suspected pathogenic antigens

Answer 14

virus (CMB, herpes, EBV, rubella)
bacteria (staph, strep, borelia)
mycoplasma

Question 15

what are suspected auto-antigens

Answer 15

type 2 collagen, proteoglycan, chondrocyte, IgG

Question 16

describe TNF alpha action on macrophages

Answer 16

increase pro-inflammatory cytokines and chemokines, increases inflammation

Question 17

describe TNF alpha action on endothelium

Answer 17

increase adhesion molecules (increased cell infiltration) and vascular endothelial growth factor (VEGF) (increased angiogenesis)

Question 18

describe TNF alpha action on hepatocytes

Answer 18

increased acute phase response –> increased CRP in serum

Question 19

describe TNF alpha action on synoviocytes

Answer 19

increased metalloproteinase synthesis –> articular cartilage degradation

Question 20

how does IL-6 cause anemia of chronic inflammation

Answer 20

inducing hepcidin production by hepatocytes

hepcidin inhibits release of iron from macrophages

Question 21

what genetic factors are associated with RA

Answer 21

HLA-DRB1 (increased risk)
HLA-DR4 (severe disease)
STAT4
infectious agents, smoking, and sex hormones

Question 22

what is seen on XR for RA

Answer 22

early erosion, soft tissue swelling

Question 23

5 steps in pathophysiology in RA

Answer 23

1. antigen presentation to B & T cells
2. T and B cells proliferate, cytokines released, angiogenesis occurs
3. synovial hypertrophy with cell accumulation in joint space
4. joint space invasion, enzymatic damage
5. bone erosion, loss of cartilage

Question 24

what causes systemic complaints in RA

Answer 24

effects of inflammatory mediators

fevers and poor appetite

Question 25

what are extra-articular features of RA

Answer 25

nodules vascular/resp system cardiovascular neurological

Question 26

where do RA nodules occur?

Answer 26

where there is pressure (achilles tendon, pulp of digits) extensor surfaces, peri-articular on tendons

Question 27

what are respiratory features of RA

Answer 27

``` pleural disease (chest pain, dyspnoea) interstitial lung disease ```

Question 28

what are cardiovascular features of RA

Answer 28

``` pericardial disease (chest pain, dyspnoea) cardiac muscle disease (due to nodules) ```

Question 29

what are vascular features of RA

Answer 29

small vessel disease | symptoms dependent on site of vasculitis (skin, bowel, nerve, eye)

Question 30

what are neurological features of RA

Answer 30

peripheral nerves may be affected median nerve (carpal tunnel, pain and/or paraesthesiae in palm or in 1st to 4th digits) worse with activity or at night

Question 31

describe Sjogren's syndrome

Answer 31

immune system disorder that accompanies RA dry eyes (eyelids sticking together) dry mouth other organ dryness

Question 32

describe Felty's syndrome

Answer 32

seropositive chronic RA splenomegaly granulocytopenia causes joint damage, leg ulcers, recurrent infections

Question 33

factors associated with poor prognosis in RA

Answer 33

``` load of disease (# of swollen and tender joints) presence of rheumatoid factor anti-CCP antibodies HLA-DR4 haplotype presence of erosions on XR ```