Scleroderma

Introduction to scleroderma Scleroderma is a connective tissue disease characterized by localized or diffuse skin and visceral connective tissue fibrosis, sclerosis and atrophy. Its main features are fibers in the skin, synovium, skeletal muscle, blood vessels and esophagus. Or hardening, some internal organs, such as the lungs, heart, kidneys and large and small arteries can have similar lesions. Some patients have only skin sclerosis, called localized scleroderma; and some patients also have visceral fibrosis and cirrhosis of heart, lung, gastrointestinal and kidney. This condition is called systemic scleroderma, often the condition Severe, poor prognosis, the disease is second only to lupus erythematosus in connective tissue disease, the number of patients is more women, the ratio of female to male is about 3:1. The age of onset is more common in 20 to 50 years old. The incidence of women of childbearing age is the most common. Children and the elderly can also be affected. It is reported that miners and workers exposed to silicon have more patients with scleroderma. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: malignant hypertension

Cause of scleroderma

Genetic factors (25%):

According to some patients with a clear family history, the incidence of HLA-B8 is increased in critically ill patients and there are chromosomal abnormalities in the relatives of the patients. It is believed that the characteristics of the genetic type may be on the dominant allele of the X chromosome.

Infection factor (20%):

Many patients often have acute infections before onset, including angina, tonsillitis, pneumonia, scarlet fever, measles, sinusitis, etc. Paramyxovirus-like inclusions have been found in patients' striated muscles and kidneys.

Connective tissue metabolism abnormalities (10%):

The patient showed extensive connective tissue lesions, and the collagen content in the skin increased significantly. There were more soluble collagen and unstable intermolecular side chains in the virus active skin lesions, and the activity of collagen synthesis was significantly increased in the fibroblast culture of the patients. .

Vascular abnormalities (15%):

Patients with Raynaud's phenomenon, not only limited to the extremities, but also in the visceral blood vessels; histopathology shows that the skin lesions and internal organs may have small blood vessels (arterial) contracture and intimal hyperplasia, so some people think that this disease is a primary blood vessel Disease, but because vascular disease is not seen in all patients, it is also considered that vascular disease is not the only cause of the disease.

Immune abnormality (20%):

This is the most important view in recent years. A variety of autoantibodies (such as anti-nuclear antibodies, anti-DNA antibodies, anti-ssRNA antibodies, antibodies against scleroderma skin extracts, etc.) can be detected in patients; The number of cells increased, the humoral immunity was significantly enhanced, and the positive rate of circulating immune complexes in systemic patients was as high as 50% or more. Most patients had hypergammaglobulinemia; some cases were often associated with lupus erythematosus, dermatomyositis, rheumatoid arthritis, Sjogren's syndrome or Hashimoto's thyroiditis is complicated. At present, most people think that this disease may be an autoimmune disease caused by a persistent chronic infection based on a certain genetic background.

Pathogenesis

(1) Theory of vascular injury: Raynaud's phenomenon is often the early manifestation of SSc, which indicates that early lesions are obvious vascular damage, not only at the end of the finger (toe), but also in the internal organs. Recently, SSc is considered to be the vascular endothelium. As a result of repeated damage to the cells, endothelial cell damage causes capillary permeability changes, platelet wall damage leads to platelet aggregation and endothelial cell proliferation, endothelial cell damage is diverse, swelling, hyperplasia, followed by thrombosis, resulting in narrowing of the lumen, Tissue ischemia, these vascular lesions are found in skin, skeletal muscle, digestive tract, lung, heart, kidney and brain. Although there are significant vascular lesions in the early stage of the disease, immunoglobulin is rarely found in the blood vessel wall. And immune complexes, so it also shows that endothelial damage is the basis of this disease.

(2) Immunology: The disease and systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, rheumatoid arthritis and other autoimmune diseases often coexist at the same time or in succession. In addition, idiopathic thrombocytopenia often occurs during the course of the disease. Purpura, autoimmune anemia, etc., there are many autoantibodies in the serum, and there are often multi-cell strains of hypergammaglobulinemia, immune complexes, etc., suggesting autoimmune diseases, these autoantibodies include: Scl -70 is also known as anti-local isomerase I antibody, anti-centromere antibody, anti-nucleolytic antibody (including different nucleolar components), anti-PM/SSc antibody, etc., the mechanism of action of these autoantibodies is not very clear, However, the corresponding target antigens are important components of nuclear metabolism. Therefore, it is suggested that the disease is caused by molecular simulation. T lymphocytes are also abnormal in the circulation and tissues of SSc, and T cells are reduced in peripheral blood. The ratio of helper lymphocytes to inhibitory T cells is increased; lymphocytes in the dermis of the skin are mainly T helper lymphocytes, and locally isolated lymphocytes can be activated after stimulation. Cytokines into fibroblasts, in short, this disease have significant abnormal humoral and cellular immune abnormalities.

