Calcium pyrophosphate deposition disease

Last updated: November 20, 2023

Summarytoggle arrow icon

Calcium pyrophosphate deposition (CPPD) disease is a crystalline inflammatory arthritis seen primarily in individuals over age 60. It results from the deposition of calcium pyrophosphate dihydrate (CPP) crystals within articular cartilage. While it is typically idiopathic, it may also be caused by joint damage, various metabolic abnormalities, or a genetic predisposition. CPPD disease can be asymptomatic or manifest with acute or chronic symptoms. Pseudogout refers to acute CPP crystal arthritis, which typically presents as sporadic flares of monoarticular synovitis affecting a large joint and can last for much longer than a typical gout flare. Chronic CPP crystal arthritis has many clinical phenotypes, the most common of which resembles severe osteoarthritis. Identification of CPP crystals on synovial fluid analysis or on imaging in a patient with typical symptoms confirms the diagnosis. Treatment is primarily symptomatic and consists of antiinflammatory medications (including intraarticular and systemic glucocorticoids, colchicine, and NSAIDs). There is currently no specific treatment targeted at CPP crystals.

Epidemiologytoggle arrow icon

  • Sex: = [1]
  • Age of onset: adults > 60 years [1]
  • Prevalence: 8–10 million adults in the US [1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Deposition of calcium pyrophosphate dihydrate (CPP or CPPD) crystals in articular cartilageparoxysmal joint inflammation and cartilage destruction → inflammatory arthritis (crystalline arthritis)

Clinical featurestoggle arrow icon

There are several distinct clinical phenotypes of CPPD disease. CPPD may also remain asymptomatic and be identified incidentally on imaging (asymptomatic chondrocalcinosis). [1][2][4]

Acute CPP crystal arthritis (pseudogout)

  • Clinical features
  • Features that differ from acute gout
    • Longer duration of acute attacks
    • Possible systemic symptoms [5]
  • Triggers: can occur spontaneously or be triggered by joint trauma/surgery or acute illness [4]

Pseudogout refers to the acute, not chronic, form of CPPD disease.

Chronic CPP crystal arthritis

Diagnosticstoggle arrow icon

There are currently no validated diagnostic criteria for CPPD disease. Diagnosis is based on the identification of CPP crystals on synovial fluid analysis and/or the presence of cartilage calcification on imaging in a patient with suggestive symptoms. [2][6]

Arthrocentesis and synovial fluid analysis (SFA) [4]

  • The most accurate diagnostic method, but crystals can often be difficult to identify. [2]
  • Expected findings

SFA can be falsely negative, as CPPD crystals are small and weakly birefringent. A negative SFA does not rule out CPPD disease. [1][6]

Imaging [1][4][8]

Laboratory studies

Treatmenttoggle arrow icon

Management of CPPD is primarily symptomatic, as there is currently no therapy that can prevent or treat CPP crystal deposition in cartilage. [1]

Referencestoggle arrow icon

  1. McCarthy GM, Dunne A. Calcium crystal deposition diseases — beyond gout. Nat Rev Rheumatol. 2018; 14 (10): p.592-602.doi: 10.1038/s41584-018-0078-5 . | Open in Read by QxMD
  2. Tedeschi SK. Issues in CPPD Nomenclature and Classification. Curr Rheumatol Rep. 2019; 21 (9): p.49.doi: 10.1007/s11926-019-0847-4 . | Open in Read by QxMD
  3. Abhishek A, Neogi T, Choi H, Doherty M, Rosenthal AK, Terkeltaub R. Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition. Arthritis & rheumatology (Hoboken, N.J.). 2018; 70 (8): p.1182-1191.doi: 10.1002/art.40517 . | Open in Read by QxMD
  4. Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med. 2016; 374 (26): p.2575-2584.doi: 10.1056/nejmra1511117 . | Open in Read by QxMD
  5. Kelley JT, Agudelo CA, Sharma V, Holland NW. Fever with Acute Arthritis in Calcium Pyrophosphate Dihydrate Deposition Disease: A Missed Explanation for Altered Mental Status in Elderly Patients?. J Clin Rheumatol. 2001; 7 (5): p.322-325.doi: 10.1097/00124743-200110000-00013 . | Open in Read by QxMD
  6. Ivory D, Velázquez CR. The forgotten crystal arthritis: calcium pyrophosphate deposition. Mo Med. ; 109 (1): p.64-8.
  7. ALEXANDER HECK, NATHANIAL NOLAN, CHRISTIAN ROJAS-MORENO. Crowned Dens Syndrome: Calcium Pyrophosphate Deposition Disease Masquerading as Osteomyelitis. J Rheumatol. 2018; 45 (10): p.1422-1423.doi: 10.3899/jrheum.170921 . | Open in Read by QxMD
  8. Miksanek J, Rosenthal AK. Imaging of calcium pyrophosphate deposition disease. Curr Rheumatol Rep. 2015; 17 (3): p.20.doi: 10.1007/s11926-015-0496-1 . | Open in Read by QxMD

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