eMedicine Specialties > Rheumatology > Crystal-Induced Arthritis

Calcium Pyrophosphate Deposition Disease

Constantine Saadeh, MD, Chief, Department of Internal Medicine, Northwest Texas Hospital; President, Allergy ARTS, LLP; Clinical Professor, Departments of Internal Medicine, Pediatrics, Microbiology, and Immunology, Texas Tech Health Science Center

Updated: Sep 3, 2009

Introduction

Background

Calcium pyrophosphate deposition disease (CPDD) is a metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate (CPPD) in and around joints, especially in articular and fibrocartilage. Although CPDD is often asymptomatic, with only radiographic changes (ie, chondrocalcinosis), various clinical manifestations may occur, including acute (pseudogout) and chronic arthritis. Although almost any joint may be involved by CPDD, the knees, wrists, and hips are most commonly affected. This condition is the most common cause of secondary metabolic osteoarthritis.

Pathophysiology

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 cartilage and synovium.¹ Hyaline cartilage is affected most commonly, but fibrocartilage, such as the meniscal cartilage of the knee, can also be involved.²

Hypotheses based on in vitro studies propose that pyrophosphohydrolase activity and inorganic phosphate content, as noted above, are generalized phenomena that occur in fibroblasts.³ Although these phenomena are generalized, the reason they occur only in joints remains unknown.

Recently, genetic defects have been identified as specific gene mutations in a few kindred families.⁴ The mutations occurred in specific genes known as 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.

Gitelman syndrome is associated with both hypokalemic metabolic acidosis and hypomagnesemia. Patients with Gitelman syndrome may have renal tubular acidosis and a history of pseudogout. As such, this diagnosis should be considered in patients with such findings. It 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 of these patients. The syndrome can mimic several other manifestations of CPDD, including osteoarthritis, carpal tunnel syndrome, and tenosynovitis with calcifications along the tendon sheath itself.⁵

Frequency

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.

Mortality/Morbidity

CPDD can be a cause of significant morbidity, either from the pain of an acute attack of pseudogout or the chronic symptoms associated with chronic arthropathy.

Race

CPDD has no racial predilection.

Sex

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

Age

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 secondary causes, such as an underlying metabolic disease, or familial causes.

Clinical

History

Clinical presentations of calcium pyrophosphate deposition disease (CPDD) can vary, but, according to McCarty, the 5 most common presentations are as follows:

