Faculty Bibliography

Illicitly distilled beverages (colloquially referred to as moonshine) account for approximately one third of alcohol consumption worldwide. Moonshine is often produced in makeshift distilling units composed of old, repurposed parts, whose component elements can leach into the distillate. Consequently, the resultant beverages may inadvertently contain harmful toxins, one of which is the metal lead. One manifestation of chronic lead toxicity-from moonshine or other forms of chronic lead poisoning-is the rheumatologic entity known as saturnine gout. With the increasing prevalence of gout over the past few decades, physicians should be aware of the association of moonshine consumption or lead toxicity with gouty arthritis. In this article, we present an overview of saturnine gout, beginning with a discussion of lead poisoning in antiquity and tracing its path to modern times. The contribution of lead to human disease and the clinical features of saturnine gout are outlined. After describing the role of lead in renal insufficiency and purine metabolism, we conclude with a discussion of specific strategies to manage this clinically important form of secondary gout.

Gout prevalence is increasing, yet management remains suboptimal. Fortunately, new insights into gout biology are permitting the development of novel, potentially more effective strategies for both gouty inflammation and urate lowering. Colchicine, a drug long used for gout, has been recently approved (for the first time ever) by the FDA, based on a new, safer dosing regimen. The recently appreciated centrality of IL-1beta in acute gouty inflammation has prompted studies of agents blocking the IL-1beta receptor or soluble IL-1beta signaling (canakinumab, rilonacept, anakinra). Novel approaches to urate lowering have led to mechanism-based therapies such as urate synthesis inhibitors (febuxostat is already FDA approved and BCX4208 is in development), URAT-1 inhibitors promoting renal uric acid excretion (lesinurad), and recombinant uricase to directly catabolize urate (pegloticase). These new treatments do not obviate the need for lifestyle and dietary management, another area in which significant scientific and clinical progress has recently been made.

In 2012 the American College of Rheumatology (ACR) established its first-ever gout treatment guidelines. These guidelines address whom to treat, how to treat, and lifestyle and medication changes to make when treating patients with gout. In this manuscript, we review the ACR guide- lines, with special attention to the issues of treating to target, and when and how to prevent attacks during urate- lowering therapy. Given that the quality of gout treatment in the USA is often suboptimal poor, these guidelines have the potential to improve the health of millions of gout sufferers in the USA and around the world.

OBJECTIVE.: To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients. METHODS.: Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure. RESULTS.: The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status. CONCLUSIONS.: NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study.