calcium pyrophosphate deposition disease
Introduction
Introduction to calcium pyrophosphate deposition Calcium pyrophosphate deposition disease is a kind of crystalline arthropathy associated with the deposition of crystals of calcium dicalcium phosphate (CPPS) involving joints and other motor systems. Therefore, it is also called pyrophosphate joint disease. Clinically, it is more common in the elderly. In the acute phase, acute self-limited synovitis (pseudogout) is the most common. Chronic arthritis is closely related to osteoarthritis, involving the whole body such as the knee and wrist. The shoulders, hips and other joints are dominant. Control measures include controlling high blood phosphorus, correcting hypocalcemia, supplementing vitamin D, preventing hyperparathyroidism, hemodialysis or kidney transplantation. But the key is to control high blood phosphorus early. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: Hyperparathyroidism Osteoporosis Gout Hyperuricemia Hypertension Arthritis Diabetes
Cause
Causes of calcium pyrophosphate deposition
(1) Causes of the disease
Although many environmental and genetic factors and calcium pyrophosphate deposition diseases have been found so far, no specific specific cause has been found so far, and the occurrence of this disease remains to be further studied.
1. Aging: It is a major factor in the deposition of calcium pyrophosphate. Previous studies have shown that the concentration of pyrophosphate in the synovial fluid of normal people increases with age, suggesting that this age-related slip The change of liquid composition is closely related to this disease. In recent years, an senile amyloid protein has been found to bind tightly to pyrophosphate or calcium ion, but this amyloid protein does not appear to be positively correlated with calcium pyrophosphate deposition disease. Moreover, histologically, the location of this amyloid deposition in cartilage is not the same as that of calcareous deposits. In addition, some indirect evidence suggests that common osteoarthritis in the elderly is positively correlated with the disease, but this correlation is also Further research is needed.
2. Genetic factors: Some familial calcium pyrophosphate deposition diseases are characterized by autosomal dominant inheritance. These patients are often accompanied by abnormalities of primary cartilage components and structures. A group of Swedish familial cokes are reported in the literature. Studies of calcium phosphate deposition have found that the loss of proteoglycans in cartilage occurs before the formation of calcium pyrophosphate crystals, while studies of articular cartilage calcium deposits in the United States and France suggest that the disease has abnormalities in pyrophosphate metabolism, intracellular The concentration of pyrophosphate is elevated, but there are no obvious abnormalities in their synovial fluid in the five calcium pyrophosphate deposition families in the UK. These findings suggest that there may be a calcium pyrophosphate deposition disease. Different mechanisms.
3. Metabolic factors: The results of in vitro experiments have led to the inference that calcium pyrophosphate deposition may be due to abnormalities in the metabolism of pyrophosphate caused by some metabolic mechanisms in the body. These possible metabolic abnormalities include:
(1) Decreased degradation of pyrophosphate due to the following reasons: 1 decrease in alkaline phosphatase concentration; 2 due to the presence of some ions that inhibit alkaline phosphatase (such as hypercalcemia caused by hyperparathyroidism, hemochromatosis) Caused by an increase in the concentration of iron ions, an increase in the concentration of copper ions caused by Wilson's disease, etc.); 3 hypomagnesemia.
(2) The nucleation reaction is accelerated due to an increase in the concentration of the nucleating agent caused by hemochromatosis or Wilson disease, so that calcium pyrophosphate is more easily deposited.
(3) Hypercalcemia itself can accelerate the deposition of calcium pyrophosphate.
(4) When hyperparathyroidism is hyperactive, parathyroid hormone can activate more adenylate cyclase, thereby increasing the source of pyrophosphate.
4. Osteoarthritis and joint damage. From the results of histological or epidemiological studies, at least in terms of the knee joint, calcium pyrophosphate deposition disease and osteoarthritis are closely related, but it has not yet been elucidated. Mechanism, and calcium pyrophosphate deposition disease secondary to some joint diseases (such as late complications of juvenile arthritis) and joint trauma is not uncommon in clinical practice. A lot of literature review about post-orthopedic calcium pyrophosphate deposition disease Reports of significantly increased prevalence, such as meniscectomy, lumbar discectomy, and osteochondritis, in general, a case of calcium pyrophosphate deposits on the basis of joint lesions, tend to be more prone to bone It is so thick that some people think that calcium pyrophosphate deposition is not an independent disease, but it should be regarded as a pathological process of many joint diseases or joint trauma. It is also believed that calcium pyrophosphate deposition itself can cause bone disease. Hyperplasia or structural reconstruction of the bone, but with one exception, rheumatoid arthritis presents a negatively correlated association with calcium pyrophosphate deposition, whether from Controlled radiology studies have supported this from the results of joint synovial fluid analysis in a large number of cases, while other studies have shown that although the concentration of pyrophosphate in the synovial fluid of patients with osteoarthritis is elevated. However, in rheumatoid arthritis cases, the concentration is reduced, this difference seems to be related to the latter's chondrocyte activity and its excessive proliferation, while rheumatoid arthritis joint synovial vasospasm focused on phosphoric acid absorption The scavenging function only plays a supporting role, and gout is also negatively correlated with rheumatoid arthritis. It has been suggested that a non-specific crystallization inhibitor in the body of rheumatoid arthritis may inhibit the crystal deposition of inorganic salts.
