Gout, Urate, and Crystal Deposition Disease

Gout is the most prevalent inflammatory arthritis in North America, affecting approximately 3.8% of the population in Canada and 5.1% in the United States (US). Epidemiological modeling through 2050 projects that high-income North America will sustain the highest age-standardized prevalence of gout globally. This rising burden is accompanied by heavy socioeconomic costs and striking demographic shifts. Driven by obesity, early-onset gout among American youth escalated by 63% over the last three decades, while nearly one-third of US adolescents now exhibit hyperuricemia, in contrast to ~20% of adults. Furthermore, profound racial inequities persist; Black patients experience a five-fold higher rate of emergency department (ED) visits for gout flares compared to White patients, and older Asian Americans face the highest overall prevalence. Primary care providers manage 70% to 80% of gout cases in both nations. Suboptimal longitudinal care has led to severe reliance on acute services. Post-ED care continuity remains poor, frequently resulting in low rates of follow-up serum urate testing, high readmission rates, and inappropriate opioid prescribing. Diagnostically, polarizing light microscopy of synovial fluid remains the gold standard, supplemented by advanced ultrasound and dual-energy computed tomography imaging, although this technology is limited by provider availability. Treatment paradigms prioritize a treat-to-target strategy to maintain serum urate levels below 6 mg/dL. Allopurinol is the preferred first-line therapy, with recent clinical data validating its safety and efficacy when progressively titrated in patients with chronic kidney disease. Second-line febuxostat requires shared decision making in the context of cardiovascular disease, while advanced, refractory tophaceous gout is managed in the US with intravenous pegloticase which can be co-administered with methotrexate to mitigate immunogenicity. Ultimately, optimizing North American gout outcomes requires improvement in health services delivery with multidisciplinary models of care serving as an emerging solution.

Background and Objectives: The nomenclature of calcium pyrophosphate deposition (CPPD) disease remains confusing, with different labels used interchangeably to describe the disease. Although ‘CPPD disease’ is the term that has been recommended by EULAR since 2011, ‘pseudogout’ remains the most frequently used label in the medical literature. This study aimed to investigate how the labels ‘CPPD disease’ versus ‘pseudogout’ affect the public’s perceptions of the illness. Methods: In this randomized controlled single-blind study, 200 members of the public watched a 2 min video describing a form of arthritis labeled as either ‘CPPD disease’ or ‘pseudogout’. Participants then completed a questionnaire assessing their perceptions of the illness using the Brief Illness Perception Questionnaire (BIPQ), with additional questions about their perceived seriousness of the illness and embarrassment associated with it, and beliefs about causes and management strategies. The primary outcome was the level of embarrassment associated with the illness. Results: Overall, embarrassment scores were low with no significant difference between the ‘CPPD disease’ and ‘pseudogout’ groups. Participants in both groups viewed the illness as being serious. There were no differences between the groups in their responses to the BIPQ, nor in their beliefs on the likely causes and management strategies. Even after a video intervention, participants’ understanding of the illness remained low. Conclusions: The labels ‘CPPD disease’ and ‘pseudogout’ do not differentially influence perceptions about the illness among members of the public. This could be due to the lack of knowledge about CPPD disease, highlighting the need to increase public awareness of this important condition.

Humans and other great apes are unique among animals in lacking functional uricase, an enzyme that breaks down urate and allows its excretion. Modern-day humans have elevated serum urate, which is associated with various chronic health issues, including gout, metabolic syndrome, and hypertension. This prompts the question: what is the evolutionary benefit of the loss of uricase function, given that it may confer an increased risk of these chronic diseases? In this review, we explore numerous possible advantages, including some less commonly discussed, such as urate’s function as an antioxidant, its roles in ancestral survival, and its metabolic role in the context of our evolutionary history and the environmental pressures that have shaped human biology. We go on to examine the tradeoffs of urate’s evolutionary advantages, and how these features may be a double-edged sword for our health in our modern environment characterized by a caloric abundance of key nutrients, such as fructose, which are intimately linked with urate production and/or metabolism. Moving forward, we suggest that future work should explore the role of our evolutionary history in the rising prevalence of gout and other modern-day metabolic diseases. We further recommend that drugs and therapeutic strategies for diseases such as gout be informed by an understanding of the rich evolutionary context from which these maladies emerged and the unifying role of serum urate across these disease states.