(3) Abnormal fiber hyperplasia: The extensive fibrosis of the skin and internal organs of this disease is due to the fact that the newly synthesized collagen replaces most or all of the subcutaneous tissue, thus tightening and hardening the skin, which is separated from the skin of the SSc patient. Some subtypes of fibroblasts can synthesize excess collagen (mainly type I and III), glycoprotein, etc. in culture, and experiments have also shown that local collagen decomposition is reduced. Current studies have shown that TGF-B (growth conversion factor) is not only Direct stimulation and secretion of PDGF- (platelet-derived growth factor) indirectly stimulates the growth of fibroblasts.

2. Pathology

The main pathological changes of SSc are connective tissue inflammatory cell infiltration, intimal hyperplasia, vascular occlusion, fibrous tissue hyperplasia and sclerosis, early skin lesions (inflammation phase), dermal interstitial edema, collagen fiber separation, small blood vessel surrounding lymphocytes Cell infiltration, vascular wall edema, elastic fiber rupture, after which, the infiltration of inflammatory cells around the blood vessels subsides, collagen swelling, acid mucopolysaccharide and collagen increase around small blood vessel fibers, to the late (hardening period), collagen fibers homogenization, and The collagen fibers in the epidermis increase, the collagen fibers proliferate, and expand deep, the small blood vessel wall thickens, the lumen becomes smaller, and even the occlusion, the late changes continue, leading to atrophy of the epidermis and appendages, calcium deposition, fascial muscles Hardening and atrophy.

Visceral lesions are basically consistent with skin lesions, showing multiple systemic sclerosis: smooth muscle (including esophageal muscle fiber bundles) showed uniform sclerosis and atrophy, intestinal wall muscle, myocardial also extensive atrophy and fibrosis; endocardial, pericardial fibers Degeneration of protein, inflammatory infiltration and collagen hyperplasia; pulmonary fibrosis and alveolar extensive fibrosis, and cystic changes; pulmonary arteriolar wall thickening, alveolar and microvascular basement membrane thickening; renal interlobular artery intimal hyperplasia, small renal The basement membrane of the ball is thickened, fibrin-like necrosis, glomerular sclerosis and renal cortical infarction are seen in severe cases; interstitial atrophy and fibrosis may also occur in the thyroid gland.

3. Chinese medicine etiology and pathogenesis

The cause of this disease is mainly congenital deficiency, spleen and kidney yang deficiency, or exogenous damp heat, wet weight in heat, wet evil and yang, or cold and cold inside, or outside is not solid, exogenous wind and cold evil, evil resistance Weiyang The evil hinders the veins, which leads to the disharmony of the camp and the qi and blood. The advancement involves the visceral disorder, the yang deficiency, and the pathological products such as phlegm condensation.

(1) Wind and cold obstruction: Insufficient congenital endowment, defensive gas is not solid, cold and cold attack, injured in the lungs, blocked in the veins, the camp is not harmonious, the veins are impassable, then there may be body pain, swollen limbs, hard skin, cough , coughing, etc.

(2) spleen and kidney yang deficiency, cold coagulation sputum: cold and cold attack, or lack of congenital endowment, spleen and kidney yang deficiency, or excessive labor injury, yang deficiency, cold from endogenous, cold is cited, cold is stagnation, blood It can't flow, and the blood flow is not smooth, so it can lead to blood stasis, collaterals blocked, then the end of the cold, the skin becomes cold and white, purple, hard skin, even muscle and skin dystrophy and muscle thin Thin skin, hair loss, pigmentation.

(3) turbidity and obstruction: cold evil hurts the lungs, lung health is damaged, lungs are not declared, and the fluid is difficult to lose, and it is concentrated as a sputum; or spleen and kidney yang deficiency, turbidity can not be turbid, if this This disease can occur when the turbidity is blocked in the skin and the skin of the tendons is dying.

(4) qi stagnation and blood stasis: anger and anger for a long time, emotional uncomfortable, can lead to qi stagnation and blood stasis, blood stasis and collaterals so that blood can not raise skin hair, so the skin is glory and hard and thin, skin changes Hard to open mouth is difficult, Qi Yu can not transport blood to reach the end of the fourth limbs, cold, body pain, and even ribs and rush.

(5) Damp heat block: the initial feeling of damp heat, wet weight in heat, wet evil damage yang, gradually appearing warm and insufficient skin tightening, so the joint changes from redness to white swelling, the beginning of another situation of the disease .

The disease begins at the beginning of the disease, but the evil stays for a long time to hinder the air machine, blood flow is not smooth, gradually lung, spleen, kidney involvement, began to damp heat, cold coagulation, choroidal stagnation mainly, into the positive damage and Yin, Yin and Yang can be strained, damaged and dirty, and more dangerous.

Scleroderma prevention

Disability analysis

(1) Lesions of scleroderma can occur in all organs and organs that are structurally and functionally related to connective tissue and have a vascular network. There is currently no specific method to prevent the development of lesions.

