DynaMed Plus - Gout PDF

26/6/2019 DynaMed Plus: Gout
Gout
Overview and Recommendations
Background
Gout is a chronic disease characterized by recurrent attacks of severe pain and swelling due to
inflammation from monosodium urate crystals in joints and tophi or painless deposition of crystals in
periarticular tissues.
Typically there are 4 stages of disease progression: asymptomatic, acute, intercritical, and chronic.
Reported prevalence of gout worldwide ranges from 0.1% to about 10%.
Rates are usually higher in men than women.
Highest rates are reported in some ethnic groups such as Taiwanese aborigines, Pacific Islanders and
Maori.
Isolated asymptomatic hyperuricemia is not clinically significant on its own, but when serum urate level is
> 6.8 mg/dL, there is an increased likelihood of crystal deposition which may result in gout.
Increased risk of gout is associated with obesity, hypertension, high consumption of alcohol or high-purine
foods, low-dose aspirin, and several types of antihypertensive medications including diuretics, beta
blockers, and most renin-angiotensin system agents.
Secondary prevention of acute gouty attacks includes modifying risk factors (such as reducing
consumption of high-purine food and alcohol, obesity, and use of diuretic therapy) and the continued use
of urate-lowering medications (see also Gout management - prevention of recurrent attacks).
Evaluation
The most common initial presentation is a self-limiting acute attack.

Typical episodes of acute gout are characterized by severe pain, erythema, warmth, and swelling of
1 or more joints, peaking within 24 hours and with spontaneous resolution within 7-14 days.
The first metatarsophalangeal joint is most commonly affected. Other frequently involved joints
include the midfoot, ankles, and knees. Gout is uncommon in axial joints.
The disease may ultimately progress to chronic tophaceous gout with persistent arthritis, white-
yellow intradermal deposits, and frequent recurrent acute attacks.
The gold standard for diagnosis is demonstration of urate crystals (needle shaped with strong negative
birefringence) in synovial fluid or tophus by polarized light microscopy.
Testing may include a serum uric acid level (although it may be lower during an attack), blood and
synovial fluid cultures and Gram stain if there is suspicion of septic arthritis, and imaging such as x-ray,
ultrasound, or computed tomography.
The differential diagnosis includes septic arthritis, calcium pyrophosphate dihydrate (CPPD) deposition
disease (pseudogout), bacterial cellulitis, rheumatoid arthritis, psoriatic arthritis, and osteoarthritis.
Management
For acute attacks:
Although acute attacks are usually self-limited with spontaneous resolution in 1-2 weeks, treatment
hastens symptom resolution and is recommended as soon as possible after the onset of an attack
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(Strong recommendation).
For attacks with mild-to-moderate pain, especially if the attacks only affect 1-2 joints, use
monotherapy with any of the following (Strong recommendation):
low-dose colchicine (1-1.2 mg orally followed by 0.5-0.6 mg 1 hour later) within 12-36 hours
of flare onset (Strong recommendation)
oral nonsteroidal anti-inflammatory drugs (NSAIDs) (Strong recommendation)
options include naproxen, indomethacin, and sulindac; all appear equally effective
Use the full dosing that is approved by the FDA or European Medicines Agency.
Corticosteroids
Potential steroid regimens include:
prednisone 0.5 mg/kg once daily for 5-10 days without taper (Strong
recommendation)
methylprednisolone 0.5-2 mg/kg IV or intramuscularly once for patients unable
to take oral medication (Weak recommendation)
An intra-articular corticosteroid injection may be considered in patients with
involvement of 1-2 joints who are unable to take oral medication (Weak
recommendation).
For attacks with severe pain, especially acute polyarticular gout or involving multiple large joints,
consider combination therapy (Weak recommendation), such as:
full dose of colchicine plus an NSAID
full dose of oral corticosteroids plus colchicine
intra-articular steroids with any other treatment
Consider interleukin-1 blockers for treatment of flares in patients with acute flares that are
refractory to treatment or if there are contraindications to other therapy (Weak recommendation).
Consider nonpharmacologic treatments in addition to medication, including rest, ice packs, and
elevation of affected joints (Weak recommendation).
Consider initiating urate-lowering therapy (ULT) during a flare, although recommendations about
this vary among guideline organizations.
See also Gout management - treatment of acute attack.
For prevention of recurrent attacks:
ULT should be considered and discussed in every patient with gout (Strong recommendation).
ULT is recommended for patients with gout and 2 or more attacks per year, tophi, urate
arthropathy, renal stones, and/or reduced kidney function (Strong recommendation).
Initiation of long-term ULT in patients after a first attack or in patients with infrequent attacks
is not recommended (Strong recommendation).
Medication selection
First-line options include xanthine oxidase inhibitors (Strong recommendation).
Usual dosing:
allopurinol 100 mg/day orally, titrated up by 100 mg/day every few weeks until
the target uric acid level is achieved, up to maximum 800 mg/day
febuxostat 40-80 mg/day
In patients with renal impairment, dosing should be adjusted according to creatinine
clearance.
Second-line options in patients with normal renal function include uricosuric agents such as
probenecid and benzbromarone (Weak recommendation).
Consider combination therapy if target serum uric acid is not reached with first-line therapy
(Weak recommendation), such as addition of a uricosuric agent to a xanthine oxidase
inhibitor.
Pegloticase is recommended only in patients with severe refractory gout who cannot tolerate
the maximum dose of conventional oral ULT (Strong recommendation). Pegloticase is not
recommended in combination with other urate-lowering therapies.
Anti-inflammatory prophylaxis with colchicine 0.5-0.6 mg once or twice daily, a nonsteroidal anti-
inflammatory drug, or corticosteroid is recommended for all gout patients when ULT is started and
should be continued for at least 6 months (Strong recommendation).
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Management of patients on ULT

For most patients, titrate ULT to a target serum uric acid level of ≤ 6 mg/dL (Strong
recommendation), although some patients may require a level of < 5 mg/dL to control
symptoms (Weak recommendation).
For patients on ULT, measure serum uric acid and creatinine levels every 2-5 weeks while up-
titrating ULT, and every 6 months after serum uric acid target is reached; regularly monitor
for side effects of ULT (Weak recommendation).
Continue ULT during an acute gout attack (Strong recommendation).
If the patient is not currently receiving ULT therapy, consider introducing ULT during an acute
attack if effective anti-inflammatory therapy was already introduced (Weak recommendation).
See also Gout management - prevention of recurrent attacks.
Related Summaries
Gout management - treatment of acute attack
Gout management - prevention of recurrent attacks
Allopurinol
Colchicine
Febuxostat
Probenecid
General Information
Description
common form of inflammatory arthritis that occurs due to deposition of monosodium urate crystals in
synovial fluid and other tissues(1, 2)
hyperuricemia (serum urate concentration > 6.8 mg/dL [408 mcmol/L]) is main risk factor for
development of gout, although only a minority of patients with hyperuricemia develop gout(1, 2)
Types
asymptomatic hyperuricemia(1, 2)
urate crystals may begin to deposit at serum urate concentration > 6.8 mg/dL (404 mcmol/L)
most patients with elevated serum uric acid will not develop gout
acute gout(1, 2)
characterized by severe pain, erythema, and swelling, often beginning in middle of night or early
morning, peaking within 24
usually self-limited with spontaneous resolution in 7-14 days
about 90% of initial attacks are monoarticular, usually affecting the first metatarsophalangeal joint
other frequently involved joints include midfoot, ankles, and knees
uncommon in axial joints
acute bursitis or tenosynovitis may occur in periarticular structures, such as the olecranon bursa
skin desquamation may occur over inflamed area
intercritical or interval gout(1, 2)
intervals between attacks are intercritical periods
subsequent attacks are usually longer in duration and involve more joints over time
crystals usually persist allowing diagnosis to be made in between attacks, although sensitivity
maybe reduced
chronic tophaceous gout(1, 2)
usually takes many years to progress
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associated with chronic joint pain, limited activity, structural damage, and frequent flares, leading to
erosive, destructive, disabling arthritis
Epidemiology
Who is most affected
men (incidence 2-6 times higher in men than in women)(1, 5)

older patients (incidence increases with age until plateauing at about age 70 years)(1, 5)
persons living in developed countries (especially in North America and Western Europe)(5)
certain ethnic groups such as Taiwanese Aboriginals, Pacific Islanders and Maori(5)
Incidence/Prevalence
reported incidence of gout worldwide ranges from 0.3-6 cases per 1,000 person-years(5)
reported prevalence of gout worldwide ranges from 0.1% to about 10%(1, 5)
1%-5% in developed countries in North America and Western Europe
< 1% in developing countries
prevalence of up to 10% reported in some ethnic groups such as Taiwanese Aborigines, Pacific
islanders and Maori
0.08% estimated global age-standardized prevalence of gout in 2010
based on retrospective cohort study
data estimated from 15 of 21 regions in Global Burden of Disease 2010 study
estimated global age-standardized prevalence of gout in 2010 not significantly different from 1990
prevalence
overall 0.08%
in men 0.13%
in women 0.03%
50% increase in gout burden in 2010 compared to 1990
overall 114,000 disability-adjusted life years (DALYs)
in men 89,000 DALYs
in women 25,000 DALYs
Reference - Ann Rheum Dis 2014 Aug;73(8):1470
prevalence of gout in United States 3.9% in 2007-2008
based on analysis of data from United States National Health and Nutrition Examination Surveys
(NHANES)
5,707 adults aged ≥ 20 years participating in NHANES (2007-2008) were asked about history of
gout diagnosis and had serum urate levels evaluated
prevalence of gout
3.9% overall
5.9% in men
2% in women
by race/ethnicity
4% among white persons
5% among African Americans
1.5% among Mexican Americans
3.4% among persons of other races and ethnicities
by age
0.4% among persons aged 20-29 years
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8% among persons aged 60-69 years
12.6% among persons aged > 80 years
increased from 2.7% in NHANES III (1988-1994)
prevalence of serum urate level > 7 mg/dL 13.2% overall
Reference - Arthritis Rheum 2011 Oct;63(10):3136 full-text
incidence and prevalence of gout in United Kingdom increased from 1997 to 2012
based on analysis data from Clinical Practice Research Datalink between 1997 and 2012
in 2012
prevalence of gout 2.49% (2.48%-2.51%)
incidence of gout 1.77 per 1000 person-years (95% CI 1.73-1.81 per 1000 person-years)
prevalence increased by 63.9% and incidence by 29.6% between 1997 and 2012
Reference - Ann Rheum Dis 2015 Apr;74(4):661 full-text
high prevalence of gout among Pacific and Maori people in New Zealand
based on analysis of Aotearoa New Zealand Health Tracker (ANZHT) database
4,295,296 persons in the ANZHT database evaluated to determine prevalence of gout in New
Zealand in 2009
overall prevalence 2.69% (95% CI 2.67%-2.71%)
prevalence in persons aged ≥ 20 years 3.75% (95% CI 3.73%-3.77%)
prevalence of gout among persons aged ≥ 20 years based on ethnicity
7.63% in Pacific people
6.06% in Maori people
3.24% in European people
1.96% in Asian people
Reference - Rheumatology (Oxford) 2012 May;51(5):901
Likely risk factors
Hyperuricemia
hyperuricemia is main risk factor for development and recurrence of gout(1)

typically defined as serum urate concentration > 6.8 mg/dL [408 mcmol/L])(1)
higher serum uric acid levels associated with increased risk of incident gout
based on systematic review
systematic review of 25 observational studies evaluating association between serum uric acid level
(SUA) and incident or recurrent gout
8 studies evaluated incident gout
17 studies evaluated recurrent gout
gout incidence rates per 1000 person-years ranged from 0.8 cases for SUA < 6 mg/dL to 70.2 cases
for SUA ≥ 10 mg/dL in 3 studies
Reference - J Rheumatol 2017 Mar;44(3):388
higher serum uric acid levels associated with increased risk of incident gout, risk higher
among men than women
based on cohort study
2,476 women and 1,951 men in Framingham Heart study without gout at baseline were
followed for 52 years (1950-2002)
304 incident cases of gout reported, including 104 among women
increasing level of serum uric acid (SUA) associated with higher incidence of gout (vs. SUA
< 5 mg/dL)
SUA Level Adjusted RR in Men Adjusted RR in Women
5-5.9 mg/dL 4.09 (95% CI 2.37-7.07) 2.42 (95% CI 1.46-4.02)
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6-6.9 mg/dL 9.53 (95% CI 5.49-16.55) 3.41 (95% CI 1.76-6.63)

