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The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician

                   Arthur L. Weaver, MD    N. Lawrence Edwards, MD         Lee S. Simon, MD
                  University of Nebraska      University of Florida            SDG LLC
                      Medical Center

   Sponsored by
                                                                            This program is supported by
                                                                         an educational grant from Takeda
                                                                      Pharmaceuticals North America, Inc.
                           The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician


       CME Information                                                                      2

       Faculty and Disclosures                                                              3

       The Gout Clinical Companion:
       The Latest Evidence and Patient Support Tools for the Primary Care Physician         4

       References                                                                          16

       CME Activity Attestation/Evaluation Form                                            18

       Posttest                                                                            20

                                           PATIENT EDUCATION TOOLS
                                   The following tear-outs can be found at the end
                                              of the Clinical Companion
                                                  – Managing Gout Pain –
                                          – Diet and Weight Management –
                                           – Medications for Treating Gout –
                                    – Adherence is Critical for Gout Management –

                                                                                      Contents   1
                      The Gout Clinical Companion:
                      The Latest Evidence and Patient Support Tools for the Primary Care Physician

    CME Information
    Needs Statement/Intended Audience
    This activity has been planned in accordance with the need to provide primary care and family physicians with a
    continuing medical education activity that addresses ongoing complex issues with the diagnosis and treatment of
    patients with gout.

    Educational Activity Learning Objectives
    Upon completion of this course, the participants should be able to:
    • Describe the factors to be considered in the diagnosis of gout
    • Describe current and emerging gout therapies, including their use at different disease stages and appropriate
      monitoring practices
    • Assess comorbidities and concomitant medications that may necessitate changes in gout management
    • Utilize patient education and counseling tools to support patient adherence to gout pharmacotherapy

    Accreditation Statement
    The France Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide
    continuing medical education for physicians.

    Credit Statement(s)
    The France Foundation designates this educational activity for a maximum of 2 AMA PRA Category 1 Credits™.
    Physicians should claim only credit commensurate with the extent of their participation in the activity.

    Commercial Support Acknowledgment
    This program is supported by an educational grant from Takeda Pharmaceuticals North America, Inc.

    The France Foundation presents this information for educational purposes only. The content is provided solely by
    faculty who have been selected because of recognized expertise in their field. Participants have the professional
    responsibility to ensure that products are prescribed and used appropriately on the basis of their own clinical judgment
    and accepted standards of care. The France Foundation and Takeda Pharmaceuticals assume no liability for the
    information herein.

    Release/Expiration Dates
    This activity is eligible for CME credit from June 2009 through June 30, 2010.

2   CME Information
Arthur L. Weaver, MD, MS, FACP, MACR (Chair)                                   Lee S. Simon, MD
Clinical Professor Medicine Emeritus                                           Consultant, Rheumatology/Internal Medicine
Department of Medicine                                                         SDG LLC
University of Nebraska Medical Center                                          Cambridge, Massachusetts
Omaha, Nebraska

N. Lawrence Edwards, MD
Professor of Medicine and Vice Chairman
Department of Medicine
University of Florida
Program Director
Department of Medicine
Shands Hospital
Gainesville, Florida

It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities.
All faculty, activity planners, content reviewers, and staff involved in the development of this activity have disclosed any significant financial interest
or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this
educational activity. The intent of this disclosure is not to prevent a faculty member with a relevant financial or other relationship from participating
in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has
identified and resolved any and all faculty conflicts of interest prior to the release of this activity.

Faculty Disclosures
The following faculty have indicated that they have relationships with industry to disclose:

Arthur L. Weaver, MD, MS, FACP, MACR, has served as a consultant for and received honoraria from Abbott Labs, Alpharma Inc, Amgen, Astellas
Pharma Inc, sanofi-aventis, Azano Pharmaceuticals, Biogen Idec, Biovail Pharmaceuticals, Bristol-Myers Squibb, Centocor, Cypress Bioscience Inc,
Endo Pharmaceuticals, Fujisawa Pharmaceutical Co, Genentech, Helsinn, Horizon Therapeutics, Human Genome Sciences, Eli Lilly and Company,
Medecision Laboratories, Merck, Merckel, Mylan, NicOx, Novartis, Ortho-McNeil, Pfizer, Primus Pharmaceuticals, Prometheus, Proprius Pharma,
Savient Pharmaceuticals, Schwarz Biosciences, Takeda Pharmaceuticals, TAP, TheraQuest Biosciences, and Wyeth Pharmaceuticals. He serves on
the Board of Directors of CORRONA.

N. Lawrence Edwards, MD, has served as a consultant for Savient Pharmaceuticals and Takeda Pharmaceuticals.

Lee S. Simon, MD, has served as a consultant for and received honoraria from AAIPharma, Abbott Labs, Affinergy, Inc, Alder Biopharmaceuticals,
Alimera Sciences, Altea Therapeutics, Antigenics, AstraZeneca, Alpha Rx, Anesiva, Bayer, BioCryst Pharmaceuticals, CaloSyn Pharma, Inc, Cerimon
Pharmaceuticals, Chelsea Therapeutics, ChemoCentryx, CombinatoRx, Cypress Pharmaceutical, Inc, Extra Pharmaceutical Co, EyeGate Pharma,
Fidelity Biosciences, Forest Laboratories, Genelabs Technologies, Genzyme Corporation, GPC-Biotech, Hisamitsu Pharmaceutical Co, IDM Pharma,
Leerink Swann and Company, Luxor, Millenium Pharmaceuticals, Inc, Neuromed Pharmaceuticals, NicOx, Nitec Pharma AG, Nomura, Novartis, Nuvo
Research Inc, Omeros, Parexel International, Pfizer, PLx Pharma, Proprius Pharmaceuticals, Purdue Pharma, Puretech Ventures, Regeneron, Rigel,
Roche, Savient Pharmaceuticals, Serono, Solace Pharmaceuticals, Takeda Pharmaceuticals, Talagen, Teva Neuroscience, Tigenix, White Mountain
Pharma, Wyeth Pharmaceuticals, and Zydus Pharmaceuticals. He has served as stock shareholder and received other financial and material
support from Savient Pharmaceuticals’ Board of Directors.

Activity Staff Disclosures
The planners, reviewers, editors, staff, CME committee, or others at The France Foundation who control content have no relevant financial
relationships to disclose.

                      The Gout Clinical Companion:
                      The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Gout is an acute inflammatory arthritic disorder              Uric acid appears to play a role in the regulation of
    characterized by painful monosodium urate crystal             multiple functions, including inflammation, locomotion,
    deposits in joints and/or soft tissues. Uric acid results     blood pressure, cognition, and glucose/fat metabolism.5
    from the breakdown of purines and is normally excreted        Hyperuricemia may also play a role in CVD, metabolic
    through the kidneys. In the majority of cases,                syndrome, diabetes, renal disease, and hypertension.6
    hyperuricemia (serum uric acid (sUA) levels > 6.8 mg/dL)
    results from inadequate renal excretion, but excessive        INCREASING INCIDENCE OF GOUT
    intake of purine or its precursors, overproduction of uric    In the period between 1988 and 1994, it is estimated that
    acid, or genetic disorders can result in serum uric acid      there were 5.1 million men and women with gout living in
    accumulation.1 In the joints these crystals cause a painful   America.7 Men are more likely than women to suffer gout,
    inflammatory arthritis, usually monoarticulated in the        with peak prevalence in the 75-84 year range
    lower extremities, commonly in the big toe (often referred    (Figure 1).8 These data were derived from the United
    to as podagra). Gout can also affect other joints, bursae     Kingdom General Practice Research Database, with
    and tendons. Deposits of uric acid crystals that occur        records from more than 1.8 million people.
    under the skin are known as tophi. These crystals can
    also collect in the kidney and cause kidney stones and
                                                                     Figure 1. Gout prevalence in 19998
    urate nephropathy. Hyperuricemia can be exacerbated by
    diet, medications, hematologic and comorbid conditions,                                     100
    and renal impairment.2 Factors favoring crystal formation                                   90           Women
    are thought to be low temperature (peripheral joints
                                                                    Prevalence (per 1000 pts)


    during sleep) and low pH (acidosis). Uric acid solubility                                   70

    decreases with low pH and aciduria has been associated                                       60

    with uric acid stone formation.3                                                             50


    The first phase of clinical gout is joint inflammation and                                   30

    can be precipitated by fluctuations in serum uric acid;                                      20

    local trauma; binges of alcohol, overeating, or fasting;
    acute illness; or exposure to cold. Clinical manifestations                                       < 24    25–34   35–44      45–54   55–64    65–74   75–84   ≥ 85

    of gouty arthritis are shared by other arthropathies and                                                                  Age Group (years)
    accurate diagnosis depends on identification of uric acid
    crystals in the synovial fluid of affected joints.
                                                                  There is also evidence that the incidence of acute gout is
    Treatment of an acute flare focuses on inflammation
                                                                  increasing (Figure 2).9 This observation supports the
    reduction and pain management. Interval or intercritical
                                                                  higher incidence in men and a general increase with age.
    gout is the phase after recovery from an acute flare,
                                                                  Part of the observed increase in the incidence of gout
    when treatment focuses on multiple strategies to lower
                                                                  over this period may be associated with increased
    sUA and prevent recurrence of the acute condition.
                                                                  physician awareness and higher diagnosis rates.
    Treatment in this asymptomatic phase is important, as
                                                                  However, results from a UK survey suggest that the
    almost 80% of individuals who suffer an acute attack
                                                                  incidence of gout was relatively stable in the 1990s.8
    experience another acute flare within 2 years.4 Chronic
    gout (formerly called chronic tophaceous gout) is the
                                                                  A number of factors have been proposed for this
    most disabling stage of this disease and can cause
                                                                  increase. These include the overall increase in longevity;
    permanent damage to the affected joints and kidneys. It
                                                                  increase in prevalence of hypertension and metabolic
    can also be characterized by large sodium urate deposits
                                                                  syndrome; the use of diuretics and low dose aspirin;
    (tophi), commonly in the hands, forearms, knees, ears, or
                                                                  dietary trends; increases in end-stage renal disease; and
                                                                  organ transplantations.10 Patients with gout are also more

