Expert Consensus Chinese Multidisciplinary Expert Consensus on the Diagnosis and Treatment of Hyperuricemia and Related Diseases Multidisciplinary Expert Task Force on Hyperuricemia and Related Diseases Key words: Consensus; Gout; Hyperuricemia; Recommendation; Uric Acid INTRODUCTION factors. A nationwide epidemiological survey of HUA is still lacking in China. The data from different regions at The prevalence of hyperuricemia (HUA) has increased various times have shown an overall increasing prevalence in China in the recent years in relation to socioeconomic of HUA in the recent years.[1,2] Epidemiological studies have developments and changing lifestyles and diets, with a trend shown that the prevalence of HUA varies greatly among toward onset at younger age. HUA has become the second geographical regions in China over the previous 10 years, most common metabolic disease after diabetes mellitus. ranging from 5.46% to 19.30%, specifically 9.2–26.2% Like gout, HUA is also associated with the occurrence and in males and 0.7–10.5% in females.[3‑7] The prevalence progression of disorders of the urinary, endocrine, metabolic, of gout varies from 0.86% to 2.20% among geographical cardio‑cerebrovascular, and other systems. Different expert regions in China, specifically 1.42–3.58% in males and panels have developed guidelines and consensuses on 0.28–0.90% in females.[1,3,8] The prevalence of both HUA HUA and gout in their respective fields. This consensus and gout increases with age and is more prevalent in males has been formulated in accordance with a systematic than that in females, in cities than that in rural areas, and medical model by a task force including rheumatologists, in coastal than that in inland areas.[9] nephrologists, endocrinologists, cardiologists, neurologists, urologists, and experts in traditional Chinese medicine. It is the first multidisciplinary expert consensus on HUA and Address for correspondence: Prof. Chang‑Lin Mei, its related diseases in China and is aimed at promoting a Department of Nephrology, Shanghai Changzheng Hospital, The multidisciplinary collaboration and providing guidelines for Second Military Medical University, Shanghai 200433, China best clinical practices. E‑Mail: [email protected] Prof. Jun‑Bo Ge, Department of Cardiology, Zhongshan Hospital, Fudan University, DEFINITION OF HYPERURICEMIA Shanghai 200032, China E‑Mail: ge.junbo@zs‑hospital.sh.cn According to epidemiological data, HUA has previously Prof. He‑Jian Zou, been defined as a fasting serum urate level >420 μmol/L in Department of Rheumatology, Huashan Hospital, Fudan University, males and >360 μmol/L in females measured on two separate Shanghai 200040, China days after a normal purine diet. The saturation level of E‑Mail: [email protected] Prof. Xin Gao, urate is 420 μmol/L (regardless of sex) in blood, so greater Department of Endocrinology, Zhongshan Hospital, Fudan University, serum urate values can cause precipitation of urate crystals, Shanghai 200032, China thus resulting in their deposition in joint cavities and other E‑Mail: [email protected] tissues. Therefore, HUA is defined herein as a serum urate level >420 μmol/L (7 mg/dl). This article is based on a study first reported in the Chin J Intern Med 2017; 56: 235‑48. EPIDEMIOLOGY OF HYPERURICEMIA This is an open access article distributed under the terms of the Creative Commons The serum urate level is affected by age, sex, race, Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, heredity, food habits, drugs, environment, and other tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. Access this article online For reprints contact: [email protected] Quick Response Code: © 2017 Chinese Medical Journal ¦ Produced by Wolters Kluwer ‑ Medknow Website: www.cmj.org Received: 09‑07‑2017 Edited by: Qiang Shi How to cite this article: Multidisciplinary Expert Task Force on DOI: Hyperuricemia and Related Diseases. Chinese Multidisciplinary Expert 10.4103/0366‑6999.216416 Consensus on the Diagnosis and Treatment of Hyperuricemia and Related Diseases. Chin Med J 2017;130:2473‑88. Chinese Medical Journal ¦ October 20, 2017 ¦ Volume 130 ¦ Issue 20 2473 PATHOPHYSIOLOGY OF HYPERURICEMIA‑RELATED nephropathy, and kidney stones. Some authors consider only gouty arthritis to be gout. SYSTEMIC IMPAIRMENT The possibility of gout should be considered when a HUA Uric acid is produced in the liver from purine compounds, patient experiences an acute attack involving a red, tender, which may originate from dietary intake or from the hot, and swollen joint, usually the metatarsophalangeal breakdown of body cells [Supplementary Figure 1].