Calcium pyrophosphate dihydrate deposition disease

Calcium pyrophosphate dihydrate disease (CPPD disease), also known as pyrophosphate arthropathy and perhaps confusingly asor pseudogout, is common, especiallydefined by the co-occurrence of arthritis with evidence of CPPD deposition within the articular cartilage.

It is mostly described in the elderly (>60 years old), and is characterised bydescribed as the depositionmost common cause of chondrocalcinosis.

Terminology 

The terminology regarding CPPD disease has been confusing, with chondrocalcinosis, CPPD, and pseudogout often used synonymously. Indeed, although initially described as chondrocalcinosis articularis, it is now understood that imaging findings of chondrocalcinosis do not always indicate CPPD disease ⁹.

In response, in 2011 the European League Against Rheumatism (EULAR) proposed a standardized terminology corresponding to clinical presentation ⁹:

• CPPD - occurrence of calcium pyrophosphate in soft tissues and cartilage.

  Terminology 

  crystals, with or without symptoms
• asymptomatic CPPD is one- chondrocalcinosis +/- changes of many causes of soft tissue calcification (chondrocalcinosis). It is not synonymous with chondrocalcinosis and not the only cause of soft tissue calcification.

  Where

  osteoarthritis, but clinically asymptomatic
• acute CPPD crystal deposition causes acute clinical manifestation, the termarthritis (formerly pseudogout should be used.) - self-limiting synovitis in the setting of CPPD
• osteoarthritis with CPPD Pyrophosphate arthropathy- typical changes of osteoarthritis is a term that describes arthropathy secondary to in the setting of CPPD
• chronic CPPD depositioncrystal inflammatory arthritis

Clinical presentation

Most patients with imaging findings of CPPD are clinically asymptomatic.

Acute CPPD crystal arthritis (pseudogout) presents with severe acute or subacute pain, swelling, erythema, and warmth, of one or more joints and is usually self-limited. HoweverThe presentation classically resembles an acute gout attack. Unlike gout, it is often used indiscriminately to refer to chondrocalcinosis toomost commonly involves the knee and more commonly involves the upper joints (shoulder, elbow, wrist).

Chronic CPPD crystal inflammatory arthritis presents with chronic, intermittent painful swelling in the peripheral joints of upper and lower extremities. 

Epidemiology

CPPD is commonest in patients over the age of 50. Men and women are equally affected. 

Pathology

The crystals are weakly positively birefringent on polarised microscopy and have a rhomboid or rod shape. Causes

Causes of CPPD can be divided into:

• idiopathic 
• hereditary 
  • AD pattern; mutation in the ANKH gene which encodes a transmembrane inorganic pyrophosphate transporter
• secondary
  • haemochromatosis
  • hyperparathyroidism
  • hypothyroidism
  • hypomagnesaemia ²
  • previous joint injury
  • ochronosis

Radiographic features

CPPD has many features of osteoarthritis with an unusual distribution, for example, they tend to be symmetric in distribution and involve non-weight bearing joints or, in the hands, mainly involve the intercarpal and MCP joints. 

Features of degenerative joint disease in joints that are not commonly affected by it (i.e. non-weight bearing joints):

• wrist joint (mainly radiocarpal and scapholunate joints)
  • SLAC wrist can be seen in advanced cases
  • a stepladder pattern of joint narrowing is classically described in which the narrowing is progressively less severe from the radiocarpal joint to the midcarpal joint
  • hook-like osteophytes
• patellofemoral joint
• shoulder joint
• elbow joint

Chondrocalcinosis can occur in many locations. Notable sites include:

• knee: medial meniscus and patellofemoral joint
• wrist: triangular fibrocartilage complex and lunotriquetral ligaments 
• spine: periodontoid tissue
  • crowned dens syndrome: acute pain and systemic inflammatory syndrome ⁵
  • intervertebral discs

Large subchondral cysts may be present.

It is controversial whether gout leads to calcification of articular fibrocartilage or hyaline cartilage ⁶. CPPD disease can be differentiated from gout on ultrasound given that echogenic monosodium urate crystals line the surface of articular cartilage, whereas echogenic CPPD calcifications are located within the cartilage itself ⁷.

Differential diagnosis

Possible imaging differential considerations include

• osteoarthritis 
  • usually have the typical weight-bearing distribution 
• giant cell tumour (GCT)
  • subchondral cysts of CPPD can be large and simulate subchondral GCT

See also

• soft tissue calcification
• differential diagnosis of erosive arthritis
• polyarticular disease