GOUT
Definition
Gout is a metabolic disease most often affecting middle-aged to elderly men and postmenopausal women.
It is the result of an increased body pool of urate with hyperuricemia.
It is typically characterized by episodic acute and chronic arthritis, due to deposition of MSU (monosodium urate) crystals in joints and connective tissue tophi, and the risk for deposition in kidney interstitium or uric acid nephrolithiasis
Etiology
Several events may precipitate acute gouty arthritis:
Dietary excess
Trauma
Surgery
Excessive ethanol ingestion
Hypouricemic therapy
Serious medical illnesses such as myocardial infarction and stroke
Epidemiology
Women represent only 5–20% of all patients with gout.
Premenopausal gout is rare; it is seen mostly in individuals with a strong family history of gout.
Kindreds of precocious gout in young females caused by decreased renal urate clearance and renal insufficiency have been described.
Most women with gouty arthritis are postmenopausal and elderly, have osteoarthritis and arterial hypertension causing mild renal insufficiency, and are usually receiving diuretics
Clinical features (Acute and Chronic Arthritis)
Acute arthritis is the most frequent early clinical manifestation of gout.
Usually, only one joint is affected initially, but polyarticular acute gout can occur in subsequent episodes.
The metatarsophalangeal joint of the first toe is often involved, but tarsal joints, ankles, and knees are also commonly affected.
Especially in elderly patients or in advanced disease, finger joints may be involved.
Inflamed Heberden's or Bouchard's nodes may be a first manifestation of gouty arthritis.
The first episode of acute gouty arthritis frequently begins at night with dramatic joint pain and swelling.
Joints rapidly become warm, red, and tender, with a clinical appearance that often mimics cellulitis.
Early attacks tend to subside spontaneously within 3–10 days, and most patients have intervals of varying length with no residual symptoms until the next episode.
After many acute mono- or oligoarticular attacks, a proportion of gouty patients may present with a chronic nonsymmetric synovitis, causing potential confusion with rheumatoid arthritis
Less commonly, chronic gouty arthritis will be the only manifestation and, more rarely, the disease will manifest only as periarticular tophaceous deposits in the absence of synovitis.
Investigations
Even if the clinical appearance strongly suggests gout, the diagnosis should be confirmed by needle aspiration of acutely or chronically involved joints or tophaceous deposits.
Acute septic arthritis, several of the other crystalline-associated arthropathies, palindromic rheumatism, and psoriatic arthritis may present with similar clinical features.
During acute gouty attacks, strongly birefringent needle-shaped MSU crystals with negative elongation are typically seen both intracellularly and extracellularly
Synovial fluid cell counts are elevated from 2000 to 60,000/L.
Effusions appear cloudy due to the increased numbers of leukocytes.
Large amounts of crystals occasionally produce a thick pasty or chalky joint fluid.
Bacterial infection can coexist with urate crystals in synovial fluid; if there is any suspicion of septic arthritis, joint fluid must also be cultured
Serum uric acid levels can be normal or low at the time of the acute attack, as inflammatory cytokines can be uricosuric and effective initiation of hypouricemic therapy can precipitate attacks.
This limits the value of serum uric acid determinations for the diagnosis of gout.
Nevertheless, serum urate levels are almost always elevated at some time and are important to use to follow the course of hypouricemic therapy.
A 24-h urine collection for uric acid can, in some cases, be useful in assessing the risk of stones, in elucidating overproduction or underexcretion of uric acid, and in deciding if it might be appropriate to use a uricosuric therapy
Excretion of >800 mg of uric acid per 24 h on a regular diet suggests that causes of overproduction of purine should be considered.
Urinalysis, serum creatinine, hemoglobin, white blood cell (WBC) count, liver function tests, and serum lipids should be obtained because of possible pathologic sequelae of gout and other associated diseases requiring treatment, and as baselines because of possible adverse effects of gout treatment
Treatment
Acute Gouty Arthritis
The mainstay of treatment during an acute attack is the administration of anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or glucocorticoids.
NSAIDs are most often used in individuals without complicating comorbid conditions.
Both colchicine and NSAIDs may be poorly tolerated and dangerous in the elderly and in the presence of renal insufficiency and gastrointestinal disorders.
In attacks involving one or two joints, intraarticular glucocorticoid injections may be preferable and effective.
Ice pack applications and rest of the involved joints can be helpful.
Colchicine given orally is a traditional and effective treatment, if used early in the attack.
One to two 0.6-mg tablets can be given every 6–8 h over several days with subsequent tapering.
This is generally better tolerated than the formerly advised hourly regimen.
The drug must be stopped promptly at the first sign of loose stools, and symptomatic treatment must be given for the diarrhea.
