CE/CME

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CE/CME INFORMATION

TARGET AUDIENCE: This activity has been de-signed to meet the educational needs of physician assistants and nurse practitioners in primary care with adult patients who may by susceptible to hyper-uricemia and gout.• Original Release Date: July 2011• Expiration Date: July 31, 2012• Estimated Time to Complete This Activity: 1

hour• Medium: Printed journal and online CE/CME

PROGRAM OVERVIEW: The primary objective of this educational initiative is to provide clinicians in primary care with the most up-to-date information regarding diagnosis and management of gout.

EDUCATIONAL OBJECTIVES: After com-pleting this activity, the participant should be better able to:• Explain the pathogenesis of hyperuricemia and

its relationship to gout.• Enumerate the serious comorbidities often pres-

ent in patients with gout that may also require intervention.

• Discuss the “gold standard” for diagnosis of gout, in addition to diagnostic criteria commonly used to identify the condition.

• Explain methods for ruling out alternate diagno-ses in patients who have risk factors for gout but a non-classic presentation.

• Describe the components of conventional gout management, in addition to newer medications now available.

FACULTY: Bonnie Dadig, EdD, PA-C, is the Chair and Program Director of the Georgia Health Sciences University (GHSU) Physician Assistant Department and a PA in the GHSU Department of Family Medi-cine outpatient clinic, Augusta. Anna Everett Wal-lace, PA-S, is a student in the PA program at GHSU.

ACCREDITATION STATEMENT:PHYSICIAN ASSISTANTSThis program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category I CME credit by the Physician Assistant Review Panel. Approval is valid for one year from the issue date of July 2011. Participants may submit the self-assessment at any time during that period.

This program was planned in accordance with AAPA’s CME Standards for Enduring Material Pro-grams and for Commercial Support of Enduring Material Programs.

Successful completion of the self-assessment is required to earn Category I CME credit. Successful completion is defined as a cumulative score of at least 70% correct.

ACCREDITATION STATEMENT: NURSE PRACTITIONERSThis program has been approved by the Nurse Practitioner Association New York State (The NPA) for 1.0 contact hour.

DISCLOSURE OF CONFLICTS OF INTER-EST: The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commer-cial interests related to the content of this CME ac-tivity: Bonnie Dadig, EdD, PA-C, and Anna Everett Wallace, PA-S, reported no significant financial rela-tionship with any commercial entity related to this activity. METHOD OF PARTICIPATION: The fee for participating and receiving CME credit for this activ-ity is $10.00. During the period July 2011 through July 31, 2012, participants must 1) read the learning objectives and faculty disclosures; 2) study the educa-tional activity; 3) go to www.clinicianreviews.com/

CECourses.aspx, follow links to the posttest for this activity, and provide payment information via our se-cure server; 4) complete the 10-question posttest by recording the best answer to each question; and 5) record their response to each of the additional evalu-ation questions.

If you have any questions, e-mail CR.evaluations @qhc.com. Upon successful completion of an on-line posttest, with a score of 70% or better, and the completion of the online activity evaluation form, a statement of credit will be made available immediately.

DISCLOSURE OF UNLABELED USE: This educational activity may contain discussion of pub-lished and/or investigational uses of agents that are not indicated by the FDA. AAPA, The NPA, and Quadrant HealthCom Inc. do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in this educational activ-ity are those of the faculty and do not necessarily represent the views of AAPA, The NPA, or Quad-rant HealthCom Inc. Please refer to the official pre-scribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER: Participants have an implied re-sponsibility to use the newly acquired information to enhance patient outcomes and their own profes-sional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s con-ditions and the possible contraindications or dan-gers in use, review of any applicable manufacturer’s product information, and comparison with recom-mendations of other authorities.

Uric acid crystals from an inflamed gouty joint, shown on light microscopy.