(2) If the hard surface area of the skin is large and widely distributed, the muscles under the skin lesions and even the skeletal muscles may have lesions, affecting the joint mobility, and the joints may collapse and deform.

2. Population prevention High-risk population refers to people who come into contact with coal mines, metal mines, silicon mines, chemical industry, etc., should strengthen the protection awareness of such personnel, do a good job in labor protection, and check the body regularly.

3. Personal prevention

(1) Primary prevention:

Most people now think that the disease is likely to be a genetic factor, coupled with a chronic infection caused by an autoimmune disease, some cases often with systemic lupus erythematosus, Hashimoto's thyroiditis, rheumatoid arthritis, Sjogren Syndrome and other factors overlap, so the above risk factors should pay more attention to prevention.

1 Remove infected lesions, pay attention to hygiene, strengthen physical exercise, and improve autoimmune function.

2 life rules, work and rest, comfortable, avoid strong mental stimulation.

3 strengthen nutrition, fasting and cold, pay attention to warming.

(2) Secondary prevention:

1 early diagnosis: diagnosis can be made according to typical skin hardening and systemic damage.

2 early treatment: glucocorticoids or their suspensions can be used for intradermal lesions, adhere to physical therapy and physical therapy, such as audio, wax therapy, etc., to improve limb contracture, increase limb function, or long-term oral vitamin E.

Scleroderma complications Complications, malignant hypertension

The following complications are prone to occur:

(1) Joint damage.

(B) damage to the gastrointestinal smooth muscle.

(3) Malnutrition.

(d) Myocardium forms fibrous tissue, which may result in permanent damage and/or functional deterioration.

(5) Kidney damage and/or renal dysfunction.

(6) The thyroid gland forms fibrous tissue.

Symptoms of scleroderma Common symptoms Skin is substantially non-... Abdominal pain Morning stiffness Skin muscle thickening, Fibrosis sweating Reduce proteinuria Joint pain Abdominal diarrhea Joint stiffness

The skin of the patient appears to be hardened, thickened, and atrophied. According to the degree of skin lesions and the location of the lesion, it can be divided into two types: localized and systemic. Localized scleroderma is mainly characterized by skin sclerosis; systemic scleroderma, also known as systemic sclerosis, can affect the skin, synovium and internal organs, especially the gastrointestinal tract, lungs, kidneys, heart, blood vessels, skeletal muscles. The system, etc., causes the function of the corresponding organ to be incomplete.

Skin performance

Early hand refers to swelling, but also involves the forearm, feet, lower limbs and face, but the lower limbs are less affected. The swelling period lasts for weeks, months, or even longer, and the edema is concave or non-concave. With erythema, skin lesions progress from the distal end of the limb to the proximal end, the skin gradually hardens, thickens, and finally adheres to the subcutaneous tissue (hardening period).

Skin lesions can be divided into edema, sclerosis and atrophy.

(1) edematous phase: manifested as thickening of the skin, tightening, wrinkles disappearing, non-depressed or swellable edema, pale or pale yellow, low skin temperature, reduced sweating, skin surface can be A small cleft palate occurs, and the fingertip fat pad disappears. In patients with localized skin lesions, early edema occurs on the fingers, back and face of the hand, and then spreads to the upper extremities, neck, shoulders, etc., diffuse type is often first caused by the trunk, then Expanding to the periphery, this period can last for several months.

(2) Intensive phase: skin thickens and hardens, fibrosis occurs, fingers and hands are shiny and tight, early skin can be red, the surface has waxy luster, no sweat, hair is scarce, skin is not easy to pinch When the facial skin is affected, the face may be stretched, the expression is fixed, the lips are thin, the radiation groove is formed around the mouth, the mouth is difficult to open, the nose is sharpened, the fingers are tapered, and the distal fingers become shorter and shorter, and ulcers may occur. Limited finger flexion and extension, tight chest tension, pigmentation and hypopigmentation in the affected area, hair thinning, skin changes can be limited to fingers, toes, hands, feet and face, can be extended to the front arm, but also from the chest and back At the beginning, it expands to the surrounding area, involving the upper arm, shoulders, abdomen and legs, usually reaching a peak in the extent and severity of endothelial damage in the 3 years of onset.

(3) atrophic phase (atrophic phase): skin atrophy and thinning like parchment, sometimes subcutaneous tissue and muscle can also shrink and harden, skin lines disappear, hair loss, smooth and thin skin, close to the bones, fingertips And the joints are prone to refractory ulcers, telangiectasia, and subcutaneous tissue calcification.

The above are typical skin lesions and processes of scleroderma. Except for Sine scleroderma without skin manifestations, other types can appear. There is no obvious boundary between these three phases, but a progressive skin lesion process.

