Gout (Podagra)

Gout is a painful inflammatory disease characterized by abnormal deposition of uric acid crystals, especially in tissues with limited blood flow, such as the synovial joint of the big toe. Acute attacks that are untreated may last from a couple days up to several weeks. Attacks often start at night. If untreated, attacks may recur with increasing frequency and longer duration Arthritis Foundation.

Deposits (tophi) may also appear on bones, tendons, and under the skin, especially on the extensor surface of joints and the antihelix of the ear. On rare occasions, deposits may occur in the cornea of the eye.

Uric acid kidney stones and nephrotoxicity are other potentially serious sequelae of gout.

Effective treatment protocols consisting of diet and lifestyle changes along with herbal or pharmaceutical interventions are available. However, if left untreated, irreversible kidney damage, chronic arthritis, and recurring exacerbations are likely.

95% of patients suffering from gout are men over the age of 30. Gout is often called the rich man's disease because it is exacerbated by over consumption of rich foods and alcohol [Pizzorno2006, pg 1703]

Please see conventional, complimentary and alternative medical treatments for important background information regarding the different types of medical treatments discussed on this page. Naturopathic, Complementary and Alternative treatments that may be considered include:

Fever/chills, tachycardia, and elevated WBC may be observed.

The two main factors leading to gout are overproduction of uric acid and the underelimination of uric acid, either or both of which can lead to precipitation of uric acid crystals. Since uric acid is more soluble in basic solutions, pH below 6.0 (acidic) tends to promote precipitation of uric acid crystals. Since uric acid is more soluble in warmer solutions, the precipitation tends to occur in cooler parts of the body, such as the helix and pinna of the ear and the feet, where blood circulation is reduced [Merck1999, pg 460].

More than one factor may contribute to the development of gout, including:

• Overproduction of uric acid:
  • Excess purines in diet.
    • Normal diet contains about 450mg of uric acid precursors; a reduced purine diet can cut this to about 300mg.
    • Foods high in purines: anchovies, sardines, organ meats (sweetbreads, kidney, liver), meat extracts. Other foods sometimes considered high in purines include yeast, meat, shellfish, herring, mackerel. Moderately high sources of protein are sometimes also considered, including dried legumes, spinach, asparagus, fish, poultry, and mushrooms [Pizzorno2006, pg 1706].
  • Excess alcohol consumption (alcohol induces nucleotide breakdown in the liver).
  • Increased purine production due accelerated cell turnover (purines are a degradation product of DNA and RNA).
    • Trauma, surgery, cancer chemotherapy, or radiation treatment.
    • Myeloproliferative diseases.
    • Lymphoproliferative disorders (lymphoma, leukemia).
    • Carcinoma or sarcoma (disseminated).
    • Hemolytic anemias.
    • Hyperproliferative skin disorders (psoriasis).
    • Cytotoxic drugs (cyclosporine).
  • Inborn errors of metabolism (genetic)
    • Family history. Polynesian.
    • Under-activity of the enzyme hypoxanthine-guanine phosphoribosyltransferase.
    • Overactivity of the enzyme phosphoribosylpyrophosphate synthetase.
    • Lesch-Nyhan Syndrome.
    • Glycogen storage disease.
• Underelimination of uric acid:
  • Excess alcohol consumption (alcohol is metabolized to lactic acid, which blocks renal excretion of uric acid).
  • Reduced renal clearance:
    • Reduced GFR due to kidney disease.
    • Diuretics (thiazide).
    • Low dose aspirin and salicylates.
    • Probenecid (low dose)
    • Ethambutol
    • Pyrazinamide
    • Lead poisoning (leaded crystal, moonshine).
• Low body pH:
  • Excess alcohol consumption (alcohol is metabolized to lactic acid).
  • Diabetic, fasting, or starvation ketoacidosis.
  • Lactic acidosis (toxemia of pregnancy, chronic beryllium disease).
• Dehydration
• Other Medications [Domino2008, pg 518]:
  • Aminophylline
  • Caffeine
  • Corticosteroids
  • Diazepam
  • Diphenhydramine
  • Diuretics (20% of secondary gout)
  • L-dopa, dopamine, L-methyldopa
  • Epinephrine
  • Methaqualone (Quaalude)
  • Nicotinic Acid
  • Salicylates
  • Sulfinpyrazone (low dose)
  • Vitamin B12
  • Vitamin C
• Associated Risk Factors [Domino2008, pg 518]:
  • Obesity (50%)
  • Hypertension (50%)
  • Vascular disease
  • Hypothyroidism
  • Hyperparathyroidism, hypoparathyroidism
  • Hyperlipidemia types II, IV, V
  • Paget's disease (osteitis deformans)
  • Calcium pyrophosphate deposition disease
  • Sarcoidosis
  • Hemoglobinopathies
  • Pernicious anemia
  • Type I glycogen storage disease
  • Down Syndrome
  • Gut sterilization by antibiotics
  • Hemoproliferative disorders
  • Carpal Tunnel Syndrome
  • Diabetes insipidus [Pizzorno2006, pg 1705]
  • Barter syndrome [Pizzorno2006, pg 1705]
  • Glucose-6-phosphate dehydrogenase deficiency [Pizzorno2006, pg 1705]

Serum urate may be elevated (70%) but is neither specific nor sensitive [Merck1999, pg 461].

