12.9 Rheumatoid Arthritis

Question 1

Other than the joints, what two other organ systems can be affected by rheumatoid arthritis? How might this manifest?

Answer 1

• Skin (nodules of macrophages, lymphocytes and necrosis)
• Lungs (pulmonary fibrosis and pleural effusion)

Question 2

Which gene mutations can cause rheumatoid arthritis in combination with which environmental factors?

Answer 2

Gene mutations: HLA-DR1/DR4

Can cause rheumatoid arthritis in combination with environmental factors such as…

Cigarette smoke and specific pathogens.

Question 3

Explain the process of citrullination, and how it can contribute to the pathophysiology of Rheumatoid Arthritis

Answer 3

• Post-translational conversion of argininine amino acid into citrulline
• In the setting of HLA-DR1/4 mutation, can lead to immune response
• This is how anti-CCP (anti-cyclic citrullinated peptide) antibodies are produced (and why they’re tested for)

Question 4

What is a pannus in the setting of rheumatoid arthritis? How is it formed? What are the effects of its formation?

Answer 4

• During RA, inflammatory cells are recruited to the joint space
• Among these are macrophages, which release inflammatory cytokines that increase synovial cell proliferation
• This leads to the formation of a pannus: a thickened synovial membrane that contains grnulation tissue (fibroblasts etc.)
• Pannus synoviocytes can release proteases, breaking down bone and articular cartilage, thus damaging joints

Question 5

How can rheumatoid arthritis disrupt the cycle of bone remodelling?

Answer 5

• Inflammatory cytokines prompt T cells to express RANKL
• Osteoclast precursors bind to RANKL, becoming osteoclasts that break down bone

Question 6

What does the Rheumatoid Factor antibody target? When/why is it tested for?

Answer 6

• Targets altered Fc domain of IgG antibodies
• This altered Fc domain can be present as a consequence of RF genetic risk factors (DR1/DR4) and environmental factors (smoking/pathogen)
• Therefore, it is often present in the joint space during RF, making it a valuable diagnostic test.

Question 7

What are two reasons why the angiogenesis that occurs in RA might be harmful?

Answer 7

1. Increased delivery of inflammatory cells
2. Increased spread to other organ systems (e.g. lungs, skin)

Question 8

What type of -arthropathy is RA? Symmetrical or no? What joints can it commonly affect initially?

Answer 8

• Polyarthropathy
• Symmetrical
• Commonly in MCP and PIP joints of hands, and MTP of feet

Question 9

List three hand deformities that might be present in RA

Answer 9

• Ulnar deviation
• Swan neck (PIP hyperextension; DIP hyperflexion)
• Buttonhole deformity (opposite of swan neck)

Question 10

How might we investigate for rheumatoid arthritis?

Answer 10

• RF/Anti-CCP blood tests
• X ray: soft tissue swelling, loss of joint space, decreased bone density
• Clinically: swanneck/buttonhole deformity, ulnar deviation

Question 11

Outline the management of Rheumatoid Arthritis, both for exacerbation and normal life

Answer 11

Exacerbation: NSAIDs and corticosteroids

Normally: DMARDS (which suppress immune activity), and biologics (which are more targeted immunosuppresion)