浙江大学医学院：痛风 Gout（PPT讲稿）

Gout 浙大医学院附属二院任跃忠

Gout 浙大医学院附属二院 任跃忠

Background y Gout is a common disorder of etabolism that can lead to deposition of monosodium urate(MSU) crystals in soft tissue, recurrent episodes of debilitating i oint inflammation, and, if untreated, joint destruction and renal damage Gout is definitively diagnosed based on t he demonstration of in asp irated synovial fluid 浙医二院

2 浙医二院 Background Gout is a common disorder of uric acid m etabolism that can lead to deposition of monosodium urate (MSU) crystals in soft tissue, recurrent episodes of debilitating j oint inflammation, and, if untreated, joint destruction and renal damage. Gout is definitively diagnosed based on t he demonstration of urate crystals in asp irated synovial fluid

Epidemiology o United States statistics-The National Health and Nutrit ion Examination Survey(2007-2008)estimated a new pre valence for gout and hyperuricemia. Gout rates were repo rted as 5. 9% among men and 2% among women (etrog enic hormones have a mild uricosuric effect). The prevale nce rate of hyperuricemia was noted as 21.2% for men an d 21.6% for women Racial differences in incidence-In the United States, t he incidence of gout is 3.11 per 1000 person-years in Afri can Americans and 1.82 per 1000 person years in whites -Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hy the US general population!The\ Health and Nutrtion Examination Survey 2007-2008.Arthritis Rheum. Oct 2011: 63(103-3136-41

3 浙医二院 Epidemiology United States statistics---The National Health and Nutrit ion Examination Survey (2007-2008) estimated a new pre valence for gout and hyperuricemia. Gout rates were repo rted as 5.9% among men and 2% among women. (estrog enic hormones have a mild uricosuric effect). The prevale nce rate of hyperuricemia was noted as 21.2% for men an d 21.6% for women. Racial differences in incidence---In the United States, t he incidence of gout is 3.11 per 1000 person-years in Afri can Americans and 1.82 per 1000 person years in whites; --------Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. Oct 2011;63(10):3136-41

Epidemiology As a rule, uric acid levels are elevated for 20 years before the onset of gout In men, the peak age of onset of gout in men is in the four th to sixth decade of life. However, onset may occur in me n in their early 20s who have a genetic predisposition and lifestyle risk factors. In women, peak age of onset is in the sixth to eighth decade of life Tophi are typically detectable clinically approximately 10 y ears after the first gout attack Olaniyi-Leyimu BY. Consider gout in patients with risk factors, regardless of age. Am Fam Physician, Jul 15 2008, 78(2): 176 院

4 浙医二院 Epidemiology As a rule, uric acid levels are elevated for 20 years before the onset of gout. In men, the peak age of onset of gout in men is in the four th to sixth decade of life. However, onset may occur in me n in their early 20s who have a genetic predisposition and lifestyle risk factors. In women, peak age of onset is in the sixth to eighth decade of life. Tophi are typically detectable clinically approximately 10 y ears after the first gout attack. Olaniyi-Leyimu BY. Consider gout in patients with risk factors, regardless of age. Am Fam Physician. Jul 15 2008;78(2):176

Etiology Uric acid is an end-stage by-product of purine metabolism. Human s remove uric acid primarily by renal excretion. ( the saturation level of 6.8 mg/dL) Ninety percent of patients with gout... underexcretion The remaini ng patients.overproduction. In rare cases, overproduction., due to a genetic disorder ( hypoxa nthine-guanine phosphoribosyl transferase.次黄吟鸟酸长精基转移 deficie ncy, glucose-6-phosphatase deficiency, fructose 1-phosphate ald olase醛缩酶 deficiency) Chronic urate nephropathy can result from the deposition of urate c rystals in the medullary interstitium and pyramids, resulting in an inf lammatory reaction that can lead to fibrotic changes 浙医二院

5 浙医二院 Etiology Uric acid is an end-stage by-product of purine metabolism. Human s remove uric acid primarily by renal excretion. (the saturation level of 6.8 mg/dL ) Ninety percent of patients with gout … underexcretion. The remaini ng patients …overproduction. In rare cases, overproduction .., due to a genetic disorder. ( hypoxa nthine-guanine phosphoribosyl transferase次黄嘌呤鸟嘌呤磷酸核糖基转移酶 deficie ncy , glucose-6-phosphatase deficiency , fructose 1-phosphate ald olase醛缩酶 deficiency) Chronic urate nephropathy can result from the deposition of urate c rystals in the medullary interstitium and pyramids, resulting in an inf lammatory reaction that can lead to fibrotic changes

Pathophysiology Gout can be considered a disorder of metabolism that allows uric acid/urate to accumulate in blood and tissues. When tissues becor aturated,., forming crystals. In addition, thE CryS are less soluble under acid conditions y reactive urate crystals are normally coated with serum protei ns(apolipoprotein apo]E or apo B)that physically inhibit th e binding of the crystals to cell receptors. A gout attack may be triggered by either a release of uncoated crystals(eg, due t o partial dissolution of a microtophus caused by changing ser um urate levels) or precipitation of crystals in a supersaturate d microenvironment (eg, release of urate due to cellular dam age) 浙医二院