7-7.9 mg/dL 22.36 (95% CI 12.31-40.61) 12.18 (95% CI 5.87-25.27)
≥ 8 mg/dL 47.9 (95% CI 24.02-95.53 ) 22.53 (95% CI 9.12-55.64)
Abbreviations: RR, relative risk; SUA, serum uric acid.
Reference - Arthritis Rheum 2010 Apr;62(4):1069 full-text
higher serum uric acid levels associated with increased risk of gout flares in dose-dependent manner
18,008 patients (mean age 54.8 years, 78.2% men) with gout between 2009 and 2012 in a United
States health plan claims database who had serum uric acid levels measured 12 months prior to first
flare were followed for up to 2 years after first flare
higher baseline serum uric acid levels associated with increased risk of flare in dose-responsive
manner (vs. serum uric acid < 5 mg/dL)
adjusted hazard ratio (HR) 1.17, 95% CI 0.99-1.38, for serum uric acid 5 mg/dL to < 6 mg/dL
adjusted HR 1.69, 95% CI 1.46-1.97, for serum uric acid 6 mg/dL to < 7 mg/dL
adjusted HR 3.85, 95% CI 3.35-4.42, for serum uric acid ≥ 9 mg/dL
higher baseline serum uric acid levels associated with shorter time to first flare
Reference - Curr Med Res Opin 2017 Jan;33(1):117
Diet
dietary factors associated with increased risk of hyperuricemia and gout include consumption of(1)
red meat
seafood
alcohol
sugar-sweetened beverages (fructose rapidly increases serum urate level)
higher consumption of meat and seafood associated with increased risk of gout while higher
consumption of dairy products associated with decreased risk
based on prospective cohort study
47,150 men in Health Professionals Follow-up Study with no history of gout at baseline were
followed for 12 years
men were asked about potential dietary risk factors for gout using food frequency
questionnaire at baseline and then every 4 years
information on weight, medication use, and medical conditions was provided at baseline and
then every 2 years
730 men developed incident gout
highest quintile of meat and seafood intake associated with increased risk of gout (vs. lowest
quintile, p = 0.02 for trend)
adjusted relative risk (RR) 1.41, 95% CI 1.07-1.86 for meat
adjusted RR 1.51, 95% CI 1.17-1.95 for seafood
highest quintile of dairy intake associated with decreased risk of gout (vs. lowest quintile)
adjusted RR0.56, 95% CI 0.42-0.74 for total intake of dairy products (p < 0.001 for trend)
adjusted RR 0.58, 95% CI 0.45-0.76 for intake of low-fat dairy products
no significant difference in risk for gout attacks with higher consumption of total protein or purine-
rich vegetables
Reference - N Engl J Med 2004 Mar 11;350(11):1093 full-text, commentary can be found in N Engl
J Med 2004 Jun 10;350(24):2520
fructose-rich beverages associated with increased risk of gout in men and women
daily intake of fructose-rich beverages associated with increased risk for gout in women
78,906 women in the Nurses' Health Study without history of gout were followed for 22 years
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adjusted relative risk (adjusted relative risk [RR]) of gout compared to consumption of < 1
serving of sugar sweetened soft drinks/month
1.74 (95% CI 1.19-2.55) for 1 serving daily
2.39 (95% CI 1.34-4.26) for ≥ 2 servings daily
adjusted RR of gout vs. consumption of < 1 serving of orange juice/month
1.41 (95% CI 1.03-1.93) for 1 serving daily
2.42 (95% CI 1.27-4.63) for ≥ 2 servings daily
adjusted RR of gout 1.62 (95% CI 1.2-2.19) with highest vs. lowest quintile of fructose intake
consumption of diet soft drinks not associated with risk of gout
Reference - JAMA 2010 Nov 24;304(20):2270
high levels of sugar sweetened soft drink and fructose consumption associated with increased
risk of gout in men
information on weight, medication use, and medical conditions was provided at
baseline and then every 2 years
compared with consumption of < 1 serving of sugar sweetened soft drinks per month,
adjusted relative risk of gout was
1.29 (95% CI 1-1.68) for 5-6 servings weekly
1.45 (95% CI 1-2.08) for 1 serving daily
1.85 (95% CI 1-3.16) for ≥ 2 servings daily
diet soft drinks not associated with risk of gout
increasing quintiles of fructose intake associated with increased risk of gout (p < 0.001),
including fructose from soft drinks, fruit juice, or fructose-risk fruits (apples and oranges)
Reference - BMJ 2008 Feb 9;336(7639):309 full-text, editorial can be found in BMJ 2008 Feb
9;336(7639):285
no additional studies identified in systematic review (BMJ Open 2016 Oct 3;6(10):e013191 full-
text)
alcohol use associated with dose-dependent increased risk of gout, with beer associated with highest
risk
information on weight, medication use, and medical conditions was provided at baseline and
then every 2 years
compared with men who did not drink alcohol, adjusted relative risk (RR) of gout was
1.09 (95% CI 0.85-1.4) for alcohol intake 0.1-4.9 g/day
1.25 (95% CI 0.95-1.64) for alcohol intake 5-9.9 g/day
2.53 (95% CI 1.73-3.7) for alcohol intake ≥ 50 g/day
consumption of beer or spirits each associated with increased risk of incident gout attack
adjusted RR 1.49 (95% CI 1.32-1.70) per serving per day for beer
adjusted RR 1.15 (95% CI 1.04-1.28) per serving per day of spirits
moderate wine consumption not associated with increased risk of gout (adjusted RR per serving per
day 1.04, 95% CI 0.88-1.22)
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Reference - Lancet 2004 Apr 17;363(9417):1277, editorial can be found in Lancet 2004 Apr
17;363(9417):1251, commentary can be found in Lancet 2004 Jul 17;364(9430):246
tomato consumption might be associated with serum urate levels ( BMC Musculoskelet Disord 2015 Aug
19;16:196 full-text)
Medication use
medications associated with increased risk of hyperuricemia and gout include(1, 2)

diuretics
cyclosporin
tacrolimus
angiotensin-converting-enzyme inhibitors
angiotensin II receptor blockers (other than losartan, which increases uric acid excretion)
beta blockers
pyrazinamide
ritonavir
low-dose aspirin
use of loop, thiazide, and thiazide-like diuretics associated with increased risk of incident gout
based on case-control study
91,530 patients with incident gout between 1990 and 2010 in United Kingdom primary care
database were compared to 91,530 matched persons without gout
current diuretic use defined as last prescription written within 180 days of gout diagnosis, and past
use defined as last prescription written > 180 prior to gout diagnosis
current diuretic use associated with increased risk of incident gout compared to past use
adjusted odds ratio (OR) 2.64 (95% CI 2.47-2.83) for loop diuretics
adjusted OR 1.7 (95% CI 1.62-1.79) for thiazide diuretics
adjusted OR 2.3 (95% CI 1.95-2.7) for thiazide-like diuretics
adjusted OR 4.65, 95% CI 3.51-6.16 for combined use of loop and thiazide diuretics
current use of potassium-sparing diuretics associated with no significant increase in risk of incident
gout (adjusted OR 1.06, 95% CI 0.91-1.23)
Reference - Arthritis Rheumatol 2014 Jan;66(1):185 full-text
diuretics, beta-blockers, angiotensin converting enzyme inhibitors, and most angiotensin II receptor
blockers associated with increased risk for gout in adults with or without hypertension
24,768 adults aged 20-79 years with incident gout were compared to 50,000 matched controls
without gout
mean follow-up 5.2 years
among adults with hypertension, current use (< 31 days) of antihypertensive agents associated with
increased risk of incident gout (vs. nonuse of antihypertensive)
relative risk (RR) 2.36 (95% CI 2.21-2.52) with diuretics
RR 1.48 (95% CI 1.4-1.57) with beta-blockers
RR 1.24 (95% CI 1.17-1.32) with angiotensin converting enzyme inhibitors
RR 1.29 (95% CI 1.16-1.43) with angiotensin II receptor blockers (other than losartan)
similar results in analyses of adults without hypertension
Reference - BMJ 2012 Jan 12;344:d8190 full-text, editorial can be found in BMJ 2012 Jan
12;344:d7961
low-dose aspirin (≤ 325 mg/day) associated with increased risk of recurrent gout attack, although
use of allopurinol may negate risk increase
724 patients with gout completed online hazard period questionnaire after recurrent gout attack and
every 3 months during intercritical period for 1 year
1,434 recurrent gout attacks reported
40.5% of patients had aspirin ≤ 325 mg/day during either hazard or control period
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aspirin ≤ 325 mg/day for 2 consecutive days associated with increased risk of recurrent gout attack
(odds ratio 1.81, 95% CI 1.3-2.51)
aspirin ≤ 325 mg/day not associated with increased risk of recurrent gout attack in patients taking
allopurinol
aspirin > 325 mg/day not associated with increased risk of recurrent gout attack
Reference - Ann Rheum Dis 2014 Feb;73(2):385 full-text
Transplantation
patients who have organ transplantation and are treated with cyclosporin have increased risk for gout
hyperuricemia occurs in about 80%
gout develops in about ≥ 10% within first few years after transplant
Reference - N Engl J Med 2003 Oct 23;349(17):1647, commentary can be found in N Engl J Med
2004 Jan 29;350(5):519-20
among renal transplant patients treated with cyclosporin in 5 studies
30%-84% had hyperuricemia
2%-28% had gout
Reference - J Am Soc Nephrol 2000 May;11(5):974 full-text
heart transplant may be associated with higher rates of hyperuricemia and gout than liver
transplant
47 patients who had heart transplantation and 75 patients who had liver transplantation aged 20-78
years without prior gout who were followed for ≥ 3 years
comparing heart transplantation vs. liver transplantation
clinical gout occurred in 25.5% vs. 2.6% (p < 0.05)
hyperuricemia occurred in 100% vs. 85.7% (p < 0.001)
factors affecting increased prevalence of hyperuricemia and gout included age, gender, rejection
episodes, hypertension, diabetes mellitus, level of uric acid prior to transplantation, cyclosporine A,
diuretics, steroids, and aspirin
Reference - Transplantation 2004 May 27;77(10):1576
Other risk factors
genetic factors associated with increased risk of hyperuricemia and gout include(1, 5)
male sex
genetic polymorphisms in urate transporters including SLC2A9, ABCG2, SLC17A1/SLC17A3, and
GCKR
ethnicity, with higher risk among Taiwanese Aboriginals, Pacific islanders and Maori
other factors and comorbidities associated with gout(1)
increasing age
menopause
chronic kidney disease
overweight, obesity, or weight gain
hypertension
hyperlipidemia
hypertriglyceridemia
congestive cardiac failure
obstructive sleep apnea
anemia
psoriasis
sickle cell anemia
hematological malignancy
lead exposure
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obesity associated with increased risk of gout

based on cohort analysis of data from randomized trial
12,866 men in Multiple Risk Factor Intervention Trial were randomized to intervention program
including smoking cessation, weight reduction, increased physical activity, and antihypertensive
treatment vs. standard care and followed for 7 years
11,896 men without gout at baseline included in analysis
408 men developed gout
compared to normal BMI (< 25 kg/m2), baseline obesity (BMI ≥ 30 kg/m2) associated with
increased risk for incident gout (adjusted odds ratio 2.6, 95% CI 1.9-3.57)
Reference - Arthritis Care Res (Hoboken) 2017 Apr;69(4):561
menopause associated with increased risk of gout
92,535 women aged 30-55 years in Nurses' Health study were asked about menopause and
postmenopausal hormone use by questionnaire every 2 years for 16 years
1,703 women developed incident gout
menopause associated with increased risk of incident gout (adjusted relative risk [RR] 1.26, 95% CI
1.03-1.55)
postmenopausal hormone use associated with reduced risk of incident gout (adjusted RR 0.82, 95%
CI 0.7-0.96)
Reference - Ann Rheum Dis 2010 Jul;69(7):1305 full-text
chronic kidney disease associated with increased risk of gout
4,717 adults aged 29-62 years in Framingham Heart Study without gout and chronic kidney disease
(CKD) were followed for 54 years (1948-2002)
464 adults developed incident CKD
371 adults developed incident gout
CKD associated with increased risk of gout (adjusted hazard ratio 2.09, 95% CI 1.41-3.08)
Reference - BMJ Open 2015 Apr 13;5(4):e006843 full-text
Possible risk factors

high-normal serum lead level associated with increased risk for gout compared with low-normal
serum lead level
based on cross-sectional study
6,153 community-dwelling adults aged 40-85 years participating in national health and nutrition
survey were stratified by serum lead level
quartile 1, 0.009-0.058 mmol/L (0.18-1.2 mcg/dL)
4.7% had gout
compared with quartile 1, quartile 4 associated with increased risk of gout (adjusted odds ratio 3.62,
95% CI 2.1-6.25)
Reference - Ann Intern Med 2012 Aug 21;157(4):233, editorial can be found in Ann Intern Med
2012 Aug 21;157(4):292
3 genetic loci (in SLC2A9, ABCG2, and SLC17A3) associated with uric acid concentration and gout
based on genome-wide study in 7,699 persons from Framingham cohort and 4,148 persons from
Rotterdam cohort
Reference - Lancet 2008 Dec 6;372(9654):1953 full-text
Factors not associated with increased risk
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high-dose aspirin, which is urosuric(2)

