JSM Arthritis

Viewing Gout as an Early Symptom of Sleep Apnea

Mini Review | Open Access | Volume 2 | Issue 1

  • 1. 221 Linden Drive, Elkins Park, PA 19027 USA
+ Show More - Show Less
Corresponding Authors
Burton Abrams, 221 Linden Drive, Elkins Park, PA 19027 USA Tel: 215-517-7766

The chronic intermittent hypoxemia which results from sleep apnea causes three effects which quickly elevate the concentration of serum uric acid, often leading to the precipitation of monosodium urate crystals, namely, gout: cell catabolism which culminates irreversibly in the generation of excess uric acid fed into the blood; serum acidosis and hypercapnia which reduces the solubility of uric acid in the blood; and gradual reduction of the kidneys’ glomerular filtration rate so that the removal of serum uric acid is slowed. This physiologic connection of gout to sleep apnea leads to the view that gout is a symptom of sleep apnea, a view supported by epidemiologic studies, common comorbidities, and clinical evidence. The importance of this view is that the incidence of gout should be used to trigger diagnosis and treatment for sleep apnea, before its life-threatening consequences develop.


•    Etiology of Gout
•    Gout flare
•    Sleep apnea
•    Monosodium urate
•    Hypoxemia


Abrams B (2017) Viewing Gout as an Early Symptom of Sleep Apnea. JSM Arthritis 2(1): 1023.


SA: Sleep Apnea; CPAP: continuous Positive Airway Pressure


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 Sir Thomas Sydenham, MD, wrote about it in 1683. A recent study by Dr. Hyon Choi [1] et al., confirms Dr. Sydenham’s observation. It is a very important clue to the etiology of gout whether or not it manifests with joint pain and inflammation, tophi, or urate kidney stones. The principal culprit is sleep apnea (SA), which is the frequent cessation of breathing for at least 10 seconds at a time, averaging at least 5 such events per hour during the sleep period. The strongest support for the view that gout is a symptom of sleep apnea is the physiology. In addition to the physiology, this mini review will present epidemiologic, shared comorbidities, and clinical evidence to date that support the view that gout is a symptom of SA.


Many arthritic gout flares are a direct result of SA. Although Kelley’s Textbook of Rheumatology [2] lists respiratory insufficiency as a cause of acidosis leading to hyperuricemia, the hypoxemia of SA 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 [3,4], 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 [5] so that removal of uric acid from the blood is slowed. Thus, with SA 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. The physiology suggests that gout, defined as the deposition of monosodium urate crystals in body tissues and fluids, starts early in the development of SA. Accurate measurement of these conditions is very elusive. 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. The monosodium urate crystals are highly inflammatory [6], not only when they form in a joint, but anywhere in the body. They are a danger signal that alerts the immune system to many dying cells [7], leading to the maturation of dendritic cells and the stimulation of T cells that may be needed to combat invading pathogens.


Two epidemiologic studies have found that gout was significantly more prevalent in a population which had been diagnosed with SA than in a population which had never been diagnosed with SA. Using data taken from nine UK general practices, [8] found that the odds ratio for SA was 2:1. A larger data base from the UK Health Improvement Network was used in [9], finding that the ratio of gout flare incidence over a one year period for those diagnosed with SA versus those never diagnosed with SA was 1.75:1, and that ratio held over population subgroups selected by age, sex, or body mass index.


Long term untreated SA is known to have many life-threatening conditions among its consequences, among which are cardiovascular diseases, diabetes, kidney disease, and hypertension [10]. These same diseases have been found to be comorbidities of gout [11]. The life-threatening diseases which are SA consequences have been shown to develop after years of untreated SA [12].


Rheumatologists reported in [13] that 54 patients were tested for SA by polysomnography, which is the gold standard for SA diagnosis. The result was that 89% were diagnosed with SA. However, the patient population selection was biased in that they were suspected to have SA by questionnaire prescreening.

One method to measure the effect of SA on uric acid was reported in [14], measuring uric acid concentration in urine excreted immediately after sleep, and normalizing its measurement to creatinine measured in the urine. These measurements were conducted on a cohort of twenty male patients diagnosed with SA by polysomnography on two successive nights of sleep - one during which they each slept without a nasal CPAP, followed by one during which they each slept using a nasal CPAP. The normalized uric acid excretion ratio from no CPAP to CPAP averaged among the participants was 1.8:1; the maximum was 6:1. These results are evidence that untreated SA induces the production of excess serum uric acid. In a telephone conversation with this author, the author of [14] opined that the average result was not higher because much of the uric acid went into urate stores.


