Hypercalcemia

Calcium pyrophosphate deposition (CPPD) disease is caused by CPP crystal accumulation in musculoskeletal tissues, leading to inflammation
Symptomatic CPPD disease (formerly known as “pseudogout”) is more common in older than younger adults and typically affects joints with previous damage. Chondrocalcinosis visible on radiographs affects 10% of adults and 50% of those older than 80 years, but most people are asymptomatic and findings are noted incidentally.1

The most common presentation is acute inflammatory monoarthritis affecting the wrists or knees, which resolves within 4 weeks
Extra-articular structures can also be affected, leading to acute inflammatory tendinitis. Crowned dens syndrome comprises 5% of CPPD disease presentations and can mimic bacterial meningitis, manifesting with acute cervical neck pain, fever, and elevated inflammatory markers with CPPD at C1 to C2, seen on computed tomography. The chronic (> 3 mo) inflammatory phenotype presents with hand or wrist symmetric polyarthritis, or with recurrent flares, and can be misdiagnosed as seronegative rheumatoid arthritis. Calcium pyrophosphate deposition disease and osteoarthritis can co-exist — underlying CPPD disease should be considered in patients with osteoarthritis at atypical locations (e.g., metacarpophalangeal joints, wrists, ankles, shoulders, elbows).2

Diagnosis can be confirmed with CPP crystals identified from synovial fluid, or the presence of the crowned dens syndrome
Although used for research, the 2023 Classification Criteria have high sensitivity (99.2%) and specificity (92.5%), thereby providing a diagnostic framework.2 Supportive diagnostic features include acute knee or wrist inflammatory arthritis in an older adult, osteoarthritis at atypical areas, or CPPD on imaging.3

Patients younger than 60 years at diagnosis should be assessed for associated metabolic diseases
Investigations for secondary causes of CPPD disease include calcium (hypercalcemia), parathyroid hormone (hyperparathyroidism), ferritin, transferrin saturation (hemochromatosis), magnesium (hypomagnesemia), and alkaline phosphatase (hypophosphatasia).2

Corticosteroids, colchicine, and nonsteroidal antiinflammatory drugs can treat acute flares4
Inflammatory arthritis lasting more than 3 months or recurrent flares (> 2/yr) should prompt rheumatology referral for consideration of chronic suppressive colchicine, hydroxychloroquine, or methotrexate (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.250933/tab-related-content).5