(two) pathogenesis
1. Metabolism of calcium pyrophosphate Pyrophosphoric acid is an intermediate product of various biochemical metabolic reactions in the body. Although several kilograms of pyrophosphate can be produced per person per day, pyrophosphorus is continuously degraded to orthophosphoric acid due to the ubiquitous pyrophosphatase in the body. Whether it is intracellular concentration or extracellular concentration is maintained at a very low level, about 1 mol / L, although there is also a high-energy phosphate bond in the pyrophosphate molecule, but for mammals, pyrophosphate has never been It is stored in the body as an energy substance.
Many biological functions of pyrophosphate have been gradually recognized, including the involvement of intracellular calcium transport, the transport of nucleotides, the regulation of enzyme activity, the storage of intracellular particles and the effects on mitosis. It plays an important role in the mineralization process of bone. The surface of pyrophosphate and hydroxyapatite has a high affinity. A certain concentration of pyrophosphate is necessary in the initial stage of nucleation of hydroxyapatite and later growth stages. Below this concentration will not initiate nucleation, and above this concentration will inhibit the entire mineralization process, alkaline phosphatase is the main extracellular pyrophosphate degrading enzyme, its activity often determines the hydroxy phosphorus The formation and growth of graystone.
The source of extracellular pyrophosphate has not been known so far, since almost all of the nucleotide-dependent biochemical reactions that produce pyrophosphate occur in cells, and pyrophosphate has been shown to be unable to diffuse easily through the cell membrane. A pyrophosphate-ADP transport system was found on the mitochondrial membrane, but no similar active or facilitated transport system was found on the cell membrane. It is speculated that extracellular pyrophosphate may be produced by the following mechanism: in cell division, Some triphosphate nucleotides leak out of the cell during injury or exocytosis. It has been shown that there is a significant increase in ATP in the synovial fluid of pyrophosphate arthritis. These triphosphate nucleotides are in extracellular pyrophosphatase. Degraded to nucleotides and pyrophosphate, which is usually quickly degraded to orthophosphoric acid by alkaline phosphatase on the outer membrane. This step requires the participation of magnesium ions, and the whole process is affected by the cell membrane. '-nucleotidase regulation.
Compared with normal knee joints, the concentration of pyrophosphate in the synovial fluid of patients with chronic pyrophosphate arthropathy and simple osteoarthritis is significantly improved, while the concentration of pyrophosphate in their plasma and urine is often normal for pyrophosphate In cases of acute membranous inflammation of calcium deposition, the concentration of pyrophosphate in synovial fluid is rarely found to increase. For patients with rheumatoid arthritis, the concentration is even lower than normal, which may be caused by an inflammatory state in the latter. Local vascular permeability is related, but the laboratory data on phosphoric acid, pyrophosphatase, alkaline phosphatase and 5'-nucleotidase have not yet achieved consistent results. Some in vitro experiments have shown that Chondrocytes may be a major source of excess pyrophosphate in the joints, especially cartilage in growing cartilage and osteoarthritis patients often significantly increase extracellular pyrophosphate concentrations.
2. The formation of calcium pyrophosphate crystals There are 12 kinds of crystal structures in calcium pyrophosphate, but it is limited to two crystal forms in human body deposition: monoclinic and triclinic crystals, different from gout sodium urate crystal deposition, pyrophosphate The deposition of calcium crystals often requires a more special physiological and biochemical environment. So far, no animal model of calcium pyrophosphate deposition disease has been established in the world. Some of the main experimental data comes from some colloids artificially established in vitro. The model consists of gelatin and collagen), and the more positive conclusions are:
(1) The magnesium ions in the tissue matrix can inhibit the initial nucleation process of the calcium pyrophosphate crystal formation and the subsequent crystal growth process, and can increase the solubility of calcium pyrophosphate. Similarly, orthophosphoric acid, chondroitin sulfate, etc. However, proteoglycans play a role of soil throughout the process: proteoglycans rely on their abundant carbon skeleton branches to form crystals by combining Ca2, Mg2, PO43- and other small molecule activators or inhibitors. Play a general regulatory role.