Measuring methods for skin involvement:

Regular testing of the extent and extent of affected skin will help determine the stage of the disease and determine the progression of the skin lesion. The improved Rodnan skin thickness integration method is a simplified semi-quantitative skin scoring method. Pinch the following 17 parts of the skin: face, chest, abdomen, left, right upper arm, left and right forearms, left and right hands, left and right fingers, left and right thighs, left and right calves, left and right feet, right Each site was scored according to the scoring criteria: normal skin thickness was 0; skin was slightly thickened to 1 point; skin was thickened to 2 points; skin was extremely thickened to 3 points, and then the scores of these 17 sites were Accumulation, this method is more accurate and reliable, can be used for clinical estimation of the disease and observational research.

2. Renault phenomenon

(1) vascular lesions of scleroderma: almost all patients with scleroderma have Raynaud's phenomenon, suggesting that vascular disease is the basis of the onset of scleroderma. When the patient is cold or emotional, there will be skin and finger (toe) skin capillary The closure of the anterior vascular artery and arteriovenous shunt causes the skin to be pale, and then the hair changes, after the end of the stimulation (warming), the vasospasm is relieved, the skin turns into flushing, accompanied by numbness, burning, tingling, usually takes 10 to 15 minutes. The finger (toe) changes to a normal color or is plaque.

(2) Primary Raynauds phenomenon: The Raynaud phenomenon is divided into two categories: the primary (idiotypic) Raynaud phenomenon, also known as Raynauds disease and the secondary Raynauds phenomenon. The cause of the former is unknown, while the latter is secondary to vascular spasms of certain diseases or known causes.

A survey of the general population showed that 4% to 15% of people had Raynaud's phenomenon, most of them had no vascular structural changes or tissue ischemic damage (primary Raynaud's phenomenon), and 50% of patients with Raynaud's phenomenon were Primary, typical primary Raynaud's phenomenon begins in adolescents, more common in 20 to 40 years old, more women than men, patients with primary Raynaud's phenomenon are basically normal in other aspects, symptoms appear in the fingers (toes), symmetric distribution .

For doctors, the important question is to determine whether the Raynaud's phenomenon is the first symptom of primary or scleroderma. If there is a phenomenon of Raynaud, it does not have depressions, ulcers, gangrene, normal folds of capillaries and erythrocyte sedimentation rate, antinuclear antibodies. Negative, it is rarely possible to have scleroderma, such as enlargement and/or reduction and disappearance of nail folds, suggesting that the patient has connective tissue disease such as scleroderma.

(3) Raynaud's phenomenon and scleroderma: 90% of patients with scleroderma have obvious Raynaud's phenomenon. The appearance of Raynaud's phenomenon is the abnormal structure of vasospasm and finger artery. Compared with normal people, patients with scleroderma have malnutrition, and In the low temperature environment, the temperature is adjusted to the excessive reaction of the blood flow to the skin, and when the environment is warmed up, the vasoconstriction is relieved, and the reaction to restore the local blood flow is also delayed.

3. Muscle, joint and bone lesions

(1) Muscle lesions: patients with scleroderma often show obvious muscle pain and muscle weakness. This may be the first non-specific symptom of scleroderma. In the late stage, muscle atrophy may also occur. On the one hand, it is limited by skin thickening and hardening. The motor function of the joint causes muscle atrophy, and diffuse scleroderma can occur in any joint, but the fingers, wrists, and elbow joints are more common, and on the other hand, fibrosis spreads from the tendon to the muscles. Related, there are secondary drug treatments, such as the use of corticosteroids and penicillamine, when the scleroderma overlaps with polymyositis or dermatomyositis patients can have significant proximal muscle weakness, serum creatine phosphokinase ( CPK) continued to increase, EMG showed increased multiphase potential, decreased amplitude and time limit, no insertional stress and fibrillation, inflammatory changes in muscle tissue biopsy, inflammatory cell infiltration, muscle fibrosis, atrophy or fibrosis.

(2) Arthritis: Arthritis occurs in the joints of the fingers, wrists, knees, ankles, etc. Joint pain can also be a non-specific symptom of early occurrence of scleroderma. Patients often have more obvious joint pain and morning stiffness, pain. From the joints along the tendon, the upper arm and calf muscles, wrists, ankles, elbows, and knee joints are aggravated with pain, and rough rubbing sounds can occur, which is caused by fibrosis and inflammation of the tendon sheath and adjacent tissues. A kind of friction sound is more common in diffuse scleroderma, suggesting a poor prognosis, and about 29% of patients may have erosive joint disease.

(3) bone lesions: X-ray examination can be found in osteoporosis, osteosclerosis, bone destruction, bone atrophy, limbs, finger bone absorption caused by shortening of the phalanx, soft tissue calcification, joint space narrowing, bone erosion and Joint stiffness is less common.

4. Digestive system lesions

80% to 90% of patients with scleroderma may have digestive system involvement, or the first symptom of scleroderma.