tea consumption may not be associated with increased risk of gout, serum uric acid levels, or
hyperuricemia
systematic review of 15 observational studies (10 cross-sectional studies, 4 cohort studies, and 1
case-control study) evaluating association of tea consumption with serum uric acid levels,
hyperuricemia, and risk of gout in 197,465 people
all results limited by significant heterogeneity
no significant association between tea consumption and
risk of gout in males or females in analysis of 2 studies
risk ratio 0.82, 95% CI 0.38-1.75, in males
risk ratio 1.55, 95% CI 0.98-2.47, in females
hyperuricemia (adjusted odds ratio 0.98, 95% CI 0.77-1.24) in analysis of 5 studies
no significant difference in serum uric acid levels between lowest and highest tea consumption
(weighted mean difference 7.41, 95% CI -2.34 to 17.15) in analysis of 7 studies
green tea consumption associated with increased serum urate level (weighted mean difference 17.2
mcmol/L, 95% CI 7-27.4 mcmol/L) in analysis of 3 studies
Reference - BMC Musculoskelet Disord 2017 Feb 28;18(1):95 full-text
coffee consumption might be associated with lower risk of gout
systematic review of 11 observational studies (6 cross-sectional studies, 3 cohort studies, and 2
case-control studies) evaluating association of coffee consumption with serum uric acid levels,
hyperuricemia, and risk of gout in 184,751 people
higher coffee intake associated with lower risk of gout (adjusted relative risk 0.43, 95% CI 0.31-
0.59) in analysis of 2 studies
no significant association between coffee consumption and
hyperuricemia (adjusted odds ratio 0.84, 95% CI 0.65-1.09) in analysis of 4 studies
serum uric acid level in analysis of 6 studies, results limited by significant heterogeneity
Reference - BMJ Open 2016 Jul 8;6(7):e009809 full-text
calcium channel blockers and losartan associated with reduced risk for gout in adults with
hypertension
24,768 adults aged 20-79 years with incident gout were compared to 50,000 matched controls
without gout
mean follow-up 5.2 years
among adults with hypertension, current use (< 31 days) of calcium channel blockers or losartan
associated with decreased risk of incident gout (vs. nonuse of antihypertensive)
relative risk (RR) 0.87 (95% CI 0.82-0.93) with calcium channel blockers
RR 0.81 (95% CI 0.7-0.94) with losartan
similar results for calcium channel blockers in analysis of adults without hypertension
longer duration of calcium channel blocker or losartan use associated with reduced risk of incident
gout in adults with hypertension (p < 0.05 for trend for each)
Reference - BMJ 2012 Jan 12;344:d8190 full-text, editorial can be found in BMJ 2012 Jan
12;344:d7961
DynaMed commentary -- study did not specify which type of calcium channel blockers were used
by patients.
higher vitamin C intake associated with lower risk of gout
46,994 men without history of gout at baseline were followed for 20 years
cumulative incidence of gout 2.8%
risk of gout compared to men with daily vitamin C intake < 250 mg (p < 0.001 for trend)
risk ratio 0.83 for daily vitamin C intake 500-999 mg
risk ratio 0.66 for daily vitamin C intake 1,000-1,499 mg
risk ratio 0.55 for daily vitamin C intake ≥ 1,500 mg
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Reference - Arch Intern Med 2009 Mar 9;169(5):502
Associated conditions
Rates of associated comorbidities
comorbidities common among patients with gout(1)

comorbidities including hypertension, chronic kidney disease, and obesity appear common among
patients with gout
5,707 adults aged ≥ 20 years participating in United States National Health and Nutrition
Examination Survey (NHANES) 2007-2008 were asked about diagnosis of gout and comorbidities
3.9% adults had diagnosis of gout
prevalence of comorbidities among patients with gout
hypertension in 73.9% (95% CI 67.9%-79.9%)
chronic kidney disease stage ≥ 2 in 71.1% (95% CI 65.4%-76.8%)
obesity (body mass index ≥ 30 kg/m2) in 53.3% (95% CI 44.8%-61.9%)
diabetes mellitus in 25.7% (95% CI 15.8%-35.6%)
nephrolithiasis in 23.8% (95% CI 16.8%-30.7%)
chronic kidney disease stage ≥ 3 in 19.9% (95% CI 15.4%-24.3%)
myocardial infarction in 14.4% (95% CI 10%-18.7%)
heart failure in 11.2% (95% CI 6.9%-15.5%)
stroke in 10.4% (95% CI 3.8%-17%)
highest prevalence of comorbidities observed among adults with both gout and hyperuricemia
Reference - Am J Med 2012 Jul;125(7):679-687.e1
most patients with gout have ≥ 1 comorbidity
407 patients with gout at 2 rheumatology clinics in Spain and Mexico reviewed
at time of inclusion (mean disease duration of 13.7 years), 93% had ≥ 1 associated disease
hypertriglyceridemia in 63%
obesity in 54%
hypertension in 45.6%
metabolic syndrome in 40%
hyperglycemia in 37%
chronic renal failure in 17%
diabetes in 15%
ischemic heart disease in 6.6%
first gout attack preceded diagnosis of associated disease in 90% of patients
Reference - J Clin Rheumatol 2009 Mar;15(2):65
prevalence of metabolic syndrome higher among patients with gout compared to patients without
gout
8,807 adults (mean age 44 years) participating in Third National Health and Nutrition Examination
Survey (NHANES-III) provided adequate data to diagnose metabolic syndrome
2.4% had physician-diagnosed gout
prevalence of metabolic syndrome 62.8% among patients with gout vs. 25.4% among patients
without gout (adjusted odds ratio 3.05, 95% CI 2.01-4.61)
Reference - Arthritis Rheum 2007 Feb 15;57(1):109 full-text
Cardiovascular disease
gout associated with increased risk of mortality from cardiovascular disease and coronary heart
disease
12/46

systematic review of 6 studies evaluating risk of mortality from cardiovascular diseases in 223,448
patients with gout
gout associated with increased risk of mortality
due to any cardiovascular disease (adjusted hazard ratio 1.29, 95% CI 1.13-1.44) in analysis
of 4 studies
due to coronary heart disease (adjusted hazard ratio 1.42, 95% CI 1.22-1.63) in analysis of 3
studies
no significant risk if mortality from myocardial infarction in 3 studies
Reference - Eur J Prev Cardiol 2015 Mar;22(3):335 full-text
gout associated with higher total and cardiovascular mortality in men
51,297 men in Health Professionals Follow-Up Study followed for 12 years
at baseline
4.4% had gout
6.9% had coronary heart disease
1% had both gout and coronary heart disease
among men with no coronary heart disease at baseline, relative risks for men with history of
gout compared to men without history of gout
total mortality 1.28 (95% CI 1.15-1.41)
cardiovascular mortality 1.33 (95% CI 1.15-1.66)
coronary heart disease 1.55 (95% CI 1.23-1.93)
nonfatal myocardial infarction 1.59 (95% CI 1.04-2.41)
among men with coronary heart disease at baseline, relative risks for men with history of gout
compared to men without history of gout
total mortality 1.25 (95% CI 1.09-1.45)
cardiovascular mortality 1.26 (95% CI 1.07-1.5)
nonfatal myocardial infarction 1.24 (95% CI 1.04-2.49)
Reference - Circulation 2007 Aug 21;116(8):894 full-text, commentary can be found in
Circulation 2007 Aug 21;116(8):880
conflicting evidence for all-cause mortality comparing febuxostat to allopurinol in patients with gout
febuxostat associated with similar rates of adverse cardiovascular events but increased
mortality compared to allopurinol in patients with gout and history of cardiovascular disease
(level 2 [mid-level] evidence)
based on randomized noninferiority trial with high dropout rate and high loss to follow-up
6,190 patients with gout, history of cardiovascular disease, and serum uric acid ≥ 7 mg/dL (≥
6 mg/dL with uncontrolled gout) randomized to febuxostat 40-80 mg orally once daily vs.
allopurinol
randomization was stratified according to estimated creatinine clearance at baseline (≥
60 mL/minute vs. 30-60 mL/minute)
patients with estimated creatinine clearance > 60 mL/minute received allopurinol 300-
600 mg orally once daily
patients with estimated creatinine clearance 30-60 mL/minute received allopurinol 200-
400 mg orally once daily
febuxostat dosage not adjusted according to creatinine clearance
56.6% patients discontinued study and 45% patients were lost to follow-up
primary composite outcome included cardiovascular death, nonfatal myocardial infarction,
nonfatal stroke, or unstable angina with urgent revascularization
noninferiority of febuxostat defined as hazard ratio of primary composite outcome < 1.3
compared to allopurinol at limit of 1-sided 98.5% CI
median follow-up 32 months
comparing febuxostat vs. allopurinol
primary composite outcome in 10.8% vs. 10.4% (98.5% CI [1-sided] upper limit 1.23,
noninferiority met)
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cardiovascular death in 4.3% vs. 3.2% (p = 0.03, NNH 91)

all-cause death in 7.8% vs. 6.4% (p = 0.04, NNH 71)
Reference - CARES trial (N Engl J Med 2018 Mar 29;378(13):1200
febuxostat associated with similar risk of all-cause death and adverse cardiovascular events
compared to allopurinol in patients ≥ 65 years old with gout (level 2 [mid-level] evidence)
24,936 patients ≥ 65 years old (median age 76 years) with gout initiating treatment with
febuxostat were propensity-score-matched to 74,808 similar patients initiating treatment with
allopurinol
99% in febuxostat group used dose ≥ 40 mg/day
31% in allopurinol group used dose ≥ 300 mg/day
at enrollment, 12.2% had preexisting cardiovascular disease, 95% had hypertension, 58% had
chronic kidney disease, 55% had diabetes, and 36% had heart failure
primary outcome was hospitalization for myocardial infarction or stroke
mean follow-up 1.1 years in febuxostat group and 1.2 years in allopurinol group
incidence rates per 100 person-years comparing febuxostat vs. allopurinol
primary outcome in 3.43 vs. 3.36 (hazard ratio [HR] 1.01, 95% CI 0.94-1.08)
all-cause death in 4.11 vs. 4.27 (HR 0.95, 95% CI 0.89-1.02)
coronary revascularization in 2.64 vs. 2.75 (HR 0.95, 95% CI 0.87-1.03)
new-onset heart failure in 5.71 vs. 5.41 (HR 1.05, 95% CI 0.98-1.12)
heart failure exacerbation in 42.7 vs. 44.1 (HR 0.94, 95% CI 0.91-0.99)
subgroup analyses comparing febuxostat to allopurinol
based on presence of preexisting cardiovascular disease
no significant difference in all-cause mortality (HR 0.97, 95% CI 0.9-1.04) or
primary outcome (HR 0.99, 95% CI 0.91-1.08) in patients without preexisting
cardiovascular disease
febuxostat associated with nonsignificant decrease in all-cause mortality (HR
0.85, 95% CI 0.72-0.99) but no significant difference in primary outcome (HR
0.97, 95% CI 0.83-1.13) in patients with preexisting cardiovascular disease
based on baseline cardiovascular risk
febuxostat associated with nonsignificant decrease in all-cause mortality (HR
0.93, 95% CI 0.86-1) but no significant difference in primary outcome (HR 0.97,
95% CI 0.89-1.06) in patients without high baseline cardiovascular risk
no significant difference in all-cause mortality (HR 0.97, 95% CI 0.86-1.1) or
primary outcome (HR 1.03, 95% CI 0.9-1.19) in patients with high baseline
cardiovascular risk
Reference - Circulation 2018 Sep 11;138(11):1116
elevated uric acid levels may be associated with increased risk for coronary artery disease, but evidence
inconsistent
hyperuricemia associated with increased risk for coronary heart disease morbidity and
mortality
systematic review of 29 prospective cohort studies evaluating association between
hyperuricemia and coronary heart disease in 958,410 individuals
hyperuricemia associated with increased risk of
coronary heart disease morbidity (adjusted relative risk [RR] 1.13, 95% CI 1.05-1.21)
in analysis 13 studies with 77,048 persons
coronary heart disease mortality (adjusted RR 1.27, 95% CI 1.16-1.39) in analysis of 13
studies with 900,782 participants (results limited by significant heterogeneity)
per 1 mg/dL increase in uric acid level, adjusted RR of coronary heart disease mortality 1.15
(95% CI 1.09-1.21) in analysis of 5 studies
Reference - Sci Rep 2016 Jan 27;6:19520 full-text
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increased serum uric acid levels associated with increased cardiovascular mortality in patients
> 70 years old
based on pooled analysis of 2 cohort studies
2,344 patients ≥ 70 years old without cardiovascular disease, renal dysfunction, or diuretic
use were followed for 12-20 years
serum uric acid ≥ 7 mg/dL (416 mcmol/L) associated with increased risk of cardiovascular
mortality compared to serum uric acid < 7 mg/dL (416 mcmol/L) (pooled adjusted hazard
ratio 1.38, 95% CI 1.16-1.61)
Reference - J Am Geriatr Soc 2013 Mar;61(3):319
elevated serum uric acid levels associated with increased risk of death from cardiovascular
disease, but not all-causes, in middle-aged men
based on population-based cohort study
1,423 middle-aged Finnish men were followed for mean 11.9 years
11% all-cause mortality and 3.9% cardiovascular mortality
compared to serum uric acid levels 3.03-5.04 mg/dL (180.3-299.9 mcmol/L), serum uric acid
levels 5.89-9.58 mg/dL (350.5-570 mcmol/L) associated with increased cardiovascular
mortality (adjusted relative risk 2.69, 95% CI 1.21-5.98), but not all-cause mortality
Reference - Arch Intern Med 2004 Jul 26;164(14):1546, commentary can be found in Arch
Intern Med 2005 May 9;165(9):1071
increased serum uric acid levels associated with increased all-cause mortality in mixed
population of patients with or at high risk of cardiovascular disease
3,098 patients aged 18-87 years evaluated for primary or secondary cardiovascular disease
prevention between 1998 and 2004 were included
43% of patients had cardiovascular disease
156 deaths (5%) occurred during 14,262 person-years of followup
each increase of 1 mg/dL (59.48 mcmol/L) in serum uric acid associated with increased risk
of death (adjusted hazard ratio 1.26, 95% CI 1.15-1.38)
Reference - Arthritis Rheum 2008 Feb;58(2):623 full-text , commentary can be found in
Arthritis Rheum 2008 Aug;58(8):2585
serum uric acid levels not associated with ischemic heart disease
based on Mendelian randomization analysis of pooled data from 2 prospective cohorts
58,072 persons (mean age 58 years) from Copenhagen General Population Study and 10,602
from Copenhagen City Heart Study were assessed for variation in SLC2A9 (rs7442295) as
means to measure association between uric acid levels and hyperuricemia with ischemic heart
disease and blood pressure
no significant association between variation in SLC2A9 (rs7442295) or serum uric acid levels
and ischemic heart disease
Reference - BMJ 2013 Jul 18;347:f4262 full-text
elevated uric acid levels not associated with increased risk of coronary heart disease and heart
failure based on Mendelian randomization analysis (J Am Coll Cardiol 2016 Feb 2;67(4):407 full-
text)
review of proposed mechanisms for uric acid mediated hypertension and cardiovascular risk (N
Engl J Med 2008 Oct 23;359(17):1811 full-text)
Neurologic disease
gout may be associated with reduced risk of neurological diseases but cause-effect relationship is
unclear(1)
gout associated with lower risk of Alzheimer's disease
59,224 patients with gout in The Health Improvement Network (THIN) between 1995 and 2013
were compared to 238,805 patients without gout
15/46
incidence rate of Alzheimer's disease 1 per 1,000 person-years in patients with gout vs. 1.5 per
1,000 person-years in individuals without gout
gout associated with lower risk of Alzheimer's disease in multivariate analysis (hazard ratio 0.76,
95% CI 0.66-0.87)
consistent results across subgroups by sex, age, social deprivation index, and history of
cardiovascular disease
Reference - Ann Rheum Dis 2016 Mar;75(3):547 full-text
gout associated with lower risk of dementia
28,769 patients with gout from Taiwan National Health Insurance Research Database between 2002
and 2008 were compared to 114,742 patients without gout
no patient had history of dementia at baseline
mean follow up 4.3-4.4 years
incidence of dementia 9.51 per 1,000 person-years in patients with gout vs. 12.54 per 1,000 person-
years in individuals without gout
gout associated with lower risk of
any type of dementia (adjusted hazard ratio [HR] 0.77, 95% CI 0.72-0.82)
vascular dementia (adjusted HR 0.76, 95% CI 0.65-0.88)
non-vascular dementia (adjusted HR 0.77, 95% CI 0.72-0.83)
Alzheimer's disease (adjusted 0.75, 95% CI 0.61-0.94)
Reference - Arthritis Res Ther 2015 May 28;17:139 full-text
gout associated with increased risk of neurological diseases during first 5 years after hospitalization
for gout, but neurological diseases may be associated with reduced risk of gout
based on analysis of database of hospital admissions and death registrations in England between
1999 and 2012
214,653 patients with gout were compared to 9 million people without gout
gout associated with increased risk of subsequent
multiple sclerosis (relative risk [RR] 1.27, 95% CI 1.03-1.55)
Parkinson's disease (RR 1.11, 95% CI 1.05-1.17)
motor neuron disease (RR 1.28, 95% CI 1.11-1.48)
association between gout and subsequent neurologic disease not significant in analysis including
only cases of neurologic disease occurring ≥ 5 years after initial gout admission
neurologic diseases associated with decreased risk of subsequent gout include
RR 0.79 (95% CI 0.69-0.89) in patients with multiple sclerosis
RR 0.83 (95% CI 0.79-0.87) in patients with Parkinson's disease
motor neuron disease associated with
no significant difference in risk of gout overall (RR 0.94, 95% CI 0.75-1.16)
reduced risk of gout ≥ 5 years after hospitalization (RR 0.35, 95% CI 0.15-0.68)
Reference - BMC Neurol 2015 Feb 28;15:16
Etiology and Pathogenesis

