gout Flashcards
define gout
- Group of diseases characterised by hyperuricaemia - increased production or decreased excretion
epidemiology of gout
2.49% in UK in 2012, 1.77/1000/year, more common in men
what is primary gout
due to rare inborn errors in metabolism or renal excretion
what is secondary gout
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
causes of underexcretion
- 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
risk factors of gout
- Hypertension * Obesity * Hypertriglyceridemia
pathophysiology of gout
- Deposition of monosodium urate monohydrate crystals in joints and soft tissues causing inflammation and pain
what is uric acid
- 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
what influences solubility of uric acid
Temperature, pH, cation concentration, articular dehydration and presence of nucleating agents
how do urate crystals cause an inflammatory response
§ 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
how does uric acid cause pain
Only cause symptoms when crystals are shed into bursa (synovial fluid sacs)
5 stages of gout
- 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
what is stage 2 - acute gouty arthritis and symptoms
§ 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
what is 3. interval gout/anticritical gout
time between acute flares of gout
what is 4. Chronic tophaceous gout
- Presence of tophi: white deposits of monosodium urate in Subcutaneous and periarticular areas § Ear lobes, fingers and Achillies tendon
what is 5. 5. Gouty neuropathy/hyperuricaemia induced renal disease
- Crystals of urate deposited around renal tubules § Inflammatory response (interstitial nephritis) § Proteinuria and renal impairment § Renal stone formation
how is gout diagnosed
- clinical history and examinations - uric acid levels not always raised - joint xray, fluid microscopy and standard bloods
treatment aims
- Relieve pain and inflammation of acute attack and terminate attack - Prevent further attacks and long term joint/organ damage - Avoid precipitating factors
treatment for acute attacks
- rest - full dose NSAIDs (7-10days) - colchicine (if nsaids c/i or do not work) - corticosteroids - combinstion therapy
colchicine dose for acute attacks of gout
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
side effects of colchicine
- cyp450 inhibitor - lots of interactions!!- Nausea and vomiting - Abdominal pain - Diarrhoea (STOP)- Rashes, peripheral neuropathy, blood dyscrasias
what is prophylaxis
-Urate lowering therapy (ULT) important to prevent long term complications
when is prophylaxis given
- 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
how is prophylaxis given
start at a low dose and titrate upwards - careful in patients with high levels, drastic changes can cause flare
which medications can be given with ULT when its started
- Colchicine - 0.5-1mg daily (reduce in renal impairment) 2. NSAID/Coxibs + GI protection - If colchicine contraindicated
first line for prophylaxis
allopurinol - xanthine oxidase inhibitor
how does allopurinol work
Pro-drug: undergoes hepatic metabolism to active metabolite - oxypurinol
dosage of allopurinol
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)
allopurinol dose adjustments for renal impairment
Can accumulate in renal impairment so lower dose (50-100mg daily)
allopurinol side effects
Rashes, hypersensitivity, GIT disturbances - generally well tolerated
interaction between allopurinol and azathioprine
-Azathioprine metabolised to mercaptopurine which is metabolised by xanthine oxidase, Allopurinol causes accumulation of mercaptopurine - bone marrow suppression!
second line gout prophylaxis
febuxostat - Non-purine selective xanthine oxidase inhibitor - 80mg OD - Increase to 120mg if uric acid levels >357umol/L after 2-4 weeks
side effects of febuxostat
§ GIT, headaches, increased LFTs, oedema, rash § Rare but serious hypersensitivity reactions
third line gout prophylaxis
Uricosuric agents such as Sulfinpyrazone, probenecid/benzbromarone (unlicenced), increase excretion by acting directly on renal tubule
what is forth line prophylaxis for gout
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
