Skip to Content

Calcium Pyrophosphate Arthritis

(Calcium Pyrophosphate Dihydrate Crystal Deposition Disease; Acute Calcium Pyrophosphate Arthritis; Chondrocalcinosis; Pyrophosphate Arthropathy; Pseudogout)


Brian F. Mandell

, MD, PhD, Cleveland Clinic

Last full review/revision Oct 2020| Content last modified Oct 2020

Calcium pyrophosphate arthritis involves intra-articular and/or extra-articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals. Manifestations are protean and may be minimal or include intermittent flares of acute arthritis, termed pseudogout or acute calcium pyrophosphate arthritis, and a degenerative arthropathy that is often severe. Diagnosis requires identification of CPPD crystals in synovial fluid. Treatment of pseudogout flares is with intra-articular corticosteroids or oral glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine.

(See also Overview of Crystal-Induced Arthritides.)

CPPD crystal deposition (chondrocalcinosis, pyrophosphate arthropathy), whether symptomatic and asymptomatic, becomes more common with age.

Asymptomatic chondrocalcinosis is common in the knee, metacarpophalangeal joints, hip, wrist, annulus fibrosus of the intervertebral disks, symphysis pubis, and spine. Men and women are affected about equally.

Etiology of Calcium Pyrophosphate Arthritis

The cause of calcium pyrophosphate arthritis is unknown. Frequent association with other conditions, such as trauma (including surgery), hypomagnesemia, hyperparathyroidism, gout, hemochromatosis, and old age, suggests that calcium pyrophosphate dihydrate (CPPD) crystal deposits are secondary to degenerative or metabolic changes in the affected tissues.

Some cases are familial, usually transmitted in an autosomal dominant pattern, with complete penetration by age 40.

Recent studies indicate that the ankyrin (ANK) protein is a central factor in producing excess extracellular pyrophosphate, which promotes CPPD crystal formation. ANK protein is a putative transporter of intracellular and microvesicle pyrophosphate to the extracellular location where CPPD crystals form.

Symptoms and Signs of Calcium Pyrophosphate Arthritis

Acute, subacute, or chronic arthritis can occur, usually in the knee or other large peripheral joints; thus, calcium pyrophosphate crystal disease can mimic many other forms of arthritis. Acute flares are sometimes similar to gout but are usually less severe. There may be no symptoms of calcium pyrophosphate arthritis between flares or continuous low-grade symptoms in multiple joints, similar to rheumatoid arthritis or osteoarthritis. These patterns tend to persist for life.

Diagnosis of Calcium Pyrophosphate Arthritis

  • Synovial fluid analysis
  • Identification of crystals microscopically

Calcium pyrophosphate arthritis should be suspected in older patients with arthritis, particularly inflammatory arthritis.

Diagnosis of calcium pyrophosphate arthritis is established by identifying rhomboid- or rod-shaped crystals in synovial fluid that are not birefringent or are weakly positively birefringent on polarized light microscopy. Joint fluid in acute flares has findings typical of inflammation; thus, coincident infectious arthritis and gout (other common causes of inflammatory joint fluid) must also be excluded. Infectious arthritis is ruled out based on Gram stain and culture findings. Gout is usually best ruled out by the absence of urate crystals in fluid from the inflamed joint. Notably a patient may have both gout and pseudogout. X-rays or ultrasonography are indicated if synovial fluid cannot be obtained for analysis; findings of multiple linear or punctate calcification in articular cartilage, especially fibrocartilages, support the diagnosis but do not exclude gout or infection. Typical ultrasonographic findings of gout (double contour sign) may simulate findings of calcium pyrophosphate crystal deposits.

Prognosis of Calcium Pyrophosphate Arthritis

The prognosis for individual flares of acute calcium pyrophosphate arthritis is usually excellent. However, chronic arthritis can occur, and severe destructive arthropathy resembling neurogenic arthropathy (Charcot joints) occasionally occurs.

Treatment of Calcium Pyrophosphate Arthritis

  • Intra-articular corticosteroids
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Colchicine maintenance

Symptoms of acute synovial effusion abate with synovial fluid drainage and instillation of a microcrystalline corticosteroid ester suspension into the joint space (eg, 40 mg prednisolone acetate or prednisolone tertiary butylacetate into a knee).

Indomethacin, naproxen, or another NSAID given at anti-inflammatory doses often stops acute flares promptly. Colchicine treatment of acute flares is identical to that of gout. Colchicine 0.6 mg orally once/day or 2 times a day may decrease the frequency of recurrent acute flares. Interleukin-1 antagonists such as anakinra can also be effective.

Key Points about Calcium Pyrophosphate Arthritis

  • Asymptomatic chondrocalcinosis becomes common with age, particularly in the knee, hip, wrist, annulus fibrosus of the intervertebral disks, and symphysis pubis.
  • Arthritis can affect the knee and large peripheral joints and mimic other forms of arthritis.
  • Examine joint fluid for characteristic rhomboid- or rod-shaped crystals in synovial fluid that are not birefringent or are weakly positively birefringent, and exclude joint infection.
  • For acute symptoms, treat with an intra-articular corticosteroid or an oral NSAID; colchicine or anakinra can also be effective.

Drugs Mentioned In This Article

Drug Name Select Trade
Indomethacin INDOCIN
prednisolone ORAPRED, PRELONE
colchicine COLCRYS
anakinra KINERET

Copyright © 2021 Merck & Co., Inc., known as MSD outside of the US, Kenilworth, New Jersey, USA. All rights reserved. Merck Manual Disclaimer