II. Epidemiology

  1. Men and post-menopausal women more commonly affected
    1. Estrogen is protective pre-Menopause by increasing Uric Acid excretion
  2. Prevalence: 2% of men over age 30 and women over age 50 years
    1. Increasing Prevalence in United States related to Obesity and aging population
    2. Affects 8 million in United States (most common inflammatory Arthropathy)
    3. Prevalence increases with age (affects 12% of those over age 80 years old)
    4. Black patients have a higher Prevalence
  3. Incidence of gout attacks
    1. Uric Acid 7 to 8.9 mg/dl: 0.5% annual Incidence
    2. Uric Acid >9 mg/dl: 4.5% annual Incidence

III. Pathophysiology

  1. See Uric Acid
  2. See Hyperuricemia
  3. Isolated and asymptomatic Hyperuricemia is common and requires no treatment
    1. Elevated levels are common, and most Hyperuricemia will not result in gout or other adverse effects
  4. Gout occurs when Uric Acid levels exceed solubility limits
    1. Monosodium urate crystals deposit in joints, Kidney, and soft tissues
    2. Crystal deposition triggers a inflammatory response from cytokines and Neutrophils
    3. Joint space is irreversibly injured with ongoing attacks

IV. Risk Factors

  1. Most common
    1. Obesity
    2. Alcohol use (especially beer)
    3. High purine diet (red meats, turkey and wild game, organ meats, seafood)
    4. Drinks sweetened with high fructose corn syrup
    5. Diuretic therapy including Thiazide Diuretics
  2. Other risks
    1. Diabetes Mellitus
    2. Hyperlipidemia
    3. Hypertension
    4. Atherosclerosis
    5. Renal Insufficiency
    6. Myeloproliferative disease

V. Causes: Triggers for acute gout attacks

  1. See Hyperuricemia
  2. See Risk Factors above
  3. Recent increase in Alcohol or purine intake
  4. Medication use (Allopurinol stopped or started, Diuretic or Chemotherapy started)
  5. Acute infection
  6. Intravenous Contrast dye exposure

VI. Presentations

  1. Monoarthritis (most common)
  2. Acute Bursitis
  3. Tenosynovitis
  4. Acute polyarticular gout

VII. Symptoms

  1. Associated Symptoms
    1. Chills
    2. Fever as high as 104 F (40 C)
  2. Severity: Very severe pain
    1. Unable to bear weight
    2. Too painful to put on socks
    3. Intollerant to light touch from blankets
  3. Regions Lower extremities
    1. First Metatarsophalangeal joint of great toe (most common)
      1. Known as Podagra
      2. Affected in 50% of first gout attacks
    2. Mid-tarsal joints
    3. Ankle Joints
    4. Knee Joints
  4. Regions upper extremities
    1. Fingers
    2. Wrists
    3. Elbows
  5. Characteristics: Joint Pain
    1. Excruciating, crushing type pain
  6. Timing: Joint Pain
    1. Acute onset of lower extremity Joint Pain, typically peaking in the first 24 hours
    2. Wakens patient from sleep

VIII. Signs

  1. Acute
    1. Joint Inflammation
      1. Erythema, tenderness and swelling at affected joint
      2. Pain extends well beyond joint
        1. Entire foot involved in some cases
      3. Asymmetric joint involvement
        1. May only involve one side with the first attack
    2. Skin over joint is tense and shiny
  2. Chronic
    1. Gouty Tophi (develop after 10 years)
      1. Subcutaneous Nodules of monosodium urate crystals and lipids, proteins and mucopolysaccharides
    2. Chronic Arthritis
      1. Chronic deposition occurs with recurrent attacks

IX. Labs

  1. Complete Blood Count
    1. Leukocytosis (may be as high as 40,000 wbc/mm3)
  2. Serum Uric Acid increased
    1. Hyperuricemia (typically defined as serum Uric Acid >6.8 mg/dl)
    2. Normal Uric Acid does not exclude gout
      1. Often normal Uric Acid levels during an acute gout flare
  3. Synovial Fluid Exam (critical if Septic Arthritis is considered)
    1. Polarizing Light Microscopy
      1. Negatively birefringent
      2. Needle shaped Uric Acid crystals
    2. Gram Stain and Culture
      1. Rule out Septic Arthritis
  4. Urine Uric Acid (24 hour collection)

