1. Gout

2. The most common cause of inflammatory arthritis in US adults (3.9% of Americans; approx. 8.3 million people; 2007-2008) Prevalence is greater in men (5.9%; 6.1 million) than women (2.0%; 2.2 million) Prevalence has increased by 1.2% points over the past 2 decades Incidence of gout 2x greater among black men than white men Men with gout have been shown to have an increased risk of all- cause mortality and cardiovascular disease mortality Cost: 2.3 million ambulatory care visit annually from 2001-2005; multiple hospitalizations; $7.7 billion attributable to gout between 2005-2011

3. Pathophysiology Caused by the deposition of monosodium urate crystals in tissues Uric acid is a metabolic by-product of purine catabolism Purines  hypoxanthine  xanthine  uric acid Reaction catalyzed by xanthine oxidase, found in the liver When the balance of dietary intake, synthesis and rate of excretion are disrupted, hyperuricemia results – Overproduction (10%) – Underexcretion (90%) Results in arthritis, soft tissue masses, nephrolithiasis and urate nephropathy

4. Pathophysiology Rees, F. et al. (2014) Optimizing current treatment of gout Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32

5. Risk Factors High Purine Diet (Red Meat, Fatty Poultry, High Fat Dairy, Seafood) Alcohol Consumption Trauma Osteoarthritis Surgery Starvation Dehydration Obesity Drugs (Allopurinol, uricosuric agents, thiazides, loop diuretics, low dose aspirin) Renal Impairment Genetic Mutations (SLC22A9, SLC22A12, ABCG2)

6. Stages of Gout Asymptomatic tissue deposition Acute Gouty Arthritis Intercritical Gout Chronic Articular and Tophaceous Gout

7. Acute Gout Often presents as involvement of a single joint or multiple joints in the lower extremities: first metatarsophalangeal (podagra; 50% of people with gout), midtarsal, ankle and knee joints Characterized by pain, erythema, swelling and warmth. Can have desquamation of skin. Can even cause fever and leukocytosis Maximal severity reached within 12-24 hours Even without treatment, attacks subside within days to several weeks

9. Chronic Gout Characterized by chronic arthritis and tophi, resulting in chronic inflammatory and destructive changes

10. Renal Complications Nephrolithiasis – Risk factors: increase uric acid excretion, reduced urine volume, and low urine pH Chronic urate nephropathy – Urate crystals can deposit in renal medullary interstitium producing inflammatory changes and fibrosis – Clinical features are non specific: renal function impairment, bland urinary sediment, mild proteinuria and serum urate concentrations often higher than expected for the degree of renal impairment. – Biopsy confirms diagnosis

11. Diagnosis DDX: Pseudogout and Septic Arthritis

12. Diagnosis 5 clinical classification criteria for gout currently exist: Rome, New York, ACR, Mexico and Netherlands These classification criteria have not been extensively validated Diagnosis should be based on combination of clinical, historical and laboratory data if arthrocentesis cannot be performed. Diagnosis is considered provisional.

13. Diagnosis Arthrocentesis should be done in patients in whom the diagnosis has not been previously established. Labs: cell count with differential, gram stain, culture, examination for crystals under polarized light microscopy

15. Treatment

20. When initiating urate lowering therapy, can precipitate acute gouty arthritis. Therefore, prophylaxis often given

22. Diet

23. Recommendations for Practice

26. References Mayo Clinic UptoDate CDC Khanna,D., et. al. 2012 American College of Rheumatology Guidelines for Management of Gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care and Research, Vol. 64, No. 10, October 2012, pp 1431-1446 Choi, H., et. al. Pathogenesis of Gout. Physiology in Medicine. Annals of Internal Medicine. Vol. 143, 2005, pp 499-516 Eggebeen, A. Gout: An Update. American Academy of Family Physicians. 2007. http://www.aafp.org/afp/2007/0915/p801.htmlhttp://www.aafp.org/afp/2007/0915/p801.html Dalbeth, N. et al. New Classification criteria for gout: a framework for progress. Rheumatology (2013).