(2) On the other hand, the crystal particles of Fe3, Fe2 and sodium urate in the matrix promote the nucleation and growth of calcium pyrophosphate crystals, and the hydroxyapatite particles can already be made due to its affinity with calcium pyrophosphate. The formed calcium pyrophosphate crystals are continuously grown. In recent years, some collagen and acidic phospholipids have also been found to promote crystal formation, but further confirmation is needed.
(3) The formation of monoclinic and triclinic crystals of calcium pyrophosphate is a slow process, often requiring a large number of intermediate crystal forms to eventually form the most stable triclinic crystal. This recurring crystal formation - dissolution - The process of re-structuring itself can change the concentration of various ions in the microenvironment around the crystal, thereby accelerating the deposition of crystals.
Histological studies have found that the deposition of calcium pyrophosphate crystals appears to be limited to the cartilage collagen matrix in the vicinity of the middle zone between fibrocartilage and hyaline cartilage (also occasionally in the joint capsule or tendon), and matrix proteins are often seen on pathological sections. Degradation or loss of glycans, and there are a large number of lipid particles positive for Sudan red staining in hypertrophic or metaplastic chondrocytes around calcium pyrophosphate crystals, which further suggests that proteoglycans act as "soil" on the cartilage matrix. The environment plays a stabilizing role, and its destruction often causes disturbance of the microenvironment, which causes the deposition of calcium pyrophosphate crystals. The deposition of lipids is the cause of crystal deposition, and the secondary results have yet to be further studied.
3. Crystal-induced inflammatory responses In vitro or in vivo experiments have demonstrated that calcium pyrophosphate crystals can cause acute inflammatory reactions, for example, in pseudo-gout, it can simultaneously activate complement through classical and alternative pathways, allowing C3 in synovial fluid. Increased concentration causes an inflammatory response; in some in vitro experiments, calcium pyrophosphate crystals can also activate Hageman factor and further produce kallikrein, bradykinin, plasmin, etc., inflammatory mediators; The activity of the biofilm cleaves lysosomes, red blood cells, and neutrophils. When the crystals are phagocytosed by neutrophils, the cells release superoxide ions, lysosomal enzymes, chemokines, and peanuts. An inflammatory medium of dilute acid. The action of this crystal with cells or inflammatory mediators is mainly caused by direct contact with crystals. In addition, calcium pyrophosphate crystals are also associated with some proteins with positive or negative charges, especially Immunoglobulins, which have a higher affinity, tend to undergo a conformational change when IgG binds to crystals, leading to further inflammatory reactions, while others, such as apo B (beta) low-density lipoprotein binds to crystals and inhibits crystal-mediated neutrophil cleavage. This similar phenomenon is also found in other crystalline arthritis, such as -2HS glycoprotein. It can inhibit hydroxyapatite-mediated neutrophil release of superoxide ions.
Chronic inflammation caused by calcium pyrophosphate deposition and its damage may be related to the persistent inflammation of the synovium and the biochemical metabolism of local cells, but the mechanism is obviously different from the acute inflammatory response, and the chronic granuloma caused by subcutaneous injection of calcium pyrophosphate The reaction can last for several weeks, and the degree of inflammatory reaction is more severe than subcutaneous injection of sodium urate. Similar fibroblast proliferation and collagen deposition can also be seen in the body's response to other crystals such as asbestos and silica.
4. The shedding of crystals has long been found that in the in vitro model established by mimicking the microenvironment in the diseased joint, calcium pyrophosphate crystals are difficult to nucleate and grow, so the focal in synovial fluid is proposed. Calcium phosphate crystals may be formed by detachment from deposited crystals in the surrounding cartilage. This process is often accompanied by a reduction in the volume of the original crystal, a change in the cartilage matrix or even a cartilage fracture. This hypothesis is confirmed by the following facts:
1 When using calcium pyrophosphate crystal solution to flush the joint cavity, it will often be counterproductive, induce or aggravate the onset of pseudogout. A similar phenomenon can also be seen in the case of a sudden decrease in calcium ion concentration in the body due to parathyroidectomy;
2 pseudogout is often secondary to joint trauma, especially acute crush injury;
3 pseudo-gout often coincides with sepsis (the dissolution of crystals due to the action of some enzymes in the body during sepsis);
4 In the replacement of thyroxine, the onset of pseudo gout was caused by a change in the colloidal matrix of the cartilage.
Other more direct evidence comes from imaging: in the case of pseudo-gout, it is often found to have a reduction in the original cartilage calcium deposits, and in the follow-up of some patients with pyrophosphate arthropathy, this cartilage The reduction of sedimentary shadows is often accompanied by localized loss of cartilage.