  Figure 2. Incidence of acute gout in Rochester, MN according                              Of special note is the role of high-fructose corn syrup. It
  to age at diagnosis at two times: 1977-1978 (n = 39) and                                  has been known for some time that fructose can induce
  1995-1996 (n = 81)9                                                                       hyperuricemia,12 but use of this sweetener has increased
                                                                                            dramatically in recent decades and recent publications
                            500                                                             support the link between sugar-sweetened soft drinks
                                                                                            and gout. Choi et al examined the relationship between
Incidence Rates x 100,000

                                                  1995–1996                                 soft drink consumption and sUA levels in participants in
                                                  1977–1978                         Men     the NHANES study.13 They stratified patients by their daily
                                                                                            consumption of sugar-sweetened soft drinks and found a
                            200                                                             positive correlation with the level of sUA (P < 0.001 for
                                                                                    Women   trend). There was also a positive correlation between the
                                                                                            number of sugar-sweetened soft drinks consumed per
                              0                                                             day and the number of individuals with hyperuricemia
                                  0      20          40         60           80   100       (P < 0.003 for trend). For example, individuals who
                                              Age at Gout Diagnosis (year)                  consumed 1-3 such drinks per day had a multivariate
                                                                                            odds ratio of 1.51 for hyperuricemia. There was no
                                                                                            correlation between diet soft drink consumption and the
                              likely to have comorbid conditions, more complicated          number of hyperuricemic individuals.
                              treatment regimens and a greater potential for drug-drug
                              interactions or toxicities.10                                 A large prospective cohort study revealed an elevation of
                                                                                            risk of gout by consumption of sugar-sweetened soft
                              RISK FACTORS                                                  drinks. Compared with men who consumed less than 1
                              Multiple factors increase the risk of gout (Table 1). As      such drink per month, the multivariate relative risks of
                              shown in Figure 2, the incidence of gout increases with       gout in men who consumed 5-6 drinks per week, 1 per
                              age. Though it is relatively rare in premenopausal women,     day, and 2 or more per day were 1.29, 1.45, and 1.85,
                              a slope similar to that of men is observed with women         respectively (P = 0.002 for trend).14 Thus the risks of
                              after approximately 60 years of age.                          hyperuricemia and gout are increased with consumption
                                                                                            of sugar-containing soft drinks.
                              Diet is also an important modifiable risk factor. Uric acid
                              is derived from purines, a component of nucleic acids.            Table 1. Risk factors for the development of gout15

                                                                                                  • Male Gender                  • Drugs
                              Conventional wisdom holds that purine-rich foods would
                                                                                                                                   – Diuretics
                              therefore add to the risk of gout, and dietary
                                                                                                  • Age
                                                                                                                                   – Cyclosporine
                                                                                                    – Longevity
                              recommendations2 were based primarily on the purine
                                                                                                                                   – Low dose aspirin
                                                                                                    – Post-menopause
                              content of the food. Choi et al studied more than 47,000
                                                                                                                                   – Niacin
                                                                                                  • Diet
                              men without gout at enrollment over a period of 12 years
                                                                                                                                 • Comorbid Conditions
                                                                                                    – High alcohol (beer >
                              to determine which types of food correlated with first
                                                                                                                                   – ESRD
                                                                                                      spirits > wine)
                                                                                                                                   – Hypertension
                              attacks of gout.11
                                                                                                    – Red/organ meats
                                                                                                                                   – Metabolic syndrome
                              The risk of developing gout in men who consumed the                     and seafood
                                                                                                    – High fructose corn
                              most meat was 1.4 times the risk of those who
                              consumed the least amount of meat. Similarly, men who
                              consumed the most seafood had a 50% higher risk than
                              low consumers. This is in contrast to dairy products,         Examination of the alcohol intake habits of the same
                              where men had almost a 45% lower risk if they had a           group of men showed that the multivariate relative risk of
                              high consumption of dairy products. Contrary to earlier       gout increases with alcohol consumption in both lean and
                              beliefs about dietary risks, consumption of purine-rich       overweight/obese individuals.16 The study also revealed
                              vegetables (such as asparagus, peas, dried beans,             differences between forms of alcohol: beer presented the
                              mushrooms and spinach) and total protein intake were          highest risk, followed by spirits; moderate wine drinking
                              not associated with increased or decreased risk of gout.      was not associated with increased risk of gout.

                        The Gout Clinical Companion:
                        The Latest Evidence and Patient Support Tools for the Primary Care Physician

      Table 2. Age adjusted relative risk of death due to various diseases by sUA level. CHD is defined as acute coronary
      myocardial infarction19

                 SUA (mg/dl)
      Disease                              0.3–4.9                       5.0–6.4                    6.5–8.4                    8.5–13.0

        All                          1.05 (0.89, 1.23)                     1.0                 1.17 (1.00, 1.37)+         1.62 (1.21, 2.17)**
        CHD                          0.97 (0.54, 1.74)                     1.0                  1.44 (0.86, 2.41)          1.52 (0.54, 4.30)
        Other heart disease          0.69 (0.40, 1.21)                     1.0                  1.10 (0.68, 1.76)         2.97 (1.53, 5.74)**
        Stroke                       0.49 (0.28, 0.86)*                    1.0                  1.16 (0.77, 1.74)         2.33 (1.22, 4.44)**
        Renal failure                0.60 (0.12, 2.98)                     1.0                  1.50 (0.46, 4.93)        8.52 (2.40, 30.28)**
        Cancer                       1.28 (0.99, 1.65)                     1.0                  1.12 (0.86, 1.46)          0.60 (0.28, 1.29)
        Hepatic disease              1.82 (1.00, 3.34)                     1.0                  0.78 (0.36, 1.69)         3.58 (1.44, 8.87)**

        RR (95% Confidence Interval); +P < 0.1; *P < 0.05; **P < 0.001

    Frequently used medications have also been found to                          DIAGNOSIS
    increase the risk for gout. Loop and thiazide diuretics, low                 Hyperuricemia is asymptomatic but crystallization of
    dose aspirin, niacin, cyclosporine, pyrazinamide,                            monosodium urate in the elbow, wrist, fingers, knee,
    ethambutol, and didanosine can decrease the excretion of                     ankle, subtalar, midfoot, and first metatarsophalangeal
    uric acid.17, 18                                                             joints can cause arthropathy with intense pain, swelling,
                                                                                 and erythema. The gold standard for diagnosis of gout is
    Heredity plays a role in gout risk, and multiple genes                       polarizing light microscopy of a synovial aspirate from the
    contribute to regulation of sUA. Since sUA is cleared                        affected joint. It can distinguish between gout, where
    primarily by the kidneys, renal impairment can contribute                    urate crystals are long and needle-shaped with strong
    to hyperuricemia. Some of the conditions associated with                     negative birefringence, and pseudogout, where calcium
    hyperuricemia and gout include insulin resistance and                        pyrophosphate crystals appear as rhomboids with weak
    hyperglycemia of type 2 diabetes, hypertriglyceridemia,                      positive birefringence (Figure 3).21
    low HDL level, hypertension, coronary atherosclerotic
    heart disease, central obesity, and chronic kidney                            Figure 3. Polarized light micrographs of joint aspirates21
    disease.8,17 Tomita et al assessed the relative risk of death
    due to various diseases as a function of sUA level
    (Table 2).19 They followed 49,413 Japanese working men
    (age < 60 years at enrollment) for 3-10 years and found
    that the men with the highest levels of sUA (8.5-13
    mg/dL) had elevated risk for death due to all causes, non-
    CHD heart disease, stroke, renal failure, and liver disease
                                                                                                  (A)                                  (B)
                                                                                     Monosodium urate crystals of      Crystals of calcium pyrophosphate
    (RR = 1.62, 2.97, 2.33, 8.52, and 3.58, respectively, all
    P < 0.01). Low levels of sUA were not associated with                             gout appear as fine yellow        associated with pseudogout are
                                                                                       needlelike crystals under        rhomboid. Arrows alongside the
                                                                                     compensated polarized light.       crystals indicate the direction of
    alterations of risk for most of these conditions, but men
    with the lowest levels of sUA (0.3-4.9 mg/dL) had a                                                                         the compensator.
    relative risk of 0.49 for death due to stroke (P < 0.05).

