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Calcium pyrophosphate dihydrate (CPPDcrystal 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.

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What Are the Causes of Pseudogout?

Pseudogout occurs when calcium pyrophosphate crystals form in the synovial fluid in the joints. Crystals can also deposit in the cartilage, where they can cause damage. Buildup of crystal in the joint fluid results in swollen joints and acute pain.

Researchers don’t fully understand why crystals form. The chance of them forming likely increases with age. Pseudogout can often run in families, so many medical professionals believe it to be a genetic condition. Other contributing factors may include:

  • hypothyroidism (underactive thyroid)
  • excess iron
  • magnesium deficiency
  • overactive parathyroid gland
  • hypercalcemia (too much calcium in the blood)
What Are the Symptoms of Pseudogout?

Pseudogout most often affects the knees, but also affects ankles, wrists, and elbows. General symptoms may include:

  • bouts of joint pain
  • swelling of the affected joint
  • fluid buildup around the joint
  • chronic arthritis
  • an analysis of joint fluid to look for calcium pyrophosphate crystals
  • X-rays of the joints to check for any damage to the joint, calcification (calcium buildup) of the cartilage, and deposits of calcium in the joint cavities

    X-ray of a knee with chondrocalcinosis.

    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.

    Rhombus-shaped calcium pyrophosphate crystal seen in a knee arthrocentesis specimen.

    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. Looking at the crystals found in the joint cavities helps your doctor make a diagnosis. This condition shares symptoms with other problems, so sometimes it may be misdiagnosed as:

  • osteoarthritis (a degenerative joint disease caused by loss of cartilage)
  • rheumatoid arthritis (a long-term inflammatory disorder that may affect several organs and tissues)
  • gouty arthritis (a disorder causing painful inflammation of the toes and feet)

Pseudogout can sometimes be associated with other illnesses, such as:

  • hemophilia (a hereditary bleeding disorder that prevents the blood from clotting normally)
  • ochronosis (a condition causing the deposit of a dark pigment in the cartilage and other connective tissues)
  • amyloidosis (an abnormal buildup of protein in the tissues)
  • hypothyroidism (underactive thyroid glands)
  • hyperparathyroidism (an excessive amount of parathyroid hormone in the blood)
  • hemochromatosis (an abnormally high level of iron in the blood)
What Are the Treatments for Pseudogout?
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.
Other medication treatments include:
  • hydroxychloroquine (Plaquenil, Quineprox)
  • methotrexate (Rheumatrex, Trexall)
  • interleukin 1 beta-antagonist (Anakinra)

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