Gouty Arthritis

1. Epidemiology
   1. Men and post-menopausal women more commonly affected
   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
   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
2. Pathophysiology
   1. See Uric Acid
   2. See Hyperuricemia
   3. Gout occurs when Uric Acid levels exceed solubility limits
   4. Monosodium urate crystals deposit in joints, Kidney, and soft tissues
   5. Isolated and asymptomatic Hyperuricemia is common and requires no treatment
3. Risk Factors
   1. Most common
      1. Obesity
      2. Alcohol use
      3. High purine diet (meats, seafood)
      4. Diuretic therapy including Thiazide Diuretics
   2. Other risks
      1. Diabetes Mellitus
      2. Hyperlipidemia
      3. Hypertension
      4. Atherosclerosis
      5. Renal insufficiency
      6. Myeloproliferative disease
4. 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
5. Presentations
   1. Monoarthritis (most common)
   2. Acute bursitis
   3. Tenosynovitis
   4. Acute polyarticular gout
6. 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. Region:
      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. Characteristics: Joint pain
      1. Excruciating, crushing type pain
   5. Timing: Joint pain
      1. Acute onset of lower extremity joint pain
      2. Wakens patient from sleep
7. 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)
      2. Chronic arthritis
         1. Chronic deposition occurs with recurrent attacks
8. Labs
   1. Complete Blood Count
      1. Leukocytosis (may be as high as 40,000 wbc/mm3)
   2. Serum Uric Acid increased (Hyperuricemia)
      1. Synovial Fluid Exam (critical if Septic Arthritis is considered)
      2. Polarizing Microscopy
         1. Negatively birefringent
         2. Needle shaped Uric Acid crystals
      3. Gram Stain and Culture
         1. Rule out Septic Arthritis
   3. Urine Uric Acid (24 hour collection)
9. Imaging: Affected joint(s)
   1. Xray of affected joint shows asymmetric swelling
10. 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
11. Differential Diagnosis
    1. Septic Arthritis (critical to distinguish)!
    2. Pseudogout
    3. Other conditions
       1. Cellulitis
       2. Reactive Arthritis
       3. Rheumatoid Arthritis
       4. Osteoarthritis
       5. Neuropathic arthritis (Charcot Joint)
12. 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
       2. Indomethacin (historically has been preferred NSAID in gout)
          1. Start: 50mg orally three times daily for 2-3 days
          2. Then: 25mg 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
       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. Use as an alternative agent due to GI toxicity
       3. Avoid in severe liver or Kidney disease
       4. Requires adjusted dosing in renal disease
       5. 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
    3. Corticosteroids
       1. Rule-out Septic Arthritis first!
       2. Use with caution in Diabetes Mellitus
       3. Effective alternative to NSAIDs (less risk of peptic ulcer)
       4. Systemic agents
          1. IV: Methylprednisolone 40 mg (consider if NPO in hospital)
          2. IM: Depo-Medrol 80 to 120 mg single dose IM
          3. Oral
             1. Prednisone 40 mg orally daily for 5 days
             2. then Prednisone 20 mg orally daily for 5 days
             3. then Prednisone 10 mg orally daily for 5 days
       5. 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
13. Prevention: Medications
    1. Contraindications
       1. Do not use in acute attack
    2. Indications
       1. Recurrent Gout (>3 gout attacks per year)
       2. Tophaceous gout
       3. Nephrolithiasis
    3. Choice of agent based on 24h Uric Acid secretion
       1. Over-producer (Used for under-excreters also)
          1. Allopurinol 100-300 mg/day
             1. Adjusted dosing in renal insufficiency
             2. See Allopurinol for initiation protocol (start with antiinflammatory agent to prevent triggering gout attack)
          2. Febuxostat (pending FDA approval in 2007)
       2. Under-Excreter
          1. Probenacid and Sulfapyrazine are now rarely used
             1. Allopurinol used now for both types of gout
          2. Probenecid 250 mg PO bid (MAX: 1500mg bid)
          3. Sulfapyrazine 50 mg PO bid (MAX: 100mg bid)
    4. Concurrently start with prophylaxis, low dose x3-6mo:
       1. Colchicine 0.6 mg PO daily to bid for 3-6 months (preferred) or
       2. Indomethacin 25 mg PO twice daily for 3-6 months (avoid due to adverse effects)
14. Prevention: General
    1. Adjunctive Uricosuric medications
       1. Losartan (Cozaar)
       2. Fenofibrate (Tricor)
    2. Adjunctive agents to consider
       1. Dairy products may be protective
          1. Choi (2004) N Engl J Med 350:1093-1103
       2. Eating cherries lowers serum Uric Acid
          1. Jacob (2003) J Nutr 133(6): 1826-9
       3. Coffee lowers gout attack risk
          1. However significant decrease only at >3 cups/day
          2. Choi (2007) Arthritis Rheumatism 56(6): 2049-55
       4. Vitamin C: 500 mg/day lowers Uric Acid 0.5 mg/dl
          1. Huang (2005) Arthritis Rheumatism 52(6):1843-7
    3. Avoid provocative factors (See Hyperuricemia)
       1. Avoid purine-rich foods (See Purine Content in Foods)
       2. Avoid Alcoholic beverages (especially beer)
       3. Avoid Thiazide Diuretics
15. Associated Conditions: Other Uric Acid Conditions
    1. Uric Acid Nephrolithiasis
    2. Asymptomatic Hyperuricemia
16. Course
    1. Gout attack episodes last 5-7 days with or without treatment
17. References
    1. Klippel (1997) Primer Rheumatic Diseases, p. 230-4
    2. Buckley (1996) Am Fam Physician 54(4): 1232-8
    3. Eggebeen (2007) Am Fam Physician 76:801-12
    4. Harris (1999) Am Fam Physician 59(4): 925-34
    5. McDonald (1998) Postgrad Med 104(6): 117-27
    6. Pittman (1999) Am Fam Physician 59(7):1799-1806
    7. Terkeltaub (2003) N Engl J Med 1647-55