Calcium Pyrophosphate Deposition Disease 

Calcium pyrophosphate deposition disease (CPDD) is a metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate (CPPD) in and around joints, especially in articular and fibrocartilage. Although CPDD is often asymptomatic, with only radiographic changes (ie, chondrocalcinosis), various clinical manifestations may occur, including acute (pseudogout) and chronic arthritis. Although almost any joint may be involved by CPDD, the knees, wrists, and hips are most commonly affected. This condition is the most common cause of secondary metabolic osteoarthritis.

Although the exact mechanism for the development of CPDD remains unknown, increased adenosine triphosphate breakdown with resultant increased inorganic pyrophosphate in the joints results from aging, genetic factors, or both. Changes in the cartilage matrix may play an important role in promoting CPPD deposition. Rare hereditary forms of CPDD occur, generally inherited in an autosomal dominant mode.

Overactivity of enzymes that break down triphosphates, such as nucleoside triphosphate pyrophosphohydrolase, has been observed in the cartilage of patients with CPDD. Therefore, inorganic pyrophosphate can bind calcium, leading to CPPD deposition in cartilage and synovium.^{[1, 2]} Hyaline cartilage is affected most commonly, but fibrocartilage, such as the meniscal cartilage of the knee, can also be involved.^[3]

Hypotheses based on in vitro studies propose that pyrophosphohydrolase activity and inorganic phosphate content, as noted above, are generalized phenomena that occur in fibroblasts.^[4] Although these phenomena are generalized, the reason they occur only in joints remains unknown.

Recently, genetic defects have been identified as specific gene mutations in a few kindred families.^[5] The mutations occurred in specific genes known as ANKH and COL, which may be involved in crystal-induced inflammation. This is related to synovial tissue and direct cartilage activation, leading to the arthritis caused by CPPD. The ANKH gene has also been shown to be involved in cellular transport of inorganic phosphate.

Gitelman syndrome is associated with both hypokalemic metabolic acidosis and hypomagnesemia. Patients with Gitelman syndrome may have renal tubular acidosis and a history of pseudogout. As such, this diagnosis should be considered in patients with such findings. It has been shown to be associated with a mutation in the gene solute carrier family 12, member 3 (SLC12A3). The cause may be related to the thiazide sensitive sodium chloride cotransporter, which is found in a variant form in most of these patients. The syndrome can mimic several other manifestations of CPDD, including osteoarthritis, carpal tunnel syndrome, and tenosynovitis with calcifications along the tendon sheath itself.^[6]

Frequency

United States

CPDD is a common condition that occurs with aging in all races. Nearly 50% of people older than 85 years have radiologic evidence of chondrocalcinosis.

Mortality/Morbidity

CPDD can be a cause of significant morbidity, either from the pain of an acute attack of pseudogout or the chronic symptoms associated with chronic arthropathy.

Race

CPDD has no racial predilection.

Sex

CPDD is slightly more common in women than in men, but the exact ratio is unknown. The female-to-male ratio is probably 1.4:1.

Age

CPDD usually occurs in individuals who are in the fifth decade of life or older, with increasing prevalence as age increases. When it occurs early, before the fourth decade of life, it is usually associated with secondary causes, such as an underlying metabolic disease, or familial causes.