GoutA Clinical OverviewBonnie Dadig, EdD, PA-C, Anna Everett Wallace, PA-S

Gout, a metabolic disorder that affects more than six million people in the United States, most commonly presents as an acute inflammatory arthritis—usually manifesting in an acutely painful, tender, and inflamed joint. Because gout can affect every organ system, however, patients with gout are vulnerable to other significant pathologies that may also require timely intervention.

G outy arthritis is a common form of inflammatory ar-thritis, occurring

more frequently in men than in women. The condition has a male–female ratio of 3 or 4 to 1, although that ratio narrows as adults age; because the uricosu-ric effects of estrogen decline with menopause, the risk for gout increases in postmenopaus-al women.1,2 Mean age at disease onset is 40 to 60 in men,3,4 with onset in women averaging seven years later.5

Apart from the pain and loss of function associated with this disorder of purine metabolism6

and the risk for a chronic form of the disease, gout is almost universally linked with serious comorbidities that require time-ly intervention. These include hypertension, dyslipidemia, hy-perglycemia and diabetes, obesi-ty, metabolic syndrome, cardio-vascular disease (CVD), renal insufficiency, and coronary heart disease (CHD).2,3,7 The presence of gout is independently associ-ated with a risk for acute myo-cardial infarction (AMI) and in-creased rates of all-cause mortality.3,8-10

EPIDEMIOLOGYIn 2007, the National Arthritis Data Workgroup11,12 estimated that about three million US adults had had “self-reported gout” in the previous year. An estimated six million US adults have been diagnosed with gout,2,11 and its incidence and prevalence are increasing. The incidence of primary gout more than doubled between 1977-1978 and 1995-1996,13 especially af-fecting the aging population. The prevalence of gout among 1,000 managed care patients ages 65 to 74 increased by at least

30% between 1990 and 1999, while prevalence among those older than 75 almost doubled during this same period.14

Numerous factors appear to contribute to these trends, in-cluding aging of the population, dietary trends (ie, increased con-sumption of red meat, organ food, game, and shellfish and re-duced consumption of low-fat dairy products), presence of cer-tain comorbid conditions (ie, hy-pertension, dyslipidemia, diabe-tes, metabolic syndrome, end-stage renal disease), the in-creasing prevalence of obesity in younger adults, use of specific prescription medications, and increased incidence of organ transplantation.1,7,8,15-19

The body’s underexcretion or overproduction of uric acid (a by-product of purine metabolism12) can lead to hyperuricemia. This condition, defined as a serum urate level exceeding 7.0 mg/dL in men or 6.0 mg/dL in wom-en20,21 (levels above 9.0 mg/dL are considered very high22), is the primary risk factor for gout.8,23,24 As with gout, the incidence of hyperuricemia has increased in recent years,20 with researchers attributing the trend to world-wide popularization of the West-ernized diet (particularly use of high-fructose corn syrup20,25) and increased use of certain medications, including thiazide diuretics, cyclosporine, and low-dose aspirin.2,20,25,26

As serum urate levels rise, the patient with hyperuricemia may experience urate supersatura-tion, often followed by crystal-lization of the excess urate into monosodium urate (MSU) crystals. Subsequently, circulat-ing MSU crystals may deposit in body tissues, especially in the joint spaces. The body’s ensu-ing inflammatory response to

the MSU deposits is gout.20 In addition to hyperuricemia,

risk factors for gout include a high-purine diet, habitual alco-hol consumption (especially beer and fortified wines27), diuretic therapy (particularly in patients with heart failure or renal insuf-ficiency), obesity, hypertension, and high levels of fructose con-sumption.7,28 Additionally, cyclo-sporine use in an organ trans-plant recipient, poorly controlled uric acid levels, and a long histo-ry of gout increase the patient’s risk for chronic tophaceous gout.24,29 Tophi may be more common in a patient with a his-tory of organ transplantation.16