X. Imaging

  1. Xray of affected joint shows asymmetric swelling

XI. Diagnosis: Requires one of the following

  1. Monosodium urate crystals in Synovial Fluid or
    1. Test Sensitivity: 84%
    2. Test Specificity: 100%
  2. Gouty Tophi with urate crystals identified on Nodule aspirate or
    1. Test Sensitivity: 30%
    2. Test Specificity: 99%
  3. Minimum of 6 criteria present from the following list
    1. Plain radiograph demonstrates subcortical cysts without erosions
    2. Plain radiograph demonstrates asymmetric swelling within a joint
      1. Test Sensitivity: 42%
      2. Test Specificity: 90%
    3. First metatarsophalangeal joint tender or swollen
      1. Test Sensitivity: 96%
      2. Test Specificity: 97%
    4. Hyperuricemia
      1. Test Sensitivity: 92%
      2. Test Specificity: 91%
    5. Unilateral first metatarsophalangeal joint Arthritis
    6. Unilateral tarsal joint Arthritis
    7. Inflammation peaked within one day
    8. Monoarthritis episode
    9. More than one acute Arthritis attack
    10. Effected joints with overlying redness
    11. Gouty Tophi suspected (but not yet confirmed by aspirate)
    12. Synovial Fluid culture negative for organisms during an Acute Monoarthritis attack
  4. References
    1. Wallace (1977) Arthritis Rheum 20(3): 895-900 [PubMed]

XII. Differential Diagnosis

  1. Septic Arthritis
    1. Critical to distinguish!
    2. Concurrent infection with gout history may occur (esp. knee, and to lesser extent in ankle, Shoulder, wrist)
  2. Pseudogout (calcium pyrophosphate deposition disease)
    1. Differentiate from gout based on Joint Fluid analysis
  3. Trauma
    1. Trauma may also precipitate a gout flare
  4. Other conditions
    1. Cellulitis
    2. Reactive Arthritis
    3. Rheumatoid Arthritis
    4. Osteoarthritis
    5. Neuropathic Arthritis (Charcot Joint)

XIII. Management: Acute attack

  1. NSAIDs (any are effective if adequately dosed)
    1. Avoid in elderly, renal or liver disease, Heart Failure, or Peptic Ulcer Disease
      1. In these cases, use Corticosteroids instead
    2. Indomethacin (historically has been preferred NSAID in gout)
      1. Start: 50 mg orally three times daily for 2-3 days
      2. Then: 25 mg orally three times daily for 4-10 days
    3. Naproxen 500 mg orally twice daily for 4-10 days
    4. Sulindac 200 mg orally twice daily for 4-10 days
  2. Colchicine (Colcrys)
    1. Less viable option (too expensive) now that generic preparations were removed from the market
      1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227796.htm
    2. Other disadvantages
      1. Gastrointestinal adverse effects (Nausea, Vomiting, Diarrhea) at treatment doses
      2. Avoid in severe liver or Kidney disease
      3. Requires adjusted dosing in renal disease
      4. No intrinsic Analgesic effect
    3. Consider 0.6 orally daily to twice daily taken as adjunct to NSAID (see above)
      1. Most beneficial if started within first 24 hours of attack
      2. May be ineffective if started >3-4 days after symptom onset
  3. Corticosteroids
    1. Precautions
      1. Rule-out Septic Arthritis first!
      2. Use with caution in Diabetes Mellitus
      3. Effective alternative to NSAIDs (less risk of peptic ulcer)
    2. Systemic agents
      1. Intravenous
        1. Methylprednisolone 40 mg (consider if NPO in hospital)
      2. Intramuscular
        1. Depo-Medrol 80 to 120 mg single dose IM
      3. Oral
        1. Start: Prednisone 40 mg orally daily for 5 days
        2. If persistent symptoms, continue as taper (not needed in many cases)
          1. Next: Prednisone 20 mg orally daily for 5 days
          2. Next: Prednisone 10 mg orally daily for 5 days
    3. Intra-articular Corticosteroid
      1. Large single joints and refractory cases to other treatment
  4. Avoid exacerbating or unhelpful measures
    1. See Prevention below
    2. Aspirin in small doses aggravates disorder
    3. Acetaminophen not helpful
    4. Phenylbutazone risks outweigh any benefits
      1. Bone Marrow suppression
      2. Aplastic Anemia

