eMedicine Specialties > Radiology > Musculoskeletal

Calcium Pyrophosphate Deposition Disease

Author: Bruce M Rothschild, MD, Professor of Medicine, Northeastern Ohio Universities College of Medicine; Adjunct Professor, Department of Biomedical Engineering, University of Akron; Adjunct Professor, Department of Anthropology, University of Kansas; Director, Arthritis Center of Northeast Ohio
Coauthor(s): Michael A Bruno, MD, Associate Professor, Departments of Radiology and Medicine, Pennsylvania State University College of Medicine; Director, Radiology Quality Management Services, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine
Contributor Information and Disclosures

Updated: Jan 29, 2010

Introduction

Background

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Calcium pyrophosphate deposition disease (CPDD) is a type of arthritis caused by the deposition of calcium pyrophosphate crystals. CPDD is divided into several varieties, primarily pseudogout and chondrocalcinosis. Synovial calcium pyrophosphate crystals, seen on polarizing microscopy, characterize pseudogout, an acute goutlike arthritis.1,2

Chondrocalcinosis is recognized as calcification within fibrous or hyaline cartilage structures. Radiologically, a dense line within the hyaline cartilage parallels the articular surface, often resulting in a calcified hyaline cartilage surface. This can be recognized grossly as a calcified sheet reflecting over the articular surface and as concretions of calcium pyrophosphate exuded beyond the subchondral articular surface. Pseudogout and chondrocalcinosis may overlap with each other and with other varieties.

Other varieties appear ill defined and include a subgroup referred to as pseudorheumatoid. Periarticular metacarpal phalangeal and interphalangeal joint calcification may be a component of that form of CPDD. Radiocarpal articular surface indentation (an unusual joint to be affected in osteoarthritis [OA]) is also considered evidence of CPDD, as are large subchondral cysts (ie, geodes), which rarely occur.

Pseudorheumatoid CPDD has a polyarticular character. One variety of idiopathic CPDD with destructive peripheral arthritis has been reported. Bony fragmentation or a crumbling appearance, which may simulate a neuropathic joint, characterizes this variety.

CPPD was recognized in non-human primates: leopard Panthera pardis, cervid Axis porcinus, Egyptian spiny-tailed lizard Uromastyx, Chrysemys picta elegans, Gopherus agassizi, and Testudo graeca, as well as in Varanus bengalensis, V niloticus, V olivaceous, V salvadorii, and V salvator.

Presentation

Demographics

  • Primary calcium pyrophosphate deposition disease is a disease of aging, affecting approximately 5% of the population aged 28-96 years. CPDD is rare until age 30 years, then increases exponentially until age 75 years, when it plateaus.
  • Calcium pyrophosphate deposition disease may be asymptomatic, with episodes of hyperacute arthritis (termed pseudogout) or may be a chronic arthritis. Morbidity is related to joint pain and disability caused by arthritis.
  • The male-to-female ratio is approximately 1:1.


Presentation and natural history
Calcium pyrophosphate deposition disease is the result of an inflammatory cascade response to the deposition of calcium pyrophosphate crystals. Enzyme or saturation abnormalities allow the formation of excess pyrophosphate, which salts out, especially in hyaline and fibrous cartilage. Individuals with CPDD may have more than one type of crystal present (eg, hydroxyapatite in addition to pyrophosphate).

A chromosome t(2;10) addition has been described in one case involving the temporomandibular joint.3,4,5,6

Calcium pyrophosphate deposition disease can be divided into primary and secondary varieties. Secondary refers to CPDD associated with rheumatoid arthritis or spondyloarthropathy.

Table 1. Distribution Pattern (%) of Nonerosive Component of Primary CPDD in Skeletal and Clinical Populations

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JointSkeletal, %Clinical, %
Shoulder3816-50
Elbow2423-33
Radiocarpal356-43
Metacarpophalangeal3019-50
Proximal interphalangeal2119
Distal interphalangeal1819
Hip1618-27
Knee5441-99
Ankle107-11
Metatarsophalangeal132
Interphalangeal42
JointSkeletal, %Clinical, %
Shoulder3816-50
Elbow2423-33
Radiocarpal356-43
Metacarpophalangeal3019-50
Proximal interphalangeal2119
Distal interphalangeal1819
Hip1618-27
Knee5441-99
Ankle107-11
Metatarsophalangeal132
Interphalangeal42

The distribution of CPDD in individuals with secondary CPDD (eg, rheumatoid arthritis, spondyloarthropathy) is identical to that noted in those with primary CPDD.

