[Full Text]. Gout: new insights into an old disease. Advances in early diagnosis and the availability of definitive treatment have significantly improved the prognosis of gout, as evidenced by the declining incidence of disabling chronic tophaceous gout. Gout (see the image below) is caused by monosodium urate monohydrate crystals; pseudogout is caused by calcium pyrophosphate crystals and is more accurately termed calcium pyrophosphate disease. Nicole Davey-Ranasinghe, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of RheumatologyDisclosure: Nothing to disclose. KOSKOFF YD, MORRIS LE, LUBIC LG. Unusual localisation of tophaceous gout. H&E stain, high power, showing that most urate crystals have been dissolved but that some pale brown-gray crystals did survive processing. 2004 Jul. Merriman TR. Medscape Medical News. [Medline]. Loffler C, Sattler H, Peters L, Loffler U, Uppenkamp M, Bergner R. Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides. Rev Med Chir Soc Med Nat Iasi. Arthritis Rheum. Nucleosides Nucleotides Nucleic Acids. 2008 Feb 9. 2017 Sep. 55 (5):967-984. Slansky HH, Kubara T. Intranuclear urate crystals in corneal epithelium. In men, uric acid levels rise at puberty, and the peak age of onset of gout in men is in the fourth to sixth decade of life. [48] Estimates for the number of US adults with self-reported gout in the previous year rose from 2.1 million in 1995 to 3 million in 2008. 1972 Jul-Aug. 15(4):381-90. 1980 Aug. 10(1):1-9. Wold A, Petscavage-Thomas J, Walker EA. McCarty DJ. [27, 28], The heritability of serum urate levels is estimated at 63%. [Full Text]. Cyclosporine-induced hyperuricemia and gout. [57] The higher prevalence of gout in elderly persons may also reflect an increased prevalence of metabolic syndrome, high rates of diuretic treatment for hypertension and chronic heart failure, and the use of low-dose aspirin. Rho YH, Zhu Y, Zhang Y, Reginato AM, Choi HK. 2018 Oct 1. [Medline]. 1991 Feb. 30(1):10-5. [Full Text]. Nagase M, Baker DG, Schumacher HR Jr. Immunoglobulin G coating on crystals and ceramics enhances polymorphonuclear cell superoxide production: correlation with immunoglobulin G adsorbed. Available at http://www.medscape.com/viewarticle/745076. During the first 6-24 months of urate-lowering therapy, acute attacks of gout often occur more frequently. Lowry F. FDA Panel Says No to Canakinumab for Gout Attacks. Singh JA, Reddy SG, Kundukulam J. J Hand Surg [Br]. [Medline]. The crystals parallel to the compensator were blue, while those perpendicular to the compensator were yellow. Acute polyarticular gout presenting as delirium. [Medline]. Available at http://www.medscape.com/viewarticle/869613. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. ... Gout Although roentgen alterations may accompany the initial bouts of gouty arthritis, the roentgenographic evaluation of most patients with clinical evidence of gout spanning many years will show no important changes. Rheumatology (Oxford). Available at https://wayback.archive-it.org/7993/20170113075756/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm116853.htm. Am J Hum Genet. 2011 Jan 17. [Medline]. Many cases of pseudogout in elderly people are idiopathic, but pseudogout has also been associated with trauma and with many different metabolic abnormalities, the most common of which are hyperparathyroidism and hemochromatosis. Rheumatology (Oxford). February 21, 2019; Accessed: February 24, 2019. Markel A. Allopurinol-induced DRESS syndrome. A few have impaired intestinal elimination of uric acid. Meyers OL, Monteagudo FS. [Medline]. A systematic literature review and a meta-analysis. Singh H, Torralba KD. Primary gout is related to underexcretion or overproduction of uric acid, often associated with a mix of dietary excesses or alcohol overuse and metabolic syndrome. [Medline]. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study. [43, 44]. 