Calcium pyrophosphate deposition

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 9 Apr 2025

Last updated: 15 Feb 2024

Calcium pyrophosphate arthritis is caused by deposition of articular calcium pyrophosphate (CPP) crystals.

It can be difficult to diagnose as CPP crystals in synovial fluid can be small, sparse, and difficult to find.

In patients <60 years of age, underlying metabolic conditions associated with calcium pyrophosphate deposition (CPPD), such as hyperparathyroidism or hemochromatosis, should be investigated.

There is no definitive treatment for CPP arthritis, but intra-articular or systemic anti-inflammatory drugs can be effective for both acute and chronic forms.

Definition

Calcium pyrophosphate deposition (CPPD) is associated with both acute and chronic arthritis. Acute calcium pyrophosphate (CPP) crystal arthritis is an acute inflammatory arthritis of one or more joints. Knees, wrists, shoulders, ankles, elbows, or hands can be affected. The chronic form of CPP arthritis mimics osteoarthritis or rheumatoid arthritis and is associated with variable degrees of inflammation.[1] CPPD typically occurs in older people but can occur in younger people with associated metabolic conditions, such as hyperparathyroidism and hemochromatosis.[2] Familial forms of the disease have been reported and often affect younger individuals.[3][4]

History and exam

Key diagnostic factors

painful and tender joints
osteoarthritis-like involvement of joints (wrists, shoulders)
sudden worsening of osteoarthritis

Full details

Other diagnostic factors

red and swollen joints
joint effusion and fluctuance
fever and malaise

Full details

Risk factors

advanced age
injury
hyperparathyroidism
hemochromatosis
family history of CPPD
hypomagnesemia
hypophosphatasia
gout
other metabolic conditions

Full details

Diagnostic tests

1st tests to order

arthrocentesis with synovial fluid analysis
radiographs of affected joints
serum calcium
serum parathyroid hormone
iron studies
serum magnesium
serum alkaline phosphatase

Full details

Tests to consider

ultrasonography
CT scan

Full details

Treatment algorithm

ACUTE

mono- or oligoarticular disease

polyarticular disease

ONGOING

chronic recurrent involvement of knee, hip, or shoulder joint with severe degeneration

with osteoarthritis-like disease or rheumatoid-like disease

Contributors

Authors

Ann K. Rosenthal, MD

Professor of Medicine

Medical College of Wisconsin

Milwaukee

Disclosures

AKR is the author of several articles cited in this topic.

Peer reviewers

Priyanka Iyer, MD

Clinical Assistant Professor

University of California, Irvine

Irvine

Disclosures

PI declares that she has no competing interests.

Ade Adebajo, MBBS, MSc, FRCP (Glasgow), FACP

Consultant Rheumatologist

Rheumatology

University of Sheffield Medical School

Sheffield

Disclosures

AA declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

McCarty DJ. Diagnostic mimicry in arthritis: patterns of joint involvement associated with calcium pyrophosphate dihydrate crystal deposits. Bull Rheum Dis. 1975;25:804-809.

Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis. 2011 Apr;70(4):563-70.Full text Abstract

Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med. 2016 Jun 30;374(26):2575-84.Full text Abstract

Martinez Sanchis A, Pascual E. Intracellular and extracellular CPPD crystals are a regular feature in synovial fluid from uninflamed joints of patients with CPPD related arthropathy. Ann Rheum Dis. 2005 Dec;64(12):1769-72. Abstract

Zhang W, Doherty M, Pascual E, et al. EULAR recommendations for calcium pyrophosphate deposition. Part II: management. Ann Rheum Dis. 2011 Apr;70(4):571-5.Full text Abstract

Creamer P. Intra-articular corticosteroid treatment in osteoarthritis. Curr Opin Rheumatol. 1999 Sep;11(5):417-21. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Acute gouty arthritis
- Acute septic arthritis
- Milwaukee shoulder syndrome
More Differentials
Guidelines
- European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis
- EULAR recommendations for calcium pyrophosphate deposition. Part II: management
More Guidelines
Videos
Aspiration and injection of the knee: animated demonstration
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Calcium pyrophosphate deposition

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

mono- or oligoarticular disease

polyarticular disease

chronic recurrent involvement of knee, hip, or shoulder joint with severe degeneration

with osteoarthritis-like disease or rheumatoid-like disease

Contributors

Authors

Ann K. Rosenthal, MD

Disclosures

Peer reviewers

Priyanka Iyer, MD

Disclosures

Ade Adebajo, MBBS, MSc, FRCP (Glasgow), FACP

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Videos

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice