Pyrophosphate arthropathy.

Pyrophosphate arthropathy, or calcium pyrophosphate dihydrate crystal deposition disease, is a disease caused by the formation and deposition of calcium pyrophosphate dihydrate crystals in connective tissue.

ICD-10 code

• M11. Other crystal arthropathies.
• M11.2 Other chondrocalcinosis.
• M11.8 Other specified crystal arthropathies.

Epidemiology

The disease pyrophosphate arthropathy occurs mainly in elderly people (over 55 years old), with almost equal frequency in men and women. According to X-ray data, the frequency of calcium pyrophosphate crystal deposition increases with age, amounting to 15% among 65-74-year-olds, 36% among 75-84-year-olds and 50% in people over 84 years old.

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What causes pyrophosphate arthropathy?

Although there is no proven information about the cause of calcium pyrophosphate dihydrate crystal deposition, there are factors associated with the disease. First of all, these include age (the disease occurs mainly in the elderly) and genetic predisposition (aggregation of cases of hindrocalcinosis in families with inheritance by an autosomal dominant trait). A history of joint trauma is a risk factor for calcium pyrophosphate dihydrate crystal deposition.

Hemochromatosis is the only metabolic and endocrine disease that is clearly associated with calcium pyrophosphate dihydrate crystal deposition disease. It has been shown that iron accumulation in patients with transfusion hemosiderosis and hemophilic arthritis leads to the deposition of these crystals.

Other possible causes of calcium pyrophosphate dihydrate crystal deposition include metabolic and endocrine disorders. Hyperparathyroidism, hypomagnesemia, and hypophosphatasia are associated with chondrocalcinosis and pseudogout. Gitelman syndrome, a hereditary renal tubular disorder characterized by hypokalemia and hypomagnesemia, is also associated with chondrocalcinosis and pseudogout. Calcium pyrophosphate dihydrate crystal deposition may occur in hypothyroidism and familial hypocalciuric hyperkalemia. Cases of acute pseudogout have been reported following intra-articular injections of hyaluronate. The mechanism of this phenomenon is unknown, but it is believed that phosphates in hyaluronate may reduce calcium concentration in the joint, leading to crystal deposition.

How does pyrophosphate arthropathy develop?

The formation of calcium pyrophosphate dihydrate crystals occurs in the cartilage, located near the surface of chondrocytes.

One of the possible mechanisms for the formation and deposition of calcium pyrophosphate dihydrate crystals is considered to be increased activity of nucleoside triphosphate pyrophosphate hydrolase enzymes. These enzymes are associated with the outer surface of the chondrocyte cell membrane and are responsible for catalyzing the production of pyrophosphates by hydrolysis of nucleoside triphosphates, especially adenosine triphosphate. Studies have confirmed that vesicles obtained by cleavage of articular cartilage collagenase are selectively saturated with active nucleoside triphosphate pyrophosphohydrolase enzymes and promote the formation of calcium- and pyrophosphate-containing minerals resembling calcium pyrophosphate dihydrate crystals. Among isozymes with ectonucleoside triphosphate pyrophosphohydrolase activity, cell membrane plasma protein PC-1 is associated with increased chondrocyte apoptosis and matrix calcification.

How does pyrophosphate arthropathy manifest itself?

In 25% of patients, pyrophosphate arthropathy manifests itself as pseudogout - acute monoarthritis lasting from several days to 2 weeks. The intensity of an attack of pseudogouty arthritis may vary, but the clinical picture resembles an acute attack of gouty arthritis. Any joints may be affected, but the first metatarsophalangeal and knee joints are most often involved (50% of cases). Attacks of pseudogouty arthritis occur both spontaneously and after exacerbations of chronic diseases and surgical interventions.

In approximately 5% of patients, the disease may initially resemble rheumatoid arthritis. In such patients, the disease manifests itself with symmetrical, often chronic, sluggish arthritis of many joints, accompanied by morning stiffness, malaise, and joint contractures. During examination, thickening of the synovial membrane, increased ESR, and in some patients, RF in a low titer are detected.

