Calcium pyrophosphate deposition disease (CPPD), characterized by the presence of calcium pyrophosphate crystals in and around joints, poses diagnostic and therapeutic challenges in rheumatology. This review provides a comprehensive overview of CPPD, focusing on its diagnosis, differential diagnosis, therapeutic challenges, and monitoring, with insights into the association between CPPD and cardiovascular risk. Diagnostics in CPPD rely on identifying CPP crystals in synovial fluid or joint tissues, with imaging modalities such as ultrasound and conventional radiography emerging as valuable tools. The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria prioritize imaging evidence of CPP crystal deposition and recurrent episodes of acute inflammatory arthritis, aiding in standardized diagnosis. Differential diagnosis includes distinguishing CPPD from gout, osteoarthritis, rheumatoid arthritis, basic calcium phosphate deposition disease, and other inflammatory arthropathies. Therapeutic challenges in CPPD management revolve around symptomatic relief, with no targeted therapy to influence CPP deposition currently available. Management strategies include symptom-directed treatments like NSAIDs, steroids and colchicine. IL-6 inhibition with tocilizumab shows promise for refractory cases. Monitoring CPPD involves assessing joint symptoms, inflammation, and cardiovascular risk factors, with regular clinical evaluation. In conclusion, CPPD presents a complex challenge in rheumatology, requiring a nuanced approach to diagnosis and management. Ongoing research is needed to deepen our understanding of CPPD mechanisms and explore novel therapeutic avenues.

Calcium pyrophosphate deposition disease is known as crowned dens syndrome or peripheral arthritis, especially of knees, hips and shoulders. The disease course is asymptomatic, with acute or chronic disease activity related to osteoarthritis, especially in the elderly. Other risk factors are joint injury, osteoarthritis and metabolic conditions such as primary hyperparathyroidism, hemochromatosis, hypophosphatasia and hypomagnesemia. Genetic background should be considered before the age of 55 years. Only recently was the value of signs and symptoms weighted, allowing the introduction of classification criteria. Biomarkers include compensated polarized light microscopy findings, laboratory values and imaging. Imaging evidence refers to calcification of the fibrocartilage or hyaline cartilage. Chondrocalcinosis defined as such cartilage calcification is most commonly due to calcium pyrophosphate deposition disease. Calcification of the synovial membrane, joint capsule, or tendon should not be scored. Ultrasonography detects calcium pyrophosphate deposits with more than 80% sensitivity rates, which is superior to conventional radiography. In the future, dual-energy computerized tomography and Raman spectroscopy are promising new techniques to assess disease activity. Currently, the primary therapeutic goal is controlling inflammatory reactions and preventing further episodes. However, only hydroxychloroquine and magnesium carbonate have shown some efficacy and reduction of pain intensity so far. As patients report more significant unmet treatment needs than patients with gout, education is an essential issue of care. The new classification criteria will allow the validation of standardized outcome parameters with the definition of remission and low disease activity for developing treat-to-target strategies to perform well-designed interventional trials evaluating new treatment options and strategies.

Calcium pyrophosphate deposition disease (CPPD) is a cause of inflammatory arthropathy that increases in prevalence with increasing age, presents in acute and chronic forms, and is characterized by the finding of positively birefringent crystals on polarized microscopy of synovial fluid. This review finds that although strides are being made in CPPD diagnosis and classification, CPPD remains a poorly understood, unrecognized, and debilitating disease. As a consequence, treatment options usually lack supportive evidence and there has been little progress in novel drug development for the condition. This article aims to discuss the updated evidence on treatment options for CPPD and identifies promising future areas for improvement.