Genetic variants are current-ly being investigated to possibly identify a predisposition to gout. The most significant ge-netic factors appear to involve mechanisms that regulate se-rum uric acid levels—particu-larly urate underexcretion.23 Other factors that contribute to underexcretion or overproduc-tion of uric acid are shown in Table 1.1,15,26,30-33

A dynamic relationship exists between gout and a number of pathologic processes. According to researchers investigating nearly 178,000 patients with gout in a managed care database, 36% had hypertension, 27% had

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Bonnie Dadig is the Chair and Program Director of the Georgia Health Sciences University (GHSU) Physician Assistant Department and a PA in the GHSU Depart-ment of Family Medicine outpatient clinic, Augusta. Anna Everett Wallace is a PA student at GHSU.

Gout: A Clinical OverviewCE/CME

TABLE 1Factors Associated With Urate Underexcretion and Urate Overproduction1,15,26,30-33

Urate underexcretion Urate overproduction

Medications/drugs Aspirin (low-dose) Cytotoxic drugs

Cyclosporine Ethanol

Ethambutol Fructose (overconsumption)

Ethanol Purine (excess)

Levodopa Vitamin B12

Loop diuretics Warfarin

Nicotinic acid

Pyrazinamide

Thiazides

Other factors Chronic renal failure Glycogen storage disorders

Dehydration Hypertriglyceridemia

Hyperparathyroidism Lymphoproliferative disorders

Obesity Myeloproliferative disorders

Hypertension Obesity

Hypothyroidism Psoriasis

Polycythemia

Lactic acidosis

Elevated insulin levels

Polycystic kidney disease

Sarcoidosis

Toxemia of pregnancy

Sources: Bhole et al. Arthritis Rheum. 20101; Weaver. Cleve Clin J Med. 200815; Zhang et al. Ann Rheum Dis. 200626; Harris et al. Am Fam Physician. 199930; Schlesinger. Curr Pharm Des. 200531; Ning and Keenan. Curr Opin Rheumatol. 201032; Menon et al. Clin Chem. 1986.33

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dyslipidemia, and 15% had dia-betes.8 In a smaller cohort study conducted in Spain and Mexico, it was demonstrated that 93% of patients with gout had one or more associated diseases, in or-der of decreasing frequency: hy-pertriglyceridemia, obesity, hy-pertension, metabolic syndrome, hyperglycemia, chronic renal failure, diabetes, and ischemic heart disease.3

Of particular clinical impor-tance in this study was a finding that the first gout attack gener-ally preceded the diagnosis of the associated diseases.3 Thus, a diagnosis of gout should lead the primary care provider to discuss modifiable risk factors with the patient—but also to investigate for comorbid illnesses that may require timely management.2

In a 12-year-long prospective study of more than 50,000 men participating in the Health Pro-fessionals Follow-Up Study,9 it was found that men with gout had a 28% increased risk for all-cause mortality, a 38% in-creased risk for CVD-related death, and a 55% increased risk for CHD-related death, com-pared with men who did not have gout (excluding other risk factors).9 Similarly, researchers for the Multiple Risk Factor In-tervention Trial10 demonstrated a clinically significant associa-tion between gout and an in-creased risk for AMI: 10.5% of men with gout, compared with 8.43% of men without gout, had an AMI during mean follow-up of 6.5 years.10

THE STAGESThe four stages of gout are asymptomatic hyperuricemia, acute gout, intercritical gout, and chronic tophaceous gout.20

Only a small percentage (0.5% to 4.5%) of patients with asymptomatic hyperuricemia will develop acute gout.28 Neverthe-less, any patient with serum urate greater than 6.8 mg/dL is

at risk for the deposition of MSU crystals into body tissues and the potential associated or-gan damage—even patients without symptoms. There is currently no evidence-based method to determine which pa-tients with asymptomatic hy-peruricemia will experience dis-ease progression.16