XIV. Prevention: Medications

  1. Contraindications
    1. Do not use in acute attack
  2. Indications
    1. Recurrent Gout
      1. Two gout attacks per year or
      2. One gout attack per year if Chronic Kidney Disease stage 2
    2. Tophaceous gout
    3. Nephrolithiasis
  3. Therapy goal
    1. Serum Uric Acid <5-6 mg/dl
  4. Xanthine Oxidase Inhibitors
    1. First-line agents for prevention
      1. Originally targeted at Uric Acid over-producers based on 24 hour Uric Acid
      2. Now used for under-excreters and over-producers
    2. Allopurinol (preferred)
      1. Dose: Start 100 mg orally daily and advance to 300 mg daily
      2. See Allopurinol for dosing guidelines, contraindications
      3. Adjusted dosing in Renal Insufficiency
      4. Genetic testing (HLA B5801) prior to use if risk of severe hypersensitivity skin reaction (Hans Chinese, Thai)
      5. See Allopurinol for initiation protocol (start with antiinflammatory agent to prevent triggering gout attack)
    3. Febuxostat (Uloric)
      1. Dose: 40 mg daily (up to 80 mg/day if Uric Acid still >6 mg/dl after 2 weeks of therapy)
      2. Contraindicated with Azathioprine (Imuran) or mercaptopurine
      3. Much more expensive than Allopurinol
  5. Other preventive agents
    1. Colchicine
      1. Dose: 0.6 mg orally daily to twice daily
    2. Pegloticase (Krystexxa)
      1. Dose: 8 mg IV every 2 weeks
      2. Indicated in severe, refractory gout (but costs $5000 per dose)
      3. Intravenous uricase with Mechanism related to Uric Acid metabolism to allantoin
    3. Probenacid
      1. Dose: 250 mg orally twice daily, gradually increased to up to 2 grams daily
      2. Originally targeted at Uric Acid under-excreted (based on 24-hour Urine Uric Acid)
        1. Now rarely used (replaced by Allopurinol used in over-production and under-excretion)
        2. May be used as adjunct to Allopurinol or febuxostat in refractory Hyperuricemia
      3. Significantly increased risk of Nephrolithiasis
        1. Maintain hydration and use Potassium citrate to prevent Nephrolithiasis
      4. Avoid in combination with Methotrexate or Ketorolac
    4. Lesinurad (Zurampic)
      1. Dose: 100 mg/day (titrated every few weeks up to max 800 mg/day)
      2. Indicated as adjunct to Allopurinol or febuxostat, for added Uric Acid control
      3. Similar to Probenacid, inhibits renal Uric Acid transporters (preventing Uric Acid reabsorption)
      4. Must be used in combination with Allopurinol or febuxostat (due to risk of renal stones, Renal Failure)
      5. Very expensive ($12/tablet) and offers little benefit over probenacid (which is one sixth of the cost)
      6. (2016) Presc Lett 23(10)
  6. Concurrently start Uric Acid lowering agents with prophylaxis, low dose for 3-6 months
    1. NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
      1. Aleve 220 mg (OTC) orally twice daily or
      2. Naprosyn 250 mg orally twice daily or
      3. Indomethacin 25 mg orally twice daily (avoid extended use due to adverse effects)
    2. Prednisone (if NSAIDs contraindicated)
      1. Maintenance: 10 mg orally daily, then 5 mg orally daily for 3-6 months
      2. Acute Exacerbation (start at first symptoms of gout recurrence): 40 mg orally for 1-3 days
        1. Have available as emergency prescription
    3. Colchicine
      1. Colchicine was a first line agent for this until generic preparations were removed from market (now too expensive)
      2. Colchicine 0.6 mg orally daily to twice daily

XV. Prevention: General

  1. Adjunctive Uricosuric medications
    1. Losartan (Cozaar)
      1. Not seen with other Angiotensin Receptor Blockers
    2. Fenofibrate (Tricor)
  2. Adjunctive agents to consider
    1. Dairy products may be protective
      1. Choi (2004) N Engl J Med 350:1093-1103 [PubMed]
    2. Eating cherries lowers serum Uric Acid
      1. Jacob (2003) J Nutr 133(6): 1826-9 [PubMed]
    3. Coffee lowers gout attack risk
      1. However significant decrease only at >3 cups/day
      2. Choi (2007) Arthritis Rheumatism 56(6): 2049-55 [PubMed]
    4. Vitamin C: 500 mg/day lowers Uric Acid 0.5 mg/dl
      1. Huang (2005) Arthritis Rheumatism 52(6):1843-7 [PubMed]
  3. Avoid provocative factors (See Hyperuricemia)
    1. Avoid purine-rich foods (See Purine Content in Foods)
      1. Especially avoid red meats (beef, lamb, pork), wild game, organ meats and shellfish
      2. Vegetable/grain high purine foods do not increase risk (nuts, oatmeal, asparagus, legumes, mushrooms)
    2. Avoid Alcoholic beverages (especially beer)
    3. Avoid fruit juice and drinks sweetened with high-fructose corn syrup
      1. Increases Uric Acid as a byproduct of ATP catabolism
    4. Avoid Thiazide Diuretics
      1. However Thiazides result in only small Uric Acid increases
      2. Hueskes (2012) Semin Arthritis Rheum 41(6): 879-89 [PubMed]
    5. Avoid weight gain
      1. Weight loss (if Overweight) lowers the gout risk

