What is gout?

Gout is a metabolic disease (fairly common) which generally affect middle-aged to elderly men and postmenopausal women. It is due to an increased body pool of uric acid with hyperuricemia (high uric acid level in blood). It is characterized by episodic acute and chronic arthritis (joint inflammation and pain), due to deposition of monosodium urate crystals in joints and connective tissue known as tophi, and the risk for deposition in kidney interstitium to form kidney stones of uric acid (uric acid nephrolithiasis).

What are the clinical symptoms of gout?

Symptoms of acute gout and chronic gout may be different from each other.

Symptoms of acute gout:

The most common and early clinical presentation of gout is acute arthritis, which affect only single joint initially, but later on many joints may be involved. The most commonly involved joint (in initial episode of arthritis) is metatarsophalangeal joint of the first toe, but other joints like tarsal joints, ankles, and knee joints are also commonly involved. Finger joints may be involved, especially in elderly persons and in advanced disease. The first episode of acute gouty arthritis generally begins at night with severe joint pain and swelling of the involved joint, which become warm, red, and tender very rapidly (can mimic cellulites sometimes). Sometimes inflamed Heberden's or Bouchard's nodes may be a first episode of gouty arthritis. The initial attack of arthritis generally subside in less than a week time, some of the patients may have intervals of varying length with no symptoms whatsoever in intervals, only to return in the next episode.

Symptoms of chronic gout:

The symptoms of chronic gout (chronic non-symmetric synovitis) appears after several episodes of acute (single or multiple joints may be involved) attacks, which may be confused with that of rheumatoid arthritis. Sometimes chronic gouty arthritis may be the only manifestation without any acute episode and rarely tophaceous (monosodium urate crystals in joints and connective tissue) deposits in the absence of synovitis.

Gout is much less common in females than in males. Of all cases of gout women constitute less than one fifth of total (with range of 5-20%). Gout in premenopausal women is rare. Gout is seen in women, only with strong family history of gout. Gout is seen only in elderly and postmenopausal women, who generally also have osteoarthritis and high blood pressure.

What factors can precipitate gout?

The factors that can precipitate gout are excess intake of food (especially foods with high purine content), trauma, surgery, excessive intake of alcohol, hypouricemic (drugs causing high uric acid level in blood) therapy, and serious medical illnesses such as myocardial infarction and stroke.

How gout is diagnosed?

Gout is generally suspected strongly by clinical symptoms, but even if strongly suspected gout should always be confirmed, because acute septic arthritis, many other crystalline-associated arthropathies, rheumatism, and psoriatic arthritis may present with similar clinical features. Diagnosis of gout can be confirmed by needle aspiration of acutely or chronically involved joints or tophaceous deposits and demonstration of strongly birefringent needle-shaped MSU (monosodium urate) crystals. These crystals are seen both intracellularly and extracellularly during acute attacks of gout. The cell count of synovial fluid is elevated from normal of 2,000 to 60,000/microliter. The synovial fluid is cloudy due to presence of white blood cells and sometimes it may be thick pasty or chalky due to presence of large number of crystals. There may also be bacterial infection in the joint (septic arthritis) and when suspected it should be confirmed by culture of the synovial fluid.

Sometimes it may be possible to demonstrate MSU (monosodium urate) crystals in the metatarsophalangeal joint of big toe and also in in knees not acutely involved with gout. Arthrocentesis of these joints is a useful technique to establish the diagnosis of gout between attacks. Arthrocentesis of these joints can help to establish the diagnosis of gout between attacks.

Contrary to the popular belief serum uric acid levels are of little diagnostic importance as serum uric acid levels may be normal or low (as inflammatory mediators like cytokines can be uricosuric and initiation of hypouricemic therapy during acute stage can precipitate attacks of gout) during time of acute attack of gout. But estimation of serum uric acid levels can be used to follow the course of hypouricemic treatment and its effectiveness. In some cases, estimation of 24 hour urine for uric acid can assess the risk of stones, in elucidating overproduction or under-excretion of uric acid, and in deciding if it might be appropriate to use a uricosuric therapy. Excretion of more than 800 mg of uric acid in 24 hours with normal diet suggests the patient is over-producer of uric acid (and purine) and use of uricosuric therapy may be beneficial.

Serum creatinine, hemoglobin, white blood cell (WBC) count (both total count and differential count), liver function tests, and serum lipid profile and urine analysis should be done to determine the pathologic sequelae of gout and also to determine the side effects of therapy of gout.

What is the role of radiography (X-ray) in gout?

X-ray is not helpful in diagnosis of gout; it can establish the extent of pathological changes due to gout. There are cystic changes, well-defined erosions with sclerotic margins often with overhanging bony edges, and soft tissue masses are characteristic radiographic features of advanced and chronic tophaceous (presence of gouty nodules ‘tophi’) gout.

How to treat gout?

The treatment of acute gout is different from that of chronic gout.