(1) Oropharynx: restricted opening, dry mucosa, hardening, tongue nipple disappeared, tongue muscle atrophy, tongue can not extend out of the mouth, periodontal disease causes difficulty in chewing, tooth loss and malnutrition, general upper pharyngeal function Unaffected, unless the pharyngeal muscles are involved, there is myositis or neuromuscular disease. At this time, the food will enter the esophagus and it will be difficult to swallow. When the patient swallows liquid food, he will cough, nasal reflux, head, Shoulder flexion can suggest primary myopathy or neurological disorders.

(2) Esophagus: 80% to 90% of patients have abnormal esophageal function, common symptoms are dysphagia, food reflux and malnutrition, dysphagia often manifests as the patient feels a sticky feeling in a certain part of the esophagus after swallowing solid food. After drinking water can be relieved, the patient's esophageal peristalsis can be weakened, and there may be a feeling of fullness and acute food ingestion.

As the primary and secondary peristalsis of the patient's distal esophagus is weakened or disappeared, the lower esophageal sphincter pressure drops, reflux esophagitis occurs, the patient may have burning pain after the sternum, nausea, reflux symptoms after eating or lying down Aggravation, esophageal reflux and esophagitis can occur in both localized and diffuse cutaneous scleroderma.

Delayed emptying due to solid food retention in the stomach exacerbates esophageal reflux and leads to fullness, nausea, vomiting, and in order to avoid these symptoms, patients often reduce their intake, resulting in weight loss and malnutrition.

Complications of esophageal disorders include: aspiration pneumonia caused by food inhalation into the lungs, cough of unknown origin, hoarseness, atypical chest pain, and local candida infection.

Esophagitis occurs only when the patient has weakened esophageal peristalsis and delayed gastric acid emptying. At this time, barium meal examination, endoscopy, and esophageal manometry are performed to help determine the nature and extent of the lesion. Barium meal examination can be seen to reduce esophageal peristalsis or Disappeared, esophageal dilatation, 1/3 of the stenosis, endoscopy showed that the mucosa has varying degrees of erosion and thinning, histopathological examination showed that the esophageal smooth muscle atrophy, replaced by fibrous tissue, submucosa and mucosal lamina propria fibrosis, esophageal test A pressure check can show a decrease in esophageal contractility.

Patients with esophageal lesions are often accompanied by significant Raynaud's phenomenon.

(3) stomach: less affected, but patients are prone to fullness, vasodilation of the antrum can be one of the causes of gastrointestinal bleeding in patients with scleroderma.

(4) Small intestine: due to intestinal wall fibrosis and smooth muscle atrophy, resulting in abnormal bowel movements, usually manifested as recurrent mild abdominal pain, diarrhea, weight loss and malnutrition, malnutrition and diarrhea due to intestinal retention, excessive bacteria Caused by the absorption disorder caused by reproduction, in patients with severe chronic pseudo-obstruction, abdominal pain, bloating and vomiting.

In patients with progressive bowel disease, occasionally cystic gas accumulation in the intestine, at this time the gas in the intestine can swell into the intestinal wall, and even expand into the abdominal cavity, which behaves like a broken bowel.

(5) colon: all segments of the colon can be affected, scleroderma patients with decreased colonic tension, less diarrhea, common constipation, lower abdominal distension and congestion, due to scleroderma patients with intestinal wall muscle atrophy, its unique asymptomatic Wide-mouth diverticulum often occurs in the transverse colon and descending colon. If the anal sphincter is involved, rectal prolapse and fecal incontinence may occur.

(6) Liver: Liver lesions are not common, but the presence of primary biliary cirrhosis is often associated with CREST syndrome.

In summary, the main causes of digestive system lesions in scleroderma are changes in innervation, atrophy of smooth muscle and fibrosis of the submucosa. The earliest damage to the intestinal tract of scleroderma is a defect of innervation, which is similar to secondary Neuronal ischemic damage in microvascular disease, early gastrointestinal smooth muscle atrophy and fibrosis of the submucosa and myometrium become the main pathological changes. This neurological defect and fibrosis together lead to irreversible dysfunction of the digestive tract.

5. Lung lesions

Pulmonary involvement in patients with scleroderma is very common, often accompanied by cardiac involvement, is the main cause of death of patients, the earliest symptoms are shortness of breath after activity; late manifestations of innocent dry cough, chest pain is usually not caused by scleroderma But it is related to musculoskeletal pain, reflux esophagitis, pleurisy or pericarditis. Patients with scleroderma have pulmonary interstitial fibrosis and pulmonary vascular disease, but a pathological change, pulmonary interstitial fibrosis In patients with diffuse scleroderma positive for anti-Sc1-70 antibody, the performance is more obvious, and pulmonary vascular disease and pulmonary hypertension are the main lung manifestations of patients with CREST syndrome. Patients with scleroderma may also appear in the course of disease. Aspiration pneumonia caused by esophageal lesions, respiratory failure caused by respiratory muscle weakness, pulmonary hemorrhage, pleural reaction, pneumothorax, right heart failure caused by pulmonary hypertension.

