GOUT

















  • Reference [2,3,4,17]
RISK FACTORS FOR GOUT
Risk factor Comment
Hyperuricemia
  • Main risk factor for developing gout
  • 15-year risk of gout with uric acid level < 6 mg/dl is around 1.1%
  • 15-year risk of gout with uric acid level ≥ 10 mg/dl is around 50%
Males
  • Gout is much more prevalent in men
  • Male:female ratio is 3-4:1
Age
  • The incidence of gout increases with age
  • This is likely secondary to decreasing renal function and possibly medications (e.g. diuretics)
Menopause
  • Estrogen promotes uric acid excretion in the kidneys
  • After menopause, excretion decreases
Obesity
  • The prevalence of gout is much higher in obese people
  • Weight loss decreases the risk
Kidney disease
  • In kidney disease, the excretion of uric acid decreases
Organ transplant recipients
  • Anti-rejection medications raise uric acid levels
Myeloproliferative disorders
  • Increase in purine turnover
High purine intake
  • Purines are metabolized to uric acid
  • High purine intake increases uric acid levels
  • High concentrations of purines are found in meats and organ meats (see diet recommendations below)
Alcohol
  • Alcoholic beverages, particularly beer and liquor, have been associated with an increased risk of gout
High-fructose corn syrup
  • High fructose corn syrup in beverages and foods has been associated with an increased risk of gout
HGPRT deficiency
  • Hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) is an enzyme involved in purine metabolism
  • HGPRT deficiency leads to increased uric acid production
  • HGPRT deficiency is a recessive X-linked trait so it is almost exclusively seen in males
  • Lesch-Nyhan syndrome is marked by complete HGPRT deficiency
Genetic defects in renal urate transporters
  • Uric acid excretion is decreased
  • Rare cause of gout



  • Reference [1,4,6]
MEDICATIONS THAT RAISE URIC ACID LEVELS
Medication Comment
Thiazide diuretics
  • Thiazide diuretics promote uric acid retention in the kidneys
Loop diuretics
  • Loop diuretics promote uric acid retention in the kidneys
Aspirin
  • Aspirin has a dose-dependent effect on uric acid excretion
  • Low-dose aspirin (≤ 325 mg/day) has a negligible effect on uric acid levels
  • The American College of Rheumatology does not recommend stopping daily low-dose aspirin in patients with gout
  • Aspirin doses of 600 - 2400 mg/day can cause significant uric acid retention
  • High-dose aspirin (> 4 grams/day) promotes uric acid excretion and can lower plasma uric acid levels
Cyclosporine
  • The immunosuppressant cyclosporine can raise uric acid levels
Niacin
  • Niacin, which can be used to treat high cholesterol, can raise uric acid levels
Tacrolimus
  • The immunosuppressant tacrolimus can raise uric acid levels
Ethambutol
  • The anti-tuberculosis drug ethambutol can raise uric acid levels
Pyrazinamide
  • The anti-tuberculosis drug pyrazinamide can raise uric acid levels
  • Pyrazinamide inhibits renal excretion of uric acid
Chemotherapy
  • Cytotoxic agents can increase purine load/turnover
Ribavirin
  • Ribavirin can cause hemolytic anemia which can lead to elevated uric acid levels
Teriparatide
(Forteo®)
  • The osteoporosis drug teriparatide can raise uric acid levels





  • Reference [1,4]
2015 ACR CRITERIA FOR DIAGNOSING GOUT
Step 1 - patient must have experienced the following:
  • At least one episode of swelling, pain, or tenderness in a peripheral joint or bursa
Step 2 - if monosodium urate crystals have been observed in fluid from an affected joint, then gout is diagnosed, and no other criteria are necessary
  • If crystals have not been observed, then proceed to Step 3
Step 3 - if patient meets Step 1 criteria, but not Step 2, then a scoring system is used based on the criteria below. A total score of ≥ 8 classifies a person as having gout.

NOTE: A person receives one score for each criteria
Criteria Finding Score
Pattern of joint involvement
  • Any involvement of the first MTP joint
2
  • Any involvement of ankle or midfoot (without involvement of 1st MTP joint)
1
Symptoms during episode
  • Erythema overlying affected joint (patient-reported or physician-observed)
  • Can’t bear touch or pressure to affected joint
  • Great difficulty with walking or inability to use affected joint
  • One symptom
1
  • Two symptoms
2
  • Three symptoms
3
Time course of episode
  • Typical episode defined by ≥ 2 of the following, regardless of treatment:
    • Time to maximal pain < 24 hours
    • Resolution of symptoms in ≤ 14 days
    • Complete resolution (to baseline level) between symptomatic episodes
  • One typical episode
1
  • Two or more typical episodes
2
Evidence of tophi
  • Draining or chalk-like subcutaneous nodule under transparent skin
  • Overlying vascularity is often present
  • Typical locations include joints, ears, olecranon bursae, finger pads, and tendons (e.g. Achilles)
  • Present
4
Uric acid level
  • Ideally measured off of urate-lowering therapy and at > 4 weeks from the start of an episode
  • < 4 mg/dl
    (< 0.24 mmol/L)
- 4
  • 6 - <8 mg/dl
    (0.36 – <0.48 mmol/L)
2
  • 8 - <10 mg/dl
    (0.48 - <0.60 mmol/L)
3
  • ≥ 10 mg/dl
    (≥ 0.60 mmol/L)
4
Negative synovial fluid analysis
  • If patient had synovial fluid evaluated during a symptomatic episode and no monosodium urate crystals were observed
  • True
- 2
Evidence of urate deposition on imaging
  • Presence of any of the following:
    • Ultrasound evidence of double-contour sign
    • Dual-energy CT imaging demonstrating urate deposition
    • X-ray evidence of gout-related joint damage of the hands and/or feet
  • Present
4












