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CPPD DISEASE DEFINITION — Pyrophosphate is a normal chemical that everyone has in the body. It is important for the healthy function of connective tissues such as bones, cartilage, and joints. However, in some cases, excess pyrophosphate complexes with calcium to form microscopic calcium pyrophosphate (CPP) crystals, which preferentially deposit in joint tissues.
Crystals sometimes do not cause symptoms; this is called "asymptomatic" calcium pyrophosphate deposition (CPPD) disease. At other times, the crystals can cause acute or more chronic (long-term) inflammation or degeneration of involved tissues. Each of these outcomes of CPP crystal deposition is a part of the spectrum of CPPD disease.
TYPES OF CPPD DISEASE — Calcium pyrophosphate deposition (CPPD) disease can present in a number of different ways. The range of presentations includes:
●Asymptomatic CPPD disease (in which the person has no symptoms, but crystals can be seen on imaging tests, such as X-rays)
●Acute calcium pyrophosphate (CPP) crystal arthritis (formerly called "pseudogout")
●Chronic CPP crystal inflammatory arthritis
●Osteoarthritis with CPPD
●Severe joint degeneration
●Spinal involvement
Acute CPP crystal arthritis (pseudogout) — Acute CPP crystal arthritis was the first type of CPPD disease to be widely recognized. It refers to sudden-onset attacks of joint pain, swelling, warmth, and difficulty using the affected joint. An attack can last for days or even weeks. The knee is affected in more than half of people with acute CPP crystal arthritis; however, the disorder can also affect the ankles, feet, shoulders, elbows, wrists, or hands.
This condition has also been called "pseudogout" because the symptoms of acute CPP crystal arthritis are very similar to those of gout, an arthritis caused by urate (uric acid) crystals rather than CPP crystals (see "Patient education: Gout (Beyond the Basics)"). Although the two disorders can cause similar symptoms, patients with pseudogout are treated somewhat differently than patients with gout. (See 'CPPD disease treatment' below.)
Chronic CPP crystal inflammatory arthritis — Some people with CPPD disease have more than a single joint involved at once. They have stiffness, pain, and swelling in multiple joints, which can last weeks to months. The pattern of involved joints is similar to those involved in acute CPP crystal arthritis. (See 'Acute CPP crystal arthritis (pseudogout)' above.)
Osteoarthritis with CPPD — CPPD can also occur in a joint with osteoarthritis, in which the cartilage has worn down. This is particularly common in the hip and knee joints. (See "Patient education: Osteoarthritis symptoms and diagnosis (Beyond the Basics)".)
Severe joint degeneration and spinal involvement — CPPD disease can lead over time to serious problems such as degeneration (breakdown) of the cartilage. When crystals form in and around the spine, it can also lead to back pain and stiffness, and sometimes compression of the spinal cord or surrounding nerves, but this type of involvement is unusual.
CPPD DISEASE RISK FACTORS — Calcium pyrophosphate deposition (CPPD) disease symptoms develop in some (but not all) people in response to the deposition of calcium pyrophosphate (CPP) crystals in the joints. The crystals first develop in the joint cartilage and eventually move to the lining of the joint (also called the synovium) or into the joint fluid, where they can cause inflammation with associated pain, swelling, and disability in the affected joint. In most people with CPPD disease, it is not known exactly why CPP crystals form and deposit in the joints, although abrupt shedding of crystals from deposits in cartilage is believed to promote acute inflammation. (See "Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease".)
Some people, particularly older adults, have CPP crystals in their joints (called "chondrocalcinosis") but never experience symptoms of acute arthritis. Chondrocalcinosis is present in up to 50 percent of people by age 90, often without or with only modest symptoms.
In addition to older age, there are several other factors that increase the risk of accumulating CPP crystals in the joints, including:
●Joint trauma – People who have previously experienced a significant injury to or surgery on a joint have an increased risk of developing CPP crystal deposits.
●Genetics – People can inherit a predisposition to CPP crystal deposition (called "familial chondrocalcinosis"); these people are more likely to develop acute CPP crystal arthritis or other features of CPPD disease earlier in life than patients with sporadic CPPD disease.
●Excess iron – People with a genetic disorder called hemochromatosis, which causes the body to store excess iron, are at an increased risk of developing CPP crystal deposits. (See "Patient education: Hereditary hemochromatosis (Beyond the Basics)".)
●Other related disorders – Several other diseases of metabolism or endocrine glands are associated with CPPD disease. These include hyperparathyroidism (overactive parathyroid glands), hypophosphatasia (an inherited metabolic bone disorder), hypomagnesemia (low levels of magnesium in the blood), Gitelman syndrome (an inherited kidney disorder), and possibly others.
CPPD DISEASE DIAGNOSIS — A health care clinician can confirm or rule out a diagnosis of calcium pyrophosphate deposition (CPPD) disease by performing an examination and tests. In many patients, a sample of joint fluid is obtained in order to determine whether calcium pyrophosphate dihydrate (CPP) crystals are present in the fluid on microscopic examination and to exclude arthritis due to other causes, such as gout or joint infection.
Synovial fluid analysis — Synovial (joint) fluid is obtained under sterile conditions through a needle inserted into the affected joint. The fluid is then analyzed to determine if crystals or infection are present. The presence of CPP crystals in a patient with joint pain and inflammation strongly supports a diagnosis of acute CPP crystal arthritis.
