Calcium Pyrophosphate Deposition Disease 

  • Author: Constantine K Saadeh, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Apr 19, 2012
 

Background

Calcium pyrophosphate deposition disease (CPDD) is a metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate in and around joints, especially in articular cartilage and fibrocartilage. Although CPDD is often asymptomatic, with only radiographic changes seen (ie, chondrocalcinosis), various clinical manifestations may occur, including acute (pseudogout) and chronic arthritis (see the images below). (See Etiology, Presentation, and Workup.)

Calcium pyrophosphate deposition disease. RadiograCalcium pyrophosphate deposition disease. Radiograph of the knee showing chondrocalcinosis involving the meniscal cartilage, as well as evidence of osteoarthritis. Calcium pyrophosphate deposition disease. RadiograCalcium pyrophosphate deposition disease. Radiograph of the wrist and hand showing chondrocalcinosis of the articular disc of the wrist and atypical osteoarthritis involving the metacarpophalangeal joints in a patient with underlying hemochromatosis.

Almost any joint may be involved by CPDD, although the knees, wrists, and hips are most often affected. This condition is the most common cause of secondary metabolic osteoarthritis. (See Presentation.)

According to McCarty, the 5 most common presentations of CPDD are as follows:

  • Asymptomatic (lanthanic) CPDD
  • Acute pseudogout
  • Pseudo-osteoarthritis
  • Pseudorheumatoid arthritis
  • Pseudoneuropathic joints

Prognosis

Patients with CPDD can experience significant morbidity due to the pain of an acute attack of pseudogout or to symptoms of chronic arthropathy. Treatment of symptomatic CPDD is important to prevent further end-organ damage, but it cannot reverse the joint disease.

Patient education

For patient education information, see the Arthritis Center, as well as Knee Pain.

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Etiology

Although the exact mechanism for the development of CPDD remains unknown, increased adenosine triphosphate breakdown with resultant increased inorganic pyrophosphate in the joints results from aging, genetic factors, or both. Changes in the cartilage matrix may play an important role in promoting CPPD deposition. Rare hereditary forms of CPDD occur, generally inherited in an autosomal dominant mode.

Overactivity of enzymes that break down triphosphates, such as nucleoside triphosphate pyrophosphohydrolase, has been observed in the cartilage of patients with CPDD. Therefore, inorganic pyrophosphate can bind calcium, leading to CPPD deposition in the cartilage and synovium.[1, 2] Hyaline cartilage is affected most commonly, but fibrocartilage, such as the meniscal cartilage of the knee, can also be involved.[3]

Hypotheses based on in vitro studies propose that pyrophosphohydrolase activity and inorganic phosphate content, as noted above, are generalized phenomena that occur in fibroblasts.[4] Although these phenomena are generalized, the reason they occur only in joints remains unknown.

Genetics

Genetic defects have been identified as specific gene mutations in a few kindred families.[5] The mutations occurred in the genes ANKH and COL, which may be involved in crystal-induced inflammation. This is related to synovial tissue and direct cartilage activation, leading to the arthritis caused by CPPD. The ANKH gene has also been shown to be involved in cellular transport of inorganic phosphate.

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Epidemiology

Occurrence in the United States

CPDD is a common condition that occurs with aging in all races. Nearly 50% of people older than 85 years have radiologic evidence of chondrocalcinosis.

Sex- and age-related demographics

CPDD is slightly more common in women than in men. The exact female-to-male ratio is unknown but is probably 1.4:1.

CPDD usually occurs in individuals who are in the fifth decade of life or older, with increasing prevalence as age increases. When it occurs early, before the fourth decade of life, it is usually associated with a secondary cause, such as an underlying metabolic disease, or with a familial cause.

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Contributor Information and Disclosures
Author

Constantine K Saadeh, MD  President, Allergy ARTS, LLP; Principal Investigator, Amarillo Center for Clinical Research, Ltd

Constantine K Saadeh, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Rheumatology, American Medical Association, Southern Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Jan Malacara, PA-C Consulting Staff, Allergy ARTS, LLP

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acknowledgments

The authors wish to thank Shannon Shaw and Michael Gaylor for their hard work in helping to prepare this article.

References

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  2. Tsui FW. Genetics and Mechanisms of Crystal Deposition in Calcium Pyrophosphate Deposition Disease. Curr Rheumatol Rep. Dec 24 2011;[Medline].

  3. Pritzker KP, Cheng PT, Renlund RC. Calcium pyrophosphate crystal deposition in hyaline cartilage. Ultrastructural analysis and implications for pathogenesis. J Rheumatol. 1988;15(5):828-35. [Medline].