• Asymptomatic (lanthanic)
  • This is usually associated with radiographic findings of chondrocalcinosis in the absence of clinical manifestations and may be the most common form of CPDD.
  • The classic radiologic findings include chondrocalcinosis of the hyaline cartilage and fibrocartilage of the knees, the fibrocartilage of the triangular ligament of the wrist, the fibrocartilage of the symphysis pubis, and the acetabulum labrum of the hips.
• Acute pseudogout
  • This is characterized by acute monoarticular or oligoarticular arthritis. Pseudogout usually involves the knee or the wrist, although almost any joint can be involved, including the first metatarsophalangeal (MTP) joint, as occurs in patients with gout. This form of CPDD accounts for 25% of cases.
  • Clinical manifestations are similar to those of acute gouty arthritis, typically presenting with an acute monoarthritis with pain and swelling, although generally not as intense. Polyarticular attacks may occur on occasion. Pseudogout may be precipitated by medical illness such as myocardial infarction, congestive heart failure, or cerebrovascular accident or may occur after surgery. Trauma may also be a precipitating factor. Events that affect serum calcium levels also may precipitate attacks of pseudogout.
  • Occasionally, pseudogout may present as a pseudoseptic syndrome with acute arthritis, fever, and leukocytosis with a left shift.
  • Aspiration of the fluid from affected joints during an acute attack usually yields mildly-to-moderately inflammatory fluid, with 10,000-50,000 WBCs/µL, more than 90% of which are neutrophils.
  • Glucose levels are usually normal.
  • Characteristically, rhomboid-shaped, weakly positively birefringent crystals are seen both intracellularly and extracellularly using compensated polarized microscopy. The presence of such crystals intracellularly is pathognomonic for acute pseudogout.
  • Septic arthritis must be excluded; therefore, Gram stain of the fluid should be performed. The results of the Gram stain are negative unless a concomitant infection is present.
• Pseudoosteoarthritis
  • Pseudoosteoarthritis often involves the metacarpophalangeal (MCP) joints, wrists, elbows, and shoulders, joints unlikely to be involved with primary osteoarthritis. It affects the knees most commonly and can involve the proximal interphalangeal (PIP) joints and spine, as occurs in patients with primary osteoarthritis. This form of CPDD accounts for 50% of all cases. Approximately half of these patients also have associated pseudogout.
  • Hooklike osteophytes are a common radiological finding in patients with a pseudoosteoarthritis condition and are usually present along the second and third metacarpal heads.
  • The presence of chondrocalcinosis on radiographs is common.
  • The differential diagnoses include hemochromatosis, hyperparathyroidism, hypothyroidism, and traumatic arthritis (as occurs in heavy-equipment machinery operators).
• Pseudorheumatoid arthritis
  • This pattern is found in approximately 5% of patients with CPDD and is associated with symmetrical inflammation of the PIP and MCP joints.
  • Clinically, these patients complain of morning stiffness and joint swelling.
  • Radiologically, erosions can be observed but are usually associated with chondrocalcinosis.
  • The erythrocyte sedimentation rate (ESR) is usually elevated.
  • The older age at onset for this condition, the lack of rheumatoid factor, and the presence of chondrocalcinosis help differentiate it from true rheumatoid arthritis. However, rheumatoid arthritis can occur in older individuals. In addition, older individuals may have low-titer–positive rheumatoid factor. Thus, the diagnosis must be made with care.
• Pseudoneuropathic joints
  • Neuropathiclike arthropathy is observed in fewer than 5% of patients with CPDD, most commonly involving the knee. This is a severe destructive arthropathy. Unlike true neuropathic arthropathy, no clear underlying neurological disorder is present.
  • Again, the presence of chondrocalcinosis can help make the diagnosis.

Revised diagnostic criteria for calcium pyrophosphate crystal deposition disease were taken from the 1997 Primer on Rheumatic Diseases and are used with permission from the Arthritis Foundation.⁶

• Criterion I - Demonstration of calcium pyrophosphate crystal deposition in tissue or synovial fluid by definitive means (eg, characteristic radiographs, diffraction analysis, or chemical analysis)
• Criterion IIa - Identification of monoclinic or triclinic crystals showing no or weakly positive birefringence by compensated polarized light microscopy
• Criterion IIb - Presence of typical radiographic calcifications
• Criterion IIIa - Acute arthritis, especially of knees or other large joints
• Criterion IIIb - Chronic arthritis, especially of knee, hip, wrist, carpus, elbow, shoulder, or MCP joint, especially if accompanied by acute exacerbation; the chronic arthritis shows the following features, which are helpful in differentiating it from osteoarthritis:
  • Uncommon sites - Wrist, MCP joint, elbow, shoulder
  • Radiographic appearance - Radiocarpal or patellofemoral joint-space narrowing, especially if isolated (eg, patella wrapped around the femur)
  • Subchondral cyst formation
  • Severity of degeneration - Progressive, with subchondral bony collapse and fragmentation with formation of intraarticular radiodense bodies
  • Osteophyte formation - Variable and inconsistent
  • Tendon calcifications, especially triceps, Achilles, obturators
• Categories
  • Definite disease: Criterion I or IIa plus IIb must be fulfilled.
  • Probable disease: Criterion IIa or IIb must be fulfilled.
  • Possible disease: Criterion IIIa or IIIb should alert the clinician to the possibility of underlying calcium pyrophosphate deposition.

