Crystal deposition disease of the shoulder at uncommon sites: Diagnostic challenges and nomenclature issues in the absence of synovial fluid analysis

Calcium pyrophosphate deposition (CPPD) disease is a common, age-related crystalline arthropathy with diverse clinical presentations. While the knees and wrists are most frequently affected, shoulder involvement is increasingly recognized, occurring in up to 13% of cases, though often underdiagnosed. This mini-review provides a comprehensive overview of the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of shoulder CPPD, contextualized by an illustrative case of a 78-year-old woman with atypical calcifications in the axillary recess and supraspinatus muscle. A key focus is the diagnostic challenge when synovial fluid analysis, the gold standard for crystal confirmation, is technically unfeasible, a common scenario in clinical practice. We systematically discuss modern imaging techniques (ultrasound, dual-energy computed tomography [CT], conventional radiography) and demonstrate the practical application of the 2023 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for establishing probable CPPD when crystal analysis is unavailable. The review addresses critical differential diagnosis considerations, particularly distinguishing CPPD from basic calcium phosphate (BCP) deposition disease, and summarizes evidence-based therapeutic strategies for acute pseudogout flares and chronic inflammatory arthritis, including emerging biologic therapies targeting the interleukin-1 (IL-1) pathway. This comprehensive resource aids clinicians managing shoulder calcifications in the absence of definitive crystal confirmation.