Although the exfoliated calcium pyrophosphate crystals are often engulfed and further processed by neutrophils or synoviocytes, this is a slow process and calcium pyrophosphate crystals can always be detected in synovial fluid during the intermittent episodes of acute attacks. The existence, however, is exactly what mechanism ultimately stops the acute attack and allows the joint to "tolerate" the existence of this "inflammation-inducing" crystal during the interictal period. So far there is no satisfactory explanation, but one thing is certain, the crystal is finally The hypothesis that a layer of inhibitory protein is wrapped is more reasonable than the hypothesis that the final structural change of the crystal causes the mechanism to change.
Prevention
Prevention of calcium pyrophosphate deposition
Population prevention
With the prolongation of life expectancy and the improvement of detection methods for patients with chronic renal failure, the detection rate of this disease has an increasing trend. The bone biopsy and radionuclide scanning can be used to diagnose the disease early.
Population control measures include controlling high blood phosphorus, correcting hypocalcemia, supplementing vitamin D, preventing hyperthyroidism, hemodialysis or kidney transplantation, but the key is to control hyperphosphatemia early.
2. Personal prevention
(1) Primary prevention:
1 control of high blood phosphorus: first should control the intake of phosphate in the diet, phosphate is mainly from protein in food, patients with advanced renal failure such as daily phosphorus intake >1.2g, and not taking phosphorus binder, then Hyperphosphatemia can occur, followed by the use of phosphorus binders as appropriate, and the use of small doses of calcium carbonate or calcium lactate under strict monitoring of blood calcium is currently the first recommended method.
2) Correcting hypocalcemia: Maintaining normal calcium balance is beneficial to bone mineralization and inhibiting hyperparathyroidism. Calcium absorption is reduced in patients with advanced renal failure, while calcium intake in diet is only 400-700 mg per day. It should be supplemented with 1~2g of elemental calcium per day to supplement calcium acetate and calcium gluconate.
3 application of active vitamin D: kidney produces 1,25-dihydroxyvitamin D failure, plays an important role in the occurrence and development of renal osteopathy, 1,25-dihydroxyvitamin D3 can make blood calcium in uremic patients The level of blood is significantly increased, and the level of blood parathyroid hormone is significantly decreased. Currently, vitamin D preparations commonly used include vitamin D2, alfacalcidol and calcitriol (Rosin Calcium).
4 Dialysis and kidney transplantation: Dialysis can partially replace renal function, while kidney transplantation can completely replace renal function, thereby treating renal bone disease.
(2) secondary prevention: the incidence of renal osteopathy is concealed, often without self-conscious symptoms, blood calcium is reduced, elevated blood phosphorus and alkaline phosphatase can be used as the basis for early diagnosis, tibia biopsy, photon absorption bone density determination and99ECT scan can improve the early diagnosis rate, the diagnosis points:
1 diagnosis basis of renal failure;
2 children are rickets, adults are mainly bone pain, and the lower limbs bear heavy bones;
3X line examination showed specific bone disease performance.
Once renal osteopathy is discovered, the above preventive measures should be implemented immediately. Subtotal thyroidectomy should be performed for patients with obvious secondary hyperparathyroidism, persistent hypercalcemia, metastatic calcification and severe itchy skin. .
(3) Tertiary prevention: When fractures and significant skeletal deformities occur, surgery can be considered to correct them, but preoperative preparation should be sufficient, such as correcting the patient's anemia, nutritional status, etc., and doing intraoperative monitoring.
Complication
Complications of calcium pyrophosphate deposition Complications hyperparathyroidism osteoporosis gout hyperuricemia hypertensive arthritis diabetes
Complications and associated diseases of calcium pyrophosphate deposits mainly include the following diseases:
1. Hyperparathyroidism: 20% to 30% of patients with calcium pyrophosphate deposits have articular cartilage calcification, 10% to 26% of parathyroid hormone (PTH), and 2% to 15% of parathyroid function Hyperthyroidism, with the increase of age, the incidence of both increased, but the latter has bone pain, osteoporosis, height reduction, bone scan bone absorption increased, blood calcium increased, etc., when the adenoma is removed, blood calcium declines, symptoms disappear , different from calcium pyrophosphate deposition.
2. Hemochromatosis: When the blood is calm, there is too much iron in the body, which can promote the nucleation of calcium pyrophosphate dihydrate and inhibit the activity of pyrophosphatase. Therefore, half of the patients with hemochromatosis have arthritis and 50% of the joints. Inflammatory patients have calcification of X-ray cartilage and increase with age, which is common in the 2nd to 5th palm joints. 50% of patients have elevated blood PTH. Most blood calcium levels are normal. Limiting calcium intake does not improve dihydrate. Deposition of calcium pyrophosphate.