    In most cases of renal failure with hyperuricemia, the                       Although it is the only certain way to diagnose gout, joint
    elevated sUA is likely a consequence of decreased uric                       aspiration and visualization of synovial fluid under a
    acid excretion. There may be a causal link between                           polarizing light microscope is infrequently used. Most
    hyperuricemia and hypertension, as shown by animal                           diagnoses are based on a profile consisting of patient and
    experiments and pilot human trials.20                                        family histories, physical exam, symptoms, other
                                                                                 medications, and sUA level, though this is not the best

way. 21 The patient history may reveal comorbidities           Figure 4. Likelihood ratio (LR) and 95% confidence interval (CI) for
frequently associated with gout as well as prior episodes      various features in the diagnosis of gout24
of joint swelling with pain in the absence of trauma.
Factors consistent with gout, such as a family history of
                                                                                    Pain and swelling
gout, exposure to cold, binge alcohol consumption, or a
history of hyperuricemia may also be discovered.
Approximately 90% of first acute gout attacks are
                                                                                      Definite tophus
monoarticular; though approximately 50% of the initial
                                                                                     Possible tophus
attacks are in the first joint of the big toe,2 the most
                                                                    MSU crystals during acute attack
common cause of pain at this site is osteoarthritis.21 The
                                                              MSU crystals during intercritical period
patient should be examined for tophi on the ear, knee,
olecranon bursa, and extensor surfaces of the forearms
                                                                 Radiographic asymmetrical swelling
and feet. Table 3 gives the American College of
                                                                      Radiographic subcortical cysts,
Rheumatology preliminary criteria for diagnosis and                                      no erosion
                                                                                                    0.1     1           10      100      1000   10000
presumptive diagnosis of gout.22,23 Figure 4 summarizes                                                                 LR and 95% CI
the likelihood ratios for the various findings leading to a                                               Less likely             More likely
diagnosis of gout. Monosodium urate crystal identification     MSU, monosodium urate

during the acute attack has the highest likelihood ratio.

Table 3. American College of Rheumatology Preliminary
                                                              An acute gout attack may be associated with fever, rigors,
Criteria for Gout22,23                                        and an elevated white blood cell count. A complete blood

 Gout may be diagnosed if one of the following
                                                              count should be considered to exclude myeloproliferative
 criteria is present:
                                                              disorders. An elevated WBC count is consistent with
 – Monosodium urate crystals in synovial fluid
                                                              septic arthritis;25 gram staining and culture of the joint
 – Tophi confirmed with crystal examination                   aspirate must be performed in these situations to assess
                                                              for septic arthritis.21 Impaired renal function can
 A presumptive diagnosis may be made with at least
 six of the following findings:
                                                              contribute to hyperuricemia, and also can affect serum
 – Asymmetric swelling within a joint on a radiograph
                                                              levels of drugs, such as allopurinol, that are renally
 – First metatarsophalangeal joint is tender or swollen       cleared. Metabolic syndrome occurs in 63% of individuals
   (ie, podagra)                                              with gout and 25% of individuals without gout.13 The
 – Hyperuricemia
 – Maximal inflammation developed within one day
                                                              components of the metabolic syndrome individually
 – Monoarthritis attack
                                                              increase the odds ratio for gout. Table 4 summarizes lab
 – More than one acute arthritis attack                       tests that should be considered for patients with
 – Redness observed over joints                               suspected gout.25
 – Subcortical cysts without erosions on a radiograph
 – Suspected tophi
 – Synovial fluid culture negative for organisms during
                                                              Hyperuricemia is a critical risk factor for gout, though sUA
   an acute attack                                            is not a reliable predictor or diagnostic test during an
 – Unilateral first metatarsophalangeal joint attack          acute attack of gout. The limit of uric acid solubility in
 – Unilateral tarsal joint attack                             human serum is approximately 6.8 mg/dL and any value
                                                              above this level is considered hyperuricemia.26 The goal of
                                                              therapeutic intervention is to maintain sUA at a level
                                                              ≤ 6.0 mg/dL. Results from many clinical laboratories
   The gold standard for diagnosis is polarized
                                                              should be interpreted with care, as there is not a
   light microscopy of a synovial aspirate from
                                                              standard criterion for the normal range of uric acid. sUA
    the affected joint. Unfortunately, this test is
                                                              levels up to 8 or 8.5 mg/dL can be considered normal,
  infrequently used. Rather, most diagnoses are               but this judgment is based on population distributions and
   based on a profile consisting of patient and               should not be used in managing patients. For men with
    family histories, physical exam, symptoms,                sUA levels below 7.0 mg/dL, the annual incidence rate of
         other medications, and sUA level.                    gouty arthritis is 0.1%.27 As the level rises to between 7.0

                             The Gout Clinical Companion:
                             The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Table 4. Investigations to consider for patients with gout25          Figure 5. sUA values during acute flares and intercritical

     Test                Comment

     Synovial fluid      Only way to establish diagnosis with                                   Crystal verified cases
     monosodium          certainty

     urate crystals

     Serum urate         Level may go down during an acute attack


     Complete blood      To exclude myeloproliferative disorders;

                                                                             Urate (mM)

     count               elevated white cell count may indicate septic

     Renal function      Hyperuricaemia can occur in renal failure;

                         reduce dose of allopurinol

     Fasting lipids,     Hyperlipidemia, diabetes, hypothyroidism,

     glucose, and        and possibly hyperthyroidism are associated
     thyroid function    with gout                                                          0

     Urinary urate       Uricosurics are contraindicated in patients
                                                                                                   Acute                 Intercritical
                                                                                                   Flare                   Segment
     excretion           with high urinary excretion of urate. Some
                         authorities advise measuring this if the
                         serum urate concentration is > 0.8 mmol/l
                         because of risk of renal stone formation
                                                                         Abnormalities detected with x-ray radiographs have not
                                                                         been found to be sufficiently sensitive or specific for the
                                                                         diagnosis of gout.18 Only 45% of patients with gout have
         and 8.9 mg/dL the incidence rate grows to 0.5%, and for         any bony changes. The typical “punched out” periarticular
         men with sUA levels ≥ 9 mg/dL the rate is almost 5%.            erosions with overhanging edges are also late
                                                                         manifestations in patients with gout, which are seen 6-12
         There are far more people with hyperuricemia than with          years after the initial acute attack. Imaging methods such
         gout, suggesting that other factors are necessary for           as computed tomography (CT), ultrasonography (US), and
         development of the clinical disease. However, some gout         magnetic resonance imaging (MRI) have been considered
         sufferers do not have hyperuricemia at the time of              as diagnostic and monitoring tools for gout.29 None of
         presentation. Serum UA may be normal at the time of the         these methods has been shown to be a viable alternative
         acute attack, but should be measured 2 weeks thereafter.        to polarized microscopy for diagnosis of gout. However,
         A low sUA 2 weeks after a flare is unusual for true gout.       several uses have been demonstrated. The number and
         An observational study of consecutive gout patients             mass of tophaceous deposits can be ascertained better
         underscores the unreliability of sUA measurements during        with CT, US, or MRI than with physical examination or
         an acute flare.28 The median sUA value during acute flares      plain radiography, and power-Doppler US may be useful
         was 7.40 mg/dL (Figure 5). The median value after               in determining the extent of inflammation in joints.
         resolution of the acute flare was 9.41 mg/dL and only a
         few of the subjects had sUA values in the normal range.         DIFFERENTIAL DIAGNOSIS OF GOUT
                                                                         Several conditions can present like gout (Table 5).21
                                                                         Patients with rheumatoid arthritis (RA) may have nodules
           Hyperuricemia is a critical risk factor for gout,             similar to gouty tophi. RA nodules on the forearm are firm
         though sUA is not a reliable diagnostic test during             and not tender, usually on the extensor surface. Gouty
           an acute attack of gout; sUA may be normal at                 tophi are usually on the olecranon bursa. Again, a single
          the time of the acute attack. A low sUA 2 weeks                positive or negative sUA value is not sufficient to
                after a flare is unusual for true gout.                  distinguish these conditions. The deposition of calcium
                                                                         pyrophosphate dehydrate (CPPD) crystals is known as

  Table 5. Differential diagnosis of acute gout23
                                                        SYNOVIAL FLUID FINDINGS

 Diagnosis                    Joint Distribution             WBC Count*           Gram stain/      Synovial fluid          Radiography
                                                                                    culture          crystals†               findings

 Gout                          Lower extremities:           2,000 to 50,000         Negative      Needle shaped,        Acute: asymmetric
                             Metatarsophalangeal,           per mm3 (2 x 109                          negative               swelling
                           midtarsal, or knee joints;      to 50 x 109 per L)                      birefringence       Chronic: periarticular
                          initial attacks may be less                                                                     erosions with
                                common in upper                                                                        overhanging edges

 Pseudogout                   Knee, wrist, or first         2,000 to 50,000         Negative         Rhomboid           Soft tissue swelling,
 (calcium                    metatarsophalangeal               per mm3                                 shaped,           chondrocalcinosis
 pyrophosphate                                                                                      weak positive         (calcification of
 deposition disease)                                                                                birefringence             cartilage)

 Septic arthritis          Knee is most commonly           > 50,000 per mm3          Positive        No crystals           Joint effusion;
                            involved (may be any                                                                        radiography results
                               joint distribution)                                                                    otherwise normal early
                                                                                                                          in the disease
 Note: This table applies to immunocompetent patients. WBC = white blood cell. *The synovial fluid WBC count should not be used alone to
 exclude infection. †Septic arthritis may coexist with crystalline arthritis.

pseudogout and has a similar presentation to gout,                        but side effects often limit the dose. NSAID use has been
though it typically occurs in older individuals and affects               associated with GI and cardiovascular side effects and
the knee, wrist and thumb. These crystals can be most                     colchicine is associated with GI effects such as nausea,
accurately distinguished by polarization microscopy                       vomiting, and diarrhea; hepatic, renal, and neuromuscular
(Figure 3). This same test is necessary to define the                     effects; and bone marrow damage.30 These side effects
contributions of sepsis and gout to inflamed joints.                      of colchicine have been observed at the therapeutic dose
Because of the clinical similarity to these other conditions              (1 g loading dose, followed by 0.5 mg every two to three
and the relative underutilization of polarizing microscopy,               hours). Though use of lower dose colchicine has been
there is considerable misdiagnosis of gout.                               suggested, clinical trials that support its effectiveness
                                                                          have not been published. Intravenous colchicine is
MANAGEMENT                                                                associated with risk of severe toxicity and should not
The treatment goals for gout are different at the various                 be used.
stages of the disease. During the initial flare, the goal is
to terminate the attack as soon as possible and minimize
the inflammation and pain. After the episode has passed,                      During the initial flare, the goal is to terminate
the goal is to protect against further attacks, largely by                   the attack as soon as possible and minimize the
managing hyperuricemia through lifestyle modification                          inflammation and pain. After the episode has
and medication. A further goal is to prevent disease                           passed, the goal is to protect against further
progression by depleting the total body urate pool with a                       attacks, largely by managing hyperuricemia
goal of sUA < 6 mg/dL and correcting the metabolic                            through lifestyle modification and medication.
problems associated with hyperuricemia.

