Gout Flashcards
Gout - Uric acid
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricaemia (uric acid > 450 µmol/l)
Gout - Acute Mx
Acute management
- NSAIDs
- intra-articular steroid injection
- colchicine* has a slower onset of action. The main side-effect is diarrhoea
- oral steroids may be considered if NSAIDs and colchicine are contraindicated. A dose of prednisolone 15mg/day is usually used
- if the patient is already taking allopurinol it should be continued
*inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
ALLOPURINOL - Indications
Indications for allopurinol:
- recurrent attacks - the British Society for Rheumatology - recommend ‘In uncomplicated gout uric acid lowering drug therapy should be started if a second attack, or further attacks occur within 1 year’
- tophi
- renal disease
- uric acid renal stones
- prophylaxis if on cytotoxics or diuretics
NB: patients with Lesch-Nyhan syndrome often take allopurinol for life
Gout Mx - Allopurinol Prophylaxis
Allopurinol prophylaxis:
- Allopurinol should not be started until 2 weeks after an acute attack has settled as it may precipitate a further attack if started too early
- Initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 300 µmol/l
- NSAID or colchicine cover should be used when starting allopurinol
Gout - Lifestyle Modifications
Lifestyle modifications
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 product
Gout - Mx - Other Points
Other points
losartan has a specific uricosuric action and may be particularly suitable for the many patients who have coexistant hypertension
calcium channel blockers also increase uric acid levels, possibly by a renal vasodilatory effect
increased vitamin C intake (either supplements or through normal diet) may also decrease serum uric acid levels
Gout - Mx if intolerant to Allopurinol?
Febuxostat is recommended as an option for the management of chronic hyperuricaemia in gout only for patients who are intolerant of allopurinol or for whom allopurinol is contra-indicated. For the purposes of this guidance, intolerance of allopurinol is defined as adverse effects that are sufficiently severe to warrant discontinuation, or to prevent full dose escalation for optimal effectiveness.
Watch out for severe hypersensitivity reactions (including Stevens-Johnson) with febuxostat, which would be a reason to discontinue this agent
Gout - Key Features
Gout is a form of inflammatory arthritis. Patients typically have episodes lasting several days when their gout flares and are often symptom free between episodes. The acute episodes typically develop maximal intensity with 12 hours/ The main features it presents with are:
pain: this is often very significant
swelling
erythema
Gout - Joints affected
Around 50% of first presentations affect the 1st metatarsophalangeal (MTP) joint. Attacks of gout affecting this area where historically called podogra. Other commonly affected joints include:
ankle
wrist
knee
If untreated repeated acute episodes of gout can damage the joints resulting in a more chronic joint problem.
Gout - Radiological Features
Radiological features of gout include:
joint effusion is an early sign
well-defined ‘punched-out’ erosions with sclerotic margins ina juxta-articular distribution, often with overhanging edges
relative preservation of joint space until late disease
eccentric erosions
no periarticular osteopaenia (in contrast to rheumatoid arthritis)
soft tissue tophi may be seen
NB: Even if you are not familiar with the x-ray changes associated with gout the presence of changes around the first metatarsophalangeal should immediately make you think of gout.
Gout - Diagnosis - Example Question
A 60-year-old man is referred to the rheumatology clinic with progressive pains in his hands. His past medical history includes hypertension for which he takes ramipril and indapamide. The referral letter includes the following bloods taken during a recent flare:
CRP 54 mg/l
Rheumatoid factor negative
Adj calcium 2.51 mmol/l
An x-ray is taken:
SEE PASSMED GOUT HAND X-RAYS
What is the most likely diagnosis?
Metastatic prostate cancer Rheumatoid arthritis Osteoarthritis Gout Primary hyperparathryoidism
The x-ray shows multiple periarticular erosions bilaterally with adjacent large soft tissue masses and relatively preserved joint spaces. In the right hand, these findings are most prominent at the 1st interphalangeal, 2nd-4th proximal interphalangeal, 1st-3rd metacarpohalangeal and carpometacarpal joints. In the left hand, the findings are most prominent at the ulnar styloid, scapholunate joint, first and fifth carpometacarpal joints, second and fifth metacarpophalangeal joints and 1st interphalangeal joint. These findings are consistent with gout.
Indapamide is a risk factor for gout.
A normal calcium goes against primary hyperparathyroidism.
Pseudogout and Haemachromatosis
Pseudogout secondary to calcium pyrophosphate crystal deposition in large joints is a well-known complication of haemochromatosis
Example:
A 45-year-old Caucasian man presents with an acutely painful left knee. He is unable to mobilise due to the pain and swelling. Prior to this episode, the patient states that he is generally active, often enjoying a round of golf every Sunday. Last week he had a minor fall onto both knees whilst clearing out the garage. He puts his current symptoms down to general aches and pain of ‘old age’.
The patient has also noticed that he is waking up more often in the night to pass urine. His wife has noticed that he is looking more ‘tanned’ despite them not going abroad on holiday this year. On further questioning, he admits to drinking 5-6 pints of ale per week. He is a non-smoker.
On examination on the Medical Assessment Unit you note significant left sided knee swelling. The joint is hot and tender to touch. There is no evidence of any surrounding skin changes.
His random glucose is measured at 18mmol/L.