3. Gout and hyperuricemia: Gout occurs in middle-aged and elderly people, easy to be complicated with hypertension, kidney disease, more diuretics, patients with renal dysfunction, so common hyperuricemia, because uric acid is dihydrate A good nucleating agent for calcium pyrophosphate, so 2% to 8% calcium pyrophosphate deposition is complicated by gout, and this deposition is not associated with hyperuricemia.
4. Hypothyroidism: due to excessive thyroid dysfunction in the blood, there may be excessive water-soluble mucopolysaccharide, which can increase the concentration of local calcium and pyrophosphate, form calcium dicalcium phosphate crystal in synovial fluid, but asymptomatic, thyroid It can promote the binding of calcium pyrophosphate dihydrate to immunoglobulin and cause arthritis.
In addition, yellow brown disease, diabetes, amyloidosis and iatrogenic Cushing's disease may also be complicated by calcium pyrophosphate.
Symptom
Symptoms of calcium pyrophosphate deposition common symptoms joint pain bone destruction osteoporosis rheumatoid arthritis calcified carpal tunnel syndrome morning stiff bone spurs form calcium deposition joint deformity
The clinical manifestations of calcium pyrophosphate deposition are highly variable. They are similar to other joint diseases. They are often classified as "false" syndromes and are classified into six subtypes according to their clinical manifestations: type A (pseudo gout) Type), type B (pseudo-rheumatic arthritis type), type C (pseudo-arthritis with recurrent acute type), type D (pseudo-arthritis without acute arthritis), type E ( Asymptomatic type, type F (pseumatic neuroarthritis type), although this classification is still widely used by clinicians, in practice these subtypes often overlap with each other due to symptoms or subtypes Transformation increases the difficulty of diagnosis and typing. When patients suffer from other joint diseases, such as osteoarthritis, they often cause unnecessary misunderstandings. Many doctors now advocate simplifying classification according to their clinical manifestations. Divided into 3 categories:
1 acute synovitis type;
2 chronic arthritis type;
3 The accidental discovery of calcium pyrophosphate deposition disease, the relationship between these three types of clinical features and the above six subtypes is now described below.
1. Acute synovitis type: Acute synovitis type is a type of pseudo gout type, which is the most common cause of single arthritis in the elderly, but clinically seen in more common in middle-aged men, calcium pyrophosphate deposition disease The acute episode can be both a manifestation of asymptomatic chondromatosis and a manifestation of pyrophosphate arthropathy, especially in older women with a history of chronic arthritis. The knee joint is the most common clinical, followed by Wrist joints, shoulder joints, ankle joints and elbow joints usually start with only one joint, and less than 10% of the total number of joints involving 2 or more joints.
The typical onset of sudden onset is sudden, rapid progress, severe pain, often accompanied by joint stiffness and swelling, reaching a peak within 6 to 24 hours. Just like the acute episode of gout, patients often describe the severity of pain as "never experienced And refused any form of pressure on the lesion, and even could not bear the light touch of the clothing or bedding. When the body was examined, the surface of the affected joint had flaky erythema on the surface of the joint, and the affected joint was often in an extended position, which was more typical. Membrane manifestations (local tissue with exudate, elevated temperature, limited joint movement, joint capsule tenderness, etc.), accompanied by elevated body temperature, elderly patients sometimes have mild clinical symptoms, especially with multiple joint lesions Need to be differentially diagnosed with other diseases.
Acute attacks are self-limiting and usually relieve within 1 to 3 weeks. Some clinically atypical cases may present as short-term recurrent episodes. A series of small episodes with mild pain may not be possible in most cases. Foreseeable, some of the following high-risk factors can induce the onset of pseudo-gout:
1 direct trauma of the joint;
2 parathyroidectomy or other surgery;
3 blood transfusion and other intravenous infusion;
4 thyroxine replacement therapy;
5 joint cavity irrigation;
6 chest infection or myocardial infarction, etc., these high-risk factors often occur 1 to 3 days before the onset of pseudo-gout.
2. Chronic arthritis type: Calcium pyrophosphate deposition disease is often manifested in the form of chronic arthritis in elderly women, and the distribution of joint lesions in intermittent acute attacks is similar to that of pseudo-gout, according to the probability of occurrence: knee Joints, wrist joints, shoulder joints, elbow joint hip joints and interphalangeal joints, 2nd and 3rd metacarpophalangeal joints, are often involved, clinically mainly characterized by chronic pain, morning stiffness, limited mobility and Impaired function, symptoms are often limited to a few joints, the affected joints are often accompanied by clinical manifestations of osteoarthritis (osteopathy, joint friction, limited mobility) and varying degrees of synovitis, the latter in the knee Joints, ankle joints and ankle joints are the most common. In cases with severe lesions, joint flexion deformity, valgus or varus deformity can be seen. The above A, B, C, D, E and F subtypes are included in chronic joints. Within the inflammatory group, the clinical manifestations between the five subtypes are slightly different and are now described below.
