Pediatric Caschin-Baker disease
Introduction
Introduction to Pediatric Kaschin-Beck Disease Kaschin-Bekdisease, Kaschin-Bekdisease, is a localized cartilage and joint deformity disease, which is a deformed osteoarthrosis with cartilage necrosis. Occurs in children and adolescents, mainly invading the bones and joints of children and adolescents, resulting in osteogenesis in the cartilage, shortening of the tubular bone and secondary deformed joint disease, resulting in tubular long bone development disorders, joint thickening, pain, Muscle relaxation, atrophy and movement disorders. The patient was characterized by short stature, short fingers, joint deformity, abnormal gait (typically limp, duck step). The disease is also known as "dwarf disease", "calculation of plate disease", "willow disease" and so on. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: dyskinesia
Cause
The cause of pediatric Caschin-Beck disease
Low selenium in the ecological environment of the ward (30%):
Originally, the former Soviet scholars proposed that the disease was caused by too much or insufficient of one or several elements. In the early days, it was thought that it was related to water, less calcium and more sputum in the soil, and more related to it. Later, it was claimed that the diseased area was water and soil. The main and non-staple foods contain phosphorus and excessive manganese and cause disease. These have not been able to find the exact basis from the patient or experimental research.
Chinese scientists have found that Kaschin-Beck disease is closely related to environmentally low selenium:
1 The distribution of the diseased area in China is generally consistent with the low-selenium soil zone. The total selenium content of most of the diseased areas is below 0.15mg/kg, and the grain selenium content is less than 0.02mg/kg;
2 The blood, urine and hair selenium content of the ward population is lower than that of the non-patient area, and a series of metabolic changes associated with low selenium can be detected in the patient;
3 When the level of selenium in the hair of the ward is rising, the condition is reduced;
4 selenium supplementation can reduce the new incidence of Kashin-Beck disease and promote the repair of metaphyseal lesions.
But there are also some important facts that do not support low selenium is the cause of this disease:
1 Some areas have low selenium and do not have Kaschin-Beck disease, such as Yulin in Shaanxi, Luonan, and some Keshan disease areas in Yunnan and Yunnan. In some areas, selenium is not very low, but this disease occurs, such as Qingzhou in Shandong. Zuoquan of Shanxi, Huo County, Ankang of Shaanxi, Ban Ma of Qinghai, etc.;
2 after selenium supplementation can not completely control the new development of the disease;
3 cell culture showed that chondrocyte growth has no special need for selenium;
4 Low selenium animal experiments can not cause cartilage necrosis similar to this disease.
At present, more people tend to think that low selenium is only a conditional factor in the onset of this disease.
Organic pollution in drinking water (25%):
In many wards in China, folks have long attributed the cause of this disease to poor water quality. Japanese scholar Yan Ze and others studied the relationship between plant organic matter in drinking water and Kashin-Beck disease, and considered ferulic acid or hydroxycinnamic acid in organic matter. May be a causative factor.
In our country from 1979 to 1982, the scientific investigation of Kaschin-Beck disease in Yongshou County and other areas, it was found that the total amount of humic acid and hydroxyhumic acid in water was positively correlated with the prevalence of Kashin-Beck disease, and the selenium content was negative. Correlation; the humic acid content in the ward is generally higher than that in the non-disease area. The isolation and identification of the organic matter in the drinking water of the ward shows that there is no significant difference between the humic acid structure and the core part of the non-disease area. Phenolphthalein, thiazolidine-containing compounds containing sulfur and nitrogen appeared more frequently in the drinking water of the ward, and were detected by electron spin resonance (ESR). It was found that there was a significant free radical signal in the drinking water of the ward, and its concentration was significantly high. In the control non-disease area; the concentration of free radicals in drinking water in the ward has a linear correlation with the content of humic acid. Some researchers believe that organic matter pollution in drinking water produces exogenous free radicals (half-free radicals) and increased free radicals. The human body can damage the chondrocytes.
So far, the relationship between organic matter pollution in drinking water and the incidence of Kashin-Beck disease has not been supported by sufficient epidemiological and experimental research data.
Mycotoxins (25%):
As early as 1943 to 1945, the former Soviet scholars proposed that the ward's grain was contaminated with some Fusarium bacteria and formed a heat-resistant toxic substance. The residents were sick of eating food containing this poison. After the 1960s, Chinese scholar Yang Jianbo et al. A lot of work has been done on this aspect, and in recent years, the following major advances have been made in the T-2 toxin:
1 ELISA method was used to detect the main food flour and T-2 toxin in corn flour, and the content was found to be significantly higher than that of non-disease commercial flour and corn flour; the granular foods such as rice, millet and yellow rice collected from all regions were collected. No or only trace amount of T-2 toxin detected;
2 Inoculate the non-disease corn with Fusarium graminearum to prepare the bacterial grain, and mix the normal feed with 10% proportion. The chicks were fed with the cartilage banded necrosis of the knee joint for 5 weeks; the T-2 toxin was detected from the bacterial grain. And HT-2 toxin (a metabolite of T-2 toxin), the pure T-2 toxin was directly applied, and the chicks were fed with the feed at 100 g/kg body weight for 5 weeks, and the degenerative changes of the knee joint cartilage appeared.