  • Reference [2]
2012 ACR recommendations for the treatment of acute gout attacks
General guidelines in all patients
  • For optimal care, initiate therapy within 24 hours of symptom onset
  • Urate-lowering therapy should be continued during an acute gout attack
  • Applying ice to affected joint(s) may be beneficial
For mild-moderate pain affecting one or a few small joints, or 1 - 2 large joints, use one of the following:
  • NSAID or COX-2 inhibitor
  • Systemic steroids
  • Colchicine
For severe pain affecting multiple joints, consider the following combination therapy:
  • NSAID + colchicine
  • Systemic steroids + colchicine
  • Intra-articular steroids + NSAIDs OR Colchicine OR Systemic steroids
For any patient, if monotherapy is ineffective, patient may be switched to another therapy or combination therapy may be tried


Medications
(FDA-approved)
Dosing
Naproxen
  • 750 mg starting dose followed by 250 mg every 8 hours until attack resolves
Indomethacin
  • 50 mg three times a day until pain is tolerable, then taper
Sulindac
  • 200 mg twice a day until satisfactory response, then taper






  • Reference [1,2]
2012 ACR recommendations for the treatment of hyperuricemia
Indications for treatment
  • Urate-lowering therapy is indicated if there is an established diagnosis of gout and any of the following:
    • Presence of tophi
    • Frequent attacks defined as ≥ 2 attacks/year
    • Chronic kidney disease - stage II (CrCl ≤ 89 ml/min) or worse
    • History of kidney stones - patients should have urine uric acid evaluation (see kidney stones for more)
General recommendations
  • Dietary and lifestyle recommendations
  • Consider stopping nonessential medications that raise uric acid levels (see medications above)
  • Urate-lowering therapy may be started during an acute attack provided effective acute treatment has been established
  • When initiating urate-lowering therapy, gout flare prophylaxis should also be started (see below)
Gout flare prophylaxis during treatment initiation
  • When initiating urate-lowering therapy, the risk of acute gout attack is increased
  • All patients should take a gout flare prophylaxis regimen when starting urate-lowering therapy
    • Gout flare prophylaxis regimens include the following:
      • Colchicine - 0.5 - 0.6 mg once or twice daily (first-line)
      • Low-dose NSAID - for example, naproxen 250 mg twice a day with PPI if necessary (first-line)
      • Low-dose corticosteroids - defined as prednisone ≤ 10 mg/day (second-line)
      • DURATION: prophylaxis should continue for at least six months and for 3 months after achieving target serum urate levels, whichever is greater. If tophi are present, prophylaxis should continue for 6 months after achieving target urate level and when there has been resolution of the tophi.
Treatment steps
  • Step 1 - initiate urate-lowering therapy
    • Target serum uric acid level should be < 6 mg/dl. A target of < 5 mg/dl may be appropriate in patients with continued symptoms.
    • Preferred first-line agent is a xanthine oxidase inhibitor - allopurinol or febuxostat
    • If patient has contraindication or cannot tolerate a xanthine oxidase inhibitor, then probenecid may be used
    • Titrate monotherapy to maximum appropriate dose in order to achieve target uric acid level
    • If allopurinol does not achieve target uric acid level, patient may be switched to febuxostat, and vice versa
    • Check serum uric acid level every 2 - 5 weeks during titration
    • All patients should receive gout flare prophylaxis as above
  • Step 2 - if target uric acid level is not achieved with xanthine oxidase inhibitor, add uricosuric drug
    • Probenecid is the first choice
    • Other uricosuric drugs (fenofibrate, losartan) may be used if appropriate.
    • NOTE: When the guidelines were published, lesinurad was not available. In addition, the diabetic drug class called SGLT2 inhibitors is also uricosuric but was not available when the guidelines were published.
  • Step 3 - if target uric acid level is not achieved with xanthine oxidase inhibitor + probenecid, use pegloticase





  • Reference [1]
2012 ACR diet and lifestyle recommendations for patients with gout
General recommendations for all patients
  • Weight loss for obese patients
  • Smoking cessation
  • Exercise
  • Stay well hydrated (≥ 1.5 liters of fluid/day)
MEAT RECOMMENDATIONS
AVOID LIMIT ENCOURAGE
Organ meats high in purines
  • Kidney, liver, sweetbreads
Serving sizes of:
  • Beef, lamb, pork
  • Anchovies, sardines, herring, mackerel, scallops, mussels
  • Low-fat or nonfat dairy products
  • High concentrations of purines are found in anchovies, sardines, herring, mackerel, scallops, mussels, waterfowl, organ meats, glandular tissue, gravies, and meat extracts
  • Moderate-high concentrations of purines are found in shellfish, fish, game meats, mutton, beef, pork, poultry, and meat-based soups and broths
  • See the U.K. Gout Society dietary recommendations pdf for more information on diet and gout
SUGAR RECOMMENDATIONS
AVOID LIMIT ENCOURAGE
  • High-fructose corn syrup-sweetened sodas, other beverages, and foods
  • Servings of naturally sweet fruit juices
  • Table sugar, sweetened beverages and desserts
  • Table salt including what is in sauces and gravies
  • Vegetables
ALCOHOL RECOMMENDATIONS
AVOID LIMIT ENCOURAGE
  • Alcohol overuse (> 2 drinks/day in men, > 1 drink/day in women)
  • Avoid all alcohol during acute attacks or periods of uncontrolled gout
  • All alcohol intake, particularly beer but also wine and liquor