Some cases of hyperuricemia are asymptomatic while others manifest particular symptoms. The typical presentation is gout, usually of a single joint, seen most often in the big toe. Other joints affected include the ankle and knee. High serum uric acid levels also result in nephrolithiasis. This presents with flank and groin pain, hematuria, nausea, and vomiting.

• Pain

  pain in ≥10 hand joints. [journals.plos.org]

  Low back pain was evaluated, keeping in view its duration and any associated radicular leg pain and joint pain of the lower limb. [imedpub.com]

  Subsequently, these crystals can lead to the development of other conditions, such as: Gout People with gout will experience sudden joint pain that can worsen over periods of 8–12 hours. [medicalnewstoday.com]

  This can make it easier and less painful to pass the stones. Additional techniques may be required. [healthline.com]

• Inflammation

  Patients with hyperuricemia had higher scores of interstitial inflammation, tubular atrophy, interstitial fibrosis, glomerulosclerosis as compared to those normouricemic patients (p < 0.05). [ncbi.nlm.nih.gov]

  European Journal of Rheumatology and Inflammation, 6(2), 149-54. Thomas AL, Majoos FL, Nuki G. Preliminary Studies With Azapropazone in Gout and Hyperuricaemia. Eur J Rheumatol Inflamm. 1983;6(2):149-54. PubMed PMID: 6673978. [wwww.unboundmedicine.com]

  Hyperuricemia Cell Purine Uric Acid SMC Proliferation Vasoconstriction Inflammation RAS COX-2 Hypertension Inflammation Renal disease progression Endothelial dysfunction and CVD Tissue hypoxia Cell death Insulin resistance 20. [slideshare.net]

  These will reduce inflammation and pain. Stronger medications include corticosteroids, such as prednisone, which also decreases inflammation. Colchicine is another medicine for treating inflammation with gout. [medicalnewstoday.com]

• Fishing

  Dietary Consumption of Omega-3 Polyunsaturated Fatty Acid May Reduce Recurrent Gout Flare Risk Dietary omega-3 polyunsaturated fatty acid-rich fish consumption, when adjusted for total purine intake, was associated with lower risk for recurrent gout flares [renalandurologynews.com]

  Risk Factors for Gout Several risk factors promote a high uric acid level and gout attacks: Increasing age and being male Intake of high-purine foods, including red meat, fish and shellfish Alcoholic beverage intake, specifically beer and spirits Diseases [lifeextension.com]

  Examples of high purine foods and drinks include: alcoholic drinks some types of fish or seafood, such as sardines shellfish, such as mussels some meats, such as bacon organ meats, such as liver and kidneys Other causes of hyperuricemia include errors [medicalnewstoday.com]

  Tomatoes Fruit Bread and cereal that are not whole-grain Butter, buttermilk, cheese, and eggs Chocolate and cocoa Coffee, tea, and carbonated beverages Peanut butter and nuts Low-fat or non-fat milk Low-fat yogurt Moderate uric acid producing foods Fish [belmarrahealth.com]

  Quit dairy meat eggs fish sugar refined oils coffee tea alcohol green tea. [wellcure.com]

• Hodgkin Lymphoma

  Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin’s lymphoma and acute lymphoblastic leukemia. [tjh.com.tr]

  "Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin's lymphoma and acute lymphoblastic leukemia / Non-Hodgkin lenfoma ve akut lenfoblastik losemili cocuklarda hiperurisemi ve tumor lizis sendromu." [go.gale.com]

  We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. [ncbi.nlm.nih.gov]

  Patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma, particularly Burkitt’s lymphoma, are at greatest risk because of the high sensitivity of the cells to chemotherapy. [link.springer.com]

• Abdominal Pain

  We describe an unusual case of a previously healthy infant with a 3 days' history of constipation, presenting acutely with abdominal pain, lethargy, and dehydration. [ncbi.nlm.nih.gov]

  abdominal pain or discomfort, bronchitis, pain in extremity, anemia and elevated liver enzymes. — Jen Christensen, CNN, "FDA approves non-statin drug to treat high cholesterol," 21 Feb. 2020 When intake of these foods exceeds the body’s ability to eliminate [merriam-webster.com]

  The adverse gastrointestinal effects include abdominal pain, diarrhea, and nausea, which occur in most patients started on colchicine. [emedicine.medscape.com]

• Erythema

  Classification Criteria a Criteria Categories Score Clinical Clinical Ankle or midfoot 1 Pattern of joint/bursa involvement during symptomatic episode(s) ever b Involvement of the first metatarsophalangeal joint 2 Characteristics of symptomatic episode(s) ever Erythema [arupconsult.com]

  Gouty tophi involving the proximal interphalangeal joint with erythema of the overlying skin. FIGURE 2. Gouty tophi involving the proximal interphalangeal joint with erythema of the overlying skin. [aafp.org]

