Table of ContentsView AllTable of ContentsTypes of CrystalsCausesSymptoms and ComplicationsDiagnosisTreatment
Table of ContentsView All
View All
Table of Contents
Types of Crystals
Causes
Symptoms and Complications
Diagnosis
Treatment
Both diseases have variable manifestations, ranging from asymptomatic disease to severe debilitating illness. Regardless, the diseases are treatable, but the specific approach will vary from person to person.
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Monosodium Urate Crystals
Monosodium urate crystals come fromuric acid, a substance that occurs naturally in the blood as a result of the metabolism of purines.
Diet and alcohol intake can affect serum uric acid levels as well. For example, meat and seafood are rich in purines, and overconsumption of these foods is associated with gout.
Foods to Eat and Avoid With Gout
Calcium Pyrophosphate Dihydrate (CPPD) Crystals
Calcium pyrophosphate dihydrate crystals, the cause of pseudogout, arise from joint cartilage. Cartilage cells (chondrocytes) naturally produce a substance called pyrophosphate. For reasons not completely understood, pyrophosphate levels may increase in cartilage, leading to the formation of CPPD crystals.
The two types of crystals are not mutually exclusive, and 5% of patients with gout also have CPPD crystals in their joints.
Pseudogout vs. Gout: What’s the Difference?
Elevated levels of uric acid in the blood must be present for the formation of monosodium urate crystals in gout to occur. Uric acid is primarily produced in the liver, as purines synthesized in the body and ingested from food are processed. Most uric acid is excreted through the urine and gut.
Diet can affect uric acid levels in the blood. Gout has historically been called the “disease of kings” because of its association with obesity and the consumption of rich foods. Although food habits and other lifestyle factors have a definite effect, your genes likely have a more important impact on the levels of uric acid in your blood.
Symptoms of Gout
Calcium Pyrophosphate Dihydrate Crystals
The causes of CPPD crystal formation in the joints are less well understood. Crystal formation in the joints may be inherited (familialchondrocalcinosis). Also, joint trauma and certain metabolic conditions may be associated with the development of pseudogout. For example,hemochromatosisandhyperparathyroidismmay be associated with the disease, as are some rare genetic disorders.
Gout
Gout is variable in its manifestations, and may affect different joints and the kidneys. Broadly, gout may cause acute or chronic inflammation of the joints, accumulation of urate crystals in soft tissues (tophi), kidney stones, or chronic kidney disease. Patients may also have more general symptoms like fever or malaise.
They usually resolve within days or weeks, and patients in between acute episodes may be completely asymptomatic. Eventually, attacks may occur more often, last longer, and do not resolve completely between episodes. This may lead to chronic gout disease, which can cause long-term joint damage.
Pseudogout
CPPD disease can also vary widely in its presentation. Patients may be asymptomatic. Symptomatic patients may have acute or chronic disease. CPPD disease attacks larger joints more commonly than gout.
Acute CPPD disease attacks may affect one or several joints. Joint injury, surgery, or severe illness may precede an attack. The knee is commonly affected, though the disease can also involve the wrists, shoulders, ankles, feet, and elbows.
Patients commonly experience pain, redness, warmth, and decreased function of the affected joint. The illness usually goes away on its own, though it may take days or weeks to do so.
Chronic CPPD disease may mimic other forms of arthritis. Symptoms may coexist with those of degenerativeosteoarthritis, which causes progressive joint degeneration.
Chronic CPPD disease may also imitaterheumatoid arthritis(RA) and present with symptoms normally associated with RA, including morning stiffness, fatigue, and restricted joint motion. This type of CPPD disease may affect multiple joints of the arms and legs, and the inflammation may wax and wane over several months.
People at higher risk of pseudogout include those with hemochromatosis (storing too much iron), low magnesium, overactive parathyroid gland, or high blood calcium.
Gout vs. Rheumatoid Arthritis: What Are the Differences?
If an acute gout attack is suspected, a physician will use your history, physical exam results, lab findings, and X-rays to support the diagnosis. Yourbloodmay be checked to determine if you havehigh levels of uric acid. Definitive diagnosis is based on the identification of monosodium urate crystals in an affected joint, especially if this is the first episode of arthritis.
If crystals in joint fluid cannot be established, your healthcare provider may still be able to make a diagnosis of gout based on your history, X-rays, and physical exam findings.
Patients with uric acid kidney stones may present with symptoms such as flank pain or blood in the urine. If kidney stones are suspected, your practitioner may order aCT scan, which can identify the presence, number, and location of kidney stones.
