Pyrophosphate arthropathy

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

ICD-10 code

• M11. Other crystalline arthropathies.
• M11.2. Another chondrocalcinosis.
• M11.8 Other specified crystalline arthropathies.

Epidemiology

The disease pyrophosphate arthropathy occurs mainly in the elderly (over 55 years), with almost the same frequency in men and women. According to the radiography data, the frequency of deposition of calcium pyrophosphate crystals increases with age, accounting for 15% among 65-74-year-olds, 36% among 75-84-year-olds and 50% in persons older than 84 years.

[1], [2], [3], [4], [5]

What causes pyrophosphate arthropathy?

Despite the lack of proven information about the cause of calcium pyrophosphate deposition of calcium dihydrate, there are factors associated with the disease. First of all, they include age (the disease occurs mainly in the elderly) and genetic predisposition (the aggregation of cases of hindrocalcinosis in families with inheritance by autosomal dominant trait). Injury of the joints in the anamnesis is a risk factor for the deposition of calcium pyrophosphate crystals dihydrate.

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

Among other possible causes, leading to the deposition of calcium pyrophosphate crystals, calcium dihydrate, metabolic and endocrine disorders should be noted. Hyperparathyroidism, hypomagnesemia and hypophosphatase are associated with chondrocalcinosis and pseudopotagra. Gitelman's syndrome is a hereditary renal tubular pathology, in which hypokalemia and hypomagnesemia are observed, is also associated with chondrocalcinosis and pseudodopa. Possible deposits of calcium pyrophosphate crystals of dihydrate in hypothyroidism and familial hypocalciuric hyperkalemia. Episodes of acute pseudogout are described on the background of intra-articular injections of hyaluronate. The mechanism of this phenomenon is unknown, but it is believed that the phosphates that make up the hyaluronate can reduce the concentration of calcium in the joint, leading to the settling of crystals.

How does pyrophosphate arthropathy develop?

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

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

How is pyrophosphate arthropathy manifested?

In 25% of patients pyrophosphate arthropathy is manifested by pseudogout - acute monoarthritis lasting from several days to 2 weeks. The intensity of an attack of pseudo-arthritis arthritis may be different, but the clinical picture resembles a sharp attack of gouty arthritis. Any joints can be affected, but the most common are the first metatarsophalangeal and knee joints (50% of cases). Attacks of pseudo-arthritis arises both spontaneously, and after exacerbations of chronic diseases and surgical interventions.

Approximately in 5% of patients, the disease at first can resemble a picture of rheumatoid arthritis. In such patients, the disease manifests itself with symmetrical, often chronic sluggish arthritis of many joints, accompanied by morning stiffness, malaise, joint contractures. When the examination reveals a thickening of the synovium, an increase in ESR, and in some patients and RF in a low titer.

Pseudostosteroarthrosis is a form of the disease that is detected in half of patients with the deposition of calcium pyrophosphate crystals dihydrate. Pseudoosteoarthrosis affects the knee, hip, ankle joints, interphalangeal joints of the hands, shoulder and elbow joints, often symmetrically, with episodes of acute attacks of arthritis of varying intensity. Deformations and flexural contractures of the joints are not characteristic. However, the deposition of calcium pyrophosphate crystals of dihydrate in the patellofemoral joint leads to valgus deformation of the knee joints.

Pseudo-arthritic attacks are more common in men, while pseudo-osteoarthritis is more common in women.

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

In many patients, the deposition of calcium pyrophosphate crystals of dihydrate passes without clinical signs of joint damage.

Classification

A generally accepted classification does not exist. However, three clinical variants of pyrophosphate arthropathy are distinguished, which include:

• pseudo-osteoarthritis;
• pseudogout;
• pseudo-rheumatoid arthritis.

The course of pyrophosphate arthropathy is accompanied by such an X-ray phenomenon as chondrocalcinosis.

[6], [7], [8], [9]

Diagnosis of pyrophosphate arthropathy

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

With pseudo-arthritis, joint damage occurs acutely or chronically. Acute arthritis can occur in one or (more rarely) several joints, more often in the knee, wrist, shoulder and ankle. The duration of the attack is from one to several months. In the chronic course of pseudogout, asymmetric lesions of the humerus, radial, metacarpophalangeal or knee joints are usually observed, the disease is often accompanied by a morning stiffness lasting more than 30 minutes.

In pseudo-osteoarthritis, in addition to the joints characteristic of osteoarthritis, other joints (wrist, metacarpophalangeal) are affected. The onset is usually gradual; The inflammatory component is more pronounced than with conventional osteoarthritis.

[10], [11], [12], [13]

Physical examination

In the acute variant of pseudogout, pain, swelling and an increase in local temperature in the affected joint are revealed (more often in the shoulder, wrist, knee). In the chronic course of pseudogout, tenderness and swelling are observed, as well as joint deformities, often asymmetric. Severity of inflammation in pseudo-osteoarthritis is somewhat greater than in osteoarthritis. There may be soreness and swelling in the area of the nodules of Geberden and Buschar. In general, pyrophosphate arthropathy should be suspected in a patient with osteoarthritis, which has severe inflammatory phenomena, or with a localization of the joint syndrome that is not characteristic for osteoarthrosis.