X-ray may show punched-out lesions in subchondral bone and/or tophi, but these lesions are neither diagnostic nor specific [Merck1999, pg 461].

• Septic arthritis (bacteria in synovial fluid culture). Emergency!
• Pseudogout (calcium pyrophosphate dihydrate crystal deposition disease = CPPD).
• Type IIa hyperproteinemia.
• Amyloidosis.
• Multicentric reticulohistiocytosis.
• Hyperparathyroidism.
• Spondyloarthropathy.
• Rheumatic and rheumatoid diseases.
• Metabolic acidosis.

• Rule out septic arthritis (needle aspiration of synovial fluid).
• Monitor CBC, renal, LFT, and urinalysis at 1 week, 6 weeks, and every 3 months during drug therapy. On unrestricted diet, urinary excretion should be at least 800mg/day; on purine-restricted diet, urinary excretion should be at least 600mg/day (if less, then patient is a hypoexcretor) [Domino2008, pg 519].
• Monitor serum urate.
• Consider X-ray of affected joints (punched out regions with preservation of joint space) [Domino2008, pg 519].
• Palliate acute symptoms:
  • Avoid treatment with urate-lowering drugs during the acute phase, as they may exacerbate symptoms [Merck1999, pg 462].
  • Eliminate dietary triggers (alcohol, high purine foods).
  • Ensure adequate hydration to reduce precipitation of uric acid and to promote excretion via the kidneys.
  • Consider splinting of the inflamed joint to minimize exacerbating motion.
  • Natural therapeutics to reduce inflammation:
    • Eicosapentanoic Acid [Pizzorno2006, pp 1707-8].
    • Vitamin E [Pizzorno2006, pp 1707-8].
    • Selenium [Pizzorno2006, pp 1707-8].
    • Folic Acid [Pizzorno2006, pp 1707-8].
    • Bromelain [Pizzorno2006, pp 1707-8].
    • Quercetin [Pizzorno2006, pp 1707-8].
    • Consider Alanine, Aspartic Acid, Glutamic Acid, and Glycine [Pizzorno2006, pp 1707-8].
    • Cherries, Blueberries, and similar red-purple fruits [Pizzorno2006, pp 1707-8].
  • NSAIDs are the drug of choice to reduce acute symptoms. Full dose until attack is controlled, then reduce to half dose [Domino2008, pg 519]. Note possibility of gastric disturbance, and hyperkalemia due to decreasing prostaglandin E2-dependent renal blood flow, especially in elderly and dehydrated patients [Merck1999, pg 462].
  • Alternatively, colchicine 1mg PO Q 12 hour until a response is obtained or until diarrhea or vomiting occurs, up to a maximum of 7mg in 48 hours. Note that electrolyte imbalances induced by diarrhea may be life threatening in brittle patients [Merck1999, pg 462]. Colchicine therapy must be initiated within 24 hours of acute onset to be effective [Domino2008, pg 519] Colchicine is derived from the plant Colchicum autummale (Autumn Crocus, Meadow Saffron). It acts as an anti-inflammatory, by inhibiting neutrophil migration. Potential side effects include bone marrow suppression, hair loss, liver damage, depression, seizures, and respiratory depression [Pizzorno2006, pg 1706]
  • Alternatively, colchicine 1mg in 20mL 0.9% NaCl solution may be administered IV in a slow push (2-5 minutes), with no more than 2mg administered in 24 hours. Note that severe bone marrow suppression and death may occur in patients receiving prophylactic oral colchicine when also given IV doses [Merck1999, pg 462].
  • Alternatively, after aspiration of the affected joint, 10 to 50mg prednisolone tebutate can be instilled into the joint space [Merck1999, pg 462].
  • Alternatively, a single dose of ACTH 40-80 IU may be injected IM to stimulate endogenous corticosteroid production [Merck1999, pg 462] [Domino2008, pg 519].
  • Alternatively, a short course of oral prednisone 20 to 30mg/day may be used [Merck1999, pg 462].
  • Other anti-inflammatories to consider include indomethacin, phenylbutazone, naproxen, and fenoprofen (Nalfon) [Pizzorno2006, pg 1706]
  • If additional pain relief is required, consider a narcotic such as Vicodin 1-2 tabs PO Q 4-6 hours PRN for pain, not to exceed 8 tabs/24 hours (do not take additional acetaminophen-containing products).
• Prevent recurrent attacks:
  • Colchicine 0.6mg Q day to TID (depending on tolerance and severity of gouty condition) can prevent most recurrences. An extra 1 to 2mg of colchicine taken at the first hint of a flare-up may abort the flare-up. Note that chronic colchicine ingestion has been associated with neuropathy or myopathy. Also note that colchicine does not halt the disease progress, but only provides symptomatic relief [Merck1999, pg 462].
• Prevent precipitation of uric acid crystals:
  • Maintain adequate hydration (at least 3 L/day, more in hot/dry climates).
  • Avoid alcohol, which metabolizes to lactic acid.
  • Avoid diets that produce ketoacidosis.
  • Manage diabetes to avoid ketoacidosis.
