Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, also known as pseudogout and pyrophosphate arthropathy, is a rheumatologic disease which is thought to be secondary to abnormal accumulation of calcium pyrophosphate dihydrate crystals within joint soft tissues. The knee joint is most commonly affected. The disease is metabolic in origin and its treatment remains symptomatic. Signs and symptoms When symptomatic, the disease classically begins with symptoms that are similar to a gout attack (thus the moniker "pseudogout"). These include: severe pain warmth swelling of one or more joints The symptoms can be monoarticular (involving a single joint) or polyarticular (involving several joints). Symptoms usually last for days to weeks, and often recur. Although any joint may be affected, the knees, wrists, and hips are most common. X-ray, CT, or other imaging usually shows accumulation of calcium within the joint cartilage, known as chondrocalcinosis. There can also be findings of osteoarthritis. The white blood cell count is often raised. Cause The cause of CPPD disease is unknown. 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 CPPD and a region of chromosome 8q. The gene ANKH is involved in crystal-related inflammatory reactions and inorganic phosphate transport. Diagnosis The disease is defined by presence of joint inflammation and the presence of CPPD crystals within the joint. The crystals are usually detected by imaging and/or joint fluid analysis. Medical imaging, consisting of x-ray, CT, MRI, or ultrasound may detect chondrocalcinosis within the affected joint, indicating a substantial amount of calcium crystal deposition within the cartilage or ligaments. Ultrasound is a reliable method to diagnose CPPD. Using ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage or fibrocartilage. By x-ray, CPPD can appear similar 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