CLINICAL GUIDELINE

Diagnosis of Acute Gout: A Clinical Practice Guideline From the

American College of Physicians
Amir Qaseem, MD, PhD, MHA; Robert M. McLean, MD; Melissa Starkey, PhD; and Mary Ann Forciea, MD; for the Clinical
Guidelines Committee of the American College of Physicians*

Description: The American College of Physicians (ACP) devel- of Recommendations Assessment, Development and Evalua-
oped this guideline to present the evidence and provide clinical tion) method.
recommendations on the diagnosis of gout.
Target Audience and Patient Population: The target audi-
Methods: This guideline is based on a systematic review of pub- ence for this guideline includes all clinicians, and the target pa-
lished studies on gout diagnosis, identified using several data- tient population includes adults with joint inflammation sus-
bases, from database inception to February 2016. Evaluated out- pected to be gout.
comes included the accuracy of the test results; intermediate
outcomes (results of laboratory and radiographic tests, such as Recommendation: ACP recommends that clinicians use syno-
serum urate and synovial fluid crystal analysis and radiographic vial fluid analysis when clinical judgment indicates that diagnostic
or ultrasonography changes); clinical decision making (addi- testing is necessary in patients with possible acute gout. (Grade:
tional testing and pharmacologic or dietary management); short- weak recommendation, low-quality evidence)
term clinical (patient-centered) outcomes, such as pain and joint
swelling and tenderness; and adverse effects of the tests. This Ann Intern Med. 2017;166:52-57. doi:10.7326/M16-0569 www.annals.org
guideline grades the evidence and recommendations by using For author affiliations, see end of text.
the ACP grading system, which is based on the GRADE (Grading This article was published at www.annals.org on 1 November 2016.

G out is caused by excess urate crystals accumulating

in body tissues and fluid, resulting in inflammatory
arthritis. Patients have joint swelling and pain during
Correctly diagnosing gout and differentiating it
from other inflammatory arthritic conditions, such as
rheumatoid arthritis, septic arthritis, and inflammatory
gout attacks, the initial stages of which are called acute episodes of osteoarthritis, is important, because treat-
gouty arthritis or acute gout flares. Progression to ment of these conditions differ. The reference standard
chronic gout may be accompanied by the accumula- for diagnosing acute gout is joint aspiration with syno-
tion of monosodium urate (MSU) crystals (known as to- vial fluid analysis for MSU. However, most patients ini-
phi) in joints, cartilage, tendons, bursae, bone, and soft tially are seen in the primary care or emergency medi-
tissue. Risk factors associated with gout include male cine setting, where synovial fluid analysis rarely is
sex, overweight or obesity, hypertension, excess alco- performed. Synovial fluid analysis is also underutilized
hol intake, diuretic use, a diet rich in meat and seafood, in rheumatology (7). Additional approaches for diag-
and poor kidney function (1– 4). The self-reported prev- nosing acute gout include clinical algorithms that incor-
alence of ever receiving a gout diagnosis is estimated porate patient signs and symptoms, ultrasonography,
to be 3.9% in U.S. adults older than age 20 (5); this dual-energy computed tomography (DECT), computed
prevalence increased by 1.0% between about 1990 tomography, and plain radiography.
and 2007 (5). An estimated $1 billion is spent annually
on ambulatory care for gout, largely on treatments and
prescription medications (6). GUIDELINE FOCUS AND TARGET POPULATION
The purpose of this American College of Physicians
(ACP) guideline is to provide guidance on diagnosing
See also:
acute gout in patients with gout symptoms, including
Related articles. . . . . . . . . . . . . . . . . . . . . . . 27, 37, 58 joint inflammation. This guideline does not apply to
Editorial comments . . . . . . . . . . . . . . . . . . . . . . 71, 73 adults who have chronic gout that was diagnosed pre-
Summary for Patients . . . . . . . . . . . . . . . . . . . . . . . I-16 viously by identification of MSU and who present with a
flare and no suggestion of a concurrent problem, such
Web-Only as a septic joint. These recommendations are based on
Supplement a background evidence review paper (8) and an evi-
CME quiz dence review sponsored by the Agency for Healthcare
Research and Quality (AHRQ) (9).