Once the presence of stones is established, your medical professional must determine the chemical composition of the stones to guide treatment. The best way to do this is to analyze stones that have already been passed. Tests of urine uric acid levels and acidity (pH) may be evaluated to further guide treatment.
Like gout, the diagnosis of CPPD disease ultimately rests on the identification of CPPD crystals in joint fluid.
Under polarized light microscopy, CPPD crystals appear blue, a property called positive birefringence. This distinguishes them from the negatively birefringent crystals of gout. SPECT CT and musculoskeletal ultrasound are also used.
If crystal analysis is not available, the diagnosis of CPPD disease may be strongly suspected based on your history and X-ray findings. Your healthcare provider may suspect that you have CPPD disease if you have acute arthritis of large joints, especially of the knees.
CPPD disease is more common in patients over 65, and may mimic osteoarthritis or rheumatoid arthritis.
The treatment of acute gout focuses on reducing pain and inflammation. This can be achieved withnonsteroidal anti-inflammatory agents(NSAIDs),steroid medications, orcolchicine.
All three types of medications can be given orally, and the choice of drug depends on patient tolerance of the drug and whether there are any coexisting diseases that preclude the use of a specific drug. Treatment should be started within 24 hours of the onset of symptoms.
In chronic gout, treatment focuses on lowering uric acid levels to prevent acute attacks. There are two main ways to do this: give drugs that lower uric acid production (allopurinol, febuxostat), or give drugs that increase urine excretion of uric acid (probenecid).
Another drug, pegloticase, actively breaks down uric acid, and can be used when other uric acid-lowering therapies are not effective.
The decision of whether to start uric acid-lowering therapy should be individualized and depends on how often a person has attacks, how high their uric acid level is, and whether tophi are present.
Although uric acid-lowering therapy prevents gout attacks in the long term, they can actually bring about or worsen an acute attack when they are first started. For that reason, these drugs are not started during an acute flare. Anti-inflammatory medications may be given when starting uric acid-lowering therapy.
Once started, therapy with uric acid-lowering medications is usually lifelong, so adhering to the medications is important. Since diet and lifestyle can affect uric acid levels, your healthcare provider may prescribe a healthy diet and avoidance of certain foods and alcohol.
How Gout Is Treated
The treatment of pseudogout aims mostly to relieve symptoms. As with gout, anti-inflammatory medications such as NSAIDs, steroids, or colchicine may be used to treat acute episodes.
If only one joint is affected, healthcare providers may try draining the fluid from the joint (arthrocentesis) and injecting steroids directly into the joint, which can rapidly relieve joint pain and inflammation. Patients with frequent CPPD attacks may be prescribed low-dose colchicine to reduce the number of episodes.
A Word From Verywell
Crystal-induced arthropathies like gout and CPPD disease can be painful and debilitating. Fortunately, a variety of treatment options exist, and the diseases can usually be managed effectively with medications.
Treatment is individualized and depends on the severity of your disease, as well as the presence of any coexisting diseases. Talk to your healthcare provider about the treatment strategy that makes the most sense for you.
5 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Elfishawi MM, Zleik N, Kvrgic Z, et al.The rising incidence of gout and the increasing burden of comorbidities: a population-based study over 20 years.J Rheumatol. 2018;45(4):574-579. doi:10.3899/jrheum.170806Harvard Health Publishing.Pseudogout (CPPD).Major TJ, Topless RK, Dalbeth N, Merriman TR.Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.BMJ. 2018 Oct 10;363:k3951. doi:10.1136/bmj.k3951American Academy of Family Physicians.Pseudogout.Sundy JS, Baraf HS, Yood RA, et al.Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.JAMA. 2011;306(7):711-720. doi:10.1001/jama.2011.1169Additional ReadingAlvarellos A, Spilberg I.Colchicine prophylaxis in pseudogout.J Rheumatol. 1986;13(4):804-805.Cleveland Clinic Center for Continuing Education.Gout and calcium pyrophosphate deposition disease.Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF.The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.Arthritis Rheum. 1987;30(8):914-918. doi:10.1002/art.1780300811Jones AC, Chuck AJ, Arie EA, Green DJ, Doherty M.Diseases associated with calcium pyrophosphate deposition disease.Semin Arthritis Rheum. 