2012 Jan 19. PLoS Genet. Changes in the cartilage matrix may play an important role in promoting CPPD deposition. Gout. [Medline]. Joint pain can have multiple causes, a reflection of the diverse joint diseases, which arise from inflammation, cartilage degeneration, crystal deposition, infection, and trauma. Isr Med Assoc J. Lioté F, Ea HK. [7, 8] The mutations were in the genes ANKH and COL, which may be involved in crystal-induced inflammation. Crystals parallel to the compensator are blue, while those perpendicular to the compensator are yellow. Ann Intern Med. Edwards NL. Calcium pyrophosphate dihydrate crystal deposition. What stops a gouty attack?. About East La Paz Family Medical Clinic. [Medline]. Stocker SL, Graham GG, McLachlan AJ, Williams KM, Day RO. [56] In women, uric acid levels rise at menopause, and peak age of onset is in the sixth to eighth decade of life. [Medline]. Radiograph of the wrist and hand showing chondrocalcinosis of the articular disc of the wrist and atypical osteoarthritis involving the metacarpophalangeal joints in a patient with underlying hemochromatosis. 1977 Nov. 7(2):97-113. For patient education information, see Arthritis and Pseudogout. Pascual E. The diagnosis of gout and CPPD crystal arthropathy. Cipolletta E, Di Matteo A, Scanu A, Isidori M, Di Battista J, Punzi L, et al. Arch Intern Med. 2019 Dec 1. [Medline]. Vázquez-Mellado J, Morales EM, Pacheco-Tena C, et al. [Medline]. Arthritis Rheum. February 6, 2008; Accessed: March 15, 2018. Rare hereditary forms of CPDD occur, generally inherited in an autosomal dominant mode. [Medline]. Unlike these other diseases, however, the symptoms of CPPD crystal deposition disease are caused by tiny CPPD crystals. Martinon F, Glimcher LH. Arthritis Care Res (Hoboken). Efficacy of anakinra in calcium pyrophosphate crystal-induced arthritis: a report of 16 cases and review of the literature. [Medline]. Arthritis Rheum. Its relation to hyperglycaemia and obesity. Agents used include the following: Because these agents change serum and tissue uric acid levels, they may precipitate acute attacks of gout. 38(5):628-32. 2017 May. 321(5):287-92. Joint Bone Spine . 2006 Apr. [17, 18] Neutrophil phagocytosis leads to another burst of inflammatory mediator production. Accessed: November 4, 2013. [Full Text]. Merola JF, Wu S, Han J, Choi HK, Qureshi AA. Consider gout in patients with risk factors, regardless of age. Tendon involvement in patients with gout: an ultrasound study of prevalence. Febuxostat. Cyclosporine A can cause an accelerated form of gout, even in premenopausal women, that can present after only a few years of hyperuricemia, particularly if the patient is also receiving diuretics. For example, the frequency of gout is higher in populations such as the Chamorros and Maori and in the Blackfoot and Pima tribes. View This Abstract Online; Crystal deposition disease. A literature review of the epidemiology and treatment of acute gout. Osteoarthritis Cartilage. 2020 Apr 28. Anne V Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, International Society for Clinical DensitometryDisclosure: Nothing to disclose. Dual-Energy Computed Tomography Demonstrating Destructive Calcium Pyrophosphate Deposition Disease of the Distal Radioulnar Joint Mimicking Tophaceous Gout. 226-9. The ANKH protein is involved in transport of inorganic pyrophosphate (PPi), which regulates calcification, bone mineralization, and bone resorption. Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al. Medscape [serial online]. Marchini GS, Sarkissian C, Tian D, Gebreselassie S, Monga M. Gout, stone composition and urinary stone risk: a matched case comparative study. [Medline]. Share cases and questions with Physicians on Medscape consult. [8] (See Treatment. Gout. Perez-Ruiz F, Herrero-Beites AM, Carmona L. A two-stage approach to the treatment of hyperuricemia in gout: The "Dirty Dish" hypothesis. [Medline]. [Medline]. [77]. Chronic tophaceous gout in untreated patient with end-stage renal disease. Corominas H, Badlissi F, Shmerling RH. Tophaceous gout and rheumatoid arthritis awareness. 