Gout

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Created by
Taylor F

Cards (90)

  • Overview - Pathophysiology
    Disease resulting from deposition of monosodium urate in: Synovial fluids, Tissues, Kidney. Building block of monosodium urate is uric acid
  • Uric acid
    End product of purine metabolism, has no functional role. Some lack the uricase enzyme necessary to metabolise. Overproduction or under-excretion leads to hyperuricemia
  • Hyperuricemia

    A serum uric acid concentration over 420 umol/L. Solubility of uric acid decreases with lower temperatures. Precipitation may require a trigger
  • Causes of hyperuricemia

    • Overproduction of uric acid: Diet (overconsumption, rich in purines), Obesity, Hypertriglyceridemia, Drugs (Diuretics, Cytotoxic drugs). Underexcretion of uric acid: Chronic kidney disease, Hypertension, Dehydration, Drugs (Alcohol, ACE/ARB, ASA, Cyclosporine, Diuretics, Levodopa, Tacrolimus)
  • Is a patient overproducing or under-excreting?
    Place person on purine free diet for 3-5 days. Measure amount of uric acid in urine in 24 hours. If > 600mg, overproducer. On a regular diet, Excretion of > 1000mg / 24h = overproducer, Less than 1000mg / 24h = under-excreter (assuming high serum uric acid)
  • Prevalence of gout is 3% world-wide and increasing. It mostly occurs later in life and is more common in men
  • Four clinical phases of gout: Asymptomatic hyperuricemia, Acute gouty arthritis, Intercritical gout, Chronic tophaceous gout
  • Asymptomatic hyperuricemia is characterized by elevated uric acid levels with no symptoms. Majority do not require drug treatment. Potential consequences include gout, urate nephropathy, nephrolithiasis, CKD
  • Acute gouty arthritis is caused by precipitation of uric acid crystals in joint space. It is characterized by sudden onset of pain, erythema, limited range of motion, and swelling of joint. Often self-resolves in 7-14 days
  • Acute gouty arthritis

    1. 90% of first attacks involve a single joint
    2. Joint involvement frequency (decreasing probability): Toes, instep, ankle, knee, wrist, fingers
    3. Possible triggers: Trauma or surgery, Starvation, Fatty food binge, Dehydration, Drugs – including urate-lowering therapy
  • Intercritical gout
    1. Asymptomatic period between flares
    2. Initial intercritical period can last 2-10 years before recurrence
    3. Period becomes shorter as disease progresses
    4. Best time for patient education and implementation of lifestyle changes
    5. Prophylactic therapy? – not necessary for everyone
  • Chronic Tophaceous Gout

    1. Tophi are uric acid deposits
    2. Uncommon in most
    3. Late complication of hyperuricemia
    4. Can develop at any site
    5. Most common: feet, hands
    6. Consequences: Joint deformity, Surrounding tissue damaged, Joint destruction and pain, Compresses nerves, Nephrolithiasis and urate nephropathy
  • Nephrolithiasis occurs in 10-25% of people with gout
  • Nephrolithiasis is caused by excessive excretion of uric acid, leading to acidic and highly concentrated urine and precipitation
  • Urate nephropathy can lead to acute massive precipitation of uric acid crystals in nephrons and chronic formation of microtophi in kidneys
  • Diagnosis

    1. Diagnosis primarily made from symptoms
    2. Baseline lab tests: CBC, Urinalysis and Serum Creatinine, BUN, Serum uric acid levels
    3. Investigate comorbidities and risk factors
  • Diagnosis
    1. X-rays not typically useful
    2. May confirm diagnosis by analysis of synovial fluid under microscope
    3. Point system: Male (2), Previous similar flare (2), Rapid onset within one day (0.5), Joint redness (1), Toe involved (2.5), Presence of HTN or CVD (1.5), High serum urate (3.5)
  • Treatment
    1. Goals of treatment: Terminate an acute attack, Prevent recurrent attacks, Prevent long-term complications, Treat modifiable risk factors – diet, drugs (ex. diuretic, ACEi/ARB)
    2. Treatment includes Lifestyle modification, Acute attack drugs, Preventative drugs
  • Non-pharmacologic treatment
    1. Should only be implemented during asymptomatic or inter-critical period
    2. Regular exercise and weight loss, Hydration, avoid, limit, Substitutes / changes: Alcohol (esp. beer), Beef, Wine instead of other alcohol, Turkey, Lamb, Vegetables, Veal, Pork, Adequate hydration (2L/d), Bacon, Sardines and shellfish, Liver, Table salt, High fructose or corn syrup foods, Fish, Sweet beverages
  • Acute Gout Flare

