Gout Attacks Twice as Likely at Night

Janis C. Kelly

December 15, 2014

A landmark study published online December 11 in Arthritis & Rheumatism by Hyon K. Choi, MD, DrPH, from Boston University School of Medicine, Massachusetts, and Sydney University, Australia, and colleagues confirmed the widely held assumption that gout is more likely to flare at night and challenged the common impression that attacks are more likely after alcohol or purine dietary indulgence.

Dr Choi, currently director of Clinical Epidemiology at Massachusetts General Hospital/Harvard Medical School in Boston, told Medscape Medical News that the 2.36-fold greater risk for nocturnal gout attacks has direct implications for clinicians treating patients with gout. "Prophylactic measures that prevent gout flares, especially at night, are likely to be more effective. For example, prophylactic drugs for gout flares, particularly those with short half-lives, may be timed appropriately to optimize their benefits," Dr Choi said.

Gout expert H. Ralph Schumacher Jr, MD, professor of medicine at the University of Pennsylvania and at the VA Medical Center, Philadelphia, Pennsylvania, commented to Medscape Medical News, "This is a beautiful study that confirms a widely held impression with carefully obtained prospective data. The only surprise was how undertreated this population was (less than 45% on allopurinol and about a quarter on prophylactic colchicine). I don't see any uric acid levels on these people. Conceivably, people with better-managed gout might have different patterns as well as fewer flares."

Dr Choi's team used data from the Boston Online Gout Study to examine risk for acute gout attacks in relation to time of day. The researchers prospectively recruited 724 patients with gout who were followed for 1 year via the Internet in a case-crossover study. Patients reported date and time of attack onset, symptoms, medication use, and possible risk factors (such as alcohol or seafood consumption) during the 24 and 48 hours before the attack. Most participants were white (89%) and male (78%).

The risk for gout flares was 2.36 times higher overnight than in the daytime and 1.26 times higher overnight than in the evening. The patients reported 1433 acute gout attacks, of which 733 occurred overnight (midnight to 7:59 am), 310 occurred between 8:00 am and 2:59 pm, and 390 occurred between 3:00 pm and 11:59 pm.

The differences in nocturnal risk persisted even among patients who had no alcohol intake and low purine intake during the prior 24 hours. These associations remained after accounting for sex, age, body mass index, and use of diuretics, gout medications, and nonsteroidal anti-inflammatory drugs (NSAIDs). During the gout flare, or the "intercritical periods" between attacks, alcohol consumption was reported by approximately 68% of participants, diuretic use by 29%, allopurinol use by 45%, NSAID use by 54%, and colchicine use by 26%. Most of the gout attacks were in the lower extremities (92%), and 90% were treated with colchicine, NSAIDs, systemic corticosteroids, intra-articular corticosteroids, or a combination.

The mechanism underlying the increased risk for nocturnal gout flare is unknown, but suspects include lower body temperature at night (leading to higher risk for uric acid crystallization), dehydration during sleep or periarticular dehydration resulting from sleep position, and a nighttime dip in blood cortisol levels.

The researchers suggested that sleep apnea might be a factor because the associated hypoxia enhances nucleotide turnover and generates purines that can be metabolized to uric acid. Dr Choi noted that sleep apnea affects roughly one third of obese men who have multiple comorbidities, which also describes the typical patient with gout. In a general population study presented at the American College of Rheumatology (ACR) 2014 Annual Meeting, Dr Choi reported that patients with sleep apnea had a 20% increased risk of developing gout.

Dr Schumacher commented, "On the role of sleep apnea, I would be really interested if [in the Boston Online Gout Study,] they had enough night workers who sleep during the day to see if they also flare during sleep. There is a suggestion of a second small increase in flares in the late afternoon or evening. Might those be related to daytime microtrauma as a different mechanism?"

Dr Choi noted that sleep apnea is common and that the associated hypoxia is treatable with noninvasive ventilation continuous positive airway pressure, which might be a useful subject for further study in the management of patients with gout.

This study was funded by grants from the National Institutes of Health, the Arthritis Foundation, and the American College of Rheumatology Research and Education Fund. The authors and Dr Schumacher have disclosed no relevant financial relationships.

Arthritis Rheum. Published online December 11, 2014. Abstract

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