1992;22(3):188-202. doi:10.1016/0049-0172(92)90019-aLawrence RC, Felson DT, Helmick CG, et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.Arthritis Rheum. 2008;58(1):26-35. doi:10.1002/art.23176Masuda I, Ishikawa K, Usuku G.A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease.Clin Orthop Relat Res. 1991 Feb;(263):272-287.Neame RL, Carr AJ, Muir K, Doherty M.UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.Ann Rheum Dis. 2003;62(6):513-518. doi:10.1136/ard.62.6.513Reginato AJ, Schumacher HR, Martinez VA.The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study.Arthritis Rheum. 1974;17(6):977-992. doi:10.1002/art.1780170611Roddy E, Doherty M.Gout. Epidemiology of gout.Arthritis Res Ther.2010;12:223. doi:10.1186/ar3199UpToDate,Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Updated December 16, 2020.UpToDate.Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Updated July 9, 2020.UpToDate.Clinical manifestations and diagnosis of gout. Updated December 1, 2019.UpToDate.Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease. Updated January 23, 2020.UpToDate.Treatment of calcium pyrophosphate crystal deposition (CPPD) disease. Updated August 28, 2020.UpToDate.Urate balance. Updated September 26, 2019.UpToDate.Kidney stones in adults: uric acid nephrolithiasis. Updated August 9, 2018.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. 2011;63(10):3136-3141. doi:10.1002/art.30520
5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Elfishawi MM, Zleik N, Kvrgic Z, et al.The rising incidence of gout and the increasing burden of comorbidities: a population-based study over 20 years.J Rheumatol. 2018;45(4):574-579. doi:10.3899/jrheum.170806Harvard Health Publishing.Pseudogout (CPPD).Major TJ, Topless RK, Dalbeth N, Merriman TR.Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.BMJ. 2018 Oct 10;363:k3951. doi:10.1136/bmj.k3951American Academy of Family Physicians.Pseudogout.Sundy JS, Baraf HS, Yood RA, et al.Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.JAMA. 2011;306(7):711-720. doi:10.1001/jama.2011.1169Additional ReadingAlvarellos A, Spilberg I.Colchicine prophylaxis in pseudogout.J Rheumatol. 1986;13(4):804-805.Cleveland Clinic Center for Continuing Education.Gout and calcium pyrophosphate deposition disease.Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF.The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.Arthritis Rheum. 1987;30(8):914-918. doi:10.1002/art.1780300811Jones AC, Chuck AJ, Arie EA, Green DJ, Doherty M.Diseases associated with calcium pyrophosphate deposition disease.Semin Arthritis Rheum. 1992;22(3):188-202. doi:10.1016/0049-0172(92)90019-aLawrence RC, Felson DT, Helmick CG, et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.Arthritis Rheum. 2008;58(1):26-35. doi:10.1002/art.23176Masuda I, Ishikawa K, Usuku G.A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease.Clin Orthop Relat Res. 1991 Feb;(263):272-287.Neame RL, Carr AJ, Muir K, Doherty M.UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.Ann Rheum Dis. 2003;62(6):513-518. doi:10.1136/ard.62.6.513Reginato AJ, Schumacher HR, Martinez VA.The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study.Arthritis Rheum. 1974;17(6):977-992. doi:10.1002/art.1780170611Roddy E, Doherty M.Gout. Epidemiology of gout.Arthritis Res Ther.2010;12:223. doi:10.1186/ar3199UpToDate,Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Updated December 16, 2020.UpToDate.Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Updated July 9, 2020.UpToDate.Clinical manifestations and diagnosis of gout. Updated December 1, 2019.UpToDate.Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease. Updated January 23, 2020.UpToDate.Treatment of calcium pyrophosphate crystal deposition (CPPD) disease. Updated August 28, 2020.UpToDate.Urate balance. Updated September 26, 2019.UpToDate.Kidney stones in adults: uric acid nephrolithiasis. Updated August 9, 2018.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. 2011;63(10):3136-3141. doi:10.1002/art.30520
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Elfishawi MM, Zleik N, Kvrgic Z, et al.The rising incidence of gout and the increasing burden of comorbidities: a population-based study over 20 years.J Rheumatol. 2018;45(4):574-579. doi:10.3899/jrheum.170806Harvard Health Publishing.Pseudogout (CPPD).Major TJ, Topless RK, Dalbeth N, Merriman TR.Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.BMJ. 2018 Oct 10;363:k3951. doi:10.1136/bmj.k3951American Academy of Family Physicians.Pseudogout.Sundy JS, Baraf HS, Yood RA, et al.Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.JAMA. 2011;306(7):711-720. doi:10.1001/jama.2011.1169
Elfishawi MM, Zleik N, Kvrgic Z, et al.The rising incidence of gout and the increasing burden of comorbidities: a population-based study over 20 years.J Rheumatol. 2018;45(4):574-579. doi:10.3899/jrheum.170806
Harvard Health Publishing.Pseudogout (CPPD).
