Gout is a common form of inflammatory arthritis that occurs due to accumulation of urate crystals. Uric acid is the byproduct of purine catabolism and the level depends on dietary purines, endogenous purine synthesis and excretion by kidneys and intestine. Gout has four stages: 1) asymptomatic gout; 2) acute gout; 3) intercritical gout (period of dormancy between gout attacks); and 4) chronic gout, which is the most common in patients who do not receive treatment for their disease.1
In gout, 90% of first attacks affect one joint, mostly the first metatarsophalangeal joint, although it can affect ankles, knees and midfoot. Gout is about 1-5% in developed countries and prevalence is up to 10% in some ethnic groups such as Taiwanese Aborigines, Pacific Islanders and Maori.
Most patients with gout have ≥ 1 comorbidities. About 93% had ≥ 1 associated disease such as hypertriglyceridemia, obesity, hypertension, hyperglycemia, diabetes and CKD.
Risk factors are hypertension, poor kidney function, consumption of alcohol, high-protein diet such as red meat, seafood, sugar-sweetened beverages (fructose rapidly increases serum urate level), using drugs such as cyclosporine, tacrolimus, ACEI, ARBs (other than losartan, which increases uric acid excretion), beta-blockers, diuretics, niacin, and baby aspirin.
Complications are pain, poly-articular flares, chronic gouty arthritis, joint destruction, carpal tunnel syndrome and renal disease.
Acute management of gout include colchicine, NSAIDS and corticosteroids.
Lower doses of colchicine (initial dose of 1.2 mg followed by 0.6 mg after one hour) showed to be as effective as higher doses (1.2 mg followed by 0.6 mg/h for six hours) for reducing pain and have fewer stomach side effects such as diarrhea. Other side effects of colchicine are nausea, vomiting, cramps, pain and sometimes headache and fatigue.
NSAIDS, including naproxen, indomethacin, and sulindac, are all equally effective. The main side effects of NSAIDs are gastrointestinal, from indigestion to ulcers, and bleeding. Acute renal injury can happen with long-term use of NSAIDS.
Corticosteroids such as prednisone 30-50mg per day taper over seven to 10 days. Steroids can be used orally, intra-articularly, if more than one joint is involved and if patients are unable to take oral medications, or intramuscularly. Adverse effects of long-term use of corticosteroids are mood disorders, elevation of blood glucose levels, fluid retention and immune suppression.
Urate-lowering treatments (ULT) to prevent recurrence of gout, such as allopurinol and febuxostat, decrease production of uric acid. In patients who experience two or more attacks per year, using ULT is indicated. To minimize occurrence of acute attack, ULT should be started with a low dose at least three weeks after the last attack. The goal of starting ULTs is to reach a serum uric acid concentration of >6 mg/dL, and preferably > 5 mg/dL, if signs and symptoms of gout continue.
If patients cannot tolerate the side effects of allopurinol, febuxostat can be used instead.
The most common side effects of febuxostat are diarrhea, abdominal pain and musculoskeletal pain.
Probenecid is also a urate-lowering medication that decreases urate levels by increasing the renal clearance of uric acid. It should be started at a low dose after the acute attack. Probenecid is indicated for people > 60-years-old and normal renal function and in those who are not overproducers of uric acid. Side effects include gastro-intestinal irritation and rash. ULTs do not reduce the risk of attacks within the first six months. Preventative therapy during ULT using low-dose colchicine or low-dose NSAIDs for more than eight weeks is suggested to prevent acute gout flares.
If other agents besides diuretics can be used to control blood pressure, it is advisable to avoid diuretics, especially if the patient has gout attacks with high serum uric acid level. The American College of Rheumatology guidelines will not suggest discontinuing low-dose aspirin used for cardiovascular prevention in patients with gout, since aspirin’s effect on increasing serum uric acid is trivial.
Among blood pressure medications, losartan has uricosuric properties, which can help to lower blood pressure as well as serum uric acid when combined with ULT medications such as allopurinol.
Non-pharmacological interventions are ice application on the affected joints; decreasing consumption of meat, seafood and alcohol; reevaluating the use of diuretics, niacin and low-dose aspirin; exercise; weight loss; and consumption of low-fat or nonfat dairy products, which are shown to have urate-lowering effects.
