Gout and polymyalgia rheumatica

Question 1

Gout and Pseudogout are both Crystal deposition diseases. what substance is deposited by Gout and Pseudogout ?

Answer 1

1) Gout - Sodium urate crystal deposition

2) Pseudogout - Calcium pyrophosphate crystal deposition

Question 2

what causes gout and which part of the body is affected?

Answer 2

1) cause: Hyperuricaemia
2) Great toe most commonly affected (75% cases)
- Can also result in tophi (white nodules) in skin and around joints (commonly ears, fingers, achilles tendon)

Question 3

what are the risk factors for gout?

Answer 3

1) family history (33%)
2) obesity
3) excess alcohol intake
4) high purine diet, diuretics
5) acute infection
6) ketosis
- Most common in men than women (5-10:1)
- Typical gout sufferer is ~50 year old overweight male

Question 4

Hyperuricemia is an excess of uric acid in the blood is the underlying cause of gout. what causes hyperuricaemia?

Answer 4

1) Impaired renal excretion:
- Idiopathic primary gout, chronic renal disease, drug therapy (i.e. thiazide diuretics,) hypertension, increased lactic acid production (exercise, alcohol, starvation), thyroidism
2) Increased production of uric acid:
- Increased purine turnover (i.e. myeloproliferative disorders, lymphoproliferative disorders (i.e leukaemia) , other cancers, psoriasis), Increased de novo purine synthesis

Question 5

how is gout diagnosed?

Answer 5

1) Serum uric acid levels usually raised:
- may be normal in acute attacks but never in lower half of normal range
- hyperuricaemia is often asymptomatic and not result in gout
2) Joint aspirate
3) Renal function test
4) X-ray to visualise joint erosion
5) you will also have a rapid response to NSAIDs

Question 6

how is an acute attack of gout treated?

Answer 6

1) NSAIDs (i.e. naproxen ): Reduce pain, swelling and duration of attack
- NOT aspirin
2) Colchicine: if NSAIDs are contraindicated
- As effective as NSAIDs but its use is often limited by toxicity. Useful for heart failure patients as does not induce fluid retention and can be given to patients on anticoagulants
3) Corticosteroids

Question 7

1) what is the MOA of naproxen?

2) what dose is given to a person with gout?

Answer 7

1) Irreversibly binds to cyclooxygenase (COX) enzymes in platelets, inactivating COX and preventing the production of prostaglandins that normally promote the inflammatory response
2) Acute gout, by mouth, initial dose of 750mg initially, then 250mg every 8 hours until attack has passed m 100–200mg daily

Question 8

Colchicine is an alkaloid extracted from autumn crocus. how does it work?

Answer 8

1) Prevents migration of neutrophils/phagocytes into gouty joints
2) Binds to tubulin resulting in depolymerisation of microtubules and reduced cell motility
2) Also prevents release of inflammatory products by these cells by preventing/limiting the phagocytosis of urate crystals

Question 9

what dose of colchicine is given for gout?

Answer 9

Acute attack: 1mg, then 0.5mg no more frequently then every 4 hours until pain is relieved OR until vomiting or diarrheoa OR Max. dose of 6mg is reached.
- Course not to be repeated within 3 days

Question 10

what are the side effects of colchicine?

Answer 10

Side effects: largely GI disturbance (nausea, diarrhoea, vomiting, abdominal pain)

Question 11

how can gout be prevented?

Answer 11

1) Withdraw thiazides and salicylates
2) Lose weight
3) Reduce alcohol consumption
4) Reduce total calorie and cholesterol intake
5) Avoid purine-rich foods (i.e. Offal, red meat, certain fish (such as anchovies, sardines), shellfish, pulses, such as lentils, peas and spinach)

Question 12

when is treatment for the prophylaxis of gout required?

Answer 12

Preventative treatment is required if:

1) Frequent recurrent attacks (more than 2 per year)
2) Tophi present
3) Signs of chronic gout (I.e. joint erosion)

Question 13

outline the treatment for the Prophylaxis of gout?

Answer 13

Drugs that reduce serum uric acid levels are used to prevent gout attacks:

1) Allopurinol inhibits uric acid synthesis
2) Uricosuric agents (probenecid and sulfinpyrazone) increase uric acid secretion
- These should not be used for acute attacks (or within a month of an acute attack) as can prolong attack indefinitely

Question 14

initiation of treatment for the prophylaxis of gout can cause an acute attack. how should this be managed?

Answer 14

Initiation of treatment may precipitate an acute attack so colchicine or NSAIDs should be used as prophylaxis and continued for at least 1 month after normouricaemia is achieved (about 3 months)
- If acute attack occurs, continue treatment but treat acute attack in own right

Question 15

Allopurinol belongs to a class of drugs called Xanthine oxidase inhibitors. what is its MOA ?

Answer 15

1) Mechanism: An analogue of hypoxanthine, it is a competitive inhibitor of xanthine oxidase, decreasing the conversion of naturally occurring hypoxanthine into uric acid.
- Alloxanthine (metabolite) also inhibits xanthine oxidase (non-competitive)

Question 16

Allopurinol can reverses tophi and renal stone formation and can be used in patients with renal impairment. what are the side effects of this drug?

Answer 16

GI disturbance and allergic reactions (skin rashes and fever), fatal skin diseases (toxic epidermal necrolysis)!

Question 17

what dose of allopurinol is used in gout?

Answer 17

Prophylaxis of gout, by mouth, initial dose of 100mg daily, preferably after food, then adjusted according to plasma or urinary uric acid concentration (maintenance doses range from 100–200mg daily (mild conditions) to 700–900mg daily (severe conditions).

