Session 10 - Group Work

Question 1

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
a) Do you agree with this diagnosis? What further test would be used for confirmation?

Answer 1

Yes because it matches the symptoms. A further test could be a biopsy from the temporal artery. Patients with polymyalgia rheumatica are at a significant risk of getting temporal (giant cell) arteritis.

Could do a CRP and general inflammatory markers.

Question 2

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
b) Do you agree with the recommended first line treatment?

Answer 2

Yes because this follows the NHS guidelines, and there is a risk of vision loss if not.

Question 3

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
c) Is this an appropriate dose? When should a maximum dose be offered with immediate effect?

Answer 3

Yes, because the maintenance dose is 40-60 mg, but if there was any visual problems then it would be >40 mg.

You need to wean them off steroids, otherwise get adrenal crisis

Need to carry a card saying he’s on long-term steroid use.

Question 4

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
d) What advice should he be given regarding the treatment?

Answer 4

Seek help immediately if he experiences any vision problems - do not stop taking the treatment immediately (it needs to be stepped down) as otherwise you can go into visual impairment.

Question 5

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
e) Methotrexate can be classed as a disease modifying anti-rheumatic drug (DMARD), which is first line treatment for managing rheumatoid arthritis. What other indications can it be used for?

Answer 5

Chemotherapy
Haemotological cancers
Crohn's disease
Psoriasis
Ectopic pregnancy

Question 6

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
f) Suggest the therapeutic action of methotrexate in these conditions.

Answer 6

Methotrexate competitively and reversibly inhibits dihydrofolate reductase (DHFR) although the mechanism in unclear.

Question 7

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
g) Why is it important to discuss the use of NSAIDs as adjuncts in the management of rheumatoid arthritis?

Answer 7

This is because NSAIDs can displace methotrexate so you’d have to adjust the dose.

Question 8

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
h) What is unusual about the dosing frequency of methotrexate considering it has a half-life of ~30 hours?

Answer 8

Weekly rather than daily. It is a never event to dose it daily!

Question 9

1) A 62-year-old man presents with sudden onset of malaise and severe periorbital headache and jaw claudication. He had discounted a sore throat as a symptom of the early stages of a winter cold. Remarkable blood results include a C - reactive protein (CRP) level of 15mg/L. He is immediately prescribed prednisolone 40 mg daily for a diagnosis of temporal (giant cell) arteritis.
i) A 23-year-old woman has newly diagnosed rheumatoid arthritis. You are considering commencing her on methotrexate. What family planning advice should you discuss with her and her partner?

Answer 9

It is teratogenic so it can cause birth defects and miscarriages (you’re inhibiting folate so your neural tube can’t produce properly, hence birth defects).

Question 10

2) A 74-year-old woman with polymyalgia rheumatica (PMR) is commenced on azathioprine to help control her myalgia as prednisolone 12.5 mg daily is proving to be inadequate.
a) Give 2 other indications for this drug

Answer 10

SLE, vasculitis, IBD, atopic dermatitis, Immunosuppression

Question 11

2) A 74-year-old woman with polymyalgia rheumatica (PMR) is commenced on azathioprine to help control her myalgia as prednisolone 12.5 mg daily is proving to be inadequate.
b) How do we monitor for potential toxicity?

Answer 11

Monitor FBC (specifically neutrophils for immunosuppression) for bone marrow suppression

Monitor LFTs for risk of hepatitis

Question 12

2) A 74-year-old woman with polymyalgia rheumatica (PMR) is commenced on azathioprine to help control her myalgia as prednisolone 12.5 mg daily is proving to be inadequate.
c) Would you expect azathioprine to be effective in reducing symptoms in this patient? What test should be carried out before initiating treatment?

Answer 12

TPMT gene is highly polymorphic in patients.

If TPMT is low, then 6-MP builds up (the active metabolite), which causes myelosuppression (bone marrow suppression) - so you’d get a low white count, low platelets (not just low neutrophils).

Question 13

3) A 56-year-old South Asian man diagnosed with rheumatoid arthritis reports a 2-month history of cough and fever at night. His appetite has been poor and he has also lost 4kg. He is being treated with naproxen and adalimumab (Humira ).
a) What diagnoses should you consider (you may need to look beyond the lecture slides which discuss TNF α inhibition)

Answer 13

TB
Lung cancer
HIV
Hepatitis

TNF-a is released in response to TB

Question 14

3) A 56-year-old South Asian man diagnosed with rheumatoid arthritis reports a 2-month history of cough and fever at night. His appetite has been poor and he has also lost 4kg. He is being treated with naproxen and adalimumab (Humira ).
b) Why may he be at risk of these conditions?

Answer 14

TB is prevalent in South Asian populations

Cancer due to the weight loss and persistent cough

Question 15

3) A 56-year-old South Asian man diagnosed with rheumatoid arthritis reports a 2-month history of cough and fever at night. His appetite has been poor and he has also lost 4kg. He is being treated with naproxen and adalimumab (Humira ).
c) What screening is carried out on patients prior to starting anti-TNF treatment?

Answer 15

Interferon gamma releasing assay
Chest x-day
Sputum culture, if productive cough

Question 16

4) A 29-year-old woman presented to her GP with a 2 week history of frequent diarrhea with mucus but no blood in the stool. It was negative for infective agents. Further investigation by a gastroenterologist found that she had intermittent thickening and inflammation of the mucosa of the sigmoid colon. Crohn’s disease was confirmed to be isolated to the sigmoid and part of the ascending colon.
a) What would be the initial therapy you would recommend for this patient?

