Robert M. Centor, MD; Robert M. McLean, MD
Disclosures: Dr. Centor has disclosed the following: Honoraria: Medscape. Dr. McLean has disclosed relationships with the following organizations: Takeda Pharmaceuticals (speakers bureau), ABIM (board member), Northeast Medical Group of Yale New Haven Health System (employment), and American College of Rheumatology (member of Quality of Care Committee; current appointment ends November 2018).
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
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Audio. Annals On Call - The Gout Wars: When Guidelines Collide: Dr. Centor discusses the recent guidelines from the American College of Physicians on gout, including diagnosis and management. He interviews Dr. Robert M. McLean, the Medical Director of Clinical Quality of the Northeast Medical Group at the Yale-New Haven Health System.
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August 7, 2018
I just finished listening to the Annals on Call podcast with Dr. Robert McLean about the differences in ACP vs. ACR recommendations for the treatment of gout. Both the ACP and ACR are missing a big underlying cause of gout which would greatly affect its effective treatment. One aspect of gout which is too often overlooked in guidelines and in practice is that most gout flares are initiated during sleep. The sleep connection has been known at least since Dr. Thomas Sydenham wrote about it in 1683. A recent study by Dr. Hyon Choi et al confirms Dr. Sydenham's observation. It is a very important clue to the pathogenesis of gout whether symptomatic or not.Many gout flares are a direct result of sleep apnea, and overcoming the sleep apnea can cure the gout. Although Kelley's Textbook of Rheumatology lists respiratory insufficiency as a cause of acidosis leading to hyperuricemia, the hypoxemia of sleep apnea actually has three effects which can lead to an overnight gout flare in short order. Effect #1 is cellular catabolism in which adenosine triphosphate degradation is accelerated, leading to nucleotide turnover which culminates irreversibly in the transient cellular generation of excess uric acid fed into the blood, faster than any food would cause. Effect #2 is transient hypercapnia and acidosis, so that the blood can hold less uric acid in solution. Effect #3 is a long term deterioration of the kidneys' glomerular filtration rate so that removal of uric acid from the blood is slowed. Thus, with sleep apnea there is an abrupt increase in the influx of uric acid in the blood, slowed efflux, and abruptly reduced storage capacity -- perfect storm conditions for monosodium urate precipitation. Furthermore, after awakening and normal breathing is restored, the first two effects dissipate so that a blood test taken during waking hours misses their peaks. And if monosodium urate has precipitated recently, then the measurement of serum uric acid is greatly undervalued.Gout has been reported to have so many of the same comorbidities already known to be consequences of long-term untreated sleep apnea (eg., cardiovascular diseases, diabetes, kidney disease, hypertension.) Recent studies have found that increasing the dosage of urate lowering drugs had no benefit for reducing major cardiovascular events or all-cause mortality in gout patients. One of the first steps for treating gout should be screening and diagnosis for sleep apnea, followed by treatment of the sleep apnea where indicated. I know from my own experience and the experiences of others that overcoming sleep apnea can prevent additional inflammatory gout flares immediately and completely. Effects #1 and #2 don't occur, and Effect #3 may reverse over following effective treatment for sleep apnea. More importantly, gout is an early warning of sleep apnea, which when heeded can lead to the early treatment of sleep apnea, thereby greatly reducing the risk for the development of sleep apnea's later developing life-threatening consequences. Overcoming the sleep apnea can save lives as well as save joints.
Centor RM, McLean RM. Annals On Call - The Gout Wars: When Guidelines Collide. Ann Intern Med. ;169:OC1. doi: 10.7326/A18-0001
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Published: Ann Intern Med. 2018;169(3):OC1.
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