Imaging — A clinician may examine the painful joint(s) or other frequently involved joints by taking X-rays or doing other imaging tests. X-ray images can reveal calcium-containing crystal deposits in the cartilage, a condition known as chondrocalcinosis. Ultrasonography (ultrasound examination) of affected joints is another imaging method that is increasingly being used to establish or confirm the diagnosis of CPPD disease or to guide synovial fluid aspiration (a "joint tap") to obtain material for synovial fluid analysis.
CPPD DISEASE COMPLICATIONS — Calcium pyrophosphate crystal deposition (CPPD) disease can lead to rapidly progressing osteoarthritis, caused by wearing down of the joint cartilage, bone cysts or spurs, and even fractures. These changes may occur in joints not usually involved in osteoarthritis, such as the knuckles and wrists.
Although treatment of episodes of acute CPP crystal arthritis can shorten the attack, treatment may not decrease the risk of developing a more chronic arthritis that in most ways resembles osteoarthritis. Treatment of this type of chronic arthritis is similar to that used for osteoarthritis. (See "Patient education: Osteoarthritis treatment (Beyond the Basics)".)
CPPD DISEASE TREATMENT — There is no treatment that can completely remove or prevent the formation of calcium pyrophosphate dihydrate (CPP) crystals. However, the joint pain and swelling generally resolve with treatment, including the following:
●Joint aspiration and/or injection – A clinician may insert a needle into the affected joint to remove the fluid and crystals that have accumulated. This can help to relieve pressure and pain. An injection of glucocorticoids (steroids) into the joint may relieve the associated joint inflammation.
●Oral medications – Joint aspiration or injection is usually preferred when one or two joints are affected but may not be recommended if more than two joints are affected during an attack. In this case, an oral medication, such as a nonsteroidal antiinflammatory drug (NSAID), an oral glucocorticoid, or colchicine, may be preferred.
Taking an NSAID such as ibuprofen (sample brand names: Advil, Motrin) or naproxen (sample brand names: Aleve, Naprosyn) can help to relieve symptoms of pain and inflammation. Prescription-strength tablets (as opposed to over-the-counter tablets) may make it more convenient to take the relatively high doses of NSAIDs that are needed to control an attack. Treatment of the acute attack of CPP crystal arthritis with oral antiinflammatory medications is usually continued only until the attack resolves. (See "Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)".)
●Joint immobilization – Patients may be advised to avoid weightbearing (walking or running if the legs or feet are involved), avoid excessive movement, and limit activity for a period of time to minimize pain and swelling. In some cases, a temporary splint will be recommended to limit joint movement.
●Treatment of related conditions – If the CPP crystal deposits are caused by a separate disorder (see 'CPPD disease risk factors' above), that condition may require treatment, although this may not affect the course of CPP crystal-related joint disease.
CPPD DISEASE PREVENTION — For patients who experience frequent episodes of acute calcium pyrophosphate (CPP) crystal arthritis, a clinician may prescribe daily colchicine (brand names: Colcrys, Mitigare). Use of this medication, which is also often used to treat or prevent gout, can reduce the number of acute attacks. The benefits and risks of preventive therapy should be discussed with a clinician.
The cost of prophylactic use of colchicine has been an issue for many patients and their clinicians. The availability of generic colchicine preparations may alleviate this concern, but the impact of this action remains uncertain. Programs are available to assist with the cost of colchicine for eligible patients; visit the NeedyMeds website for more information. (See "Patient education: Gout (Beyond the Basics)" and "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)".)
SUMMARY
●Acute calcium pyrophosphate (CPP) crystal arthritis is a form of arthritis that develops in people with deposits of CPP crystals in joints.
●The symptoms of an acute CPP crystal arthritis attack include joint pain, swelling, and warmth, often with impaired use of the affected joint. (See 'Acute CPP crystal arthritis (pseudogout)' above.)
●The treatment of acute CPP crystal arthritis is aimed at relieving symptoms by reducing inflammation in the joint. Treatment may include oral antiinflammatory agents, such as a nonsteroidal antiinflammatory drug (NSAID), colchicine, or a glucocorticoid (steroid). Needle drainage of joint fluid and/or injection of a glucocorticoid into the joint to alleviate pressure and reduce inflammation is often effective.
Immobilization (rest) of the affected joint is an important part of therapy. If the calcium pyrophosphate deposition (CPPD) disease is caused by a separate disorder, treating that condition may be necessary to prevent complications of the related disease; however, this may not affect the course of CPP crystal joint disease. (See 'CPPD disease treatment' above.)
●Some patients who suffer from frequent acute attacks of CPP crystal arthritis may be given a longer course of colchicine to help prevent future episodes. (See 'CPPD disease prevention' above.)
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Gout (The Basics)
Patient education: Calcium pyrophosphate deposition disease (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Gout (Beyond the Basics)
Patient education: Hereditary hemochromatosis (Beyond the Basics)
Patient education: Osteoarthritis treatment (Beyond the Basics)
Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease
Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease
Treatment of calcium pyrophosphate crystal deposition (CPPD) disease
The following organizations also provide reliable health information.
●National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
●National Institute of Arthritis and Musculoskeletal and Skin Diseases
(301) 496-8188
●American College of Rheumatology/Association of Rheumatology Health Professionals
(404) 633-3777
●The Arthritis Foundation
(800) 283-7800
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Michael A Becker, MD, who contributed to an earlier version of this topic review.