329958-overview [Medline]. Cartilage calcification of the ankle joint is associated with osteoarthritis in the general population. Am J Kidney Dis. October 3, 2016; Accessed: October 6, 2016. This video describes the pathophysiology, causes, symptoms, and treatment of gout. 9(3):243-50. Ann Intern Med. Recent developments in crystal-induced inflammation pathogenesis and management. [50], In the United Kingdom from 2000 to 2007, the incidence of gout was 2.68 per 1000 person-years—4.42 in men and 1.32 in women, and increasing with advancing age. [Medline]. Arthritis Care Res (Hoboken). Pseudogout has been recognized as having an underlying genetic component; however, comorbid conditions (such as osteoarthritis) and environmental factors are thought to play a much stronger role. Can drugs trigger CPPD acute attacks?. Rheumatology (Oxford). [Medline]. Available at http://www.medscape.com/viewarticle/830663?nlid=64464_2224&src=wnl_edit_medp_rheu&spon=27. The reason for this is unknown. 17(1):79-83. Atlanta, Ga: Arthritis Foundation; 1997. [Medline]. Treatment of the acute phase of pseudogout follows the same approaches as are used in gout, and colchicine is effective for prophylaxis. Ann Rheum Dis. [Medline]. CPDD usually occurs in individuals who are in the fifth decade of life or older, with increasing prevalence as age increases. 191 (39):E1070-E1077. 45 (7):1007-12. Boumans D, Hettema ME, Vonkeman HE, Maatman RG, van de Laar MA. [Medline]. [72, 73], Risk for vascular disease is increased in patients with gout, particularly women, according to a retrospective cohort study from the United Kingdom that included 8386 patients with gout and 39,766 matched controls. [10]. Ann Rheum Dis. Lower right image depicts synovium. 62(4):1060-8. Anne V Miller, MD Chief, Rheumatology Division; Assistant Professor of Internal Medicine, Department of Medicine, Division of Rheumatology, Southern Illinois University School of Medicine Deposition of these crystals is most commonly reported in synovium, bone, skin, cartilage, tendon, ligament, and kidney, but involvement of a range of other musculoskeletal and non-musculoskeletal tissues also occurs. Genetic factors associated with gout and hyperuricemia. 6(3):221-7. A retrospective analysis of a large cohort. Medscape Medical News. 2012 Nov. 51(11):2070-4. Right images depict anterior cruciate ligament. 19(4):221-2. Gout. Please confirm that you would like to log out of Medscape. Gout is an inflammatory disease where uric acid precipitates into crystals that deposit in various joints around the body, causing pain and inflammation. Slideshow, encoded search term (Calcium Pyrophosphate Deposition Disease) and Calcium Pyrophosphate Deposition Disease, Trending Clinical Topics for October 2018. 59(11):1540-8. Gout is one of the oldest diseases in the medical literature, Curr Opin Rheumatol. J Rheumatol. Arthritis Rheum. [Medline]. [Medline]. Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C, RDEA594-203 Study Group. [Medline]. J Rheumatol. 1991 Apr. [34, 35] A study of 514 male twin pairs did show a strong concordance in hyperuricemia among monozygotic (MZ) twins (53%) as compared with dizygotic (DZ) twins (24%), but it did not show a significant difference between MZ and DZ twins with regard to the lifetime prevalence of gout. Secondary gout is related to medications or conditions that cause hyperuricemia, such as the following 2008 Jul 15. Zurampic (lesinurad) [package insert]. However, onset may occur in men in their early 20s who have a genetic predisposition and lifestyle risk factors. The knee joint is most commonly affected. 2012 Aug 20. 2016 Jun 23. Among individuals with hyperuricemia, the HR of all-cause mortality was 1.07 and the adjusted HR of cardiovascular mortality was 1.08. 2011 Mar. 2008;58:S878. [Full Text]. US Food and Drug Administration. 2016 Aug 7. [Guideline] Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. The prevalence varies widely from country to country. Gout in Maoris. 2014 Aug 27. Rheumatol Int. [Medline]. Ahuja and colleagues described the association of concomitant septic arthritis with crystal arthropathy in a large case series. J Clin Rheumatol. She works in Orange, CA and 3 other locations and specializes in Internal Medicine/Pediatrics and Pediatrics. Rose BS. The light-retarding (phase-shifting) characteristics of urate crystals allow them to be recognized by polarizing microscopy (see the image below). Gout. H&E stain, high power, under polarized light to highlight rhomboidal crystals. [Medline]. 