Treatment of Gout (Acute and Chronic)

Gout is an important topic for all 3 USMLE steps. Below is a summary of key potential facts that may be questioned in these exams with regards to the treatment of Gout.

Treatment of Acute Attacks of Gout

-First the diagnosis should be confirmed. Septic arthritis has the potential to look exactly like gout, hence the initial step is always arthrocentesis unless the patient has a known diagnosis.

-Next step is pain management. Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and ACTH are the mainstays of treatment. Co-existent health conditions determine which drugs are used. For example renal failure may contraindicate use of certain NSAIDS.

-When comorbidities limit the use of NSAIDs or colchicine, intra-articular steroid injection may be indicated.

-One must remember that control of the underlying hyperuricemia is contraindicated until the acute attack is controlled as it may intensify and prolong the attack. However if the patient is already on allopurinol or probenecid, they should be continued.

Medications for acute gout:

Nonsteroidal anti-inflammatory drugs
NSAIDs are the first drugs of choice in most patients (typically indomethacin is used except in elderly because of CNS adverse effects). Contraindications to NSAIDS use include peptic ulcer disease or GI bleeding, renal failure, abnormal liver function and patients on warfarin (selective COX-2 inhibitors like celecoxib can be used). Additional caution in needed for those patients who are on ACE inhibitors as both ACE inhibitors and NSAIDS can decrease the GFR. NSAIDS are given at full dose for about 4-5 days and then dose is gradually decreased.


Colchicine
Colchicine is a mitotic inhibitor and has now become a second line treatment because of risk of adverse effects. To be effective colchicine therapy must be initiated within 24 hours of onset of the acute attack. Common adverse effects include diarrhea and vomiting, in 80% of patients. A number of dosing regimens are proposed with recent recommendations favoring lower doses with a maximum of 2.5 mg/24 hours and 6 mg over 4 days. Contraindication to colchicine include severe renal insufficiency (GFR less than 10 mL/min), hepatic dysfunction and biliary obstruction.

Colchicine is one agent that can be used in acute gout as well as for Gout prophylaxis (0.6mg BID). Myopathy is an important side effect of chronic colchicine therapy.

Corticosteroids
Corticosteroids can be given to patients with gout who cannot use NSAIDs or colchicine, but ACTH is generally preferred over steroids.

Treatment of Chronic Gout

-Firstly attempt should be made at avoiding the use of medications that elevate uric acid. For example thiazides should be avoided and losartan should be considered in stead. (Losartan is uricosuric at 50 mg/day doses). If the patient has tophaceous disease, probenecid should not be used.

-Probenecid (uricosuric agent) and allopurinol (decrease production of uric acid) are the two main drugs used. Probenecid is preferred by some.

-Patients with very high uric acid excretion will benefit from Allopurinol. It is also the drug of choice in patients with existing renal disease.

Medications for chronic gout:


Probenecid 
Probenecid inhibits tubular reabsorption of uric acid. Some physicians recommend alkalizing the urine when starting probenecid to reduce the risk for renal stone formation. All patients should be advised to drink plenty of liquids (>2L a day).


Allopurinol
Allopurinol is xanthine oxidase inhibitor and thus reduces the generation of uric acid. Therefore, it should be used in patients who overproduce uric acid (also used in patients at risk of tumor lysis syndrome). Common side effects include dyspepsia, headache, diarrhea, and rash. Allopurinol hypersensitivity is a wellknown but rare complication with high mortality. Allopurinol is also associated with the drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. For these reasons Allopurinol should be discontinued in patients who develop a rash.


Febuxostat
Febuxostat is a newer nonpurine selective inhibitor of xanthine oxidase, and is a potential alternative to allopurinol.


Other treatments:


Rasburicase
Rasburicase is an extremely potent (and expensive) drug that can metabolize uric acid into soluble substances. It is used in treatment of tumor lysis syndrome. It is very prone to causing allergic reaction and its role in treatment of gout is not clear.


Diet and Activity
Foods very high in purines include hearts, sweetbreads (eg, pancreas, thymus), smelt, sardines, mussels, anchovies, trout, haddock, scallops, mutton, veal, liver, bacon, salmon, kidneys, and turkey. These should be avoided as much as possible. Patients with gout should limit alcohol as it can precipitate gout. This is especially true for beer and hard alcohol but mild-moderate wine drinking is well tolerated by most.

Increasing dairy intake, folic acid intake, and coffee consumption may reduce gout flares. Weight reduction in patients who are obese can improve hyperuricemia.