Causes
gout is caused by inflammation secondary to monosodium urate crystal deposition in joints and peri-
articular tissues(1, 2)
hyperuricemia and crystal deposition may be caused by
urate underexcretion (more common than overproduction)
primary hyperuricemia
secondary hyperuricemia
renal impairment
polycystic kidney disease (autosomal dominant polycystic kidney disease)
chronic renal failure
16/46
hypertension
drugs
low-dose aspirin
diuretics, such as thiazides, furosemide, and other loop diuretics
cyclosporine
ethanol
ethambutol
pyrazinamide
levodopa
niacin (nicotinic acid)
metabolic/endocrine causes
dehydration
lactic acidosis
hyperparathyroidism
ketosis
hypothyroidism
toxemia of pregnancy (hypertensive disorders of pregnancy)
obesity
sarcoidosis
urate overproduction
primary hyperuricemia may rarely occur due to single gene disorders, such as
glycogen storage diseases
hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency (Lesch-Nyhan
syndrome)
secondary hyperuricemia may occur due to
dietary factors
excessive purine intake
excessive fructose consumption
hematologic causes
lympho-/myeloproliferative disorders
polycythemia
drugs
cytotoxic agents
excess ethanol intake
vitamin B12
warfarin (Clin Chem 1986 Aug;32(8):1557 PDF)
psoriasis
obesity
Reference - Rheumatology (Oxford) 2017 Jul 1;56(7):e1, correction can be found in Rheumatology
(Oxford) 2017 Jul 1;56(7):1246, Am Fam Physician 1999 Feb 15;59(4):925 full-text, commentary
can be found in Am Fam Physician 2000 Apr 15;61(8):2343
Pathogenesis
uric acid is metabolic byproduct of purine catabolism
serum uric acid levels determined by amounts of
ingested purines
endogenous purine synthesis
excretion by kidneys and gut
as level of uric acid increases, risk of supersaturation and crystal formation increases
hyperuricemia is defined as serum urate concentration 6.8 mg/dL (408 mcmol/L), above which crystals
form at physiological pH and temperature in vitro
gout flares occur due to acute inflammatory response to deposited uric acid crystals
17/46
crystals stimulate release of humoral and cellular inflammatory mediators

flares typically self limited
time between flares is referred to as intercritical period, during which low-grade synovitis may persist
chronic gouty arthritis may develop in patients with gout after > 10 years
cytokines, chemokines, proteases, and oxidants stimulated during acute attack also play role in
chronic inflammation
tophi may be present
pathognomonic feature of advanced gout
occurs due to organized chronic inflammatory granulomatous response involving innate and
adaptive immune cells
may result in chronic gouty synovitis, cartilage loss, and bone erosion
Reference - (1), Ann Intern Med 2005 Oct 4;143(7):499
History and Physical

History
Chief concern (CC)
acute gout(1, 2)
characterized by sudden onset of joint tenderness, erythema, warmth, and swelling accompanied by
extreme pain
may be associated with fever or other systemic symptoms
typically affects foot or ankle
chronic tophaceous gout(1, 2)
may present with subcutaneous nodules in soft tissues and/or persistently stiff or swollen joints
usually presents in setting of years of recurrent gouty attacks
atypical presentations reported include(1)
tophaceous disease without previous flares
flares or tophi in locations other than peripheral joints such as eye, nose, spine, and viscera
difficulty walking, tophi, and first metatarsophalangeal joint involvement appear to be more
common in patients with gout than in patients with other causes of swollen joints
983 patients (mean age 58 years, 71.4% male) with ≥ 1 swollen joint or subcutaneous tophus within
2 weeks of study entry were evaluated
509 patients (52%) had monosodium urate crystal-proven gout
clinical features associated with gout in multivariate analysis
having ≥ 1 episode of swollen joint associated with difficulty walking (adjusted odds ratio
[OR] 7.34, 95% CI 1.17-46.06)
presence of tophus (adjusted OR 7.29, 95% CI 2.42-21.99)
resolution of symptoms within 2 weeks (adjusted OR 3.58, 95% CI 1.85-6.95)
serum urate level > 6 mg/dL (0.36 mmol/L) (adjusted OR 3.35, 95% CI 1.57-5.81)
first metatarsophalangeal joint involvement during current episode (adjusted OR 2.83, 95%
CI 1.37-5.81)
first metatarsophalangeal joint involvement during this episode or previous episodes (adjusted
OR 2.3, 95% CI 1.18-4.49)
joint erythema adjusted (OR 2.13, 95% CI 1.06-4.29)
joint involvement among patients with gout
first metatarsophalangeal joint (MTP) in 39.4%
knee, ankle, or midfoot in 37.1%
elbow or wrist or hand in 14.9%
polyarticular in 8.6%
18/46
joint involvement among patients without gout

knee only in 56.8%
any lower extremity joint in 30.1%
wrist or hand plus knee in 8%
polyarticular in 51.%
Reference - Arthritis Care Res (Hoboken) 2015 Sep;67(9):1304 full-text
History of present illness (HPI)
disease progression is variable(1, 2)

most patients with asymptomatic hyperuricemia will not develop gout
acute gout attack (flares)
characterized by severe joint pain, erythema, and swelling, often beginning in middle of night
or early morning, peaking within 24 hours
patient may remember prodrome period of mild joint pain or tingling
usually self-limited with spontaneous resolution in 7-14 days
patients often cannot tolerate socks or weight of bed sheet during acute attack and may be
unable to support own weight
most common site is first metatarsophalangeal joint, with other sites in foot and ankle
commonly affected
patients may report history of recurrent self-limiting flares
chronic gout
typically takes many years to progress
involved joints persistently stiff and swollen
tophi may be present
most common occur in joints, ears, bursae, finger pads, and tendons
patients may have history of discharging tophaceous material, or associated infection or
ulceration
ask about common triggers of flares including(1)
medical or surgical illness
dehydration
dietary factors such as consumption of alcohol or purine-rich foods
ask about associated comorbidities such as obesity and hypertension(1)
Medication history
ask about medications associated with hyperuricemia and gout, including

low-dose aspirin
diuretics, such as thiazides, furosemide, and other loop diuretics
cyclosporine
ethanol
ethambutol
pyrazinamide
levodopa
niacin (nicotinic acid)
cytotoxic agents
excess ethanol intake
vitamin B12
warfarin (Clin Chem 1986 Aug;32(8):1557 PDF)
19/46
Past medical history (PMH)
ask about conditions associated with risk for gout, including

renal impairment
polycystic kidney disease (autosomal dominant polycystic kidney disease)
chronic renal failure
hypertension
metabolic/endocrine conditions
dehydration
lactic acidosis
hyperparathyroidism
ketosis
hypothyroidism
toxemia of pregnancy (hypertensive disorders of pregnancy)
obesity
sarcoidosis
hematologic conditions
lympho-/myeloproliferative disorders
polycythemia
psoriasis
obesity
Physical
Skin
acute gout may present with soft tissue erythema, warmth, and swelling overlying affected joint(1)
skin desquamation may occur over inflamed area(1)
Extremities
assess for swollen, red, tender joint during attack

usually unilateral first metatarsophalangeal joint in first attack
other commonly affected joints
foot
ankle
knee
wrist
finger
elbow
Reference - BMJ 2006 Jun 3;332(7553):1315 full-text
first metatarsophalangeal joint, knee, ankle, and midfoot are commonly involved in patients
with gout
983 patients (mean age 58 years, 71.4% male) with ≥ 1 swollen joint or subcutaneous tophus
within 2 weeks of study entry were evaluated
509 patients (52%) had monosodium urate crystal-proven gout
joint involvement among patients with gout
20/46
first metatarsophalangeal joint (MTP) in 39.4%

knee, ankle, or midfoot in 37.1%
elbow or wrist or hand in 14.9%
polyarticular in 8.6%
joint involvement among patients without gout
knee only in 56.8%
any lower extremity joint in 30.1%
wrist or hand plus knee in 8%
polyarticular in 51.%
Reference - Arthritis Care Res (Hoboken) 2015 Sep;67(9):1304 full-text
first metatarsophalangeal joint arthritis may be present in up to 75% of patients with gout
systematic review of 45 studies evaluating characteristics of first metatarsophalangeal joint
(MTP) in 5,478 patients with gout
prevalence of acute first MTP arthritis in gout
at any point during course of disease in 73% (95% CI 65%-80%) in analysis of 11
studies with 2,464 patients, results limited by significant heterogeneity
at disease onset in 43-76% in 5 studies
features of acute first MTP arthritis included
rapid onset of extremely severe pain and tenderness
moderate swelling, erythema, and inflammation
pain during intercritical periods
hallux valgus
osteoarthritis
moderate to high levels of general disability and walking disability
restricted joint motion
Reference - BMC Musculoskelet Disord 2016 Feb 11;17:69 full-text
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Common Sites for Gout. : .
assess for signs of tophi, including(4, 5)