Acute Gout                                                                The European League Against Rheumatism (EULAR)
The first priority in managing acute flares of gout is to                 evidence-based recommendation for first-line treatment
reduce the intensity and length of the episode. The                       of acute gout is NSAID and/or oral colchicines.31 The
primary means of managing this stage of the disease is                    EULAR guidelines also support intra-articular or systemic
with NSAIDs, corticosteroids, and colchicine. Prompt                      administration of corticosteroids, especially in cases
treatment increases effectiveness of these medications,                   where NSAIDs or colchicine are contraindicated. Aspirin

                                                   The Gout Clinical Companion:
                                                   The Latest Evidence and Patient Support Tools for the Primary Care Physician

                      Table 6. Pharmacotherapy for acute gout23

                     Therapy/dosing                                                                                          Cautions                              Comments

                     NSAIDs                                                                                                  Use with caution in older             Any NSAID is effective
                       Indomethacin (Indocin), 50 mg three times daily for four to                                           patients and in patients with
                         10 days                                                                                             renal insufficiency, heart failure,
                       Naproxen (Naprosyn), 500 mg twice daily for four to 10 days                                           peptic ulcer disease, or liver
                       Sulindac (Clinoril), 200 mg twice daily for four to 10 days                                           disease and in those receiving
                                                                                                                             anticoagulation therapy

                     Corticosteroids                                                                                         Avoid in patients with joint          Intra-articular therapy
                      Prednisone, 20 to 40 mg daily for two or three days, then                                              sepsis and use cautiously in          may be the treatment of
                         taper over 10 to 14 days                                                                            patients with diabetes                choice if only one or two
                      Intra-articular methylprednisolone (Depo-Medrol), one 20- to                                                                                 accessible joints are
                         40-mg dose                                                                                                                                involved
                      Intramuscular methylprednisolone, one 80- to 120-mg dose

                     Colchicine, 0.6 mg orally two or three times daily                                                      Avoid in patients with severe         Avoid intravenous use;
                      Suggested renal dosing (based on creatinine clearance):                                                renal or hepatic impairment           best if used within the
                      > 50 mL per minute (0.83 mL per second): 0.6 mg twice daily                                            because it can lead to bone           first 24 hours of the
                      35 to 50 mL per minute (0.58 to 0.83 mL per second):                                                   marrow suppression and                attack; the most
                         0.6 mg daily                                                                                        neuromyopathy                         common adverse effects
                      10 to 34 mL per minute (0.17 to 0.57 mL per second):                                                                                         are nausea, vomiting,
                         0.6 mg every two or three days                                                                                                            and diarrhea; reduce the
                      < 10 mL per minute (0.17 mL per second): avoid                                                                                               dosage in older patients

                         NOTE: NSAIDs or corticosteroids are first-line therapies, depending on comorbidities; colchicine is an effective second-line therapy.
                         NSAID = nonsteroidal anti-inflammatory drug.

                should be avoided because it has been associated with                                                       UA excretion at the kidney tubule level. Acetoacetate is
                increased sUA concentration. Aspirin is a weak organic                                                      the metabolic product of ethyl alcohol and can also have
                acid. Even at low doses, aspirin can competitively inhibit                                                  this effect.

     Figure 6. Algorithm for treatment of acute gout2                                                                       Table 6 gives an overview of the commonly used
                                                                                                                            therapies for acute gout flares, including contraindications
                 Confirm Diagnosis
                 •   Monosodium urate crystals in synovial fluid                                                            and known drug interactions. Figure 6 summarizes the
                 •   Classic arthritis in patient with history of crystal-proven gout
                                                                                                                            stepwise introduction of NSAIDs, steroids, and colchicine
                 NSAID Risk Factors                                                                                         for the management of acute gout.2
                 •   Age > 65 years (relative risk factor)
                 •   CrCl < 50 mL per minute (0.84 mL per s)
                 •   Poorly compensated CHF                                                                                 Several emerging therapies for acute gout are based on
                 •   History of, or active peptic ulcer disease
                 •   Anticoagulation therapy                                                                                the observation that gout is an inflammatory condition,
                 •   Hepatic dysfunction
                                                                                                                            and that uric acid crystals play a role in this process.32
                                                                                                                            Macrophage secretion of cytokines such as IL-1 and
        No                                                   Yes
                                                                                                                            TNF-α is stimulated by uric acid, and inflammation could
     Treat with NSAID                           More than one joint involved?                                               be decreased by inhibiting IL-1 and TNF-α secretion.
                                                                                                                            Several IL-1 antagonists such as anakinra, rilonacept, and
                                  No                                                    Yes                                 canakinumab address this signaling mechanism and are
                                                                                                                            under clinical investigation.33,34
                     Joint accessible to injection?          No           Contraindication to steroids?

                                                              No                                            Yes
                                                                                                                            Transition from Acute to Chronic Management
               Intra-articular corticosteroid injection                                                                     The intercritical periods are the interludes between gouty
                                                      Oral prednisone                           Analgesics and joint rest   arthritis attacks. There are two related goals of disease
                                                      Intramuscular triamcinolone               Oral colchicine
                                                                                                                            management in these periods, preventing future attacks
     (CrCl = creatinine clearance; CHF = congestive heart failure)
                                                                                                                            and addressing the problem of hyperuricemia. The timing

for consideration of urate-lowering therapy is after the        Subjects were randomized to receive either 0.6 mg
acute attack has fully resolved and the patient has been        colchicine bid or placebo administered in a double-blind
stable for at least 1-2 weeks.35                                format. GI side effects triggered a dose reduction to once
                                                                per day (QD). Allopurinol was initiated at 100 mg po QD
Though symptoms are reduced during the intercritical            and escalated by 100 mg per dose (50 mg with renal
period, sUA can be elevated. What is the status of              impairment) at 2-3 week intervals, until the target of sUA
synovial crystals during the intercritical period? Pascual      < 6.5 mg/dL was reached. The study drug was continued
examined synovial fluid from asymptomatic knees of              for 3 months after the subject achieved an sUA < 6.5
patients with gout who were not receiving urate-lowering        mg/dL. All subjects reached this sUA goal. NSAID use was
pharmacotherapy.36 Half of the knees had been inflamed,         allowed for acute flares but chronic NSAID use was not
and urate crystals were detected in the aspirates of            permitted. Oral colchicine use during flares was not
36/37 (97%) of these joints. In contrast, crystals were         permitted.
detected in only 8/37 knees that had never been inflamed
(P < 0.00001). Cellular infiltration levels were higher in
                                                                 Figure 7. Mean number of acute gout flares is diminished by
the knees with crystals than in those without (449 vs 64         colchicine treatment during transition to allopurinol38
cells/mm, P < 0.00002). These findings suggest that
monosodium urate crystals persist in the joints of patients
with gout who do not receive urate-lowering therapy, and                                    (P = 0.022)   (P = 0.033)   (P = 0.008)
that the joints with crystals are populated with
                                                                   Mean # of Flares

inflammatory cells even in the absence of symptoms. A
subsequent study confirmed crystals in 43/43 synovial                                 2.0                                             Colchicine
                                                                                                                                      0.6 mg bid
fluid samples from knee and metatarsophalangeal joints                                1.5
of patients with intercritical gout who were not receiving                            1.0

hypouricemic therapy.37 Crystals were observed at a                                   0.5

somewhat lower rate (34/48) in synovial fluid from                                     0
                                                                                            0–3 mos        3–6 mos       Overall
patients receiving hypouricemic therapy. The median sUA
levels of the 2 groups were 8.4 mg/dL and 5.9 mg/dL,                                                         Time
respectively. Three factors correlated with the absence of
crystals: longer times since the last attack, lower levels of
sUA, and longer duration of therapy. Thus, it is important      There were 12 flares in the colchicine group and 65 in
to discuss chronic preventive treatment in patients with        the placebo group (Figure 7). These occurred in 33% and
gout.                                                           77% of the subjects, respectively (P = 0.008). Multiple
                                                                flares occurred in 14% and 63% of the subjects,
There is a danger of precipitating acute flares by              respectively (P = 0.004). The average duration of flares
changing the sUA concentration too rapidly.35 Colchicine        was not different between the groups. This study
(0.6 mg once or twice daily) or NSAIDs (eg, naproxen 250        supports the prophylactic use of colchicine during the
mg/day) are recommended to reduce inflammation in the           transition to allopurinol during the intercritical period.
transition from management of acute flares with NSAIDs          Since there were multiple acute flares after colchicine
or glucocorticoids to uric acid lowering strategies.35,17       termination, it is recommended that colchicine treatment
Colchicine dosing is limited by its GI side effects (such as    is continued for 6 months after the initiation of
diarrhea) and bone marrow suppression. In the presence          allopurinol.
of renal disease, lower doses of colchicine should be
used; there is danger of axonal neuromyopathy or
rhabdomyolysis, especially with macrolide or statin use.35
Neither colchicine nor NSAIDs will modify sUA levels.             It is recommended that prophylactic colchicine
                                                                    or NSAID treatment is continued for at least
Clinical support for the effectiveness of low-dose                     6 months after the initiation of xanthine
colchicine during initiation of allopurinol was provided by                     oxidase inhibitors.
a study of 43 subjects with crystal-verified chronic gout.38