2012 Jan. 71(1):157-8. Am Fam Physician. 2016 Aug. 35 (8):2039-44. Gout is caused by monosodium urate monohydrate crystals; pseudogout is caused by calcium pyrophosphate (CPP) crystals and is more accurately termed calcium pyrophosphate disease (CPPD). 2008 Sep. 58(9):2587-90. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Differentiation of crystal arthropathy from septic arthritis is the primary aim of the diagnostic workup process. Pseudogout is a form of arthritis that causes pain, stiffness, tenderness, redness, warmth, and swelling in some joints. Ann Rheum Dis. Ryan LM. 2007. Sundy JS, Baraf HS, Yood RA, et al. Ann Rheum Dis. Calcium pyrophosphate deposition disease (CPDD) is a metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate in and around joints, especially in articular cartilage and fibrocartilage. 2010 Jan. 49(1):141-6. [Full Text]. Arthritis Care Res (Hoboken). The inorganic pyrophosphate is produced in large part by ectonucleotide phosphodiesterase pyrophosphatase (ENPP1), a catalytic enzyme found in chondrocytes of cartilage, and the pyrophosphate is exported potently by the membrane transporter ANKH. Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle. Ann Rheum Dis. [Medline]. Akahoshi T, Murakami Y, Kitasato H. Recent advances in crystal-induced acute inflammation. Forman JP, Choi H, Curhan GC. Calcium pyrophosphate deposition disease (CPPD) is a type of crystal arthropathy which affects middle-aged and old populations. 336(7639):309-12. J Rheumatol. Untreated chronic tophaceous gout can lead to severe joint destruction and, rarely, renal impairment. [Medline]. White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, et al. Gout. Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Kim KY, Ralph Schumacher H, Hunsche E, Wertheimer AI, Kong SX. Chehab MR, Goyal J, Schlesinger N. Tophaceous Pustule-like Rash in a Patient with Gout. Gout develops in the setting of excessive stores of uric acid in the form of monosodium urate. Geriatrics. [Medline]. Arthritis Rheum. Crystal Arthropathy (Crystal Arthropathies): Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis. Prevalence and Natural Course of Transverse Ligament of the Atlas Calcification in Asymptomatic Healthy Individuals. JAMA. It is defined by the presence of a distinctive type of crystal: calcium pyrophosphate dihydrate (CPPD). [Medline]. 2011 Apr. Ultrasound detection of cartilage calcification at knee level in calcium pyrophosphate deposition disease. A focus on the dorsal scapho-lunate ligament. Gout: an independent risk factor for all-cause and cardiovascular mortality. [Medline]. Terkeltaub RA. Filippou G, Adinolfi A, Cimmino MA, Scirè CA, Carta S, Lorenzini S, et al. 13(2):124-30. 2008 Dec 6. Arthritis Rheum. 168(10):1104-10. [Medline]. [Medline]. Semin Arthritis Rheum. 2020 Jun. [11, 12, 13]. FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat). 2005 Oct. 7(10):656-60. Ann Rheum Dis. Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. [Medline]. [Medline]. Available at [Full Text]. [emedicine.medscape.com] Soft Tissue Mass. Calcium pyrophosphate dihydrate crystal arthropathy (CPPA) is a well known but heterogeneous disease with a variable presentation and course. 2011 May. 23(2):192-202. Elevated risk has been reportd with recombinant zoster vaccine and other vaccine, but not influenza vaccine. 2004 Oct. 29(5):486-93. [Medline]. Treatment of symptomatic CPDD is important to prevent further end-organ damage, but it cannot reverse the joint disease. Lancet. 2018 Feb. 77 (2):270-276. 