    Four options: NSAIDs, Corticosteroids, Colchicine, Combinations
  • Acute Gout Flare - NSAIDs

    1. Most common first-line choice
    2. Any NSAID can be used: Naproxen, Ibuprofen, Ketoprofen, Indomethacin, Celecoxib
    3. Use high doses for first 24-72h, then find lowest effective dose
    4. May be used in combination with other acute options – NSAID + colchicine
    5. Consider adding GI protection - PPI
  • Acute Gout Flare - NSAIDs
    High dose regimens: nsaid initial dosing, maintenance dosing: Naproxen 500mg TID, 250-500mg BID, Ibuprofen 600-800mg TID, 400-600mg TID, Ketoprofen 75mg QID, 25-50mg q6-8h, Indomethacin 50mg TID, 25mg BID-TID, Celecoxib 400mg stat, then 200mg in 12h, 100-200mg BID
  • NSAIDs for acute gout flare will significantly reduce symptoms in majority of patients, speed resolution, and are likely comparable in efficacy to corticosteroids and colchicine
  • NSAIDs and their dosing
    • Naproxen: 500mg TID, 250-500mg BID
    • Ibuprofen: 600-800mg TID, 400-600mg TID
    • Ketoprofen: 75mg QID, 25-50mg q6-8h
    • Indomethacin: 50mg TID, 25mg BID-TID
    • Celecoxib: 400mg stat, then 200mg in 12h, 100-200mg BID
  • Treatment - Acute Gout Flare
    1. Efficacy and safety of NSAIDs in reducing symptoms and speeding resolution
    2. Corticosteroids as an alternative first-line choice with dosing information and tapering guidelines
    3. Intra-articular steroid injection as a preferred option with limitations and considerations
    4. Caution and efficacy of corticosteroids in specific conditions
    5. Colchicine as an early treatment with dosing, onset of effect, mechanism of action, and dosing adjustments for renal and hepatic impairment and drug interactions
  • NSAIDs will significantly reduce symptoms in the majority of patients and speed resolution
  • NSAIDs are likely comparable in efficacy to corticosteroids and colchicine but have more adverse drug reactions than corticosteroids and less than colchicine
  • Prednisone is the most commonly used corticosteroid for acute gout flare
  • Corticosteroids can be given orally, intra-articularly, intravenously, or intramuscularly
  • Corticosteroids are tapered over 3-5 days for short-term courses and may not need tapering if on concomitant therapy
  • Intra-articular steroid injection is the preferred option for acute gout flare if access to experienced physician and only 1-2 affected joints
  • Colchicine inhibits WBC motility in the joint space, reducing inflammation and may prevent urate deposition in synovial fluid
  • Colchicine should only be initiated within 24 hours of a flare and may abort the attack within 2-3 days with significant improvement in 24 hours
  • Common side effects of colchicine include GI symptoms, fatigue, and serious side effects like hematologic abnormalities and myopathy/rhabdomyolysis
  • Colchicine may interact with statins, potentially increasing statin levels and causing additive effects
  • Colchicine dosing with strong 3A4 or P-GP inhibitors
    0.6mg, then 0.3mg 1h later; do not repeat for 3 days
  • Colchicine dosing with moderate 3A4 inhibitors
    1.2mg stat; do not repeat for 3 days
  • Strong 3A4 or P-GP Inhibitors
    • HIV protease inhibitors
    • Verapamil / Diltiazem
    • Ritonavir
    • Grapefruit juice
    • Azole antifungals
    • Erythromycin
    • Cyclosporine
    • Clarithromycin
    • Amiodarone
  • Moderate 3A4 Inhibitors
    • Verapamil / Diltiazem
    • Ritonavir
    • Grapefruit juice
    • Azole antifungals
    • Erythromycin
    • Cyclosporine
    • Clarithromycin
    • Amiodarone
  • Colchicine common side effects in Acute Gout Flare