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Gout: why is this curable disease so seldom cured?
  1. Michael Doherty1,
  2. Tim L Jansen2,
  3. George Nuki3,
  4. Eliseo Pascual4,
  5. Fernando Perez-Ruiz5,
  6. Leonardo Punzi6,
  7. Alexander K So7,
  8. Thomas Bardin8
  1. 1Department of Rheumatology, City Hospital, Nottingham, UK
  2. 2Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  3. 3Department of Rheumatology, University of Edinburgh, Centre for Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK
  4. 4Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Alicante, Spain
  5. 5Department of Rheumatology, Rheumatology Division, Hospital Universitario Cruces, Vizcaya, Spain
  6. 6Department of Rheumatology, Rheumatology Unit, University of Padova, Padova, Italy
  7. 7Department of Musculoskeletal Medicine, University Hospital of Lausanne, Lausanne, Switzerland
  8. 8Department of Rheumatology, Hopital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen, Paris, France
  1. Correspondence to Dr Michael Doherty, Academic Rheumatology, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK; Michael.Doherty{at}


Gout is the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is ‘cure’. However, audits show that only a minority of patients with gout receive adequate advice and treatment. Suboptimal care and outcomes reflect inappropriately negative perceptions of the disease, both in patients and providers. Historically, gout has been portrayed as a benign and even comical condition that is self-inflicted through overeating and alcohol excess. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Urate-lowering treatment is underprescribed and often underdosed. Appropriate education of patients and doctors, catalysed by recent introduction of new urate-lowering treatments after many years with no drug development in the field, may help to overcome these barriers and improve management of this easily diagnosed and curable form of potentially severe arthritis.

  • Gout
  • Arthritis
  • Treatment

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Gout is now the most common kind of inflammatory arthritis in men and an increasingly frequent cause of inflammatory joint disease in women, with a prevalence exceeding that of rheumatoid arthritis. Overall, 1–2% of European adults1–3 and 3.9% of US adults4 ,5 are affected, but this rises with age to 7% of men over the age of 65 and to 3% of women aged over 85 years.2 ,5 The disease is strongly heritable, with other risk factors including metabolic syndrome (obesity, hypertension, hyperlipidaemia and hyperglycaemia), chronic renal impairment and certain drug treatments, including diuretics.6–8

Of all forms of chronic arthropathy, gout is the one we understand the best. It is a true crystal deposition disease caused by persistent elevation of serum urate (sUA) levels above the saturation point for monosodium urate (MSU) crystal formation (approximately 404 µmol/l).9 An initial period of asymptomatic hyperuricaemia10 is associated with silent formation of sodium urate crystals in and around peripheral joints.11–13 Eventually, however, this ongoing crystal deposition results in symptomatic clinical problems. Usually, though not exclusively, the first presentation is acute, self-limiting ‘attacks’ of extremely painful synovitis that result from shedding of crystals into the joint space from the articular cartilage where they form.13 Importantly, however, subclinical chronic crystal-induced inflammation and the mechanical effects of densely packed crystals (‘tophi’) on articular cartilage and bone may result in irreversible joint damage and associated symptoms, a condition referred to as ‘chronic tophaceous gout’.13–16

In general, a confident diagnosis of typical acute attacks of gout (eg, podagra) is possible from the clinical features alone,17 ,18 although less typical presentations require confirmation of crystal presence in joint or tophus aspirates—the ‘gold standard’ for definitive diagnosis—or demonstration of the double contour sign on joint ultrasonography.17 ,18 Diagnosis and management in most cases is straightforward and can be undertaken in primary care, although in patients with significant comorbidity, especially renal impairment, or intolerance to allopurinol, secondary specialist referral may be required. Effective treatment strategies to reduce sUA levels sufficiently to prevent further crystal formation and to dissolve existing urate crystals, thus eliminating the causative agent and effectively ‘curing’ the disease,8 ,13 ,17 have been available for many years. In addition to symptomatic treatment of acute attacks and lifestyle modification to address modifiable risk factors, nearly all patients require long-term treatment with urate-lowering treatment (ULT).8 ,17 There is available support from current evidence-based management guidelines to aid diagnosis18 and to guide clinical decision-making.8 ,17

Regrettably, however, studies show that only a minority of gout patients receive effective lifestyle advice and ULT, the majority continuing to have recurrent attacks and being at risk of further joint damage and other complications.19–23 When questioned about the adequacy of gout management and treatment, patients’ and practitioners’ responses differ, with practitioners often feeling that management was adequate and patients expressing concerns about ineffective medication and reporting discontinuation of treatment and the need for more information.24

