• Arthritis, Rheumatoid
• Chondrocalcinosis
• Crystal arthropathies
• Prevalence
• Classification

The 2023 ACR/EULAR Classification Criteria for calcium pyrophosphate deposition (CPPD) disease were recently approved.1 These criteria used an adjusted domain scoring system including demographic, clinical and radiological characteristics, and synovial fluid crystal analysis. Their development was driven by the necessity to address diagnostic challenges arising from variable clinical presentations and the complexity of analysing synovial fluid seeking for CPP crystals, with their primary purpose being to identify patients eligible for inclusion in research studies.2 Differential diagnosis of CPPD-disease mostly involves rheumatoid arthritis (RA) for chronic-CPP crystal inflammatory arthritis, gout for acute-CPP crystal arthritis and osteoarthritis (OA) with CPPD (often identified incidentally).3 Particularly, discerning between chronic-CPP crystal arthritis and seronegative-RA can be challenging due to overlapping joint involvement, seronegativity, potential treatment responses and occasional coexistence.4–6

We performed a retrospective cross-sectional analysis within a real-world clinical setting. Our objectives were to evaluate the proportion of patients diagnosed with seronegative-RA who fulfilled the CPPD-disease classification criteria, and to identify demographic and clinical differences among them based on whether they met or not the criteria. The cohort included all patients from an RA clinic who were visited during September to December 2022. Data were collected retrospectively from medical records, including demographic, clinical, serological biomarkers and imaging variables (conventional X-ray and/or ultrasound). The classification criteria were subsequently applied. Statistical analysis included χ² tests and t-tests to assess group differences.

We identified 364 RA patients, and excluded those positive for RF and/or anti-citrullinated protein antibodies. The final cohort included 96 patients, 24.4% of the initial sample. Of these, 74.7% were female, with a mean age at symptom onset of 59.3 (±16.4) years and average disease duration of 8.35 years.

Of the 96 patients, 18 (18.9%) met the CPPD-disease criteria. Table 1 summarises their characteristics, based on whether they met or not the criteria.

Patients who met the criteria were older (p=0.048) and exhibited a distinct clinical presentation. Experiencing more than one typical episode of acute arthritis, defined by acute onset/worsening of joint pain with swelling/warmth resolving irrespective of treatment within 14 days, was more common in patients fulfilling the criteria (72.2% vs 33.8%). Within our cohort, none of the patients manifested only one typical episode, likely attributable to the inherent bias in the inclusion criteria, which involved patients with a prior diagnosis of RA known for experiencing recurrent episodes. Joint clinical involvement locations did not significantly differ between the two groups, but majority of the patients who met the criteria exhibited wrist involvement (88.8%), whereas metacarpophalangeal and interphalangeal joint involvement were more common in seronegative-RA without CPPD. In our cohort, none of the patients had positive synovial fluid crystals but we found a highly significant association (p=0.000) between the presence of chondrocalcinosis (CC) and the criteria fulfilment. In our cohort, the identification of imaging evidence of CC demonstrated absolute specificity, corroborating the substantial weight assigned to it in the classification criteria. Notably, it is essential to recognise that while radiographic CC supports the diagnosis of CPPD-disease, the absence of such findings does not exclude it, as highlighted in existing literature.4 Similarly, a significant association (p=0.000) was demonstrated between criteria fulfilment and OA occurring in locations typical of CPPD-disease: bilateral radiocarpal, scaphoid/trapezium/trapezoid without the involvement of trapeziometacarpal, second/third metacarpophalangeal joints. This OA pattern was observed in 55.5% of individuals fulfilling the criteria. Notably, no significant treatment disparities were detected between the subgroups. Among patients positive for CPPD-disease criteria, 74% were treated with disease-modifying antirheumatic drugs.

In summary, our study underscores the importance of imaging within the classification criteria, highlighting its utility in distinguishing between seronegative-RA and CPPD-disease. This distinction is particularly valuable in scenarios where differential diagnosis is challenging, as it may carry important prognostic and therapeutic implications.