Other domestic units have also carried out some work on the relationship between mycotoxins and Kaschin-Beck disease. At present, the dominant fungi in cereals in different wards are different, and there is also a lack of consistent pathogenic fungi and their strains. The detection results of mycotoxins in food are also Inconsistent, in addition, due to technical limitations, T-2 toxins and their metabolites have not yet been detected from patients with Kashin-Beck disease.
Experimental animal model study (5%):
In order to explore the etiology and pathogenesis, many scholars at home and abroad have devoted themselves to the study of experimental animal models of this disease. Chinese researchers generally use cartilage damage as the basic morphological index for determining animal models, but in the past they used rats or dogs. In the experiments, most of the seesaw and articular cartilage were seen in the lack of qualitative changes in scattered chondrocyte necrosis, matrix degeneration, and small cell-free areas, which lacked qualitative differences compared with the control group. It is difficult to judge its value. In recent years, it has been more successful in experiments conducted on the food and water of the rhesus monkeys. After feeding the water or grain in the ward for 6 months or 18 months, most of the monkeys have articular cartilage and In the deep layer of the epiphyseal cartilage, there were focal changes, banded necrosis and a series of secondary changes after necrosis.
It basically reproduces the pathological development process and main pathological features of Kaschin-Beck disease. The experimental results suggest that there are pathogenic factors in the water and food in the ward; the pathogenic effect of such pathogenic factors on experimental animals does not follow the disease. The condition of the district is reduced and weakened.
So far, it has not been proven that there is a naturally occurring Kaschin-Beck disease in the animal kingdom. In the past, the joints of livestock or dogs in the ward have been swollen and cautious, which is far from the Kaschin-Beck disease of humans. It is mentioned in foreign countries that it can be compared with this disease. One:
1 Osteoochondrosis of livestock: This disease is similar to Kaschin-Beck disease in the development of articular cartilage and epiphyseal cartilage necrosis and development of secondary osteoarthrosis, but the most typical change is chondrocyte differentiation. Obstruction and local hypertrophy of chondrocyte accumulation, although Kaschin-Beck disease can be seen uneven thickness of the tarsal plate, but the existing materials have not proved that before the cartilage necrosis, the accumulation of hypertrophic chondrocytes as the basis,
2 bird's tibial dysplasia (tibial dyschondroplasia): its basic lesion is that the epiphyseal cartilage matrix can not be calcified, cartilage internalization bone stops, although sometimes considered equivalent to osteochondrosis of livestock, but because there is no cartilage necrosis, and Articular cartilage is not affected, so it has nothing in common with human KBD.
(two) pathogenesis
1. A large number of T-2 toxins (Fusarium oxysporum toxin) were detected directly from the ward, the patient and the locally marketed cereals (corn and wheat), and the pure T-2 toxin was used at 100 g/d. The dose is mixed with normal feed to feed the chicks, the cartilage necrosis of the chicks, and the cartilage joint disease occurs. The lesion characteristics are similar to those of the mammalian cartilage joint disease. The disease mainly occurs in the young animals, and the joint cartilage and the epiphyseal cartilage appear selectively. Necrosis, separation of osteochondritis, and subsequent cartilage joint deformation, it has been clarified that the mechanism of action of T-2 toxin on various tissues and organs of the body is to inhibit the synthesis of protein and DNA, leading to osteonecrosis of the bone. Experimental pathological studies prove that T-2 The toughness of articular cartilage caused by toxins is in the transition zone of rapid growth of cell growth and hypertrophy. The deep changes of the epiphyseal cartilage seen in human large bone lesions are essentially the same, the chondrocyte damage caused by T-2 toxin, Mainly damage of the cell membrane system, mitochondrial swelling, endoplasmic reticulum expansion, which is due to membrane permeability change, intracellular ion and water balance disorder, cell edema, mitochondria Injury will inevitably affect its energy supply function, thus causing cell metabolism disorders. Chondrocyte membrane structure damage is the main feature of early ultrastructural changes before chondrocyte necrosis. Further damage will lead to chondrocyte necrosis. The causative agent of the disease is the T-2 toxin produced by Fusarium contaminated by food in the ward. The carrier is wheat (flour) and corn in the ward, not rice. The related factors are the unique natural, social and ward. Living environment, etc.
