TOC  |  Rheumatology  

Gout Arthritis - Hyperuricemia                         REF: ACP- PIER 2007 |  Gout 2010.pdf  

acute monoarthritis usually.


  • Alcohol intake (As little as 1-2 drinks can precipitate an attack in persons who are predisposed to gout ).
  • Medications (Among the most common medications that can precipitate acute gout attacks are thiazide diuretics and cyclosporine. Drugs that can cause hyperuricemia include other loop diuretics, pyrazinamide, ethambutol, nicotinic acid, vitamin B12, cancer chemotherapy, low dose salicylates, and levodopa)
  • Renal insufficiency (As renal function declines, so does clearance of uric acid - uric acid retention; renal insufficiency may thus predispose to gout. Gout in end-stage renal disease is not the norm, however. Renal function should also be considered when determining the most appropriate therapies for management)
  • Metabolic syndrome (The insulin-resistance syndrome is characterized by hyperlipidemia, hyperuricemia, central obesity, hypertension, and glucose intolerance)
  • Among the most common medications that can precipitate acute gout attacks are thiazide diuretics and cyclosporine. Drugs that can cause hyperuricemia include other loop diuretics, pyrazinamide, ethambutol, nicotinic acid, vitamin B12, cancer chemotherapy, salicylates (low dose), and levodopa
  • Inherited metabolic disorders (Hypoxanthine-guanine phosphoribosyl transferase deficiency, phosphoribosylpyrophosphate synthetase overactivity, and glucose-6-phosphatase deficiency are some heritable disorders that lead to purine overproduction and thus predispose to gout.  Bartter's syndrome, polycystic kidney disease, and Down's syndrome are some genetic disorders that can lead to hyperuricemia via decreased renal clearance of urate)

Physical Exam:

  • Very tender, swollen joint, often sensitive to very light touch (e.g., from a bedsheet)
  • Erythema of soft tissues overlying affected joint; Superficial desquamation of skin over the affected joint as the attack subsides
  • Tophi present as nodular deposits of monosodium urate with yellowish color, sometimes with surrounding erythema; they occur in a distribution similar to rheumatoid nodules on extensor surfaces of extremities, on finger pads, and along tendons, but may also be seen on the helix of the ear or eyelid.


Triad of acute monoarthritis, hyperuricemia, & a response to colchicine Rx.
Needle-shaped, sharply pointed, strongly negative birefringent urate crystals in synovial fluid or soft tissue aspirates.
(versus the Pseudo-gout which has the deposition of crystalline calcium dihydrate pyrophosphate - the blunted, weakly positive birefringent crystals.)

Look for at least 6 of the following 12 criteria for confirming the diagnosis of gout:
(American College of Rheumatology)

  1. Maximum joint inflammation within 1 day
  2. More than one attack over time
  3. Monoarticular arthritis (although gout can be polyarticular)
  4. Redness of joint
  5. Great metatarsophalangeal pain or swelling
  6. Unilateral great metatarsophalangeal involvement
  7. Unilateral tarsal involvement
  8. Suspected tophus
  9. Hyperuricemia
  10. Asymmetrical swelling within the joint on x-ray
  11. Subcortical cysts without erosion on x-ray
  12. Joint fluid culture negative for organisms during attack



Advise patients with gout that they should not consume ethanol.

Low purine diet: Consider alterations in diet to eliminate most high-purine foods from an animal source, including:

  • Organ meats, such as brain, kidney, liver, and pancreas (sweetbreads)
  • Red meat
  • Gravies, consommé, and broth
  • Scallops, anchovies, sardines, and herring
  • Milk and eggs

Acute Attacks Rx ("Put out the fire")