Acute gout develops when de-position of MSU crystals in the joints initiates an inflammatory response. In the typical history, the patient experiences sudden-onset severe pain, swelling, and erythema. The pain often starts in the middle of the night or ear-ly morning,34 waking the patient from sleep and peaking within 24 hours of onset. At this time, the patient is often unable to bear weight comfortably on the affected joint. The patient may also report fever and flu-like malaise resulting from the re-lease of interleukin 1-b (IL-1b), IL-1 receptor, cytokines, and prostaglandins.16,24,35 Usually in these early attacks, symptoms re-solve spontaneously within three to 14 days.16,24

After resolution of an acute attack, the patient enters the in-tercritical stage, another asymp-tomatic stage that may last for months or years—or indefinite-ly. During the intercritical stage, MSU crystal deposition continues, adding crystals in and around the affected joint or joints, possibly continuing to inflict damage (in some patients, substantial), and in many cases resulting in additional attacks and pain.16 Any subsequent acute gout attacks the patient may experience are likely to last longer than the initial attack and to involve additional joints or tendons.24

Some patients, especially those who do not receive ade-quate treatment for hyperurice-mia,2 progress to develop chronic tophaceous gout. This is a deform-ing disease process in which the

joints may become stiff and swollen, and subcutaneous nod-ules or whitish-yellow intrader-mal deposits may be present un-der taut skin, anywhere in the body.16

PATIENT PRESENTATION AND HISTORYTypically, a patient with gout will present with a chief com-plaint of a painful, tender, in-flamed joint (classically de-scribed in Latin as calor, rubor, dolor, et tumor6). However, clini-cians must also be aware of un-usual presentations and consider gout in the differential whenever a patient with a history of gout or pertinent risk factors presents with unexplained clinical find-ings.32 The history of present ill-ness will vary according to the stage of the disease.

About 90% of recognized ini-tial attacks of gout are monoar-ticular, usually occurring in one of the lower extremities.16 While the first metatarsophalangeal (MTP) joint is affected in about 50% of gout cases (podagra, the Greek term for gout),2,35 eventu-ally patients with gout have a 90% chance of involvement with the MTP joint (see Figure 1). According to Zhang et al,26 pa-tients with hyperuricemia and an affected MTP joint have an 82% chance of having gout.2,26

Because such a large propor-tion of patients have the classic presentation of rapid-onset warmth, redness, and tender-ness at the MTP, knee, or ankle and surrounding soft tissue, cases with a differing presenta-tion are likely to be misdiag-nosed or overlooked, or a cor-rect diagnosis is delayed.26 In many documented cases, gout was the ultimate diagnosis—but one that was reached only inci-dentally because of unusual clinical presentation, ranging from entrapment neuropathy to a pancreatic mass.32

The presence of hyperurice-mia and other risk factors must be investigated. Also relevant in the history of an acute gout at-tack may be a preceding event that has caused damage or stress to the joint, such as infection, trauma, or surgery. Other pos-sible triggers for an attack in-clude alcohol ingestion, acidosis, use of IV contrast media, diuret-ic therapy, chemotherapy, recent hospitalization or surgery, and initiation or termination of urate-lowering therapy with the xanthine oxidase inhibitor allo-purinol.2,30 According to Prima-testa et al,8 the risk for flares is increased in patients with car-diometabolic comorbidities.

The medication history of a patient with gout may include

Gout: A Clinical Overview

FIGURE 1

In about half of patients with monoarticular gout, the attack occurs in the metatarsophalangeal joint (podagra).

low-dose aspirin (but not stan-dard-dose aspirin, which is uri-cosuric2), diuretics, cyclospo-rine, cytotoxic agents, and vitamin B12, which may contrib-ute to hyperuricemia.24 Addi-

tionally, ethambutol, pyrazin-amide, levodopa, nicotinic acid, didanosine, niacin, and warfarin may raise uric acid levels.15,30,33