(1) Type B (pseudo-rheumatic arthritis type): About 10% of patients have progressive, symmetrical, multi-joint development, which may have morning stiffness, increased erythrocyte sedimentation rate, and so on. Rheumatoid arthritis is confused, but this type occurs in the wrist, elbow, shoulder, knee and other large joints, and is rarely accompanied by tenosynovitis and extra-articular systemic manifestations. Only 10% of patients have rheumatoid factor-positive, imaging Osteoporosis and cartilage calcification are typical manifestations, but rarely associated with osteoporosis and bone destruction, which can be distinguished from rheumatoid arthritis.
(2) Type C (pseudo-arthritis with repeated acute attacks): This type is common in elderly women, most often invading the knee joint, showing a symmetric distribution, intermittent acute attacks and bone spur formation, severe cases can lead to Joint destruction, deformation or contracture, patients often accompanied by Heberden nodules typical of osteoarthritis.
(3) D type (pseudo-arthritis without repeated acute attacks): general clinical manifestations and prevalence are similar to C type, but there is no acute attack, calcium pyrophosphate crystals can also be found in joint synovial fluid, serious It can also lead to degenerative changes and deformities of the joints, and cartilage calcification can be seen imaging.
(4) Type E (asymptomatic): This type of patient usually has no clinical manifestations, and is common in the elderly, especially in people over 80 years of age. Usually patients undergo routine physical examination or trauma X The line examination was discovered by chance. The proportion of patients who usually have no clinical manifestations is very large. There is no exact statistics yet. However, like the diagnosis of osteoarthritis, whether it is clinical manifestations or imaging findings, We can't easily make a diagnosis at any of these points. A detailed medical history and a comprehensive physical examination are essential at all times. Compared with other types, this type is more prone to knee inversion and wrist. Discomfort.
(5) F-type (pseudo-neuropathic arthritis type): Sometimes the imaging of chronic pyrophosphate arthrosis is similar to the signs of hypertrophic Charcot joints (hence the name "pseudo-neuropathic arthritis"). However, Charcot joints are usually accompanied by severe neurological diseases, and other manifestations of neurological diseases are often more obvious. From clinical symptoms, they can be differentiated from chronic pyrophosphate arthropathy. In some elderly women, hip joint lesions are X-slices showed a manifestation of atrophic Charcot joints, and joint destruction was severe, but the final pathological report suggested that the lesions of the hip joint were only hydroxyapatite deposition, but not related to calcium pyrophosphate deposition. Not sure.
There is still a lack of clinical reports on the detailed natural course of chronic pyrophosphate arthropathy. The literature reports that in those cases with severe symptoms and knee deformities, 60% of patients still have their condition controlled or improved, and for those The prognosis of patients with only small and medium joints is more optimistic. However, there are still a small number of cases with more serious progressive joint destruction, especially knee, shoulder and hip damage. This situation seems to be limited to elderly women. The patient's usual joint pain is more obvious at night or at rest, often with recurrent joint blood, and the prognosis is poor.
3. Accidental discovery of calcium pyrophosphate deposition: This type of patient is relatively rare, and its clinical manifestations are as follows:
(1) Atypical joint manifestations and spinal lesions: Some familial calcium pyrophosphate deposits with severe spinal rigidity have been referred to as pseudo-ankylosing spondylitis, but in some familial cases, Some eventually develop true ankylosing spondylitis. The acute onset of spondyloarthropathy has not been confirmed clinically, but some self-limiting lumbar or cervical spondylosis may be related to pseudogout. In addition, when calcium pyrophosphate is deposited The ligamentum flavum (especially the ligamentum flavum of the neck 3-6) or the intervertebral disc that has undergone degenerative changes may cause some elderly patients to have clinical manifestations similar to the onset of acute meningitis, although this deposition rarely causes Lesions of the spinal nerve roots.
(2) tendonitis and tenosynovitis: due to the deposition of calcium pyrophosphate in the onset of acute inflammation, clinically seen in the triceps tendon, flexor tendon and Achilles tendon, tenosynovitis in the hand extensor and flexor tendon sheath can be Occurrence, in which flexor tenosynovitis is often accompanied by carpal tunnel syndrome, and the damage of the median and sacral nerves seems to be more related to this soft tissue inflammation, rather than the arthritis itself, the clinically caused tendon rupture is extremely rare .
