> Table of Contents > Gout
Ryan B. Feeney, PharmD
Michael C. Barros, PharmD, BCPS, BCACP
Paul N. Williams, MD, FACP
image BASICS
  • Gout is an inflammatory arthritis related to a hyperuricemia (serum uric acid [SUA] level >6.8 mg/dL) (1).
  • Acute gouty arthritis can affect ≥1 joints; the first metatarsophalangeal joint is most commonly involved at presentation (podagra).
  • Although hyperuricemia is necessary for the development of gout, it is not the only determining factor.
  • Characterized by deposition of monosodium urate (MSU) crystals that accumulate in joints and soft tissues, resulting in acute and chronic arthritis, soft-tissue masses called tophi, urate nephropathy, and uric acid nephrolithiasis
  • After an initial flare, a second flare occurs in ˜60% of patients within 1 year and 78% within 2 years of the initial attack (2).
  • Management involves treating acute attacks and preventing recurrent disease by long-term reduction of SUA levels through pharmacology and lifestyle adjustments
Annual incidence of gout (3):
  • Uric acid 7 to 8.9 mg/dL is 0.5%.
  • Uric acid >9 mg/dL is 4.5%.
  • Increasing prevalence over the past decades (3)
  • 2007 to 2008 prevalence of gout in the United States (3)
    • Men 5.8% (6.1 million)
    • Women 2.0% (2.2 million)
  • 2008 prevalence of hyperuricemia in the United States (3)
    • Men 21.2% (SUA >7.0 mg/dL)
    • Women 21.6% (SUA >5.7 mg/dL)
  • Hyperuricemia results from urate overproduction, underexcretion, or often a combination of the two.
  • Gout occurs when MSU, a product of purine metabolism, precipitates out of solution and accumulates in joints and soft tissues.
  • Transient changes in urate solubility caused by local temperature decrease, trauma, or acidosis may lead to an acute gouty attack.
  • Urate crystals that precipitate trigger an immune response.
  • Left untreated, this crystal deposition leads to permanent joint damage and tophus formation.
  • Phosphoribosyl pyrophosphate (PRPP) deficiency and hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) deficiency (Lesch-Nyhan syndrome) are inherited enzyme defects associated with overproduction of uric acid.
  • Polymorphisms in the URAT1 and SLC 2A9 (GLUT9) renal transporters are hereditary enzyme defects resulting in primary underexcretion of uric acid.
  • Age >40 years
  • Male gender
  • Increased purine uptake (meats and seafood)
  • Alcohol intake (especially beer)
  • High fructose intake
  • Obesity
  • Hyperuricemia
  • Congestive heart failure
  • Coronary artery disease
  • Dyslipidemia
  • Renal disease
  • Organ transplant
  • Hypertension
  • Hyperinsulinemia
  • Metabolic syndrome
  • Diabetes mellitus
  • Urate-elevating medications:
    • Thiazide diuretics: ethambutol
    • Loop diuretics (less of a risk vs. thiazides)
    • Niacin
    • Calcineurin inhibitors (cyclosporine and tacrolimus)
    • Acetylsalicylic acid (not recommended in high doses)
  • Maintain optimal weight.
  • Regular exercise
  • Diet modification (purine-rich foods)
  • Reduce alcohol consumption (beer and liquor).
  • Maintain fluid intake and avoid dehydration.
  • Hypertension
  • Dyslipidemia
  • Nontraumatic joint disorders
  • Heart disease
  • Urinary tract disease
  • Diabetes mellitus
  • Metabolic syndrome
  • Obesity
  • Renal disease
  • Examine suspected joint(s) for tenderness, swelling, and range of motion (ROM).
  • Assess for presence of firm nodules known as tophi.
  • In patients with chronic gout, tophi can frequently be found in the helix of the ear, over the olacrenon process, or on the Achilles tendon.
  • Patients with untreated chronic gout can have evidence of joint inflammation and deformity.
Acute bursitis, tendonitis, septic arthritis, pseudogout (calcium pyrophosphate deposition disease), cellulitis, osteoarthritis
  • SUA (may be normal during an acute flare)
  • CBC (can see elevation of WBC during an acute gout flare)
  • Synovial fluid analysis: urate crystals (negatively birefringent under polarizing microscopy), cell count (WBC usually 2,000 to 5,000 cells/mm3); culture to rule out infection. Some guidelines suggest that gout can be diagnosed clinically without synovial fluid analysis.