* This paper, written by Amir Qaseem, MD, PhD, MHA; Robert M. McLean, MD; Melissa Starkey, PhD; and Mary Ann Forciea, MD, was developed for the
Clinical Guidelines Committee of the American College of Physicians. Individuals who served on the Clinical Guidelines Committee from initiation of the
project until its approval were Mary Ann Forciea, MD† (Chair); Thomas D. Denberg, MD, PhD† (Immediate Past Chair); Michael J. Barry, MD†; Cynthia Boyd,
MD, MPH†; R. Dobbin Chow, MD, MBA†; Nick Fitterman, MD†; Linda L. Humphrey, MD, MPH†; Devan Kansagara, MD, MCR†; Scott Manaker, MD, PhD†;
Robert M. McLean, MD†; Sandeep Vijan, MD, MS†; and Timothy J. Wilt, MD, MPH†. Approved by the ACP Board of Regents on 7 November 2015.
† Author (participated in discussion and voting).

52 © 2017 American College of Physicians

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 ACP Guideline on Diagnosis of Acute Gout CLINICAL GUIDELINE

METHODS Table. The American College of Physicians' Guideline

Systematic Review of the Evidence Grading System*
The evidence review was conducted by the
Quality of Strength of Recommendation
AHRQ's Southern California Evidence-based Practice Evidence
Center–RAND Corporation. Additional methodological Benefits Clearly Outweigh Risks Benefits Finely Balanced
details may be found in the Appendix (available at www and Burden or Risks and Burden With Risks and Burden
.annals.org) as well as in the accompanying article (8) Clearly Outweigh Benefits

and full report (9). Reviewers searched several data- High Strong Weak
bases for studies published from database inception Moderate Strong Weak
Low Strong Weak
through February 2016 and included prospective and
cross-sectional studies. The study population included Insufficient evidence to determine net benefits or risks
all adults aged 18 years or older with suspected gout
(such as an acute episode of joint inflammation). * Adopted from the classification developed by the GRADE (Grading
of Recommendations Assessment, Development, and Evaluation)
The systematic review evaluated diagnostic tests workgroup.
for gout. Evaluated outcomes included accuracy of
the test results (sensitivity, specificity, and positive and
Moderate-quality evidence showed that several clinical
negative predictive value); intermediate outcomes (re-
algorithms based on clinical signs and symptoms have
sults of laboratory and radiographic tests, such as se- good specificity and sensitivity (>80%) for diagnosing
rum urate and synovial fluid crystal analysis and radio- gout compared with assessment of synovial fluid MSU
graphic or ultrasonography changes); clinical decision crystals. Many algorithms had a higher sensitivity in pa-
making (additional testing and pharmacologic or di- tients with a longer history of flares (>2 years) than in
etary management); short-term clinical (patient- those with more recent-onset symptoms (≤2 years). The
centered) outcomes, such as pain and joint swelling components of the clinical algorithms varied; however,
and tenderness; and adverse effects of the tests. most included the following clinical characteristics:
Grading the Evidence and Developing more than 1 attack of acute arthritis, maximum inflam-
Recommendations mation developing within 1 day, redness observed
This guideline was developed by the ACP Clinical over joints, painful or swollen first metatarsophalangeal
Guidelines Committee (CGC) according to the ACP joint, proven or suspected tophi, and the comorbid risk
guideline development process, details of which may factor of hyperuricemia. Details on each algorithm are
provided in the accompanying evidence review (8).
be found in the methods paper (10). The CGC used the
evidence tables in the accompanying systematic review DECT
(8) and full report (9) when reporting the evidence and Low-quality evidence from 3 observational studies
graded the recommendations by using the ACP sys- (20 –22) showed that DECT had a sensitivity of 85% to
tem, which is based on the GRADE (Grading of Recom- 100% and specificity of 83% to 92% for predicting gout
mendations Assessment, Development and Evaluation) compared with assessment of synovial fluid MSU crys-
method (Table). tals or clinical algorithms.
Peer Review Ultrasonography
The AHRQ evidence review was sent to invited Low-quality evidence (20, 23–27) showed that
peer reviewers and posted on the AHRQ Web site for ultrasonography had a wide range in sensitivity and
public comments. The guideline was peer reviewed specificity for diagnosing acute gout compared with as-
through the journal and posted online for comments sessment of synovial fluid MSU crystals or clinical algo-
from ACP Regents and Governors, who represent ACP rithms. Pooled sensitivity from 4 trials (12, 17, 19, 28)
members at the regional level. showed 74% sensitivity (95% CI, 52 to 88) and 88%
specificity (95% CI, 68 to 96).

