This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Rheumatology
(Oxford) following peer review. The definitive publisher-authenticated version Rheumatology (2013)
doi: 10.1093/rheumatology/ket154 First published online: April 22, 2013 is available online at:
New classification criteria for gout: a framework for progress
Nicola Dalbeth1, Jaap Fransen2, Tim L Jansen3, Tuhina Neogi4, H. Ralph Schumacher5,
William J Taylor6, Steering Committee for the Gout Classification Criteria Project.
1. University of Auckland, Auckland, New Zealand
2. Department of Primary and Community Care, Radboud University Nijmegen Medical
Center, Nijmegen, the Netherlands
3. Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen,
4. Clinical Epidemiology Research & Training Unit, Boston University School of Medicine,
Boston MA, USA
5. University of Pennsylvania and VA Medical Center, Philadelphia PA, USA
6. University of Otago, Wellington, New Zealand.
Corresponding author: Assoc Prof Nicola Dalbeth, Department of Medicine, Faculty of
Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New
Zealand. Phone +64 9 3737999 x82568. Fax +64 9 3737677. Email:
Word count: 2,211, Tables: 2, Figures: 1.
Running title: Gout classification criteria
Disclosures: The authors have no relevant financial disclosures.
The definitive classification or diagnosis of gout normally relies upon the identification of
monosodium urate (MSU) crystals in synovial fluid or from tophi. Where microscopic
examination of synovial fluid is not available or is impractical, the best approach may differ
depending upon the context. For many types of research, clinical classification criteria are
necessary. The increasing prevalence of gout, advances in therapeutics, and the development
of international research collaborations to understand the impact, mechanisms and optimal
treatment of this condition emphasize the need for accurate and uniform classification criteria
for gout. Five clinical classification criteria for gout currently exist. However, none of the
currently available criteria has been adequately validated. An international mixed-methods
project is currently underway to develop new validated gout classification criteria. These
criteria will be an essential step forward to advance the research agenda in the modern era of
Keywords: gout, classification, urate, research
Classification criteria are designed to mimic a gold-standard in order to distinguish between
disease and no disease or between different diseases. Their purpose is to ensure relative
homogeneity of participants of clinical research, including clinical trials and epidemiological
studies. Unbiased and reliable classification criteria are essential for research in rheumatic
disease. Specific recommendations exist regarding development and validation of
classification criteria for rheumatic disease . Development requires identification of
possible inclusion and exclusion criteria. A large sample of patients with and without disease
should be studied to determine which criteria (or combination of criteria) best differentiate
those with and without disease. The final classification criteria should then be validated in a
large sample of cases and controls distinct from patients used to develop the criteria.
Why do we need gout classification criteria?
The classification of a patient as having of gout normally relies upon the identification of
monosodium urate (MSU) crystals in synovial fluid or tissue . Where examination of
synovial fluid is impractical, the best approach differs depending upon the context: in clinical
management of individual patients, all available information should be carefully weighed and
considered by the physician, whereas in clinical research, classification criteria are necessary.
Important advances have been made that emphasize the need for robust gout classification
criteria. These advances include new (and expensive) pharmaceuticals and the need for
accurate case-definition for recruitment into clinical trials; the advent of new imaging
modalities that have the potential to change the way gout is classified; and the need for
accurate phenotyping for large genetic studies, such as genome-wide association studies.
Because of potential anticipated as well as unknown adverse effects of new agents for gout
(including biologics), classification criteria need to have acceptable high specificity to ensure
trial enrolment is targeting those with definite gout. At the same time, with the rise in
incidence/prevalence of gout worldwide, uniform criteria with appropriate sensitivity and
specificity are needed for epidemiologic studies as well as the phenotyping for genetic
studies. New imaging modalities that were not available when prior criteria were developed
need to be evaluated for their utility in aiding accurate classification of persons with gout.
Limitations of current gout classification criteria
There have been five published classification criteria for gout [3-7] (Table 1). None of the
published gout criteria meet the requirements for valid classification criteria (Table 2). The
Rome and New York criteria [3, 4] identify key features of gout but were not developed
through observed prospective data and have been tested only to a limited extent. A study of
22 patients with clinically diagnosed gout in Sudbury, Massachusetts found that eight patients
satisfied the Rome criteria only, four the New York criteria only and ten satisfied both sets
(sensitivity of 0.82 and 0.64 for the Rome and New York criteria respectively) . A much
larger study of consecutive rheumatology clinic attendees from six European centres (59
patients with gout and 761 patients with other rheumatic diseases) reported that the
specificity of both sets were very high (0.99 for both Rome and New York) but the sensitivity
was not (0.64 and 0.80 for the Rome and New York criteria, respectively) . The inclusion
of tophi as key features may limit the sensitivity of these criteria in patients in early disease,
since only 31% of patients with gout had a definite tophus in the larger study.
