Patterns and Predictors of Acute Calcium Pyrophosphate Crystal Arthritis (Pseudogout) Flares

Abstract

Objective: Pseudogout is a crystalline arthritis that causes episodes of joint inflammation, and is the most dramatic manifestation of calcium pyrophosphate deposition disease (CPPD). The rate at which pseudogout flares occur has not been well-described. We characterized pseudogout flares in detail and determined the rate and predictors of pseudogout flares in an academic medical center cohort. Methods: We performed a retrospective cohort study among a random sample of pseudogout patients identified in the Partners HealthCare electronic medical record (EMR), 1990-2017. Pseudogout was defined by synovitis, plus synovial fluid calcium pyrophosphate crystals and/or x-ray chondrocalcinosis. For each pseudogout patient we reviewed the EMR from the date of first episode (index date) through the last clinical note in the EMR for evidence of a recurrent flare. Subjects with no follow-up after the index date were excluded. For the first episode and each documented flare of pseudogout we collected data on the affected joint(s), treatments, and clinical data from the preceding 30 days. We calculated flare rate overall and separately in men and women. We compared characteristics of patients that did and did not have >1 recurrent pseudogout flare using Fisher’s exact and t-tests. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for pseudogout flare for baseline and time-varying covariates using multivariable Cox regression models that accounted for clustered data. Results: We identified 70 pseudogout patients with a total of 111 pseudogout episodes. Recurrent flares of pseudogout occurred in 24% of patients with 7% of patients experiencing at least 5 total flares. The median interval between flares was 5.7 months (range 0.4-110.5 months). Approximately half of recurrent flares occurred in a previously unaffected joint and most were in the hands, wrists, and knees. Flare rate was 11.4 (95% CI 11.3-11.5) per 100 person-years overall, 14.2 (95% CI 14.0-14.3) per 100 person-years in women, and 7.1 (95% CI 6.9-7.2) per 100 person-years in men. Patients with >1 recurrent flare were more likely to have received no treatment during the index episode compared to those that did not flare (23.5% vs. 5.3%, p=0.04). The risk of pseudogout flare was increased in patients with cancer (HR 2.98, 95% CI 1.33-6.68) and chronic kidney disease (HR 2.92, 95% CI 1.10-7.76). Conclusion: Pseudogout flares occurred in approximately one-fourth of patients in this tertiary care cohort, and often occurred in previously unaffected joints. The flare rate was similar to prior reports in gout; in contrast to gout, the flare rate was twice a high in women compared to men.