ACCURACY OF TESTS, ALGORITHMS, AND DIAGNOSTIC ACCURACY BASED ON JOINT SITE

CLASSIFICATION SYSTEMS AND NUMBER OF JOINTS
Clinical Algorithms Incorporating Clinical Signs Insufficient evidence exists regarding whether the
and Symptoms joint site or number of joints involved affected the ac-
Eleven studies assessed the sensitivity and specific- curacy of diagnostic tests based on clinical signs and
ity of clinical algorithms versus evaluation of synovial symptoms because no studies were identified that di-
fluid MSU crystals for diagnosing gout (11–21) and re- rectly tested this association.
ported widely varying results. Evaluated algorithms in-
cluded the Rome criteria, New York criteria, American
Rheumatology Association criteria, Janssens diagnostic
DIAGNOSTIC ACCURACY BASED ON
rule, Clinical Gout Diagnosis criteria, monoarthritis of SYMPTOM DURATION
the first metatarsophalangeal joint, SUGAR (Study Insufficient evidence exists regarding the effect of
for Updated Gout Classification Criteria), and 2015 symptom duration (that is, time since beginning of
American College of Rheumatology and European flare) on the accuracy of gout diagnosis based on clin-
League Against Rheumatism gout classification criteria. ical signs and symptoms.
www.annals.org Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 53

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 CLINICAL GUIDELINE ACP Guideline on Diagnosis of Acute Gout

Figure. Summary of the American College of Physicians guideline on diagnosis of gout.

Summary of the American College of Physicians Guideline on Diagnosis of Gout

Disease/Condition Acute gout

Target Audience All clinicians

Target Patient Population Adults with joint inflammation suspected to be gout

Interventions Evaluated Clinical history and physical examination, serum urate assessment, ultrasonography, DECT, computed tomography, plain
radiography, joint aspiration by physicians and synovial fluid analysis using polarizing microscopy, combinations of
aforementioned tests as identified in the literature

Outcomes Evaluated Accuracy of the test results (sensitivity, specificity, positive and negative predictive value); intermediate outcomes
(results of laboratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiographic
or ultrasonography changes); clinical decision making (additional testing, pharmacologic or dietary management);
short-term clinical (patient-centered) outcomes, such as pain, joint swelling, and tenderness; and adverse effects of
the tests, including pain, infection, radiation exposure, and effects of false-positive or -negative results

Potential Benefits Accurate diagnosis of gout, leading to appropriate treatment

Potential Harms None reported for DECT. No studies reported for ultrasonography or clinical examination/algorithms

Synovial fluid aspiration for MSU analysis associated with nonserious adverse events, such as mild postprocedure pain

Misdiagnosis or delayed diagnosis, leading to inadequate or inappropriate treatment

Recommendation Recommendation: ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that
diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality
evidence)

Clinical Considerations Synovial fluid analysis is considered the reference standard for gout diagnosis, although it may be difficult to perform
in primary care.

Synovial fluid analysis should be used in the following clinical circumstances:

The joint can be aspirated without substantial patient discomfort by an experienced clinician who can minimize the risk of
infection.
A reliable and accurate source (including a polarizing microscope and a trained operator) is available to detect the presence of
urate crystals.
The clinical situation is ambiguous, and a probability of infection exists.

Clinical algorithms are shown to have sensitivities and specificities >80%, although little evidence exists that they can be used
to distinguish septic joints.

DECT = dual-energy computed tomography; MSU = monosodium urate.

FACTORS AFFECTING THE ACCURACY ciated with synovial fluid aspiration for MSU analysis
OF SYNOVIAL FLUID ASPIRATION AND and reported 1 occurrence of septic arthritis and 11
nonserious adverse events, such as mild postprocedure
CRYSTAL ANALYSIS
pain (32). None of the identified studies reported ad-
Insufficient evidence exists to determine what fac-
verse effects from other diagnostic tests (ultrasonogra-
tors influence the accuracy of gout diagnosis from 3
phy or clinical examination). Evidence from 1 observa-
studies that reported conflicting results (29 –31).
tional study from Korea (30) that assessed factors
associated with misdiagnosis or delayed diagnosis of
ADVERSE EFFECTS OF DIAGNOSTIC TESTS acute gout showed that misdiagnosis or delayed diag-
Insufficient evidence exists regarding adverse ef- nosis may result in longer hospitalization and delays in
fects associated with diagnostic tests for gout. Evidence joint aspiration after a gout attack begins. Reviewers
from 1 observational study from a referral center pro- found no evidence for patient-reported outcomes, such
cedure clinic (21) reported no adverse events associ- as pain and subsequent infection from joint aspiration
ated with DECT or with aspiration of synovial fluid, al- and synovial fluid analysis, the accuracy and reliability
though procedures for detecting adverse events were of synovial fluid analysis in primary care, or how often
not reported. One study assessed adverse events asso- joint aspiration is difficult or impossible in primary care.
54 Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 www.annals.org

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 ACP Guideline on Diagnosis of Acute Gout CLINICAL GUIDELINE

