Investigators supported by the ACR and EULAR have released their first-ever draft classification criteria for calcium pyrophosphate deposition disease (CPPD). If approved by the two organizations, the criteria will help clinicians more accurately diagnose and treat CPPD and encourage renewed research.
“CPPD is very prevalent in older adults, but research has lagged behind other types of arthritis for many reasons,” said criteria project co-leader Sara K. Tedeschi, MD, MPH, Co-Director, Fast Track Clinic for Giant Cell Arteritis, Brigham and Women’s Hospital, and Assistant Professor of Rheumatology, Harvard Medical School. “One of these is the absence of validated classification criteria that would allow us to identify relatively homogenous groups of patients for research.”
Dr. Tedeschi introduced the draft criteria during The Newly-Drafted ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease (CPPD) on Monday, November 14. The session, including extensive Q&A, is available for on-demand viewing for registered ACR Convergence participants through October 31, 2023, on the virtual meeting website.
Development of the criteria began in 2019 using a four-phase process applied to similar projects supported by the ACR and EULAR. The draft criteria are under review by both organizations.
The writing group identified 420 candidate criteria for CPPD, Dr. Tedeschi explained, including 264 clinical items, 90 imaging items, and 66 laboratory items. A series of expert consensus sessions reduced the potential classification criteria to 53 items, 23 of which were imaging-based.
Multiple imaging modalities are acceptable, Dr. Tedeschi noted, including conventional radiographs, ultrasound, computed tomography (CT), and dual-energy computed tomography (DECT).
An international multidisciplinary working group published CPPD reference images earlier in 2022, including basic calcium phosphate images to compare with CPPD images.
The initial 53 classification criteria were validated using de-identified patient data covering the spectrum of potential CPPD. These paper cases were provided by rheumatologists from 13 sites across six countries. A total of 418 cases were submitted and adjudicated by two blinded independent experts.
Paper cases were ranked to establish classification criteria, which must be applied in a specific order:
- Entry criterion of ever having had at least one episode of joint pain, swelling, or tenderness
- Absolute exclusion criteria of all symptoms more likely explained by an alternate condition such as rheumatoid arthritis, gout, psoriatic arthritis, osteoarthritis, etc.
- Sufficient criteria of either crowned dens syndrome (CDS) or synovial fluid analysis demonstrating CPP crystals in a joint with swelling, tenderness, or pain
- The additive criteria score
Candidate criteria were ranked, combined, eliminated, and weighted to create eight domains:
- Age at onset of joint symptoms
- Time-course and symptoms of inflammatory arthritis
- Sites of typical episode(s) of inflammatory arthritis in peripheral joints
- Related metabolic diseases
- Synovial fluid crystal analysis from a symptomatic joint
- Osteoarthritis of hand/wrist on imaging
- Imaging evidence of CPPD in symptomatic peripheral joint(s)
- Number of peripheral joints with evidence of CPPD on an imaging modality regardless of symptoms
The candidate criteria were validated using a fresh cohort of 617 paper cases and adjudicated. All criteria were weighted by expert committees and given a positive or negative point score, explained Abhishek Abhishek, MD, PhD, MBBS, FRCP, Professor of Rheumatology, Nottingham Biomedical Research Centre, University of Nottingham, United Kingdom.
The additive scores for cases were tested in the derivation cohort. A score of at least 57 had 87.9 percent specificity for CPPD and 97.8 percent sensitivity. When tested in the validation cohort, a score of at least 57 had 92.5 percent specificity for CPPD and 99.2 percent sensitivity.
Imaging features and recurrent typical episodes of acute inflammatory arthritis carry the greatest weights.
“These criteria match the clinical picture of CPPD as primarily an inflammatory arthritis among older adults, typically manifesting with acute inflammatory features and a predilection for knee and wrist joints,” Dr. Abhishek said. “When exclusion criteria are not met, the presence of CDS or detection of CPP crystals in synovial fluid in a symptomatic joint are sufficient. Patients without these sufficient features can be classified by a score of 57 or higher representing a combination of imaging and clinical features.”
Imaging domains account for nearly half the weighting, up to a maximum of 48 of the required 57 points, he added.
“We didn’t specify a combination of imaging and clinical features, but that is how the scoring worked out,” Dr. Tedeschi said. “Ultrasound, CT, and DECT are more sensitive than conventional radiography, and all methods have similar specificity. Future revisions to these draft criteria may reflect further research updates.”