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24-05-2017 | Gout | Editorial | Article

Taking gout seriously

Fernando Pérez-Ruiz

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.

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