Faculty Bibliography

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

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

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

The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.

Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics

Gout is a commonly occurring medical condition that can lead to significant morbidity. Therapies available for the treatment of both acute and chronic gouty arthritis have not changed significantly since the 1960s. Although these treatments are well established, they are often contraindicated in the presence of various different comorbidities, including diabetes, renal insufficiency, hypertension and gastrointestinal disease, all of which can occur frequently in patients with gout. Therefore, new treatments are needed. This review describes recent advances in therapeutics for gout, including drugs designed to reduce levels of urate and to inhibit acute or chronic inflammation. While some of these strategies are currently available, others are undergoing regulatory evaluation or are at earlier stages of development