Calcium Pyrophosphate Arthritis

The cause of calcium pyrophosphate arthritis is unknown. Frequent association with other conditions, such as trauma (including surgery), hypomagnesemia Hypomagnesemia Hypomagnesemia is serum magnesium concentration 1.8 mg/dL ( 0.70 mmol/L). Causes include inadequate magnesium intake and absorption or increased excretion due to hypercalcemia or drugs such... read more , hyperparathyroidism Pathophysiology Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism, vitamin... read more , gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more , hemochromatosis Hereditary Hemochromatosis Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. Manifestations can include systemic symptoms, liver disorders... read more , 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.

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.

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 Microscopic Examination of Crystals in Joints 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.

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 Neurogenic Arthropathy Neurogenic arthropathy is a rapidly destructive arthropathy due to impaired pain perception and position sense, which can result from various underlying disorders, most commonly diabetes and... read more (Charcot joints) occasionally occurs.

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 Nonopioid Analgesics Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more given at anti-inflammatory doses often stops acute flares promptly. Colchicine treatment of acute flares Treatment of acute flares Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more 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.