|Calcium pyrophosphate dihydrate disease|
|Classification and external resources|
Micrograph showing crystal deposition in an intervertebral disc. H&E stain.
|ICD-9||[712.3 275.49 [712.3]]|
|DiseasesDB||10832 DDB 30784|
|eMedicine||med/1938 radio/125 orthoped/382 emerg/221|
Calcium pyrophosphate dihydrate disease (CPPD), (formerly Pseudogout) is a rheumatologic disorder with varied symptoms arising due to the accumulation of crystals of calcium pyrophosphate dihydrate in the connective tissues. It is more commonly known by alternative names that specify certain clinical or radiographic findings, although neither is synonymous with CPPD. 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. Pyrophosphate arthropathy is a term that may refer to either of the above. Statistically, the knee joint is the most commonly affected.
CPPD crystal deposition disease is a polyarticular arthritis (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. ref name="PMID"/> Although, in theory, any joint may be affected, statistics show that the knees, wrists, and hips are the most commonly attributed areas. In rare cases, pseudogout may affect the spinal canal and cause damage to the spinal cord. The exact cause of CPPD is unknown, although increased breakdown of adenosine triphosphate (the molecule used as energy currency in all animals), which results in increased pyrophosphate levels in joints, is thought to be one reason why crystals may develop. There is some recent evidence suggesting that 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.
One genetic study found an association between chondrocalcinosis and a region of chromosome 8q.
Signs and symptoms 
People with this disorder usually first visit the doctor because inflammation is causing pain in one or more joints. 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. In general, the white blood cell count is raised. In rare instances, patients may also have signs of carpal tunnel syndrome. This condition can also be associated with Milwaukee shoulder syndrome.
Radiography has a large role to play in the diagnosis of chondrocalcinosis, with radiographs, CT scans, MRIs, ultrasound, 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. 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 hematoxylin and eosin, 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 chondrocalcinosis bears a risk of causing organ damage, treatment is not advised if the condition is not causing pain. For acute pseudogout, 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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