Further blood tests are shown below:
Hb 138 g/l
Platelets 120 * 109/l
WBC 7.0 * 109/l
Na+ 138 mmol/l K+ 4.0 mmol/l Urea 6.2 mmol/l Creatinine 88 µmol/l CRP 72 mg/L
What is the most likely cause of his acutely swollen knee?
> Pseudogout Ruptured Baker's cyst Septic arthritis Gout Haemarthrosis
This gentleman presents with arthralgia, polyuria and skin colour changes. These symptoms in a gentleman of this age and ethnicity suggest hereditary haemochromatosis. Polyuria and significantly elevated random blood glucose suggest diabetes.
Acute Gout Mx when NSAIDs and colchicine are CI/not tolerated - Example Question
A 55-year-old man is referred to rheumatology for management of severe tophaceous gout. The patient had been experiencing intermittent gout attacks over the previous few years, typically affecting the first metatarsophalangeal joints of both feet. However, during the last two months the patient had developed inflammation of multiple small joints of his hand preventing the patient from continuing his work as a train driver. A trial of Colchicine prescribed by the patient’s General Practitioner had been discontinued after the patient experienced severe diarrhoea. Past medical history included an upper GI bleed secondary to a duodenal ulcer six months previously.
Examination demonstrated severe asymmetrical inflammation of multiple metacarpalphalangeal, distal interphalangeal and proximal interphalangeal joints across both hands. Yellow-white tophi were present across the inflamed joints. Blood tests taken prior to clinic attendance are listed below.
Hb 15.2 g/dl
Platelets 265 * 109/l
WBC 6.5 * 109/l
Na+ 134 mmol/l K+ 4.2 mmol/l Urea 9.5 mmol/l Creatinine 175 µmol/l eGFR 62 ml/min Urate 370 µmol/l
What is the best treatment for this patient’s acute gout?
Intra-articular steroid injection Naproxen Allopurinol Febuxostat > Short course prednisolone
The best option in this case is a short course of oral prednisolone (30 mg daily for five days). Two randomised controlled trials have shown this treatment to have a similar efficacy compared to NSAIDs. Intra-articular steroid injection is felt to be an effective treatment for acute gout affecting large joints, but is less appropriate for treatment of multiple small joints of the hands. Naproxen would be contra-indicated in this case due to the history of peptic ulceration and renal impairment.
Allopurinol and Febuxostat are both used to lower serum urate levels as part of gout prophylaxis and have no role in the treatment of an acute attack.
Gout Mx: Febuxostat
Febuxostat is a non-purine xanthine oxidase inhibitor approved by NICE for use in individuals, such as this patient, who are intolerant of allopurinol or in whom allopurinol is contra-indicated.
Urate lowering therapy is indicated in recurrent attacks of acute gout, although there are no firm guidelines as to when to initiate therapy. Target serum uric acid levels are usually taken as less than 360 micromol / L.
Gout Mx in patients intolerant of Allopurinol: Example Question
A 65-year-old man was referred to rheumatology for advice regarding the management of his gout. The patient had suffered intermittent episodes of inflammation of the first metatarsophalangeal joint of both feet over the past ten years. The frequency of these episodes had been increasing, with 6 episodes in the past year. In addition, the patient’s right knee had recently become inflamed with microscopy of synovial aspirate demonstrating needle shaped crystals with negative birefringence.
Colchicine and NSAIDs had been used effectively to provide symptomatic relief to the patient during an acute attack. Allopurinol had been previously trialled as prophylaxis at a dose of 200 mg daily, although was stopped after the patient’s renal function was noted to have deteriorated after allopurinol was initiated. Lifestyle modifications have also been attempted.
Other medical problems included type 2 diabetes, hypertension, hypercholesterolaemia and chronic renal failure. Regular medications were ramipril, metformin and simvastatin.
On examination the patient was noted to be obese without evidence of current joint inflammation. Tophi were noted on examination of the patient’s ears. Blood tests taken prior to clinic attendance are listed below.
Hb 16.5 g/dl
Platelets 150 * 109/l
WBC 8.6 * 109/l
Na+ 137 mmol/l K+ 4.7 mmol/l Urea 11.2 mmol/l Creatinine 190 µmol/l eGFR 45 ml/min Calcium (adjusted) 2.3 mmol/l Urate 395 µmol/l
What is the best strategy for gout prophylaxis in this patient?
Prednisolone 10 mg daily Colchicine > Febuxostat Naproxen Reduced dose allopurinol
Urate lowering therapy is indicated in recurrent attacks of acute gout, although there are no firm guidelines as to when to initiate therapy. Target serum uric acid levels are usually taken as less than 360 micromol / L. Febuxostat is a non-purine xanthine oxidase inhibitor approved by NICE for use in individuals, such as this patient, who are intolerant of allopurinol or in whom allopurinol is contra-indicated.
Prednisolone, colchicine and naproxen are all used in the acute treatment of gout. Extended use of colchicine and NSAIDs can be considered to reduce the risk of gout relapse during the instigation of allopurinol therapy but have no role as prophylactic therapy in isolation.
Allopurinol can cause renal, hepatic and severe skin reactions (allopurinol hypersensitivity syndrome) and is best avoided in this patient given previous worsening of renal function with a relatively low dose of allopurinol.
