Calcium pyrophosphate crystal deposition (CPPD)

Abstract

Calcium pyrophosphate crystal deposition (CPPD) in articular cartilage is a common age-related phenomenon. Recent important advances in our understanding of the pathophysiology of pyrophosphate metabolism include the identification of a mutation within the ANK gene which associates with familial CPPD, and elucidation of the interleukin-1β‎‎ (IL-1β‎‎)-dependent mechanisms by which crystals invoke an inflammatory response. Risk factors for CPPD include age, prior joint damage and osteoarthritis, genetic factors, and occasionally metabolic diseases (hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia). CPPD is commonly asymptomatic or may present as osteoarthritis with CPPD, acute calcium pyrophosphate (CPP) crystal arthritis, or chronic CPP crystal inflammatory arthritis. Although radiographic chondrocalcinosis is often taken to be synonymous with CPPD, other calcium crystals can also have this appearance and definitive diagnosis requires identification of CPP crystals by compensated polarized light microscopy of aspirated synovial fluid. Recently, the ultrasonographic appearances of CPPD have been described. Treatment of CPPD is targeted to the clinical presentation. Acute CPP crystal arthritis is treated by aspiration and injection of glucocorticosteroid, local ice packs, non-steroidal anti-inflammatory drugs (NSAIDS), low-dose colchicine, oral or parenteral glucocorticosteroids, or adrenocorticotrophic hormone (ACTH). Treatment of osteoarthritis with CPPD is very similar to the treatment of osteoarthritis alone. There is no specific therapy for chronic CPP crystal inflammatory arthritis: options include NSAID, low-dose colchicine, low-dose glucocorticosteroid, methotrexate, and hydroxychloroquine. Recommendations for the management of CPPD are derived from a small evidence base and largely based on clinical experience and extrapolation from gout. Further research into diagnosis and management including novel treatment strategies such as IL-1β‎‎ blockade is much needed.