Intravenous colchicine is occasionally used, e.g., as pre- or postoperative prophylaxis in 1- to 2-mg doses when patients cannot take medications orally.
Life-threatening colchicine toxicity and sudden death have been described with the administration of >4 mg/d IV.
The IV colchicine should be given slowly through an established venous line over 10 min in a soluset.
The total dose should never exceed 4 mg.
NSAIDs given in full anti-inflammatory doses are effective in ~90% of patients, and the resolution of signs and symptoms usually occurs in 5–8 days.
The most effective drugs are any of those with a short half-life and include indomethacin, 25–50 mg tid; ibuprofen, 800 mg tid; or diclofenac, 50 mg tid.
Oral glucocorticoids such as prednisone, 30–50 mg/d as the initial dose and gradually tapered with the resolution of the attack can be effective in polyarticular gout.
For single or few involved joints intraarticular triamcinolone acetonide, 20–40 mg, or methylprednisolone, 25–50 mg, have been effective and well tolerated.
Adrenocorticotropic hormone (ACTH) as an intramuscular injection of 40–80 IU in a single dose or every 12 h for 1–2 days can be effective in patients with acute polyarticular refractory gout or in those with a contraindication for using colchicine or NSAIDs
Hypouricemic Therapy
Ultimate control of gout requires correction of the basic underlying defect, the hyperuricemia.
Attempts to normalize serum uric acid to <300–360 mol/L (5.0–6.0 mg/dL) to prevent recurrent gouty attacks and eliminate tophaceous deposits entail a commitment to long-term hypouricemic regimens and medications that generally are required for life.
Hypouricemic therapy should be considered when, as in most patients, the hyperuricemia cannot be corrected by simple means (control of body weight, low-purine diet, increase in liquid intake, limitation of ethanol use, and avoidance of diuretics).
The decision to initiate hypouricemic therapy is usually made taking into consideration the number of acute attacks (urate lowering may be cost effective after two attacks), serum uric acid levels [progression is more rapid in patients with serum uric acid >535 mol/L (>9.0 mg/dL)], patient's willingness to commit to lifelong therapy, or presence of uric acid stones.
Urate-lowering therapy should be initiated in any patient who already has tophi or chronic gouty arthritis.
Uricosuric agents, such as probenecid, can be used in patients with good renal function who underexcrete uric acid, with <600 mg in a 24-h urine sample.
Urine volume must be maintained by ingestion of 1500 mL of water every day.
Probenecid can be started at a dosage of 250 mg twice daily and increased gradually as needed up to 3 g in order to maintain a serum uric acid level <300 mol/L (5 mg/dL).
Probenecid is generally not effective in patients with serum creatinine levels of >177 mol/L (2.0 mg/dL).
These patients may require allopurinol or benzbromarone (not available in the United States).
The latter is another uricosuric drug that is more effective in patients with renal failure.
Recent reports have identified that losartan, fenofibrate, and amlodipine have some mild uricosuric effects.
The xanthine oxidase inhibitor allopurinol is by far the most commonly used hypouricemic agent and is the best drug to lower serum urate in overproducers, urate stone formers, and patients with renal disease.
It can be given in a single morning dose, 100–300 mg initially and increasing up to 800 mg if needed.
In patients with chronic renal disease, the initial allopurinol dosage should be lower and adjusted depending on the serum creatinine concentration; for example, with a creatinine clearance of 10 mL/min, one would generally use 100 mg every other day.
Doses can gradually be increased to reach the target urate level; however, more studies are needed to provide exact guidance.
Patients with frequent acute attacks may also require lower initial doses to prevent exacerbations.
Toxicity of allopurinol has been recognized increasingly in patients with renal failure who use thiazide diuretics and in those patients allergic to penicillin and ampicillin.
The most serious side effects include skin rash with progression to life-threatening toxic epidermal necrolysis, systemic vasculitis, bone marrow suppression, granulomatous hepatitis, and renal failure.
Patients with mild cutaneous reactions to allopurinol can reconsider the use of a uricosuric agent or undergo an attempt at desensitization to allopurinol.
They can also pay increased attention to diet and should be aware of new alternative agents under investigation
Urate-lowering drugs are generally not initiated during acute attacks but after the patient is stable and low-dose colchicine has been initiated to decrease the risk of flares that often occur with urate lowering.
Colchicine prophylaxis in doses of 0.6 mg one to two times daily is usually continued, along with the hypouricemic therapy, until the patient is normouricemic and without gouty attacks for 6 months or as long as tophi are present.
New urate-lowering drugs undergoing investigation include a PEGylated uricase and a new specific xanthine oxidase inhibitor, febuxostat