Skip to main content
Top

24-05-2017 | Gout | Editorial | Article

Taking gout seriously

Author: Fernando Pérez-Ruiz

print
PRINT
insite
SEARCH

Gout is a considerably prevalent disease in developed countries, and the most common form of inflammatory arthritis [1]. Therefore, rheumatologists among other healthcare providers devoted to inflammatory joint diseases, should consider gout as much a ‘sexy disease’ as rheumatoid arthritis (RA).

RA has become the most important disease for rheumatology practice, as a paradigm of chronic, inflammatory, systemic disease mostly targeting joint involvement. This is because whether uncontrolled or insufficiently controlled to target it is associated with severe joint involvement – as for pain and limited motion – and in the long term it is associated with the development of serious disease defined as the presence of progressive structural joint damage with irreversible loss of quality of life, increased cardiovascular (CV) risk [2], systemic involvement, and premature death [3].

Gout has traditionally been considered a self-inflicted, exogenous-factors-driven disease, supposedly contrary to RA. Recent evidence shows that genetic factors play may play a significant role in the development of gout [4] – as they do in RA – modulated by exogenous factors – as they do in RA [5]. The main differences between gout and RA, from an academic point of view are: firstly, we know for sure the single pathologic mechanism (urate crystals) causing gout; in second place, gout is a ‘curable’ condition as far as we can invert the mechanism causing gout with relatively inexpensive urate-lowering therapies and treat to serum urate target approach; finally, gout is not well-understood by most physicians, including rheumatologists [6].

Despite historical cohorts of the pre-urate-lowering medication era showing a progressive increase in severity and seriousness – pain, swelling, and development of tophi with radiographic structural damage through the natural history in most patients with untreated disease [7] – recently a non-interventional approach to hyperuricemia of gout has been recommended because of the lack of specifically designed controlled trials to support such an intervention [8]. Tophus-related joint damage is associated with poorer patient-reported outcomes and the development of subcutaneous tophi is associated with increased risk in mortality rate mainly due to an excess of CV events [9], even in patients with recent onset gout [10].

Proper control of inflammation in RA is associated with a lower risk of CV events [11]. A reduction in the mortality gap for RA has closed in recent years, most plausibly associated with better treatment and better control of inflammation [12] especially with the tighter control of systemic inflammation achieved with biologic medications [13]. By contrast, this mortality gap has persisted in patients with gout throughout the last decades [14]; this persistence of episodes of inflammation is causing gout to replace RA as a common cause of hospitalization, with increasing healthcare costs due to emergency room visits [15] and similar admission costs to that of RA [16].

There is recent evidence that both the use of colchicine [17] and of urate-lowering therapy allopurinol may be associated with a lower risk of CV events and all-cause mortality [18]. However, initiation of urate-lowering treatment has not been associated with reduced mortality [19]:  this may be explained because despite gout prevalence and incidence increasing suboptimal management persists [20]. A small percentage of patients are prescribed long-term urate-lowering treatment with an unexplained, extraordinary wide range of variability [21] and patients are not commonly treated to target serum urate, as shown in audits of clinical practice [22].

We really need specifically designed prospective studies to ascertain that proper control of gout, as it has been shown in RA, is associated with an improvement in outcomes, including mortality. An enormous investment effort will be needed for such a task, as it has been for other diseases, such as RA.

We know for sure that gout is a severe disease. It can also become a serious disease, so let's take it seriously.

About the author

Fernando Pérez-Ruiz

Fernando Pérez-Ruiz is Chief of the Rheumatology Division, Cruces University Hospital, Head of the Investigation Group for Arthritis at BioCruces Health Research Institute, and Associated Professor of the Department of Medicine in the Basque Country University in Vizcaya, Spain. Disclosures


Full biography

print
PRINT
Literature
  1. Smith EU, Diaz-Torne C, Perez-Ruiz F, March LM. Epidemiology of gout: an update. Best Pract Res Clin Rheumatol. 2010;24:811-27.
  2. Solomon DH, Greenberg J, Curtis JR, et al. Derivation and internal validation of an expanded cardiovascular risk prediction score for rheumatoid arthritis: a Consortium of Rheumatology Researchers of North America Registry Study. Arthritis Rheumatol. 2015;67:1995-2003.
  3. Myasoedova E, Gabriel SE, Matteson EL, Davis JM, III, Therneau TM, Crowson CS. Decreased cardiovascular mortality in patients with Incident rheumatoid arthritis (RA) in recent years: dawn of a new era in cardiovascular disease in RA? J Rheumatol. 2017 [Epub ahead of print]; doi:10.3899/jrheum.161154.
  4. Kottgen A, Albrecht E, Teumer A, et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013;45:145-154.
  5. Traylor M, Curtis C, Patel H, et al. Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study. Rheumatology (Oxford). 2017 [Epub ahead of print]; doi:10.1093/rheumatology/kex048.
  6. Doherty M, Jansen TL, Nuki G, et al. Gout: why is this curable disease so seldom cured? Ann Rheum Dis. 2012;71:1765-1770.
  7. Gutman AB. The past four decades of progress in the knowledge of gout, with an assessment of the present status. Arthritis Rheum. 1973;16:431-445.
  8. Qaseem A, Harris RP, Forciea MA. Management of acute and recurrent gout: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166:58-68.
  9. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73:177-182.
  10. Vincent ZL, Gamble G, House M, et al. Predictors of Mortality in People with Recent-onset Gout: A Prospective Observational Study. J Rheumatol. 2017;44:368-373.
  11. Solomon DH, Reed GW, Kremer JM, et al. Disease activity in rheumatoid arthritis and the risk of cardiovascular events. Arthritis Rheumatol. 2015;67:1449-1455.
  12. Zhang Y, Lu N, Peloquin C, et al. Improved survival in rheumatoid arthritis: a general population-based cohort study. Ann Rheum Dis. 2017;76:408-413.
  13. Solomon DH, Curtis JR, Saag KG, et al. Cardiovascular risk in rheumatoid arthritis: comparing TNF-alpha blockade with nonbiologic DMARDs. Am J Med. 2013;126:730.
  14. Fisher MC, Rai SK, Lu N, Zhang Y, Choi HK. The unclosing premature mortality gap in gout: a general population-based study. Ann Rheum Dis. 2017 [Epub ahead of print]; doi:10.1136/annrheumdis-2016-210588.
  15. Garg R, Sayles HR, Yu F, et al. Gout-related health care utilization in US emergency departments, 2006 Through 2008. Arthritis Care Res (Hoboken). 2013;65:571-577.
  16. Lim SY, Lu N, Oza A, et al. Trends in gout and rheumatoid arthritis hospitalizations in the United States, 1993-2011. JAMA. 2016;315:2345-2347.
  17. Solomon DH, Liu CC, Kuo IH, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis. 2016;75:1674-1679.
  18. Larsen KS, Pottegard A, Lindegaard HM, Hallas J. Effect of allopurinol on cardiovascular outcomes in hyperuricemic patients: a cohort study. Am J Med. 2016;129:299-306.
  19. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Effect of allopurinol on all-cause mortality in adults with incident gout: propensity score-matched landmark analysis. Rheumatology (Oxford). 2015;PM:26170376.
  20. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015;64:661-667.
  21. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Eligibility for and prescription of urate-lowering treatment in patients with incident gout in England. JAMA. 2014;312:2684-2686.
  22. Perez-Ruiz F, Carmona L, Yebenes MJ, et al. An audit of the variability of diagnosis and management of gout in the rheumatology setting: the gout evaluation and management study. J Clin Rheumatol. 2011;17:349-355.

Related content