XVI. Associated Conditions: Other Uric Acid Conditions

XVII. Course

  1. Gout attack episodes last 5-7 days with or without treatment

XVIII. Resources

Images: Related links to external sites (from Bing)

Related Studies (from Trip Database) Open in New Window

Ontology: Gout (C0018099)

Definition (MEDLINEPLUS)

Gout is a common, painful form of arthritis. It causes swollen, red, hot and stiff joints.

Gout happens when uric acid builds up in your body. Uric acid comes from the breakdown of substances called purines. Purines are in your body's tissues and in foods, such as liver, dried beans and peas, and anchovies. Normally, uric acid dissolves in the blood. It passes through the kidneys and out of the body in urine. But sometimes uric acid can build up and form needle-like crystals. When they form in your joints, it is very painful. The crystals can also cause kidney stones.

Often, gout first attacks your big toe. It can also attack ankles, heels, knees, wrists, fingers, and elbows. At first, gout attacks usually get better in days. Eventually, attacks last longer and happen more often.

You are more likely to get gout if you

  • Are a man
  • Have family member with gout
  • Are overweight
  • Drink alcohol
  • Eat too many foods rich in purines

Gout can be hard to diagnose. Your doctor may take a sample of fluid from an inflamed joint to look for crystals. You can treat gout with medicines.

Pseudogout has similar symptoms and is sometimes confused with gout. However, it is caused by calcium phosphate, not uric acid.

NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Definition (NCI_NCI-GLOSS) A condition marked by increased levels of uric acid in the blood, joints, and tissue. The buildup of uric acid in the joints and tissues causes arthritis and inflammation.
Definition (MSH) Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi.
Definition (CSP) hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi.
Concepts Disease or Syndrome (T047)
MSH D006073
ICD9 274.9, 274
ICD10 M10 , M10.9, M10.99
SnomedCT 190844004, 90560007
LNC LA14305-9
French GOUTTE, Goutte non précisée, Goutte
English GOUT, Gout, unspecified, gout, gout (diagnosis), Gout NOS, Gout [Disease/Finding], Gout, unspecified, site unspecified, gouts, gout disorder, Gouts, Gout NOS (disorder), Gout (disorder), gout; in, Gout, NOS, Gout
Portuguese GOTA, Gota NE, Gota
Spanish GOTA, Gota no especificada, gota, SAI (trastorno), gota, SAI, gota (trastorno), gota, Gota
German GICHT, Gicht, unspezifisch, Gicht, nicht naeher bezeichnet, Gicht, Urikopathie
Dutch jicht, niet-gespecificeerd, jicht; bij, Jicht, niet gespecificeerd, jicht, Jicht, Arthritis urica
Italian Gotta non specificata, Gotta
Japanese 痛風、詳細不明, 痛風, ツウフウショウサイフメイ, ツウフウ
Swedish Gikt
Czech dna (nemoc), Dna, Dna, blíže neurčená
Finnish Kihti
Russian PODAGRA, ПОДАГРА
Korean 통풍, 상세불명의 통풍
Croatian GIHT
Polish Skaza moczanowa, Dna moczanowa, Podagra, Skaza dnawa
Hungarian Köszvény, Köszvény, nem meghatározott
Norwegian Gikt

Ontology: Podagra (C0221168)

Concepts Disease or Syndrome (T047)
ICD10 M10
SnomedCT 267501002, 67148009
English podagra, Podagra, Podagra (disorder)
Spanish Podagra, podagra (trastorno), podagra
Portuguese Podagra
Dutch podagra
French Podagre
German Podagra
Hungarian Podagra
Czech Podagra
Italian Podagra
Japanese ポダグラ, ポダグラ