CE/CME

Gout
A Clinical Overview
Bonnie 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
Uric acid crystals from an inflamed gouty joint, significant pathologies that may also require timely
shown on light microscopy.
intervention.

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
•E stimated 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 ASSISTANTS
This 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 PRACTITIONERS
This 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.

Clinician Reviews
July 2011 • Vol 21, No 7
29
 CE/CME Gout: A Clinical Overview
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
EPIDEMIOLOGY
In 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
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.
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
Clinician Reviews
July 2011 • Vol 21, No 7
30
TABLE 1
Factors 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
the MSU deposits is gout.20 Genetic variants are current-
In addition to hyperuricemia, ly being investigated to possibly
risk factors for gout include a identify a predisposition to
high-purine diet, habitual alco- gout. The most significant ge-
hol consumption (especially beer netic factors appear to involve
and fortified wines27), diuretic mechanisms that regulate se-
therapy (particularly in patients rum uric acid levels—particu-
with heart failure or renal insuf- larly urate underexcretion.23
ficiency), obesity, hypertension, Other factors that contribute to
and high levels of fructose con- underexcretion or overproduc-
sumption.7,28 Additionally, cyclo- tion of uric acid are shown in
sporine use in an organ trans- Table 1.1,15,26,30-33
plant recipient, poorly controlled A dynamic relationship exists
uric acid levels, and a long histo- between gout and a number of
ry of gout increase the patient’s pathologic processes. According
risk for chronic tophaceous to researchers investigating
gout.24,29 Tophi may be more nearly 178,000 patients with
common in a patient with a his- gout in a managed care database,
tory of organ transplantation.16 36% had hypertension, 27% had
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 STAGES
The 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
Clinician Reviews
July 2011 • Vol 21, No 7
31
FIGURE 1
In about half of patients with monoarticular gout, the attack
occurs in the metatarsophalangeal joint (podagra).
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
HISTORY
Typically, 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
 CE/CME Gout: A Clinical Overview