Treatment of acute attacks (acute gouty arthritis) of gout:

The mainstay of treatment of acute gouty attack is use of anti-inflammatory drugs such as NSAIDs (nonsteroidal anti-inflammatory drugs), colchicine, or glucocorticoids. If there is no other complication NSAIDs are the most commonly used drugs. NSAIDs as well as colchicines may not be tolerated well by elderly patients, especially in presence of renal insufficiency and gastrointestinal disorders like ulcer. In acute attacks involving one joint (or two at the most) intraarticular (directly inside the joint) glucocorticoid injections may be used effectively and sometimes preferred. Rest to the affected joint and ice packs can be used as general measure. Colchicine (one to two tablets of 0.6 mg are given 3-4 times a day for several days and gradually tapered) is very effective (used traditionally) in aborting acute attacks of gout if used early in the attack. Colchicine must be stopped at the first sign of loose stool and symptomatic treatment for diarrhea started. Intravenous colchicine is only given as preoperative or postoperative prophylaxis at the dose of 1-2 mg with an established venous line slowly (over 10 minutes). The dose of intravenous colchicine should never exceed 4 mg per day as there are incidences of life threatening colchicine toxicity and sudden death if dose is more than 4 mg per day.

NSAIDs are very effective (effective in approximately 90% patients) if used at the anti-inflammatory doses. The signs and symptoms usually subside in 5–8 days, especially with short acting NSAIDs like indomethacin (25-50 mg three times a day), diclofenac (50 mg three times a day) and ibuprofen (800 mg three times a day). NSAIDs with short half life are more effective than long half life. Oral glucocorticoids (like prednisone, 30–50 mg/day and tapered over time as the signs and symptoms improve) are used, especially if more joints are involved. For single joint (or only a few joints) involvement the glucocorticoids used are intraarticular triamcinolone acetonide, 20–40 mg, or methylprednisolone, 25–50 mg (intraarticular use can be more effective with lesser side effects). In refractory gout or if colchicine or NSAIDs are contraindicated, intramuscular injection of 40–80 IU of adrenocorticotropic hormone (ACTH) as a single dose or every 12 hourly for 1–2 days can be very effective.

Treatment of chronic gout:

The ultimate aim of treatment of chronic gout is correction of the underlying defect, which is hyperuricemia (high uric acid level in blood). The main goal of treatment of chronic gout is to bring serum uric acid level to below 5-6 mg per 100 ml, which is essential to prevent recurrent gouty attacks and eliminate tophaceous deposits. The treatment is generally life long and need commitment from patient’s side. Hypouricemic treatment should only be considered if general measures (control of body weight with daily regular exercise, consumption of low-purine diet, increase in liquid intake, limiting alcohol consumption, and avoidance of diuretics as diuretics are generally hyperuricemic) can not control or correct hyperuricemia. Before deciding to initiate hypouricemic treatment the number of acute attacks (hypouricemic therapy may be cost effective after two attacks), serum uric acid levels (progression is more rapid in patients with serum uric acid 9.0 mg/100 ml), patient's willingness to commit to lifelong therapy, and presence of uric acid stones should be considered. In presence of tophi or chronic gouty arthritis hypouricemic therapy should be initiated straight away.

Uricosuric (excrete uric acid through urine) agents, such as probenecid, can be used in patients with good renal function who underexcrete uric acid, with less than 600 mg in a 24-hour urine sample. Urine volume should be maintained by drinking of 1500 ml of water every day to prevent uric acid crystal deposition in urinary bladder. The dose of probenecid is 250 mg twice daily initially and increased as needed gradually up to 3 gram per day to maintain a serum uric acid level less than 5 mg/100 ml. if serum creatinine levels is more than 2.0 mg/100 ml probenecid is generally not effective and require allopurinol or benzbromarone (an uricosuric drug effective in renal insufficiency, but not available in many countries including United States) for treatment. Losartan, fenofibrate, and amlodipine also have some mild uricosuric effects but not commonly used in gout.

The most commonly used hypouricemic drug and is the best drug to lower serum urate in overproducers, uric acid stone formers, and patients with renal disease is allopurinol a xanthine oxidase inhibitor drug. The dose of allopurinol is 100-300 mg as a single morning dose and increased gradually up to 800 mg per day if needed. In renal failure or renal insufficiency patients the initial dose of allopurinol should be lower and adjusted depending on the serum creatinine concentration (e.g. with a creatinine clearance of 10 ml/minute, generally 100 mg of allopurinol is used on alternate days) and dose gradually increased to achieve the target uric acid level. Patients with frequent attacks also need small initial dose of allopurinol.

Side effects of allopurinol are more common in patients with renal failure who also use thiazide diuretics and in patients who are allergic to penicillin and ampicillin. The most serious side effects of allopurinol are skin rash (which may progression to life-threatening toxic epidermal necrolysis), systemic vasculitis, bone marrow suppression, granulomatous hepatitis, and renal failure. Some patients may have mild cutaneous reactions to allopurinol and they should consider the use of a uricosuric agent (like probenecid) or attempt desensitization to allopurinol. They can also pay increased attention to diet and should be aware of new alternative agents under investigation (see below). Urate-lowering drugs (like allopurinol) are usually not given during acute attacks (given after the patient is stable) and low-dose colchicine should be initiated to decrease the risk of precipitation of attack of gout seen after lowering uric acid. Colchicine prophylaxis (in the dose of 0.6 mg one to two times daily) is usually continued, along with the hypouricemic therapy, until the patient is normouricemic (normal uric acid level) or without gouty attacks for 6 months or as long as tophi are present.

N.B. Febuxostat (a specific xanthine oxidase inhibitor) is under investigation and development.