Primary CPDD can also be divided into familial, metabolic, and idiopathic varieties. The pattern of joint involvement differs among the varieties.

The familial variety of CPDD tends to occur earlier in life than the idiopathic variety. Metabolic causes and associations with CPDD include hypothyroidism, hyperparathyroidism, hypophosphatasia, hypomagnesemia, gout, ochronosis, Wilson disease, acromegaly, Paget disease, and Gitelman syndrome (GS).

Table 2. Joint Distribution Pattern (%) of CPDD in Familial, Idiopathic, and Metabolic (eg, hemochromatosis [hemo] and ochronosis [ochro]) Varieties

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JointFamilial, %
Idiopathic, %
Metabolic
Hemo, %
Metabolic
Ochro, %
Shoulder1916-50049-86
Elbow1423-33119-29
Radiocarpal246-431003-29
Metacarpophalangeal5-1440-504429
Hip1018-27043-57
Knee6241-998963-99
Ankle0-157-11330
Metatarsophalangeal8-10200
Spine0-151-170-15100
JointFamilial, %
Idiopathic, %
Metabolic
Hemo, %
Metabolic
Ochro, %
Shoulder1916-50049-86
Elbow1423-33119-29
Radiocarpal246-431003-29
Metacarpophalangeal5-1440-504429
Hip1018-27043-57
Knee6241-998963-99
Ankle0-157-11330
Metatarsophalangeal8-10200
Spine0-151-170-15100

Among the metabolic varieties, hemochromatosis produces less shoulder involvement and greater wrist, metacarpal phalangeal, knee, and ankle involvement, while ochronosis produces greater shoulder, hip, knee, and spine involvement.

Hemochromatosis is a disorder of iron metabolism in which iron accumulates in and damages body tissues, including joints.

Wilson disease consists of abnormal metabolic accumulation, specifically of copper.

Ochronosis is another storage disease in which homogentisic acid accumulates as a result of a deficiency of the metabolizing enzyme.

Gitelman syndrome (GS), a variant of Bartter syndrome, is an autosomal recessive renal tubular disorder resulting from loss-of-function mutations in the Na-Cl cotransporter (SLC12A3) gene, located in the distal convoluted tubule.7

While the metabolic varieties of CPDD are usually inherited (ie, genetic), an acquired form of hemochromatosis (analogous to hydroquinone-induced ochronosis) reportedly occurs, either from ingesting excess amounts of iron or secondary to excess iron release in hemolytic anemia.

Additional clinical signs include confusion, fever, meningismus, cervicobrachial pain, and occipital and temporal headaches.8

Treatment

  • No radiographic intervention is indicated.
  • Calcium pyrophosphate deposition disease is treated medically or surgically.
  • Occasionally, ultrasound guidance may be provided to assist with arthrocentesis, but this is usually not necessary.
  • Surgical removal of extensive crystal deposits, especially from the temporomandibular joint.9

Differential Diagnoses

Ankylosing Spondylitis
Osteochondroma and Osteochondromatosis
Diffuse Idiopathic Skeletal Hyperostosis
Osteosarcoma, Classic
Gout
Osteosarcoma, Variants
Knee, Meniscal Tears (MRI)
Rheumatoid Arthritis, Hands
Neuropathic Arthropathy (Charcot Joint)
Rheumatoid Arthritis, Spine
Osgood-Schlatter Disease
Septic Arthritis
Osteoarthritis, Primary
Spinal Stenosis
Osteochondritis Dissecans
Synovial Osteochondromatosis

Other Problems to Be Considered

Basic calcium phosphate crystal deposition
Calcinosis
Calcium oxalate arthritis
Chondrosarcoma
Erosive OA
Hydroxyapatite arthritis
Joint replacement failure
Juxtacortical chondroma
Neoplasm
Osteonecrosis
Prosthetic joint breakdown
Secondary OA
Spondyloarthropathy
Tumoral calcinosis

More on Calcium Pyrophosphate Deposition Disease

Overview: Calcium Pyrophosphate Deposition Disease
Imaging: Calcium Pyrophosphate Deposition Disease
Follow-up: Calcium Pyrophosphate Deposition Disease
Multimedia: Calcium Pyrophosphate Deposition Disease
References
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References

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  4. Mikami T, Takeda Y, Ohira A, Hoshi H, Sugiyama Y, Yoshida Y, et al. Tumoral calcium pyrophosphate dihydrate crystal deposition disease of the temporomandibular joint: identification on crystallography. Pathol Int. Nov 2008;58(11):723-9. [Medline].

