Gout Flashcards
How long do flare-up episodes typically last for in gout?
few days; acute episodes typically develop maximal intensity within 12hours
What are the key features of a flare up of gout?
- pain - often very significant
- swelling
- erythema
What is the most commonly affected joint in gout?
Metatarsophalangeal (MTP) joint - around 70%
What were attacks of gout in the first MTP traditionally called?
podagra
What are 4 joints commonly affected by gout?
- First MTP
- Ankle
- Wrist
- Knee
What can repeated acute episodes of gout lead to?
can damage the joints resulting in a more chronic joint problem
What are 6 radiological features of gout?
- Joint effusion is an early sign
- Well-defined ‘punched-out’ erosions with sclerotic margins in a juxta-articular distribution, often with overhanging edges
- Relative preservation of joint space until late disease
- Eccentric erosions
- No periarticular osteopenia (in contrast to rheumatoid arthritis)
- Soft tissue tophi may be seen
What is gout and what is its cause?
form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium
caused by chronic hyperuricaemia (uric acid >0.45 mmol/L)
What are 3 groups of causes of gout?
- Decreased excretion of uric acid
- Increased production of uric acid
- Lesch Nyhan syndrome
What are 3 situations when there is decreased excretion of uric acid?
- Drugs: diuretics, pyrazinamide, low-dose aspirin
- Chronic kidney disease/ renal failure
- Alcohol
- Lead toxicity
- Pre-eclampsia
What are 6 conditions where there is increased production of uric acid?
- Myeloproliferative/lymphoproliferative disorder
- Cytotoxic drugs
- Severe psoriasis
- Exercise
- Diet rich in purines
- Lesch-Nyhan disease
What is Lesch Nyhan syndrome?
Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency; inherited in x-linked recessive fashion
What is the inheritance pattern of Lesch-Nyhan syndrome?
x-linked recessive therefore only seen in boys
What are 5 features of Lesch-Nyhan syndrome?
- Gout
- Renal failure
- Neurological deficits
- Learning difficulties
- Self-mutilation
What is the first line management of acute gout?
- NSAIDs or colchicine
If the first line treatment of gout involves NSAIDs how should they be prescribed?
maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled
gastroprotection (e.g. a proton pump inhibitor) may also be indicated
What is the onset of colchicine to treat acute episodes of gout like?
slower onset of action
What is the main side effect of colchicine?
diarrhoea
What medication can be considered to treat gout if NSAIDs and colchicine are contraindicated?
oral steroids: dose of prednisolone 15mg/day usually used
another option is intra-articular steroid injection
What should be done is a patient is being treated for an acute episode of gout but is already taking allopurinol?
allopurinol should be continued
What is another name for the maintenance therapy sometimes used in gout?
urate-lowering therapy
When is urate-lowering therapy indicated in gout?
all patients after their first attack of gout
What are 7 situations when urate-lowering therapy is particularly recommended?
- 2 or more attacks in 12 months
- Tophi
- Chronic gouty arthritis
- Renal disease
- Uric acid renal stones
- Prophylaxis if on cytotoxics or diuretics
- Young age of onset
What is the first-line urate-lowering therapy?
allopurinol
What is thought about the timing of starting urate-lowering therapy?
used to think you shouldn’t start until 2 weeks after acute attack as starting too early may precipitate further attack, but this evidence now looks weak
delay in starting still supported - better to make long-term drug decisions while not in pain, so best delayed until inflammation has settled at ULT is better discussed when the patient is not in pain
What is the dosing of allopurinol that is used for urate-lowering therapy?
initial dose of 100mg od with dose titrated every few weeks to aim for serum uric acid of <300 µmol/l
What is the aim for serum uric acid levels with gout urate-lowering therapy?