visible or palpable soft tissue masses
asymptomatic intradermal/subcutaneous nodules or lesions
white or yellowish deposits
taut overlying skin
22/46
Gout. : Tophaceous gout in the second toe.
23/46
Polyarticular Gout. : Polyarticular gouty arthritis is an uncommon initial manifestation of gout but
becomes more common late in the course of untreated gout and is often associated with tophaceous
deposits.
Diagnosis
Making the diagnosis
gold standard is demonstration of urate crystals in synovial fluid analysis or in tophus by polarized light
microscopy(1)
3e Initiative multinational recommendations on the diagnosis and management of gout
for a definite diagnosis of gout, monosodium urate monohydrate (MSU) crystals should be
identified (3e Initiative Level 2b, Grade D)
if identification of crystals not possible, a diagnosis of gout can be supported by classical clinical
features such as podagra, tophi, rapid response to colchicine and/or characteristic imaging findings
(3e Initiative Level 2b, Grade B)
presumptive diagnosis can be made based on following
presence of hyperuricemia
careful patient and family history including questions regarding
comorbidities (for example, hypertriglyceridemia, diabetes, coronary heart disease,
hypertension, metabolic syndrome)
previous similar episodes of acute joint pain and swelling in absence of trauma
identification of current medications that may be associated with hyperuricemia
physical exam including
joints
extensor surfaces of forearms and feet
common sites for tophi (for example, ear, knee, olecranon bursa)
other clinical features
duration of joint pain
fever (low-grade or high)
Reference - Cleve Clin J Med 2008 Jul;75 Suppl 5:S17
gout often misdiagnosed
based on medical record review of random sample of 200 patients with at least 2 ambulatory claims
for diagnosis of gout
121 patients (61%) considered to have probable or definite gout by consensus of rheumatologists
Reference - Arthritis Rheum 2007 Feb 15;57(1):103
Differential diagnosis
septic arthritis is key differential diagnosis(1)

presentation and appearance of joint may be indistinguishable from gout, but septic arthritis requires
emergency treatment with drainage and antibiotics
definitive diagnosis made by fluid analysis
synovial fluid findings consistent with septic arthritis include
absence of crystals
elevated white blood cell count > 50,000 cells/mcL suggests septic arthritis, but cannot rule
out crystal arthritis
polymorphonuclear cells > 90% may be associated with increased likelihood of septic
arthritis, but evidence inconsistent
Gram stain may be positive in about 50%-67% of adults and about 30% of children with
septic arthritis; negative Gram stain does not rule out septic arthritis
24/46
blood cultures may be positive even if synovial fluid culture is negative

other types of inflammatory arthritis include(1, 2)
calcium pyrophosphate dihydrate deposition (CPPD) disease (pseudogout)
basic calcium phosphate (BCP) deposition disease
psoriatic arthritis
reactive arthritis
rheumatoid arthritis
osteoarthritis
other conditions in the differential include(2)
sarcoidosis
bacterial cellulitis
bacterial cellulitis usually distinguished by warmth and erythema that is not confined to the
skin immediately overlying the joint and the joint itself is not affected
Testing overview
synovial fluid analysis
identification of monosodium urate monohydrate (MSU) crystals is diagnostic (ACP Weak
recommendation, Low-quality evidence; 3e Initiative Level 2b, Grade D)
gram stain and culture may be performed to rule out septic arthritis (blood culture may also be
useful)
serum uric acid usually elevated, but may be lower during an attack
imaging studies allow visualization of affected joint and may include
x-ray
ultrasound
computed tomography
multinational recommendations for additional tests for comorbidity in patients with gout and/or
hyperuricemia
assess renal function (3e Initiative Level 2c, Grade C) (see Diagnosis section of Chronic kidney
disease (CKD) in adults for additional information)
assess for risk of cardiovascular diseases (3e Initiative Level 2c, Grade C) (see Cardiovascular risk
prediction and Screening for risk factors for cardiovascular disease in adults for additional
information)
Clinical prediction rules
American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) 2015 gout
classification criteria
classification criteria intended for identification of participants' eligibility for clinical study and not for
diagnosis
also available as online calculator or 2-page form PDF from The University of Auckland, New Zealand
ACR/EULAR 2015 gout Classification Criteria
diagnosis of gout can be made based on
history of ≥ 1 episode of pain/tenderness or swelling in peripheral joint/bursa
either
identification of monosodium urate monohydrate (MSU) crystals in synovial fluid of
symptomatic joint/bursa or tophus
≥ 8 points based on clinical, laboratory, and imaging assessments
clinical assessment
pattern of joint/bursa involvement during any symptomatic episode(s) (0-2
points possible)
25/46
involvement of any joint/bursa only during polyarticular episodes =

0 points
involvement of ankle or mid-foot but no involvement of first
metatarsophalangeal joint during monoarticular or oligoarticular
episode = +1 point
involvement of first metatarsophalangeal joint during monoarticular
or oligoarticular episode = +2 points
presence of characteristics of affected joint during any symptomatic
episode(s) (each present characteristic contributes 1 point, with 0-3 points
possible)
erythema over affected joint (as reported by patient or observed by
physician) = +1 point
intolerance to touch or pressure affected joint = +1 point
great difficulty with walking or use of affected joint = +1 point
time course of any symptomatic episode(s) (0-2 points possible)
typical episode defined as ≥ 2 of the following (regardless of
inflammatory treatment)
maximal pain within 24 hours of symptomatic episode onset
symptom resolution within 14 days
complete resolution between symptomatic episodes
only 1 typical episode = +1 point
recurrent (≥ 2) typical episodes = +2 points
clinical evidence of tophus (0 or 4 points possible)
tophus defined as draining or chalk-like nodule under transparent
skin, with or without overlying vascularity, at a typical location such
as joint, ear, olecranon bursa, finger pad, or tendon
absence = 0 points
presence = +4 points
laboratory assessments
serum urate levels (use highest reading on record) (-4, 0, 2, 3, or 4 points
possible)
measure serum urate by uricase method, ideally when patient not
having urate-lowering treatment and during intercritical period
(usually > 4 weeks after symptomatic episode onset) (if possible,
retest under ideal conditions)
assign points based on serum urate levels
< 4 mg/dL (< 0.24 mmol/L) = subtract 4 points
≥ 4 to < 6 mg/dL (≥ 0.24 to < 0.36 mmol/L) = 0 points
≥ 10 mg/dL (≥ 0.6 mmol/L) = 4 points
if synovial fluid analysis from joint/bursa with current or past symptoms
performed by trained observer and no MSU crystals identified, subtract 2
points
imaging assessments
using either ultrasound or dual-energy computed tomography (DECT), if
evidence of urate deposition in joint/bursa with current or past symptoms
add 4 points
using conventional radiography, if evidence of erosion seen in hands and/or
feet (excluding distal interphalangeal joints), add 4 points
Reference - Ann Rheum Dis 2015 Oct;74(10):1789 full-text, also published in Arthritis Rheumatol
2015 Oct;67(10):2557 full-text, correction can be found in Ann Rheum Dis 2016 Feb;75(2):473
2010 Clinical diagnostic criteria

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2010 clinical prediction rule without joint fluid analysis may help diagnose gout (level 2 [mid-level]
evidence)
based on derivation study and validation study without complete blinding of reference standard
381 patients (mean age 57 years, 75% male) with monoarthritis were analyzed
216 patients (56.7%) had monosodium urate crystals in synovial fluid (reference standard)
63.7% of 328 patients who had gout diagnosed by family physician had positive result on
reference standard
factors identified and points assigned to develop clinical prediction rule for acute gouty
arthritis clinical and laboratory
3.5 points for serum uric acid > 5.88 mg/dL (350 mmol/L)
2.5 points for first metatarsophalangeal joint involvement
2 points for male sex
2 points for previous patient-reported attack
1.5 points for hypertension or presence of ≥ 1 cardiovascular disease (angina pectoris,
myocardial infarction, heart failure, cerebrovascular accident, transient ischemic attack,
or peripheral vascular disease)
1 point for joint redness
0.5 points for onset within 1 day
prevalence of gout by score
2.8% for score ≤ 4 (total 72 patients)
27% for score > 4 to < 8 points (total 63 patients)
80.4% for score ≥ 8 points (total 245 patients)
Reference - Arch Intern Med 2010 Jul 12;170(13):1120
390 patients (mean age 61 years, 70% male) with monoarthritis were evaluated using 2010 clinical
prediction rule
219 patients (56%) had monosodium urate crystals in synovial fluid (reference standard)
assessors evaluating joint fluid (reference standard) were not fully blinded to clinical data
used for scoring test, although they did not know final clinical score
mean clinical score 8.6 in patients with gout vs. 5.2 in patients without gout (p < 0.001)
diagnostic performance of clinical score
score of ≥ 8 had positive predictive value 87%
score of ≤ 4 had negative predictive value 95%
Reference - Rheumatology (Oxford) 2015 Apr;54(4):609
ACR/EULAR 2015 criteria has high specificity while 2010 clinical prediction rule has high
sensitivity for classification of gout (level 2 [mid-level] evidence)
based on diagnostic cohort study without ACR/EULAR applied as in clinical practice
381 patients with monoarthritis presenting to Dutch family physicians between 2004 and 2007 were
assessed
57% patients had monosodium urate crystals (reference standard)
as the patient information was collected prior to the release of the 2015 ACR/EULAR criteria,
criteria were mapped to existing data
diagnostic performance of gout classification criteria
ACR/EULAR 2015 had
sensitivity 68%
specificity 98%
positive predictive value 98%
negative predictive value 70%
ACR/EULAR 2015 (clinical criteria alone) had
sensitivity 68%
specificity 84%
2010 clinical prediction rule with score ≥ 8 had
sensitivity 91%
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specificity 71%
Reference - Rheumatology (Oxford) 2017 Aug 1;56(8):1335
Blood tests
serum uric acid level(1, 2)

urate levels usually elevated, but may be lower during an attack
if uncertainty of diagnosis exists, retest serum urate levels after flare resolution
hyperuricemia is not sufficient for diagnosis, as majority of patients with hyperuricemia do not
develop gout
about 14% patients may have serum uric acid level ≤ 6 mg/dL during acute gout attack
based on pooled data from 2 randomized trials
339 patients (mean age 51 years) with acute gout randomized to etoricoxib vs. indomethacin
for 7 days had serum urate levels assessed before and after treatment
serum urate levels during acute attack (before treatment)
14.1% had serum urate ≤ 6 mg/dL (357 mcmol/L)
32.1% had serum urate ≤ 8 mg/dL (476 mcmol/L)
Reference - J Rheumatol 2009 Jun;36(6):1287
other findings on blood tests nonspecific for diagnosis of gout but indicative of systemic inflammation
include(1)
elevated acute-phase reactants during flare
neutrophil predominant leukocytosis
other laboratory tests for use in assessment of associated disorders include(1)
serum creatinine to assess for chronic kidney disease
lipid screening to assess for dyslipidemia
glucose levels to assess for diabetes mellitus
Imaging studies
X-ray
at first presentation, x-ray often normal with nonspecific soft tissue swelling of affected joint(2)
bone erosion may be present in advanced gout, and often presents as sclerotic rim and overhanging edge(2)
tophi often seen as soft tissue opacities(2)
x-ray may help rule out fracture(2)
Ultrasound
can aid in joint aspiration and identifying articular urate deposition, tophi, and inflammatory signs such as
effusion and synovitis(1, 2)
features for acute gout nonspecific and include
periarticular soft-tissue edema
hypervascularity within and around joint
Reference - Curr Opin Rheumatol 2009 Mar;21(2):124
features for chronic gout
hyperechoic, irregular band over superficial margin or articular cartilage (double contour sign)
tophi appearing as hypoechoic to hyperechoic inhomogeneous areas surrounded by small anechoic
rim
less specific features may be observed using Power Doppler
28/46
bone erosion
joint effusions
synovial hypertrophy
hypervascularity
some ultrasound findings appear significantly more common in patients with gout compared to
patients with other joint disease (level 2 [mid-level] evidence)
based on 2 diagnostic case-control studies without validation
comparing findings on ultrasound images of 37 gouty joints vs. 33 joints with disease other than
gout
double contour sign identified in 92% vs. 0% (p < 0.001)
tophaceous material (hypoechoic to hyperechoic, inhomogeneous material surrounded by
small anechoic rim) identified in 100% gouty metatarsophalangeal joints and 100% gouty
metacarpophalangeal joints vs. 0% controls (p < 0.001)
erosions adjacent to tophaceous material identified in 65% gouty metatarsophalangeal joints
and 25% gouty metacarpophalangeal joints vs. 1 joint (4%) (p < 0.05 for both comparisons)
Reference - Rheumatology (Oxford) 2007 Jul;46(7):1116
comparing 91 men with primary gout (confirmed by crystals on joint aspiration) and 42 age-
matched controls
ultrasound to assess abnormalities in 26 joints, 6 bursae, 8 tendons, 20 tendon compartments,
4 ligaments, and 18 articular cartilages was done between acute attacks
findings in specific locations that were more common in patients with gout (p < 0.0005)
included
hyperechoic aggregates in 3 areas - radiocarpal dorsal recess, knee lateral recess, and
first metatarsophalangeal dorsal recess
hyperechoic aggregates and/or hyperechoic linear bands in 4 areas - triceps tendon,
wrist extensor tendons, quadriceps tendon, and patellar tendon
double contour sign in 2 areas - first metatarsal dorsal cartilage and femoral condyle
cartilage
Reference - Ann Rheum Dis 2014 Aug;73(8):1522
Dual energy computed tomography (DECT)
CT of affected joint may be useful for

