RA - Pathology/Aetiology

Question 1

What guidelines do we use to classify RA?

Answer 1

2010 EULAR/ACR Classification (European Leaque against Rheumatism/American College of Rheumatology)

Question 2

What criteria do we use to classify the types/levels of RA?

Answer 2

Under the 2010 EULAR/ACR Classification its done by:

• No./size of joints involved
• Serology (-ve, low +ve or high +ve tests for RF & ACPA)
• Acute Phase Reactants (ESR/CRP)
• Duration (>6wks of symptoms)

Question 3

Who gets RA?

Answer 3

3x more common in women

Can occur at any point after 16yrs but mostly in 4th/5th decade

Question 4

What factors contribute to Development of RA?

Answer 4

Genetics

• HLA-DR1
• HLA-DR4

Environmental:

• Certain infections
• Silica Exposure
• Smoking

Question 5

What infections predispose to RA?

Answer 5

Viruses esp - CMV/EBV

Others include:
E. Coli
Mycoplasma
Periodontal Disease (Porphyromonas Gingivalis)
Gut Microbes

Question 6

In short how does RA work?

Answer 6

repeated insults to the synovium in genetically predisposed patients leads to immune complex & ACPA/RF production –> Chronic inflammation + Neovascularisation of the synovium

Question 7

Describe the changes in the synovium seen in RA…

What do we call the fibrovascular tissue that forms over the hyperplastic intimal lining?

Answer 7

Inflammatory cells in the joint space release lots of cytokines (specifically TNF-A, IL-6 & IL-17) which stimulated synovial membrane to proliferate

This creates a Pannus - a thick, swollen synovial membrane with granulation tissue - containing fibroblasts, myofibroblasts & inflammatory cells

Question 8

What cell types are involved in Rheumatoid Synovitis?

Answer 8

T Cells
B Cells
Macrophages
Fibroblasts

Question 9

What major inflammatory mediators are involved in Rheumatoid Synovitis?

Answer 9

ACPA (anti-citrullinated Protein Antibodies)
Rheumatoid Factor

TNF-Alpha
IL-6
IL-17
IFN-gamma

Question 10

What inflammatory cell predominates in the synovial fluid ?

Answer 10

Neutrophils

Question 11

How is cartilage damaged during RA?

Answer 11

Synovial fibroblasts from the intimal layer invade the articular cartilage & produce several classes of proteases (E.g. Metalloproteinases) that break down cartilage matrix allowing it to wear down under mechanical pressures

Question 12

How is bone damaged during RA?

Answer 12

RANKL produced by Synovial Fibroblasts and macrophages activate osteoclasts

Question 13

How does RA affect CVD?

Answer 13

Altered Lipid Metabolism –> Increased coronary artery disease

Question 14

How does fatigue & Reduced cognitive function come about from RA?

Answer 14

Dysregulates the HPA (Hypothalamic-Pituitary-Adrenal) Axis

Question 15

How does RA affect the liver?

Answer 15

Elevated Acute-phase response

Also IL-6 increases Hepcidin hormone production –> Iron dysregulation –> Anaemia

Question 16

How does RA affect he lungs?

Answer 16

Fibrosis and Interstitial Lung Disease (ILD)

Question 17

How does RA affect the muscles and bone?

Answer 17

Sarcopenia (breakdown) and Osteoporosis can occur

Question 18

What are some other consequences of RA on the rest of the body?

Answer 18

Secondary Sjogren Syndrome

Also Chronic Inflammation leads to:

• Vasculitis
• Nodules
• Scleritis
• Amyloidosis