Using specific and sensitive methods to detect about 80% of patients with pulmonary dysfunction, most lung lesions have no obvious clinical symptoms, until pulmonary fibrosis is aggravated, symptoms appear when pulmonary hypertension occurs, at this time lung function test shows Restrictive ventilation disorders, which may have a reduction in lung volume [eg, reduced vital capacity (FVC)] or a decrease in carbon monoxide diffusion, which may reflect impaired gas exchange function, caused by pulmonary interstitial fibrosis or pulmonary vascular disease, if A decrease of less than 40% of the predetermined value, or a rapid decrease in the amount of carbon monoxide diffusion and/or a rapid decrease in lung capacity suggest a poor prognosis.

Pulmonary interstitial fibrosis caused by neutrophilic alveolitis can be detected by CT and/or bronchoalveolar lavage. X-ray examination is relatively insensitive, but if abnormal, it can be shown: bilateral pulmonary interstitial The texture is enhanced, and there is a reticular-nodular change in the lower parenchyma of the lung. When there is active alveolitis, high-resolution CT examination may have a "hairy glass"-like change. Bronchoalveolar lavage fluid examination shows an increase in cells, and the patient can express Pulmonary hypertension is a difficult problem in the control of scleroderma for obvious dyspnea and carbon monoxide diffusion. Pulmonary hypertension is the most difficult problem in scleroderma control. It is often difficult to find clinically before the occurrence of severe irreversible pulmonary hypertension, using two-dimensional echocardiography. Non-invasive testing helps early detection of the presence of pulmonary hypertension.

6. Heart disease

It can be manifested as myocarditis, pericarditis or endocarditis. The obvious clinical signs of various heart diseases indicate poor prognosis.

The main symptoms of scleroderma heart involvement include shortness of breath after activity, palpitations, chest discomfort and pericarditis, congestive heart failure, pulmonary hypertension and arrhythmia, clinical manifestations, cardiac manifestations and anti-Scl-70 antibodies or antibodies The presence of RNA polymerase antibodies is associated.

Patients with scleroderma can cause pulmonary heart disease due to lung damage, causing right heart failure, and simple pulmonary hypertension without pulmonary fibrosis is rare, almost only in CREST syndrome.

Cardiac conditions can be estimated by various examination methods, but it is necessary to note that many heart symptoms are caused by lung lesions of scleroderma. Therefore, attention should be paid to the presence of ventricular diastolic function and pulmonary hypertension. Pulmonary damage, palpitations, chest pain or syncope of dermatosis can be caused by arrhythmia or pericardial disease. Echocardiography or ECG monitoring is helpful for diagnosis. Patients with angina pectoris can perform angiographic examination to determine whether there is coronary arteriosclerosis or ECG. Can show abnormal cardiac conduction and arrhythmia, if combined with 24h ECG monitoring is more valuable, the most common arrhythmia is ventricular premature contraction (pre-contraction), pre-atrial contraction (pre-contraction), room Upper tachycardia, abnormal atrioventricular or indoor conduction is rare, diffuse scleroderma may have a decrease in left ventricular ejection fraction, and radiofrequency radionuclide scan after patient exercise, 40% to 50% of patients There may be abnormalities, 15% of patients also have abnormal performance at rest, echocardiography found abnormal left and right ventricular function, especially left ventricular diastolic function Often more common, short-term shortness of breath after exercise may be an early manifestation of diastolic dysfunction.

Autopsy found that 30% to 70% of patients with scleroderma had fibrin or fibronectin pericarditis, and 30% to 40% of patients had small or large pericardial effusion.

7. Kidney disease

Kidney involvement can occur in 75% of patients, with clinical manifestations of hypertension, proteinuria, and azotemia. The most severe renal impairment in patients with scleroderma is rapid hypertension and/or rapid progression of renal function. Failure, the scleroderma renal crisis (SRC).

(1) Hypertension: 25% of patients with scleroderma have hypertension, which is one of the manifestations of kidney involvement. Hypertension is often caused by elevated diastolic blood pressure. The appearance of hypertension often indicates poor prognosis.

(2) proteinuria: patients often have intermittent proteinuria and / or microscopic hematuria, a small number of patients with a large number of proteinuria or nephrotic syndrome, sometimes proteinuria and hypertension and azotemia can be combined, this type The patient has a poor prognosis.

(3) azotemia: more than one-fourth of patients may have elevated blood urea nitrogen, creatinine clearance decreased, acute renal failure, blood urea nitrogen increased more significantly than serum creatinine, suggesting renal blood Insufficient flow, such as accompanied by malignant hypertension, patients may present with oliguric renal failure, renal failure in patients with scleroderma is not completely irreversible, after dialysis and appropriate medication, some patients with renal function can be restored, leading to kidney The common cause of functional failure is heart failure, infection, dehydration, surgery and other stress conditions, and patients with renal failure have a poor prognosis.