  […] consumption References:[3][1][4][5][6][7][8] Pathophysiology Clinical features Acute gouty arthritis Triggers: anything that leads to hyperuricemia (see “Etiology” above) Arthritis: usually monoarticular during first attacks Acute severe pain with overlying erythema [amboss.com]

  Allopurinol, erythema multiforme, and renal insufficiency. BMJ. 1996; 312(7024): 173–174. Terkeltaub RA. Clinical practice. Gout. N Engl J Med. 2003; 349(17): 1647–1655. Luk AJ, Levin GP, Moore EE, et al. [journals.viamedica.pl]

  Gout is associated with the acute onset of pain and erythema in the big toe, forefoot, heel, knee, or other joints. [ncbi.nlm.nih.gov]

• Arthritis

  Learn about this topic in these articles: types of crystalloid arthritis In arthritis: Crystalloid arthritis …uric acid excretion, leading to hyperuricemia. [britannica.com]

  Of 777 participants, 52 (6.7%) had developed gouty arthritis. [ncbi.nlm.nih.gov]

  Acute gouty arthritis consists of painful episodes of inflammatory arthritis and represents the most common manifestation of gout. [themedicalbiochemistrypage.org]

  Various conditions can result in monoarticular arthritis, including infection, acute CPPD arthritis, other crystalline deposition disorders, atypical rheumatoid arthritis and palindromic rheumatism, other monoarticular arthritis, sarcoid arthritis, trauma [clevelandclinicmeded.com]

• Arthralgia

  The most frequently reported adverse effects are diarrhea, back pain, headaches, and arthralgias. Also, patients should be monitored for thromboembolic events and increased hepatic transaminases. [clevelandclinicmeded.com]

• Seizure

  Acute uric acid nephropathy has been described almost uniformly in patients with massive uric acid overload (malignancies with rapid cell destruction, epileptic seizures). Severe hyperuricosuria and intratubular uric acid precipitation result. [ncbi.nlm.nih.gov]

  Hyperuricaemic acute renal failure after epileptic seizures. Lancet 1975; II(7931): 385–7 CrossRef Google Scholar 96. Meisel AD, Diamond HS. Hyperuricosuria in the Fanconi syndrome. [link.springer.com]

The initial investigations carried out to confirm the diagnosis should include a complete blood count, urinalysis, blood urea, serum uric acid, as well 24-hour urine sample collection for determining uric acid levels. The next step of investigation involves assessing the type of hyperuricemia. For identifying primary hyperuricemia, various enzyme assays are conducted which include hypoxanthine-guanine phosphoribosyltransferase levels as well as glucose-6 phosphate dehydrogenase levels among others. Secondary hyperuricemia may be due to decreased excretion or excessive production. These two can be differentiated by assessing a 24-hour urine sample for uric acid without dietary restriction.

• Nephrolithiasis

  OUTCOME: The development of nephrolithiasis during follow-up. MEASUREMENTS: Nephrolithiasis is determined based on ultrasonographic findings. [ncbi.nlm.nih.gov]

Treatment for hyperuricemia involves the use of drugs which either inhibit xanthine oxidase and hence synthesis of uric acid, or drugs which accelerate uric acid excretion from the body [28]. Xanthine oxidase inhibitors include allopurinol as a first choice in the USA [17] and febuxostat; Uricosuric drugs include drugs like probenecid and benzbromarone [14] [18]. Another upcoming class of drugs includes those which degrade uricase and include rasburicase and pegloticase [14] [18].

Treatment for hyperuricemia is not advised when it is asymptomatic as it is likely to remain asymptomatic for years [28]. However, uric acid lowering treatment with allopurinol, an effective and economical option [28] [20], is indicated in patients who have had more than one episode of acute gout, all patients with chronic gout and tophi as well as patients with uric acid nephrolithiasis [28]. Other cases where allopurinol is indicated include the inherited enzyme deficiency disorders, such as Lesch-Nyhan Syndrome and Kelley-Seegmiller syndromes, as well as the uses for prophylaxis before chemotherapy for cancer [28].

FDA approved dose of allopurinol in patients with preserved renal function have been reinforced by EULAR guidelines [4] [25]. The starting dose is 100 mg daily which may be increased by another 100 mg over one to four weeks, in order to achieve a serum urate level of >6mg/dL [28] [21]. Uricosuric agents like probenecid are used as a last resort, despite their rapid mode of action [17], because of the need for frequent dosing, the 24-hour urine analysis prior to beginning therapy [28] and the increased likelihood of causing urolithiasis in people with acidic urine [19].

Patients should also be educated to modify their diet and lifestyle as adjunctive therapy; this includes avoiding red meat, shellfish and alcohol as well as incorporating exercise in one’s daily routine [28]. Uric acid levels must be maintained at 5-6 md/dL, as above this level uric acid solubility decreases and starts to deposit in the body [26].

Hyperuricemia is said to have a higher rate of morbidity in elderly people and women, as well as in those people who have hypertension [25]. Studies have shown that when hyperuricemia occurs with a chronic disease it usually has an increased mortality [13].