Several epidemiological and other studies demonstrate an increase in the severity and prevalence of gout.1 ,4 ,7 ,21 ,25–28 Although this may be partly attributed to increased longevity and consequent comorbidity (renal impairment, hypertension and treatment with diuretics) and to the continuing increase in prevalence of obesity and metabolic syndrome, there is also evidence that suboptimal management of gout contributes to the problem.2 ,21 ,29–33

Why, then, despite the possibility of early and accurate diagnosis, the availability of effective treatment and our insight into the severity and consequences of the disease, is gout managed so ineffectively? Perhaps it is time to reappraise our approach to gout in order to identify and address the shortcomings in the way this curable joint disease is managed.


We searched the Medline database for articles published in English language using the search terms ‘gout’, ‘hyperuricaemia’, ‘hyperuricemia’, ‘tophi’ and ‘monosodium urate’ published after 1 January 1980. We searched also, in combination with the previous terms or alone, the keywords ‘therapy’, ‘management’, ‘cure’ and ‘treatment’. In addition we included further material that was judged relevant—for example, abstracts presented to recent editions of EULAR congress, books and primary publications. The list of references has been repeatedly reviewed by the authors throughout the writing process.

Common perceptions of gout in the general population

Many people consider gout to be a self-inflicted disorder that is benign rather than serious and often regarded as humorous. It is not difficult to trace the source of these common misconceptions. Historically the condition has been linked to men's excessive alcohol (especially port) intake, rich food and debauchery and this patrician ‘disease of kings’ was regarded as the revenge of the lower class against those who could afford such bad behaviour (figure 1) and of women against men within a patriarchal society.34 Even today some, be they a patient or not, believe that gout is due to the patient's own shortcomings and a lack of discipline and that their condition is well deserved. Recent epidemiological studies continue to stereotype patients with gout by emphasising these lifestyle factors, which are nowadays more associated with lower income,35 and are by no means the only risk factors for the disease. Indeed, genetic factors play an important part in the pathogenesis of primary gout.36 Most patients have a genetically determined inability to increase renal uric acid excretion by the kidneys when urate levels are raised, and recent studies are beginning to shed light on the renal transporters involved in this causative defect.37

Figure 1

‘Punch Cures the Gout, the Colic and the “tisick”’ by James Gillray (1799). This figure is only reproduced in colour in the online version.

Apparently there is something funny about a grown man who suddenly and dramatically out of the blue develops the ‘worst pain he has ever experienced’ within just a few hours, hobbling about and not allowing anyone to touch him. Perhaps having a reddened swollen toe as the cause of such extreme pain makes it more comical. Many people have seen the 19th century cartoons by Gillray and others, which graphically emphasise this humorous element (figure 2). Current patient information and advertising material relating to gout also often include cartoons that serve to reinforce this perception of the disease. This stigmatisation is unique to gout and is never a feature, for example, of literature relating to rheumatoid arthritis.

Figure 2

‘The Gout’ by James Gillray (1799). This figure is only reproduced in colour in the online version.

Most people think that the term ‘gout’ refers just to the acute attacks, which last a few days. Crystal deposition is, however, continuing during the sometimes long symptom-free intervals between such flares when seemingly nothing is happening. They are not aware that, although not symptomatic at all times, gout is nevertheless a potentially destructive arthritis, associated with chronic inflammation, joint damage, disfigurement, loss of mobility and reduced health-related quality of life.38–40 The growing evidence associating gout and hyperuricaemia with cardiorenal disease and shortened life expectancy41 is also underappreciated.

These distorted perceptions of the nature of gout have a marked negative effect on patients’ attitudes to their gout and its treatment. They are often embarrassed to seek help and reluctant to accept or act on the diagnosis of gout, as they see it as a slur on their lifestyle.42 ,43 Already plagued with feelings of guilt they imagine that their doctor will view their condition as entirely self-inflicted and that as a consequence they will not be taken seriously.42 ,43 These misconceptions also lead patients to underestimate the importance of long-term ULT to eliminate the causative crystals, so contributing to poor adherence to treatment.44 ,45

Doctors’ knowledge of gout and their approach to treatment

Primary care practitioners

Because of its prevalence and the ready availability of effective treatments, gout is largely managed by general practitioners (GPs) in primary care and the vast majority of patients are never referred for a specialist opinion.46 Unfortunately, however, the approach to gout management by most GPs is also beset with misconceptions and myths.20 ,31–33

