|Calcium pyrophosphate dihydrate disease|
|Classification and external resources|
|ICD-9-CM||[712.3 275.49 [712.3]]|
|DiseasesDB||10832 DDB 30784|
|eMedicine||med/1938 radio/125 orthoped/382 emerg/221|
Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, also known as pseudogout and pyrophosphate arthropathy is a rheumatologic disorder with varied symptoms and signs arising from the accumulation of crystals of calcium pyrophosphate dihydrate in the connective tissues. The alternative names emphasize particular aspects of the clinical or radiographic findings. The knee joint is the most commonly affected.
Calcium pyrophosphate dihydrate crystals are associated with a range of clinical syndromes, which have been given various names, based upon which clinical symptoms or radiographic findings are most prominent. A task force of the European League Against Rheumatism (EULAR) made recommendations on preferred terminology. Accordingly, calcium pyrophosphate deposition (CPPD) is an umbrella term for the various clinical subsets, whose naming reflects an emphasis on particular features. For example, pseudogout refers to the acute symptoms of joint inflammation or synovitis: red, tender, and swollen joints that may resemble gouty arthritis (a similar condition in which monosodium urate crystals are deposited within the joints). Chondrocalcinosis, on the other hand, refers to the radiographic evidence of calcification in hyaline and/or fibrocartilage. "Osteoarthritis (OA) with CPPD" reflects a situation where osteoarthritis features are the most apparent. Pyrophosphate arthropathy is a term that can refer to several of these situations.
The exact cause of CPPD is unknown, although increased breakdown of adenosine triphosphate (ATP; the molecule used as energy currency in all living things), which results in increased pyrophosphate levels in joints, is thought to be one reason why crystals may develop.
Familial forms are rare. One genetic study found an association between chondrocalcinosis and a region of chromosome 8q.
The gene ANKH is involved in crystal-related inflammatory reactions and inorganic phosphate transport.
Excessive calcium (due to hypomagnesemia) has a potential relationship with chondrocalcinosis, and magnesium supplementation may reduce or alleviate symptoms.
Hyperparathyroidism, hypothyroidism, hemochromatosis, hypophosphatemia, hypomagnesemia and renal osteodystrophy are often also associated with chondrocalcinosis. Other diseases associated with chondrocalcinosis are Wilson's disease and osteoarthritis. In some cases, traumatic arthritis can cause chondrocalcinosis.
Signs and symptoms
The disorder is more common in older adults. It may be asymptomatic, or it can be associated with osteoarthritis, or it can present as an acute or chronic inflammatory arthritis that causes pain in one or more joints. The white blood cell count is often raised.
The arthritis is usually polyarticular (i.e., it leads to an inflammation of several joints in the body), although it may begin as monoarticular (i.e., confined to just one joint). CPPD crystals tend to form within articular tissues. In theory, any joint may be affected, but statistics show that the knees are the most commonly affected joints, as well as wrists and hips. In rare cases, pseudogout may affect the spinal canal and cause damage to the spinal cord.
Two elements are considered: radiology and joint fluid analysis.
Radiology has a large role to play in the diagnosis of chondrocalcinosis, with radiographs, CT scans, MRIs, US, and nuclear medicine all having a part. CT scans and MRIs show calcific masses (usually within the ligamentum flavum or joint capsule), however radiography is more successful. At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. As with most conditions, chondrocalcinosis can present with similarity to other diseases such as ankylosing spondylitis and gout.
Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method suffers from poor sensitivity, specificity, and inter-operator agreement.
These two modalities currently define CPPD disease but lack diagnostic accuracy, and are potentially epiphenomenological.
Because any medication that could reduce the inflammation of chondrocalcinosis bears a risk of causing organ damage, treatment is not advised if the condition is not causing pain. For acute pseudogout, treatments include intra-articular corticosteroid injection, systemic corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or, on occasion, high-dose colchicine. In general, NSAIDs are administered in low doses to help prevent chondrocalcinosis. However, if an acute attack is already occurring, higher doses are administered. If nothing else works, hydroxychloroquine or methotrexate may provide relief. Research into surgical removal of calcifications is underway, however this still remains an experimental procedure.
CPPD affects people of all cultures and ethnic origins, and, in the United States, around 50% of the population over 85 years of age are affected. It may cause considerable pain, but it is never fatal. Women are at a slightly higher risk than men, with an estimated ratio of occurrence of 1.4:1.
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