                       The Gout Clinical Companion:
                       The Latest Evidence and Patient Support Tools for the Primary Care Physician

     Use of a transition medication such as NSAIDs or                Figure 8. Purine metabolism
     colchicine has become standard practice during the
     intercritical period.                                                                                           Degradation of
                                                                                                       ATP depletion nucleic acids
                                                                               Degradation of
     Chronic Gout                                                                                            AMP         GMP
                                                                                                           Adenosine   Guanosie
     The goal for the management of chronic gout is to                           Amino acids                Adenine    Guanine
     prevent further attacks and disease progression, largely
     through lifestyle modification and medication that                           Glutamate

     maintains the sUA < 6 mg/dL. Lifestyle and diet                                 NH3                      IMP
                                                                          UREA                 Glutamine
     modifications can have a positive impact on sUA. Obesity
     is a common and growing risk factor. The success rate of                                              Inosine

     weight reduction efforts is low, but patients should be
     encouraged to lose excess weight as part of their gout                                           Hypoxanthine

     management program. A pilot study in 13 men showed                                               XO
     that a modified diet, including caloric restriction resulted
     in weight loss, improvements in lipid profile, sUA                                                    Xanthine

     decrease, and frequency of acute gout attacks.39 Though                                          XO
     this study was not placebo controlled and had only a
     small number of participants, it suggests positive                                                 Uric Acid

     disease-related results from dietary control. To manage                                     Uricase
     the formation side of the uric acid balance, foods with
     high amounts of purine, such as animal and seafood                                                    Allantoin

     protein content, should be avoided. Recommendations for
     management of food and beverage consumption are
     summarized in a food pyramid provided in the tools
     section.                                                       XANTHINE OXIDASE INHIBITORS
     Several steps in the purine metabolic cascade (Figure 8)       Allopurinol is a xanthine oxidase inhibitor that has been
     are amenable to pharmacotherapy. The purines that enter        available in the US for more than 40 years. Data pooled
     the pathway can be derived from amino acids, from              from several clinical studies show a dose-dependent
     nucleic acid metabolism, or from ATP degradation (the          reduction in sUA (Figure 9). For every 100 mg/day dose
     primary mechanism in humans). Purines are metabolized          increment, there is approximately a 1 mg/dL decrease in
     by a series of enzymes, ultimately leading to urea and         serum uric acid.31
     ammonia generation. Unlike non-primate mammals,
     humans have no functional uricase, so the end product of       About 20% of patients who take allopurinol report side
     purine metabolism is uric acid. The two reactions              effects, most commonly gastrointestinal intolerance
     catalyzed by xanthine oxidase (XO) and the step catalyzed      and skin rashes. A rare but serious adverse reaction is
     by uricase mediate the uric acid level and can be              allopurinol hypersensitivity syndrome, and features may
     influenced by pharmacotherapy.5                                include fever, skin rash, eosinophilia, hepatitis,
                                                                    progressive renal insufficiency, and death.40 Caution is
     The xanthine oxidase inhibitors allopurinol and febuxostat     needed in patients with renal failure, those taking
     inhibit the formation of uric acid; rasburicase and the        azathioprine or mercaptopurine, and those taking
     experimental enzyme PEGylated uricase decrease uric            warfarin, since allopurinol can heighten the
     acid by degrading UA to allantoin, which is more highly        anticoagulation effect.41 It is recommended that
     soluble and can be excreted by the kidneys. Another            allopurinol be started at 100 mg/day and titrated in steps
     approach is to increase the renal excretion of uric acid       of 100 mg/day at 3-4 week intervals, with a maximum
     with a uricosuric agent such as probenecid.                    dose of 800 mg/day.42 Though allopurinol can be used in
                                                                    patients with renal insufficiency, a dose reduction has

Figure 9. Dose dependent relationship between allopurinol dose                                                                   measurements, was reached in 53% of patients receiving
and serum uric acid (r = 0.70, P < 0.01)31                                                                                       80 mg febuxostat, 62% of those receiving 120 mg
                                                                                                                                 febuxostat, and 21% of those receiving allopurinol
                                        15                                                                                       (P < 0.001 for the comparison of each febuxostat group
SUA mg/dl and 95% Confidence Interval

                                                                                                                                 with the allopurinol group).
                                                                                                                                 The larger (N = 1072) placebo-controlled APEX trial
                                          9                                                                                      (Allopurinol- and Placebo-Controlled Efficacy Study of
                                          7                                                                                      Febuxostat) was a 28-week study of placebo, febuxostat
                                                                                                                                 (80 mg, 120 mg or 240 mg), and allopurinol (300 mg) in
                                          4                                                                                      patients with gout, some of whom were renally
                                                                                                                                 compromised.47 Renally impaired subjects in the
                                          1                                                                                      allopurinol group received 100 mg instead of 300 mg.
                                         -1                                                                                      The primary endpoint was the same as in the FACT trial.
                                        -2                                                                                       As seen in Figure 10, all concentrations of febuxostat
                                              N = 115     4       46       77       50        3        27       9         2      were associated with higher proportions of patients
                                                 0.00            200.00            400.00            600.00            1000.00   achieving the primary endpoint than allopurinol or
                                                        100.00            300.00            500.00            800.00
                                                                                                                                 placebo (P < 0.001). Allopurinol was also superior to
                                                                       Allopurinol (mg/day)                                      placebo in this measure (P < 0.001). Overall rates of
                                                                                                                                 adverse events were similar in the groups, but diarrhea
                                        been proposed, depending on the level of creatinine                                      and dizziness were more frequent in the high dose
                                        clearance. This scheme has never been shown to protect                                   febuxostat group. Withdrawals due to gout flares were
                                        patients from allopurinol toxicity. Recent publications                                  more common in the febuxostat groups.
                                        demonstrate that following this guideline leads to
                                        undertreatment of hyperuricemia and no reduction in                                       Figure 10. Febuxostat and allopurinol efficacy in several phase 3
                                        allopurinol-associated toxicity.43                                                        clinical trials. Data are percent of subjects with sUA < 6 mg/dL
                                                                                                                                  at the final visit. APEX and FACT included higher doses of
                                        In a randomized study of dosing adherence, no acute                                       febuxostat (data not shown)46,47,48,50
                                        flares were observed after 2 years of continuous
                                        medication with allopurinol.44 Patients who received                                                      80
                                                                                                                                                                        72*         74*
                                        intermittent therapy (2 months per year) with allopurinol                                                 70          67*#                             Febuxostat 40 mg
                                        continued to suffer acute attacks up to 3 years of                                                        60                                           Febuxostat 80 mg
                                        observation (P < 0.005). This suggests that continued
                                                                                                                                   Subjects (%)

                                                                                                                                                  50    45‡
                                        adherence to a xanthine oxidase inhibitor regimen is                                                      40                          39
                                        beneficial for the long-term management of gout.                                                          30

                                        In February 2009, the FDA approved another xanthine
                                        oxidase inhibitor, febuxostat, for the chronic management                                                      CONFIRMS       APEX         FACT
                                        of hyperuricemia in patients with gout.45
                                                                                                                                     *P < 0.001 vs allopurinol
                                                                                                                                     #P < 0.001 vs febuxostat 40 mg
                                        The large Febuxostat versus Allopurinol Control Trial                                        ‡Non-inferior to allopurinol

                                        (FACT)46 study addressed the relative efficacy of
                                        febuxostat and allopurinol in 760 patients with gout and
                                        sUA ≥ 8.0 mg/dL. Subjects received 80 mg or 120 mg                                       The 6 month CONFIRMS trial49 assessed urate-lowering
                                        febuxostat or 300 mg allopurinol daily for 52 weeks. A                                   efficacy and safety of daily febuxostat (40 mg or 80 mg)
                                        fixed dose of allopurinol was used in this study, though                                 or allopurinol (300 mg) in subjects with gout and sUA
                                        optimal allopurinol dosing requires titration. The primary                               ≥8.0 mg/dL.50 Subjects (N = 2269) were randomized to
                                        endpoint, sUA < 6.0 mg/dL at the last 3 monthly                                          the 3 treatment groups. Subjects with moderate CKD in

                        The Gout Clinical Companion:
                        The Latest Evidence and Patient Support Tools for the Primary Care Physician

      Table 7. Substances acting in the kidney that affect uric acid levels and their underlying mechanisms51