A number of conditions have been associated with CPDD. When CPDD is diagnosed, especially in a patient younger than 60 years, a metabolic workup should be performed, including measurements of serum calcium, magnesium phosphorus, alkaline phosphatase, iron, total iron-binding capacity (TIBC), transferrin saturation and ferritin, and thyroid-stimulating hormone.

• True associations - Familial (autosomal dominant), prior trauma or prior surgery, hyperparathyroidism, hemochromatosis, hypophosphatasia, hypomagnesemia, aging
• Probable associations - Hypothyroidism, gout, familial hypercalciuria
• Possible associations - Acromegaly, diabetes mellitus, ochronosis, Wilson disease

Physical

The physical examination findings vary depending on the form of CPDD in a given patient, who may present with an acute arthritis or different patterns of chronic arthritis.

• Acute pseudogout: Physical examination findings show an acutely inflamed joint with swelling, effusion, warmth, tenderness, and pain on range of motion similar to acute gouty arthritis. This typically occurs in the knee but may occur in the wrists, shoulders, ankles, hands, and feet.
• Pseudoosteoarthritis: Physical examination findings show a picture similar to osteoarthritis, sometimes with unusual joint predilection. If a patient has osteoarthritis involving the MCP joints and wrists, consider CPDD associated with an underlying metabolic disease.
• Pseudorheumatoid arthritis: Physical examination findings show a picture similar to rheumatoid arthritis with synovitis in a symmetrical polyarticular pattern, especially involving the wrists and MCP joints.

Causes

See Pathophysiology.

Differential Diagnoses

Other Problems to Be Considered

Basic calcium phosphate deposition disease
Lyme arthritis

Workup

Laboratory Studies

• General laboratory studies usually are not helpful in calcium pyrophosphate deposition disease (CPDD). WBC count and ESR may be elevated.
• Evaluating for an underlying metabolic disease (eg, hemochromatosis, hyperparathyroidism, hypothyroidism) is reasonable, especially in younger patients.
• Laboratory tests can include serum calcium, phosphorus, and magnesium and alkaline phosphatase levels; iron levels; TIBC; transferrin saturation and ferritin; and thyroid-stimulating hormone and free thyroxine levels.
• The diagnosis of acute pseudogout is made by performing compensated polarized microscopy after aspiration of fluid from the involved joint.
  • The most commonly involved joint is the knee, followed by the wrist, the MCP joints, the elbows, and the MTP joints.
  • The crystals are rhomboid-shaped, weakly positively birefringent, and difficult to see. If intracellular, an acute attack of pseudogout is strongly suggested.
    
    

    

    Calcium pyrophosphate deposition disease. Appearance of calcium pyrophosphate dihydrate crystals obtained from the knee of a patient with pseudogout. The crystals are rhomboid-shaped and weakly positively birefringent 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 compensator are blue, while crystals 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 compensator were blue, while crystals perpendicular to the compensator were yellow. However, crystals have been rotated 90%, resulting in a color change in both crystals. The direction of the compensator was unchanged and is indicated by the black arrow.

    
    
  • Gout and pseudogout can coexist, even in the same joint; therefore, the presence of gout does not rule out the possibility of pseudogout and vice-versa.
• Ultrasonography may be helpful in diagnosing pseudogout.
  
  

  

  Wrist chondrocalcinosis.

  
  
• Septic arthritis can present as monoarticular arthritis and, therefore, can mimic acute pseudogout. If septic arthritis is suggested clinically, even if crystals are seen on compensated polarized microscopy, it must be evaluated and, possibly, treated.