(3) bursitis olecranon, subhumeral and sacral bursitis is a rare clinical manifestation of this disease, more common in cases of calcium pyrophosphate deposition in the body, bursitis is likely due to pyrophosphate Calcium is caused by the displacement of tissues around the bursa (articular cartilage, joint capsule and tendon) onto the bursa, not because of the direct deposition of calcium pyrophosphate on the synovial sac.
(4) Nodular calcium pyrophosphate deposits: nodular calcium pyrophosphate deposits are clinically rare, involving both extra-articular and intra-articular, visible in the elbow, knuckle, mandibular, acromioclavicular and hip Joints, such nodules are often isolated, and cartilage-like metaplasia is often seen in the nodules. When this happens, local histopathological biopsy is often needed to exclude malignant transformation.
In short, the clinical manifestations of calcium pyrophosphate deposition disease are diverse. It has been called the imitation master of arthritis, which has brought difficulties to the diagnosis and treatment of this disease. The performance of the six subtypes is different and each has its own characteristics. According to McCarty, type A patients account for about 25% of the total number of patients with calcium pyrophosphate deposition, type B accounts for 5%, type C and type D each account for 25%, and other types account for 20%. In general, except for usual In addition to the clinical manifestations of E type, the other five subtypes still have some common features. For example, the disease usually only involves large joints, with knees, wrists, shoulders, ankles, elbow joints being the most common, usually caused by a joint. Symptoms of other systems outside the joint are rare, which is quite different from some autoimmune joint diseases. The acute manifestation of this disease is mainly the symptoms of acute synovitis. Because of its severe pain, it often needs to be differentiated from acute gout attacks. The performance of chronic arthritis is differentiated from osteoarthritis and neuropathic arthritis. When clinical manifestations are not typical, it is often required to assist in the examination of joint fluid.
Examine
Examination of calcium pyrophosphate deposition disease
1. Identification of calcium pyrophosphate crystals: The laboratory diagnosis of calcium pyrophosphate deposition disease mainly relies on phase contrast polarized light microscopy to identify calcium pyrophosphate crystals in joint synovial fluid, and synovial fluid extracted from the diseased joints of patients with pseudo gout. The appearance is usually turbid or bloody, and its viscosity is significantly lower than the normal value, often accompanied by an increase in the number of cells [(2 ~ 80) × 109 / L], more than 80% of the neutrophils The routine examination of synovial fluid in chronic pyrophosphate arthropathy varies greatly, sometimes similar to the performance of pseudo-gout, and sometimes it can be almost completely normal.
Calcium pyrophosphate crystals are almost invisible under ordinary light microscope. The gold standard for identification is to determine the spatial structure of the crystal by infrared spectroscopy or X-ray diffraction of the crystal. However, this inspection method often needs to be compared. The amount of crystals is time consuming and expensive to operate, and it is not practical. In conventional laboratories, phase difference polarized light microscopy is usually used for diagnostic purposes. Under this special microscope, a large number of cells can be found in synovial cells. Weakly positive birefringent rod-shaped crystals with a diameter of 2 to 10 m. These crystals are often combined by two ends. Although calcium pyrophosphate crystals are stable in vitro, it is best to keep the freshness of the synovial fluid so as not to follow The prolongation of the microscopic examination time causes the dissolution of the crystal or some artificial illusion; for the pathological specimens to be examined, it is best to preserve and stain in a neutral environment to avoid decomposition of the crystal due to the decalcification reaction. What needs to be identified under the microscope is sodium urate crystals, because the crystals are easily precipitated when the temperature is lowered in vitro, and they are often swallowed by white blood cells. However, an acicular shape, optical properties showed a weak negative birefringence.
2. Other laboratory tests: The joints of patients with pseudo-gout must undergo routine Gram staining and bacterial culture to exclude the possibility of septic arthritis, and sometimes both cases can coexist at the same time. In addition, pseudogout often causes A stress change in the body's blood, in addition to elevated blood levels, may be accompanied by C-reactive protein, increased plasma viscosity and increased erythrocyte sedimentation rate, which involves multiple large joints or patients with other interstitial inflammation in pseudo-gout This is especially noticeable.
Patients with chronic pyrophosphate arthropathy may be associated with mild anemia, and plasma viscosity and elevated serum ferritin are not uncommon, but these biochemical or serological changes are often not significantly different from those of normal age.
1. X-ray performance: Calcium pyrophosphate deposition disease mainly manifests in X-ray film: calcification and joint disease.
