In the literature there have been few case reports of systemic lupus erythematosus (SLE) and gout occurring concomitantly in the same patient.1–3 Hyperuricaemia is relatively frequent in SLE, with a reported prevalence of 25–41%,4 for which there are several predisposing factors: many patients have nephritis and renal insufficiency, receive diuretics and some are on low-dose aspirin, all contributing to decreased uric acid excretion.1–3 Nevertheless, they rarely develop gout clinically. Besides age and gender distribution of both diseases, many other factors may play a role in this association.

First, it is known that the inflammatory response in acute gouty arthritis largely arises from the interaction between polymorphonuclear leukocytes and monosodium urate (MSU) crystals. In SLE, it has been demonstrated that these cells have impaired chemotactic activity and phagocytosis, which may hamper the reaction to MSU crystals.4

Secondly, it is thought that complement plays an important role in the pathogenesis of gouty arthritis, as MSU crystals activate both classical and alternative pathways of complement in synovial fluid.5 As active SLE is characterized by decreased serum and synovial complement levels, in these situations it is expected that inflammatory response to MSU crystals will be impaired. This view is further supported by the fact that most cases of gout occur when SLE is quiescent, with complement levels in the normal range.1,3

Alterations in the structure of MSU crystals may provide another explanation. It has been demonstrated that Apo B lipoprotein binds to the crystal surface, thereby physically inhibiting particle–cell interaction and subsequent phagocytosis of MSU and membrane activation.3 Apo B lipoprotein levels may be elevated in SLE, by a process that can be related to the disease itself and/or induced by corticosteroids, one of the cornerstone treatments in these patients.6

Additionally, it is well known that corticosteroids are powerful suppressors of the inflammatory response, blocking vasodilatation and increased vascular permeability and reducing neutrophils chemotaxis and phagocytosis, and likely impede clinical typical gout attacks.3

Furthermore, in clinical practice routine microscopy evaluation of synovial fluid is unfortunately underused, so gout attacks may be misdiagnosed as lupus arthritis flares. Consequently, gout diagnosis is late, with high rates of tophaceous forms.2,4

More recently, the knowledge about inflammasome contribution to the pathogenesis of certain diseases has progressed. Inflammasome is a term used to describe multimeric cytoplasmic protein complexes that detect pathogen-associated and danger-associated molecular patterns (PAMPS and DAMPs respectively) and mediate the activation of caspase-1, the primary enzyme responsible for activation of the pro-inflammatory cytokines IL-1β and IL-18. Several types of inflammasomes exist, but the best studied is the Nod-like receptor protein 3 (NLRP3) inflammasome.7,8 The importance of inflammasome and IL-1 β activation in gout is clearly established, however in SLE it is an emerging concept. It is noteworthy that both uric acid and DNA are DAMPs, and both induce NLRP3 inflammasome, although the exact molecular details of this pathway in both conditions are not entirely known. It has been demonstrated that NLRP3 plays an important role in lupus nephritis animal models.9 Moreover, it has been shown that anti-dsDNA antibodies activate NLRP3 inflammasome in monocytes/macrophages by binding to toll-like receptor 4 and inducing the production of mitochondrial reactive oxygen species.10 As gout and SLE share this pathway in their pathogenesis, that appears to be related with SLE activity and nephritis,9,10 it seems reasonable to think that it could play a role in the interplay between both diseases. As previously stated, gout attacks are less common in active lupus. The authors hypothesize there could be a counterregulatory mechanism in inflammasome pathway. However, further research is needed to clarify this subject.