Overview.
Calcium pyrophosphate deposition disease is a crystalline arthropathy involving the joints and other locomotor systems associated with the deposition of calcium pyrophosphate dihydrate (CPPS) crystals, and is therefore also called pyrophosphate arthropathy. It occurs in the elderly, with acute self-limiting synovitis (pseudogout) being the most common in the acute phase, and chronic arthritis closely related to osteoarthritis, mainly affecting the large joints of the body such as the knees, wrists, shoulders, hips, and other joints.
Etiology
Although many environmental and genetic factors have been found to be related to calcium pyrophosphate deposition disease, a generalized specific etiology has not yet been found, and the occurrence of this disease has yet to be further studied.
1. Aging
Aging is a major correlate of calcium pyrophosphate deposition disease. Research results show that the concentration of pyrophosphate in the synovial fluid of normal knee joints increases with age, suggesting that this age-related change in the composition of synovial fluid is closely related to this disease.
2. Genetic factors
Some familial calcium pyrophosphate deposition diseases show an autosomal dominant mode of inheritance. These patients are often associated with primary cartilage composition and structural abnormalities.
3. Metabolic factors
Calcium pyrophosphate deposition disease may be due to abnormalities in pyrophosphate metabolism caused by disorders of certain metabolic mechanisms in the body. These possible mechanisms of metabolic abnormalities include:
(1) Decreased degradation of pyrophosphate due to: (1) Decrease in alkaline phosphatase concentration; (2) Presence of some alkaline phosphatase inhibiting ions; (3) Hypomagnesemia.
(2) Accelerated nucleation reactions due to elevated concentrations of nucleating agents caused by hemochromatosis or Wilson’s disease, making calcium pyrophosphate more easily deposited.
(3) Hypercalcemia itself can accelerate calcium pyrophosphate deposition.
(4) In hyperparathyroidism, parathyroid hormone can activate more adenylate cyclase, thereby increasing the source of pyrophosphate.
Symptoms
Many physicians now prefer to simplify the classification by dividing it into 3 categories according to their clinical manifestations: the acute synovitis type; the chronic arthritis type; and the calcium pyrophosphate deposition disease type found incidentally. They are described below:
1. Acute synovitis
Acute synovitis is the pseudogout type A, which is the most common cause of monoarthritis in the elderly. A typical acute attack starts suddenly, progresses rapidly, with severe pain, often accompanied by joint stiffness and swelling, and reaches its peak within 6 to 24 hours. The skin surface of the affected joints is usually flaky and erythematous, and the affected joints are often in an extended position, with typical synovitis manifestations, which may be accompanied by elevated body temperature.
2. Chronic arthritis type
Calcium pyrophosphate deposition disease is often manifested in the form of chronic arthritis in elderly female patients, which is mainly characterized by chronic pain, morning stiffness, restricted movement and impaired function, and the symptoms are often limited to a few joints. The affected joints are often characterized by osteoarthritis and varying degrees of synovitis, the latter being most common in the knee, radial wrist and glenohumeral joints. In severe cases, flexion deformity, valgus or valgus deformity, etc. Subtypes B, C, D, E, and F are included in the chronic arthritis type, with slight variations in clinical manifestations among these five subtypes.
Examination
1. Laboratory tests
(1) Identification of calcium pyrophosphate crystals The laboratory diagnosis of calcium pyrophosphate deposition disease is based on the identification of calcium pyrophosphate crystals in synovial fluid by phase contrast polarized light microscopy. The synovial fluid extracted from the diseased joints of patients with pseudogout is usually turbid or bloody in appearance, with a marked decrease in viscosity compared with the normal value, often accompanied by an elevated cell count [(2-80) × 109/L], with more than 80% of the cells being neutrophils; whereas the routine examination of synovial fluid in chronic pyrophosphate arthropathy varies greatly, and sometimes it can be similar to the manifestation of pseudogout, and at other times it can be almost completely normal. Sometimes it can be similar to pseudogout, while sometimes it can be almost completely normal.
(2) Other laboratory tests The joint extracts of patients with pseudogout must be routinely stained with Gram’s stain and cultured for bacteria to exclude the possibility of septic arthritis, which can sometimes coexist with both conditions. In addition, pseudogout often causes a stressful change in the body’s blood, which may be accompanied by increased C-reactive protein, plasma viscosity, and sedimentation in addition to elevated blood counts, especially if pseudogout involves multiple large joints or if the patient has other interstitial inflammatory conditions.
Patients with chronic pyrophosphate arthropathy may be mildly anemic, and elevated plasma viscosity and serum ferritin are not uncommon, but these biochemical or serologic changes are often not significantly different from those in normal subjects of the same age.
2. Other auxiliary examinations
(1) X-ray manifestations Calcium pyrophosphate deposition disease mainly manifests two aspects of calcification and arthropathy on X-ray: (1) calcification Calcium deposition of cartilage most often involves fibrocartilage (such as meniscus of the knee joint, deltoid bone of the wrist and pubic symphysis), followed by hyaline cartilage (such as hyaline cartilage of the knee, glenohumeral joint and hip joint), and the X-ray manifestation is the coarse linear hyperdense shadow parallel to the hypoechondrium, but not connected to the latter. Hyperdense shadow. Usually only one joint is involved unilaterally, with the knee being the most common. (2) Arthropathy The basic X-ray manifestations of pyrophosphate arthropathy are in fact the basic manifestations of osteoarthritis, including cartilage loss, cartilage sclerosis, cysts, and the formation of bone capillaries.
