Faculty Bibliography

From an epidemiologic view, gout is an increasingly prevalent and increasingly pressing clinical problem. This fact, together with technical advances in biology, pharmacology, and imaging techniques, have led to a decade of increasingly rapid progress in our collective understanding of gout and hyperuricemia. Here we review some of the most important recent advances in gout over the past 12 to 18 months.

After nearly 50 years, new drugs are now available or in development for gout. Febuxostat (approved 2009) selectively inhibits xanthine oxidase, preventing uric acid formation and lowering serum urate. Pegloticase (approved 2010) is a recombinant chimeric mammalian uricase that corrects the intrinsic human uricase deficiency. Pegloticase reduces serum urate, and may have particular efficacy against tophi. IL-1beta is now understood to be a central actor in acute gouty inflammation. Three IL-1beta antagonists - anakinra, rilonacept and canakinumab (all US FDA approved for other uses) - are being evaluated for gout treatment and/or prophylaxis. The renal urate resorbing transporters URAT1 and GLUT9 have been recently characterized as targets of uricosuric drugs; two pipeline drugs, RDEA594 and tranilast, inhibit these transporters and are promising urate-lowering therapies. 2011 Future Science Ltd

OBJECTIVE: Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the interreader reproducibility of this modality is not well established. We therefore assessed agreement using a systematic approach. METHODS: Fifty male subjects ages 55-85 years were recruited during primary care visits to an urban Veterans Affairs hospital, and were assessed by musculoskeletal ultrasound (US) of the knees and first metatarsophalangeal (MTP) joints to evaluate for the double contour sign and tophi as evidence of MSU crystal deposition. Images were read by 2 blinded rheumatologists trained in musculoskeletal US, and the degree of concordance was determined for individual subjects, total joints, femoral articular cartilage (FAC), and first MTP joints. Subjects were further categorized into 3 diagnostic groups: gout, asymptomatic hyperuricemia (no gout, serum uric acid [UA] >/=6.9 mg/dl), and controls (no gout, serum UA </=6.8 mg/dl), and reader concordance within these 3 groups was assessed. RESULTS: We observed almost perfect agreement between readers for 1) individual subjects (yes/no; n = 50, 100% agreement, kappa = 1.000), 2) total joints (n = 200, 99% agreement, kappa = 0.942), 3) FAC (n = 100, 99% agreement, kappa = 0.942), and 4) first MTP joints (n = 100, 99% agreement, kappa = 0.942). Furthermore, findings by side (right/left) and diagnostic group (gout, asymptomatic hyperuricemia, control) showed substantial to almost perfect concordance for all measures. MSU deposition was seen most commonly in gout patients, and deposition was also seen in some subjects with asymptomatic hyperuricemia, but in only 1 control. CONCLUSION: Musculoskeletal US is reliable for detecting MSU deposition in FAC and first MTP joints in gout and asymptomatic hyperuricemia

Many drugs can cause myopathies, and such myopathies may range widely from asymptomatic elevations in the serum creatine phosphokinase levels to severe myalgias, cramps, exercise intolerance, muscle weakness, and even rhabdomyolysis. In this article, some of the commonly used drugs that may induce myopathies, as well as the clinical phenotypes, diagnosis, and management of these syndromes are reviewed

BACKGROUND: Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied. METHODS: A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease. RESULTS: The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III). CONCLUSION: Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications

Over the past decade, the pace of investigation in the field of gout has accelerated tremendously. New advances have led to deeper insight into the processes of inflammation and innate immunity, and new treatments are now available, or likely to become available in the near future. Some of the more interesting new findings in the field of gout are presented in the context of gout biology and treatment overall. Gout epidemiology, current understanding of renal urate handling, recent investigations into the mechanism of inflammation in acute gout, dietary factors in gout development, the potential role of hyperuricemia in cardiovascular and renal disease, and treatments that are either newly available or in development are discussed