visualizing tophi, especially intra-articular tophi (mean Hounsfield units of tophi usually 170 on
CT)
visualizing bone erosion
guiding needle aspiration
assessing complications
dual-energy CT may be useful for diagnosis of non-tophaceous gout in patients with synovial fluid
analysis negative for urate crystals (level 2 [mid-level] evidence)
based on diagnostic cohort study without independent validation
91 patients having clinically-indicated injection or aspiration of a peripheral joint were assessed
using dual-energy CT
patients with tophaceous gout were excluded
47.3% (43 patients) had urate crystals in joint fluid aspirate by polarizing microscopy or electron
microscopy (reference standard)
performance characteristics of dual-energy CT for diagnosing gout
sensitivity 90%
specificity 83%
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in patients with false negative dual-energy CT, 4 of 4 were within 6 weeks of their first attack
of gout
in additional cohort with 30 patients with suspected gout but with either absence of crystals on
aspiration or inability to obtain synovial fluid
dual-energy CT was positive for gout in 14 patients (47%)
12 of these agreed to have joint aspiration
gout detected by microscopy in 11 of 12 of these patients
Reference - Ann Rheum Dis 2015 Jun;74(6):1072 full-text
dual-energy CT may be highly specific for detection of gout (level 2 [mid-level] evidence)
based on prospective diagnostic case-control study
40 patients with crystal-confirmed gout (17 with tophaceous gout) and 40 controls with other
arthritic conditions had dual-energy CT scan of all peripheral joints and physical exam by
rheumatologist
dual-energy CT scans were interpreted by radiologist blinded to diagnosis
for detection of gout, dual-energy CT had
78% sensitivity (95% CI 62%-89%)
93% specificity (95% CI 80%-98%)
Reference - Ann Rheum Dis 2012 Sep;71(9):1466
DynaMed commentary -- the population from this study was significantly different from the one
above in that this one had a significant percentage with tophaceous gout and for the study above
tophaceous gout was part of the exclusion criteria
CT reported to provide more specific images of tophaceous gout than x-ray, ultrasound, or magnetic
resonance imaging
based on diagnostic cohort study without diagnostic uncertainty
4 men (mean age 56 years) with chronic tophaceous gout confirmed by needle aspiration had CT
scan, magnetic resonance imaging (MRI), ultrasonography, and x-ray of affected joint
tophi affected knee joints in 3 men and olecranon processes of elbow in 1 man
CT scans identified round and oval opacities with mean density about 160 Hounsfield units (specific
for monosodium urate crystals)
MRI, ultrasound, and x-ray were not specific for gout
MRI identified lesions with low-to-intermediate signal intensity
color Doppler ultrasound identified hypoechogenic areas and increased vascularity in 3 cases
x-ray identified soft tissue thickening but no calcifications or ossifications
Reference - Ann Rheum Dis 2002 Jan;61(1):52 PDF
symptomatic gout associated with higher frequency and larger volume of urate crystal deposits on
DECT compared to patients with asymptomatic hyperuricemia (level 2 [mid-level] evidence)
based on diagnostic case-control study
33 patients with non-tophaceous crystal-proven gout and 25 patients with serum urate ≥ 540
mcmol/L without gout symptoms had DECT scans of both feet
comparing DECT findings in patients with gout vs. patients with asymptomatic hyperuricemia
urate deposition in 82% vs. 24% (p < 0.001)
volume of urate deposits 0.62 cm3 vs. 0.023 cm3 (p = 0.007)
similar results in subgroup analyses with patients with early or late gout
Reference - Ann Rheum Dis 2015 May;74(5):908, commentary in Ann Rheum Dis 2015
Sep;74(9):e50
Comparative diagnostic performance of imaging modalities
double contour sign on ultrasound and identification of monosodium urate crystal deposits using
DECT may each have moderate sensitivity for diagnosis of gout (level 2 [mid-level] evidence)
based on systematic review with wide confidence intervals
systematic review of 11 studies evaluating imaging modalities for diagnosis of gout in 942 patients
7 studies evaluated ultrasound
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3 studies evaluated dual energy computed tomography (DECT)

1 study evaluated x-ray
reference standard was presence of monosodium urate crystals in synovial fluid
mean gout disease duration ≥ 7 years
performance of ultrasound features for diagnosis of gout in analysis of 5 studies
double contour sign had sensitivity 83% (95% CI 72%- 91%) and specificity 76% (95% CI
68%-83%)
detection of tophi had sensitivity 65% (95% CI 34%- 87%) and specificity 80% (95% CI
38%- 96%)
performance of identification of MSU crystal deposition on DECT for diagnosis of gout in analysis
of 3 studies
sensitivity 87% (95% CI 79%-93%)
specificity 84% (95% CI 75%-90%)
Reference - Ann Rheum Dis 2015 Oct;74(10):1868 full-text
for diagnosing gout, x-ray may be more specific and ultrasound may be more sensitive (level 2 [mid-
level] evidence)
based on diagnostic cohort study with unclear blinding of reference standard
105 adults aged 31-89 years with clinical suspicion of gout had x-ray and high-resolution ultrasound
reference standards were microscopy of aspirate or clinical and laboratory findings
55 patients (52%) had definite diagnosis of gout
19 patients were excluded from analysis as definite diagnosis could not be
for gout diagnosis, presence of ≥ 1 positive x-ray sign (soft-tissue opacifications, articular and
periarticular bone erosions, osteophytes at margins of opacifications or erosions) had
for gout diagnosis, presence of ≥ 1 ultrasound finding (bright stippled foci, hyperechoic soft-tissue
areas, hypoechoic streaks between and around hyperechoic areas, hypervascularization on color
Doppler, articular and periarticular bone erosions) had
Reference - Eur Radiol 2008 Mar;18(3):621
Biopsy and pathology
tophus is pathognomonic(1)
biopsy of tophus shows chronic foreign body granulomatous inflammation surrounding
monosodium urate crystals (Cleve Clin J Med 2008 Jul;75 Suppl 5:S5)
fine needle aspiration of gouty tophus may be performed
small whitish material may be visible macroscopically
microscopic appearance
aggregates of crystalline material
occasional histiocytes
multinucleate giant cells less common
slender, rod-shaped crystals with pointed ends in smear background
crystals strongly (negatively) birefringent
crystals may also appear as aggregates of dense, amorphous material that stain dark
grayish with Giemsa-based stains
Reference - Cancer 2002 Jun 25;96(3):157 full-text
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Tophaceous Material Viewed under Light Microscopy, Demonstrating Numerous Needle-

Shaped Monosodium Urate Crystals. : Note the acellular nature of this material; in contrast, to
be diagnostic, joint fluid should have polymorphonuclear leukocytes containing crystals.
Tophaceous Material Viewed under Polarized Microscopy, Demonstrating the Ability of

Monosodium Urate Crystals to Bend Light.
32/46
Tophaceous Material Viewed under Polarized Microscopy with Color Compensator,

Demonstrating Birefringence. : Note that crystals orthogonal to each other are colored yellow
rather than blue; crystals at angles midway between maximally bright crystals do not transmit
the light (angle of extinction).
Synovial fluid analysis

identification of monosodium urate monohydrate (MSU) crystals in synovial fluid using polarizing light
microscopy provides definitive diagnosis(1, 2)
American College of Physicians 2016 recommendation for diagnosis of gout
use synovial fluid analysis for diagnostic testing in patients with suspected acute gout, if
(ACP Weak recommendation, Low-quality evidence)
joint can be aspirated without substantial patient discomfort or risk of infection by an
experienced clinician
reliable and accurate resource is available to detect presence of urate crystals, including
polarizing microscope and trained operator
clinical uncertainty and probability of infection exists
Reference - Ann Intern Med 2017 Jan 3;166(1):52
crystals characteristics
needle shaped and 1-20 micrometer in length
negative birefringence under polarized light (yellow when parallel and blue when
perpendicular to axis of polarizer)
may be intracellular or extracellular
while most commonly identified during acute flare, crystals may also be present in patients in
between attacks
additional synovial fluid findings(1, 2)
during acute gout flare, synovial fluid typically appears yellow, cloudy, and non-viscous
high number of white blood cells may be present (can be > 50,000 cells per mm3) with neutrophil
predominance
gram stain and culture of synovial fluid useful to exclude septic arthritis
Treatment
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Treatment of acute attack
although acute attacks typically spontaneously resolve within 1-2 weeks, early initiation of treatment for
flare recommended to hasten symptom resolution (EULAR Grade D, Level 4 overall, EULAR Grade A,
Level 1b for colchicine within 12 hours; ACR Evidence C)
in patients with mild-moderate pain, use monotherapy with any of the following (ACR Evidence A; ACP
Strong recommendation, High-quality evidence)
colchicine (1-1.2 mg orally followed by 0.5-0.6 mg 1 hour later) within 12-36 hours of flare onset
(EULAR Grade A, Level 1b; ACR Evidence C; ACP Strong recommendation, Moderate-quality
evidence)
oral nonsteroidal anti-inflammatory drugs (NSAIDs), with options including naproxen,
indomethacin, and sulindac (EULAR Grade A, Level 1b; ACR Evidence A; ACP Strong
recommendation, High-quality evidence)
all appear equally effective
use full dosing approved by FDA or European Medicines Agency
corticosteroids
potential steroid regimens include
prednisone ≥ 0.5 mg/kg once daily for 5-10 days without taper (ACR Evidence A)
prednisone ≥ 0.5 mg/kg once daily for 2-5 days followed by taper for 7-10 days and
then discontinuation (ACR Evidence C)
prednisolone 30-35 mg/day orally for 3-5 days (EULAR Grade A, Level 1b)
methylprednisolone 0.5-2 mg/kg IV or intramuscularly once for patients unable to take
oral medication (ACR Evidence B)
consider intra-articular corticosteroid injection in patients with involvement of 1-2 joints
unable to take oral medication (ACR Evidence B)
for attacks with severe pain, especially if acute polyarticular gout or involving multiple large joints,
consider combination therapy, such as (ACR Evidence C)
full dose of colchicine plus an NSAID
full dose of oral corticosteroids plus colchicine
intra-articular steroids with any other treatment
interleukin-1 blockers may be considered in patients with flare and refractory to other therapies
canakinumab (EULAR Grade A, Level 1b; ACR Evidence C)
anakinra (EULAR Grade C, Level 3; ACR Evidence B)
consider nonpharmacologic treatments in addition to medication, including rest, ice packs, and elevation
of affected joints (ACR Evidence B)
consider initiation of urate-lowering therapy to prevent flares, although recommended timing varies with
guideline organization (see below)
see Gout management - treatment of acute attack for details
Prevention of recurrent attacks
consider and discuss urate-lowering therapy (ULT) for every patient with gout (ACP Strong
recommendation, Moderate-quality evidence; EULAR Grade A, Level 1b)
ULT is recommended for patients with gout and
tophus or tophi on physical exam or imaging (ACR Evidence A)
≥ 2 attacks per year (ACR Evidence A)
chronic kidney disease stage 2 or worse (ACR Evidence C)
history of urolithiasis (ACR Evidence C)
during acute attack as long as effective anti-inflammatory management initiated (ACR
Evidence C)
initiation of long term ULT in patients after first attack or in patients with infrequent attacks not
recommended (ACP Strong recommendation, Moderate-quality evidence)
medication options
34/46
first-line options include xanthine oxidase inhibitors

usual dosing
allopurinol
100 mg/day orally initially (EULAR Grade A, Level 1b; ACR Evidence B)
gradually increasing every few weeks until the target uric acid level is achieved,
up to maximum 800 mg/day (ACR Evidence C)
febuxostat 40-80 mg/day
adjust dosing based on creatinine clearance in patients with renal impairment (EULAR Grade
C, Level 3)
FDA warns of increased risk of death with febuxostat use
boxed warning required due to increased risk of death with febuxostat use compared to
allopurinol use for gout
approval limited for use in patients not treated effectively or with severe adverse events with
allopurinol
Reference - FDA Drug Safety Communication 2019 Feb 21
second-line options in patients with normal renal function include uricosuric agents such as
probenecid and benzbromarone (EULAR Grade B, Level 2b; ACR Evidence B)
lesinurad, FDA approved for the treatment of hyperuricemia associated with gout when used
in combination with a XOI in patients who have not reached target serum uric acid levels with
XOI monotherapy
consider combination therapy if target serum uric acid is not reached with first-line therapy (ACR
Evidence B), such as addition of urosuric agent to xanthine oxidase inhibitor
pegloticase
recommended only in patients with severe refractory gout or in those who cannot tolerate
appropriate maximum dose of conventional oral ULT (EULAR Grade A, Level 1b; ACR
Evidence A)
not recommended in combination with other urate lowering therapies
provide anti-inflammatory prophylaxis (with colchicine 0.5-0.6 mg once or twice daily, a nonsteroidal
anti-inflammatory drug, or corticosteroid) is for all gout patients when ULT is started and continue for at
least 6 months (EULAR Grade B, Level 2b; ACR Evidence A)
management of patients on ULT
for most patients, titrate ULT to a target serum uric acid level of ≤ 6 mg/dL (EULAR Grade C,
Level 3; ACR Evidence A)
some patients may require a level of < 5 mg/dL to control symptoms (EULAR Grade C, Level 3;
ACR Evidence B)
for patients on ULT, measure serum uric acid and creatinine levels every 2-5 weeks while up
titrating ULT and every 6 months after serum uric acid target is reached (ACR Evidence C)
regularly monitor for side effects of ULT (ACR Evidence C)
continue ULT during an acute gout attack (ACR Evidence C)
see Gout management - prevention of recurrent attacks for details
Complications and Prognosis