       Urate-increasing agents
         Pyrazinamide                                  Trans-stimulation of URAT1
         Nicotinate                                    Trans-stimulation of URAT1
         Lactate, β-hydroxybutyrate, acetoacetate      Trans-stimulation of URAT1
         Salicylate (low dose)                         Decreased renal urate excretion
         Diuretics                                     Increased renal tubular reabsorption associated with volume depletion,
                                                       may stimulate URAT1
         Cyclosporine                                  Increased renal tubular reabsorption associated with decreased glomerular
                                                       filtration, hypertension, interstitial nephropathy
         Tacrolimus                                    Similar to cyclosporine
         Ethambutol                                    Decreased renal urate excretion
       Urate-decreasing agents
         Probenecid                                    Inhibition of URAT1
         Sulfinpyrazone                                Inhibition of URAT1
         Benzbromarone                                 Inhibition of URAT1
         Losartan                                      Inhibition of URAT1
         Salicylate (high-dose)                        Inhibition of URAT1
         Fenofibrate                                   May inhibit URAT1
         Amlodipine                                    Increased renal urate excretion

     the allopurinol group received 200 mg. Proportions of all         treatment, it need not be discontinued. The gout flare
     subjects achieving the primary endpoint of sUA < 6.0              should be managed concurrently, as appropriate for the
     mg/dL at the final visit were 45%, 67%, and 42% in the            individual patient.
     febuxostat 40 mg, febuxostat 80 mg, and allopurinol
     groups, respectively. Efficacy for febuxostat 40 mg was           URICOSURIC
     similar to allopurinol, but febuxostat 80 mg was superior         Renal clearance of uric acid is a key aspect of its
     to both febuxostat 40 mg and allopurinol (P < 0.001 for           homeostasis, and kidney is the target of many drugs that
     both comparisons). In subjects with CKD, efficacy with            influence sUA. Probenecid is a second-line treatment for
     febuxostat 80 mg was also greater (72%; P < 0.001) than           gout. It inhibits urate transporter-1 (URAT1) which is
     with febuxostat 40 mg (50%) or allopurinol (42%). In              expressed at the apical brush-border membrane of
     these subjects, febuxostat 40 mg showed greater efficacy          kidney proximal tubular epithelial cells and is a major
     than allopurinol (P < 0.021). Rates of all adverse events         contributor to uric acid reuptake.51 It has been shown to
     were comparable across groups or by renal function.               be effective in 65% of patients with gout who did not
     These results suggest that febuxostat is an effective             achieve the British 2007 guideline52 goal of sUA < 5
     urate-lowering compound that may be especially useful             mg/dL with allopurinol.53 Because it acts at the proximal
     in patients with gout and CKD.                                    tubules on the organic ion transport system, there are
                                                                       multiple drug interactions, which limit its usefulness in
     The recommended starting dose of febuxostat for                   patients who are treated with other therapeutic agents.
     treatment of hyperuricemia in patients with gout is 40 mg         Table 7 highlights probenecid and other drugs that
     once daily.45 For patients who do not achieve a sUA less          increase or decrease sUA through renal mechanisms.
     than 6 mg/dL after 2 weeks with 40 mg, febuxostat 80              Note that aspirin can have different effects, which depend
     mg is recommended. No dose adjustment is necessary                on the dose. At low levels it can decrease urate excretion,
     when administering febuxostat in patients with mild to            yet at high levels it can increase the excretion of urate.
     moderate renal impairment or mild to moderate hepatic             Probenecid is not recommended in patients with renal
     impairment. If a gout flare occurs during febuxostat              impairment or a history of nephrolithiasis, but may be

useful in patients who are intolerant or not adequately         SUMMARY
treated with xanthine oxidase inhibitors. Yet there is a        Gout remains a debilitating and often misdiagnosed
need to ensure that these patients be able to drink 8           disease. The gold standard for diagnosing gout, polarizing
glasses of water each day to minimize nephrolithiasis.          light microscopy of synovial aspirates, is not frequently
                                                                done, and the disease is usually diagnosed on the basis
ADHERENCE                                                       of clinical and laboratory tests and elimination of other
Urate lowering is generally considered a life long              possible diagnoses such as rheumatoid arthritis and
commitment and therefore patient adherence with uric            septic arthritis.
acid lowering strategies is critical for many reasons. First,
regular diet and use of medication enhance achievement          An initial gout attack is followed by an intercritical period
of sUA goals, which improves long term management of            and then a time of chronic management. The second and
flares and tophi. Second, positive and negative                 third phases can be punctuated by acute flares.
fluctuations of sUA levels caused by intermittent               Therapeutic management is aimed first at reducing the
adherence are associated with acute flares. Patients            inflammation and pain of the initial attack, controlling risk
experiencing extreme pain during an acute flare are likely      factors for subsequent attacks, and then with gradually
to doubt the effectiveness of their medication and stop         stabilizing serum uric acid at a level below 6 mg/dL.
taking it, exacerbating the sUA fluctuations. Acute flares      Lifestyle approaches that decrease the risk of subsequent
can be diminished by using colchicine in the transition         flares include diet control and weight loss. Gout is often
period between acute and chronic management, but                found with other conditions such as hypertension, CVD,
again, sufficient dosing by the provider and adherence by       renal disease, diabetes, and obesity, which present
the patient are critical to improving outcomes.                 metabolic and pharmacologic challenges. Managing these
                                                                comorbidities should be one of the goals of a gout
Despite the importance of lifestyle and medication              management program. Pharmacologic tools for managing
adherence, flares can occur even with good patient              serum uric acid include probenecid, allopurinol, and the
adherence, and may not occur without it. The process of         recently approved febuxostat. NSAIDs and colchicine are
reducing sUA must be undertaken in a controlled manner,         used to treat acute attacks and for prophylaxis. These
since abrupt fluctuations in sUA can trigger a flare and        drugs must be administered properly and adhered to by
subsequent nonadherence. Additionally, useful lifestyle         the patient for optimal results.
changes such as diet control and weight loss are
extremely difficult for most patients to achieve on a
consistent and lasting basis. Perhaps patient awareness                     PATIENT EDUCATION TOOLS
of sUA levels can enhance adherence to lifestyle and              Several Patient Education Tools are provided in
medication changes, though clinical trials have not been          the following section. These tools can be copied
undertaken to test this notion. However, there is evidence        and shared with patients to help them understand
to show that clinicians do not monitor sUA on a regular           gout and to increase their adherence to lifestyle
basis and do not follow patients with gout on a regular           recommendations and medication. Since self-
basis.54 Also, less than 50% of patients who were started         management is an important part of treating gout,
on allopurinol continued its use after the initial                these tools are designed to make 4 crucial topics
prescription.55 This reinforces the need for clinicians to        more accessible for patients:
educate their patients and ensure that they are followed
on a regular basis like other chronic diseases. Since             •   Managing Gout Pain
                                                                  •   Diet and Weight Management
intercritical and chronic gout management is
                                                                  •   Medications for Treating Gout
complicated, it is important that patients are engaged in
                                                                  •   Adherence is Critical for Gout Management
the campaign to control sUA levels. Tools to increase
adherence and patient self-management are provided at             In addition to the summary of information on each
the end of this piece.                                            topic, several Internet resources are offered for
                                                                  patients who want to gather further information.

                         The Gout Clinical Companion:
                         The Latest Evidence and Patient Support Tools for the Primary Care Physician

     1. Pittman JR, Bross MH. Diagnosis and management of gout.          15. Bieber JD, Terkeltaub RA. On the brink of novel therapeutic
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     2. Harris MD, Siegel LB, Alloway JA. Gout and hyperuricemia.
     Am Fam Physician. 1999;59(4):925-934.                               16. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G.
                                                                         Alcohol intake and risk of incident gout in men: a prospective
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                                                                         21. Dore RK. The gout diagnosis. Cleve Clin J Med.
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     nephrolithiasis: the National Health and Nutrition Examination
     Survey III, 1988-1994. Am J Kidney Dis. 2002;40(1):37-42.           22. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu
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     9. Arromdee E, Michet CJ, Crowson CS, O'Fallon WM, Gabriel          24. Zhang W, Doherty M, Pascual E, et al. EULAR evidence-
     SE. Epidemiology of gout: is the incidence rising? J Rheumatol.     based recommendations for gout. Part I: Diagnosis. Report of a
     2002;29(11):2403-2406.                                              task force of the Standing Committee for International Clinical
                                                                         Studies Including Therapeutics (ESCISIT). Ann Rheum Dis.
     10. Luk AJ, Simkin PA. Epidemiology of hyperuricemia and gout.      2006;65(10):1301-1311.
     Am J Manag Care. 2005;11:S435-S442.
                                                                         25. Underwood M. Diagnosis and management of gout. BMJ.
     11. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G.           2006;332(7553):1315-9.
     Purine-rich foods, dairy and protein intake, and the risk of gout
     in men. N Engl J Med. 2004;350(11):1093-1103.                       26. Mandell BF. Clinical manifestations of hyperuricemia and
                                                                         gout. Cleve Clin J Med. 2008;75(Suppl 5):S5-S8.
     12. Perheentupa J, Raivio K. Fructose-induced hyperuricaemia.
     Lancet. 1967;2(7515):528-531.                                       27. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic
                                                                         hyperuricemia. Risks and consequences in the Normative Aging
     13. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft          Study. Am J Med. 1987;82(3):421-426.
     drinks, diet soft drinks, and serum uric acid level: the Third
     National Health and Nutrition Examination Survey. Arthritis         28. Logan JA, Morrison E, McGill PE. Serum uric acid in acute
     Rheum. 2008;59(1):109-116.                                          gout. Ann Rheum Dis. 1997;56(11):696-697.

     14. Choi HK, Curhan G. Soft drinks, fructose consumption, and       29. Perez-Ruiz F, Naredo E. Imaging modalities and monitoring
     the risk of gout in men: prospective cohort study. BMJ.             measures of gout. Curr Opin Rheumatol. 2007;19(2):128-133.

