Patient education: Calcium pyrophosphate crystal deposition (CPPD) disease (Beyond the Basics)
- Michael A Becker, MD
Michael A Becker, MD
- Section Editor — Crystal Diseases
- Professor Emeritus of Medicine
- University of Chicago Pritzker School of Medicine
CPPD DISEASE DEFINITION
Calcium pyrophosphate (CPP) is a normal chemical that everyone has in their body. It is important for the healthy function of connective tissues such as bones, cartilage, and joints. However, in some cases, excess CPP builds up and forms microscopic "crystals," which can deposit in 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:
●Asymptomatic CPPD disease (in which the person has no symptoms, but crystals can be seen on imaging tests)
●Acute calcium pyrophosphate (CPP) crystal arthritis (formerly called "pseudogout")
●Chronic CPP crystal inflammatory arthritis
●Osteoarthritis with CPPD
●Severe joint degeneration
ACUTE CPP CRYSTAL ARTHRITIS (PSEUDOGOUT)
Acute calcium pyrophosphate (CPP) crystal arthritis is a form of calcium pyrophosphate deposition (CPPD) disease and was the first type of CPPD 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 over 50 percent of patients 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 (sometimes referred to as 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.)
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: Hemochromatosis (hereditary iron overload) (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, while urate crystals are equally supportive of a diagnosis of acute gout.
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), oral glucocorticoid, or colchicine, may be preferred.
Taking an NSAID such as ibuprofen (sample brand names: Advil, Motrin), indomethacin (sample brand name: Indocin), 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 weight bearing (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 name: Colcrys). 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: Reducing the costs of medicines (Beyond the Basics)".)
●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.
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: Hemochromatosis (hereditary iron overload) (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
●National Institute of Arthritis and Musculoskeletal and Skin Diseases
●American College of Rheumatology/Association of Rheumatology Health Professionals
●The Arthritis Foundation
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- Jones AC, Chuck AJ, Arie EA, et al. Diseases associated with calcium pyrophosphate deposition disease. Semin Arthritis Rheum 1992; 22:188.
- O'Duffy JD. Clinical studies of acute pseudogout attacks: comments on prevalence, predispositions, and treatment. Arthritis Rheum 1976; 19 Suppl 3:349.
- Fam AG, Topp JR, Stein HB, Little AH. Clinical and roentgenographic aspects of pseudogout: a study of 50 cases and a review. Can Med Assoc J 1981; 124:545.
- Alvarellos A, Spilberg I. Colchicine prophylaxis in pseudogout. J Rheumatol 1986; 13:804.
- Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med 2016; 374:2575.
- Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011; 70:563.
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