Whether it is from macroscopic or microscopic chemical environment, the population of Kaschin-Beck disease is in a low-selenium ecological environment, that is, the selenium content of ecological substances in the ward, from water, soil, grain to human hair, blood content is significantly lower than In non-disease areas, supplementation with selenium can effectively correct the selenium nutrition level of children in the ward and promote the repair of dry sputum. Selenium and its compounds are an antioxidant. Selenium-containing glutathione peroxidase can catalyze lipids. Reductive decomposition of hydroperoxide and hydrogen peroxide to prevent damage to the cell membrane, maintain cell membrane integrity and stability, tissue selenium deficiency, reduced antioxidant capacity, in addition to causing oxidative damage of the cell membrane system, can also lead to protein , free radical damage of nucleic acids, etc., resulting in decreased tissue enzyme activity, collagen denaturation and decreased DNA. Children's plasma sulfhydryl (ie, total plasma sulfhydryl, non-protein sulfhydryl and protein-bound sulfhydryl groups) is associated with a lack of selenium, suggesting that children The antioxidant defense system in the body is damaged.
Studies have shown that selenium has an antagonistic effect on T-2 toxins (including other Fusarium toxins), which can reduce lipid peroxidation damage. Because selenium is a component of glutathione peroxidase, it can participate in many biological processes. Protects the body from a series of foreign compounds. The antioxidant effect of selenium is mainly reflected in the inhibition of peroxidation, the decomposition of peroxides to eliminate harmful free radicals, the repair of cell membrane molecules, etc., and the T-2 toxin mainly affects the liver. The ATP content of cells, and selenium has a protective effect on the reduction of ATP in the liver caused by T-2 toxin, which can protect the mitochondrial membrane, microsomal membrane and lysosomal membrane of liver cells from damage. These effects still need to be further studied to confirm that low selenium The relationship with Kashin-Beck disease is still controversial. It has been found that there are non-disease points in the low selenium area, and there are some disease points in the high selenium area. On the one hand, there is a significant dose between the early lesion level and the selenium level. The effect relationship, on the other hand, in selenium for three to three years in three different types (ie, moderately active, mildly active, and relatively stationary), with more than 1% of new cases of metaphyseal disease each year and 4 % of new cases of osteophytes, and found that the content of selenium is not directly related to X-ray metaphyseal lesions. From the effect of selenium prevention and treatment for many years, the selenium group is compared with the control group. Most of the net improvement rate is 10% to 30%, so it cannot be said that the disease is caused by selenium deficiency alone. This disease is also related to the lack of various elements such as manganese, phosphorus and zinc, which needs further research and confirmation.
Switching to deep water wells, drinking boiled water, the incidence of Kashin-Beck disease is significantly reduced, water can prevent the occurrence of Kaschin-Beck disease, so that the patient's condition is reduced or relatively stable, alanine aminotransferase in children after the change of water The activity of lactate dehydrogenase and alkaline phosphatase decreased, which was significant compared with that before water change. Therefore, it is considered that Kaschin-Beck disease is related to organic poisoning in water. It is also considered that the occurrence of Kashin-Beck disease is not related to drinking water. Further research is still needed.
2. Mechanism of cartilage damage Chinese researchers mainly have the following three kinds of insights:
One opinion is that the biochemical basis of cartilage damage in this disease is a disorder of sulfur metabolism. Chondroitin sulfate (Chs) is an important component of cartilage matrix. Researchers with this knowledge found that the excretion of Chs in the urine of patients with this disease increased. The degree of sulfation is reduced, the molecular weight is reduced, and the proportion of various aminopolysaccharides in the urine is dysregulated. They believe that these changes suggest a sulphur utilization disorder, and the sulfation of Chs in the body is affected by the sulfation factor (SF) produced by organs such as the liver and kidney. Regulated, they found that the serum SF activity of children with this disease was significantly lower than that of local healthy control children, who were lower than non-disease control children. They believed that sulfur metabolism disorder was the result of decreased SF activity, and the pathogenic factor of this disease was A series of cartilage damage is caused by interfering with the biological function of SF.
Another opinion is that the membrane defect state of cells is the biochemical basis for the pathogenesis of this disease. They found that the phospholipids of the erythrocyte membrane lipid composition decreased, the molecular ratio of cholesterol/phospholipid increased, and phospholipids in phospholipids. The acetylcholine (PC) is mainly decreased, the sphingomyelin (SM) changes are small, and the molecular ratio of SM/PC is increased. These changes mean the aging of the biofilm. The above situation is also seen in the cartilage of the autopsy material of the patient. In the analysis, they believe that the combination of low temperature, low selenium and monotonous food (insufficient intake of phospholipids) leads to weak membrane system and reduced antioxidant capacity.
There is also a view that exogenous free radicals can cause both chondrocyte necrosis and abnormal metabolism of chondrocytes. The latter will synthesize and secrete abnormal matrix rich in type I collagen, which occurs rapidly, with small particle size and crystallinity. Low abnormal mineralization, which led to the pathological chemical process of the disease, the mice were fed with ward and water, and the type I collagen in the cartilage matrix was increased, and the ratio of type I/II was increased.