The 1977 American Rheumatism Association (ARA) criteria, now over 30 years old, were
informed by data to identify the acute arthritis of primary gout  (Table 1). Survey criteria
that do not require joint aspiration were also described for use in epidemiological studies (11
items). The cases and controls were drawn from 706 patients submitted by 38
rheumatologists across the US. Only patients with rheumatoid arthritis (RA), acute calcium
pyrophosphate crystal arthritis and acute septic arthritis were accepted as controls. Important
disease mimics including osteoarthritis and psoriatic arthritis were not included. The gold-
standard chosen for the classification criteria was physician diagnosis. Many patients had
incomplete data (for example, approximately half of the cases and the controls did not have
synovial fluid analysis). The observed performance of the proposed clinical criteria that do
not require joint or tophus aspiration was sensitivity 85% and specificity 97%. External
validation of the clinical components of ARA criteria against a gold standard of synovial
fluid analysis has been reported in two studies [10, 11]. In these studies the sensitivity was
70% and 80%, specificity was 79% and 64%. In contrast, in patients with crystal proof,
sensitivity of 2 of 3 clinical components of the Rome criteria was 67% and specificity was
These results underscore the need for better criteria and that the gold-standard for diagnosis
remains identification of MSU crystals in synovial fluid, preferably in the acute phase.
Notwithstanding the problems of classification for acute gouty arthritis, there is also a need
for classification criteria for intercritical or chronic gout. In most clinical research settings,
participants will not have acute gout at the time of evaluation so that it is clearly necessary to
develop classification criteria that do not require current evidence of active joint
There have been two further criteria recently proposed for diagnosis, not classification,
developed in Mexico and the Netherlands [6, 7] (Table 1). The study from Mexico
considered only patients with physician-diagnosed gout from rheumatology clinics. It
proposed a simplified version of the 1977 ARA criteria based on the frequency of the items
present in this population of patients. Because there were no control patients, the specificity
of the suggested criteria could not be determined. A second study from this group showed a
very high sensitivity (97%) and specificity (96%) in rheumatology clinic patients with crystal
proven gout and other rheumatic diseases (osteoarthritis, spondyloarthritis, rheumatoid
arthritis) . However, the non-gout control patients in this study did not undergo synovial
fluid analysis and the high rate of tophi (81%) in the gout cases limit general applicability.
The Dutch study aimed to develop a diagnostic decision aid for general practitioners, rather
than classification criteria. The patients for this study were required to have monoarthritis, so
that the decision rule is not applicable to patients who present with more than one affected
joint. Discriminating features included risk factors for gout (such as serum urate levels, male
gender and cardiovascular disease) rather than actual manifestations of gout.
MSU crystal identification: the ‘gold standard’
For most rheumatic diseases, a pathological diagnosis is not available and the gold-standard
is often expert physician judgement (ideally made over a reasonable follow-up duration).
This is not the case in gout, where the identification of tissue or synovial fluid MSU crystals
is considered pathognomonic and the gold standard for diagnosis. Although the pathological
diagnosis of gout through identification of MSU crystals is a major advantage when
developing gout classification criteria, this ‘gold standard’ does have its limitations. Most
importantly, MSU crystal identification is dependent on an operator who requires adequate
training in synovial fluid crystal analysis [13, 14]. Other joint crystals and artefacts may
mimic MSU crystals, and both false positive and false negative results may occur [15-17].
Another important consideration is that synovial fluid MSU crystals are present in a
proportion of patients with asymptomatic hyperuricaemia; that is, elevated serum urate
concentrations without overt clinical manifestations of gout [18, 19]. Whether these people
should be considered as having gout can be debated. MSU crystals may also be present in
patients presenting with joint inflammation due to concomitant rheumatic conditions
including septic arthritis, acute calcium pyrophosphate crystal arthritis, psoriatic arthritis, and
rarely rheumatoid arthritis, but these patients should still be classified as having gout but with
confounding features. Following long-term intensive urate-lowering therapy, a negative urate
balance is reached and MSU crystals will become undetectable . A further barrier to
crystal identification may be expertise in joint aspiration; while joint aspiration is standard in
secondary rheumatology care, these skills may not be universally present in primary care
where most gout is diagnosed and managed. Furthermore, gout frequently presents in small
joints that may be poorly accessible to joint aspiration. Therefore, inclusion of MSU crystal
identification as the gold standard for classification development risks oversampling patients
with large joint arthropathy or tophaceous gout (if tophi are easily accessible for aspiration),
which may be a source of bias when developing classification criteria using MSU crystals as
the gold standard.