Diagnostic criteria for the disease of deposition of calcium pyrophosphate crystals dihydrate.

• 1. Detection of characteristic crystals of calcium pyrophosphate dihydrate in tissues or synovial fluid, detected by means of polarization microscopy or by X-ray diffraction.
• 2A. Identification of monoclinic or triclinic crystals that do not possess or have weak positive birefringence in polarization microscopy using a compensator.
• 2B. The presence of a typical chondrocalcinosis on radiographs.
• 3A. Acute arthritis, especially the knee or other large joints.
• 3B. Chronic arthritis, especially involving the knee, hip, wrist, metacarpal, elbow, shoulder or metacarpophalangeal joints, during which accompany acute attacks.

The diagnosis of pyrophosphate arthropathy is considered reliable if the first criterion or combination of criteria 2A and 2B is detected. In those cases when only criterion 2A or only 2B is detected. The diagnosis of pyrophosphate arthropathy is probable. Presence of criteria FOR or ST, ie. Only characteristic clinical manifestations of the disease, allows to consider the diagnosis of pyrophosphate arthropathy possible.

Laboratory diagnostics of pyrophosphate arthropathy

A characteristic laboratory feature of any form of pyrophosphate arthropathy is the detection of these crystals in the synovial fluid. Usually crystals that have a rhomboid shape and positive birefringence are detected in the synovial fluid by polarization microscopy with a compensator. The crystals look blue when parallel to the compensator beam, and yellow when perpendicular to it.

In cases of pseudogout and pseudo-rheumatoid arthritis, the synovial fluid has a low viscosity, cloudy, contains polymorphic-nuclear leukocytes from 5000 to 25 000. In pseudo-osteoarthrosis, the synovial fluid, on the other hand, is transparent, viscous, less than 100 cells leucocyte.

The study of blood does not play a big role in the diagnosis of pyrophosphate arthropathy. The inflammatory process with pyrophosphate arthropathy may be accompanied by peripheral blood leukocytosis with a shift to the left, an increase in ESR and a level of CRP.

Instrumental diagnostics of pyrophosphate arthropathy

Radiography of joints. Radiographs of knee joints, pelvis and hands with seizure of 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 the calcification of hyaline articular cartilage, which on the roentgenogram looks like a narrow linear shadow that repeats the contour of the articular parts of the bones, and resembles a "bead-like" thread. The identification of an isolated narrowing of the knee of the patella-femoral joint or degenerative changes in the metacarpophalangeal joints of the hands often also indicates pyrophosphate arthropathy.
• Nonspecific signs. Degenerative changes: narrowing of the cracks, osteosclerosis with the formation of subchondral cysts are non-specific, since they can occur both in pyrophosphate arthropathy due to hemochromatosis, and in isolated pyrophosphate arthropathy and Wilson-Konovalov's disease.

Additional research

Given the association of pyrophosphate arthropathy with a number of metabolic disorders (hemochromatosis, hypothyroidism, hyperparathyroidism, gout, hypophosphatase, hypomagnesemia, familial hypocalcauric hypercalcemia, acromegalia, ochronosis), patients with newly diagnosed calcium pyrophosphate crystals need to determine the serum levels of calcium, phosphorus, magnesium, iron, , ferritin, thyroid hormones and ceruloplasmin.

[14], [15], [16]

Differential diagnostics

Differentiate pyrophosphate arthropathy from the following diseases:

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

[17], [18], [19], [20]

Indications for consultation of other specialists

It is necessary to consult a rheumatologist to confirm the diagnosis.

Example of the formulation of the diagnosis

Pyrophosphate arthropathy, pseudo-osteoarthritic form.

[21], [22], [23], [24], [25], [26], [27], [28]

Treatment of pyrophosphate arthropathy

Objectives of treatment

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

Indications for hospitalization

Hospitalization is necessary for exacerbation of the disease and inefficiency of anti-inflammatory therapy.

Non-pharmacological treatment of pyrophosphate arthropathy

Decrease in body weight, use of heat and cold, orthoses, exercises, joint protection.

Medication of pyrophosphate arthropathy

An asymptomatic variant of pyrophosphate arthropathy (with the occasional detection of X-ray signs of the disease) does not require treatment. In an acute attack of pseudogout, NSAIDs, colchicine, glucocorticosteroids intravenously or intra-articularly are used. The constant intake of colchicine in a dose of 0.5-0.6 mg from 1 to 3 times a day is effective in patients with frequent attacks of pseudo-gout. If there are signs of pseudoosteoarthrosis of large supporting joints, the same treatment methods are used as with other forms of osteoarthritis.

Specific means of treatment does not exist. Treatment of concomitant diseases, such as hemochromatosis, hyperparathyroidism and hypothyroidism, does not lead to resorption of calcium pyrophosphate crystals, in rare cases a decrease in the number of seizures is noted.

Surgical treatment of pyrophosphate arthropathy

Possible endoprosthetics in the case of degenerative changes in the joint

What is the prognosis of 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% had no changes, and only patients had a negative dynamics, which required 11% of them to undergo surgery.