The above aminopolysaccharide, collagen and cell membrane system changes provide useful clues for exploring the mechanism of cartilage damage, but there is still a large distance to explain how the disease selectively acts on specific parts of cartilage and initiates a series of characteristic changes. .
3. Pathology The disease is mainly invading the bone and joint system. Other tissues and systems, such as muscle tissue, endocrine gland, digestive system, and circulatory system can also be involved. The nature of the lesion is generally changed to malnourished degeneration, mainly invading cartilage. The hyaline cartilage part of the bone type (such as the limb bone) is internalized, the lesion is symmetrical, the joint is thickened, and the short limb deformity is usually negative. The joints with more activity are the most affected. The pathological changes of the cartilage tissue are mainly the following two. Kind:
(1) Basic pathological changes of cartilage: firstly invade the epiphyseal cartilage plate, secondly involving the articular cartilage, osteophyte curvature, uneven thickness, uneven arrangement of chondrocytes, ossification disorder and growth delay, pause, etc., capillary of bone marrow Invading the deep layer of the cartilage plate, often part of the cartilage band is cut off or divided into cartilage islands. This is a characteristic of this disease. Sometimes it can be calcified in the matrix of part of the cartilage band to form a transverse bone beam. These phenomena can cause bone growth to pause or Delayed, the cartilage matrix of the epiphyseal cartilage plate is also softened, where the chondrocytes can completely disappear and the nearby chondrocytes aggregate.
The disease mainly involves the bones of the cartilage osteogenesis, especially the limb bones, which are characterized by degeneration and necrosis of the hyaline cartilage and accompanying absorption, repair changes, common coagulative necrosis of chondrocytes, nucleus pyknosis, fragmentation, dissolution disappearance, Residual red-stained cell shadow (Fig. 5), and the residual image disappears, the matrix is red-stained, becomes a foci-like, band-like acellular zone, and the necrotic area can be further disintegrated, liquefied, and the chondrocytes viable around the necrotic foci often have Reactive hyperplasia, the formation of cartilage cell clusters of different sizes (Fig. 6), pathological calcification can occur in the necrotic site near the bone tissue; the blood vessels and connective tissue of the primary bone marrow invade the necrotic foci, appearing ossification, ossification, Finally, the cartilage necrosis of the bone tissue is mainly involved in the mature chondrocytes (hypertrophic chondrocytes), showing a near-bone distribution. When the necrosis is enlarged, it will also affect other levels of chondrocytes. The necrotic foci are often multiple and vary in size. , in the form of dots, flakes or strips.
(2) tarsal cartilage lesions: the necrosis of the epiphyseal cartilage mainly occurs in the mast cell layer, and the severe one can penetrate the whole layer of the tarsal plate. After the necrosis occurs in the deep layer of the tarsal plate, the blood vessels from the metaphysis can not be invaded. Normal The cartilage osteogenesis stops; however, the proliferating layer of chondrocytes that survive above the necrotic foci can continue to proliferate and differentiate, resulting in this local thickening of the epiphyseal plate. Degenerative calcification often occurs along the proximal edge of the necrotic foci. The metaphyseal end of the necrotic fossa deposits bone, forming an irregular bone piece or transverse beam, indicating that the normal ossification process is paused, while the other parts of the tarsal osteogenesis continue, resulting in uneven thickness of the tarsal plate. The ossification lines are jagged.
When the necrotic foci runs through the entire tarsal plate, the absorption of necrotic material in both directions of the nucleus and the metaphysis is mechanized and ossified, which finally leads to the early closure of the tarsal plate. The longitudinal growth of the tubular bone stops early, resulting in Short finger (toe) or short limb deformity.
The correspondence between the pathological changes of the epiphyseal cartilage and the X-ray changes is shown in Table 1.
Due to the rich blood vessels in the metaphysis, the absorption, mechanization and ossification of the epiphyseal cartilage after necrosis are more rapid, so the X-ray image can be significantly aggravated or improved in a short period of time (months to 1 year).
(3) Articular cartilage lesions: Articular cartilage begins with the same dystrophic lesions, cartilage destruction gradually occurs, the articular surface is rough and uneven, cartilage ulcer often occurs, affecting joint activity, inducing pain, and some cartilage can fall off to form "articular rat "In severe cases, the edge of the articular cartilage proliferates and has a discoidal bulge. After that, there is often a bone, so the joint becomes thicker, the synovial membrane also has a villous proliferation, the villi detachment can become a free body, and the synovium around the cartilage is also Usually hypertrophy, can constitute cartilage and tibia, and the bone end is more enlarged, the edge is irregular, in addition, the bone is often generally loose, trabecular bone destruction, absorption, can form vacuoles and cyst-like structures, and can be accompanied Proliferative changes, bones are significantly thinner, can be loose and spongy, bone marrow cavity dilatation, necrosis and vacuoles often appear in the marrow, muscles, organs and endocrine glands are accompanied by malnutrition degeneration The lesion.
