Rheumatoid Arthritis

Question 1

What are the articular presenting symptoms of RA?

Answer 1

• Swollen, tender small joints (especially hands and feet)
• PIP and metotarsalphalangeal joints most common, any joint but NOT DIP
• Worse in the morning with morning stiffness
• Better in the afternoon
• Fixed deformities

Question 2

What are the extra-articular involvement of RA?

Answer 2

• Subcutaneous rheumatoid nodules
• Visceral nodules (asymptomatic) in the lungs
• Vasculitis that presents as ulcers and rashes
• Pleural effusion
• Pericarditis effusion
• Myocarditis
• Uveitis, scleritis
• Lymphadenopathy

Question 3

What is the pathophysiology of RA?

Answer 3

Unknown antigen (post viral, genetic susceptibility) activates CD4 cells. These cells then go onto creating a greater inflammatory response:
- Plasma cells: secrete rheumatoid factor (RF), anti-CCP
- Macrophages, monocytes: secrete MMPs
- CD4 cells directly provoke inflammatory response through TNF - a and IL-1
All this leads to chronic inflammation of the synovium and extra-articular sites.
Eventually hyperplasia and hypertrophy of the synovium leads to formation of the pannus.
The pannus invades into the bone cartilage, tendons and ligaments leading to the bony deformities (z thumb, swan neck, boutonniere, ulnar deviation, palmar subluxation)

Question 4

How do we diagnose RA?

Answer 4

Criteria of diagnosing RA is based on:

1. Number of joints involved (small joints more sig than large joints)
2. Serology: RF and anti-CCP (anti-CCP is more specific)
3. ESR and CRP
4. Duration of symptoms (>6 weeks is significant)

Question 5

What are the main DDx of RA?

Answer 5

1. Psoriatic arthritis: asymmetrical, DIP involvement, skin lesions especially on elbows and scalp
2. SLE: DIP also spared, non-fixed deformity, ANA and anti-dsDNA positive
3. OA: DIP involved, less likely small joint involvement, x-ray: Loss of joint space, osteophytes, subchondral cysts, subchondral sclerosis (LOSS)

Question 6

How do we manage RA? Outline 1st line, adjunct therapy, and what therapy is available is 1st line is ineffective.

Answer 6

1st line: DMARDs
- Methotrexate * best
- Sulfasalazine
- Leflunomide 
Adjunct: NSAID (any)
- Ibuprofen
- Diclofenac
- Naproxen
Adjunct: Corticosteroid 
- Predinisolone 1-10mg orally od
Other:
Biological agents (TNF-alpha inhibitor)
- Infliximab (Ab to TNF-alpha)

Question 7

What is the MoA of methotrexate? Why does it require monitoring?

Answer 7

MoA: folic acid inhibitor, therefore it acts against the replication of fast replicating cells (cells of the bone marrow)
Implication: “Methotrexate Mondays” and folic acid every other day of the week.

Monitoring is mandatory:

• eGFR and UECs: renal failure
• LFTs: liver fibrosis
• FBE: pancytopaenia due to bone marrow suppression