gout
GOUT
Gout is a condition that resulted from deposition of monosodium urate crystals in various tissues (eg joints, connective tissue, kidney).
The patient experiences acute and chronic arthritis, soft tissue inflammation, tophus formation, gouty nephropathy and nephrolithiasis.
Primary hyperuricemia is called when uric acid saturation arises without coexisting diseases or drugs that alter uric acid production and excretion.
While in secondary hyperuricemia there is an excessive uric acid production or diminished renal clearance that occurs as a result of a disease, drug, dietary product or toxin.

Principles of Therapy

Treatment for Acute Gouty Arthritis

  • Therapeutic goal: Rapid alleviation of pain & inhibition of inflammation as quickly as possible after the onset of gout until after the attack is terminated (1-2 weeks)
  • Long term goals: Prevent further attacks, eliminate tophi & prevent joint destruction
  • Indications:
    • Presence of tophus/tophi
    • Attacks of  ≥2 a year
    • Chronic kidney disease stage 2 or worse
    • Past urolithiasis
Long-term Treatment for Chronic Gouty Arthritis 

Hypouricemic Therapy
  • Indications include the following:
    • Frequent & disabling attacks of gouty arthritis (≥2-3 attacks/year)
    • Clinical or radiographic signs of chronic gouty arthritis
    • Presence of tophaceous deposits
    • Urate nephropathy/nephrolithiasisImpending cytotoxic chemotherapy for lymphoma or leukemia
    • Long term use of diuretics or with chronic kidney disease
    • Primary gout that started at a young age
  • Therapeutic goal is to promote crystal dissolution & prevent crystal formation by maintaining the serum urate level at <0.36 mmol/L (<6.0 mg/dL); <5 mg/dL may be needed to control attacks
  • Should be started only after an acute attack is well controlled (about 2 weeks after the attack) to prevent prolonged attacks or rebound flares
  • Once started, the same dose must be maintained even during subsequent acute attacks
    • Hypouricemic therapy is a lifelong treatment & adjunctive lifestyle modification is important

Pharmacotherapy

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Eg Indomethacin, Naproxen, Ibuprofen, Sulindac, Ketoprofen, Piroxicam, Tenoxicam
  • Considered as one of the 1st-line therapies for acute gouty arthritis
  • Fast-acting NSAIDs at maximum dose for short term use are the oral drugs of choice for symptom relief in acute gouty arthritis provided that there are no contraindications to their use
    • Relieve pain & reduce inflammation

  • Proton pump inhibitors (eg Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole) or H2 receptor blockers (eg Ranitidine, Famotidine) may help prevent the development of GI ulcers in patients taking NSAIDs
  • Alternative drug therapy should be considered in patients with history of peptic ulcer disease, hypertension, renal impairment & cardiac failure
  • COX-2 Inhibitors
    • Alternative treatment for those at risk of peptic ulcer disease, intolerant of non-selective NSAIDs or in those presenting with an acute gouty attack of several days duration
    • Similar cautions as for non-selective NSAIDs should be exercised in those with renal impairment, cardiac failure, hypertension & active peptic ulcer disease

Colchicine

  • Considered as one of the 1st-line therapies for acute gouty arthritis especially as attack prophylaxis & chronic kidney disease patients with proper dose adjustments
    • As effective as NSAIDs but slower in reducing severity of acute attack

  • Alternative drug for those with contraindications to NSAIDs, including COX-2 inhibitors
  • Poorly tolerated by elderly due to gastrointestinal effects
    • High risk of toxicity with side effects (ie nausea, vomiting, abdominal pain, profuse diarrhea) more common in patients with impaired renal or hepatic function
    • Dose of 500 mcg 6-12 hourly has been recommended to prevent toxic side effects

  • A study showed that lower dose regimen of Colchicine has comparable efficacy with higher dose regimen
  • Low doses may be used as prophylaxis against acute attacks during the initiation of urate lowering therapy

Corticosteroids

  • Short course can be considered in elderly people & those with renal insufficiency, hepatic dysfunction, cardiac failure, peptic ulcer disease & hypersensitivity/refractory to NSAIDs or Colchicine & other treatments
  • May be given locally through intra-articular injection or systemically through oral or parenteral administration
  • In those with monoarthritis, an intra-articular aspiration & intra-articular injection of long-acting corticosteroid is highly effective in terminating the attack
    • Safe & well-tolerated; side effects are are due to short courses

  • Should not be given to patients with gouty arthritis who have concomitant septic arthritis

Biologic Interleukin-1 (IL-1) Inhibitors

  • Eg Anakinra, Canakinumab
  • Treatment option for patients with severe attacks of acute gouty arthritis refractory to other agents
  • Anakinra provides relief of symptoms & is preferred for acute attacks because of its short half-life
  • Canakinumab is a long-acting monoclonal antibody which can be considered in patients with history of multiple attacks refractory to other agents

Long-term Treatment for Chronic Gouty Arthritis 

Xanthine oxidase inhibitors

  • Eg Allopurinol, Febuxostat
  • In the 2012 American College of Rheumatologist (ACR) & 2013 Taiwan guidelines, either Allopurinol or Febuxostat is recommended as 1st line urate-lowering treatment for gout; while in the 2016 European League Against Rheumatism (EULAR) & 2017 British Society of Rheumatologist (BSR) guidelines Allopurinol is recommended as the 1st line urate-lowering treatment for gout & Febuxostat may substitute Allopurinol if with treatment failure after upward dose titration with 1 xanthine oxidase inhibitor &/or drug intolerance to Allopurinol
  • Initial long term treatment of recurrent uncomplicated gout
  • For patients taking Allopurinol, dose adjustment should be made for patients with renal impairment
  • Colchicine or low dose NSAIDs may be used to reduce the frequency of acute attacks during initiation of Allopurinol therapy until the patient is free of acute attacks for 6 month or target serum urate level is achieved for 1 month
  • Prior to initiation of Allopurinol therapy, it is recommended that HLA-B*5801 screening be done especiallyin patients at high risk for severe Allopurinol hypersensitivity (AHS) reaction (eg Koreans with  > stage 3 chronickidney disease, Han Chinese, Thai)

Uricosuric agents

  • Eg Probenecid, Benzbromarone, Sulphinpyrazone
  • Probenecid is an alternative urate-lowering treatment in cases where Allopurinol &/or Febuxostat is contraindicated or not tolerated, except in patients with creatinine clearance of <50 mL/min
  • Probenecid & Sulphinpyrazone may be used as alternative to Allopurinol in patients with normal renal function but not in patient with concomitant urolithiasis
  • Benzbromarone may be used in patients with mild-moderate renal insufficiency
    • Small risk of hepatotoxicity should be considered

Uricolytic Agents

  • Eg Pegloticase
  • A polyethylene glycol conjugate that lowers uric acid levels by catalyzing the conversion of uric acid to the more water-soluble compound Allantoin
  • Pegloticase is recommended for adult patients with severe debilitating chronic tophaceous gout refractory &/or intolerant to conventional urate-lowering treatments
    • Also recommended for patients with severe chronic tophaceous gout with erosive joint involvement

Urine-alkalinizing Agent

  • Eg Potassium Citrate
  • Increase urine pH to prevent stone formation & promote dissolution of stones
  • Target urine pH is 6.5-7

Non-Pharmacological Therapy

Physical Treatments

  • Rest & elevate the affected joint
  • Hold bedclothes away from affected joint
  • Apply ice pack & expose in a cool environment
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