Calcium pyrophosphate dihydrate crystal deposition disease
|Calcium pyrophosphate dihydrate disease|
|Micrograph showing crystal deposition in an intervertebral disc. H&E stain.|
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 resultant 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.
Signs and symptoms
The disorder is more common in older adults. The disease is often occult until crystal deposits are coincidentally detected and diagnosed by a pathologist in various orthopedic specimens. 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.
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.
Two elements are considered: radiology and joint fluid analysis.
Radiology has a large role to play in finding 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, CPPD 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.
Because any medication that could reduce the inflammation of CPPD 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 CPPD. 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.
CPPD crystal deposition disease was originally described over 50 years ago.
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 refers to several of these situations.
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