7 浙医二院 Pathophysiology Gout can be considered a disorder of metabolism that allows uric acid/urate to accumulate in blood and tissues. When tissues become super saturated, …, forming crystals. In addition, the crystals also are less soluble under acid conditions. reactive urate crystals are normally coated with serum protei ns (apolipoprotein [apo] E or apo B) that physically inhibit th e binding of the crystals to cell receptors. A gout attack may be triggered by either a release of uncoated crystals (eg, due t o partial dissolution of a microtophus caused by changing ser um urate levels) or precipitation of crystals in a supersaturate d microenvironment (eg, release of urate due to cellular dam age)

Clinical---History Podagra is the initial joint manifestation in ca-o gout ca ses. Eventually, it is involved in of cases Other than the great toe, the most common sites of gouty arthritis are the ankle, wrist, and knee. In early gout, only 1 or 2 joints are usually involved Gout attacks begin abruptly and reach maximum intensit y within 8-12 hours. The joints are and exquisite y tender; even a bed sheet on the swollen joint is uncomf ortable. Untreated, the first attacks resolve spontaneously in less than 2 weeks. Gout initially presents as polyarticul ar arthritis in 10% of patients 浙医二院

8 浙医二院 Clinical---History Podagra is the initial joint manifestation in 50% of gout ca ses. Eventually, it is involved in 90% of cases. Other than the great toe, the most common sites of gouty arthritis are the ankle, wrist, and knee. In early gout, only 1 or 2 joints are usually involved. Gout attacks begin abruptly and reach maximum intensit y within 8-12 hours. The joints are red, hot, and exquisitel y tender; even a bed sheet on the swollen joint is uncomf ortable. Untreated, the first attacks resolve spontaneously in less than 2 weeks. Gout initially presents as polyarticul ar arthritis in 10% of patients

Clinical---History The pattern of symptoms in untreated gout changes over time. The attacks become more polyarticular. Although m ore joints may become involved, inflammation in a given j oint may become less intense. More proximal and upper. extremity joints become involved. Attacks occur more freq uently and last longer Eventually, patients may develop chronic polyarticular art hritis. Patients with gout are profoundly more likely to dev elop renal stones 浙医二院

9 浙医二院 Clinical---History The pattern of symptoms in untreated gout changes over time. The attacks become more polyarticular. Although m ore joints may become involved, inflammation in a given j oint may become less intense. More proximal and upper￾extremity joints become involved. Attacks occur more freq uently and last longer. Eventually, patients may develop chronic polyarticular art hritis. Patients with gout are profoundly more likely to dev elop renal stones

Clinical-Physical Examination The classic location of tophi is along the helix of the ear., includin g the fingers, toes, prepatellar bursa, and along the olecranon. Rar ely, a creamy discharge may be present All manitestations of gout in the eye are secondary to deposition of urate crystals within the ocular tissue Gout. Chronic tophaceous gout Gout. Tophaceous deposits on elbow in an untreatedpatientwithend Gout Tophaceous deposits in ear stage renal disease 10

10 浙医二院 Clinical--Physical Examination The classic location of tophi is along the helix of the ear …, includin g the fingers, toes, prepatellar bursa, and along the olecranon. Rar ely, a creamy discharge may be present . All manifestations of gout in the eye are secondary to deposition of urate crystals within the ocular tissue •Gout. Tophaceous deposits on elbow •Gout. Tophaceous deposits in ear •Gout. Chronic tophaceous gout in an untreated patient with end￾stage renal disease

Workup -Approach Considerations 少 Arthrocentesis关节穿刺术 of the affected joint is mandatory for all pati ents with new onset of acute monoarthritis. Tophi also may be aspi rated for crystal analysis under polarizing microscopy Septic arthritis must be diagnosed and treated promptly, because ir reversible damage can occur wIthin and the joint can be completely destroyed within 24-48 hours Send joint fluid for fluid analysis, including cell count and differentia I, Gram stain, culture and sensitivity, and microscopic analysis for c rystals In gout, crystals of monosodium urate (MSU) appear as ped intracellular and extracellular crystals. pseudogout shows cal cium pyrophosphate,焦磷酸盐(CPP) crystals, which appear shorter th an MSU crystals and are often 长斜方形的 浙医二院

11 浙医二院 Workup –Approach Considerations Arthrocentesis关节穿刺术 of the affected joint is mandatory for all pati ents with new onset of acute monoarthritis . Tophi also may be aspi rated for crystal analysis under polarizing microscopy Septic arthritis must be diagnosed and treated promptly, because ir reversible damage can occur within 4-6 hours, and the joint can be completely destroyed within 24-48 hours. Send joint fluid for fluid analysis, including cell count and differentia l, Gram stain, culture and sensitivity, and microscopic analysis for c rystals. In gout, crystals of monosodium urate (MSU) appear as needle-sha ped intracellular and extracellular crystals. ..pseudogout shows cal cium pyrophosphate焦磷酸盐 (CPP) crystals, which appear shorter th an MSU crystals and are often rhomboidal.长斜方形的