Imaging Studies

• Radiological studies are important in the diagnosis of CPDD. The studies usually include the hands and wrists, pelvis, and knees. The pelvic radiograph should include an anteroposterior view that includes the symphysis pubis and hips.
• Chondrocalcinosis is usually found in the articular cartilage or meniscal cartilage of the knee, the triangular ligament of the wrist, the symphysis pubis, or the glenoid or acetabulum labra. Recently, chondrocalcinosis has been noticed in other areas of the wrist (aside from the fibrocartilage), such as in the distal radioulnar joint and in the midcarpal joint, as well as in the pisotriquetral joint. In addition, it has been reported in the spine as calcification of the ligamentum flavum.⁷
• In some situations, hemochromatosis can produce specific radiographic findings, such as large hooklike osteophytes, especially around the second to the fifth MCP joints. However, these findings also can occur in patients with CPDD alone.
• Radiography is still the criterion standard in the diagnosis of CPPD. Even routine MRI has not been shown to be as sensitive as radiography in detecting the presence of the CPPD deposits. However, 4T MRI holds better promise in detecting these crystals.
  

  

  Calcium pyrophosphate deposition disease. Radiograph of the knee showing chondrocalcinosis involving the meniscal cartilage, also showing 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.

  
  
• Ultrasonography has been significantly beneficial in the visualization of the crystals.
  
  

  

  Wrist chondrocalcinosis.

  
  

Procedures

• Arthrocentesis is the most important procedure to perform, especially in patients with acute pseudogout, in order to examine the fluid using compensated polarized microscopy and to perform fluid cultures.

Histologic Findings

Histologic changes associated with CPDD correspond to calcium deposits and inflammation due to cartilage fragments. These changes are nonspecific, but calcium deposits inside the chondrocartilage is perhaps the most typical finding in patients with this condition. The pathognomonic finding with compensated polarized microscopy is weakly positive birefringent crystals, typically intracellular, that are usually rhomboid in shape.

Treatment

Medical Care

Management of calcium pyrophosphate deposition disease (CPDD) depends on the clinical manifestations.

• Lanthanic or asymptomatic CPDD should not be treated unless it is a possible manifestation of other syndromes such as hyperparathyroidism or hemochromatosis. Treatment of the latter conditions is important to prevent further end-organ damage but cannot reverse the joint disease.
• Acute pseudogout may be treated by joint aspiration and intraarticular corticosteroid injection, systemic corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or, occasionally, high-dose colchicine.
  • Intraarticular corticosteroid injections, such as 40-80 mg (depending on the size of the joint) of methylprednisolone or triamcinolone, into the affected joint have the advantage of avoiding the adverse systemic effects of NSAIDs. Short courses of systemic corticosteroids may be used for polyarticular attacks of pseudogout.
  • Using NSAIDs also can be considered, generally in higher doses during the acute attack and in lesser doses for prevention. Be aware of toxicity, which is common in elderly patients, including gastrointestinal and renal toxicities. Cyclooxygenase-2 (COX-2) selective NSAIDs (ie, COX-2 inhibitors) may be as effective as traditional NSAIDs with less toxicity, although this has not been rigorously tested.
  • Oral colchicine, or even intravenous colchicine, can be considered for the treatment of acute pseudogout. Colchicine should be a treatment of last resort because of its poor therapeutic ratio.
  • Preventing acute attacks is difficult. The use of small doses of colchicine (0.6 mg qd/bid) or NSAIDs have been tried, with variable success.
• Treatment for pseudoosteoarthritis is similar to that for typical osteoarthritis.
• Patients with a pseudorheumatoid arthritis can be treated with small doses of corticosteroids, such as prednisone at 5 mg/d.
• Methotrexate has been shown to be effective in isolated observations in patients who have severe disease with particular emphasis on joint destruction. However, this was attempted only in patients with the pseudorheumatoid presentation.⁸
• Recent studies have suggested that the inflammasome complex plays a pivotal role for interleukin-1 in pseudogout attacks.⁹ Therefore, anakinra (Kineret) is a potential alternative in patients with calcium pyrophosphate disease. This was reported in a single individual, a 71-year-old man with recurrent pseudogout attacks in multiple joints that were resistant to therapy with anti-inflammatory drugs, including glucocorticoids. This could also be important in patients with renal insufficiency (such as this patient), in whom nonsteroidal drugs can be problematic.⁹

Surgical Care

Theoretically, surgically removing calcifications from the joint might be of benefit, but this is currently considered an experimental procedure.

