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Calcium Pyrophosphate Deposition Disease Differential Diagnoses

  • Author: Constantine K Saadeh, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jul 15, 2016
 
 

Diagnostic ConsiderationsGitelman syndromeSeptic arthritisOther differentials

Gitelman syndrome is associated with hypokalemic metabolic acidosis and hypomagnesemia. Patients with Gitelman syndrome may have renal tubular acidosis and a history of pseudogout. Consequently, this diagnosis should be considered in patients with such findings.

Gitelman syndrome has been shown to be associated with a mutation in the gene solute carrier family 12, member 3 (SLC12A3). The cause may be related to the thiazide-sensitive sodium chloride cotransporter, which is found in a variant form in most patients with the syndrome.

Gitelman syndrome can mimic several other manifestations of calcium pyrophosphate deposition disease (CPDD), including osteoarthritis, carpal tunnel syndrome, and tenosynovitis with calcifications along the tendon sheath itself.[1]

Septic arthritis can present as monoarticular arthritis and, therefore, can mimic acute pseudogout. Therefore, a Gram stain of the fluid should be performed. The results of the Gram stain will be negative unless a concomitant infection is present.

If septic arthritis is suggested clinically, even if crystals are seen on compensated polarized microscopy, it must be evaluated and, possibly, treated.

The differential diagnosis for pseudo-osteoarthritis includes hemochromatosis, hyperparathyroidism, hypothyroidism, and traumatic arthritis (as occurs in heavy-equipment machinery operators).

Basic calcium phosphate deposition disease and Lyme arthritis are also included in the differential diagnosis of CPDD.

Differential Diagnoses

 
 
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, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; 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, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Neil J Barkin, MD, FAAOS Consulting Surgeon, Capitol Orthopaedics & Rehabilitation, LLC

Neil J Barkin, MD, FAAOS is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

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

Paul E Di Cesare, MD, FACS Professor, Department of Orthopedic Sugery, University of California, Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting; Smith & Nephew Consulting fee Consulting

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Jegan Krishnan, MBBS, FRACS, PhD Professor, Chair, Department of Orthopedic Surgery, Flinders University of South Australia; Senior Clinical Director of Orthopedic Surgery, Repatriation General Hospital; Private Practice, Orthopaedics SA, Flinders Private Hospital

Jegan Krishnan, MBBS, FRACS, PhD, is a member of the following medical societies: Australian Medical Association, Australian Orthopaedic Association, and Royal Australasian College of Surgeons

Disclosure: Nothing to disclose.

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.

Dinesh Patel, MD, FACS Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital

Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons

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

Anne Tesar, PA-C Physician Assistant, Capitol Orthopaedics and Rehabilitation, LLC

Anne Tesar, PA-C is a member of the following medical societies: American Academy of Physician Assistants

Disclosure: Nothing to disclose.

Acknowledgments

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

References
  1. Zabotti A, Della Siega P, Picco L, Quartuccio L, Bassetti M, De Vita S. Gitelman syndrome disclosed by calcium pyrophosphate deposition disease: early diagnosis by ultrasonographic study. Reumatismo. 2016 Jun 23. 68(1):53-5. [Medline].

  2. Beutler A, Rothfuss S, Clayburne G. Calcium pyrophosphate dihydrate crystal deposition in synovium. Relationship to collagen fibers and chondrometaplasia. Arthritis Rheum. 1993 May. 36(5):704-15. [Medline].

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

  4. 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].

  5. 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. 1986 May. 77(5):1689-93. [Medline].

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

  7. Williams CJ. The role of ANKH in pathologic mineralization of cartilage. Curr Opin Rheumatol. 2016 Mar. 28(2):145-51. [Medline].

  8. Ramos YF, Bos SD, van der Breggen R, Kloppenburg M, Ye K, Lameijer EW, et al. A gain of function mutation in TNFRSF11B encoding osteoprotegerin causes osteoarthritis with chondrocalcinosis. Ann Rheum Dis. 2014 Apr 17. [Medline].

  9. Patel T, Ryan L, Dubois M, Carrera G, Baynes K, Mannem R, et al. The prevalence of chondrocalcinosis of the symphysis pubis on CT scan and correlation with calcium pyrophosphate dihydrate crystal deposition disease. Clin Rheumatol. 2016 Mar. 35(3):771-3. [Medline].

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

  11. [Guideline] Zhang W, Doherty M, Bardin T, Barskova V, Guerne PA, 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. [Medline].

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

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

  14. Gutierrez M, Di Geso L, Salaffi F, Carotti M, Girolimetti R, De Angelis R, et al. Ultrasound detection of cartilage calcification at knee level in calcium pyrophosphate deposition disease. Arthritis Care Res (Hoboken). 2014 Jan. 66(1):69-73. [Medline].

  15. Filippou G, Adinolfi A, Iagnocco A, Filippucci E, Cimmino MA, Bertoldi I, et al. Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. A systematic literature review and a meta-analysis. Osteoarthritis Cartilage. 2016 Jun. 24(6):973-81. [Medline].

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

  17. 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. 2009 Jul. 76(4):424-6. [Medline].

  18. Ottaviani S, Brunier L, Sibilia J, Maurier F, Ardizzone M, Wendling D, et al. Efficacy of anakinra in calcium pyrophosphate crystal-induced arthritis: a report of 16 cases and review of the literature. Joint Bone Spine. 2013 Mar. 80(2):178-82. [Medline].

  19. Moltó A, Ea HK, Richette P, Bardin T, Lioté F. Efficacy of anakinra for refractory acute calcium pyrophosphate crystal arthritis. Joint Bone Spine. 2012 Dec. 79(6):621-3. [Medline].

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

  21. Ea HK, Lioté F. Advances in understanding calcium-containing crystal disease. Curr Opin Rheumatol. 2009 Mar. 21(2):150-7. [Medline].

  22. 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. 1986 Jul. 45(7):603-5. [Medline].

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

  24. 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. 1988 Mar. 31(3):408-13. [Medline].

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

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

  27. 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. 2005 Nov. 34(11):714-21. [Medline].

  28. 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. 2008 Oct. 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.
Intraoperative photographs demonstrate extensive precipitate deposition of the calcium pyrophosphate crystals in the articular cartilage, meniscus, and synovium of a knee. Left images depict femoral and tibial surfaces. Right images depict anterior cruciate ligament.
Intraoperative photographs demonstrate extensive precipitate deposition of the calcium pyrophosphate crystals in the articular cartilage, meniscus, and synovium of a knee. Upper left image depicts anterior horn medial meniscus. Lower left image depicts undersurface of meniscus. Upper right image depicts medial femoral condyle. Lower right image depicts synovium.
 
 
 
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