Medical history should in-clude a thorough assessment of

the comorbidities associated with gout. In addition to the conditions mentioned previous-ly, patients with a history of polycystic kidney disease, dehy-dration, lactic acidosis, hyper-parathyroidism, toxemia of pregnancy, hypothyroidism, or sarcoidosis may have elevated urate levels due to underexcre-tion—and thus may be vulnera-ble to gout.30 History of gout in a first-degree relative is associ-ated with an increased risk for gout.36

The social history should ad-dress alcohol use or abuse. The clinician should also inquire about how gout is impacting the daily life of the patient. Diet and exercise habits should be as-sessed37 (see “Patient Educa-tion,” below).

PHYSICAL EXAMINATIONThe physical exam begins with evaluation of the skin and ex-tremities for the classic features of gout. Affected joints will be exquisitely tender, and patients may be febrile. Most cases are monoarticular, but polyarticular involvement is likely in patients with advanced disease (and can, particularly in women, be mis-taken for rheumatoid arthri-tis).2,16 In patients with chronic tophaceous gout, there may be whitish-yellow skin deposits, subcutaneous nodules, and areas of taut skin. The lower-extremi-ty joints and tendons, as well as the wrists, fingers, and elbows, are commonly affected16 (see Figure 2, page 33).

DIAGNOSISDiagnostic criteria that are cur-rently available (and have long been in use) include the Ameri-can College of Rheumatology/American Rheumatism Associa-tion (ACR/ARA) preliminary criteria,34 the New York crite-ria,21 and the Rome criteria.38 The specifics of each are listed in Table 2.21,34,38,39

The gold standard for gout di-agnosis is detection of MSU crystals in a sample of synovial fluid aspirated from the affected joint or from a tophus and exam-ined by polarized light micros-copy.24 This is of significant im-portance to the clinician who is faced with a questionable diag-nosis.16 However, crystal visual-ization is not ordinarily available to the primary care clini-cian,2,17,40 and it is not always necessary if a careful history and physical exam are conducted in a patient with hyperuricemia or other risk factors for gout. A presumptive diagnosis may be acceptable in a patient with the classic presentation of acute gout: rapid onset of severe pain in a swollen, erythematous joint and symptoms peaking within 24 hours. The presence of tophi is pathognomonic for chronic tophaceous gout.41

In cases of questionable or un-usual manifestation of gout, however, various imaging tech-niques and crystal visualization may be indicated.32

In order to compare the effec-tiveness of the latter technique with conventional diagnostic criteria for gout, Malik et al39 conducted a pilot study involv-ing 82 patients who had under-gone synovial fluid analysis with polarized light microscopy. Pa-tients were surveyed about the clinical features of their disease, as listed in the three standard sets of criteria for diagnosis of gout. Compared with the “gold standard” of urate crystal detec-tion (which is one of the Rome criteria38), the study authors found the ACR/ARA prelimi-nary criteria,34 the New York criteria,21 and the Rome crite-ria38 generally unsatisfactory.

In the study, among patients with confirmed presence of MSU crystals:

• 87% reported more than one attack of acute arthritis (ACR/ARA34)

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Gout: A Clinical OverviewCE/CME

TABLE 2Comparison of Criteria for Diagnosis of Gout21,34,38,39

Abbreviations: ACR/ARA, American College of Rheumatology/American Rheumatism Association; MSU, monosodium urate; MTP, metatarsophalangeal.