(1) Calcification:
1 Cartilage Calcium deposits most often involve fibrocartilage (such as the knee joint meniscus, the triangular and pubic symphysis of the wrist), followed by hyaline cartilage (such as the knee, ankle and hip joint hyaline cartilage), X-ray findings A thick, linear, high-density shadow that is parallel to the subchondral bone but not connected to the latter, usually involving only one joint on one side, with the knee joint being the most common;
2 Calcification of the joint capsule is less common than cartilage calcium deposition, mainly involving the metacarpophalangeal joint and knee joint, but severe joint capsule calcification can sometimes stimulate the occurrence of osteochondroma, calcification of diffuse bursa is more rare, but sometimes Found in the subacromial sac, olecranon and sac sac, the calcification of the tendon occurs mostly in the Achilles tendon and triceps tendon, also as a typical linear high-density shadow, unlike the formation of hydroxyapatite deposits. Isolated coin-like high-density shadows, cartilage calcareous deposits and soft-tissue calcification are a dynamic process that can be aggravated as the disease progresses, but at a reduced thickness of the cartilage itself, during an intermittent episode of acute attack or when the lens is from the cartilage In the case of shedding, the X-ray findings of the lesion may be reduced. It is important to emphasize that the manifestation of calcification on the X-ray is not an essential prerequisite for the diagnosis of calcium pyrophosphate deposition.
(2) Arthropathy: The basic X-ray manifestation of pyrophosphate arthropathy is actually the basic manifestations of osteoarthritis, including cartilage loss, cartilage sclerosis, cyst and callus formation, but the following two points can be associated with simple osteoarthritis Phase identification:
1 The main joints and joints of pyrophosphate arthropathy are different from osteoarthritis. The lesions mainly involve the ankle joint, the metacarpophalangeal joint, the ankle joint, the elbow joint, the ankle joint (separation of the scaphoid bone), and the joint of the scaphoid. And the gap between the stocks;
2 pyrophosphate arthropathy will be typical on the X-ray, more osteophytes and subchondral cyst formation, common in the knee joint and wrist joint. When the patient's articular plain film shows the above typical performance, even if no signs of cartilage calcium deposition are found, it may be inclined to consider pyrophosphate arthropathy, but clinically, coexistence of pyrophosphate arthropathy and osteoarthritis is often encountered. It is necessary to make judgments based on their respective different parts and typical performances.
A group of pyrophosphate arthritis X-ray films for 5 years of monitoring showed that the prognosis is still optimistic, the most common situation is bone remodeling and osteophyte development, and progressive bone and cartilage destruction It is rare, the latter is more common in pseudoneuropathic arthritis, often accompanied by severe wear of bone and cartilage and disintegration of bone.
The wear of the bone edges, especially the smoother X-ray changes of the joints, although not characteristic of pyrophosphate arthropathy, is more common in actual cases, common in the front of the distal femur, the ulna Distal and ankle joints.
2. Arthroscopy
3. Polarized light microscopy
4. Pathological examination: Unlike sodium urate crystals, calcium pyrophosphate crystals are not deposited in all connective tissues, but are often limited to various structures of the motor system. A large number of pathological results show that crystals are usually deposited first. Cartilage, in a few cases, can also deposit in the joint capsule and tendon, and the crystal deposition of the synovial membrane, bursa or tendon sheath is secondary to the former.
Calcium pyrophosphate crystals are most often deposited in the middle zone of cartilage. Large specimens can be seen with small bead-like "stone" deposits in the middle. Microscopically, small sediment points can be seen with clear boundaries, mostly round, and often with hypertrophic cartilage. The cavities are adjacent, but with the development of crystal deposition, the surface of the cartilage is often involved. The cartilage around the crystal deposition often loses the metachromaticity, showing the fibrosis phenomenon, accompanied by the metaplasia and proliferation of chondrocytes, hypertrophy The chondrocytes often have accumulation of lipid droplets and proteoglycans. Partial or total destruction of the cartilage can be seen in severe cases. In the subchondral bone, thick trabecular bone and large cysts are formed, sometimes small cysts are broken. And fusion can lead to fractures.
In the synovium, calcium pyrophosphate crystals are usually deposited in the interstitial space and synovial cells on the surface of the synovial membrane. The surrounding points are often surrounded by fibroblasts and connective tissue. The acute phase is characterized by the proliferation of synovial cells. A large number of neutrophils and lymphocytes infiltrate, while the chronic phase is characterized by significant fibrosis, mononuclear infiltration and giant cell granuloma formed around the lens. Calcium pyrophosphate deposition of the joint capsule and tendon sheath The pathological changes are similar to those of the synovium.
In summary, in addition to medical history and physical examination, the search for calcium pyrophosphate crystals in synovial fluid is the most important means for diagnosing calcium pyrophosphate deposition. If a large number of diameters in cells are observed under phase contrast polarized light microscopy, it is about 2~ 10m weak positive birefringence rod crystal, combined with clinical symptoms and X-ray cartilage calcium deposition, joint capsule calcification or osteophyte formation can basically give the diagnosis of this disease, but must also carry out joint fluidX
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