PBL 3

Question 1

At what age does rheumatoid arthritis occur

Answer 1

25-50 isa

Question 2

What are the symptoms of rheumatoid arthritis

Answer 2

• hand/wrist pain
• fatigue
• general stiffness
• knee pain
• hand redness and swelling
• difficulty sleeping
• reduced grip strength
• shoulder pain
• back pain
• general weakness
• numbness and tingling in hands and feet
• joints feel warm to the touch
• dry eyes and mouth
• weight loss
• joint looks red and discoloured

Question 3

What is a pannus

Answer 3

• this is a hyper proliferation of the synovial membrane

Question 4

How do you diagnose of rheumatoid arthritis

Answer 4

Joint involvement

• 1 large joint = 0
• 2-10 large joints = 1
• 1-3 small joints = 2
• 4-10 small joints = 3
• > 10 joints (at least 1 small joint = 5

Serology

• Negative RF and negative ACPA = 0
• Low positive RF or low positive ACPA = 2
• High positive RF or high positive ACPA = 3

Actue phase reactants

• Normal CRP and normal ESR = 0
• Abnormal CRP or abnormal ESR = 1

Duration of symptoms

• <6 weeks = 0
• > 6 weeks = 1

have great than or equal to 6/10 for diagnosis

Question 5

What are the two things that you are trying to treat in RA

Answer 5

• pain relief

- modification of disease progression

Question 6

What does DMARDs stand for

Answer 6

Disease modifying anti-rheumatics

Question 7

What is the gold standard for RA treatment

Answer 7

methotrexate

Question 8

describe the treatment pathway for RA

Answer 8

pain manegement (newly diagnosed RA) 
- NSAIDs and narcotics(opioids) 

First line disease treatment mild RA
- Methotrexate and second line DMARD

Second line disease treatment (moderate RA)
- methotrexate and TNF alpha inhibitor therapy

Second line disease treatment (severe RA)
- Methotrexate and rituximab

Novel disease treatments (unmanageable RA)
- Surgical interventions

Question 9

when should methotrexate be given

Answer 9

Orally once a week on the same day

• 2.5mg tablets
• Start between 5-10mg a week
• If oral form does not work subcutaneous or intramuscular injection

Question 10

How does methotrexate works

Answer 10

• folic acid antagonists
• methotrexate enters the cell through the folate carrier
• glutamate it added to it and it becomes polyglutamted within the cell
• it inhibits dihydrofolate reductase
• thus blocking the conversion of dihydrofolate to tetrahydrofolate
• this blocks synthesis for RNA and DNA
• also inhibits thymidylate synthetase

Question 11

1 State the two different types of synovial joints that connect the C1 and C2 vertebrae

Answer 11

Pivot joint

Planar joints or facet joints

Question 12

What is the name of the overgrowth of the synovium in RA and explain how this affects the joint.
(3 marks)

Answer 12

Pannus (1/2 mark)
It grows over and into the articular cartilage (1/2 mark), it produces cytokines that attack the cartilage and break it down, (1 mark) plus the cytokines also induce chondrocytes to differentiate as osteoclasts that break down the perarticular bone. (1 mark)

Question 13

What is the method of action of methotrexate

Answer 13

Methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis. (Students might just state that it is a folic acid inhibitor that is fine) (1 mark) This is involved in purine metabolism, and cell proliferation so prevent immune cell proliferation (1 mark) and also thymidyalte synthase so blocks DNA replication in addition. (1 mark) Another mechanism of MTX is the inhibition of the binding of Interleukin 1 beta to its cell surface receptor (1 mark).

Question 14

Explain why there are also flexion contractures that develop in RA?
(2 marks)

Answer 14

The long extensor flexor tendons run in tendon sheaths that are also affected by the disease process and become damaged and rupture (1 mark) and the flexor muscles are stronger they pull the fingers into a flexion deformity (1 mark)

Question 15

Explain why biological drugs against IL17 seem not be as effective as other cytokines in treating rheumatoid arthritis?

Answer 15

There are a cocktail of cytokines and IL17 is just 1. While IL17 seems important for directing the synovitis it may not be as important for the disease progression. So TNF and IL1 and IL6 biologicals seem to have a better modification of the whole disease profile than IL17. IL17 biologicals though are useful for psoriasis as the disease process in localised to the skin and is not a systemic as RA

Question 16

In a rheumatoid arthritis patient with cervical vertebral involvement on examination they have hyper-reflexia, explain why?

Answer 16

Compression of the spinal cord and to the axons for the corticospinal tract in particular causing the loss of the descending CST activity of the lower motor neurons. There might even be a Babinski sign present in these patients

Question 17

Explain why when prescribing methotrexate for rheumatoid arthritis patients their liver and full blood count is regularly monitored?

Answer 17

Methotrexate will inhibit any cell that is dividing, so it will affect the hematopoietic stem cells so you need to check the blood monthly for any adverse effects on the blood. Also the liver has regenerative capacity and so you also need to check that there is no liver damage that would compromise the patient. As women are more likely to be diagnosed with RA and might be of child bearing age you also need to give advice about getting pregnant and telling the doctor if they plan to get preganant so the medication can be changed or modified and all patients might need to take a folic acid supplement.