Medication

Medical therapy for acute pseudogout is similar to that for gout, including NSAIDs, intraarticular or occasionally systemic corticosteroids, and, rarely, oral or intravenous colchicine. NSAIDs or, occasionally, low-dose prednisone may be beneficial for chronic arthropathies due to calcium pyrophosphate deposition disease (CPDD).

Nonsteroidal anti-inflammatory drugs

NSAIDs are very effective for the treatment of acute pseudogout and may be used for prophylaxis to prevent recurrent attacks of pseudogout. These agents may also be useful for symptomatic treatment of chronic arthropathies associated with CPDD. NSAID use is limited by toxicity (eg, renal, GI), which is common in elderly patients. COX-2 selective NSAIDs may be as effective as traditional NSAIDs with less GI toxicity.

Indomethacin (Indocin)

Traditional NSAID used to treat acute gouty arthritis. Used in a similar fashion for acute pseudogout. Blocks COX and, thereby, the generation of proinflammatory prostaglandins. Use maximum dose initially, tapering over 2 weeks depending on clinical response.

Dosing

Adult

50 mg PO tid/qid for 1-3 d depending on response, then taper

Pediatric

Not established

Interactions

Coadministration with aspirin increases risk of serious NSAID-induced adverse event; may decrease effects of various antihypertensive medications including ACE inhibitors, beta-blockers, and diuretics; may increase PT if patient on oral anticoagulants; phenytoin levels may be increased

Contraindications

Documented hypersensitivity; peptic ulcer disease; renal insufficiency; thrombocytopenia, patient on anticoagulation

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

GI toxicity, including nausea, dyspepsia, abdominal pain, diarrhea, and peptic ulcer disease; renal toxicities, including acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis; avoid in third trimester of pregnancy

Anti-inflammatory agents

If given PO or, rarely, IV, these agents can be used to treat acute pseudogout. Toxicity is significant; therefore, other therapies should be considered first. Low-dose colchicine may be useful for long-term prophylaxis of pseudogout attacks.

Colchicine

Inhibits microtubules and, thereby, may inhibit neutrophil chemotaxis and phagocytosis. Also may inhibit prostaglandin generation.

Dosing

Adult

Acute pseudogout: 0.6 mg PO q1h until relief or GI toxicity; not to exceed 6 mg
Alternatively: 1 mg IV in 20 mL isotonic sodium chloride solution without glucose over 20 min; may repeat in 6 h; not to exceed 4 mg in 24-h period; do not use if patient on oral colchicine and do not give further colchicine by any route for at least 1 wk
Prophylaxis: 0.6 mg PO qd/bid; decrease dose for renal insufficiency

Pediatric

Not established

Interactions

Sympathomimetic agent toxicity and effect of CNS depressants significantly increased

Contraindications

Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Risk of renal failure, hepatic failure, permanent hair loss, bone marrow toxicity, disseminated intravascular coagulation, and oligospermia; dose-dependent GI toxicity, especially diarrhea; rarely neuropathy or myopathy

Corticosteroids

These agents are potent anti-inflammatory that are very useful in the treatment of acute pseudogout in patients who are not good candidates for NSAIDs and are much less toxic than colchicine. Can be given PO/IV or intraarticularly. PO prednisone used for an acute attack of pseudogout is generally tapered over a 2-week period. Intraarticular corticosteroids (eg, methylprednisolone) are very effective for treatment of acute pseudogout. However, intraarticular dexamethasone promotes CPPD crystal formation by chondrocytes. The general dose for methylprednisone is 20-80 mg or its equivalent, depending on the size of the joint. This treatment has minimal toxicity and few contraindications (septic arthritis). Low-dose prednisone may be used for long-term treatment of pseudorheumatoid arthritis.

Prednisone (Sterapred)

Can be given PO to abort an attack of pseudogout. Can be given IV if patient cannot take PO. Intraarticular corticosteroids first choice of therapy due to excellent safety profile.