TABLE 2 the comorbidities associated The gold standard for gout di-
Comparison of Criteria for Diagnosis with gout. In addition to the agnosis is detection of MSU
of Gout21,34,38,39 conditions mentioned previous- crystals in a sample of synovial
ly, patients with a history of fluid aspirated from the affected
ACR/ARA preliminary criteria34 polycystic kidney disease, dehy- joint or from a tophus and exam-
MSU monohydrate crystals in synovial fluid dration, lactic acidosis, hyper- ined by polarized light micros-
parathyroidism, toxemia of copy.24 This is of significant im-
or
pregnancy, hypothyroidism, or portance to the clinician who is
at least six of the following: sarcoidosis may have elevated faced with a questionable diag-
• More than one attack of acute arthritis urate levels due to underexcre- nosis.16 However, crystal visual-
• Maximum inflammation within 24 hours tion—and thus may be vulnera- ization is not ordinarily available
• Monoarthritic attack ble to gout.30 History of gout in to the primary care clini-
a first-degree relative is associ- cian,2,17,40 and it is not always
• Redness apparent over the joints
ated with an increased risk for necessary if a careful history and
• Pain or swelling in the first MTP joint gout.36 physical exam are conducted in a
• Unilateral first MTP joint attack The social history should ad- patient with hyperuricemia or
• Unilateral tarsal joint attack dress alcohol use or abuse. The other risk factors for gout. A
• Suspected or confirmed tophus clinician should also inquire presumptive diagnosis may be
about how gout is impacting the acceptable in a patient with the
• Hyperuricemia
daily life of the patient. Diet and classic presentation of acute
• Radiographic evidence of asymmetric swelling in a joint exercise habits should be as- gout: rapid onset of severe pain
• Radiographic evidence of subcortical cysts with no erosions sessed37 (see “Patient Educa- in a swollen, erythematous joint
• Negative organism findings in synovial fluid culture tion,” below). and symptoms peaking within
24 hours. The presence of tophi
• Attack starting at night
PHYSICAL EXAMINATION is pathognomonic for chronic
New York criteria 38 The physical exam begins with tophaceous gout.41
evaluation of the skin and ex- In cases of questionable or un-
MSU crystals in synovial fluid or tissue or tophus
tremities for the classic features usual manifestation of gout,
or of gout. Affected joints will be however, various imaging tech-
at least two of the following: exquisitely tender, and patients niques and crystal visualization
• History or observation of at least two attacks of painful may be febrile. Most cases are may be indicated.32
limb swelling, remitting within one week monoarticular, but polyarticular In order to compare the effec-
• History or observation of podagra involvement is likely in patients tiveness of the latter technique
• Tophi with advanced disease (and can, with conventional diagnostic
particularly in women, be mis- criteria for gout, Malik et al39
•H
 istory or observation of a good response to colchicine
(ie, major reduction in objective signs of inflammation within taken for rheumatoid arthri- conducted a pilot study involv-
24 hours of therapy onset) tis).2,16 In patients with chronic ing 82 patients who had under-
tophaceous gout, there may be gone synovial fluid analysis with
Rome criteria21 whitish-yellow skin deposits, polarized light microscopy. Pa-
At least two of the following criteria: subcutaneous nodules, and areas tients were surveyed about the
• History of attacks of painful, swollen joints, with abrupt onset of taut skin. The lower-extremi- clinical features of their disease,
and initial remission within one to two weeks ty joints and tendons, as well as as listed in the three standard
• Serum uric acid level > 7.0 mg/dL in men or > 6.0 in women
the wrists, fingers, and elbows, sets of criteria for diagnosis of
are commonly affected16 (see gout. Compared with the “gold
• Tophi Figure 2, page 33). standard” of urate crystal detec-
• MSU crystals in synovial fluid or tissues tion (which is one of the Rome
Abbreviations: ACR/ARA, American College of Rheumatology/American Rheumatism Association;
DIAGNOSIS criteria38), the study authors
MSU, monosodium urate; MTP, metatarsophalangeal. Diagnostic criteria that are cur- found the ACR/ARA prelimi-
Sources: Kellgren et al. Epidemiology of Chronic Rheumatism. 196321; Wallace et al. Arthritis rently available (and have long nary criteria,34 the New York
Rheum. 197734; Bennett and Wood. Third International Symposium. 196838; Malik et al. J Clin
Rheumatol. 2009.39
been in use) include the Ameri- criteria,21 and the Rome crite-
can College of Rheumatology/ ria38 generally unsatisfactory.
low-dose aspirin (but not stan- tionally, ethambutol, pyrazin- American Rheumatism Associa- In the study, among patients
dard-dose aspirin, which is uri- amide, levodopa, nicotinic acid, tion (ACR/ARA) preliminary with confirmed presence of
cosuric2), diuretics, cyclospo- didanosine, niacin, and warfarin criteria,34 the New York crite- MSU crystals:
rine, cytotoxic agents, and may raise uric acid levels.15,30,33 ria,21 and the Rome criteria.38 • 87% reported more than
vitamin B12, which may contrib- Medical history should in- The specifics of each are listed one attack of acute arthritis
ute to hyperuricemia.24 Addi- clude a thorough assessment of in Table 2.21,34,38,39 (ACR/ARA34)

Clinician Reviews
July 2011 • Vol 21, No 7
32

FIGURE 2
Tophi in the finger joints of a patient with gout.
• 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/ARA 34) 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 DIAGNOSIS
Conditions 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 pseudo­gout.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
Clinician Reviews
July 2011 • Vol 21, No 7
33
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 Tests
Diagnostic 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/MANAGEMENT
According to current evidence,
treatment is not indicated for
asymp­tomatic hyperuricemia.16
Acute Gout Management
Pharmacologic 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
 CE/CME Gout: A Clinical Overview
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
Tomlinson report that febuxo-
51
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-
Clinician Reviews
July 2011 • Vol 21, No 7
34
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 Education
Educating 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
CONCLUSION
Patients 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
Our CE/CME
posttest can be
taken or viewed at
www.Clinician
Reviews.com.
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