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  7. Volpe A, Caramaschi P, Thalheimer U, Fava C, Ravagnani V, Bambara LM. Familiar association of Gitelman's syndrome and calcium pyrophosphate dihydrate crystal deposition disease--a case report. Rheumatology (Oxford). Sep 2007;46(9):1506-8. [Medline].

  8. Salaffi F, Carotti M, Guglielmi G, Passarini G, Grassi W. The crowned dens syndrome as a cause of neck pain: clinical and computed tomography study in patients with calcium pyrophosphate dihydrate deposition disease. Clin Exp Rheumatol. Nov-Dec 2008;26(6):1040-6. [Medline].

  9. Fahey M, Mitton E, Muth E, Rosenthal AK. Dexamethasone promotes calcium pyrophosphate dihydrate crystal formation by articular chondrocytes. J Rheumatol. Jan 2009;36(1):163-9. [Medline].

  10. Tan KB, Scolyer RA, McCarthy SW, Schatz J, Nabarro M, Lee K, et al. Tumoural calcium pyrophosphate dihydrate crystal deposition disease (tophaceous pseudogout) of the hand: a report of two cases including one with a previously unreported associated florid reactive myofibroblastic proliferation. Pathology. Dec 2008;40(7):719-22. [Medline].

  11. Mizutani H, Ohba S, Mizutani M. Tumoral calcium pyrophosphate dihydrate deposition disease with bone destruction in the shoulder. CT and MR findings in two cases. Acta Radiol. May 1998;39(3):269-72. [Medline].

  12. Kaushik S, Erickson JK, Palmer WE. Effect of chondrocalcinosis on the MR imaging of knee menisci. AJR Am J Roentgenol. Oct 2001;177(4):905-9. [Medline].

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  32. Stucki G, Hardegger D, Bohni U. Degeneration of the scaphoid-trapezium joint: a useful finding to differentiate calcium pyrophosphate deposition disease from osteoarthritis. Clin Rheumatol. 1999;18(3):232-7. [Medline].

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Further Reading

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Keywords

calcium pyrophosphate deposition disease, CPDD, calcium pyrophosphate dihydrate deposition disease, calcium pyrophosphate dihydrate crystal deposition disease, pseudogout, chondrocalcinosis, apical plate excrescences, calcium crystal arthritis, pyrophosphate arthropathy, pseudorheumatoid, calcium pyrophosphate crystals, hypothyroidism, hyperparathyroidism, hypophosphatasia, hypomagnesemia, gout, ochronosis, Wilson disease, acromegaly, Paget disease

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Contributor Information and Disclosures

Author

Bruce M Rothschild, MD, Professor of Medicine, Northeastern Ohio Universities College of Medicine; Adjunct Professor, Department of Biomedical Engineering, University of Akron; Adjunct Professor, Department of Anthropology, University of Kansas; Director, Arthritis Center of Northeast Ohio
Bruce M Rothschild, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Rheumatology, International Skeletal Society, New York Academy of Sciences, Sigma Xi, and Society of Skeletal Radiology
Disclosure: Nothing to disclose.

Coauthor(s)

Michael A Bruno, MD, Associate Professor, Departments of Radiology and Medicine, Pennsylvania State University College of Medicine; Director, Radiology Quality Management Services, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine
Michael A Bruno, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America, Society of Nuclear Medicine, and Society of Skeletal Radiology
Disclosure: Nothing to disclose.

Medical Editor

Hussein M Abdel-Dayem, MD, Chief, Nuclear Medicine Service, Department of Radiology, Professor of Radiology, St Vincent's Catholic Medical Centers of New York
Disclosure: none None None

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Theodore E Keats, MD, Professor, Departments of Radiology and Orthopedics, University of Virginia School of Medicine
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington
Felix S Chew, MD, MBA, EdM is a member of the following medical societies: American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

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