Dosing

Adult

Initial: 40 mg PO qd for 3 d; taper over 2 wk depending on clinical response

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of corticosteroids; monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; no absolute contraindications; severe bacterial, viral, or fungal infection; active peptic ulcer disease; diabetes mellitus

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

With long-term use, abrupt discontinuation may cause adrenal crisis; high doses may cause hyperglycemia, edema, infections, obesity, avascular necrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, and growth suppression in children

Follow-up

Deterrence/Prevention

• Preventing acute attacks of pseudogout is difficult. Small doses of colchicine (0.6 mg qd/bid) or NSAIDs have been tried, with variable success.

Complications

• Pain
• Chronic arthropathy

Prognosis

• Patients with calcium pyrophosphate deposition disease (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 cannot reverse the joint disease.

Patient Education

• For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education article Knee Pain.

Miscellaneous

Medicolegal Pitfalls

• Legal pitfalls associated with calcium pyrophosphate deposition disease (CPDD) are rare, but the most important is a failure to aspirate the joint in the setting of an acute attack, even if the patient has multiple attacks of pseudogout. This is important because septic arthritis can mimic pseudogout.

Multimedia

Media file 1: Calcium pyrophosphate deposition disease. Radiograph of the knee showing chondrocalcinosis involving the meniscal cartilage, also showing evidence of osteoarthritis.

Media file 2: 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.

Media file 3: Calcium pyrophosphate deposition disease. Appearance of calcium pyrophosphate dihydrate crystals obtained from the knee of a patient with pseudogout. The crystals are rhomboid-shaped and weakly positively birefringent as seen by compensated polarized microscopy. The black arrow indicates the direction of the compensator.

Media file 4: 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 compensator are blue, while crystals perpendicular to the compensator are yellow.

Media file 5: Calcium pyrophosphate deposition disease. High-powered view of calcium pyrophosphate dihydrate crystals with compensated polarized microscopy. The crystals parallel to compensator were blue, while crystals perpendicular to the compensator were yellow. However, crystals have been rotated 90%, resulting in a color change in both crystals. The direction of the compensator was unchanged and is indicated by the black arrow.

Media file 6: Wrist chondrocalcinosis.

References

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

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9. 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].

10. Doherty M. Calcium pyrophosphate deposition disease and other crystal deposition diseases. Curr Opin Rheumatol. Oct 1990;2(5):789-96. [Medline].

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

12. 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].

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

14. 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].

15. 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].

16. 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].

17. 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].

18. 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].

Keywords

calcium pyrophosphate deposition disease, CPDD, chondrocalcinosis, pseudogout, pyrophosphate arthropathy, lanthanic, acute pseudogout, pseudoosteoarthritis, pseudorheumatoid arthritis, pseudo-rheumatoid arthritis, pseudo-osteoarthritis, pseudoneuropathic joints, pseudo-neuropathic joints, calcium pyrophosphate dihydrate, CPPD, gout, pseudo-gout, arthritis, pseudoarthritis, pseudo-arthritis, osteoarthritis

Contributor Information and Disclosures

Author

Constantine Saadeh, MD, Chief, Department of Internal Medicine, Northwest Texas Hospital; President, Allergy ARTS, LLP; Clinical Professor, Departments of Internal Medicine, Pediatrics, Microbiology, and Immunology, Texas Tech Health Science Center
Constantine 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.

Medical Editor

Kristine M Lohr, MD, MS, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology and Women's Health, University of Kentucky School of Medicine
Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Medical Women's Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Lawrence H Brent, MD, Associate Professor of Medicine, 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 of Immunologists, American College of Physicians, and American College of Rheumatology
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University 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: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

Thank you to Shannon Shaw and Michael Gaylor for all their hard work on helping prepare this article. The authors and editors of eMedicine also gratefully acknowledge the contributions of previous coauthor, Jan Malacara, PA-C, to the development and writing of this article.

Clinical trials

Ultrasound and X-Ray in Detecting Articular Cartilage Calcification

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