Major TJ, Topless RK, Dalbeth N, Merriman TR.Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.BMJ. 2018 Oct 10;363:k3951. doi:10.1136/bmj.k3951
American Academy of Family Physicians.Pseudogout.
Sundy JS, Baraf HS, Yood RA, et al.Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.JAMA. 2011;306(7):711-720. doi:10.1001/jama.2011.1169
Alvarellos A, Spilberg I.Colchicine prophylaxis in pseudogout.J Rheumatol. 1986;13(4):804-805.Cleveland Clinic Center for Continuing Education.Gout and calcium pyrophosphate deposition disease.Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF.The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.Arthritis Rheum. 1987;30(8):914-918. doi:10.1002/art.1780300811Jones AC, Chuck AJ, Arie EA, Green DJ, Doherty M.Diseases associated with calcium pyrophosphate deposition disease.Semin Arthritis Rheum. 1992;22(3):188-202. doi:10.1016/0049-0172(92)90019-aLawrence RC, Felson DT, Helmick CG, et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.Arthritis Rheum. 2008;58(1):26-35. doi:10.1002/art.23176Masuda I, Ishikawa K, Usuku G.A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease.Clin Orthop Relat Res. 1991 Feb;(263):272-287.Neame RL, Carr AJ, Muir K, Doherty M.UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.Ann Rheum Dis. 2003;62(6):513-518. doi:10.1136/ard.62.6.513Reginato AJ, Schumacher HR, Martinez VA.The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study.Arthritis Rheum. 1974;17(6):977-992. doi:10.1002/art.1780170611Roddy E, Doherty M.Gout. Epidemiology of gout.Arthritis Res Ther.2010;12:223. doi:10.1186/ar3199UpToDate,Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Updated December 16, 2020.UpToDate.Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Updated July 9, 2020.UpToDate.Clinical manifestations and diagnosis of gout. Updated December 1, 2019.UpToDate.Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease. Updated January 23, 2020.UpToDate.Treatment of calcium pyrophosphate crystal deposition (CPPD) disease. Updated August 28, 2020.UpToDate.Urate balance. Updated September 26, 2019.UpToDate.Kidney stones in adults: uric acid nephrolithiasis. Updated August 9, 2018.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. 2011;63(10):3136-3141. doi:10.1002/art.30520
Alvarellos A, Spilberg I.Colchicine prophylaxis in pseudogout.J Rheumatol. 1986;13(4):804-805.
Cleveland Clinic Center for Continuing Education.Gout and calcium pyrophosphate deposition disease.
Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF.The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.Arthritis Rheum. 1987;30(8):914-918. doi:10.1002/art.1780300811
Jones AC, Chuck AJ, Arie EA, Green DJ, Doherty M.Diseases associated with calcium pyrophosphate deposition disease.Semin Arthritis Rheum. 1992;22(3):188-202. doi:10.1016/0049-0172(92)90019-a
Lawrence RC, Felson DT, Helmick CG, et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.Arthritis Rheum. 2008;58(1):26-35. doi:10.1002/art.23176
Masuda I, Ishikawa K, Usuku G.A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease.Clin Orthop Relat Res. 1991 Feb;(263):272-287.
Neame RL, Carr AJ, Muir K, Doherty M.UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.Ann Rheum Dis. 2003;62(6):513-518. doi:10.1136/ard.62.6.513
Reginato AJ, Schumacher HR, Martinez VA.The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study.Arthritis Rheum. 1974;17(6):977-992. doi:10.1002/art.1780170611
Roddy E, Doherty M.Gout. Epidemiology of gout.Arthritis Res Ther.2010;12:223. doi:10.1186/ar3199
UpToDate,Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Updated December 16, 2020.
UpToDate.Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Updated July 9, 2020.
UpToDate.Clinical manifestations and diagnosis of gout. Updated December 1, 2019.
UpToDate.Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease. Updated January 23, 2020.
UpToDate.Treatment of calcium pyrophosphate crystal deposition (CPPD) disease. Updated August 28, 2020.
UpToDate.Urate balance. Updated September 26, 2019.
UpToDate.Kidney stones in adults: uric acid nephrolithiasis. Updated August 9, 2018.
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. 2011;63(10):3136-3141. doi:10.1002/art.30520
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