<300 µmol/l
When should you give lower initial doses of allopurinol for ULT?
if patient has a reduced eGFR
What should be given alongside allopurinol when started for ULT?
colchicine cover should be considered
NSAIDs can be used if colchicine cannot be tolerated
this may need to be continued for 6 months
What is the second line ULT when allopurinol is not tolerated or is ineffective?
febuxostat (also a xanthine oxidase inhibitor)
What are 2 agents that may be tried for ULT to treat refractory cases of gout?
- Uricase (urate oxidase) - enzyme that catalyses conversion of urate to degradation product allantoin. present in certain mammals but not humans
- Pegloticase - persistent symptomatic and severe gout; is a polyethylene glycol modified mammalian uricase, can achieve rapid control
How is pegloticase administered for refractory and severe gout?
infusion once every 2 weeks
What are 5 lifestyle modifications to manage gout?
- Reduce alcohol intake and avoid during an acute attack
- Lose weight if obese
- Avoid food high in purines e.g. liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products
- Considerstopping precipitating drugs e.g. thiazides
- Increased vitamin C intake
Which particularly anti-hypertensive should you consider starting in patients with gout and why?
Losartan - specific uricosuric action
What investigations are usually required for gout?
no initial investigations are required when managing people with typical gout-like symptoms - clinical diagnosis (history and examination), other than ruling out septic arthritis if indicated
What are the 3 phases that the natural history of gout can occur in?
- Long period of asymptomatic hyperuricaemia
- Period during which acute attacks of gouty arthritis are followed by variable intervals (months to years) when there are no symptoms
- Final period of chronic tophaceous gout, where people have nodules affecting joints
What group of patients is gout more common in?
men and older people
What can gout in a period younger than 30 years of age suggest?
renal or enzymatic disorders, often associated with genetic causes
What are 3 diseases that gout is an independent risk factor for?
- Chronic kidney disease
- Myocardial infarction
- Cardiovascular disease mortality
How long will attacks of gout usually subside within?
1-2 weeks
How can a definitive diagnosis of gout be made, if it were to be performed?
synovial fluid analysis (not practical in primary care)
needle-shaped, negatively birefringent crystals
What are 7 situations when you should seek diagnosis from a specialist for gout?
- Diagnosis is uncertain
- Underlying systemic illness
- Gout occurs during pregnancy or in a person under 30 years of age
- Persistent symptoms despite treatment
- ULT required but allopurinol and febuxostat not tolerated/contraindicated or inadequate in lowering serum uric acid levels to target
- Complications are present
- Person is at risk of averse effects of drug treatment
What score is available to help diagnosis gout?
Acute gout diagnois sscore
What is pseudogout?
form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the synovium
What are 5 risk factors for pseudogout?
- Haemochromatosis
- Hyperparathyroidism
- Acromegaly
- Low magnesium, low phosphate
- Wilson’s disease
What are 3 joints most commonly affected by pseudogout (CPPD deposition)?
- Knee
- Wrist
- Shoulders
What will joint aspiration show in pseudogout?
weakly positive birefringent rhomboid-shaped crystals
What will an x-ray show in pseudogout?
chondrocalcinosis; in knee this can be seen as linear calcifications of the meniscus and articular cartilage
What are 3 aspects of management of pseudogout?
- Aspiration of joint fluid to exclude septic arthritis
- NSAIDs OR
- Intra-articular, intra-musscular or oral steroids as for gout
What is the method of action of allopurinol?
inhibits xanthine oxidase
What are 3 adverse effects of allopurinol?
- Severe cutaneous adverse reaction (SCAR)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Stevens-Johnson syndrome
What are 3 ethnic groups are increased risks of dermatological reactions from allopurinol?
Chinese, Korean, Thai
What shoult patients at high risk of severe cutaneous adverse reaction be screened for?
HLA-B *5801 allele
What are 3 drugs that allopurinol interacts with?
- Azathioprine - can lead to high levels of 6-mercaptopurine in combination, so need to reduce dose/ avoid combo
- Cyclophosphamide - allopurinol reduces its renal clearance, can cause marrow toxicity
- Theophylline - allopurinol increases plasma concentration by inhibiting its breakdown