Answer 16

Severe Crohn’s
Corticosteroids - Prednisolone is the first line treatment
THEN
Azathioprine if it doesn’t work

Mild-moderate Crohn’s
Give Azathioprine first-line (NICE)

Question 17

4) A 29-year-old woman presented to her GP with a 2 week history of frequent diarrhea with mucus but no blood in the stool. It was negative for infective agents. Further investigation by a gastroenterologist found that she had intermittent thickening and inflammation of the mucosa of the sigmoid colon. Crohn’s disease was confirmed to be isolated to the sigmoid and part of the ascending colon.
b) How does your recommended initial treatment help to treat the Crohn’s disease exacerbation?

Answer 17

It is an immunosuppressor which prevents IL-1 and IL-6 production by macrophages. It inhibits all stages of T-cell activation.

Question 18

4) A 29-year-old woman presented to her GP with a 2 week history of frequent diarrhea with mucus but no blood in the stool. It was negative for infective agents. Further investigation by a gastroenterologist found that she had intermittent thickening and inflammation of the mucosa of the sigmoid colon. Crohn’s disease was confirmed to be isolated to the sigmoid and part of the ascending colon.
c) Your recommended therapy should be given until remission is confirmed. Why should therapy be then slowly titrated down to end treatment?

Answer 18

Otherwise it can lead to adrenal crisis

Question 19

5) A 60 year man (PMH hypertension, osteoarthritis; heavy smoker; good exercise tolerance; prescribed medication is bendroflumethiazide and aspirin with prn (as required) ibuprofen) was admitted to hospital dehydrated with a 6 week history of progressive dysphagia and is diagnosed at endoscopy with oesophageal cancer. A CT scan of thorax and abdomen suggests this has not spread. His case is discussed at the upper GI malignancy multidisciplinary meeting. He attends the outpatient clinic one week after discharge.

He is offered surgical resection of the tumour and neoadjuvant chemotherapy.

a) What is the meaning of neoadjuvant in this context? What is the role of the chemotherapy?

Answer 19

Neoadjuvant therapy is the administration of therapeutic agents before a main treatment

Chemotherapy kills rapidly dividing cells - the most common complication (could be) neutropenic sepsis.

Question 20

5) A 60 year man (PMH hypertension, osteoarthritis; heavy smoker; good exercise tolerance; prescribed medication is bendroflumethiazide and aspirin with prn (as required) ibuprofen) was admitted to hospital dehydrated with a 6 week history of progressive dysphagia and is diagnosed at endoscopy with oesophageal cancer. A CT scan of thorax and abdomen suggests this has not spread. His case is discussed at the upper GI malignancy multidisciplinary meeting. He attends the outpatient clinic one week after discharge.

He is offered surgical resection of the tumour and neoadjuvant chemotherapy.

He agrees to have chemotherapy and is to start in the next few days. The regimen is fluorouracil (also known as 5FU), cisplatin and epirubicin. These drugs are given together and are known as the ECF regimen.

b) What tests do you want to do prior to dosing his chemotherapy, particularly in view of his PMH and his clinical presentation?

Answer 20

INR because he is on aspirin treatment.

GFR - thiazide direct and no problems with elimination clearance, hypertensive (might have renal artery stenosis); old; dehydrated (oesophageal cancer and can’t swallow). 5-FU as a chemotherapeutic agent is particular bad for the bowel.

LFTs

Echocardiogram - ejection fraction - see how much blood is going across the valves and they can use that and the size of the heart to tell you how well it’s functioning. Ensure there are no valvular/structural abnormalities

Ensure a thorough check of patient drug history

Question 21

5) A 60 year man (PMH hypertension, osteoarthritis; heavy smoker; good exercise tolerance; prescribed medication is bendroflumethiazide and aspirin with prn (as required) ibuprofen) was admitted to hospital dehydrated with a 6 week history of progressive dysphagia and is diagnosed at endoscopy with oesophageal cancer. A CT scan of thorax and abdomen suggests this has not spread. His case is discussed at the upper GI malignancy multidisciplinary meeting. He attends the outpatient clinic one week after discharge.

He is offered surgical resection of the tumour and neoadjuvant chemotherapy.

He agrees to have chemotherapy and is to start in the next few days. The regimen is fluorouracil (also known as 5FU), cisplatin and epirubicin. These drugs are given together and are known as the ECF regimen.

c) How is the dose likely to be worked out, what information is needed? Why is it calculated in this way?

Answer 21

Height and weight aka BMI and surface area - gives you an idea of how far the drug will dose

Fractional kill hypothesis

Question 22

5) A 60 year man (PMH hypertension, osteoarthritis; heavy smoker; good exercise tolerance; prescribed medication is bendroflumethiazide and aspirin with prn (as required) ibuprofen) was admitted to hospital dehydrated with a 6 week history of progressive dysphagia and is diagnosed at endoscopy with oesophageal cancer. A CT scan of thorax and abdomen suggests this has not spread. His case is discussed at the upper GI malignancy multidisciplinary meeting. He attends the outpatient clinic one week after discharge.

He is offered surgical resection of the tumour and neoadjuvant chemotherapy.

He agrees to have chemotherapy and is to start in the next few days. The regimen is fluorouracil (also known as 5FU), cisplatin and epirubicin. These drugs are given together and are known as the ECF regimen.

You read the side effect profile of this regimen and discover there is a moderately high chance of him becoming thrombocytopenic to the extent of causing easy bruising and bleeding.

d) What advice should you give him about his existing medication?

Answer 22

Stop taking aspirin
Thrombocytopenia will have a similar effect to aspirin so have the two together you’ll have no platelets, and bleed together and die.