Like the necrotic foci of the epiphyseal cartilage, the lesions of the articular cartilage are also near-bone, that is, the cartilage cells in the deep maturation are first involved, often forming a typical banded necrosis, due to the slow absorption of necrotic material, necrosis. It has a long time, so the proliferative chondrocyte mass in the peripheral part of the necrotic foci is often more noticeable. In the larger necrotic foci, when the necrotic material disintegrates and liquefies, it forms a fissure or cyst (Fig. 8), in gravity and friction. Under the action of mechanical action, the surface cartilage tissue is easy to peel off (separate osteochondritis), forming a joint free body (articular rat), while the local articular surface leaves ulcers of different sizes, and the severe articular cartilage can be The destruction of the whole layer disappears, causing a large piece of bone to be naked. At the edge of the articular surface, there is often a cartilage hyperplasia reaction with cartilage necrosis, which leads to thickening of the joint edge (Fig. 10), and can be ossified to form a bone edge. The organism, thereby causing the patient to increase the bone end, joint deformation and activity limitation, late joint synovial connective tissue hyperplasia, calcification and ossification, more serious joints, due to changes in articular cartilage The process of necrosis, disintegration and repair of hyperplasia was repeated, so that advanced cases showed changes in osteoarthritis, but bone joint stiffness was never seen. Monoclonal immunohistochemistry showed that type II of articular cartilage Collagen expression is reduced, type I collagen is increased; proliferating chondrocyte mass is expressed by type I, II, III, and VI collagen.
See Table 2 for the correspondence between articular cartilage pathology and X-ray changes in this disease.
The absorption mechanism of articular cartilage necrosis can only start from the normal gap of the bone plate shell, the repair reaction is relatively weak, and the lesion development is slow. Therefore, the lesion of the articular surface (bone end) under the X-ray is often better than the lesion of the metaphysis. The development was late, the repair process developed slowly, and it changed little over a long period of time.
Prevention
Pediatric Caschin-Beck disease prevention
Based on the current understanding of the etiology of this disease, comprehensive preventive measures are still advocated, including:
Improving water and grain quality In view of research, it shows that water in the ward and food are related to the disease, especially the serious pollution of Fusarium in food, changing water, changing grain or improving the quality of grain, is the main measure to prevent this disease in the group, Heilongjiang Province The 10-year prevention and treatment experience of the relevant areas shows that this Law is valid.
(1) Water improvement: The improvement of water quality can be started from two aspects:
1 Adding medicine to water, such as adding halogen base, sodium sulfate, sulfur, gypsum or grass ash extract;
2 Purify water quality, such as deep wells, spring water, drinking filtered water or boiling water, etc., in view of the low salinity of drinking water in the ward, and the heavy natural pollution, efforts should be made to improve water quality. The conditions can be based on local hydrogeology. Conditions to deep wells, or to introduce good quality spring water into the village, should strengthen the protection of drinking water sources, prevent pollution, poor water quality, high organic content can be built according to local conditions, water filtration facilities, centralized filtration, unified water supply.
(2) Changing the grain: changing the rations of the residents in the ward from the grain produced by the ward to the treasury grain or changing the dry land to the paddy field, and changing the staple corn to rice, the disease can be basically controlled. (Corn, wheat) Fusarium is seriously polluted, but the shell of rice makes the rice isolated from pollution and does not cause disease. However, large-scale control uses rice for food or change of staple food for rice. It is often restricted by objective conditions, and some children's canteens are established. To make children susceptible to children, children eat non-disease food or staple rice.
(3) Food protection: improve the harvesting conditions, improve the quality of cereals, reduce the entry of pathogenic substances into the human body, and reduce the incidence rate. Specific measures include improving agricultural operations, increasing mechanization levels, and reducing the pollution of grain contact with soil during grain harvesting. Opportunity, advocate cutting, transport, hit, cool four fast, strictly control the moisture of the grain into the warehouse below 15%, improve storage conditions.
Complication
Pediatric Caschin-Beck disease complications Complications
The joints of the extremities are thickened, deformed, dyskinesia, bone destruction and hyperplasia.
Symptom
Symptoms of pediatric Caschin-Beck disease Common symptoms Joint pain Muscle soreness and fatigue Muscle atrophy Limb shortening Malformation Difficulty violent pain Ants sensation Loss of appetite knuckles thickening
The disease has obvious locality, and the disease course is long after the onset, and the development is relatively slow, ranging from 2 to 3 years, many years, and decades.
1. Conscious symptoms Most patients have no obvious symptoms at the beginning of the disease. Often, the finger joints or elbow joints have been thickened or bent unconsciously. Some patients feel weak at the early stage of the disease, are prone to fatigue, have loss of appetite, have sore muscles, and have ants on their limbs. Rows, numbness and other abnormal feelings or convulsions, after the morning, the joints of the limbs are tight, pain and paresthesia, walking and squatting are difficult.