SUMMARY Current evidence is insufficient to support the use of

Although synovial fluid analysis has been the refer- DECT or ultrasonography to diagnose acute gout.
ence standard for gout diagnosis, it often is difficult to
perform in primary care and even rheumatologic set-
tings. Furthermore, accurate detection of urate crystals
AREAS OF INCONCLUSIVE EVIDENCE
requires a polarizing microscope and a trained opera- Insufficient evidence exists to determine the clinical
tor. Evidence for alternatives to synovial fluid MSU crys- utility of serum urate alone, computed tomography, or
tal analysis for diagnosing acute gout would be helpful plain radiography for diagnosing gout. Evidence also is
but is limited. An accurate clinical algorithm that could insufficient to determine the effects of joint site, num-
be used in primary care would be especially valuable. ber of affected joints, duration of symptoms, or practi-
The evidence review found moderate-quality evidence tioner type on the diagnostic accuracy of various tests.
that several clinical prediction tools have sensitivities Further validation of clinical algorithms is needed.
and specificities greater than 80% for diagnosing early-
From the American College of Physicians and University of
onset gout compared with the reference standard of
Pennsylvania Health System, Philadelphia, Pennsylvania; and
synovial fluid MSU crystal analysis. Evidence on
Yale School of Medicine, New Haven, Connecticut.
whether clinical algorithms can rule out such conditions
as septic joints is limited. Evidence showing variation in
Note: Clinical practice guidelines are “guides” only and may
the sensitivity and specificity of both DECT and ultra-
not apply to all patients and all clinical situations. Thus, they
sonography for diagnosing acute gout is also limited,
are not intended to override clinicians' judgment. All ACP
leading to uncertainty about the usefulness of these clinical practice guidelines are considered automatically with-
tests in the primary care setting. drawn or invalid 5 years after publication or once an update
The Figure summarizes the recommendations and has been issued.
clinical considerations.
Disclaimer: The authors of this article are responsible
for its contents, including any clinical or treatment
RECOMMENDATION
recommendations.
ACP recommends that clinicians use synovial fluid
analysis when clinical judgment indicates that diagnos- Financial Support: Financial support for the development of
tic testing is necessary in patients with possible acute this guideline comes exclusively from the ACP operating
gout. (Grade: weak recommendation, low-quality budget.
evidence)
Synovial fluid analysis has been the reference stan- Disclosures: Dr. Barry reports grants and personal fees from
dard for gout diagnosis. Misdiagnosis or delayed diag- Informed Medical Decisions Foundation and Healthwise, out-
nosis of acute gout may result in unnecessary surgery; side the submitted work. Dr. Boyd reports royalties from
hospitalization; delays in adequate treatment, such as UptoDate, outside the submitted work. Dr. Manaker reports
antibiotics for septic joints; and unnecessary prescrib- personal fees from work as a grand rounds speaker, lecturer,
ing of long-term treatment. In the absence of an consultant, and expert witness on documentation, coding,
evidence-based alternative, joint aspiration and syno- billing, and reimbursement to hospitals, physicians, depart-
vial fluid analysis should be done if the joint can be ments, practice groups, professional societies, insurers, and
aspirated without substantial patient discomfort by an attorneys (defense, plaintiff “qui tam,” U.S. attorneys general,
experienced clinician who can minimize the risk for in- and the Office of the Inspector General); personal fees from
fection; a reliable, accurate source (including a polariz- work as an expert witness in workers' compensation and med-
ing microscope and a trained operator) is available to ical negligence; dividend income from stock held by his
detect the presence of urate crystals; the clinical situa- spouse in Pfizer and Johnson and Johnson; and meal and
tion is ambiguous; and a significant probability of infec- travel expenses for serving on the CMS Hospital Outpatient
tion exists. Panel, the American Medical Association/Specialty Society
If these criteria cannot be met, the clinician should Relative Value Unit Update Committee, and the Board of Di-
either refer the patient to a source that can meet the rectors of CHEST Enterprises, a subsidiary of the American
College of Chest Physicians. Authors not named here have
criteria or use his or her clinical judgment. Clinical judg-
disclosed no conflicts of interest. Authors followed the policy
ment is especially appropriate in situations that are less
regarding conflicts of interest described at www.annals.org/aim
clinically ambiguous and where there is not a signifi-
/article/745942. Disclosures can also be viewed at www
cant probability of infection. For example, joint aspira- .acponline.org/authors/icmje/ConflictOfInterestForms.do
tion would not be essential in a patient with podagra, a ?msNum=M16-0569. All financial and intellectual disclosures
history of appropriate risk factors (such as age), and no of interest were declared, and potential conflicts were
sign of an overlying skin wound. This patient may ap- discussed and managed. No CGC members were recused
propriately be considered to have gout and treated ap- from voting on this guideline due to conflicts. A record
propriately (see accompanying guideline on gout of disclosures and management of conflicts of interest is kept
management [33]). The current evidence is insufficient for each CGC meeting and conference call and can be viewed
to recommend a single clinical algorithm for diagnos- at www.acponline.org/about-acp/who-we-are/leadership
ing gout. However, several promising algorithms /committees-boards-councils/clinical-guidelines-committee
showed sensitivities and specificities greater than 80%. /disclosure-of-interests-for-clinical-guidelines-committee.
www.annals.org Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 55

