Acute Calcium Pyrophosphate Crystal Arthritis Flare Rate and Risk Factors for Recurrence

Abstract

Objective Little is known about acute calcium pyrophosphate (CPP) crystal arthritis flare rates and risk factors for recurrence. We characterized flares and determined the rate and predictors of acute CPP crystal arthritis flares in an academic medical center cohort. Methods We performed a retrospective cohort study among a random sample of patients with acute CPP crystal arthritis identified in the Partners HealthCare electronic medical record, 1991–2017. Flare was defined as self-limited, acute-onset synovitis with synovial fluid CPP crystals and/or chondrocalcinosis, not better explained by another cause. We calculated incidence rates (IR) for acute CPP crystal arthritis flare among all subjects and by sex. We estimated HR for recurrent flare using univariate Cox models that accounted for within-person correlated data. Results We identified 70 patients with acute CPP crystal arthritis with a total of 111 flares. Recurrent flares occurred in 24% of patients; half of flares occurred in a previously unaffected joint. The acute CPP crystal arthritis flare rate was 11.4 per 100 person-years overall (95% CI 8.2–15.4), 14.2 in women (95% CI 9.6–0.1), and 7.1 in men (95% CI 3.4–13.0). Cancer (HR 2.98, 95% CI 1.33–6.68) and chronic kidney disease (HR 2.92, 95% CI 1.10–7.76) were associated with a higher rate for recurrent flare. Conclusion Recurrent flares occurred in about one-fourth of patients with acute CPP crystal arthritis and often occurred in previously unaffected joints. The acute CPP crystal arthritis flare rate was twice as high in women as in men.

Risk of cardiovascular events in patients having had acute calcium pyrophosphate crystal arthritis

“…Unmeasured confounding is also possible in any observational cohort study. Approximately 25% of patients with one episode of acute CPP crystal arthritis have a subsequent episode, and this study design was unable to assess whether recurrent episodes (or future treatments such as NSAIDs and glucocorticoids) occurred and/or mediate CV risk 3. The index date of acute CPP crystal arthritis was based on a documented episode and likely does not represent the true onset of CPPD disease; indeed, much remains unknown regarding the natural history of CPPD including disease evolution over time.…”

“…Acute CPP crystal arthritis, historically known as ‘pseudogout’, is the most widely recognised manifestation of CPPD. This acute inflammatory arthritis is characterised by acute monoarticular or oligoarticular joint pain and swelling, often with warmth and limited range of motion, and recurs in approximately 25% of patients 3. Episodes of acute CPP crystal inflammatory arthritis are triggered by articular cartilage releasing CPP crystals into the joint, leading to NLRP3 inflammasome activation and interleukin-1 (IL-1) β release 4 5…”

Mixed Crystal Disease: A Tale of 2 Crystals

“…A report published in this issue of The Journal estimated the recurrence rate of acute calcium pyrophosphate (CPP) crystal arthritis and its associated factors 1 on 111 patients with a first acute flare of CPP arthritis. Of these, 13 were considered to have gout on top of fulfilling the study's definition of acute CPP crystal arthritis: 1 had monosodium urate (MSU) crystals documented on a different occasion in a different joint, 1 had simultaneous observation of MSU and CPP crystals in the same joint, 7 had prior podagra, and 4 had been diagnosed with gout based on elevated uric acid and synovitis in a joint different from that in which CPP arthritis was diagnosed.…”

An Update on the Diagnosis and Management of Calcium Crystal Disease

“…A recent study from the USA found that the incidence of acute CPP crystal arthritis flare was 11.4 per 100 person-years with flares being twice as common in women than in men [ 22 ]. In this study, Yates et al analysed CPPD flares in 70 patients from a single health care system and found that recurrence occurred in approximately one-fourth of patients with acute CPP crystal arthritis and often in previously unaffected joints [ 22 ]. Subsequently, further work from this group identified other factors associated with acute flares of CPPD including OA, RA, gout, male sex, chemotherapy use, loop and thiazide diuretic use [ 23 ].…”