Gout not a priority during training

Compared with other musculoskeletal conditions, gout receives scant attention in undergraduate medical curricula and GP training programmes.44 In addition, because gout is not a hospital-based disease, resident doctors’ exposure to patients with gout and their experience of gout management is limited.44

Continuing medical education courses that highlight new developments in a disease or its treatment are often sponsored by the pharmaceutical industry. The low priority of gout in postgraduate meetings and the infrequency of management updates in recent decades may in part be attributable to the absence of new drugs for gout for many years.44 With little focus on the condition until very recently, there has been less published information available and less awareness, particularly of secondary or unusual presentations of gout. Textbooks and such teaching and information as there has been about gout have, not infrequently, been outdated. The lack of interest in the disease among hospital specialists has also tended to reinforce the impression amongst GPs that gout is not a serious condition.46

Diagnostic methods not optimal

Joint aspiration to detect MSU crystals to establish a definitive diagnosis18 is not a viable option for most primary care practitioners.23 For most GPs, the diagnosis is usually based on a clinical history and sUA levels. sUA, however, has little diagnostic utility since levels are often normal during an acute flare and very often raised in patients with joint pain due to some other cause.18

Long-term complications underestimated

The main focus for GPs is on treating acute attacks, rather than on long-term elimination of MSU crystals and prevention of future joint damage (figures 3 and 4).32 Practitioners often underestimate the extent of the loss of mobility and functional impairment associated with gout and the impact that this has on their quality of life.40 ,47–49 Patients may be advised to correct modifiable lifestyle factors and be prescribed non-steroidal anti-inflammatory drugs for the acute attack and to reduce flares, but the concept of ongoing crystal deposition and its complications is poorly understood and often not explained,42 ,43 and long-term ULT is often neglected.14 ,44 ,50 Recognition of the importance of early, lifelong and adequately dosed targeted treatment of hyperuricaemia is not what it should be,14 ,44 ,51 and with gout now increasingly recognised as an independent risk factor for chronic kidney disease, hypertension and cardiovascular disease, early treatment is essential to avoid complications.52 ,53

Figure 3

Big toe and tophus in x-ray imaging showing the damage caused by urate crystal deposition. (Image courtesy of Michael Doherty.)

Figure 4

Chronic tophaceous gout of the hand showing deforming arthropathy and obvious tophi. (Image courtesy of Michael Doherty.) This figure is only reproduced in colour in the online version.

Treatment not titrated to target serum uric acid levels

Even when ULT is initiated, usually with allopurinol, it is often given at a fixed dose and not titrated to achieve a specific target sUA level. As a consequence, many patients are undertreated and their urate crystal deposition continues to progress.54 sUA needs to be lowered to <6 mg/dl (<360 µmol/l) to achieve crystal dissolution.8 There is evidence that the lower the sUA achieved, the faster will be the dissolution of tophi,55 and the sooner the patient will be ‘cured’ with no further acute attacks and no crystals detected in their joints.8 ,9 The use of sUA levels to monitor the disease and the success of treatment is undervalued.8 ,44 Adherence and treatment outcomes may be improved when patients know their sUA levels and the aim of treatment and are actively involved in targeted monitoring of their treatment.44

Patients need more information

Provision of patient information on gout and its treatment is often suboptimal.32 ,42–44 Gout flares provoked by initiating ULT at a fixed dose, usually without prophylaxis, may lead patients to stop the drug, because they mistakenly believe that treatment has failed; they are then quite often mislabelled as ‘intolerant’ to ULT. A clear explanation of the different stages of treatment (treatment of the acute attack and subsequent initiation of ULT with a non-steroidal anti-inflammatory drug or colchicine for flare prophylaxis) and what to expect from treatment, as well as the reason for long-term ULT, is often not given.31 ,32 This leads to misinterpretation of events by the patient and poor adherence to treatment. Although adherence is a problem with any long-term medication, it appears to be lower in gout than in other chronic conditions.45 ,56

Management guidelines not followed

The low adherence of primary care physicians to published evidence-based treatment guidelines for the diagnosis and management of gout57 undoubtedly reflects inadequate dissemination of these guidelines. Contributing factors may include the lack of involvement of GPs in guideline development, publication of guidelines only in specialist rheumatology journals (even though GPs are the main target audience) and the absence of financial incentives to audit and improve standards of care. For example, in the UK there is no Quality and Outcomes Framework (a performance management and payment scheme for GPs) for the treatment of gout, as there is for other prevalent diseases that are managed mainly in primary care.