Pseudosteoarthrosis is a form of the disease detected in half of patients with calcium pyrophosphate dihydrate crystal deposition. Pseudosteoarthrosis affects the knee, hip, ankle joints, interphalangeal joints of the hands, shoulder and elbow joints, often symmetrically, with possible episodes of acute arthritis attacks of varying intensity. Deformations and flexion contractures of the joints are not typical. However, calcium pyrophosphate dihydrate crystal deposition in the patellofemoral joint leads to valgus deformity of the knee joints.

Pseudo-gout attacks occur more often in men, while pseudo-osteoarthrosis is more typical for women.

Deposits of calcium pyrophosphate dihydrate crystals in the axial spine can sometimes cause acute neck pain accompanied by muscle rigidity, fever, resembling meningitis, and in the lumbar spine can lead to acute radiculopathy.

In many patients, calcium pyrophosphate dihydrate crystal deposition occurs without clinical signs of joint damage.

Classification

There is no generally accepted classification. However, there are three clinical variants of pyrophosphate arthropathy, which include:

• pseudoosteoarthrosis;
• pseudogout;
• pseudorheumatoid arthritis.

The course of pyrophosphate arthropathy is accompanied by such a radiological phenomenon as chondrocalcinosis.

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Diagnosis of pyrophosphate arthropathy

The most commonly affected joints are the shoulder, wrist, metacarpophalangeal and knee joints, with any number of joints involved.

In the pseudogout variant, joint damage is acute or chronic. Acute arthritis can occur in one or (less frequently) several joints, most often in the knee, wrist, shoulder and ankle joints. The duration of an attack is from one to several months. In the chronic course of pseudogout, asymmetric damage to the shoulder, radial, metacarpophalangeal or knee joints is usually observed, the disease is often accompanied by morning stiffness lasting more than 30 minutes.

In pseudoosteoarthrosis, in addition to the joints characteristic of osteoarthrosis, other joints (wrist, metacarpophalangeal) are also affected. The onset is usually gradual; the inflammatory component is more pronounced than in normal osteoarthrosis.

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Physical examination

In the acute form of pseudogout, pain, swelling and an increase in local temperature in the affected joint (usually in the shoulder, wrist and knee) are detected. In the chronic course of pseudogout, pain and swelling are observed, as well as joint deformations, often asymmetrical. The severity of inflammation in pseudoosteoarthrosis is somewhat greater than in osteoarthrosis. Pain and swelling in the area of the Heberden and Bouchard nodes may occur. In general, pyrophosphate arthropathy should be suspected in a patient with osteoarthrosis who has pronounced inflammatory phenomena or with a localization of the joint syndrome that is not typical for osteoarthrosis.

Diagnostic criteria for calcium pyrophosphate dihydrate crystal deposition disease.

• 1. Detection of characteristic calcium pyrophosphate dihydrate crystals in tissues or synovial fluid, revealed by polarization microscopy or X-ray diffraction.
• 2A. Detection of monoclinic or triclinic crystals that have no or weak positive birefringence using polarization microscopy with a compensator.
• 2B. Presence of typical chondrocalcinosis on radiographs.
• 3A. Acute arthritis, especially of the knees or other large joints.
• 3B. Chronic arthritis, especially involving the knee, hip, wrist, metacarpal, elbow, shoulder or metacarpophalangeal joints, the course of which is accompanied by acute attacks.

The diagnosis of pyrophosphate arthropathy is considered reliable if the first criterion or a combination of criteria 2A and 2B is detected. In cases where only criterion 2A or only 2B is detected, the diagnosis of pyrophosphate arthropathy is probable. The presence of criteria 3A or 3B, i.e. only characteristic clinical manifestations of the disease, allows the diagnosis of pyrophosphate arthropathy to be considered possible.

Laboratory diagnostics of pyrophosphate arthropathy

The characteristic laboratory sign of any form of pyrophosphate arthropathy is the detection of these crystals in the synovial fluid. Usually, the crystals, which are rhomboid in shape and positively birefringent, are detected in the synovial fluid by polarizing microscopy with a compensator. The crystals appear blue when parallel to the compensator beam and yellow when perpendicular to it.