(4) scleroderma kidney crisis: 10% of patients with scleroderma may have kidney crisis, 80% of which are in the first 4 years of the disease, usually in the winter, patients with kidney crisis can Sudden typical malignant hypertension, manifested as headache, vision loss, convulsions, seizures, confusion, and even coma, and other nervous system changes, as well as congestive heart failure and rapid progressive renal failure, patients often increase diastolic blood pressure Mainly, hypertensive encephalopathy can occur, accompanied by optic disc edema, fundus hemorrhage and exudation, increased plasma renin activity, and patients with microangiopathic hemolytic anemia and thrombocytopenia. This condition is more common in normal blood pressure. Like patients, kidney crises often rapidly evolve into oliguric renal failure within a few weeks, reportedly occurring in 10% to 40%, most of which range from malignant hypertension to less than 3 deaths. At the time of the month, patients with localized scleroderma with anti-central antibody were more likely to have no kidney crisis.

Risk factors for renal crisis in patients with scleroderma include: diffuse skin lesions, new unexplained anemia, anti-RNA polymerase III antibodies, high-dose glucocorticoid use, and low-dose cyclosporine A The application can promote the emergence of renal crisis, rather than malignant hypertension, abnormal urine test, increased plasma renin levels, anti-centromere antibodies and anti-topoisomerase antibody positive are not predictors of scleroderma kidney crisis.

8. Other clinical manifestations

(1) Depression: 50% of patients with scleroderma have depression, and the degree of performance is related to the patient's personality characteristics and care and care, but not related to the condition.

(2) Sexual dysfunction: more common in patients with scleroderma, especially in male patients usually secondary to neurovascular disease.

(3) Dry eyes, dry mouth: This is a common manifestation of patients with scleroderma. Small salivary gland biopsy shows fibrotic changes without lymphocyte infiltration peculiar to Sjogren's syndrome, in the vast majority of patients No anti-SSA (Ro) antibody and anti-SSB (La) antibody were detected, indicating that the mucosal dryness of patients with scleroderma is different from that of Sjogren's syndrome.

(4) neurological diseases: scleroderma without central nervous system involvement, but may involve peripheral nerves, such as trigeminal neuropathy, carpal tunnel syndrome, etc., neurological abnormalities are often secondary to microvascular disease, such as the phenomenon of Raynaud Adrenergic neuroreactivity is related, and gastrointestinal manifestations are also associated with impaired cholinergic nerve function, indicating that patients with scleroderma have autonomic dysfunction.

(5) hypothyroidism: 25% of patients have hypothyroidism, which is related to thyroid fibrosis or autoimmune thyroiditis, the patient's serum may have anti-thyroid antibodies, the pathological manifestations of lymphocytic infiltration.

(6) Pregnancy: Patients with scleroderma often have abnormal menstruation, so the pregnancy rate is lower than normal, spontaneous abortion occurs, and the ratio of premature and low birth weight is higher than normal, but this does not mean scleroderma patients. Can not be pregnant during the course of the disease, usually pregnancy does not aggravate the condition of systemic sclerosis, but pregnancy can aggravate reflux esophagitis and heart symptoms.

9. Scleroderma and malignant tumors

The incidence of malignant tumors in patients with scleroderma is 2.1 times that of the same age group. The incidence of cancer in elderly patients and anti-topoisomerase antibody-positive patients is increased. Patients can develop lung cancer on the basis of pulmonary fibrosis. Reports of concurrent breast cancer.

10. CREST syndrome

This is a special symptom subtype of systemic sclerosis, mainly characterized by subcutaneous calcareous deposition, Raynaud's phenomenon, abnormal esophageal peristalsis, finger (toe) sclerosis and skin telangiectasia, subcutaneous calcareous deposits can be seen in 40% of patients The more characteristic deposition sites are the hands, especially the fingers, as well as the bony prominences, such as the olecranon area of the elbow, and the tissues surrounding the joint, such as the tendon sheath and the bursa, etc., virtually any part can appear, deposition The calcium forms an irregular shape, a non- tender lumps ranging in diameter from a few millimeters to a few centimeters. The overlying skin can be normal, can be inflamed or form an ulcer, and the skin from the rupture is like a white sputum, ruptured. The skin is prone to infection. Patients with this syndrome have obvious Raynaud's phenomenon, the incidence rate is 100%, the patient's esophageal peristalsis is weakened, and the same clinical symptoms as systemic sclerosis esophageal involvement may occur. Finger (toe) hardening, from the distal end Beginning to gradually expand to the proximal end, local skin thickening, formation of sausage-like changes, sometimes accompanied by finger (toe) distal bone absorption, skin telangiectasia can appear in the hand, nails, face The neck, chest, and back, the intrinsic progress is slow, the visceral involvement is mild, and the prognosis is good, but such patients may have pulmonary interstitial lesions and pulmonary hypertension, and may also be complicated by primary biliary cirrhosis.