  • Alkalize urine to reduce precipitation of uric acid in the kidneys and urinary tract. This is a balancing act - if the urine is made too alkaline then calcium oxalate crystals will precipitate instead [Merck1999, pg 462].
    • Sodium bicarbonate 5g TID.
    • Alternatively, trisodium citrate 5g TID.
    • Alternatively, acetazolamide 500mg HS.
• Lower uric acid levels in body:
  • Maintaining low serum levels of uric acid ( < 0.45mg/dL) can slowly (months to years) resolve deposits of uric acid crystals, thus preventing progression of the disease.
  • Reduce consumption of foods high in purines: anchovies, sardines, organ meats (sweetbreads, kidney, liver), meat extracts. Other foods sometimes considered high in purines include yeast, meat, shellfish, herring, mackerel. Moderately high sources of protein are sometimes also considered, including dried legumes, spinach, asparagus, fish, poultry, and mushrooms
  • Increase excretion of uric acid:
    • Avoid alcohol, which inhibits excretion of uric acid.
    • Probenecid 500mg tab. Indicated if urinalysis indicates patient is a hypoexcretor Start with 1/2 tab bid, increasing by 500mg/day each month to 4 tab bid or until symptoms are controlled. Avoid NSAIDs, which antagonize probenecid (use acetaminophen). Initiation of probenecid treatment may give a temporary exacerbation of symptoms. Wait until acute symptoms have subsided, and maintain NSAID and/or colchicine dosage until probenecid treatment has been established. Contraindicated with uric acid overproduction, uric acid stones, renal impairment. Caution with tophi [Merck1999, pg 462] [Domino2008, pg 519].
    • Alternatively, sulfinpyrazone 100mg tab. Start with 1/2 tab bid, slowly increasing to 4 tab bid. Avoid NSAIDs, which antagonize sulfinpyrazone (use acetaminophen). Sulfinpyrazone is more effective than probenecid, but is also more toxic. Initiation of sulfinpyrazone treatment may give a temporary exacerbation of symptoms. Wait until acute symptoms have subsided, and maintain NSAID and/or colchicine dosage until sulfinpyrazone treatment has been established [Merck1999, pg 463].
    • Fenofibrate (TriCor, Lofibra, Triglide, Lipofen, Antara) 160mg/day augments urate clearance [Domino2008, pg 519]:
  • Destroy uric acid:
    • Rasburicase (Elitek) is a urate-oxidase enzyme that metabolizes uric acid, and is indicated when substantial purine overload is expected, as in cancer chemotherapy. See black-box warnings regarding anaphylaxis reactions and contraindications in patients with glucose-6 phosphate dehydrogenase deficiency or methemoglobinemia. Administration is by IV drip (not bolus) [Domino2008, pg 519]:
• Prevent conversion of purines into uric acid:
  • If serum levels of uric acid exceed 0.9mg/dL, allopurinol (Zyloprim) 100mg/day in divided doses, increased by 100mg/d each week to a maximum of 600mg/day can be used to prevent the conversion of purines into uric acid [Domino2008, pg 519]: Initiation of allopurinol treatment may give a temporary exacerbation of symptoms. Wait until acute symptoms have subsided, and maintain NSAID and/or colchicine dosage until allopurinol treatment has been established. Potential side effects of allopurinol include mild GI distress, potentially dangerous skin rashes, hepatitis, vasculitis, and leukopenia. Contraindicated with bone marrow suppression, liver disease, and concomitant cytotoxic drugs. [Merck1999, pg 463] [Domino2008, pg 519].
• A new drug, febuxostat (Uloric) is in the final approval stage by the FDA, and is promoted as being safer than allopurinol in patients with impaired kidney function. Dosing is 80-120mg/day [Domino2008, pg 519]:
• Excise large superficial tophi (consider biopsy using anhydrous specimen container).
• Other dietary interventions:
  • Reduce fat intake to decrease uric acid retention [Domino2008, pg 519] [Pizzorno2006, pp 1706-7].
  • Reduce refined carbohydrate intake to reduce uric acid production [Pizzorno2006, pp 1706-7]
  • Limit protein intake to 0.8 g/Kg body weight, since excess protein enhances production of uric acid. Note however that amino acids help enhance excretion of uric acid [Pizzorno2006, pg 1706]
  • Increase complex carbohydrate intake [Pizzorno2006, pg 1706]
• Treat comorbidities and predisposing factors.
  • Obesity: Weight reduction in obese individuals significantly decreases serum uric acid levels. A low-glycemic diet designed to improve insulin sensitivity is alkalinizing, which also benefits gout [Pizzorno2006, pg 1707].
  • Hypertension
  • Dyslipidemia
  • Diabetes

Damage to the kidney (nephritis) caused by the excess uric acid leads to a vicious downward spiral of decreased excretion of uric acid, increased levels of retained uric acid, and increased kidney damage.

With proper adherence to preventative measures most patients can live normal lives.