Gout

Pathophysiology:

· inflammatory arthritis caused by deposition of monosodium urate crystals in synovial fluid and other tissues (ie. tophi)

· associated with hyperuricemia

· ddx of acute gout includes other crystal-induced arthritides (e.g., calcium pyrophosphate dihydrate) and a septic joint

Epidemiology/risk factors:

· More common in men than women

· Prevalence increases with age

· Comorbid conditions: HTN, insulin resistance, metabolic synd, CKD, CHF and organ transplant

· Associated meds: thiazide diuretics, cyclosporine, low dose ASA

· Dietary associations: increased intake of dietary purines (particularly meat and seafood), ethanol (especially beer and spirits), soft drinks, and fructose

Triggers for acute flares:

· Recent diuretic use

· Etoh

· Hospitalization

· Surgery

· Initiation of a urate lowering drug (“mobilizes urate stores”)

Acute treatment:

· NSAIDs: naproxen, indomethacin

o Avoid in: the usual, renal insuff, CHF, bleeding d/o etc.

· Colchicine: 1.2mg po x1, followed by 0.6mg po one hour later

o Avoid or reduce dose: in renal insuff, liver dysfunction: avoid use with CYP3A4 drugs, such as cyclosporine, clarithromycin, etc.

· Oral corticosteroids: 30-60mg po daily x 2 days, then gradually reduce over 10 days

o Caution in: pts with hyperglycemia, CHF

· Intraarticular corticosteroids: usually 40mg of depo medrol (depending on the joint)

o Avoid in: pts with serious concern for septic arthritis

· IL-1 antagonists: newer agents, $$, (anakinra, rilonacept, canakinumab)

Prophylaxis: consists of urate-lowering therapy (ULT) and flare prophylaxis while initiating ULT

Urate lowering therapy:

· Xanthine Oxidase inhibitors: block the synthesis of uric acid during purine metabolism; can be used regardless of whether there is overproduction of urate or underexcretion

o Allopurinol: avg daily dose is 300mg, but often need higher doses

§ Caution with renal insuff, several drug-drug interactions including azathioprine, 6-mp, warfarin. Hypersensitivity syndrome is rare, but can be fatal, more common with higher doses

o Febuxostat: starting dose is 40mg daily

§ Can be used in pts with mild-mod renal insufficiency; use in pts with intolerance or poor response to allopurino

· Uricosurics: blocks renal tubular urate reabsorption. Can be used in patients with underexcretion of urate (up to 90% of patients with gout), but are used less frequently than XO inhibitors and are contraindicated in patients with h/o nephrolithiasis

o Probenecid: starting dose is 250mg daily

§ Avoid with CrCl <30, h/o nephrolithiasis

· Uricase agents: uricase is a non-human mammalian enzyme that converts uric acid into soluble allantoin (rasburicase is similar and used in TLS)

o Pegloticase, a pegylated modified porcine recombinant uricase (used only in chronic refractory cases of gout)

§ Administered IV; significant rates of infusion reactions

Flare Prophylaxis: (advised during first 6 months of ULT)

· Colchicines 0.6mg once or twice daily

· NSAIDs daily

(Victoria Kelly MD, 4/19/11)