Calcium pyrophosphate dihydrate crystal deposition (CPPD) disease refers to the precipitation of calcium pyrophosphate dihydrate (CPP) in connective tissues that may be asymptomatic or may be associated with several clinical syndromes, including acute and chronic arthritis.¹ CPP was formerly abbreviated and commonly referred to as “CPPD,” but the abbreviation is now reserved for “CPP deposition.” Alternative names (Table 1) representing specific clinical or radiographic features of CPPD disease include pseudogout, chondrocalcinosis, and pyrophosphate arthropathy.²

Pseudogout/acute CPP crystal arthritis is used to describe acute attacks of CPP crystal-induced arthritis that clinically resembles the arthritis that is commonly encountered in gout.^3,4 The term acute CPP crystal arthritis is now preferred in place of pseudogout.

Chondrocalcinosis (CC) refers to radiographic calcification in hyaline cartilage and/or fibrocartilage and does not confirm the diagnosis of CPP-related arthritis as it can be present in other types of crystal deposition diseases or be asymptomatic.^2,5

Pyrophosphate arthropathy is the term used for a chronic structural arthropathy related to CPP deposition.^2,5

CPP crystal deposition disease

CPPD

Chondrocalcinosis (CC)

Pseudogout

Pyrophosphate arthropathy

• Acute CPP crystal arthritis/pseudogout: Monoarticular attacks most commonly involve the knee and wrist but can be polyarticular (Fig. E1). Patients, especially the elderly, can have systemic manifestations such as fever and altered mental status and therefore diagnostic aspiration is essential to rule out septic arthritis. Situations that may trigger acute CPPD crystal arthritis are described in Box E1.⁶
• Asymptomatic disease (“asymptomatic CPPD”)
• Pseudogout (acute CPP crystal arthritis)
• Pseudo-RA (chronic CPP crystal inflammatory arthritis): Symmetric polyarthritis
• Pseudo-OA, with or without superimposed acute attacks (OA with CPPD)
• Pseudo-neuropathic joint disease
• Crowned-dens syndrome caused by crystal deposition in the ligamentum flavum of the cervical spine, either asymptomatic or causing acute neck pain
• Pseudo-polymyalgia rheumatica (pseudo-PMR): Pain and stiffness in the neck and shoulder girdle mimicking PMR

• Idiopathic
• Familial
• Trauma
• Metabolic and endocrine disorders (Table 3): Hyperparathyroidism, hypophosphatasia, hemochromatosis, hypomagnesemia, Gitelman syndrome, Bartter syndrome, gout, ochronosis, acromegaly, Wilson disease, familial hypocalciuric hypercalcemia, X-linked hypophosphatemic rickets.^5,7

• Gouty arthritis (Table 4)
• Septic arthritis
• RA
• Spondyloarthritis (ReA, PsA)
• PMR

Table 5 describes metabolic diseases predisposing to CPPD disposition. Section II describes the differential diagnosis of acute monoarticular and oligoarticular arthritis and crystal-induced arthritides. An algorithm for evaluation and treatment of CPPD is shown in Fig. 2.⁵

• Arthrocentesis will demonstrate the presence of weakly positive birefringent rhomboid-shaped crystals by compensated polarized light microscopy (Fig. E3).⁵
• Synovial fluid should always be analyzed for cell count with differential, crystals, Gram stain, and culture because acute CPP crystal arthritis/pseudogout and septic arthritis can coexist.
• Evaluate for possible metabolic causes, especially in younger patients aged <55 yr or patients with florid polyarticular disease. Box 2 describes screening blood tests for metabolic diseases associated with CPPD crystal deposition.⁶

• Plain radiographs (Figs. E4, E5, and E6) often reveal CC located parallel to subchondral bone.⁵
  1. Classic locations for CC (see Fig. E1) include knee menisci (Fig. E7), wrist triangular fibrocartilage, symphysis pubis, and glenoid and acetabular labra.^5,8
• Musculoskeletal ultrasound can detect deposition of CPP crystals within the hyaline cartilage and/or fibrocartilage. In contrast to urate crystal deposits in gout, CPP crystals often deposit within the substance of the hyaline cartilage and fibrocartilage, providing a means to distinguish CPP from urate deposition that occurs on the surface of the hyaline cartilage as seen in gout (Fig. E8).⁸
• Early studies suggest that dual-energy CT scan can differentiate mineral deposits through color-coded images and may aid in the diagnosis of CPPD from other crystal arthropathies.^9,10

General measures such as immobilization of inflamed joint

• Monoarticular pseudogout:
  1. Aspiration followed by intraarticular corticosteroid injection (often superior to systemic treatment in the elderly)
• Polyarticular pseudogout:
  1. Oral corticosteroids, colchicine, or NSAIDs, if not contraindicated

Prophylaxis: Colchicine 0.6 mg twice daily or once daily as tolerated

• Pseudo-RA or refractory disease: Hydroxychloroquine or methotrexate
• Anakinra (Interleukin-1 receptor antagonist): Treatment and prophylaxis of polyarticular acute CPP crystal arthritis unresponsive to oral corticosteroids
• Treat underlying metabolic disease
• Management options for CPPD are summarized in Boxes E3 and E4

Structural joint damage may occasionally occur, requiring arthroplasty in rare cases.¹²

Rheumatology

Acute CPP crystal arthritis/pseudogout attacks have been reported to occur in the setting of surgical procedures, diuresis, bisphosphonate administration, and hyaluronate joint injections.

Pseudogout (Patient Information)

Gout (Related Key Topic)