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 CLINICAL GUIDELINE ACP Guideline on Diagnosis of Acute Gout

Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, 1684-90. [PMID: 24796335] doi:10.1136/annrheumdis-2013-204
American College of Physicians, 190 N. Independence Mall 976
West, Philadelphia, PA 19106; e-mail, aqaseem@acponline 15. Kienhorst LB, Janssens HJ, Fransen J, Janssen M. The validation
.org. of a diagnostic rule for gout without joint fluid analysis: a prospective
study. Rheumatology (Oxford). 2015;54:609-14. [PMID: 25231179]
doi:10.1093/rheumatology/keu378
Current author addresses and author contributions are avail-
16. Taylor WJ, Fransen J, Dalbeth N, Neogi T, Schumacher HR,
able at www.annals.org. Brown M, et al. Performance of classification criteria for gout in early
and established disease. Ann Rheum Dis. 2016;75:178-82. [PMID:
25351521] doi:10.1136/annrheumdis-2014-206364
References 17. Taylor WJ, Fransen J, Jansen TL, Dalbeth N, Schumacher HR,
Brown M, et al. Study for updated gout classification criteria:
1. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight
identification of features to classify gout. Arthritis Care Res
change, hypertension, diuretic use, and risk of gout in men: the
(Hoboken). 2015;67:1304-15. [PMID: 25777045] doi:10.1002/acr
Health Professionals Follow-up Study. Arch Intern Med. 2005;165:
.22585
742-8. [PMID: 15824292]
18. Jatuworapruk K, Lhakum P, Pattamapaspong N, Kasitanon N,
2. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol
Wangkaew S, Louthrenoo W. Performance of the existing classifica-
intake and risk of incident gout in men: a prospective study. Lancet.
tion criteria for gout in Thai patients presenting with acute arthritis.
2004;363:1277-81. [PMID: 15094272]
Medicine (Baltimore). 2016;95:e2730. [PMID: 26844519] doi:10
3. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich .1097/MD.0000000000002730
foods, dairy and protein intake, and the risk of gout in men. N Engl J
19. Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Be-
Med. 2004;350:1093-103. [PMID: 15014182]
rendsen D, et al. 2015 Gout classification criteria: an American Col-
4. Krishnan E. Chronic kidney disease and the risk of incident gout lege of Rheumatology/European League Against Rheumatism col-
among middle-aged men: a seven-year prospective observational laborative initiative. Ann Rheum Dis. 2015;74:1789-98. [PMID:
study. Arthritis Rheum. 2013;65:3271-8. [PMID: 23982888] doi:10 26359487] doi:10.1136/annrheumdis-2015-208237
.1002/art.38171
20. Huppertz A, Hermann KG, Diekhoff T, Wagner M, Hamm B,
5. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia Schmidt WA. Systemic staging for urate crystal deposits with dual-
in the US general population: the National Health and Nutrition Ex- energy CT and ultrasound in patients with suspected gout. Rheuma-
amination Survey 2007-2008. Arthritis Rheum. 2011;63:3136-41. tol Int. 2014;34:763-71. [PMID: 24619560] doi:10.1007/s00296-014-
[PMID: 21800283] doi:10.1002/art.30520 2979-1
6. Li C, Martin BC, Cummins DF, Andrews LM, Frech-Tamas F, Yadao 21. Bongartz T, Glazebrook KN, Kavros SJ, Murthy NS, Merry SP,
AM. Ambulatory resource utilization and cost for gout in United Franz WB 3rd, et al. Dual-energy CT for the diagnosis of gout: an
States. Am J Pharm Benefits. 2013;5:e46-54. accuracy and diagnostic yield study. Ann Rheum Dis. 2015;
7. Perez-Ruiz F, Carmona L, Yébenes MJ, Pascual E, de Miguel E, 74:1072-7. [PMID: 24671771] doi:10.1136/annrheumdis-2013
Ureña I, et al; GEMA Study Group, Sociedad Española de Reuma- -205095
tologı́a. An audit of the variability of diagnosis and management of 22. Glazebrook KN, Guimarães LS, Murthy NS, Black DF, Bongartz T,
