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 occurs when uric acid saturation arises without coexisting diseases or drugs that alter uric acid production or excretion, while secondary hyperuricemia is a condition where excessive uric acid production or diminished renal clearance occurs as a result of a disease, drug, dietary product or toxin. 

Gout Treatment

Principles of Therapy

Treatment for Acute Gouty Arthritis

  • Therapeutic goal: Rapid alleviation of pain and inhibition of inflammation as quickly as possible after the onset of gout until after the attack is terminated (1-2 weeks)

Long-term Treatment for Gouty Arthritis

Urate-Lowering Therapy

  • Indications for initiation of therapy include the following:
    • Presence of tophaceous deposits, eg ≥1 subcutaneous tophi
    • Frequent and disabling attacks of gouty arthritis (≥2 attacks/year)
    • Clinical signs or radiographic damage attributable to gout
  • May also be initiated in patients with history of >1 flare but have <2 flares per year and patients having their first flare and chronic kidney disease stage ≥3, serum urate level of >9 mg/dL or urolithiasis
  • Therapeutic goal is to promote crystal dissolution and prevent crystal formation by maintaining the serum urate level at <6.0 mg/dL (<0.36 mmol/L)
  • It is preferred to continue urate-lowering therapy indefinitely than to stop it if treatment is well tolerated
    • Urate-lowering therapy is a lifelong treatment and adjunctive lifestyle modification is important
  • A treat-to-target strategy is recommended for patients on urate-lowering therapy wherein doses are adjusted based on serial serum urate levels in order to achieve a target level of <6.0 mg/dL 
    • All patients on urate-lowering therapy should continue treatment to attain and maintain target level 
  • On initiation of urate-lowering therapy, concomitant anti-inflammatory prophylaxis with NSAIDs, Colchicine or Prednisone/Prednisolone can be given and continued for at least 3-6 months, with ongoing evaluation and continuous prophylaxis for persistent flares

Pharmacotherapy

Treatment for Acute Gouty Arthritis

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

Colchicine

  • Considered as one of the 1st-line therapies for acute gouty arthritis especially as attack prophylaxis and for 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
  • Lower dose regimen of Colchicine has comparable efficacy but fewer adverse events than higher dose regimen and is thus preferred
  • Low doses may be used as prophylaxis against acute attacks during the initiation of urate-lowering therapy

Corticosteroids

  • Considered as one of the 1st-line therapies for acute gouty arthritis
  • Short course can be considered in elderly people and those with renal insufficiency, hepatic dysfunction, cardiac failure, peptic ulcer disease and hypersensitivity/refractory to NSAIDs or Colchicine and other treatments
  • May be given locally through intra-articular injection or systemically through oral or parenteral administration
    • Parenteral glucocorticoids are preferred over interleukin-1 (IL-1) inhibitors or adrenocorticotropic hormone (ACTH) when oral dosing is not possible
  • In those with monoarthritis, an intra-articular aspiration and intra-articular injection of long-acting corticosteroid are highly effective in terminating the attack
    • Safe and 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, intolerant or who have contraindications to other agents
  • Anakinra provides relief of symptoms and 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 Gouty Arthritis 

Xanthine Oxidase Inhibitors

  • Eg Allopurinol, Febuxostat
  • Inhibit production of urate from hypoxanthine and xanthine
  • Allopurinol is recommended as the 1st-line urate-lowering treatment for gout, including patients with chronic kidney disease stage ≥3 
    • Febuxostat, a 2nd-line option, may substitute Allopurinol if with treatment failure after upward dose titration with 1 xanthine oxidase inhibitor and/or drug intolerance to Allopurinol 
  • Treatment should be initiated with low doses of Allopurinol and Febuxostat followed by subsequent titration
    • For patients taking Allopurinol, dose adjustment (start at lower dose) should be made for all patients especially those with renal impairment
  • Prior to initiation of Allopurinol therapy, it is recommended that HLA-B*5801 screening be done especially in patients at high risk for severe Allopurinol hypersensitivity (AHS) reaction (eg Korean, Han Chinese, Thai)
  • Allopurinol desensitization may be performed in patients with a prior Allopurinol allergic response who cannot be given other oral urate-lowering therapy
  • Changing to an alternative oral urate-lowering therapy agent may be done in gout patients receiving Febuxostat with a history of cardiovascular disease or a new CV event 
  • Allopurinol or Febuxostat is preferred over Probenecid in patients with chronic kidney disease stage ≥3 
  • Changing to a second xanthine oxidase inhibitor over adding a uricosuric agent may be done in gout patients taking their first xanthine oxidase inhibitor at indicated and maximally tolerated dose who are not at serum urate target and/or have frequent gout flares (≥2 flares/year) or non-resolving subcutaneous tophi  

Uricosuric Agents

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

Uricolytic Agent

  • 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 and/or intolerant to conventional urate-lowering treatments
    • Serum uric acid level not on target despite treatment with xanthine oxidase inhibitors, uricosuric agents and other interventions, and who have non-resolving subcutaneous tophi or frequent flares of gout (≥2 flares/year)
    • Severe chronic tophaceous gout with erosive joint involvement

Non-Pharmacological Therapy

Physical Treatments

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