16   References
30. Nuki G. Colchicine: its mechanism of action and efficacy in       45. Febuxostat [package insert]. Available at:
crystal-induced inflammation. Curr Rheumatol Rep.                     http://www.uloric.com/?gclid=CLWJ_KyHipkCFQsMGgod8G6ykg.
2008;10(3):218-227.                                                   Accessed April 2009.

31. Zhang W, Doherty M, Bardin T, et al. EULAR evidence-based         46. Becker MA, Schumacher HR Jr, Wortmann RL, et al.
recommendations for gout. Part II: Management. Report of a            Febuxostat compared with allopurinol in patients with
task force of the EULAR Standing Committee For International          hyperuricemia and gout. N Engl J Med. 2005;353:2450-2461.
Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum
Dis. 2006;65;1312-1324.                                               47. Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects
                                                                      of febuxostat versus allopurinol and placebo in reducing serum
32. Pillinger MH, Rosenthal P, Abeles AM. Hyperuricemia and           urate in subjects with hyperuricemia and gout: a 28-week,
gout: new insights into pathogenesis and treatment. Bull NYU          phase III, randomized, double-blind, parallel-group trial. Arthritis
Hosp Jt Dis. 2007;65(3):215-221.                                      Rheum. 2008;59(11):1540-1548.

33. Αnakinra [package insert]. Available at:                          48. Joseph-Ridge N. FDA presentation available at:
http://www.fda.gov/Cder/foi/label/2003/anakamg062703LB.pdf.           http://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4387s1-
Accessed April 2009.                                                  02-Takeda.pdf. Accessed May 2009.

34. Rilonacept [package insert]. Available at:                        49. Assessing the efficacy and safety of oral febuxostat in
http://www.regeneron.com/ARCALYST-fpi.pdf. Accessed April             subjects with gout. Available at:
2009.                                                                 http://clinicaltrials.gov/ct2/results?term=NCT00430248.
                                                                      Accessed June 2009.
35. Shumacher HR Jr, Chen LX. The practical management of
gout. Cleve Clin J Med. 2008;75(Suppl 5):S22-25.                      50. Becker M, Schumacher HR, Espinoza L, et al. A phase 3
                                                                      randomized, controlled, multicenter, double-blind trial (RCT)
36. Pascual E. Persistence of monosodium urate crystals and           comparing efficacy and safety of daily Febuxostat (FEB) and
low-grade inflammation in the synovial fluid of patients with         Allopurinol (ALLO) in subjects with gout. American College of
untreated gout. Arthritis Rheum. 1991;34(2):141-145.                  Rheumatology 2008 Annual Scientific Meeting. Abstract L11.
                                                                      Available at: http://acr.confex.com/acr/2008/webprogram/
37. Pascual E, Batlle-Gualda E, Martínez A, et al. Synovial fluid     Paper3414.html#top. Accessed June 2009.
analysis for diagnosis of intercritical gout. Ann Intern Med.
1999;131(10):756-759.                                                 51. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann
                                                                      Intern Med. 2005;143(7):499-516.
38. Borstad GC, Bryant LR, Abel MP, et al. Colchicine for
prophylaxis of acute flares when initiating allopurinol for chronic   52. Jordan KM, Cameron JS, Snaith M, et al. British Society for
gouty arthritis. J Rheumatol. 2004;31(12):2429-2432.                  Rheumatology and British Health Professionals in Rheumatology
                                                                      Guideline for the Management of Gout. Rheumatology.
39. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J.        2007;46:1372-1374.
Beneficial effects of weight loss associated with moderate
calorie/carbohydrate restriction, and increased proportional          53. Reinders MK, van Roon EN, Jansen TL, et al. Efficacy and
intake of protein and unsaturated fat on serum urate and              tolerability of urate-lowering drugs in gout: a randomised
lipoprotein levels in gout: a pilot study. Ann Rheum Dis.             controlled trial of benzbromarone versus probenecid after
2000;59:539-543.                                                      failure of allopurinol. Ann Rheum Dis. 2009;68;51-56.

40. Wortmann RL. Recent advances in the management of gout            54. Sarawate CA, Brewer KK, Yang W. Gout medication
and hyperuricemia. Curr Opin Rheumatol. 2005;17(3):319-324.           treatment patterns and adherence to standards of care from a
                                                                      managed care perspective. Mayo Clin Proc. 2006;81(7):925-
41. Terkeltaub RA. Gout. N Engl J Med. 2003;349:1647-1655.            934.

42. Allopurinol [package insert]. Available at:                       55. Sarawate CA, Patel PA, Schumacher HR, et al. Serum urate
http://zyloprim.us/Zyloprim.pdf. Accessed April 2009.                 levels and gout flares: analysis from managed care data. J Clin
                                                                      Rheumatol. 2006; 12:61-65.
43. Dalbeth N, Stamp L. Allopurinol dosing in renal impairment:
walking the tightrope between adequate urate lowering and
adverse events. Semin Dial. 2007;20(5):391-395.

44. Bull PW, Scott JT. Intermittent control of hyperuricemia in
the treatment of gout. J Rheumatol. 1989;16(9):1246-1248.

                                                                                                                               References    17
                         The Gout Clinical Companion:
                         The Latest Evidence and Patient Support Tools for the Primary Care Physician

     Attestation/Evaluation Form
     To obtain credit, participants are required to:

     1. Read the learning objectives, review the activity, and complete the posttest.
     2. Complete this Attestation/Evaluation form.
     3. Send or fax these forms to:        The France Foundation • Gout Clinical Companion
                                           230 Shore Road • Old Lyme, CT 06371
                                           Tel: 860-434-1650 • Fax: 860-434-5390

     First Name: _________________________________ Last Name: _____________________________________

     Address: __________________________________________________________________________________

     City: ___________________________________________ State: ____________ ZIP: ____________________

     E-mail: ________________________________________________ Tel: _______________________________
     Your certificate will be sent to this e-mail address

     Degree(s):      K MD/DO        K PharmD/RPh            K NP    K PA    K RN      K Other______________________

     Specialty:      K Primary Care       K Family Practice        K Other______________________

                     Indicate the number of AMA PRA Category 1 Credits™ you are claiming _____ (Max 2 credits)

          Signature:______________________________________________________ Date:____________________
                                  I certify that I have completed this activity as designated.

     Was this activity fair, balanced, objective, and free from commercial bias?    K Yes          K No
     If no, please state reason(s) ____________________________________________________________________

     4 = strongly agree; 3 = agree; 2 = disagree; 1 = strongly disagree
     a)____ What I learned in this activity has increased my confidence in understanding the latest clinical evidence for
            current and emerging gout therapies
     b)____ What I learned in this activity will improve my ability to manage my patients with gout
     c)____ What I learned at this activity will result in an improvement in my patients’ health

18   Attestation/Evaluation Form
d)____ Do you intend to make changes or apply new knowledge to your practice as a result of this activity?
       ____ Yes, I plan to make changes*
       ____ I’m not sure, but I’m considering changes*
       ____ No, I already practice these recommendations
       ____ No, I don’t think this applies to my practice

*If yes or considering changes, please list what you intend to do differently or incorporate into your clinical practice as a
result of this educational activity.

What are the top 3 barriers that might inhibit your ability to incorporate any of the above changes into your clinical practice?
1. _______________________________________________________________________________________
2. _______________________________________________________________________________________
3. _______________________________________________________________________________________

How did you learn about this CME activity?       K Received via mail   K Received copy from colleague         K Other

Number of years in practice:      K≤5         K 6-10     K 11-15       K 16-20       K 21-25       K > 25

How many of your patients are being managed for gout?         K ≤ 5%      K 6-20%        K 21-40%      K 41-60%      K > 60%

May we contact you in the future with a brief survey to assess how you have used the information presented at this activity
or to assess other educational needs?      K Yes      K No

4 = strongly agree; 3 = agree; 2 = disagree; 1 = strongly disagree
Upon completion of this activity, I will be able to:
a)____ Describe the factors to be considered in the diagnosis of gout
b)____ Describe current and emerging gout therapies, including their use at different disease stages and appropriate
       monitoring practices
c)____ Assess comorbidities and concomitant medications that may necessitate changes in gout management
d)____ Utilize patient education and counseling tools to support patient adherence to gout pharmacotherapy

Please rate the overall content presented at this activity:   K Too basic     K Appropriate      K Too complex

Recommendations for future CME topics in this disease area: ___________________________________________


                                                                                                        Attestation/Evaluation Form   19
                       The Gout Clinical Companion:
                       The Latest Evidence and Patient Support Tools for the Primary Care Physician

     1. Which of the following is not a risk factor for gout?
        a. Male gender
        b. Beer
        c. Dairy products
        d. High fructose corn syrup
        e. Diuretics
        f. All of the above

     2. The therapeutic goal for serum uric acid is:
        a. ≤ 6.0 mg/dL
        b. ≤ 6.8 mg/dL
        c. ≤ 7.0 mg/dL
        d. ≤ 8.5 mg/dL

     3. The decisive diagnostic criterion for gout is:
        a. Elevated serum uric acid (≥ 7.0 mg/dL)
        b. Podagra with extreme pain
        c. Overall clinical profile, including podagra, fever, age, and gender
        d. Monosodium urate crystals in synovial aspirate

     4. Serum uric acid should be reduced aggressively and rapidly after an acute gout attack to prevent
        subsequent attacks.
        a. True
        b. False

     5. Allopurinol and febuxostat lower serum uric acid principally by inhibiting:
        a. Xanthine oxidase
        b. Renal reuptake of uric acid by URAT1
        c. Intestinal absorption of nucleic acids
        d. Activity of inflammatory cytokines

     6. Which statement is not true of intercritical periods?
        a. Colchicine reduces flares during the transition to xanthine oxidase inhibitor maintenance therapy
        b. Intermittent dosing of xanthine oxidase inhibitors prevents tachyphylaxis and is more effective than constant
           chronic dosing in preventing flares
        c. Serum uric acid should be assessed regularly as an index of control

20   Posttest
                                 The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Patient Education:
    Managing Gout Pain
    Gout is a very painful inflammatory condition. Your health care provider will give you food and lifestyle
    recommendations as well as medication that will help you manage gout in the long term. If you are suffering an
    acute episode of gout, your main concern is likely pain relief.

