A 56 y/o patient presents with an acutely inflamed great toe, suspicious for gout. The medical student examines and concurs with the diagnosis of gout. The patient is diabetic with slight renal insufficiency (CrCl ~ 40 ml/min). His labs are normal except for an elevated serum uric acid (9.1 mg/dL). The only meds the patient is currently on is metformin. The student wants to treat the patient with oral colchicine.

Do you concur or not? Why or why not? What other options might be considered for the acute and chronic gout?

Colchicine may be an option as well as some other agents discussed below. Let's first briefly discuss the pathophysiology of gout and hyperuricemia.

Pathophysiology - uric acid is a breakdown product of purines. Purines are usually from increased dietary intake, conversion of DNA purines to uric acid after treatment with chemotherapeutic drugs, and/or synthesis of purine bases in the body. A patient can be an overproducer of uric acid or an underexcreter of uric acid. Some patients may be unfortunate enough to have both processes. Ethanol (esp beer) can promote gout by both mechanisms. This determination may affect your treatment.

Aspiration of the affect joint usually confirms the diagnosis. However, getting a patient to consent to a joint aspiration in a joint so exquisitely painful that even a sheet on top of the joint causes severe pain can be difficult. Microscopic examination of aspirated fluid with polarized light can detect uric acid crystals (needle shaped crystals). Colchicine, besides being therapeutic, can also serve as a diagnostic tool. Importantly, joint aspiration and microscopic joint fluid examination can also rule out pseudogout, septic joints, etc.

Some drugs can induce hyperuricemia/gout. The list includes: aspirin/salicylates (< 2 grams/day), ethanol, diuretics, niacin, PZA, L-DOPA, cytotoxic drugs, etc. Evaluate the patient for use of these drugs and evaluate if these agents might be discontinued.

Patients can be underexcretors or overproducers of uric acid as mentioned earlier. Certain pharmacological agents can increase excretion of uric acid (uricosuric agents) and some will decrease production.

Acute therapy is targeted at relief of pain vice reduction of uric acid levels. Colchicine is a mainstay of acute gout treatment. Oral and IV forms are available. Oral is most commonly used. Usual starting dose is 1mg to start, then 0.5 mg po every 2 hours until either symptoms resolve, abdominal pain/diarrhea ensues, or a total dose of 8mg is reached. Incidence of GI side effects is high (50-80%). IV colchicines may avoid some of the GI side effects. In patients with renal insufficiency, the dose should be cut in half.

NSAIDs - can also be used first line. Some authors have suggested an NSAID (usually indomethacin) is the drug of choice for acute gout. Acute GI toxicity is less than with colchicine. GI bleeding and ulceration is less likely with short-term use. NSAIDs are also renal toxic. Use with caution is patients with renal compromise, ulcer disease, etc. Probably all NSAIDs are effective in treating acute gout. There's no evidence that one NSAID (indomethacin, naproxen, ibuprofen) is any better than another for acute gout.

ACTH - can be used to treat acute gout. 40-80 u IM every 6-8 hours for 2-3 days is a common dose with stepwise reduction in dose. Intra-articular steroids have also been used. Oral prednisone 30-60mg a day for 3-5 days has also been used.

Chronic treatment - if an underexcretor - probenecid or sulfinpyrazone are uricosuric agents, which improve renal uric acid excretion. Urinary alkalinization and maintenance of adequate hydration are useful adjuncts. Probenecid is not effective in patients when Cr Cl < 30-50 ml/min. Main side effects of these agents are GI and rash. Probenecid can impair renal secretion of some drugs, esp weak organic acids (penicillins, cephalosporins, furosemide, etc).

Overproducers should use allopurinol, a xanthine oxidase inhibitor. This should only be started after the acute attack is treated and over. Allopurinol can cause a flare of disease by liberating tissue stores of urate. Allopurinol should be adjusted for renal function. Usual dose is 300mg/day. The dose is adjust based on CrCl - 10-20 ml/min - 200mg QD, <10ml/day - 100mg ever 1-2 days, < 3 ml/min - 100mg at 'extended intervals'. Goal of therapy is a serum uric acid level of < 6 mg/dL. Main side effects of allopurinol are rash and LFT elevation.