Who Should Receive Prophylaxis for Gout?

December 26, 2006

A 70 year old male, former alcoholic, with a past history of gout diagnosed by joint aspiration, presents with his second episode of right 1st metatarsal erythema, swelling and severe pain in the last 6 months.

Commentary By Pamela Rosenthal, MD Assistant Professor of Medicine, Division of Rheumatology


Question 1. Is there any specific rule you follow when deciding to start someone on colchicine prophylaxis? e.g. >x # episodes in 1 year. 


Gout prophalaxis is guided by the frequency and intensity of gouty attacks.  It's a clinical decision.  A rare attack that is easily treated with NSAIDS (or, in some patients, colchicine or steroids) may not require prophalaxis, whereas attacks that occur +/- 3 times a year and are associated with debilitating discomfort often do.  Low dose daily colchicine is generally well tolerated, whereas frequent gout attacks are not.  Low dose colchicine can be associated with gastrointestinal side effects particulary in patients with renal failure or with neuromyopathies. In fact, dosing of prophylactic colchicine should be adjusted for GFR.


Please remember high purine diets and alcohol consumption (beer is worst, wine is the best), as well as obesity contribute to gout attack risk.  These are all life style factors that can be modified. Also, while diuretics are excellent first-line agents  for hypertension, their use typically results in increased serum urate levels.  Physicians treating hypertension should typically consider alternative therapies in their patients with troublesome gout.


Question 2: Should you start allopurinol before or after starting colchicine?   Do you use the serum uric acid level to guide you?


While this topic is somewhat controversial, it is probably not necessary to use allopurinol (or an alternative urate-lowering agent, see below) for patients whose gouty attacks are well-controlled on daily colchicine and have no contraindications to its use.

Pharmacologic urate-lowering therapy is indicated when:

  • Daily or BID colchicine is not adequate to control attacks 
  • Tophi are present (colchicine will not reduce tophi)
  • X-rays demonstrate gouty erosions (essentially, tophi in bone)
  • The patient had renal stones (kidney tophi), or urinary uric acid > 1100mg/day putting a patient at increased risk for renal stones
  • Serum uric acid >12mg/dl – although this is a relative indication (at the present time, we don't generally treat hyperuricemia in patients without gout or uric acid kidney stones)
  • The patient's gout is affecting their kidney function,  as in gouty nephropathy

Allopurinol is the main stay of antihyperuricemic therapy.  It can treat hyperurecemia regardless of etiology and is typically a once daily medication.  Nonetheless, drug reactions associated with allopurinol, especially rashes can be extremely problematic, and Stevens-johnson may rarely occur.  Febuxostat is a newer xanthine-oxidase inhibitor that may soon have FDA approval.  Uricase, a recombinant protein that our species is missing, making us gout susceptible, is available to treat tumor lysis syndrome. In contrast to alloprinol, Probenecid stimulates the renal excretion of uric acid.  It is very effective in a group of patients with a normal GFR who nonetheless under-excrete uric acid (< 800mg uric acid IN A 24 urine ncollection).  However it is a TID medication and requies copious fluid intake to avoid kidney stones, and most patients don't like the bother. 


Urate lowering therapy should always be initiated after first placing the patient on a stable regimen of colchicine.  While a lowered urate is desirable in the long run, in the short run it can actually induce attacks as insoluble urate crystals get released from pre-existing stores.  The target urate concentration depends upon the patient.  In a patient whom you are just trying to reduce attacks, a level of about 6.0 should suffice.  However, if you need to actually reduce the body burden of deposited urate (ex, tophi), a lower level (perhaps in the 4-5 range) will do so, much more effectively.          

Question 3: Does anyone really do 24 hr urines anymore to determine whether the person is an over-excretor or under-producer?  Likewise is there ever a role for probenecid? 

Per the above, most gout therapy is empiric.  However a 24 hour urine collection for uric acid level would be helpful in a circumstance when a person was allopurinol intolerant and a question arose regarding the possible merit of probenecid.  If a patient turned out to be an under-excretor, Probenecid would be the right approach


Question 4. I just admitted a patient with gout on allopurinol and colchicine, for an unrelated problem.  What should i do about his gout meds? 

Generally, leave them alone.  Prophylactic gout medications are in place as long-term therapies and anything you do, whether holding colchicine or allopurinol, or increasing allopurinol, may put the patient at risk for attacks  (and necessitate the delayed process of restarting the meds). Of course, if the patient is at risk, or having a direct toxicity to one of these medications, they will need to be discontinued.   If you have any questions about this management, call rheumatology; we will be happy to provide input.  


A decision tree model from Uptodate (subscription required)