Complications
complications due to untreated gout or persistent hyperuricemia may include(1, 2)

recurrent and polyarticular flares
advanced gout with tophi and/or chronic gouty arthritis
complications of tophaceous gout
joint erosion or destruction(1)
carpal tunnel syndrome (Medicine (Baltimore) 2017 Mar;96(9):e6245 full-text)
renal disease
forms of hyperuricemia-induced renal disease include
35/46
uric acid nephrolithiasis (kidney stones)

acute uric acid nephropathy (associated with chemotherapy and tumor lysis syndrome)
chronic kidney disease resulting from urate crystal deposition
Reference - Cleve Clin J Med 2008 Jul;75 Suppl 5:S13
hyperuricemia may be associated with renal failure
48,177 adults > 20 years old Japan screened for serum uric acid levels in 1993 were evaluated
for later registration in dialysis programs using computer registries
calculated incidences for end-stage renal disease per 1,000 screened patients
1.22 for men without hyperuricemia (urate < 7 mg/dL [416 mcmol/L])
4.64 for men with hyperuricemia (urate ≥ 7 mg/dL [416 mcmol/L])
0.87 for women without hyperuricemia (urate < 6 mg/dL [357 mcmol/L])
9.03 for women with hyperuricemia (urate ≥ 6 mg/dL [357 mcmol/L])
Reference - Am J Kidney Dis 2004 Oct;44(4):642
hyperuricemia associated with reduction in eGFR and increased risk of renal failure
739 patients with serum uric acid > 7 mg/dL and/or taking urate-lowering therapy (ULT) for >
1 month between 2003 and 2005 in Taiwan were followed for mean 4.25 years
baseline uric acid ≥ 6 mg/dL associated with reduction in estimated glomerular filtration rate
in dose-responsive manner (p < 0.001 for trend )
144 patients (19.4%) developed renal failure
higher baseline uric acid associated with increased risk of renal failure (adjusted hazard ratio
1.07, 95% CI 1-1.14 per 1 mg/dL increase)
adjusted HR 1.27 (95% CI 1.1-1.46) in patients with proteinuria
adjusted HR 1.07 (95% CI 0.99-1.17) in patients without proteinuria
impact of hyperuricemia on risk of kidney failure greater in patients with
Reference - PLoS One 2017;12(1):e0170393 full-text
hospitalization associated with increased risk of acute arthritic flares in patients with gout
429 adults with gout were evaluated
158 (mean age 59 years, 73% male) were diagnosed between 1989 and 1992 and followed for
median 5 years
271 (mean age 60 years, 72% male) were diagnosed between 2009 and 2010 and followed for
median 4.7 years
169 patients were hospitalized (454 total hospitalizations) (only 1 flare per hospitalization was
included in analysis)
cardiovascular disease was most common reason for hospitalization (23%-28% of admissions)
in-hospital acute arthritic flare (gout flare) defined as new-onset inflammatory arthritis attributed to
gout by providers
gout flare in 23 patients (28 total hospitalizations)
hospitalization associated with increased risk of gout flare compared to no hospitalization (relative
risk 10.2, 95% CI 6.8−14.5)
in-hospital gout flare associated with increased hospital stay compared to hospitalizations without
gout flares (adjusted mean increase in hospital stay 1.8 days, p < 0.001)
Reference - J Rheumatol 2018 Aug;45(8):1188
erectile dysfunction
increased erectile dysfunction in men with gout
based on prospective population-based cohort study
38,438 men (mean age 63 years) with gout and 154,332 age-, enrollment time-, and body
mass index-matched men without gout (control) from medical database were assessed for
incident erectile dysfunction (ED) for median 5 years
incident ED 11.9 per 1,000 person-years in men with gout vs. 10.5 per 1,000 person-years in
controls (adjusted hazard ratio 1.15, 95% CI 1.09−1.21)
Reference - J Rheumatol 2018 Aug;45(8):1192
36/46
gout associated with increased incidence of erectile dysfunction in population-based cohort study (J
Rheumatol 2015 Oct;42(10):1898)
gout may not be associated with increased risk of fragility fractures
31,781 patients (mean age 63 years) with gout were matched to 122,961 controls and followed for
median 10.8 years
5.8% had a first fragility fracture during follow-up
no significant difference in rate of fragility fractures comparing patients with gout to patients
without gout
among patients with gout
21% were prescribed ULT within 3 years of diagnosis and continued treatment for ≥ 6 months
no significant difference in rate of fragility fracture at 1 or 3 years comparing patients who
received ULT vs. patients who did not
Reference - CMAJ 2018 May 14;190(19):E581-E587 full-text
Prognosis
acute attacks usually self-limiting within 1-2 weeks with complete resolution of joint inflammation(1)
recurrence
reported risk of recurrence after initial attack
about 60% recurrence within 1 year
about 78% within 2 years
about 84% within 3 years
> 90% will have recurrence at 10 years
subsequent attacks usually last longer and may involve more joints
Reference - Cleve Clin J Med 2008 Jul;75 Suppl 5:S5 PDF
in patients not receiving urate-lowering therapy, advanced gout with tophi reported to occur > 10 years
after initial acute attack(1)
gout (and hyperuricemia) may be associated with increased risk of coronary artery disease
mortality
all-cause mortality appears higher in patients with gout compared to patients without gout in
United Kingdom between 1999 and 2014
information on > 10 million patients from 575 general practices in The Health Improvement
Network (THIN) database in United Kingdom from 1999 to 2014 used to identify patients
with incident gout and matched controls
44,783 patients with incidence gout and 223,365 matched controls without gout
identified between 1999 and 2006
58,478 patients with incident gout and 291,552 matched controls without gout
identified between 2007 and 2014
deaths per 1,000 person-years in patients with gout vs. controls
29.1 vs. 23.5 between 1999 and 2006
23 vs. 18.8 between 2007 and 2014
incident gout associated with higher all-cause mortality
adjusted hazard ratio (HR) 1.1, 95% CI 1.06-1.15, for 1999-2006
adjusted HR 1.09, 95% CI 1.05-1.13, for 2007-2014
Reference - Ann Rheum Dis 2017 Jul;76(7):1289
presence of subcutaneous tophi, older age, loop diuretic use, Maori or Pacific ethnicity, and
elevated serum creatinine associated with increased risk of all-cause mortality in patients with
gout for < 10 years
295 patients (mean age 59 years, 70.5% male) with gout for < 10 years in New Zealand were
followed for mean 5.1 years
37/46
115 patients (39%) had history of cardiovascular disease

51 patients (17.3%) had subcutaneous tophi
43 patients (14.6%) died (standardized mortality ratio [SMR] 1.96, 95% CI 1.44-2.62)
presence of subcutaneous tophi associated with increased risk of
all cause mortality (adjusted hazard ratio [HR] 2.85, 95% CI 1.49-5.44)
cardiovascular cause of mortality (adjusted HR 3.13, 95% CI 1.38-7.1)
non-cardiovascular cause of mortality (adjusted HR 3.48, 95% CI 1.25-9.63)
other factors associated with increased risk of all-cause mortality
older age (vs. age < 50 years)
70-80 years (HR 9.96, 95% CI 3.3-30.03)
80-91 years (HR 9.39, 95% CI 2.68-32.89)
loop diuretic use (adjusted HR 3.99, 95% CI 2.15-7.4)
Maori or Pacific ethnicity (adjusted HR 2.48, 95% CI 1.17-5.29)
serum creatinine (adjusted HR 1.04, 95% CI 1-1.07 per 10 mcmol/L change)
Reference - J Rheumatol 2017 Mar;44(3):368
history of cardiovascular event, subcutaneous tophi, loop diuretic use, higher serum urate
level, and older age associated with increased risk for mortality in patients with gout
706 patients (mean age 58 years, 93.8% male) with gout in Spain were followed for mean
47.2 months
30.5% had ≥ 1 subcutaneous tophi
34.6% had > 4 joints involved
25.3% had history of cardiovascular event
64 patients (9.1%) died (standardized mortality ratio [SMR] 2.37, 95% CI 1.82-3.03)
SMR 1.57 (95% CI 1.18-2.05) in men vs. 4.5 (95% CI 2.06-8.54) in women
38 patients had death attributed to cardiovascular cause
factors associated with increased risk of mortality in multivariate analysis
previous cardiovascular event (adjusted hazard ratio [HR] 2.32, 95% CI 1.27-4.23)
presence of tophi (adjusted HR 2.05, 95% CI 1.29-3.28)
loop diuretic use (adjusted HR 1.98, 95% CI 1.11-3.51)
serum urate level (adjusted HR 1.16, 95% CI 1.03-1.32 per 59.5 mmol/L)
age (adjusted HR 1.08, 95% CI 1.05-1.11 per year)
Reference - Ann Rheum Dis 2014 Jan;73(1):177
Prevention and Screening

Prevention
treatment of asymptomatic hyperuricemia to reduce risk of gout not recommended in United States or
Europe(2)
consider discontinuation or modification of diuretics and other medications associated with increased risk
of gout(2)
encourage patient to adopt lifestyle modifications, such as(2)
decreased consumption of meat, seafood, and alcohol
weight loss
DASH diet may reduce risk of gout in men (level 2 [mid-level] evidence)
44,444 male health professionals aged 40-75 years without history of gout had dietary intake
assessed once every 4 years using food frequency questionnaire and were stratified by
quintiles based on DASH dietary pattern score or Western dietary pattern score
DASH dietary pattern score based on high intake of fruits, vegetables, nuts and
legumes, low fat dairy products, and whole grains and low intake of sodium, sweetened
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beverages, and red and processed meats

Western dietary pattern score based on based on high intake of red and processed
meats, French fries, refined grains, sweets, and desserts
3.9% had incident gout over 26-year follow-up
compared to lowest quintile
highest quintile for DASH dietary pattern score associated with reduced risk of gout
(adjusted relative risk 0.68, 95% CI 0.57-0.8)
highest quintile for Western dietary pattern score associated with increased risk of gout
(adjusted relative risk 1.42, 95% CI 1.16-1.74)
Reference - BMJ 2017 May 9;357:j1794 full-text
see also DASH diet
Screening
screening not practical
serum uric acid level has very-low positive predictive value for gout in population with joint pain
Reference - J Gen Intern Med 1988 Sep-Oct;3(5):435
Guidelines and Resources

Guidelines
International guidelines
multinational evidence-based recommendations for diagnosis and management of gout can be found in
Ann Rheum Dis 2014 Feb;73(2):328
international expert consensus statement on febuxostat in management of gout can be found in Clin
Rheumatol 2010 Aug;29(8):835
United States guidelines
American College of Physicians (ACP) clinical practice guidelines on

diagnosis of acute gout can be found in Ann Intern Med 2017 Jan 3;166(1):52, supporting
systematic review can be found in Ann Intern Med 2017 Jan 3;166(1):27
management of acute and recurrent gout can be found in Ann Intern Med 2017 Jan 3;166(1):58,
supporting systematic review can be found in Ann Intern Med 2017 Jan 3;166(1):37
American College of Rheumatology (ACR) guidelines on management of gout

part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia
can be found in Arthritis Care Res (Hoboken) 2012 Oct;64(10):1431 full-text, commentary can be
found in Ann Intern Med 2013 Jun 18;158(12):903
part 2: therapy and anti-inflammatory prophylaxis of acute gouty arthritis can be found in Arthritis
Care Res (Hoboken) 2012 Oct;64(10):1447 full-text, commentary can be found in Ann Intern Med
2013 Jun 18;158(12):903
American College of Radiology (ACR) Appropriateness Criteria for chronic extremity joint pain -
suspected inflammatory arthritis can be found at ACR 2016 PDF
American College of Foot and Ankle Surgeons/American Association of Nurse Practitioners