2. Physical examination can be divided into 3 or 3 degrees according to clinical findings:
(1) Mild or early: the finger joints are slightly thickened, the fingers are slightly curved toward the palm side, and the fingertips are drooping.
(2) Moderate or advanced: joint thickening, deformation, dyskinesia and muscle atrophy, first seen in the fingers, toes and tendons, wrists, metacarpophalangeal joints, followed by elbows, knee joints, a few patients in the joints free The body can lead to frictional bone or cause joint lock and severe pain.
(3) Severe or advanced: shoulder joints, hip joints and vertebrae joints may have hyperplastic deformation and dyskinesia, muscle atrophy of limbs, short fingers and short limbs, joint dislocation or subluxation, short stature, difficulty in squatting, generation Compensatory lumbar protrusion, gait swing like "duck step".
Examine
Pediatric Caschin-Beck disease check
1. General routine examination of blood is normal, there may be biochemical metabolic abnormalities:
(1) The patient's blood, urine, selenium in the hair, vitamin E and glutathione peroxidase activity are low.
(2) The activity of lactate dehydrogenase, alanine aminotransferase, creatine kinase, -hydroxybutyrate dehydrogenase and alkaline phosphatase in blood is increased.
(3) The total amount of erythrocyte membrane phospholipids decreased, lecithin decreased significantly, neurophospholipid increased, the ratio of cholesterol/phospholipid to neurophospholipid/lecithin increased, erythrocyte fragility increased, fluidity decreased, anti-oxidation and anti-hemolytic Reduced ability, increased red blood cell lipid peroxidation products, etc.
(4) urinary creatine, urinary hydroxyproline, urinary mucopolysaccharide and urinary total sulphur increased, creatinine decreased, these biochemical metabolic changes can occur before X-ray changes, epidemiological observation confirmed, population monitoring in epidemic areas The above indicators can be used for early diagnosis and can be used as a reference to reflect the degree of activity.
Liver and kidney function are mostly in the normal range, and immune function is generally low, such as E-rosette formation rate, T lymphocyte transformation rate and C3 are low, and adrenal cortical stress reserve function also declines.
2. Examination of bone and cartilage metabolism In addition to osteochondral damage and skeletal muscle atrophy, other organ organs have not been proven to have any regular changes, and there is still no reliable for cartilage and secondary bone changes. In addition, the simple and easy laboratory testing methods, in addition, the bone disease that has formed in this disease can last for life, some laboratory tests done by the researchers in the early years, which are inherent in the disease, Which are the results of secondary reactions or combined with other diseases, and are not easy to distinguish. In recent years, some tests have been carried out for the study of pathogenesis, and have significance for the observation group. The application to individuals is of little value. Here are some of the main Research result.
(1) The activity of plasma alkaline phosphatase (ALP) is increased, especially in children with Kashin-Beck disease with typical changes of X-ray. Compared with healthy controls in non-disease areas and healthy controls in non-disease areas, there is no significant liver, kidney, etc. In the case of organ damage, ALP is mainly derived from bone, reflecting the active function of osteoblasts.
(2) Hydroxylysine in urine increased significantly, and increased with the severity of the disease reflected by X-ray, but the hydroxyproline change of collagen degradation products was not regular, and some reported urinary hydroxyproline. There is an increasing trend in active critically ill areas, and some reports are the opposite.
(3) The excretion of chondroitin sulfate (Chs) in urine increased, reflecting the decomposition of cartilage matrix and the degree of sulfation of Chs. The electrophoretic mobility of Chs in urine was significantly changed by cellulose acetate membrane electrophoresis. Large, indicating that the molecular weight of Chs becomes smaller.
(4) The blood sulfation factor is low in activity (see above).
3. Examination related to muscle metabolism Because the skeletal muscle atrophy occurs earlier in this disease, some people have measured some components that reflect muscle metabolism. The results of early and recent years are similar. The basic changes are blood creatine and creatinine. Reduced, urinary creatine content increased significantly, urine creatinine was low or the change was not significant.
4. Red blood cell morphology and function changes Under the light microscope, the frequency of target red blood cells in the blood of children with this disease increases, and the deformed red blood cells (thorn cells and oral cells) increase under scanning electron microscopy, which all suggest the disease. The erythrocyte membrane has structural and functional abnormalities. We have already discussed the reduction of the total phospholipids in the erythrocyte membrane of the patient, and the proportion of various components in the phospholipids is abnormal, indicating that the lipid bilayer structure of the erythrocyte membrane has a certain change. In terms of function, it was found that the activity of Na, K-ATPase on the erythrocyte membrane decreased, and the actin of one of the erythrocyte skeleton proteins increased. The fluorescence polarization technique showed that the fluidity of the erythrocyte membrane was slightly decreased.