gout in the rheumatology setting: the gout evaluation and manage- Manek NJ, et al. Identification of intraarticular and periarticular
ment study. J Clin Rheumatol. 2011;17:349-55. [PMID: 21946457] uric acid crystals with dual-energy CT: initial evaluation. Radiology.
doi:10.1097/RHU.0b013e3182314d40 2011;261:516-24. [PMID: 21926378] doi:10.1148/radiol.1110
8. Newberry J, FitzGerald JD, Motala A, Booth M, Maglione MA, 2485
et al. Diagnosis of gout: a systematic review in support of an Amer- 23. Lai KL, Chiu YM. Role of ultrasonography in diagnosing gouty
ican College of Physicians clinical practice guideline. Ann Intern arthritis. J Med Ultrasound. 2011;19:7-13.
Med. 2017;166:27-36. doi:10.7326/M16-0462 24. Lamers-Karnebeek FB, Van Riel PL, Jansen TL. Additive value for
9. Newberry SJ, FitzGerald J, Maglione MA, O’Hanlon CE, Han D, ultrasonographic signal in a screening algorithm for patients pre-
Booth M, et al. Diagnosis of Gout. Comparative Effectiveness Review senting with acute mono-/oligoarthritis in whom gout is suspected.
no. 158. (Prepared by the Southern California Evidence-based Prac- Clin Rheumatol. 2014;33:555-9. [PMID: 24510062] doi:10.1007
tice Center under contract no. 290-2012-00006-I.) AHRQ publication /s10067-014-2505-6
no. 15(16)-EHC026-EF. Rockville: Agency for Healthcare Research 25. Rettenbacher T, Ennemoser S, Weirich H, Ulmer H, Hartig F,
and Quality; 2016. Klotz W, et al. Diagnostic imaging of gout: comparison of high-
10. Liu Y, Li ZC, Chen JB, Yu TT, Cui C, Zhang HB. Therapeutic effi- resolution US versus conventional X-ray. Eur Radiol. 2008;18:621-30.
cacy of small doses of colchicine combined with glucocorticoid for [PMID: 17994238]
acute gouty arthritis. Medical Journal of Chinese People's Liberation 26. Zufferey P, Pascal Z, Valcov R, Fabreguet I, Dumusc A, Omoumi
Army. 2015;40:652-5. P, et al. A prospective evaluation of ultrasound as a diagnostic tool in
11. Malik A, Schumacher HR, Dinnella JE, Clayburne GM. Clinical acute microcrystalline arthritis. Arthritis Res Ther. 2015;17:188.
diagnostic criteria for gout: comparison with the gold standard of [PMID: 26198435] doi:10.1186/s13075-015-0701-7
synovial fluid crystal analysis. J Clin Rheumatol. 2009;15:22-4. [PMID: 27. Löffler C, Sattler H, Peters L, Löffler U, Uppenkamp M, Bergner R.
19125136] doi:10.1097/RHU.0b013e3181945b79 Distinguishing gouty arthritis from calcium pyrophosphate disease
12. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü TF. and other arthritides. J Rheumatol. 2015;42:513-20. [PMID:
Preliminary criteria for the classification of the acute arthritis 25399385] doi:10.3899/jrheum.140634
of primary gout. Arthritis Rheum. 1977;20:895-900. [PMID: 28. Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan
856219] P, et al; EULAR Standing Committee for International Clinical Studies
13. Janssens HJ, Janssen M, van de Lisdonk EH, Fransen J, van Riel Including Therapeutics. EULAR evidence based recommendations
PL, van Weel C. Limited validity of the American College of Rheuma- for gout. Part I: diagnosis. Report of a task force of the Standing
tology criteria for classifying patients with gout in primary care [Let- Committee for International Clinical Studies Including Thera-
ter]. Ann Rheum Dis. 2010;69:1255-6. [PMID: 19910298] doi:10 peutics (ESCISIT). Ann Rheum Dis. 2006;65:1301-11. [PMID:
.1136/ard.2009.123687 16707533]
14. Richette P, Clerson P, Bouée S, Chalès G, Doherty M, Flipo RM, 29. Gordon C, Swan A, Dieppe P. Detection of crystals in synovial
et al. Identification of patients with gout: elaboration of a question- fluids by light microscopy: sensitivity and reliability. Ann Rheum Dis.
naire for epidemiological studies. Ann Rheum Dis. 2015;74: 1989;48:737-42. [PMID: 2478085]