  • Screen for uric acid overproduction—24-hour urinary uric acid in those patients with gout onset before the age of 25 years or had a history of urolithiasis (1)[C].
  • Radiograph is normal early in disease but can reveal
    • Swelling in acute gout
    • Periarticular erosions with periosteum overgrowth in chronic gout
  • Urate kidney stones are radiolucent and thus invisible on radiograph.
Topical ice as needed (4)[B]
  • Acute treatment
    • General principles:
      • Acute gouty arthritis attacks should be treated with pharmacologic therapy (4)[C].
      • Pharmacologic treatment should be initiated within 24 hours of acute gout attack onset (4)[C].
      • Ongoing pharmacologic urate-lowering therapy should not be interrupted during an acute gout attack (4)[C].
      • Choice of agent is based on severity of pain and the number of joints involved (4).
    • Mild/moderate gout severity (≤6 of 10 on visual analog pain scale, particularly for an attack involving only one or a few small joints or one to two large joints)
      • NSAIDs:
        • Naproxen (Naprosyn, Anaprox, Aleve): 750 mg followed by 250 mg q8h for 5 to 8 days (4)[A]
        • Indomethacin (Indocin): 50 to 150 mg/day for 2 to 7 days (4)[A]
        • Sulindac (Clinoril): 200 mg BID for 7 to 10 days (4)[A]
        • Celecoxib (Celebrex)
        • Not FDA approved but can be considered in selected patients with contraindications or intolerance to NSAIDs (4)[B].
          • Dose at 800 mg once followed by 400 mg on day 1, then 400 mg BID for 1 week (4)[B]
      • Corticosteroids
        • Those with an acute flare involving one to two large joints can consider intra-articular corticosteroids; can consider using PO corticosteroids in combination.
        • For other acute flares, use PO corticosteroids:
          • Prednisone (Sterapred): 0.5 mg/kg/day for 5 to 10 days followed by discontinuation (4)[A] or alternately 2 to 5 days at full dose followed by tapering for 7 to 10 days and then discontinuing (4)[C]
          • Methylprednisolone (Medrol) dose pack (4)[C]
          • Triamcinolone acetonide (Trivaris): 60 mg IM single dose followed by oral corticosteroids (4)[C]
      • P.423

      • Colchicine (Colcrys)
        • Used for gout attacks where the onset was <36 hours prior to treatment initiation (4)[A]
        • Begin a loading dose of 1.2 mg followed by 0.6 mg 1 hour later, followed by 0.6 mg once or twice daily 12 hours later, until the gout attack resolves (4)[C].
        • Dose reduction recommended in moderate to severe kidney disease and in those on inhibitors of cytochrome P450 3A4 and P-glycoprotein (clarithromycin, erythromycin, cyclosporine, and disulfiram) (4).
    • Severe gout (≥7 of 10 on visual analog pain scale, involving ≥4 joints with arthritis involving >1 region, or involving three separate large joints)
      • Initial combination therapy is an option and includes the use of full doses of the following (4)[C]:
        • Colchicine and NSAIDs
        • PO corticosteroids and colchicine
        • Intra-articular steroids with all other modalities
    • For patients not responding to initial pharmacologic monotherapy, add a second agent (4)[C].
  • Chronic treatment
    • Indications for pharmacologic urate-lowering therapy include any patient with
      • Tophus or tophi by clinical exam or imaging study (1)[A]
      • Frequent attacks of acute gouty arthritis (≥2 attacks/year) (1)[A]
      • Chronic kidney disease (CKD) stage 2 or worse (1)[C]
      • Past urolithiasis (1)[C]
    • Treat to the serum urate:
      • Minimum serum urate target is <6 mg/dL (1)[A].
      • Serum urate target may need to be <5 mg/dL to improve gout signs and symptoms (1)[B].
    • Urate-lowering agents can be prescribed during an acute attack provided that effective anti-inflammatory prophylaxis has been initiated prior to urate-lowering therapy (1)[C].