The physiology described above suggests that gout occurs early in the development of SA, whereas its life-threatening consequences have been shown to develop after years of untreated SA. Thus an arthritic gout flare can be used to trigger diagnosis and treatment for SA, before its life-threatening consequences develop. After SA is successfully treated, Effects #1 and #2 no longer occur, and Effect #3 may reverse over several months of effective treatment for sleep apnea [15,16]. Thus successful SA treatment would be expected to minimize new gout manifestations, and may even reverse those previously occurring, because the SA-induced peaks in serum uric acid concentration no longer occur. In order to show that gout is indeed a symptom of SA, it is important to show that overcoming SA prevents additional gout manifestations without the use of urate lowering drugs. I know from my own experience and the experiences of others that overcoming SA prevents additional arthritic gout flares immediately and completely. What is needed is a two part clinical trial. Part 1 would test a randomly selected cohort of gout patients for SA to determine the prevalence of SA in the gout population. In Part 2, those found in Part 1 with SA should be treated for it to determine the degree of gout mitigation due to SA treatment. Because SA is so grossly under diagnosed [17], in both of the referenced epidemiologic studies a significant number of individuals in the group never diagnosed with SA may indeed have had that disease. Thus, the ratios found in both studies need to be considered as lower bounds. If all members of both groups had undergone SA testing, the actual ratios may be much higher.


One of the first steps for treating gout should be screening and diagnosis for SA, followed by treatment of the SA where indicated. More importantly, gout should be considered to be an early warning of SA, which when heeded can lead to the early treatment of SA, thereby greatly reducing the risk for the development of SA’s later developing life-threatening consequences. Using a gout flare as a sentinel event leading to the diagnosis and treatment of SA can save lives along with saving joints.


1. Choi HK, Niu J, Neogi T, Chen CA, Chaisson C, Hunter D, et al. Nocturnal risk of gout attacks. Arthritis Rheumatol. 2015; 67: 555-562.

2. Firestein GS, Budd RC, Gabriel SE. Kelley’s Textbook of Rheumatology 9th edition. Elsevier Saunders 2012.

3. Hasday JD, Grum CM. Nocturnal increase of urinary uric acid: creatinine ratio.A biochemical correlate of sleep-associated hypoxemia. AmRev Respir Dis. 1987; 135: 534-538.

4. Grum CM. Cells in crisis. Cellular bioenergetics and inadequate oxygenation in the intensive care unit. Chest. 1992; 102: 329-330.

5. Ahmed SB, Ronksley PE, Hemmelgarn BR, Tsai WH, Manns BJ, Tonelli M, et al. Nocturnal hypoxia and loss of kidney function. PLoS One. 201; 6: 0019029.

6. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440: 237-241.

7. Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003; 425: 516- 521.

8. Roddy E, Muller S, Hayward R, Mallen CD. The association of gout with sleep disorders: a cross-sectional study in primary care. BMC Muscoskelet Disord. 2013; 14: 119.

9. Zhang Y, Peloquin CE, Dubreuil M, Roddy E, Lu N, Neogi T, et al. Sleep Apnea and the Risk of Incident Gout: A Population-Based, Body Mass Index-Matched Cohort Study. Arthritis Rheumatol. 2015; 67: 3298- 3302.

10. Chiang CL, Chen YT, Wang KL, Su VY, Wu LA, Perng DW, et al. Comorbidities and risk of mortality in patients with sleep apnea. Ann Med. 2017; 49: 377-383.

11. Chien-Fang Huang, Ju-Chi Liu, Hui-Chuan Huang, Shao-Yuan Chuang, Chang-I Chen, Kuan-Chia Lin. Longitudinal transition trajectory of gouty arthritis and its comorbidities: a population-based study. Rheumatol Int. 2017; 37: 313-322.

12. Huang QR, Qin Z, Zhang S, Chow CM. Clinical patterns of obstructive sleep apnea and its comorbid conditions: a data mining approach. J Clin Sleep Med. 2008; 4: 543-550.

13. Cantalejo Moreira M, Veiga Cabello RM, García Díaz V, Racionero Casero MA, Zapatero Gaviria A. Gout, hyperuricaemia,sleep apnoea-hypopnoea syndrome and vascular risk. Rheumatology (Oxford). 2013; 52: 1619-1622.

14. Sahebjani H. Changes in urinary uric acid excretion in obstructive sleep apnea before and after therapy with nasal continuous positive airway pressure. Chest. 1998; 113: 1604-1608.

15. Kinebuchi S, Kazama JJ, Satoh M, Sakai K, Nakayama H, Yoshizawa H, et al. Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apneoa syndrome. Clin Sci (Lond). 2002; 107: 317-322

16. Koga S, Ikeda S, Yasunaga T, Nakata T, Maemura K. Effects of nasal continuous positive airway pressure on the glomerular filtration rate in patients with obstructive sleep apnea syndrome. Intern Med. 2013; 52: 345-349.

17. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997; 20: 705-706.

Abrams B (2017) Viewing Gout as an Early Symptom of Sleep Apnea. JSM Arthritis 2(1): 1023

Received : 16 Jun 2017
Accepted : 08 Aug 2017
Published : 08 Oct 2017
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X