5. Serum zymogram was detected by biochemical automatic analyzer. It was found that the plasma aspartate aminotransferase (GOT), alanine aminotransferase (GPT), lactate dehydrogenase (LDH), and -hydroxybutyrate dehydrogenase ( -HBDH), creatine kinase (CK), -glutamyltransferase (-GT), etc. were higher than the control group, although these changes were mild, but statistically significant differences, and in multiple Repeated examinations in the ward can suggest that the disease removes bone and cartilage is involved, and there may be minor, reversible damage to other tissue cells.
6. The selenium, selenium, urinary selenium and erythrocyte selenium in patients with this disease are related to the low selenium in the body. The activity of glutathione peroxidase (GSH-Px) in selenium is decreased. Consistently, the content of lipid peroxide in blood is significantly higher than that in non-disease control population. It should be noted that these changes mainly reflect the difference between the ward and the non-ward population; the same population living in the ward No matter whether there is any regularity difference between the disease group, the disease reorganization, or the ward health group.
7. Immune function status The scientific investigation of the KBD disease in Yongshou County showed that there was no significant change in the patient's immunoglobulin IgG, IgA, IgM, but the report from Inner Mongolia reported that the IgM of the diseased children was significantly lower than that of the control group.
In the investigation of Yongshou County, 9 antibodies (including anti-chondrocyte antibody, anti-myocardial antibody, anti-mitochondrial antibody, anti-skeletal muscle antibody, etc.) in the patient's serum were negative, suggesting that the disease is not an autoimmune disease.
If the cartilage necrosis of this disease is limited to the original range of the epiphyseal plate or articular cartilage, the X-ray can not be displayed; only after the necrosis, there will be secondary repair changes, pathological calcification, ossification, or adjacent bone. When the structure causes damage or deformation, it shows various X-ray changes. X-ray images of bone changes secondary to cartilage necrosis have been shown in Table 1, 2, X-ray signs classification:
In the scientific investigation of Kaschin-Beck disease in Yongshou County, Chinese scholars summarized the X-ray signs of this disease into the following five categories:
1. The calcification zone is thinned, blurred, interrupted, and disappeared: the "calcification zone" here refers to both the temporary calcification zone of the deep layer of the tarsal cartilage, and the calcification zone of the hypertrophic chondrocytes around the ossification of the humerus. When cartilage necrosis involves these parts, the absorption of the original calcium salt disappears, and the calcification zone on the X-ray becomes thin, blurred, interrupted, and disappeared.
2. Depression, hardened metaphysis, sacral nucleus edge or bone end depression, suggesting that cartilage necrosis can not be osteogenesis, but the survival of cartilage around the necrotic foci can continue to be osteogenesis, metaphysis, bone end, ossified nucleus The hardening of the periphery suggests that there is an increase in pathological calcium salt deposition or more scar tissue, so the density is high on the X-ray.
3. Calcification zone re-emergence refers to the re-emergence of a calcification zone on the temporal side of the metaphyseal depression, suggesting that the calcified mast cell layer reappears in the cartilage tissue of the upper part of the epiphyseal necrosis.
4. Deformation of the iliac crest, the early closure of the iliac crest shows that a part of the cartilage around the ossification nucleus is necrotic, the osteogenesis of the cartilage is blocked, and the rest of the cartilage osteogenesis is carried out as usual, resulting in various abnormalities of the nucleus. The early closure of the sacral line indicates that the full-thickness necrosis occurs in the local or full-length of the tarsal plate, and then it is mechanized and ossified. The X-ray shows that the sacral line is pierced earlier than the normal cognac closure age.
5. Joint thickening, short finger (toe) deformity is the X-ray sign of the disease in the late stage, due to secondary osteoarthrosis can occur joint deformation.