56 Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 www.annals.org

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 ACP Guideline on Diagnosis of Acute Gout CLINICAL GUIDELINE
30. Park JW, Ko DJ, Yoo JJ, Chang SH, Cho HJ, Kang EH, et al. 32. Taylor WJ, Fransen J, Dalbeth N, Neogi T, Ralph Schumacher H,
Clinical factors and treatment outcomes associated with failure in the Brown M, et al. Diagnostic arthrocentesis for suspicion of gout is safe
detection of urate crystal in patients with acute gouty arthritis. Korean and well tolerated. J Rheumatol. 2016;43:150-3. [PMID: 26628602]
J Intern Med. 2014;29:361-9. [PMID: 24851071] doi:10.3904/kjim
doi:10.3899/jrheum.150684
.2014.29.3.361
31. Pollet S, Coiffier G, Albert JD, Chales G, Guggenbuhl P, 33. Qaseem A, Harris RP, Forciea MA, for the Clinical Guidelines
Perdriger A. Concordance between fresh joint fluid analysis by Committee of the American College of Physicians. Management of
the rheumatologist and joint fluid analysis at the laboratory: prospec- acute and recurrent gout: a clinical practice guideline from the
tive single-center study of 180 samples. Joint Bone Spine. 2015;82: American College of Physicians. Ann Intern Med. 2017;166:58-68.
161-5. [PMID: 25649725] doi:10.1016/j.jbspin.2014.11.005 doi:10.7326/M16-0570

ANNALS OF INTERNAL MEDICINE JUNIOR INVESTIGATOR AWARDS

Annals of Internal Medicine and the American College of Physicians rec-

ognize excellence among internal medicine trainees and junior investiga-
tors with annual awards for original research and scholarly review articles
published in Annals in each of the following categories:

• Most outstanding article with a first author in an internal medicine resi-

dency program or general medicine or internal medicine subspecialty
fellowship program

• Most outstanding article with a first author within 3 years following com-
pletion of training in internal medicine or one of its subspecialties

Selection of award winners will consider the article’s novelty; methodolog-

ical rigor; clarity of presentation; and potential to influence practice, pol-
icy, or future research. Judges will include Annals Editors and representa-
tives from Annals’ Editorial Board and the American College of Physicians’
Education/Publication Committee.

Papers published in the year following submission are eligible for the
award in the year of publication. First author status at the time of manu-
script submission will determine eligibility. Authors should indicate that
they wish to have their papers considered for an award when they submit
the manuscript, and they must be able to provide satisfactory documen-
tation of their eligibility if selected for an award. Announcement of awards
for a calendar year will occur in January of the subsequent year. We will
provide award winners with a framed certificate, a letter documenting the
award, and complimentary registration for the American College of Physi-
cians’ annual meeting.