In such forms of the disease as pseudogout and pseudorheumatoid arthritis, the synovial fluid has low viscosity, is turbid, and contains polymorphonuclear leukocytes from 5,000 to 25,000. In pseudoosteoarthrosis, the synovial fluid, on the contrary, is transparent, viscous, with a leukocyte level of less than 100 cells.

Blood tests do not play a major role in diagnosing pyrophosphate arthropathy. The inflammatory process in pyrophosphate arthropathy may be accompanied by peripheral leukocytosis of the blood with a shift to the left, an increase in ESR and CRP levels.

Instrumental diagnostics of pyrophosphate arthropathy

Joint radiography. Radiographs of the knee joints, pelvis, and hands, including the wrist joints, are most indicative for detecting changes associated with the deposition of calcium pyrophosphate crystals.

• Specific signs. The most characteristic radiographic manifestation of the disease is calcification of the hyaline articular cartilage, which on the radiograph looks like a narrow linear shadow repeating the contour of the articular sections of the bones and resembles a "bead-like" thread. The detection of isolated narrowing of the patellofemoral joint space or degenerative changes in the metacarpophalangeal joints of the hands often also indicates pyrophosphate arthropathy.
• Non-specific signs. Degenerative changes: narrowing of the gaps, osteosclerosis with the formation of subchondral cysts - are non-specific, since they can occur both in pyrophosphate arthropathy caused by hemochromatosis, and in isolated pyrophosphate arthropathy and Wilson-Konovalov disease.

Additional research

Given the association of calcium pyrophosphate arthropathy with a number of metabolic disorders (hemochromatosis, hypothyroidism, hyperparathyroidism, gout, hypophosphatasia, hypomagnesemia, familial hypocalciuric hypercalcemia, acromegaly, ochronosis), patients with newly diagnosed calcium pyrophosphate crystals need to have serum levels of calcium, phosphorus, magnesium, iron, alkaline phosphatase, ferritin, thyroid hormones, and ceruloplasmin determined.

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Differential diagnostics

Pyrophosphate arthropathy is differentiated from the following diseases:

• gout;
• osteoarthritis;
• rheumatoid arthritis;
• septic arthritis.

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Indications for consultation with other specialists

A consultation with a rheumatologist is necessary to confirm the diagnosis.

Example of diagnosis formulation

Pyrophosphate arthropathy, pseudoosteoarthrosis form.

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Treatment of pyrophosphate arthropathy

Treatment goals

• Reduction of pain syndrome.
• Treatment of concomitant pathology.

Indications for hospitalization

Hospitalization is necessary in case of exacerbation of the disease and ineffectiveness of anti-inflammatory therapy.

Non-drug treatment of pyrophosphate arthropathy

Weight loss, use of heat and cold, orthoses, exercise, joint protection.

Drug treatment of pyrophosphate arthropathy

The asymptomatic variant of pyrophosphate arthropathy (with accidental detection of radiographic signs of the disease) does not require treatment. In case of an acute attack of pseudogout, NSAIDs, colchicine, and glucocorticosteroids are used intravenously or intra-articularly. Regular administration of colchicine at a dose of 0.5-0.6 mg 1 to 3 times a day is effective in patients with frequent attacks of pseudogout. In the presence of signs of pseudoosteoarthrosis of large supporting joints, the same treatment methods are used as for other forms of osteoarthrosis.

There are no specific treatments. Treatment of concomitant diseases such as hemochromatosis, hyperparathyroidism, and hypothyroidism does not result in the resorption of calcium pyrophosphate crystals; in rare cases, a reduction in the number of attacks is noted.

Surgical treatment of pyrophosphate arthropathy

Endoprosthetics is possible in case of degenerative changes in the joint

What is the prognosis for pyrophosphate arthropathy?

In general, pyrophosphate arthropathy has a relatively favorable prognosis. Observations of 104 patients over five years showed that 41% of them showed improvement, 33% of the condition remained unchanged, and only patients had negative dynamics, requiring surgical intervention in 11% of them.