X-ray diagnosis of the imaging features of the disease: X-ray diagnosis of the disease by hand, wrist-based, if necessary, plus the ankle joint and the foot of the positive position, the change of the humeral metaphysis occurred earlier, the change is faster, However, some minor changes can be seen not only in this disease, but also in healthy children or other bone diseases in non-disease areas. The distal end of the phalanx is a non-sacral nucleus. Due to anatomical and physiology, the X-ray visualization of the bone end damage of this disease is better. Late, the development is slow, but it is more meaningful in diagnosis, especially in the early stage of the disease. When the patient has no obvious clinical symptoms, the X-ray findings of the phalangeal lesions can be obtained first, usually the hand X-ray film is taken first, and the hand is dried. The change of the temporal end is used as the basis for early diagnosis of X-ray. If necessary, the lateral position of the ankle joint and the positive position of the foot can be added. The diagnostic criteria for X-ray of Kaschin-Beck disease in 1982 are as follows:
1 metacarpophalangeal:
A. Cognac:
a. The early calcification zone of the metaphysis has a small depression or calcification interruption, accompanied by local trabecular structure disorder;
b. The pre-calcification zone is hardened and widened, not complete; c. The various types of depressions with hardening at the metaphysis; d. The presence of a calcified zone in the temporal side of the depression (excluding the middle section of the little finger and the proximal section of the thumb),
B. Bone end:
a. The bony joint surface is fuzzy and thin, interrupted, rough and irregular, and changes in a sawtooth shape;
b. The bony joint surface is straight, concave, and hardened;
c. Defects at the edge of the bone or calcified ossification near the bone;
d. Bone end deformation, joint bone hyperplasia, trabecular bone structure disorder, cystic change,
C. Bones:
a. The face of the ankle joint is blurred, sunken, and calcified;
b. The nucleus is close to or partially close to the metaphysis;
c. line limitation premature fusion or local hardening;
d. The edge of the nucleus is blurred, the interruption is not complete or the depression is hardened;
e. The nucleus is abnormal in morphology, destroying the residue, disappearing or reproducing,
2 wrist bones:
A. The edge is limited, rough, hardened;
B. Limitations of defects or destruction;
C. deformation, crowding or cystic change;
D. Destruction, lack (not appearing or disappearing),
3 distance, calcaneus:
A. The edges are fuzzy, rough, and the bone structure is disordered;
B. articular surface defects and/or hardening;
C. collapse, harden;
D. The calcaneus shortens the deformation,
4, phalanges:
A. The toe bone changes like the phalanx;
B. The metaphysis of the toe base has a depression and hardening.
The above X-ray signs need to be closely integrated with the clinic. In non-disease areas, it is not possible to diagnose Kaschin-Beck disease only based on X-ray signs. If you live in a ward for more than 6 months, you can diagnose the disease according to the following principles:
1 The bone end has any X-ray signs;
2 other X-ray signs have two or more;
3 X-ray signs of a single site should be combined with clinical or additional X-ray films of other parts, positive for diagnosis, negative for observation;
4X line signs are not clear and have clinical manifestations, should be used as observation targets.
In addition, according to the extent of the lesion shown by X-ray, it can be staged, and the early stage is limited to the early calcification of the metaphysis, the trabecular structure is disordered, the epiphyseal surface and the carpal bone, and the distal phalanx articular surface is blurred and hardened or rough. The mid-stage nucleus was close to the metaphysis, and the cognac was prematurely converged. The late cognac was completely fused, the metacarpophalangeal bone was shortened, and the bone end was thickened and deformed.
Diagnosis
Diagnosis and diagnosis of pediatric Caschin-Beck disease
If the patient is from a prevalent area of the disease, it is obviously chronic, the symmetry joint is coarse and deformed, and the body is short and the diagnosis is not difficult. In the epidemic area, if the child has joint pain, activity is not working, or there is friction sound, it should first Think of this disease, can further X-ray examination of bones and joints, especially X-ray examination of the fingers, in order to determine the diagnosis early, laboratory examination has only auxiliary diagnostic effect on the disease.
Based on years of research and practical experience, China developed the diagnostic criteria for this disease in 1995.
1. Principle of diagnosis
According to the contact history of the ward, symptoms and signs, as well as the fingers of the hand bone X-ray film, the wrist joint surface, the temporary calcification zone of the metaphysis and the multiple symmetry depression of the nucleus, the changes of hardening, destruction and deformation can be diagnosed. In this disease, X-ray refers to multiple symmetry changes at the distal end of the bone as a characteristic indication for this disease.
2. Diagnostic and grading standards
(1) Severity diagnosis:
1 early:
Children who have not completely healed with dryness have the following four items: A., C. or B., C. or B., D. or only C., diagnosed as early.
A. Hand, wrist or ankle, knee joint activity is mildly limited, pain.
B. Multiple symmetry of the end of the finger flexion.
C. Hand, wrist X-ray film has a temporary calcification zone of the osteoarticular surface or metaphysis or a different degree of depression, hardening, destruction and deformation of the nucleus.
D. Increased serum enzyme activity, increased levels of creatinine, hydroxyproline, and mucopolysaccharide.
2I degree: On the basis of early changes, multiple symmetry fingers or other limbs are thickened, flexion and extension activities are limited, pain, mild muscle atrophy, and different degrees of X-ray changes at the metaphyseal or bone ends.
3II degree: On the basis of I degree, symptoms, signs are aggravated, short finger (toe) deformity occurs, and X-ray changes appear early and early closure of the sacral line.
4III degree: On the basis of II degree, symptoms, signs, X-ray changes aggravated, short limbs and short deformities appeared.
(2) Active and inactive diagnosis: Children with Kashin-Beck disease who have not fully healed, have any of the following diagnostic activities, otherwise they are inactive.
1 hand, wrist X-ray film showed a temporary calcification of the metaphysis, widening, hardening, deep depression.
2 serum enzyme activity increased, uric acid, hydroxyproline, mucopolysaccharide content increased.
Different from the rheumatism and rheumatoid diseases in children, the results of laboratory tests can help identify.