Hospital specialists

Unfortunately it appears that knowledge of gout and its management among hospital specialists, including rheumatologists and renal physicians, may not be much better than that of primary care practitioners.44 ,46 ,58 This can be attributed to a host of influences: the low profile of gout in specialist training; the slow progress in mastering the disease pathology and its treatment; the scarcity until recently of any new drug development in the field; the delay in updating of treatment guidelines and the general lack of publications on the subject.

Gout not a priority during training

Just as in undergraduate and primary care programmes, gout management does not feature as a priority in rheumatology specialist training courses.44 Consequently, rheumatologists appear to lack interest in this common, diagnosable and curable disease, regarding it as minor and less academic than rheumatoid arthritis and other conditions in their specialty.46 If anything, rheumatologists are more likely to dwell on the unusual presentations of gout rather than the commonly occurring, simple and straightforward forms of the disease.44 ,59 It has been suggested that specialists do not take gout seriously enough and the potential for damage and disability is again not recognised.46

Been there, done that

There is also the perception that the pathology and treatment of gout was conquered decades ago and it is therefore relatively mundane and unexciting compared with other rheumatic diseases, such as rheumatoid arthritis, for which the causation remains unknown and definitive treatments are still sought.46

New drug development stimulates interest

Sad to say, perhaps the most important reason for the lack of interest in gout for many years has been the absence, until very recently, of new treatments. Before that, there had been no new drug developments for gout for more than four decades.44 ,60 By contrast, there have been many new treatments, including biological agents, for other inflammatory diseases, and the substantial accompanying pharmaceutical industry support may have diverted attention from other musculoskeletal conditions such as gout. This lull in drug development may also have contributed to the relative paucity of papers on gout compared, for example, with those on rheumatoid arthritis.44

ULTs such as allopurinol, benzbromarone, probenecid and sulphinpyrazone have been available and used for many years.60 ,61 The search for alternative targeted gout treatments has resulted in new ULTs such as febuxostat (a selective non-purine xanthine oxidase inhibitor) which is now available for treatment of hyperuricaemia in patients with gout,62 and pegloticase (a pegylated porcine-like uricase) for treatment of hyperuricaemia in patients with severe gout who are refractory to conventional treatment.14 ,63 Other ULTs under advanced investigation in clinical trials include uricosurics such as lesinurad (RDEA594—a urate transporter inhibitor).14 ,50 ,64 ,65 Recently investigated possible new treatments for acute gout include the interleukin-1 (IL-1) receptor antagonist anakinra, an IL-1 receptor fusion protein (rilonacept) and a human monoclonal anti-IL-1β antibody (canakinumab).14 ,50 ,64 ,65

These new drug developments are serving to focus attention on gout and to raise the profile of the disease.46 They have already been instrumental in renewing interest in the disease and its management in both primary and secondary care settings. Much of the stimulus for this renewed interest has come from the new clinical and scientific evidence that has emerged from the development programmes of the new drugs and from the educational initiatives associated with their marketing.46


There is a wide variety of barriers to effective care for gout, which is a very common and uniquely curable, chronic inflammatory arthritis. These barriers largely reflect commonly held negative stereotypes of the patient with gout and poor knowledge and interest in gout among doctors. Appropriate education, possibly assisted by recent drug development and new scientific evidence is opening a new ‘window of opportunity’ in gout management and should improve the standard of care.


MD attests that all authors had authority over manuscript preparation and the decision to submit the manuscript for publication. MD and TB wrote the first draft and proposed the figures. MD, TB, TLJ, GN, TB, EP, FP-R, LP AKS revised the whole manuscript, ran the literature search and contributed with suggestions and discussions. We thank Michael Doherty for kindly providing the photographs in figures 3 and 4.


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  • Funding We thank Denis Bilotta on behalf of inScience Communications, a Springer Healthcare business, who provided editorial assistance for the preparation of this manuscript. This assistance is acknowledged by MD and funded by Menarini Group.

  • Competing interests MD has received consultancy or speaker fees from Ardea Biosciences, Ipsen, Menarini, Novartis and Savient. TLJ has received consultancy fees from Abbott and consultancy and speaker fees from Menarini, Ipsen, Roche and UCB. GN and TB received consultancy and/or speaker fees from Ardea Biosciences, Biocryst, Ipsen, Menarini, Novartis and Savient. EP received consultancy fees from Menarini and Savient. FP-R received consultancy and speaker fees from Menarini and Novartis and consultancy fees from Ardea Biosciences. LP received consultancy or speaker fees from Abbott, Fidia, Menarini, Merck and Pfizer. AKS received consultancy and/or speaker fees from Ardea Biosciences, Ipsen, Menarini and Novartis.

  • Provenance and peer review Not commissioned; externally peer reviewed.