Please refer questions to Mary Beth Schaeffer at mschaeffer@acponline

.org or visit www.annals.org/aim/pages/junior-investigator-awards

www.annals.org Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 57

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 Current Author Addresses: Drs. Qaseem and Starkey: Ameri- Search Strategy
can College of Physicians, 190 N. Independence Mall West, The systematic literature search included studies
Philadelphia, PA 19106. identified by using PubMed (from 1946), EMBASE
Dr. McLean: Yale University School of Medicine, 46 Prince (from 1972), the Cochrane Library (from 1945), and the
Street, New Haven, CT 06519.
Web of Science (from 1949) through February 2016 as
Dr. Forciea: University of Pennsylvania Health System, 3615
Chestnut Street, Philadelphia, PA 19104. well as unpublished or non–peer-reviewed studies
identified through ClinicalTrials.gov and the Web of
Science. Studies were not limited to those published in
Author Contributions: Conception and design: A. Qaseem, M.
English.
Starkey, M.J. Barry, N. Fitterman.
Analysis and interpretation of the data: A. Qaseem, M. Star- Quality Assessment
key, M.A. Forciea, M.J. Barry, C. Boyd, L.L. Humphrey, D. Kan- The QUADAS-2 (Revised Quality Assessment of Di-
sagara, S. Vijan, T. Wilt.
agnostic Accuracy Studies) was used to assess the qual-
Drafting of the article: A. Qaseem, M. Starkey, T.D. Denberg,
ity of individual studies for risk of bias (34, 35); AMSTAR
S. Manaker.
Critical revision for important intellectual content: A. Qaseem, (A Measurement Tool to Assess Systematic Reviews)
M. Starkey, M.A. Forciea, T.D. Denberg, M.J. Barry, C. Boyd, was used to assess the quality of existing systematic
R.D. Chow, L.L. Humphrey, S. Manaker, S. Vijan, T. Wilt. reviews (36). This guideline rates the evidence and rec-
Final approval of the article: A. Qaseem, R. McLean, M. Star- ommendations by using the ACP guideline grading
key, M.A. Forciea, T.D. Denberg, M.J. Barry, C. Boyd, R.D. system, which is based on GRADE (Table 1).
Chow, N. Fitterman, L.L. Humphrey, D. Kansagara, S. Manaker,
S. Vijan, T. Wilt. Population Studied
Statistical expertise: A. Qaseem. Studies were limited to adults aged 18 years or
Administrative, technical, or logistic support: A. Qaseem, M. older with suspected gout (such as an acute episode of
Starkey. joint inflammation).
Collection and assembly of data: A. Qaseem, M. Starkey.
Interventions Evaluated
Studies evaluated clinical history and physical ex-
amination, serum urate assessment, ultrasonography,
APPENDIX: DETAILED METHODS DECT, computed tomography, plain radiography, joint
The evidence review was conducted by the South- aspiration by physicians and synovial fluid analysis us-
ern California Evidence-based Practice Center–RAND ing polarizing microscopy, and combinations of the
Corporation to address the following key questions: aforementioned tests as identified in the literature.
Key Question 1 Comparators
a. What is the accuracy of clinical signs and symp- Interventions were compared with joint synovial
toms and other diagnostic tests (such as serum urate, fluid aspiration and microscopic assessment for MSU
ultrasonography, computed tomography, DECT, and crystals performed by practitioners (such as rheuma-
plain radiography), alone or in combination, compared tologists and laboratory personnel) with different levels
with synovial fluid analysis in diagnosing acute gouty of expertise or experience.
arthritis, and how does the accuracy affect clinical deci-
Outcomes
sion making, clinical outcomes and complications, and
Outcomes evaluated included accuracy of the test
patient-centered outcomes?
results (sensitivity, specificity, and positive and negative
b. How does the diagnostic accuracy of clinical
predictive value); intermediate outcomes (results of
signs and symptoms and other tests vary by affected
laboratory and radiographic tests, such as serum urate
joint site and number of joints?
and synovial fluid crystal analysis and radiographic or
c. Does the accuracy of diagnostic tests for gout
ultrasonography changes); clinical decision making
vary by duration of symptoms (that is, time from the
(additional testing and pharmacologic or dietary man-
beginning of a flare)?
agement); short-term clinical (patient-centered) out-
d. Does the accuracy of synovial fluid aspiration
comes, such as pain and joint swelling and tenderness;
and crystal analysis differ by the type of practitioner and adverse effects of the tests, including pain, infec-
who is performing the aspiration or the crystal analysis? tion, radiation exposure, and effects of false-positive or
-negative results.
Key Question 2
a. What are the adverse effects (including pain, in- Timing
fection at the aspiration site, radiation exposure) or Studies considered timing in terms of symptom re-
harms (related to false-positive, false-negative, and in- lief (1 to 2 days minimum), whether symptoms occurred
determinate results) associated with tests used to diag- early versus later or after a flare, and whether adverse
nose gout? outcomes occurred immediately.
www.annals.org Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017

 Setting Web-Only References
The studies were conducted in primary care (out- 34. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Re-
patient) or acute care settings or outpatient rheumatol- itsma JB, et al; QUADAS-2 Group. QUADAS-2: a revised tool for the
quality assessment of diagnostic accuracy studies. Ann Intern Med.
ogy practices or academic medical centers. 2011;155:529-36. [PMID: 22007046] doi:10.7326/0003-4819-155-8-
201110180-00009
Target Audience 35. Santaguida PL, Riley CM, Matchar DB. Assessing risk of bias as a
The target audience for this guideline includes all domain of quality in medical test studies. In: Chang SM, Matchar DB,
clinicians. Smetana GW, Umscheid CA, eds. Methods Guide for Medical Test
Reviews. Rockville: Agency for Healthcare Research and Quality;
2012.
Target Patient Population
36. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel
The target patient population includes adults pre- C, et al. Development of AMSTAR: a measurement tool to assess the
senting with symptoms suggesting acute gout (such as methodological quality of systematic reviews. BMC Med Res Meth-
an acute episode of joint inflammation), with or without odol. 2007;7:10. [PMID: 17302989]
a previous gout diagnosis.

Peer Review
The AHRQ evidence review was sent to invited
peer reviewers and posted on the AHRQ Web site for
public comments. The guideline was peer reviewed
through the journal and posted online for comments
from ACP Governors and Regents. All comments were
read and carefully considered by the authors, and im-
portant issues were discussed by the CGC.
Details of the ACP guideline development process
are provided in the ACP methods paper (10).

Annals of Internal Medicine • Vol. 166 No. 1 • 3 January 2017 www.annals.org

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/935961/ on 03/08/2017