{"title":"Calcium pyrophosphate deposition disease","authors":"Prof Tristan Pascart MD , Georgios Filippou MD , Prof Frédéric Lioté MD , Silvia Sirotti MD , Charlotte Jauffret MD , Prof Abhishek Abhishek PhD","doi":"10.1016/S2665-9913(24)00122-X","DOIUrl":null,"url":null,"abstract":"<div><div>Calcium pyrophosphate deposition (CPPD) disease is a consequence of the immune response to the pathological presence of calcium pyrophosphate (CPP) crystals inside joints, which causes acute or chronic inflammatory arthritis. CPPD is strongly associated with cartilage degradation and osteoarthritis, although the direction of causality is unclear. This clinical presentation is called CPPD with osteoarthritis. Although direct evidence is scarce, CPPD disease might be the most common cause of inflammatory arthritis in older people (aged >60 years). CPPD is caused by elevated extracellular-pyrophosphate concentrations in the cartilage and causes inflammation by activation of the NLRP3 inflammasome. Common risk factors for CPPD disease include ageing and previous joint injury. It is uncommonly associated with metabolic conditions (eg, hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia) and genetic variants (eg, in the <em>ANKH</em> and osteoprotegerin genes). Apart from the detection of CPP crystals in synovial fluid, imaging evidence of CPPD in joints by mainly conventional radiography, and increasingly ultrasonography, has a central role in the diagnosis of CPPD disease. CT is useful in showing calcification in axial joints such as in patients with crowned dens syndrome. To date, no treatment is effective in dissolving CPP crystals, which explains why control of inflammation is currently the main focus of therapeutic strategies. Prednisone might provide the best benefit–risk ratio for the treatment of acute CPP-crystal arthritis, but low-dose colchicine is also effective with a risk of mild diarrhoea. Limited evidence suggests that colchicine, low-dose weekly methotrexate, and hydroxychloroquine might be effective in the prophylaxis of recurrent flares and in the management of persistent CPP-crystal inflammatory arthritis. Additionally, biologics inhibiting IL-1 and IL-6 might have a role in the management of refractory disease.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0000,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266599132400122X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Calcium pyrophosphate deposition (CPPD) disease is a consequence of the immune response to the pathological presence of calcium pyrophosphate (CPP) crystals inside joints, which causes acute or chronic inflammatory arthritis. CPPD is strongly associated with cartilage degradation and osteoarthritis, although the direction of causality is unclear. This clinical presentation is called CPPD with osteoarthritis. Although direct evidence is scarce, CPPD disease might be the most common cause of inflammatory arthritis in older people (aged >60 years). CPPD is caused by elevated extracellular-pyrophosphate concentrations in the cartilage and causes inflammation by activation of the NLRP3 inflammasome. Common risk factors for CPPD disease include ageing and previous joint injury. It is uncommonly associated with metabolic conditions (eg, hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia) and genetic variants (eg, in the ANKH and osteoprotegerin genes). Apart from the detection of CPP crystals in synovial fluid, imaging evidence of CPPD in joints by mainly conventional radiography, and increasingly ultrasonography, has a central role in the diagnosis of CPPD disease. CT is useful in showing calcification in axial joints such as in patients with crowned dens syndrome. To date, no treatment is effective in dissolving CPP crystals, which explains why control of inflammation is currently the main focus of therapeutic strategies. Prednisone might provide the best benefit–risk ratio for the treatment of acute CPP-crystal arthritis, but low-dose colchicine is also effective with a risk of mild diarrhoea. Limited evidence suggests that colchicine, low-dose weekly methotrexate, and hydroxychloroquine might be effective in the prophylaxis of recurrent flares and in the management of persistent CPP-crystal inflammatory arthritis. Additionally, biologics inhibiting IL-1 and IL-6 might have a role in the management of refractory disease.
期刊介绍:
The Lancet Rheumatology, an independent journal, is dedicated to publishing content relevant to rheumatology specialists worldwide. It focuses on studies that advance clinical practice, challenge existing norms, and advocate for changes in health policy. The journal covers clinical research, particularly clinical trials, expert reviews, and thought-provoking commentary on the diagnosis, classification, management, and prevention of rheumatic diseases, including arthritis, musculoskeletal disorders, connective tissue diseases, and immune system disorders. Additionally, it publishes high-quality translational studies supported by robust clinical data, prioritizing those that identify potential new therapeutic targets, advance precision medicine efforts, or directly contribute to future clinical trials.
With its strong clinical orientation, The Lancet Rheumatology serves as an independent voice for the rheumatology community, advocating strongly for the enhancement of patients' lives affected by rheumatic diseases worldwide.