Calcium pyrophosphate deposition (CPPD) disease is a common type of arthritis that occurs when calcium pyrophosphate crystals deposit in the joint and surrounding tissues, which are often painful and create symptoms similar to gout. There is a lack of research on CPPD, even though it affects between 8-10 million U.S. adults.
Brigham and Women’s Hospital researchers from the Division of Rheumatology, Inflammation and Immunity are working to better understand CPPD and improve patient care. Sara K. Tedeschi, MD, MPH, co-director of the Fast Track Clinic for Giant Cell Arteritis at the Brigham, answers questions about CPPD and how her team’s recent studies are raising awareness and helping to establish research infrastructure for the disease.
Q: What is calcium pyrophosphate deposition (CPPD) disease?
Tedeschi: CPPD disease is a common crystalline arthritis that generally affects older adults and can cause various symptoms due to the deposition of calcium pyrophosphate crystals in joint tissues. The most well-recognized manifestation is acute joint pain and swelling, which has traditionally been called “pseudogout” due to its clinical similarity with gout. CPPD disease can also manifest as chronic joint inflammation, historically called “pseudo-rheumatoid,” given the similarity to rheumatoid arthritis. CPPD disease frequently co-exists with osteoarthritis and can affect joints that are not typically affected by primary osteoarthritis, such as the shoulders. People with CPPD can have one or more of these manifestations over a lifetime.
Q: Why is CPPD a main area of interest in your research?
Tedeschi: CPPD disease is estimated to affect 8-10 million adults in the United States. This is similar to the number of adults with gout, yet our understanding of CPPD disease lags far behind our knowledge of gout and other types of inflammatory arthritis. Targeted treatments to dissolve calcium pyrophosphate crystals do not currently exist, and the handful of medications for treating CPPD symptoms are not always effective. We have a lot to learn about CPPD disease so that we can ultimately improve patient care.
Q: How are you and your colleagues expanding awareness about CPPD? Do you have any recent findings that you are most excited about?
Tedeschi: We recently identified that patients with CPPD disease had a greater risk for cardiovascular disease than those without CPPD. Our first study, published in Arthritis Care & Research (Hoboken), was a nationwide study among U.S. veterans that included >23,000 patients with any form of CPPD disease identified by diagnosis codes. Patients with CPPD disease had a 25% greater risk for a non-fatal cardiac event (myocardial infarction, stroke, coronary revascularization, or acute coronary syndrome), even after adjusting for traditional cardiovascular risk factors and medications relevant to cardiovascular disease. We then studied this question among 1,200 patients with pseudogout—the acute inflammatory manifestation of CPPD disease—that were identified at Mass General Brigham using a machine learning algorithm developed by our group, which is highly accurate for identifying patients with pseudogout. Among patients that had had an episode of pseudogout, the risk for a non-fatal cardiac event was 90% greater in the first two years after that episode, and two-fold greater up to 10 years later after adjusting for cardiovascular risk factors and medications. This was published in the Annals of the Rheumatic Diseases. These two studies provide novel evidence that CPPD disease is a risk factor for cardiovascular disease. The next step is to try to understand why.
Q: Do you have ongoing research studies attempting to answer questions about CPPD?
Tedeschi: We are working on two major international collaborations to establish a research infrastructure for CPPD. The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) are co-sponsoring the development of classification criteria to identify patients with CPPD for inclusion in clinical research. I serve on the Steering Committee, and we presented the results at the ACR meeting in November 2022 in Philadelphia, PA. The Outcomes Measures in Rheumatology (OMERACT) CPPD Working Group, which I co-chair, is developing a core set of outcome measures that will be recommended for clinical trials in CPPD.
Our group at Brigham and Women’s Hospital has established a prospective registry of patients with CPPD, the BRIgham Cppd (BRIC) Registry. Participants answer surveys every six months and participate in in-person study visits. We also presented preliminary data from the BRIC Registry at the ACR annual meeting to share our findings, including that patients with CPPD experience pain comparable to those with gout and osteoarthritis and often have greater unmet treatment needs than gout patients.
Q: How do you think this research will impact or has already impacted patient care?
Tedeschi: The upcoming ACR/EULAR CPPD classification criteria will facilitate research on CPPD by helping investigators identify patients for clinical research studies, including future treatment trials that are sorely needed. The development of a set of core outcome domains by the OMERACT CPPD working group will complement the ACR/EULAR classification criteria, providing a framework for what information to collect during clinical trials.
The BRIC Registry has tremendous potential to increase our understanding of the natural history of CPPD, including subsets of patients that may respond to specific treatments.