Etiology
The etiology of CPPD is not known. The hallmark of the disease is the deposition of calcium pyrophosphate (CPP) crystals in the midzone of articular hyaline and fibrocartilage. These crystals typically occur in the pericellular matrix around phenotypically altered articular chondrocytes.[11][12] Factors that promote CPPD crystal formation include alterations in the structure and composition of the pericellular matrix and overproduction of the pyrophosphate component of the CPPD crystal by chondrocytes.[13][14][15] It is likely that chondrocyte phenotypic changes are initiated by aging or injury and may be mediated through factors such as transforming growth factor-beta.[16] The reasons behind the associations of the metabolic conditions with CPPD are not well understood.
Pathophysiology
CPP crystals can be shed from cartilage into the articular space, where they may induce an inflammatory response and cause acute CPP crystal arthritis.[17] However, the conditions under which they elicit inflammation remain unknown, as they can also be found in noninflamed joints between attacks.[18] It has been speculated that crystal size and the nature of their adherent proteins may influence this process. In addition, CPP crystals can have direct catabolic effects on articular tissues. They can elicit the production of cytokines and proteases that degrade cartilage.[19]They may also produce mechanical damage. It is likely that both inflammatory and noninflammatory processes contribute to the severe joint degradation associated with articular CPP crystals.
Classification
Clinical patterns[1]
In 2023 a group of experts supported by the American College of Rheumatology and European League Against Rheumatism (EULAR) established the first set of classification criteria for CPPD disease.[5] The goal of this work was to design a scoring system to classify CPPD, so that entry criteria for carefully controlled studies of CPPD could be uniformly applied. The criteria begin by requiring the presence of joint pain, swelling, and tenderness that are not explained by other diagnoses. Individuals with Crowned dens syndrome or CPP crystals noted on synovial analysis of an affected joint are classified as having CPPD disease. Beyond these exceptions, there are weighted criteria including clinical features such as the location of joint involvement, age, associated diseases, imaging and radiographic abnormalities that are included in the score.
CPPD has a clinically heterogeneous presentation with 3 well-described clinical patterns of disease. CPPD can also be asymptomatic and other rare forms have been described. The nomenclature recommendations by EULAR eliminate the use of the term “pseudo”.[2]
Acute CPP crystal arthritis (previously known as pseudogout)
An acute, typically monoarticular inflammatory arthritis often affecting large joints such as the knee.
Chronic CPP inflammatory arthritis
A polyarticular inflammatory arthritis affecting large and small joints.
Osteoarthritis with CPPD
A chronic noninflammatory polyarticular arthritis, with or without superimposed acute attacks of inflammatory arthritis.
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