  • Indomethacin/Indocin 50 mg tid PO until all Sx have resolved for 48 hrs.
  • Colchicine 0.5-0.6 mg PO every 1-2 hours until symptoms subside or GI intolerance occurs (Max 6 mg in 24 hr, and no more than 1.2 mg/d thereafter). or
    IV 1-3 mg initially, then 0.5 mg q6h
    until relief, intolerable side effects of abd. cramping or diarrhea occurs, or max of 4 mg IV without improvement. [2 mg iv diluted in 10-20 mL of normal saline and infused through a freely flowing IV over 3-5 minutes. May repeat 2 mg iv dose 6 hours after first dose if needed. Maximum dose, 4 mg in 24 hours. NO MORE colchicine should be given by ANY route for 7 days after maximum iv dose is given]
    [Adverse Reactions:
    Nausea, vomiting, or diarrhea are typical manifestations of GI toxicity and are frequently dose related.
    Dermatitis, Urticaria, Alopecia, Purpura
    Bone marrow supression can be life threatening if maximum doses are exceeded.
    Myopathy and neuropathy can occur at any dose.
    Dose must be modified according to renal function to avoid dose-related toxicity.

    Avoid use in patients undergoing dialysis patients since dialysis does not remove the drug.
    Use in elderly persons may not be advisable.
  • Corticosteroid
     Prednisone 40-60 mg/d PO (in divided doses) until symptoms begin to subside, then rapidly taper over several days .
    IM injection:
    Triamcinolone acetonide (Kenalog), 60 mg.
    Methylprednisolone (DepoMedrol), 40-80 mg. May repeat in 24 hours if necessary.
    Intraarticular injections:
    Triamcinolone hexacetonide (Aristospan Intralesional), 40 mg for large joints, 5-20 mg for small joints.
    Methylprednisolone acetate (DepoMedrol), 40-80 mg for large joints, 20-40 mg for small joints.
    Betamethasone acetate (Celestone), 1.5-6 mg
  • ACTH 40 u IM every 8-24 hours as needed
  • Triamcinolone acetonide (Kenalog/Aristocort) 60 mg IM, or
    Prednisone 30-50 mg PO daily, tapering over 7 days.

Prophylaxis against acute attacks ("Make the matches damp")

  • Colchicine 0.6 mg 1-3x/day. (Generally after starting urate-lowering drug & urate level has been controlled, & no acute attack for 1-3 months)
  • Indomethacin 50 mg bid or Ibuprofen 400-800 mg tid with meals.
  • Urate-lowering agents ("Remove the matches from the body")
    Allopurinol /Zyloprim 300 mg/day PO usually  (for hyperuricemia associated with overproduction, urin. uric acid excretion>700 mg/24h, nephrolithiasis, prophylaxis before chemotherapy,)
  • Uricosuric agents:
    (for under-excretion of uric acid <700 mg/24h, GFR >50 mL/min, no acute gout, no kidney stone history)
    Probenecid /Benemid 500-1000 mg bid PO
    0.5 to 2 g/d, divided bid and dose adjusted until serum uric acid level normalizes.
    Twice daily dosing required. Not effective in patients with renal insufficiency.
    Sulfinpyrazone/Anturane 50-200 mg bid PO

    - Usual dose, 300-400 mg/d, but may increase up to 800 mg/d if patient does not respond to maintenance doses.
    - As effective as probenecid and well tolerated. Monitoring of renal function is advisable.
    Benzbromarone 25-120 mg daily.

Recognize that optimal management of acute gout requires control of inflammation as well as pain relief.

  • Consider treatment with nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, colchicine, and analgesics, alone or in combination, to manage acute gout.
  • Use NSAIDs or narcotics (or both) for adequate analgesia.
  • Note that the choice of agents for acute gout depends largely on patient characteristics and especially on the presence or absence of concomitant disease.
  • Be aware that traditional NSAIDs have usually been the first-line therapy owing to their combined analgesic and anti-inflammatory effects; newer cyclooxygenase-2-selective NSAIDs have similar efficacy but have not been widely studied as treatment of acute gout.
  • Use corticosteroids when NSAIDs are deemed unsafe in elderly persons, patients with renal insufficiency or active GI ulceration, and those receiving concurrent anticoagulation or other interacting drugs, or after surgery.
  • Use a local steroid injection of a single involved joint (e.g., knee, ankle, elbow, or wrist) if other interventions have been ineffective or are relatively contraindicated.
  • Do not give NSAIDs to patients with renal insufficiency or elderly persons with other risk factors for NSAID gastropathy.
  • Do not give full dose colchicine to patients with renal insufficiency.
  • Be aware that patients with peptic ulcer disease may not tolerate NSAIDs.
  • Recognize that patients with diabetes may develop increasing hyperglycemia while taking corticosteroids.

