Rheumatoid Arthritis

Question 1

what is rheumatoid arthritis

Answer 1

Chronic, autoimmune systemic illness characterised by symmetrical, peripheral polyarticular arthritis

Question 2

Signs

Answer 2

Pain 
stiffness
Swelling
Ulnar deviation of hands
Functional impairment
Systemic signs

Question 3

Symptoms

Answer 3

Tenderness
Swelling
restricted movement 
heat 
redness
systemic symptoms

Question 4

Systemic consequences

Answer 4

2o to chronic inflammation - vasculitis, scleritis, amyloiditis
CVS - altered lipid metabolism, increased acute phase reactants (ESR+CRP) and endothelial activation
Dysregulation of HPA - fatigue, decreased cognitive function
Liver - anaemia (IL-6 increases hepcidin production from hepatocytes (iron regulatory hormone)
Lung - interstitial lung disease, fibrosis
Sarcopenia
Osteoporosis
2o Sjögrens
Malignancy

Question 5

What score is used to assess RA

Answer 5

Disease activity score
<2.4 - clinical remission
>5.1 - eligible for biologic therapy

Question 6

Investigations for RA

Answer 6

Immunology - RF (IgG, IgM), anti-CCP Abs

Scans - MSK USS (shows inflammation)

Question 7

Cause of RA

Answer 7

Genetic - association with HLA-DRB1 locus (HLA-DR4 serotype)

Environmental - smoking, chronic infection (EBV, CMV, E.coli, mycoplasma, periodontal disease, gut microbes)

Question 8

Classification of RA

Answer 8

A - joint involvement (small or large, number)
B - Serology (RF & ACPA)
C - Acute Phase reactants (CRP & ESR)
D - Duration of symptoms (< or > 6 weeks)

Question 9

Treatment of RA

Answer 9

NSAIDs
Disease modifying Anti-rheumatic drugs (DMARDs)
Biologics
Corticosteroids (oral, IM, I-A)

Question 10

Types of DMARDs

Answer 10

METHOTREXATE
Sulfasalazine
Hydroxychloroquine
Leflunomide

Question 11

Types of biologics used in RA

Answer 11

TNFa inhibitors 
Anti-B cell - Rituximab 
Anti-T cell - Abatacept 
IL-1 inhibitors - anakinra
IL-6 inhibitors - Tocilizumab

Question 12

When do biologics work best

Answer 12

Enhanced use when used with methotrexate

Question 13

Toxicity problems with biologics

Answer 13

Injection site reaction
Injection
Malignancy

Question 14

What is rheumatoid synovitis characterised by

Answer 14

Inflammatory cell infiltration (neutrophils)
Synoviocyte proliferation
Neoangiogenesis
Leading to bone and cartilage destruction

Question 15

What is bone destruction mediated by

Answer 15

Osteoclasts under influence of RANKL produced by RA synovium

Question 16

What do autoantibodies in RA recognise

Answer 16

Joint antigens - i.e. type II collagen

Systemic antigens - i.e. glucose phosphate isomerase

Question 17

What type of proteins does anti-CCP attack

Answer 17

Keratin 
Fibrinogen 
Collagen 
Fibronectin 
a-enolase
Vimentin

Question 18

What does Rheumatic factor attack

Answer 18

Fc portion of self IgG

Question 19

Synovitis process in RA

Answer 19

Villous hyperplasia
Infiltration of T cells, B cells, macrophages and plasma cells
Intimal cell proliferation - fibroblasts
Production of cytokines and proteases –> neoangiogenesis
Increased vascularity

Question 20

What are the T cell cytokines

Answer 20

IFN-y and IL-17 (less of these in RA synovial)

Abatacept

Question 21

what are the B cell cytokines

Answer 21

IL-6 and TNF-a

Rituximab

Question 22

What do inflammatory cytokines do

Answer 22

Induce expression of endothelial cell adhesion molecules
Activate synovial fibroblasts, chondrocytes, osteoclasts
Promote angiogenesis
Suppress T-regs
Activate leukocytes
Promote autoAb production

Question 23

What cytokine mediates systemic effects

Answer 23

IL-6

• acute-phase response
• anaemia
• cognitive dysfunction
• lipid metabolism dysregulation