The 1977 ARA classification criteria for the acute arthritis of primary gout include plain
radiographic changes of asymmetric swelling within a joint, and subcortical cysts without
erosions . These changes may be observed in conditions other than gout and are a late
feature of disease . Other plain radiographic features of gout such as soft-tissue
opacifications with densities between soft tissue and bone, articular and periarticular bone
erosions, and osteophytes at margins of opacifications or erosions have low sensitivity (31%)
but high specificity (93%) for a clinical diagnosis of gout .
No published classification criteria include advanced imaging techniques for detection of
gout. Recent reports suggest that ultrasonography (US) and dual energy computed
tomography (DECT) may allow accurate identification of some patients with gout. The
double contour sign on US is defined as “a hyperechoic band over anechoic cartilage” 
and is thought to represent MSU crystals coating articular cartilage . A number of
different groups have reported that the presence of the double contour sign on US has high
specificity for gout (95-100%), with variable sensitivity (21-92%) [22, 23, 25-28]. Only a
few imaging studies have used microscopic proven disease as a gold standard [23, 26]. A
complicating issue is that these US features can also be present in people with asymptomatic
hyperuricaemia [18, 28, 29]. DECT is a recently developed imaging method that allows
visualisation of urate deposits through detection of the chemical composition of urate. High
sensitivity and specificity has been reported for crystal proven gout by several groups [30-
33]. It should be noted that most advanced imaging studies have examined the classification
accuracy in patients with established disease, where joint aspirate could be achieved, or other
clinical criteria would be satisfied. False negative cases have been reported . The role of
these techniques for gout classification in patients with early disease and any additional
benefit over microscopic or clinical criteria requires careful consideration.
Scope of gout classification criteria
The purpose of classification criteria is to robustly define cases of gout for the purposes of
research. It is not intended that these criteria are used for gout diagnosis in clinical practice.
In clinical practice, the diagnosis of gout should be made by microscopy, and if this is not
possible, a tentative clinical diagnosis is made taking into account history, examination,
imaging and laboratory findings in an individualised manner. Gout may present in a number
of different ways: recurrent flares, chronic gouty arthropathy, and tophaceous disease. Gout
classification criteria should accurately capture patients with these various disease states.
However, the scope of classification criteria does not include definition of these disease states
in patients with gout. Furthermore, the classification of gout applies to patients with clinical
features of gout, and does not aim to define a ‘pre-gout’ state that may potentially be
characterised by deposition of urate crystals in the absence of clinical manifestations.
A strategy to develop new gout classification criteria
The American College of Rheumatology (ACR) and European League Against Rheumatism
(EULAR) have recently funded an international project to develop new gout classification
criteria. The intent of criteria derived from this work is to improve the case-definition for
gout amongst both primary and secondary care populations. The intended use of
classification criteria in this setting includes case ascertainment for recruitment into clinical
studies, including observational studies and randomised controlled trials. Following item
generation processes involving both physicians and patients , two parallel approaches
will be used to determine the key combination of elements that best define gout. The first
approach will involve prospectively recruiting 860 patients with suspected gout into a
multicentre international study. All participants will have synovial or tissue analysis (by an
observer certified in crystal identification) to determine true-status classification. The second
approach will be a paper patient exercise where thirty patient profiles that represent a
spectrum of gout probability will be ranked by an expert panel. Additional data will be a
systematic review of the diagnostic utility of advanced imaging for gout and analysis of
trade-offs of sensitivity and specificity for different contexts of classification. A structured
consensus process will then integrate these sources of data into agreed classification criteria.
The overall project strategy is shown schematically in Figure 1. The final criteria will be in a
format similar to the 2010 ACR/EULAR RA criteria . It is possible that different but
equivalent versions of criteria will be recommended (with or without advanced imaging).
The final criteria will be externally validated using a test sample from the multicentre
international study and an existing primary care dataset.
Gout is now the most common inflammatory arthritis . The increasing prevalence of
gout, advances in therapeutics, and the development of large international research
collaborations to understand the impact, mechanisms and optimal treatment of this condition
emphasize the need for accurate and robust classification criteria for this disease. These
criteria will be an essential step forward to progress the research agenda in the modern era of
1. Unbiased and reliable classification criteria are essential for research in rheumatic
2. Current classification criteria for gout are limited by low sensitivity and incomplete
3. An international project is underway to develop classification criteria that closely
mimic crystal-proven gout.
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