In patients with recurrent acute attacks or more than 1 or 2 acute attacks in 1 year:

  • Administer uric acid-lowering agents to achieve a serum uric acid level <5 mg/dL, if possible
  • Recognize that therapy may be required lifelong
  • Consider 24-hour urinalysis quantitating uric acid secretion and creatinine to identify whether the patient is an “undersecretor” of uric acid (<600 mg/d while consuming a low-purine diet)
  • Use uricosuric agents or xanthine oxidase inhibitors (or both) to decrease uric acid levels; if urate oxidase becomes available in the United States, it may be an alternative method of decreasing urate levels in patients who are intolerant of other therapies
  • Do not initiate treatment with any uric acid-lowering agents during an acute gout attack; wait for 1 or 2 weeks for the attack to completely resolve
  • Consider using colchicine to prevent acute gout attacks when initiating uric acid-lowering therapy

When initiating treatment with allopurinol, a xanthine oxidase inhibitor:

  • Begin with half of the projected dose and increase to the full projected dose in 2 to 3 weeks to minimize exacerbations
  • Use a lower projected dose in patients with renal insufficiency
  • Caution patients to immediately report side effects, such as rash
  • Consider initiating treatment with uricosuric agents in patients who are probably secreting <600 mg of uric acid daily while consuming a low-purine diet
  • Note that uricosurics are generally not effective in patients with renal insufficiency and a creatinine clearance <40 mL/min, necessitating use of allopurinol
  • Recognize that once-daily allopurinol may be more convenient for patients and increase adherence to therapy
  • Do not use uricosuric agents in patients with nephrolithiasis


Commonly Used Nonsteroidal Anti-inflammatory Drugs  (NSAID) in Treatment of Acute Gout
  • Indomethacin (Indocin) 25-50 mg po qid
  • Ibuprofen (Motrin, Advil) 600-800 mg po tid-qid
  • Naproxen (Naprosyn) 500 mg po bid
  • Meclofenamate (Meclomen) 200 mg po ×1 then 100 mg tid-qid
  • Sulindac (Clinoril) 200 mg po bid
  • Celecoxib (Celebrex) 200 mg po bid
  • Meloxicam (Mobic) 7.5-15 mg po qd
  • Ketorolac (Toradol) 60 mg im
    Can be given iv or im in patients who cannot tolerate po medication. Intravenous dose is half that of im dose. Dose should be reduced in patients > 65 years.
    Intramuscular ketorolac has been shown to be as effective as oral indomethacin in the treatment of acute gout attacks (69; 70). Do not use ketorolac in any form for more than 5 days


Primary Hyperuricemia
  1. Increased production of purine
    • Idiopathic
    • Specific enzyme defects (eg, Lesch-Nyhan syndrome, glycogen storage diseases)
  2. Decreased renal clearance of uric acid (idiopathic)

Secondary hyperuricemia

  1. Increased purine catabolism and turnover
    • Myeloproliferative disorders
    • Lymphoproliferative disorders
    • Carcinoma & sarcoma (disseminated)
    • Chronic hemolytic anemias
    • Cytotosic drugs
    • Psoriasis
    • Rhabdomyolysis
  2. Decreased renal clearance of uric acid
    1. Intrinsic kidney disease
    2. Functional impairment of tubular transport:
      • Drug-induced (eg, thiazides, probenecid)
      • Hyperlacticacidemia (eg, lactic acidosis, alcoholism)
      • Hyperketoacidemia (dg, diabetic ketoacidosis, starvation)
      • Diabetes insipidus (vasopressin-resistant)
      • Bartters syndrome