Hyperuricemia occurs due to overproduction, underexcretion or a combination of these two mechanisms [1]. Overproduction or ‘renal overload type’ [1] of uric acid occurs only in a minority of patients and may be due enzyme defects resulting in either increased de novo synthesis of purines or their increased breakdown [3]. According to a study, hyperuricemia in children was most often due to an attack of gastroenteritis, with upper respiratory tract infections and cardiac problems being the next most common causes [27]. Underexcretion of uric acid occurs in the majority of patients suffering from hyperuricemia and is involved in diabetic ketoacidosis, excessive intake of aspirin, diuretics (such as thiazides and loop-diuretics), antituberculous drugs (such as pyrazinamide and ethambutol) and cyclosporine A [6]. It is also the leading cause for hyperuricemia leading to gout [4].

Hyperuricemia occurring due to a combination of both overproduction and underexcretion of uric acid is seen mostly after alcohol consumption [22]. According to studies conducted in the United States, the progressive increase in obesity, hypertension, diabetes and kidney problems is associated with a concomitant increase in serum uric acid levels [2].

Although the upper limit of uric acid in children is 5mg/dL, the likelihood of developing hyperuricemia increases with age especially over 65 years. This is due to an increased prevalence of conditions associated with hyperuricemia such as hypertension, chronic kidney disease, metabolic syndrome, diabetes and cardiac diseases and increased intake of diuretics and aspirin in this age range [14] [15] [16]. It has also been noted that hyperuricemia occurs more often in men than in women, and according to a survey the men to women ratio is between 7:1 and 9:1 [12]. However, the incidence is higher is post-menopausal women [23].

According to research, the levels of serum uric acid depend on many genes. It is seen more often in African Americans, due to a higher rate of obesity, renal disease and hypertension [11], in Maoris, Samoans and Filipinos, due to their genetic makeup and dietary factors such as increased intake of seafood [10], and in certain native races of the Pacific, due to a lower rate of uric acid excretion [24].

Hyperuricemia is classified into three types: overproduction, underexcretion and mixed type. The overproduction type of hyperuricemia is seen in conditions like Lesch-Nyhan Syndrome, where there is deficiency of the hypoxanthine guanine phosphoribosyl transferase enzyme because of a deficiency of the HPRT gene, intake of purine rich foods, and after cytolysis occurring due to chemotherapy in leukemias [29]. It also occurs after ingestion of purine rich foods such as red meat and seafood [7] [8]. Research has shown that fructose particularly increases serum uric acid levels by accelerating the metabolism of nucleotides containing adenine. This has been further proved by a study showing that serum uric acid levels were found to be 35% higher six hours after ingestion of five apples [9].

The underexcretion type of hyperuricemia occurs in familial juvenile hyperuricemic nephropathy due to abnormality of the uromodulin gene sudden weight loss; with the mixed type is seen in cases of deficiency of glucose 6-phosphatase enzyme as a result of a defective glucose 6-phosphatase gene and increased intake of alcohol [29]. Hyperuricemia is usually seen in patients suffering from the metabolic syndrome. In fact, studies are now showing that hyperuricemia itself may be a risk factor for cardiovascular disease [5]. The transporters found to be associated with urate transport include URAT1, a urate/anion exchanger, hOAT1, a human organic anion transporter and UAT, another urate transporter. Studies have found that variants of the gene SLC2A9 are strongly associated with uric acid transport [26]. Humans and other primates excrete uric acid as the end product of purine metabolism because they lack the enzyme uricase, which in other animals breaks down uric acid to a more soluble product: allantoin [28].

The best method to prevent hyperuricemia is to modify the diet so that it includes less quantities of foods contributing to a high serum uric acid level like red meat, seafood, beans and peas, and more quantities of foods which tend to lower uric acid levels. The latter includes eggs, cheese and starches, to name a few. Regular exercise, weight reduction, keeping blood pressure under control and drinking plenty of water daily also help prevent the development of hyperuricemia.

Hyperuricemia is the presence of excessive uric acid in the body. The normal level of uric acid in adult females is 360 µmol/L or 6 mg/dL and in adult males it is 400 µmol/L or 6.8 mg/dL. Uric acid is the byproduct of protein metabolism and is also produced as a result of cell turnover. Most of the uric acid is eliminated from the body via the urine and the rest via the gastrointestinal system. Excessive production or defective excretion may result in high serum uric acid levels.

Hyperuricemia is a condition in which the levels of uric acid in the blood rise above the normal limit. This increase may be silent or may start causing problems like gout or renal stones. There are many etiological factors that can be responsible for the development of hyperuricemia, such as genetic, dietary, renal diseases or simply the taking certain drugs. The treatment depends upon whether the hyperuricemia is silent or manifested. In case there are signs and symptoms of high serum uric acid such as tophaceous gout or kidney stones, then appropriate treatment should be sought so as to keep the uric acid within normal limits. The long term outcome depends on the reason behind the raised uric acid levels and how well it is treated and followed-up.

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