(2) Arthroscopy
(3) Polarized light microscopy.
(4) Pathologic examination Unlike sodium urate crystals, calcium pyrophosphate crystals are not deposited within all connective tissues, but tend to be confined to various structures of the locomotor system. Numerous pathologic findings have shown that the crystals are usually deposited first in the cartilage and, in rare cases, in the joint capsule and tendons, while deposition of crystals in the synovium, bursa, or tendon sheaths is secondary to the former.
Diagnosis
The diagnosis of calcium pyrophosphate deposition disease relies on:
1. direct evidence of the presence of calcium pyrophosphate crystals in synovial fluid or tissue (mainly biopsies of joint capsules and tendon sheaths);
2. radiographic manifestations of joints or soft tissues.
Differential diagnosis
1. diseases differentiated from pseudogout.
2. Diseases differentiated from chronic pyrophosphate arthropathy.
Complications
Complications and concomitant diseases of calcium pyrophosphate deposition disorder mainly include the following diseases:
1 hyperparathyroidism
Calcium pyrophosphate deposition disease patients 20% to 30% have articular chondrocalcinosis, 10% to 26% have elevated parathyroid hormone (PTH), and 2% to 15% have hyperparathyroidism, and the complication rate of both increases with age.
2. Hemochromatosis
Hemochromatosis, the body has too much iron, can promote calcium pyrophosphate dihydrate nucleation, but also inhibit the activity of pyrophosphatase, so hemochromatosis in half of the patients with arthritis, 50% of arthritis with X-ray calcification of the cartilage, and with the age of the increase. It is common in the 2nd to 5th intermetacarpal joints. 50% of patients have elevated blood PTH and most have normal calcium levels. Limiting calcium intake does not improve calcium pyrophosphate dihydrate deposition.
3. Gout and hyperuricemia
Gout occurs in middle-aged and old people, easily combined with hypertension, renal lesions, and the application of diuretics is more. Most patients have renal dysfunction, so hyperuricemia is common. Since uric acid is a good nucleating agent for calcium pyrophosphate dihydrate, 2% to 8% calcium pyrophosphate deposition complicates gout.
4. Hypothyroidism
As hypothyroidism has excessive hydrophilic mucopolysaccharides in the blood, it can increase the local concentration of calcium and pyrophosphate, and form calcium pyrophosphate dihydrate crystals in the synovial fluid, but without symptoms. Thyroxine, on the other hand, promotes the binding of calcium pyrophosphate dihydrate to immunoglobulins, triggering arthritis.
Treatment
Since there is no specific drug for the cause of calcium pyrophosphate deposition, the treatment of the disease remains symptomatic and supportive.
1. Treatment of acute synovitis
(1) Intra-articular fluid aspiration and injections Often, simply aspirating the joint fluid by itself can provide great relief, and sometimes this is the only treatment. In those patients with recurrent joint fluid collections, glucocorticoids may be injected into the joint cavity with a clear joint fluid culture or negative gram stain. Joint flushing should only be used in stubborn recurrent cases or in cases that do not respond to intra-articular glucocorticoid injections.
(2) Oral medications Common analgesics or non-steroidal anti-inflammatory drugs may provide further relief to the patient based on local manipulation of the joint, but should be used with caution in the elderly. Colchicine can relieve some symptoms in the acute phase, but it seems as if it is not very effective in preventing pseudogout attacks. Whether non-steroidal anti-inflammatory drugs are effective in cases of polyarticular attacks or in cases where the joints do not respond to localized treatment is still controversial.
2. Treatment of chronic pyrophosphate arthropathy
The aim of treatment in the chronic stage can also only be to relieve symptoms and maintain and improve joint function.
(1) Principles of treatment Reducing body weight, using crutches or other walking aids, learning to use the joints in the correct way, and moderately increasing muscle strength and tone can mechanically reduce the stress and wear and tear on the joints, and stabilize and improve their condition.
(2) Hormone therapy Intra-articular glucocorticoid injections can also improve clinical symptoms in the chronic phase.
(3) Symptomatic drugs As in the treatment of pseudogout, analgesics and non-steroidal anti-inflammatory drugs should be used with caution in elderly patients with chronic pyrophosphate arthropathy, and dosage should be observed when applying them. In general, the clinical preference is to give analgesics and avoid repeated administration of non-steroidal anti-inflammatory drug therapy.
(4) Surgery Arthroplasty can be considered for large joints with progressive destruction or very severe damage.
Prognosis
The prognosis of the disease is favorable. In the case of other diseases, the prognosis depends on the complication.
Prevention
Preventive measures include controlling high blood phosphorus, correcting low blood calcium, supplementing vitamin D, preventing hyperparathyroidism, hemodialysis or kidney transplantation. However, the key is to control high blood phosphorus at an early stage.
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