(ACFAS/AANP) clinical consensus statement on etiology, diagnosis, and treatment of gouty arthritis of
the foot and ankle can be found in J Foot Ankle Surg 2018 Nov - Dec;57(6):1207
39/46
United Kingdom guidelines
British Society for Rheumatology (BSR) guideline on management of gout can be found in Rheumatology
(Oxford) 2017 Jul 1;56(7):e1 full-text, correction can be found in Rheumatology (Oxford) 2017 Jul
1;56(7):1246
European guidelines
European League Against Rheumatism (EULAR) evidence-based recommendations on management of

gout can be found in Ann Rheum Dis 2017 Jan;76(1):29
European League Against Rheumatism (EULAR) points to consider for reporting, screening, and
preventing selected comorbidities in chronic rheumatic diseases in daily practice can be found in Ann
Rheum Dis 2016 Jun;75(6):965 full-text
Spanish Society of Rheumatology (SER) clinical practice guideline on management of gout can be found
at SER 2013
Dutch Society for Rheumatology (Nederlandse Vereniging voor Reumatologie [NVR]) clinical practice
guideline on management of gout can be found at NVR 2013 [Dutch]
Asian guidelines
Japanese Society of Gout and Nucleic Acid Metabolism guideline on management of hyperuricemia and
gout can be found in Nucleosides Nucleotides Nucleic Acids 2011 Dec;30(12):1018 or at Minds guideline
listing (医療情報サービスマインズ) [Japanese 日本語]
Review articles
review of gout: state of the art after decade of developments can be found in Rheumatology (Oxford) 2018
Mar 13 early online
Agency for Healthcare Research and Quality (AHRQ) comparative effectiveness review
update on diagnosis of gout can be found at AHRQ Comparative Effectiveness Review 2016
Nov:158 PDF
update on management of gout can be found at AHRQ Comparative Effectiveness Review 2016
Nov:176 PDF
review can be found in Am Fam Physician 2014 Dec 15;90(12):831 full-text
review can be found in Lancet 2010 Jan 23;375(9711):318, editorial can be found in Lancet 2010 Jan
23;375(9711):254
brief "what you should do" review can be found in BMJ 2010 Nov 15;341:c6155, commentary can be
found in BMJ 2011 Jan 11;342:d115
review of chronic gout can be found in Curr Med Res Opin 2010 Dec;26(12):2813
review on gouty tophus can be found in Curr Rheumatol Rep 2015 Mar;17(3):19
review on imaging tools to measure treatment response in gout can be found in Rheumatology (Oxford)
2018 Jan 1;57(suppl‗1):i27 full-text
review on imaging of gout can be found in Best Pract Res Clin Rheumatol 2016 Aug;30(4):638
review of imaging modalities for diagnosis of gout can be found in Ann Rheum Dis 2015
Oct;74(10):1868 full-text
treatment reviews
review of education and non-pharmacological approaches for gout can be found in Rheumatology
(Oxford) 2018 Jan 1;57(suppl‗1):i51 full-text
review of recent pharmacological advances in management of gout can be found in Rheumatology
(Oxford) 2018 Jun 1;57(6):951
review on management of gout can be found at Aust Prescr 2016 Aug;39(4):119 full-text
40/46
review of acute management and prevention of gout can be found in Pharmacotherapy 2016
Aug;36(8):906
review on treat to target in gout can be found in Rheumatology (Oxford) 2018 Jan
1;57(suppl‗1):i20 full-text
review of the safety of treatment options available for gout can be found in Expert Opin Drug Saf
2017 Jan 30:1
review of 2017 update on colchicine can be found in Rheumatology (Oxford) 2018 Jan
1;57(suppl‗1):i4
review of treatment of hyperuricemia in gout can be found in Ther Adv Musculoskelet Dis 2016
Aug;8(4):145 full-text
review of the role of IL-1 in gout: from bench to bedside can be found in Rheumatology (Oxford)
review of new and pipeline drugs for gout can be found in Curr Rheumatol Rep 2016 Jun;18(6):32
review of cardiac and renal protective effects of urate-lowering therapy can be found in Rheumatology
(Oxford) 2018 Jan 1;57(suppl‗1):i47 full-text
review of how to prevent allopurinol hypersensitivity reactions can be found in Rheumatology (Oxford)
review of ophthalmic manifestations of gout and uric acid crystal deposition can be found in Clin Exp
Ophthalmol 2017 Jan;45(1):73
case presentation can be found in N Engl J Med 2011 Feb 3;364(5):443, commentary can be found in N
Engl J Med 2011 May 12;364(19):1876, Postgrad Med 2012 Sep;124(5):151
case presentation of management of gout can be found in JAMA 2012 Nov 28;308(20):2133
case report of chronic tophaceous gout in 67-year-old man can be found in QJM 2016 Oct;109(10):681
case report of miliarial gout in 53-year-old man can be found in QJM 2016 Dec;109(12):811
review of diagnosis of acute monoarthritis in adults can be found in Am Fam Physician 2016 Nov
15;94(10):810
MEDLINE search
to search MEDLINE for (Gout) with targeted search (Clinical Queries), click therapy, diagnosis, or
prognosis
Patient Information
handouts from
EBSCO Health Library or in Spanish
Patient UK
information from
American College of Rheumatology or in Spanish
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Arthritis Foundation
Gout and Uric Acid Education Society
ICD Codes
ICD-9 codes
274.0 gouty arthropathy

274.00 gouty arthropathy, unspecified
274.01 acute gouty arthropathy
274.02 chronic gouty arthropathy without mention of tophus (tophi)
274.03 chronic gouty arthropathy with tophus (tophi)
41/46
274.1 gouty nephropathy

274.10 gouty nephropathy, unspecified
274.11 uric acid nephrolithiasis
274.19 other gouty nephropathy
274.8 gout with other specified manifestations
274.81 gouty tophi of ear
274.82 gouty tophi of other sites, except ear
274.89 gout with other specified manifestations
274.9 gout, unspecified
790.6 other abnormal blood chemistry
V77.5 special screening for gout
ICD-10 codes
M10 gout
M10.0 idiopathic gout
M10.1 lead-induced gout
M10.2 drug-induced gout
use additional external cause code (Chapter XX), if desired, to identify drug
M10.3 gout due to impairment of renal function
M10.4 other secondary gout
M10.9 gout, unspecified
optional subclassification codes to indicate site of involvement for M10
0 multiple sites
1 shoulder region
2 upper arm
3 forearm
4 hand
5 pelvic region and thigh
6 lower leg
7 ankle and foot
8 other
E79.0 hyperuricaemia without signs of inflammatory arthritis and tophaceous disease
E79.1 Lesch-Nyhan syndrome
M14.0 gouty arthropathy due to enzyme defects and other inherited disorders, such as
D57 sickle-cell disorders
D57.0 sickle-cell anaemia with crisis
D57.1 sickle-cell anaemia without crisis
D57.2 double heterozygous sickling disorders
D57.3 sickle-cell trait
D57.8 other sickle-cell disorders
I43.8 cardiomyopathy in other diseases classified elsewhere
References
General references used
1. Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016 Oct 22;388(10055):2039-2052
2. Neogi T. Gout. Ann Intern Med. 2016 Jul 5;165(1):ITC1-ITC16
3. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the
management of gout. Ann Rheum Dis. 2017 Jan;76(1):29-42
4. Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 2012 American
College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and
42/46
pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012

Oct;64(10):1431-46 full-text
5. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and
risk factors. Nat Rev Rheumatol. 2015 Nov;11(11):649-62
Recommendation grading systems used

American College of Physicians (ACP) guideline grading system
strength of recommendation
Strong - benefits clearly outweigh risks and burden, or risks and burden clearly outweigh
benefits
Weak - benefits closely balanced with risks and burden or uncertainty in estimates of benefits,
risks, and burdens
Insufficient - balance of benefits and risks cannot be determined
quality of evidence
High - randomized trials without important limitations, or overwhelming evidence from
observational studies
Moderate - randomized trials with important limitations (inconsistent results, methodologic
flaws, indirect, or imprecise), or exceptionally strong evidence from observational studies
Low - observational studies or case series
Insufficient - evidence is conflicting, poor quality, or lacking
Reference - ACP methods for development of clinical practice guidelines and guidance statements
(Ann Intern Med 2010 Aug 3;153(3):194)
3e Initiative guideline grading system

Oxford Centre for Evidence Based Medicine (CEBM) classifications used in 3e Initiative
recommendations
CEBM levels of evidence
Level 1a - systematic review with homogeneity of randomized controlled trials (RCTs)
Level 1b - individual RCT with narrow confidence interval
Level 1c - all or none case series
Level 2a - systematic review with homogeneity of cohort studies
Level 2b - individual cohort study or low-quality RCT
Level 2c - "outcomes" research, ecological studies
Level 3a - systematic review with homogeneity of case-control studies
Level 3b - individual case-control study
Level 4 - case series, poor-quality cohort and case-control studies
Level 5 - expert opinion without explicit critical appraisal, or based on physiology,
bench research or "first principles"
CEBM grades of recommendation
Grade A - consistent level 1 studies
Grade B - consistent level 2 or 3 studies or extrapolations from level 1 studies
Grade C - level 4 studies or extrapolations from level 2 or 3 studies
Grade D - level 5 evidence or troublingly inconsistent or inconclusive studies of any
level
Reference - 3e Initiative multinational evidence-based recommendations on diagnosis and
management of gout (Ann Rheum Dis 2014 Feb;73(2):328 full-text)
American College of Rheumatology (ACR) grades of recommendation

Evidence A - supported by > 1 randomized trial, or ≥ 1 meta-analysis
Evidence B - derived from single randomized trial, or nonrandomized studies
Evidence C - consensus opinion of experts, case studies, or standard of care
Reference - ACR guidelines for management of gout (Arthritis Care Res (Hoboken) 2012
Oct;64(10):1447 full-text)
43/46
European League Against Rheumatism (EULAR) levels of evidence

Level Ia - meta-analysis of randomized controlled trials
Level Ib - randomized controlled trial
Level IIa - controlled trial without randomization
Level IIb - quasi-experimental study
Level III - nonexperimental descriptive studies (comparative, correlation, or case-control studies)
Level IV - expert committee reports or opinion or clinical experience of respected authorities, or
both
Reference - EULAR evidence based recommendations for gout (Ann Rheum Dis 2006
Oct;65(10):1312 full-text)
Synthesized Recommendation Grading System for DynaMed Plus

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Guideline recommendations summarized in the body of a DynaMed topic are provided with the
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Strong recommendations are used when, based on the available evidence, clinicians (without
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Special acknowledgements
Jefferson R. Roberts, MD (Assistant Clinical Professor, University of Hawaii, John A. Burns School of
Medicine; Chief of Rheumatology Service and Chief of Medical Simulation, Tripler Army Medical
Center; Hawaii, United States)
Dr. Roberts declares no relevant financial conflicts of interest.
Elinor Mody, MD (Medical Director of Gretchen and Edward Fish Center for Women's Health, Brigham
and Women's Hospital; Massachusetts, United States)
Dr. Mody has declared that she has no financial conflicts of interest.
Allen Shaughnessy, PharmD, M Med Ed, FCCP (Professor of Family Medicine and Director of Master
Teacher Fellowship, Tufts University Family Medicine Residency; Cambridge Health Alliance;
Massachusetts, United States)
Dr. Shaughnessy declares no relevant financial conflicts of interest.
Alan Ehrlich, MD (Executive Editor; Associate Professor of Family Medicine, University of

Massachusetts Medical School; Massachusetts, United States)
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Dr. Ehrlich declares no relevant financial conflicts of interest.
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How to cite
National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):
DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T115215,
Gout; [updated 2018 Dec 01, cited place cited date here]. Available from
https://www.dynamed.com/topics/dmp~AN~T115215. Registration and login required.
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26/6/2019 DynaMed Plus: Gout

The most common initial presentation is a self-limiting acute attack.

Management of patients on ULT

men (incidence 2-6 times higher in men than in women)(1, 5)

3.7% among persons aged 50-59 years

Likely risk factors

hyperuricemia is main risk factor for development and recurrence of gout(1)

6-6.9 mg/dL 9.53 (95% CI 5.49-16.55) 3.41 (95% CI 1.76-6.63)

medications associated with increased risk of hyperuricemia and gout include(1, 2)

Other risk factors

obesity associated with increased risk of gout

Possible risk factors

Factors not associated with increased risk

high-dose aspirin, which is urosuric(2)

Reference - Arch Intern Med 2009 Mar 9;169(5):502

Rates of associated comorbidities

comorbidities common among patients with gout(1)

based on systematic review

cardiovascular death in 4.3% vs. 3.2% (p = 0.03, NNH 91)

Etiology and Pathogenesis

crystals stimulate release of humoral and cellular inflammatory mediators

History and Physical

Chief concern (CC)

joint involvement among patients without gout

History of present illness (HPI)

disease progression is variable(1, 2)

ask about medications associated with hyperuricemia and gout, including

Past medical history (PMH)

ask about conditions associated with risk for gout, including

assess for swollen, red, tender joint during attack

first metatarsophalangeal joint (MTP) in 39.4%

Common Sites for Gout. : .

assess for signs of tophi, including(4, 5)

Gout. : Tophaceous gout in the second toe.

septic arthritis is key differential diagnosis(1)

blood cultures may be positive even if synovial fluid culture is negative

Clinical prediction rules

involvement of any joint/bursa only during polyarticular episodes =

2010 Clinical diagnostic criteria

serum uric acid level(1, 2)

Dual energy computed tomography (DECT)

CT of affected joint may be useful for

Comparative diagnostic performance of imaging modalities

3 studies evaluated dual energy computed tomography (DECT)

Biopsy and pathology

Tophaceous Material Viewed under Light Microscopy, Demonstrating Numerous Needle-

Tophaceous Material Viewed under Polarized Microscopy, Demonstrating the Ability of

Tophaceous Material Viewed under Polarized Microscopy with Color Compensator,

Synovial fluid analysis

Treatment of acute attack

Prevention of recurrent attacks

first-line options include xanthine oxidase inhibitors

Complications and Prognosis

complications due to untreated gout or persistent hyperuricemia may include(1, 2)

uric acid nephrolithiasis (kidney stones)

115 patients (39%) had history of cardiovascular disease

Prevention and Screening

beverages, and red and processed meats

Guidelines and Resources

United States guidelines

American College of Physicians (ACP) clinical practice guidelines on

American College of Rheumatology (ACR) guidelines on management of gout

American College of Foot and Ankle Surgeons/American Association of Nurse Practitioners