Referral of the month - gout
Dr Rakhi Seth, consultant rheumatologist, advises on managing this case of frequent acute gout.
Thank you for seeing this 66-year-old man to help with both the acute management and prevention of his gout.
He’s had classical episodes of gout affecting his big toe for years, but these have been increasing in frequency to the point that he is now suffering one attack every few weeks. His latest uric acid level, taken between episodes, was 580micromol/L.
His management is complicated by his comorbidity, medication and intolerances.
Of most significance is his history of cardiac failure, CKD, duodenal ulcer and atrial fibrillation. He is on the usual combination of cardiac failure drugs, including furosemide. He is also on warfarin and a PPI.gm
In terms of his acute attacks, our options are very limited. NSAIDs are contraindicated in view of his warfarin – and would not be ideal anyway given his CKD and previous duodenal ulcer. We have tried colchicine but this proved ineffective. We have also given him prednisolone, but this caused severe dyspepsia, despite his ongoing PPI.
In terms of prophylaxis, we did start allopurinol – with simple analgesic cover - but this caused a rash and had to be withdrawn.
So we have reached something of a therapeutic impasse, both in terms of the acute attacks and prevention. I appreciate that it might help to reduce or stop his diuretic, but doing so inevitably results in a worsening of his cardiac failure.
Thanks for your expert advice.
Thank you for referring this gentleman with gout for advice on how best to manage his condition.
Firstly, in terms of this gentleman’s acute gout attacks, it is important to treat them as soon as they occur. During an acute attack, it is helpful to rest, elevate and cool (with ice packs) the affected joint or joints, in addition to commencing appropriate treatment. I agree that in terms of acute attacks, NSAIDs are contraindicated in view of his warfarin, chronic renal impairment and previous duodenal ulcer.
I understand that colchicine proved ineffective for him. It would be helpful to know what dose he was started on and for how long it was continued? I recommend colchicine at a dose of 500mcg twice daily for an acute attack of gout given his chronic renal impairment – if mild to moderate.
I would also recommend an up to date blood test to check his renal function in order to ensure he is on the correct dose of colchicine, if appropriate, and that we also review a complete list of his medications to avoid any potential drug interactions.
Colchicine is contraindicated in patients with eGFR <10ml/min/1.73m2 and doses should be reduced in patients with eGFR 10-50ml/min/1.73m2, and in the elderly. Colchicine should be used cautiously in patients receiving statins (which I suspect he may be on given his history of cardiac failure), particularly given his renal impairment, as there are case reports of myopathy and rhabdomyolysis following combined use of colchicine and statins.
It also appears that a course of oral steroids in this gentleman caused severe dyspepsia, despite treatment with a PPI, and so I agree that oral steroids are best avoided in this case.
Another highly effective option to treat an acute attack is to aspirate the affected joint and then to inject it with a corticosteroid. Not only will this help confirm the diagnosis of gout through the analysis of synovial fluid for uric acid crystals, it will also help exclude concurrent infection; and treat the affected joint promptly. Alternatively a single injection of an intramuscular corticosteroid is an option in patients like this gentleman in whom NSAIDs, colchicine or oral steroids are contraindicated, ineffective, or poorly tolerated.
In this gentleman where response to monotherapy with colchicine appears to have been insufficient, combinations of treatment can be used such as colchicine with intra-articular or intramuscular steroid.
Another option to treat an acute attack effectively is to use an IL-1 inhibitor such as canakinumab, anakinra or rilonacept, however these are not currently approved by NICE.
Secondly we should address modifications of his lifestyle and his risk factors. I understand that he is on diuretics including furosemide to treat his cardiac failure, in which case this treatment clearly needs to be continued. When diuretics are being used to treat hypertension however, it is helpful to consider an alternative antihypertensive while ensuring blood pressure is controlled.
I have not received his complete medication list yet, however if he is on an ACE inhibitor for his hypertension or cardiac failure then I would consider switching this to losartan, which has a uricosuric effect. Similarly, although fenofibrate should not be used as a primary urate-lowering treatment (ULT), it may be considered as an adjunct as it also has a uricosuric effect.