Question 18

what is the counseling for allopurinol?

Answer 18

1) Withdraw therapy immediately if get a rash (if mild, may retry with caution)
2) May precipitate an acute attack of gout; Acute attacks can be avoided if NSAIDS (not aspirin or salicylates) or colchicine are taken for at least 1 month after hyperuricaemia is corrected.

Question 19

how do Uricosuric agents work and when are they used?

Answer 19

1) they Increase uric acid secretion by direct action on renal tubule
2) Useful in patients who fail to respond or develop severe adverse effects to allopurinol
3) Patients may respond to a combination of uricosuric agents and allopurinol, when failed to respond to either drug alone
- avoid in renal insufficiency and renal stones

Question 20

Pseudogout is an inflammation of joints caused by the deposition of calcium pyrophosphate. who is most likely to get Pseudogout, and which parts of the body are commonly affected?

Answer 20

1) Most common in elderly women
2) Knees, shoulders and wrists most commonly affected
- Acute attacks are less severe than gout and often resemble osteoarthritis
- May occur secondary to other diseases (i.e. osteoarthritis, hyperparathyroidism, hypothyroidism and haemochromatosis)

Question 21

how is Pseudogout diagnosed?

Answer 21

1) Diagnosed through presence of small brick-shaped pyrophosphate crystals in synovium
2) Blood tests may show raised WBC count and normal serum calcium
3) X-ray may show calcification of articular cartilage (chrondrocalcinosis)

Question 22

what is the treatment for pseudogout?

Answer 22

1) Treatment is with rest, joint aspiration and NSAIDs
Local corticosteroid injections can sometimes be useful
2) Chronic form of disease may lead to joint erosion so need specialist treatment (often DMARDs)

Question 23

what is Juvenile idiopathic arthritis?

Answer 23

1) Most common form of arthritis in children and adolescents. Joint and limb pains are common in children but arthritis is rare

Question 24

how is Juvenile idiopathic arthritis treated?

Answer 24

1) NSAIDS for to relieve pain and stiffness
2) Many children do not require DMARDs
- Methotrexate is effective
- Sulfasalazine is an alternative (avoid for systemic-onset Juvenile idiopathic arthritis)
3) Corticosteroids may be required for systemic disease
Biologics
- Consideration of which can be used based on age and treatment history

Question 25

what is Polymyalgia Rheumatica and what are the symptoms?

Answer 25

1) Polymyalgia rheumatica is a rheumatic disorder associated with moderate-to-severe musculoskeletal pain and stiffness
2) PMR associated with abrupt onset of stiffness and pain in proximal muscles of shoulder and/or pelvic girdle, stiffness worse after rest, malaise, fever, weight loss, anorexia

Question 26

what is giant cell arteritis and what are the symptoms?

Answer 26

1) Giant cell arteritis is a form of vasculitis, a group of disorders that results in inflammation of blood vessels. This inflammation causes the arteries to narrow, impeding adequate blood flow.
2) GCA associated with localised headache, scalp tenderness, facial pain, visual symptoms (i.e. double vision or sudden loss of vision)

Question 27

who is affected by Polymyalgia rheumatica and giant cell arteritis?

Answer 27

Affects the elderly (rare in those <50yrs) and is more common in females than males (3:1)

Question 28

outline the Investigations for PMR/GCA

Answer 28

1) Blood tests - increased ESR (>30mm/hr) and normocytic anaemia
2) Temporal artery biopsy (esp. if GCA is suspected)
Before or within a week of starting treatment
3) Exclude other diagnoses :
- Malignancy, arthritis, referred pain etc

Question 29

what is the treatment for PMR/GCA ?

Answer 29

1) systemic corticosteroids Prednisolone:
- PMR 10-15mg daily
- GCA 40-60mg daily
2) Treatment continued until remission of disease activity before gradually decreasing dose
3) require treatment for longer than 2 years since relapse is common (50%) if treatment is discontinued at 2 years.
- Patients require osteoporosis prophylaxis and must carry STEROID card

Question 30

what is the MOA of Prednisolone?

Answer 30

Binds irreversibly to glucocorticoid receptors, preventing them from binding to steroid response elements and modifying gene expression. Modification of gene expression leads to systemic suppression of inflammation.

Question 31

what is the counselling and dose for prednisolone?

Answer 31

1) Adrenal suppression can occur with long term use, leading to inability of body to produce natural corticosteroids (i.e. cortisol). Treatment should not be abruptly stopped!
- Dose taken in morning to reduce affects on circadian rhythms
2) Polymyalgia rheumatica; i 10-15mg daily, until remission of disease is achieved; then, reduce dose gradually to maintenance dose (usually 7.5-10mg daily)

Question 32

Discuss the problems of using steroids for a prolonged period of time ?

Answer 32

Associated with increased risk of osteoporosis/fracture, muscle wasting, mood changes, growth suppression, diabetes, Cushing’s syndrome and adrenal atrophy, increased blood pressure..

Question 33

summarise the withdrawal of steroids that have been taken for a prolonged period of time

Answer 33

Withdrawal can be abrupt, if disease is unlikely to
relapse and treatment duration is less than 3 weeks
1) Gradual withdrawal is required in the following instances due to suppression of the adrenal axis (reduced adrenal function) :
- if patient has received treatment for >3 weeks, had repeated courses, has other causes of adrenal suppression, received dose >40mg od, taken short course within 1 yr of long-term therapy, given repeat doses in evening

Question 34

how is Corticosteroid-induced osteoporosis treated?

Answer 34

1) Bisphosphonate
2) Calcitriol
3) Hormone replacement therapy (if appropriate)