    • Anti-inflammatory prophylaxis required when initiating urate-lowering therapy include the following:
      • First line
        • Low-dose colchicine: 0.6 mg once or twice daily (4)[A]
        • Low-dose NSAIDs with proton pump inhibitor if indicated: naproxen 250 mg PO BID (4)[C]
      • Second line: Use of colchicine and NSAIDs both are not tolerated, contraindicated, or ineffective:
        • Low-dose prednisone or prednisolone at ≤10 mg/day (4)[C]
      • Treatment duration for the greater of
        • At least 6 months (4)[A] or
        • 3 months after achieving serum urate appropriate for the patient with no tophi on exam (4)[B], or for 6 months after achieving serum urate appropriate for the patient with ≥1 tophi on exam (4)[C]
    • Pharmacologic urate-lowering agents:
      • Allopurinol (Zyloprim): xanthine oxidase inhibitor (1)[A]
        • Starting dose should be no higher than 100 mg/day (1)[B]
        • Starting dose should be 50 mg/day in stage 4 CKD or worse
        • Gradually titrate the dose upward q2-5wk to appropriate maximum dose (1)[C]
        • Dose can be >300 mg/day, even with renal impairment, as long as accompanied by patient education and monitoring of drug toxicity; maximum FDA-approved dosage is 800 mg/day (1)[B].
        • Regularly monitor for allopurinol hypersensitivity syndrome (AHS), pruritus, rash, elevated hepatic transaminases, and eosinophilia.
        • Screening for the HLA-B*5801 allele for AHS should be performed in those of Korean descent with stage 3 CKD or worse and Han Chinese or Thai descent irrespective of renal function (1)[A].
      • Febuxostat (Uloric): selective xanthine oxidase inhibitor (1)[A]
        • No renal or hepatic adjustments needed for mild-to-moderate hepatic or renal impairment
        • Starting dose 40 mg/day; may be titrated to 80 mg/day
        • In select instances, may dose up to 120 mg/day (not FDA approved) (1)[A]
      • Probenecid: uricosuric agent (1)[B]
        • Alternative first line urate-lowering therapy; use if at least one xanthine oxidase inhibitor is contraindicated or not tolerated (1)[B].
        • May be used in addition to allopurinol or febuxostat if serum urate target not achieved
        • Multiple drug interactions exist, as well as risk of urolithiasis with this agent.
        • Not recommended if creatinine clearance (CrCl) is <50 or with patient history of urolithiasis (1)[C].
        • Starting dose is 250 mg BID; gradually titrate to 2,000 mg/day
  • Other treatment
    • Acute treatment: adrenocorticotropic hormone (ACTH): 25 to 40 IU SC (4)[A]; especially in those NPO
    • Pegloticase in select severe instances (1)
Large tophi that are infected or interfering with joint motion may need to be surgically removed.
Patient Monitoring
  • SUA q2-5wk while titrating urate-lowering treatment to goal (1)[C]
  • Regularly monitor CBC, renal function, liver function test, and urinalysis.
  • General lack of evidence regarding specific recommendations, although the American College of Rheumatology has outlined the following (1)[C]:
  • General measures:
    • Weight loss for obese patients
    • Healthy overall diet
    • Exercise
    • Smoking cessation
    • Stay well hydrated
  • Avoid
    • Organ meats high in purine content (sweetbreads, liver, kidney) (1)[A]
    • High-fructose corn syrup-sweetened sodas, other beverages, or foods
    • Alcohol overuse (>2 servings per day for men and >1 serving per day for women) (1)[A]
    • Any alcohol use in gout during periods of frequent gout attacks or advanced gout under poor control
  • Limit
    • Serving sizes of beef, lamb, pork, and seafood with high purine content such as sardines and shellfish (1)[B]
    • Servings of naturally sweetened fruit juices
    • Table sugar and sweetened beverages and desserts
    • Table salt, including in sauces and gravies
    • Alcohol (particularly beer) in all gout patients (1)[B]
  • Encourage
    • Low-fat or nonfat dairy products
    • Vegetables
  • Dietary and lifestyle modifications (1)[B]
  • Patient instructions on initiating treatment on signs and symptoms of an acute gout attack without the need to consult health care provider for each attack (1)[B]
  • Discussion that gout is caused by excess uric acid and that effective urate-lowering therapy is essential treatment (1)[B]
Gout can usually be successfully managed with proper treatment.
1. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64(10):1431-1446.
2. Doghramji PP. Managing your patient with gout: a review of treatment options. Postgrad Med. 2011;123(3):56-71.
3. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10): 3136-3141.
4. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res. 2012;64(10):1447-1461.
  • M10.9 Gout, unspecified
  • M10.00 Idiopathic gout, unspecified site
  • M10.30 Gout due to renal impairment, unspecified site
Clinical Pearls
  • MSU crystals found in synovial fluid aspirate are pathognomonic for gout.
  • Acute gout and sepsis can coexist.
  • Asymptomatic hyperuricemia does not require treatment.
  • Losartan possesses uricosuric properties, therefore it may be an excellent agent if patient is hypertensive.