gout

Question 1

define gout

Answer 1

• Group of diseases characterised by hyperuricaemia - increased production or decreased excretion

Question 2

epidemiology of gout

Answer 2

2.49% in UK in 2012, 1.77/1000/year, more common in men

Question 3

what is primary gout

Answer 3

due to rare inborn errors in metabolism or renal excretion

Question 4

what is secondary gout

Answer 4

occur either do to drugs or as a consequence of another disorder * Over consumption of foods high in purines * Overproduction - 10%: excessive cell turnover, cell lysis, enzyme mutations * Underexcretion - most common

Question 5

causes of underexcretion

Answer 5

1. Hyperuricaemia 2. Large urate loads filtered through glomerulus 3. Urate reabsorption in proximal tubule increases, to avoid dumping of insoluble urate into urinary tractRenal failure, alcohol consumption, diuretics, aspirin, ciclosporin, omeprazole

Question 6

risk factors of gout

Answer 6

• Hypertension * Obesity * Hypertriglyceridemia

Question 7

pathophysiology of gout

Answer 7

• Deposition of monosodium urate monohydrate crystals in joints and soft tissues causing inflammation and pain

Question 8

what is uric acid

Answer 8

• Uric acid is a weak acid (pKa 5.8) , At physiological pH it is ionised - monosodium urate and if supersaturation occurs it leads to crystal formation

Question 9

what influences solubility of uric acid

Answer 9

Temperature, pH, cation concentration, articular dehydration and presence of nucleating agents

Question 10

how do urate crystals cause an inflammatory response

Answer 10

§ A proinflammatory cascade of cytokines, chemotactic factors, TNF § Inflammatory cell accumulation (monocytes and mast cells in the early phase, neutrophils in the late phase) § IL-1beta has been shown to be critically related to the inflammatory response in gout

Question 11

how does uric acid cause pain

Answer 11

Only cause symptoms when crystals are shed into bursa (synovial fluid sacs)

Question 12

5 stages of gout

Answer 12

1. Asymptomatic hyperuricaemia (long period before gout manifests) 2. Acute gouty arthritis 3. Interval gout/anticritical gout4. Chronic tophaceous gout 5. Gouty neuropathy/hyperuricaemia induced renal disease

Question 13

what is stage 2 - acute gouty arthritis and symptoms

Answer 13

§ Severe pain, red, hot, swollen and painful joints § Begins abruptly - max intensity 8-12hrs § Weight bearing impossible § Erythema § Synovitis § Leucocytosis (increased in white blood cell count) § Confusion in elderly - If left untreated it will stop after about 7 days but will cause desquamation of overlying skin

Question 14

what is 3. interval gout/anticritical gout

Answer 14

time between acute flares of gout

Question 15

what is 4. Chronic tophaceous gout

Answer 15

• Presence of tophi: white deposits of monosodium urate in Subcutaneous and periarticular areas § Ear lobes, fingers and Achillies tendon

Question 16

what is 5. 5. Gouty neuropathy/hyperuricaemia induced renal disease

Answer 16

• Crystals of urate deposited around renal tubules § Inflammatory response (interstitial nephritis) § Proteinuria and renal impairment § Renal stone formation

Question 17

how is gout diagnosed

Answer 17

• clinical history and examinations - uric acid levels not always raised - joint xray, fluid microscopy and standard bloods

Question 18

treatment aims

Answer 18

• Relieve pain and inflammation of acute attack and terminate attack - Prevent further attacks and long term joint/organ damage - Avoid precipitating factors

Question 19

treatment for acute attacks

Answer 19

• rest - full dose NSAIDs (7-10days) - colchicine (if nsaids c/i or do not work) - corticosteroids - combinstion therapy

Question 20

colchicine dose for acute attacks of gout

Answer 20

Administer ASAP - less effective over time - 0.5mg 2-4 times a day until relief of joint pain or development of GI side effect or 6mg taken - do not repeat within 3 days - Lower dose of 0.5mg every 8 hours in elderly and renal impairment - Response after 6 hours, pain relief after 12 hours and resolution within 24-72 hours

Question 21

side effects of colchicine

Answer 21

• cyp450 inhibitor - lots of interactions!!- Nausea and vomiting - Abdominal pain - Diarrhoea (STOP)- Rashes, peripheral neuropathy, blood dyscrasias

Question 22

what is prophylaxis

Answer 22

-Urate lowering therapy (ULT) important to prevent long term complications

Question 23

when is prophylaxis given

Answer 23

• Consider when patient suffers 2 or more acute attacks a year □ Tophi, chronic gouty arthritis, joint damage, renal impairment, urolithiasis (kidney stones) , diuretic use, young onset

Question 24

how is prophylaxis given

Answer 24

start at a low dose and titrate upwards - careful in patients with high levels, drastic changes can cause flare

Question 25

which medications can be given with ULT when its started

Answer 25

1. Colchicine - 0.5-1mg daily (reduce in renal impairment) 2. NSAID/Coxibs + GI protection - If colchicine contraindicated

Question 26

first line for prophylaxis

Answer 26

allopurinol - xanthine oxidase inhibitor

Question 27

how does allopurinol work

Answer 27

Pro-drug: undergoes hepatic metabolism to active metabolite - oxypurinol

Question 28

dosage of allopurinol

Answer 28

Start 100mg daily and increased every 3-4 weeks in response to treatment and serum urate levels (<300umol/L)- Usual maintenance 300mg daily (100-600mg)

Question 29

allopurinol dose adjustments for renal impairment

Answer 29

Can accumulate in renal impairment so lower dose (50-100mg daily)

Question 30

allopurinol side effects

Answer 30

Rashes, hypersensitivity, GIT disturbances - generally well tolerated

Question 31

interaction between allopurinol and azathioprine

Answer 31

-Azathioprine metabolised to mercaptopurine which is metabolised by xanthine oxidase, Allopurinol causes accumulation of mercaptopurine - bone marrow suppression!

Question 32

second line gout prophylaxis

Answer 32

febuxostat - Non-purine selective xanthine oxidase inhibitor - 80mg OD - Increase to 120mg if uric acid levels >357umol/L after 2-4 weeks

Question 33

side effects of febuxostat

Answer 33

§ GIT, headaches, increased LFTs, oedema, rash § Rare but serious hypersensitivity reactions

Question 34

third line gout prophylaxis

Answer 34

Uricosuric agents such as Sulfinpyrazone, probenecid/benzbromarone (unlicenced), increase excretion by acting directly on renal tubule

Question 35

what is forth line prophylaxis for gout

Answer 35

Canakinumab given as SC injection for severe refractory tophaceous gout - Target IL1b associated with inflammatory response induced by urate crystals - Not approved for acute flares by NICE