    Your health care provider may have given you non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, or
    steroids to help deal with your pain and inflammation. Proper dosing should be followed. The side effects of
    NSAIDs tend to increase at higher doses and may include indigestion, nausea, heartburn, unusual belching,
    bloating, diarrhea, headache, or dizziness. Since NSAIDs have different efficacy and side effects in different
    people, there may be a “trial and error” period until the best medication for you can be identified.

    Colchicine can be used during the acute stage of gout, and is also beneficial in the transition from acute pain
    management to the uric acid management phase. It can reduce acute flares while medications to reduce uric acid
    are started.

    Corticosteroid medications have anti-inflammatory activity and may also offer pain relief. Prolonged high level
    steroid use has been associated with high blood pressure, diabetes, weak bones, stomach ulcers, obesity,
    increased body hair, eye problems such as cataracts or glaucoma, adrenal gland problems, and a weaker immune

            Class                 Examples                Activity          Used When?                 Major Considerations

           NSAID            Ibuprofen, Naproxen,             Pain,            Acute gout              Potentially cost saving
                                  Sulindac,             inflammation                             Avoid with renal or hepatic failure
                                Indomethacin                                                    Potential adverse effects: digestive,
                                                                                                 bleeding, heart failure, or asthma

         Colchicine               Colchicine            Inflammation         Acute gout,       Potential of nausea, vomiting, diarrhea,
                                                                             transition to                 and dehydration
                                                                                chronic         Caution and dose reduction needed
                                                                              treatment             if colchicine used previously
                                                                                               Potential of weakness or bone marrow

         Systemic               Prednisone,             Inflammation          Acute gout     Potential for high blood pressure, diabetes,
       Corticosteroid        Methylprednisolone,                                                weak bones, stomach ulcers, obesity,
                               Triamcinolone                                                 increased body hair, eye problems, adrenal
                                 acetonide                                                     gland problems, and a weaker immune

    Pain is a very personal phenomenon. The threshold and optimal management solution vary between patients, and
    several approaches may be necessary. It is important that you share with your provider any negative effects you
    experience, other medications you are taking, and other conditions such as hypertension, diabetes, or kidney
    disease you might be suffering.

    American College of Rheumatology: http://www.rheumatology.org/public/factsheets/diseases_and_conditions/gout.asp
    WebMD Pain Management Health Center: http://www.webmd.com/pain-management/default.htm
    Pain Relief for Gout: http://www.disabled-world.com/artman/publish/article_2409.shtml

                                                             Managing Gout Pain
                                The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Patient Education:
    Diet and Weight Management
    Gout is a disease that is due in part to an excess of uric acid (UA) in the blood. This substance is a natural product of
    digestion and is removed by the kidney into the urine. Too much uric acid in the blood can result from excessive intake
    or inadequate removal.

    Uric acid is derived from food and drink. This food pyramid shows how different foods influence serum UA. While fish,
    meat, beer, and high-fructose containing foods have the negative effect of raising uric acid, low fat dairy products and
    exercise/weight control have a positive effect. Fruit contains fructose and should be taken in moderation. Products
    such as sweetened soda contain high-fructose corn syrup and should be avoided. Vitamin C has a positive effect on
    gout outcomes and is recommended in moderation as a supplement.

                                                                                           Increase UA
                                                                                           Decrease UA
                                                                                           UA Neutral

    Weight control is important for gout management but is very difficult for most people. Eating less and regular exercise
    are critical components to losing weight. Patients who achieve weight loss benefit from improved metabolism, better
    cardiovascular health, and more energy for everyday activities.

    Your health care provider can help you with weight control, an exercise program, and designing a healthy diet plan.

    Weight loss:
    Patient Information: Weight Loss Treatments: http://www.uptodate.com/patients/content/topic.do?topicKey=~HoG5SqvDWI_wqG
    Weight Watchers: http://www.weightwatchers.com/index.aspx

    Gout Diet: Foods to Avoid: http://arthritis.about.com/cs/gout/a/foodstoavoid.htm

                                                       Diet and Weight Management
                                 The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Patient Education:
    Medications for Treating Gout
    The main medications available for treating the different phases of gout are shown in this table. Your health care
    provider will recommend the best plan for you.

           Class                 Examples                   Activity          Used When?                 Major Considerations

          NSAID             Ibuprofen, Naproxen,               Pain,           Acute gout                Potentially cost saving
                                  Sulindac,               inflammation                              Avoid with renal or hepatic failure
                                Indomethacin                                                       Potential adverse effects: digestive,
                                                                                                    bleeding, heart failure, or asthma

        Systemic               Prednisone,                Inflammation         Acute gout      Potential for high blood pressure, diabetes,
      Corticosteroid        Methylprednisolone,                                                  weak bones, stomach ulcers, obesity,
                              Triamcinolone                                                        increased body hair, eye problems,
                                acetonide                                                        adrenal gland problems, and a weaker
                                                                                                              immune system

        Colchicine               Colchicine               Inflammation         Acute gout,       Potential of nausea, vomiting, diarrhea,
                                                                               transition to                 and dehydration
                                                                                  chronic         Caution and dose reduction needed
                                                                                treatment             if colchicine used previously
                                                                                                 Potential of weakness or bone marrow

    Xanthine Oxidase             Allopurinol         Inhibit formation           Chronic        Generally well tolerated; renal clearance
        Inhibitor                Febuxostat             of uric acid            treatment        of allopurinol limits its use with renally
                                                                                                             impaired patients

        Uricosuric              Probenecid              Increased                Chronic            Potential for headache; joint pain,
                                                     excretion of uric          treatment         redness, or swelling; loss of appetite;
                                                       acid in urine                                    nausea or vomiting (mild)
                                                                                                  Not for patients with uric acid stones
                                                                                                           in kidney or bladder
                                                                                                             Drug interactions

    Use these drugs as directed by your provider. Skipping doses may result in decreased effectiveness, or in some cases,
    acute flares. Your provider has recommended a specific drug or set of drugs on the basis of your condition, general
    health status, other drugs you might be taking, and other conditions you might have. It is critical that you describe
    these other conditions and medications during your examination. If you experience discomfort or side effects contact
    your doctor or provider immediately, and consult your provider before beginning any other new medications.

    How to Treat Gout with Diet and Medication                             Gout
    http://arthritis.about.com/od/gout/ht/treatgout.htm                    http://www.podiatrychannel.com/gout/index.shtml
    Health Section: Gout                                                   National Institute of Arthritis and Muscular Skeletal
    http://www.nytimes.com/2005/06/20/health/menshealth/20gow              and Skin Diseases
    er.html?scp=5&sq=gout&st=cse                                           http://www.niams.nih.gov/Health_Info/Gout/default.asp

                                                           Medications for Treating Gout
                               The Gout Clinical Companion:
The Latest Evidence and Patient Support Tools for the Primary Care Physician

    Patient Education:
    Adherence Is Critical for Gout Management
    Gout is a result of crystal formation in joints. These deposits are composed of uric acid (UA, also known as
    urate), which crystallizes if its concentration gets too high. Uric acid is a natural breakdown product of food
    and drink. Our kidneys excrete uric acid into the urine for elimination. In healthy people, this process is in
    balance and the UA stays within a normal range. Most people with gout have impaired kidney removal of uric
    acid, so UA increases in the blood.

    Management of gout consists of lifestyle modification and medications for painful attacks, prophylaxis, and
    elevated UA. The medications vary in the different phases of the disease, but the one thing that doesn’t
    change is the importance of adherence to the regimen your health care provider gives you. Gout is a chronic
    disease with acute flares, and the disease management effort is devoted to minimizing the frequency and
    intensity of these episodes. Following the instructions from your provider will help control your serum uric
    acid (sUA) and reduce the risk of painful flares.

    The strategy for controlling sUA has several aspects. Diet is very important, and your provider will give you
    guidance on which foods and drinks are helpful or dangerous. Briefly, animal protein, refined carbohydrates,
    and beer are bad; low-fat dairy, daily exercise, and weight control are good. Consistent adherence to
    medication is also critical. Rapid fluctuations (both up and down) in sUA levels are believed to be triggers for
    acute flares. So while the objective of preventive therapy is to lower sUA levels, if it happens too quickly an
    acute episode can occur. This often leads to discontinuation of medication (“It doesn’t work”), more sUA
    fluctuations, and more exacerbations.

    Since gout is a chronic disease of uric acid accumulation and the preventive medications work over months
    or years, it is critical that the patient play an active role in gout management. Adherence to diet, medication,
    weight control, and exercise are crucial components in the battle to control uric acid levels, reduce acute
    gout flares, and minimize other consequences of the disease.


    The Role of Diet in the Management of Gout: a Comparison of Knowledge and Attitudes to Current Evidence

    Personal Health; Gout Hobbles Plenty of Commoners, Too

                                            Adherence Is Critical for Gout Management
Sponsored by
                             This program is supported by
                          an educational grant from Takeda
                       Pharmaceuticals North America, Inc.

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