All patients with gout should be given appropriate information about the causes and consequences of gout and hyperuricaemia, how to manage acute attacks, lifestyle advice about diet and alcohol consumption and obesity. It will be helpful to address these factors in more detail when we review him in clinic.
I recommend a well-balanced diet low in fat and added sugars and high in vegetables and fibre. I would encourage including skimmed milk, low fat yogurt and cherries in his diet. I also suggest keeping well-hydrated with water, particularly in patients with gout and a history or urolithiasis.
I strongly recommend avoiding alcohol, sugar-sweetened drinks containing fructose, purine-rich foods such as red-meat and offal (e.g. beef, kidney, liver and sweetbreads), oily fish (e.g. anchovies, herring, mackerel and sardines) and foods rich in yeast extracts (e.g. Marmite, Bovril, Vegemite).
I suggest screening for cardiovascular risk factors such as smoking, hypertension, diabetes mellitus, dyslipidaemia, obesity and renal disease, given his history, and that these are managed appropriately.
Thirdly, let’s discuss treatment with ULT to target urate levels, taking into account his hyperuricaemia at 580micromol/L, and previous intolerance to allopurinol, which I understand caused a rash so was withdrawn.
ULT is advised in this gentleman with gout, particularly given his renal impairment (eGFR <60ml/min), and diuretic treatment. It is also advised in patients with gout who have tophi, chronic gouty arthritis, joint damage, urolithiasis and in those who develop primary gout at young age.
ULT aims to reduce and maintain the serum uric acid (sUA) level at or below a target level of 300umol/L to prevent urate crystal formation and to dissolve away existing crystals.
Although allopurinol is the recommended first line ULT to consider in gout, I understand that this gentleman developed a rash on it and so it was withdrawn. In this case I would avoid reintroducing it. It is worth mentioning that in renal impairment, I recommend starting allopurinol at a lower dose of 50mg once daily and titrating up slowly, aiming to achieve the target sUA of 300umol/L, while monitoring renal function. It is also worth remembering that allopurinol and warfarin can interact, so monitoring the INR is important in these circumstances.
An alternative ULT is febuxostat, which is also a xanthine-oxidase inhibitor and may be used in patients in whom allopurinol is not tolerated. I recommend starting at a dose of 80mg daily and if necessary increasing after four weeks to 120mg daily to achieve therapeutic target. Febuxostat should, however, be avoided in patients with ischaemic heart disease or congestive cardiac failure, so may be best avoided in this gentleman.
Another option for ULT that may be an option for this gentleman however is a uricosuric agent such as sulfinpyrazone, probenecid or benzbromarone. These can be used in patients who are resistant to or intolerant of xanthine-oxidase inhibitors, and out of these three uricosuric agents, benzbromarone (50-200mg/day) can be used in patients with mild to moderate renal impairment.
Once an appropriate ULT has been commenced, it should be continued during an acute attack, while treating the acute attack effectively as discussed.
Finally, I recommend flare prophylaxis with colchicine 500mcg once or twice daily, in this gentleman while initiating an appropriate ULT, and this may be continued for up to six months. NSAIDs with PPI cover may also be used as flare prophylaxis in the absence of a contraindication.
In summary, I think we can help effectively manage this gentleman’s gout in order to prevent further acute attacks of gout, while taking into account his significant comorbidities, medications and intolerances.
Dr Rakhi Seth
- Gout is the most common inflammatory arthritis and lifestyle modification and risk factors should be addressed such as avoidance of alcohol and purine-rich foods.
- Acute attacks of gout should be treated promptly with NSAIDs, colchicine, or steroids (PO, IA, IM), or a combination of these treatments, taking into account patients comorbidities, potential medication interactions and previous intolerances.
- ULT should be offered to all patients with gout, aiming for a serum uric acid level of 300umol/L while monitoring their renal function.
- Flare prophlyaxis with NSAIDs, or colchicine should be started when initiating a ULT, and be continued for up to six months, again taking into account comorbidities and intolerances, and monitoring where required.
Dr Rakhi Seth is a consultant rheumatologist at University Hospital Southampton NHS Foundation Trust