[10] joint of the first toe, ankle, knee, and other joints. In chronic Approximately 2/3rd of all uric acid is excreted via the kidneys, recurrent attacks of gout, patients may manifest with and the rest is excreted through the digestive tract. Uric acid affection of the upper limb joints and the formation of tophi. undergoes glomerular filtration and renal proximal tubular According to the course of disease, gout is divided into four reabsorption, secretion, and postsecretion reabsorption. phases: (1) asymptomatic HUA, (2) acute attack of gouty The unabsorbed portions are excreted in the urine arthritis, (3) intercritical gouty arthritis, and (4) chronic [Supplementary Figure 2].[11,12] The production and excretion gouty arthritis.[27] of uric acid are balanced under normal circumstances, but factors that cause overproduction or underexcretion of uric Key points for gout diagnosis acid can lead to HUA [Supplementary Material 1].[10] 1. Gouty arthritis: This condition is more common in young and middle‑aged men. The initial onset of gouty When the serum urate level exceeds its saturation arthritis is often in the first metatarsophalangeal joint, concentration, the precipitated urate crystals directly attach ankle, midfoot, or knee. It develops abruptly and peaks to and deposit in joints and soft tissues around the joints, renal within 24 h. Usually, only one joint is initially affected. tubules, blood vessels, and other sites, thus resulting in the The initial attack may last for several days to several chemotaxis of neutrophils and macrophages. The interaction weeks and then resolve completely and spontaneously. between these cells and the crystals leads to the release of Recurrent attacks affect an increasing number of joints pro‑inflammatory factors (interleukin [IL]‑1β, IL‑6, etc.), and are associated with a longer duration of symptoms metalloproteinase 9, hydrolase, and other enzymes,[13‑15] and a shorter interval between episodes of arthritis which can cause acute and chronic inflammatory injuries 2. Tophi: Twenty years after the first onset of symptoms, of the articular cartilage, bone, kidney, vascular intima, and approximately 70% of untreated patients develop tophi, other tissues.[16] which are often found at the metatarsophalangeal joint The damage to multiple organs caused by HUA, involving of the first toe, the auricle, the extensor side of the the heart, brain, and kidneys, may be due to complex forearm, the finger joints, and the elbow. A tophus can mechanisms, such as increased generation of oxygen‑free be as small as a sesame seed or even larger than an egg. radicals, which damage vascular endothelial cells,[17‑21] and When a tophus is extruded, ulceration or fistula may be upregulation of endothelin and downregulation of nitric formed with a white bean curd‑like discharge oxide synthase expression, thus resulting in vasomotor 3. Synovial fluid examination: Through polarized light dysfunction. These phenomena lead to the oxidative microscopy, birefringent needle‑shaped sodium urate modification of low‑density lipoprotein cholesterol and crystals can be observed in symptomatic synovial fluid, subsequent atherosclerosis,[22] which damages mitochondria which is valuable for a definite diagnosis and lysosomes[23] and results in apoptosis of renal tubular 4. Type‑B ultrasonic scan: The typical intra‑articular epithelial cells and cardiomyocytes. In addition, the “snow storm sign” and “double‑contour sign” are renin–angiotensin–aldosterone system is activated, thereby valuable for diagnosis. Intra‑articular hyperechoic spots causing vascular remodeling and organ damage,[16,24] and and a mass with acoustic shadows are common images the inflammatory response is stimulated, thus resulting in indicative of tophi[28] platelet aggregation and adhesion.[25,26] 5. Dual‑energy computed tomography (DECT): This technique can reveal the specific distinction between tissues and periarticular urate crystals, which is useful DIAGNOSIS OF HYPERURICEMIA AND GOUT for diagnosis[29,30] Hyperuricemia 6. X‑ray: Swollen soft tissue can be observed in early A diagnosis of HUA is established when fasting serum urate acute arthritis. Recurrent attacks may destroy articular levels exceed 420 μmol/L after consumption of a normal cartilage edges, irregular articular surfaces, and daily diet on two separate days. Hematological malignancies, stenosis of the joint space on X‑ray films. Patients with chronic renal failure, congenital metabolic abnormalities, tophaceous deposits may have punched‑out osteolytic poisoning, some drugs, and other factors can elevate serum lesions with a sharp edge. The lesions appear as a urate level [Supplementary Materials 1 and 2]. HUA patients semicircle or continuous arc. Bone hyperplasia reactions younger than