1986 Jun. Arthritis Res Ther. [76], Similarly, Solomon and colleagues reported a reduced risk of a CV event in patients with gout who take colchicine. [Full Text]. Skeletal Radiol. Symptoms of gout or pseudogout include the following: Podagra (initial joint manifestation in 50% of gout cases and eventually involved in 90%; also observed in patients with pseudogout and other conditions), Arthritis in other sites – In gout, the instep, ankle, wrist, finger joints, and knee; in pseudogout, large joints (eg, the knee, wrist, elbow, or ankle), Monoarticular involvement most commonly, though polyarticular acute flares are not rare, and many different joints may be involved simultaneously or in rapid succession, In gout, attacks that begin abruptly and typically reach maximum intensity within 8-12 hours; in pseudogout, attacks resembling those of acute gout or a more insidious onset that occurs over several days, Without treatment, symptom patterns that change over time; attacks can become more polyarticular, involve more proximal and upper-extremity joints, occur more often, and last longer, In some cases, eventual development of chronic polyarticular arthritis that can resemble rheumatoid arthritis. Gout has an increased prevalence in some populations but is rare in others. October 01, 2019. [Medline]. Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta KappaDisclosure: Nothing to disclose. A genetic predisposition exists for pseudogout. 2017 Sep 28. Semin Arthritis Rheum. Filippou G, Adinolfi A, Iagnocco A, Filippucci E, Cimmino MA, Bertoldi I, et al. Anecdotal evidence links hyaluronic acid and granulocyte colony-stimulating factor as risk factors. Naredo E, Uson J, Jiménez-Palop M, Martínez A, Vicente E, Brito E, et al. Joint Bone Spine. [Medline]. Medscape Medical News. Genetically high plasma vitamin C and urate: a Mendelian randomization study in 106 147 individuals from the general population. Agents used in this setting include the following: Therapy to control the underlying hyperuricemia generally is contraindicated until the acute attack is controlled (unless kidneys are at risk because of an unusually heavy uric acid load). [Medline]. 2010 Jan 23. 34(6):1381-5. The gout patient in general practice. Nguyen C, Ea HK, Palazzo E, Lioté F. Tophaceous gout: an unusual cause of multiple fractures. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from acutely inflamed joint. [Medline]. Urate crystals can form in people who have high levels of uric acid in the blood. [Medline]. [Medline]. [Medline]. Hall AP, Barry PE, Dawber TR, McNamara PM. Magnetic resonance imaging in rheumatic disorders of the spine and sacroiliac joints. Fast Five Quiz: Are You Prepared to Confront Gout? 46 (7):748-750. 200 (5):1802-1816. The radiographic hallmark of CPPD is the presence of chondrocalcinosis and secondary osteoarthritic changes. 2006. ms crystal harmonyhow to ms crystal harmony for Lacks S, Jacobs RP. Wilmington, DE: AstraZeneca Pharmaceuticals. [3, 4, 5] If untreated, these disorders can lead to joint destruction and, in the case of uric acid crystals, renal damage. Symptoms of gout or pseudogout include the following: 1. Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital The genetics of hyperuricaemia and gout. Risk of gout flares after vaccination. 353(23):2450-61. A total of 440 patients with septic arthritis were identified; in 40 of these patients crystals were also seen on synovial fluid analysis. Gout. [10] A genetic predisposition for hyperuricemia exists; except in rare genetic disorders, however, the development of gout in hyperuricemic individuals appears to be mediated by environmental factors. Mod Rheumatol. The degree of asymptomatic hyperuricemia and the risk of gout. Although gout is associated with hyperuricemia, gout attacks are triggered not by a particular level of uric acid but typically by acute changes in the level of uric acid. Park YK centrifugation for monosodium urate crystals in corneal epithelium you Prepared to Confront gout? Williams,! In this gene have been noted to occur more frequently in the treatment of the ankle joint is associated allopurinol! Of Eastern China elevated risk has been reportd with recombinant zoster vaccine other... Features of crystal deposition diseases puig JG, Michan AD, Carotti M, Khanna,!, while those perpendicular to the compensator ] genome-wide association study reduced risk of gout! 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