The clinical phenotypes of calcium pyrophosphate deposition disease: data from the international cohort for the ACR/EULAR classification criteria

 

Tristan Pascart, Augustin Latourte, Sara K Tedeschi, Nicola Dalbeth, Tuhina Neogi, Robert Terkeltaub, Hyon K Choi, Abhishek Abhishek, on behalf of the ACR/EULAR CPPD classification criteria working group.

 

Affiliation(s):

 

 

Context: Calcium pyrophosphate deposition (CPPD) disease is an umbrella term comprising various acute and chronic clinical phenotypes. The prevalence of different phenotypes and their associations are not well understood. The objectives of this study were to describe the distribution of the main clinical phenotypes of CPPD disease in an international cohort of patients and to explore the demographic, clinical and imaging features associated with different clinical phenotypes.

Methods: Patients from the derivation and validation cohorts recruited for the development of the 2023 ACR/EULAR criteria were included in this analysis if they fulfilled the criteria for CPPD disease. The prevalence of three clinical phenotypes (acute CPP crystal arthritis, persistent CPP crystal arthritis, crowned dens syndrome) were determined. We evaluated the association of clinical features, imaging findings, and metabolic/familial predispositions with each of the 3 phenotypes using multivariable logistic regression, with adjustment for age and sex (model 1) and for all covariates (model 2) in separate models.

Results: A total of 618 patients (56% female) with mean (standard deviation) age of 74.0 (11.9) years were included. Twenty-nine percent had features of two or more clinical phenotypes. Overlap between the clinical phenotypes are shown in the Venn diagram (figure 1). The prevalence of acute CPP crystal arthritis was almost universal (97.4% 95%CI (95.8;98.5), while persistent CPP crystal inflammatory arthritis was less common (25.6% 95%CI (22.2;29.2)), and the crowned dens syndrome (7.3% 95%CI (5.4;9.6)) was infrequent. Only 9 patients did not have inflammatory manifestations to date (1.4% 95%CI (0.7;2.7)) and presented with mechanical pain with CPPD in joints not typically affected with OA. 

Overall, 332/602 (55.1%) of patients with acute CPP crystal arthritis had >1 lifetime. Patients with recurrent acute CPP crystal arthritis more frequently had an episode involving the knee (OR 3.75 95%CI (2.47-5.71)) or wrist (OR 2.10 95%CI (1.37-3.23)) than those who had a single acute episode. Otherwise, no other clinical feature, imaging feature, or risk factors were more likely to be associated with recurrent episodes compared with single ones.

Patients with persistent CPP crystal inflammatory arthritis (n=158/618) were less likely to have developed CPPD symptom onset in older age groups (model 2 adjusted OR 0.04 95% CI (0.01;0.13) for those >80 years old age group than those <50) and were less likely to have associated metabolic conditions or a family history (adjusted OR 0.49 95%CI (0.30;0.80)). On the other hand, this phenotype was associated with higher likelihood of having had an episode of acute wrist arthritis (adjusted OR 2.77 95%CI (1.70;4.53)), and metacarpophalangeal (MCP) joint 2 and/or 3 osteoarthritis (adjusted OR 1.87 95%CI (1.16;3.02)) and scaphotrapezio-trapezoid (STT) osteoarthritis (adjusted OR 1.72 95%CI (1.06;2.79)) on conventional radiography.

The crowned dens syndrome (n=47) was associated with male sex (adjusted OR 2.44 95%CI (1.23;4.81)) and was inversely associated with acute episodes of peripheral arthritis (OR 0.26 95% CI (0.06;1.22) for >1 acute peripheral episode than one or no episodes). STT osteoarthritis was associated with crowned dens syndrome (OR 2.77 95%CI (1.21;6.34), as was increasing number of joints with chondrocalcinosis (OR 1.45 95%CI (1.14-1.84) for each additional joint).

Conclusion: The overwhelming phenotype of CPPD disease reported in this large international cohort collected for the purpose of developing and validating classification criteria was acute CPP crystal arthritis, which was recurrent in half of the cases. A quarter of patients experienced persistent CPP crystal inflammatory arthritis, usually at a younger age, and this phenotype was associated with acute wrist arthritis and radiographic features of MCP and STT osteoarthritis. The crowned dens syndrome was a rare phenotype associated with more extensive chondrocalcinosis in peripheral joints, and with features of hand OA.

(Fig. 1)