  4. Ryan LM, Wortmann RL, Karas B. Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease. J Clin Invest. May 1986;77(5):1689-93. [Medline].

  5. Zaka R, Williams CJ. Genetics of chondrocalcinosis. Osteoarthritis Cartilage. Sep 2005;13(9):745-50. [Medline].

  6. Doherty M, Hamilton E, Henderson J. Familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in English families. Br J Rheumatol. Feb 1991;30(1):10-5. [Medline].

  7. Ryan LM. Calcium pyrophosphate dihydrate crystal deposition. In: Weyand CM, Wortman R, Klippel JH, eds. Primer on Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation; 1997:226-9.

  8. Saffar P. Chondrocalcinosis of the wrist. J Hand Surg [Br]. Oct 2004;29(5):486-93. [Medline].

  9. Ellabban AS, Kamel SR, Omar HA, El-Sherif AM, Abdel-Magied RA. Ultrasonographic diagnosis of articular chondrocalcinosis. Rheumatol Int. Dec 23 2011;[Medline].

  10. Ea HK, Liote F. Calcium pyrophosphate dihydrate and basic calcium phosphate crystal-induced arthropathies: update on pathogenesis, clinical features, and therapy. Curr Rheumatol Rep. Jun 2004;6(3):221-7. [Medline].

  11. Announ N, Palmer G, Guerne PA, Gabay C. Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure. Joint Bone Spine. Jul 2009;76(4):424-6. [Medline].

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  14. Halverson PB, McCarty DJ. Patterns of radiographic abnormalities associated with basic calcium phosphate and calcium pyrophosphate dihydrate crystal deposition in the knee. Ann Rheum Dis. Jul 1986;45(7):603-5. [Medline].

  15. Pritzker KP. Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. Curr Opin Rheumatol. Jul 1994;6(4):442-7. [Medline].

  16. Rachow JW, Ryan LM, McCarty DJ. Synovial fluid inorganic pyrophosphate concentration and nucleotide pyrophosphohydrolase activity in basic calcium phosphate deposition arthropathy and Milwaukee shoulder syndrome. Arthritis Rheum. Mar 1988;31(3):408-13. [Medline].

  17. Rothschild BM, Woods RJ. Osteoarthritis, calcium pyrophosphate deposition disease, and osseous infection in Old World primates. Am J Phys Anthropol. Mar 1992;87(3):341-7. [Medline].

  18. Ryan LM, Rachow JW, McCarty DJ. Synovial fluid ATP: a potential substrate for the production of inorganic pyrophosphate. J Rheumatol. May 1991;18(5):716-20. [Medline].

  19. Suan JC, Chhem RK, Gati JS, et al. 4 T MRI of chondrocalcinosis in combination with three-dimensional CT, radiography, and arthroscopy: a report of three cases. Skeletal Radiol. Nov 2005;34(11):714-21. [Medline].

  20. Yamazaki H, Uchiyama S, Kato H. Median nerve and ulnar nerve palsy caused by calcium pyrophosphate dihydrate crystal deposition disease: case report. J Hand Surg Am. Oct 2008;33(8):1325-8. [Medline].

 
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Calcium pyrophosphate deposition disease. Radiograph of the knee showing chondrocalcinosis involving the meniscal cartilage, as well as evidence of osteoarthritis.
Calcium pyrophosphate deposition disease. Radiograph of the wrist and hand showing chondrocalcinosis of the articular disc of the wrist and atypical osteoarthritis involving the metacarpophalangeal joints in a patient with underlying hemochromatosis.
Calcium pyrophosphate deposition disease. Appearance of calcium pyrophosphate dihydrate crystals obtained from the knee of a patient with pseudogout. The crystals are rhomboid-shaped with weakly positive birefringence, as seen by compensated polarized microscopy. The black arrow indicates the direction of the compensator.
Calcium pyrophosphate deposition disease. High-powered view of calcium pyrophosphate dihydrate crystals with compensated polarized microscopy. The black arrow indicates the direction of the compensator. Crystals parallel to the compensator are blue, while those perpendicular to the compensator are yellow.
Calcium pyrophosphate deposition disease. High-powered view of calcium pyrophosphate dihydrate crystals with compensated polarized microscopy. The crystals parallel to the compensator were blue, while those perpendicular to the compensator were yellow. However, the crystals have been rotated 90%, resulting in a color change in both of them. The direction of the compensator was not changed and is indicated by the black arrow.
Wrist chondrocalcinosis.
 
 
 
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