Sources: Kellgren et al. Epidemiology of Chronic Rheumatism. 196321; Wallace et al. Arthritis Rheum. 197734; Bennett and Wood. Third International Symposium. 196838; Malik et al. J Clin Rheumatol. 2009.39

ACR/ARA preliminary criteria34

MSU monohydrate crystals in synovial fluid

orat least six of the following:

• More than one attack of acute arthritis

• Maximum inflammation within 24 hours

• Monoarthritic attack

• Redness apparent over the joints

• Pain or swelling in the first MTP joint

• Unilateral first MTP joint attack

• Unilateral tarsal joint attack

• Suspected or confirmed tophus

• Hyperuricemia

• Radiographic evidence of asymmetric swelling in a joint

• Radiographic evidence of subcortical cysts with no erosions

• Negative organism findings in synovial fluid culture

• Attack starting at night

New York criteria38

MSU crystals in synovial fluid or tissue or tophus

orat least two of the following:

• History or observation of at least two attacks of painful limb swelling, remitting within one week

• History or observation of podagra

• Tophi

• History or observation of a good response to colchicine (ie, major reduction in objective signs of inflammation within 24 hours of therapy onset)

Rome criteria21

At least two of the following criteria:

• History of attacks of painful, swollen joints, with abrupt onset and initial remission within one to two weeks

• Serum uric acid level > 7.0 mg/dL in men or > 6.0 in women

• Tophi

• MSU crystals in synovial fluid or tissues

• 86% reported monoarthritis attack (ACR/ARA34)

• 89% had hyperuricemia (ACR/ARA34 and Rome,38

with the latter giving effec-tive, specific parameters)

• 100% had negative results on joint fluid culture (ACR/ARA34)

• 90% reported an attack starting at night (ACR/ARA34).

The positive predictive values for these signs and symptoms are 38%, 39%, 74%, 50%, and 45%, respectively, according to Malik et al.39 The presence of tophi (cited by all three sets of criteria but “proven or suspect-ed” in the ACR/ARA34) had the highest positive predictive value for gout (91%) and a likelihood ratio of 15.56, which was at least three times higher than any of the other listed criteria. A veri-fied response to colchicine, one of the New York criteria,21 had the second highest positive pre-dictive value at 86%.39

In summary, the ACR/ARA,34 the New York,21 and the Rome criteria38 had specificity of 79%, 83%, and 89%, respectively; sensitivity of 70%, 70%, and 67%, respectively; and positive predictive values for gout of 66%, 70%, and 77%, respective-ly. The Rome criteria38 had the

highest specificity and highest positive predictive value, per-haps making them most helpful for clinicians who lack access to synovial fluid analysis.

DIFFERENTIAL DIAGNOSISConditions to be considered and ruled out before a diagnosis of gout can be made are:

• Pseudogout • Septic arthritis • Psoriatic arthritis • Rheumatoid arthritis • Erosive osteoarthritis• Bacterial cellulitis• Sarcoid arthropathy.16,28,42,43 Unlike gout (in which com-

pensated polarized light micros-copy reveals needle-shaped urate crystals with strong negative bi-refringence), pseudogout is char-acterized by calcium pyrophos-phate dihydrate crystals; these are rhomboid-shaped, with weak positive birefringence.42 Addi-tionally, radiographic imaging will reveal soft tissue swelling and chondrocalcinosis of the joint in pseudo gout.44

The patient with septic arthri-tis, most likely affecting the knee, will have a white blood cell (WBC) count exceeding 50,000/mm3 and a positive cul-ture of the synovial fluid, with absence of crystals.28

Chronic tophaceous gout can

mimic rheumatoid arthritis in ap-pearance and joint distribution, and patients affected by either condition may develop a posi-tive rheumatoid factor. Exami-nation of synovial fluid for MSU crystals and radiographic imag-ing will be of value in making a distinction.

Osteoarthritis is usually evi-denced by joint space narrowing on x-ray.42

Bacterial cellulitis will present similarly to gout, but the ery-thema of bacterial cellulitis will more likely extend beyond the involved joint.16

Sarcoid arthropathy often pre-sents as a polyarthritis, as in ad-vanced gouty arthritis. Howev-er, in sarcoid arthropathy, serum calcium and angiotensin-con-verting enzyme will likely be el-evated.43 Synovial or tendon sheath biopsy will show non-ca-seating granulomas, which are the hallmark for sarcoid disease. Additionally, joint fluid analysis will demonstrate a predomi-nance of mononuclear or poly-morphonuclear cells.43

Diagnostic TestsDiagnostic tests to consider are analysis and culture of the syno-vial fluid, complete blood count (CBC), blood urea nitrogen (BUN), creatinine, radiography, ultrasonography, serum uric acid, and blood culture if septic arthritis is suspected.28 While serum urate levels may be nor-mal during an acute gout attack, measurement may still be help-ful for comparison, since eleva-tion is a likely finding two weeks after an attack—if the patient was, in fact, experiencing an acute gout attack.42

Since renal dialysis increases the risk for gout, pseudogout, and septic arthritis, synovial flu-id analysis is essential in patients undergoing renal dialysis.42

Various imaging techniques may aid in confirming a diagno-sis of gout and monitoring its

progression, but further studies are needed to more clearly de-fine the role of these techniques in management of gout.45 Plain radiographic evidence of asym-metric swelling in a joint (one of the ACR/ARA preliminary cri-teria34) was shown to have a 60% positive predictive value for a di-agnosis of gout.39 Late in the dis-ease process, an affected joint may be affected by characteristic “punched out” intra-articular le-sions, with a normal amount of joint space.45

Ultrasound is a safe and inex-pensive test that can reveal soft tissue edema and increased vas-cularity during an acute gout at-tack. Chronic changes include the double contour sign and to-phus-like lesions surrounded by a thin, anechoic rim.45

CT will also show tophi and bony erosion. While CT is more specific than other techniques, it is also more expensive and ex-poses the patient to increased ra-diation. MRI can help monitor the complications of gout, espe-cially entrapment neuropathies.45

TREATMENT/MANAGEMENTAccording to current evidence, treatment is not indicated for asymp tomatic hyperuricemia.16

Acute Gout ManagementPharmacologic treatments avail-able for an acute gout attack in-clude NSAIDs, colchicine, and local or systemic corticoste-roids.24,46 At the onset of an at-tack, patients should start high-dose NSAID therapy, and continue for two to three days after symptoms are resolved.6 Oral indomethacin (50 mg tid) or oral ibuprofen (800 mg tid) are both reasonable options.6 It may be prudent to consider a proton pump inhibitor (eg, omeprazole) to protect the gas-tric mucosa in patients who are susceptible to gastrointestinal problems.27

In addition to high-dose

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Gout: A Clinical Overview

Tophi in the finger joints of a patient with gout.

FIGURE 2

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NSAID therapy, adding colchi-cine (1.2 mg by mouth at onset of symptoms, followed by 0.6 mg one hour later) has proven to be effective in relieving the symptoms of gout, but its serious gastrointestinal adverse effects, particularly diarrhea, must be considered.6,47

In patients with monoarticu-lar gout who cannot tolerate NSAIDs, intra-articular aspira-tion and corticosteroid injec-tions may provide relief. Long-acting triamcinolone, ad-ministered by intra-articular in-jection, has been found to relieve pain and inflammation in pa-tients with gout. Septic arthritis must be ruled out by way of joint aspiration and culture before in-jection of corticosteroids.47

Oral or IM-administered corticosteroids may be consid-ered for patients with polyartic-ular involvement. Prednisone (60 mg/d, tapered over 10 days) is an appropriate option for out-patients or inpatients; methyl-prednisone (80 to 120 mg IM) may be suitable for inpatients.6 Again, septic arthritis must be ruled out before corticosteroids are administered.47

For the patient who is current-ly taking a thiazide diuretic for hypertension, substituting a dif-ferent medication may be war-ranted; the angiotensin receptor blocker losartan, for example, has uricosuric action.27,29,47 Non-pharmacologic strategies, such as rest, ice, elevation, and avoiding trauma to the affected joint, are also recommended.27

Of note, allopurinol therapy should be neither initiated nor discontinued during an acute gout attack.27

