Calcium pyrophosphate deposition (CPPD) disease: a review of pathophysiology, clinic and diagnosis

Abstract

Calcium pyrophosphate deposition (CPPD) disease represents a crystal-induced arthropathy characterized by the deposition of calcium pyrophosphate dihydrate crystals within the articular joints and adjacent soft tissues. The manifestation of CPPD can present in a variety of clinical forms, including acute pseudogout episodes, chronic inflammatory arthritis, a variant associated with osteoarthritis, and the “crowned dens” syndrome; alternatively, it may be identified incidentally during radiological assessments. The condition is predominantly observed in individuals aged over 60 years, with its incidence escalating in correlation with advancing age. The presence of CPP crystals activates the innate immune response, subsequently eliciting an inflammatory cascade. Among the mechanisms implicated in this inflammatory process are the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome, and the secretion of matrix metalloproteinases. The elevation of pro-inflammatory cytokines such as IL-6, IL-8, TNF-α, and pro-IL-1β exacerbates the inflammatory state within the affected joint. Although there is a marginally higher prevalence of CPPD in females, this gender disparity is not deemed statistically significant. CPPD may also manifest in younger and middle-aged populations, necessitating vigilance regarding potential metabolic disorders or hereditary conditions in such cases. The diagnosis of CPPD is predominantly established through a combination of clinical assessment and imaging modalities. The definitive diagnostic criterion involves the identification of CPP crystals in synovial fluid utilizing polarized light microscopy. Clinically, CPPD can be misdiagnosed as rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), infectious arthritis, and other crystal-related arthropathies. The recently developed classification criteria by ACR/EULAR in 2023 are intended to enhance the precision of diagnosis. This review seeks to encapsulate the pathophysiology, clinical presentation, and diagnostic approaches related to CPPD disease, informed by contemporary literature.

Keywords

Calcium pyrophosphate deposition (CPPD) / crystals / inflammatory arthritis

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