Management of Chronic and Intercritical Gout Urate-lowering therapy, such as allopurinol (50 to 300 mg/d29), should be considered for patients who experience frequent attacks (ie, three or more per year), pa-

tients with chronic tophi, pa-tients with radiographically demonstrated joint damage,47 or patients with a documented state of uric acid overproduction.29

Allopurinol dosage should be adjusted based on creatinine clearance; dosing as high as 800 mg/d has been recommended in patients with normal renal func-tion.2 Again, allopurinol should never be started or discontinued during an acute attack,27 because abrupt fluctuations in uric acid levels may heighten the inflam-mation. The target serum urate level is 6.0 mg/dL.29

Febuxostat, which received FDA approval in 2009, was the first oral urate-lowering treat-ment to be approved since the 1960s. Like allopurinol, this nonpurine xanthine oxidase in-hibitor blocks uric acid synthe-sis.48,49 In a trial reported by Becker et al,50 67% of patients who took febuxostat 80 mg/d reached the target serum urate level (ie, < 6.0 mg/dL), compared with 45% of those who took 40 mg/d of febuxostat and 42% of those taking 300 mg/d of allopu-rinol. While incidence of ad-verse events was low in all treat-ment groups, Hu and Tomlinson51 report that febuxo-stat is tolerable in patients who are hypersensitive to allopuri-nol. As with other urate-lower-ing medications, gout flares are common during the early period of febuxostat use.51

For patients with gout that does not respond to conventional urate-lowering therapy, new op-tions are being introduced. Two agents, each a recombinant form of the enzyme urate oxidase, are designed to convert uric acid into allantoin, which can then be ex-creted in the urine. Late in 2010, one of these agents, pegloticase, was approved for use in patients with refractory gout.48 In one clinical trial, tophi were reported dissolved in 40% of patients who took pegloticase, but 58% of pa-

tients did not achieve the target-ed response (ie, serum urate < 6.0 mg/dL), and 77% of patients ex-perienced gout flares.52 Infusion reactions occurred in 26% to 31% of patients, and Reinders and Jansen52 recommended the clinical evaluation of glucocorti-coids and other anti-inflammato-ry agents to prevent the forma-tion of antibodies involved in these reactions.

The second agent, rasburi-case, has been approved for treatment and prevention of acute hyperuricemia in adult cancer patients. Rasburicase is now being investigated for use in patients with nonresponsive to-phaceous gout.53-55 It can be ad-ministered in the form of monthly infusions.54

Patient EducationEducating the patient about modifiable risk factors, such as diet, alcohol consumption, and adherence to the medication regimen, should be a priority.

Patients should be encouraged to target and maintain an ideal body weight, through diet and moderate physical exercise, as a strategy to normalize serum urate levels.27,47 However, they should be advised to avoid “crash dieting,” as this may precipitate a gout attack.27 In the recommend-ed low-purine diet, consumption of red meat and shellfish is re-stricted,17 whereas consumption of soy, nonfat milk and other low-fat dairy products, cherries and other fruits, and increased vegetable protein is encour-aged.31,37 Consumption of alco-hol, especially beer and fortified wines, should be limited.27,47

Avoiding trauma to joints af-fected by gout (including the stress of bearing excess weight) can help patients limit future attacks.7,27

CONCLUSIONPatients with gout often have the characteristic presentation

of an acutely tender, inflamed joint, but since gout is a systemic disorder, the clinician must also consider the possibility of gout in almost any organ system. Gout is a common disease, and its diagnosis can alert the astute clinician to investigate for cer-tain metabolic disorders requir-ing intervention. Hyperlipid-emia, metabolic syndrome, hypertension, chronic kidney disease, obesity, cardiovascular disease, and diabetes are all con-ditions associated with gout.

Recognizing the opportunity to offer preventive care mea-sures and recommend lifestyle modifications to the patient with gout allows the clinician to play an important role in the pa-tient’s care. CR

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