Scleroderma examination

1. General inspection

Some patients may have anemia, hemoglobin is reduced, the most common cause of anemia is hyperplasia of hypoplasia associated with chronic inflammation, or iron deficiency, folic acid or vitamin B12 malabsorption due to gastrointestinal involvement and secondary iron deficiency anemia or giant Immature erythrocyte anemia, microangiopathic hemolytic anemia is often associated with kidney involvement, caused by fibrin present in the renal arterioles, patients may have blood eosinophilia, elevated platelets, kidney involvement There were proteinuria, hematuria, leukocyteuria and various casts, serum creatinine, elevated urea nitrogen, decreased creatinine clearance, 17-hydroxyl urinary, and 17-ketocortisol.

Patients may have increased ESR, but C-reactive protein is generally normal, serum albumin is reduced, globulin is increased, and there may be polyclonal gamma globulinemia, IgG, IgA, IgM elevation, cryoglobulin elevation, blood The content of fibrinogen in the middle increased, and the measured time value of the skin affected or unaffected by the patient was significantly longer than normal, which was 5 to 12 times higher than normal.

2. Immunological examination

Human laryngeal cancer cells (Hep-2) are used as substrates to detect antinuclear antibodies, which are positive in about 95% of patients. The fluorescent karyotypes can be spotted, nucleolar and anticentromere. Speckle and nucleolar types are more meaningful for the diagnosis of scleroderma, especially diffuse scleroderma. Anti-nucleolar antibodies are relatively specific for the diagnosis of scleroderma, which can be seen in 20% to 30% of patients. The anti-nucleolytic antibody related to scleroderma is an anti-RNA polymerase I, II, III antibody, which can be seen in 5% to 40% of diffuse scleroderma. The incidence of heart and kidney involvement is high, and anti-central antibody Can be seen in 50% to 90% of CREST syndrome, 60% to 80% of localized scleroderma and 10% of patients with diffuse scleroderma, occasionally patients with Raynaud's phenomenon, rarely seen in other connective tissue diseases, The anti-centromere antibody is considered to be a labeled antibody to CREST syndrome, and the antibody-positive patient is prone to skin telangiectasia and subcutaneous calcareous deposition, which has fewer lung diseases than the antibody-negative person, and its titer does not change with time. And the course of the disease, the early diagnosis of CREST syndrome and the classification of scleroderma have help.

The highly specific anti-nuclear antibody for scleroderma diagnosis is an anti-topoisomerase I antibody, originally called Scl-70 antibody (70kD), which recognizes ribozyme DNA topoisomerase I, which occurs in 20% to 40%. Diffuse scleroderma, a marker antibody called scleroderma, is associated with diffuse skin involvement, interstitial lung disease, and involvement of other internal organs. It is rarely seen in other diseases, nor is it resistant to silk. Antibodies appear at the same time.

Anti-Th RNP (ribonucleoprotein) antibodies can occur in 14% of localized scleroderma, anti-PM-Sel antibodies, formerly known as anti-PM-1 antibodies, can be seen in 25% of localized scleroderma and polymyositis overlap In patients with characteristics, anti-U3 RNP, anti-fibrillarin antibody, is also very specific for the diagnosis of scleroderma, and is related to skeletal muscle, intestinal involvement and pulmonary hypertension. Anti-U1 RNP can be seen at 5% to 10%. Scleroderma patients and 95% to 100% of patients with mixed connective tissue disease characterized by scleroderma, anti-SSA and/or anti-SSB antibodies present in patients with scleroderma and Sjogren's syndrome overlap Sm antibody and anti-dsDNA antibody are negative, anti-cardiolipin antibody IgG type negative or IgM type low titer positive, 30% can be rheumatoid factor positive, but the titer is lower, 7% can appear lupus cells.

50% of patients may have increased circulating immune complexes, decreased complement C3, C4, and immunoregulatory T cell detection: increased number of helper T cells (Th, CD4), decreased number of T cells (Ts, CD8), and lymphatic test in vitro Cell conversion rate decreases.

3. Skin capillary angioscopy and hemorheology examination

In patients with systemic sclerosis, the folds of the capillaries show that most of the capillaries are blurred, the number of vasospasm is significantly reduced, and the abnormal vasospasm is increased, accompanied by edema and exudation, the vascular branch is obviously dilated and curved, and the blood flow is slow, and some With bleeding points, it has been reported that the change of nailfold microcirculation in systemic sclerosis is consistent with the severity of involvement of internal organs, so it can indirectly reflect the involvement of internal organs.

Patients with systemic sclerosis have abnormal blood rheology, which is characterized by whole blood specific viscosity, plasma specific viscosity and whole blood reduction viscosity, and red blood cell electrophoresis time prolonged.

Blood flow examination showed that the blood flow velocity at the extremities slowed down, the blood flow decreased, and the blood vessel elasticity was poor.

4. Histopathological examination

Fibrosis and microvascular occlusion are characteristic pathological changes in all affected tissues and organs in patients with systemic sclerosis.

(1) Skin pathological examination: early, dermal interstitial edema, swelling of collagen fiber bundle, lymphocytic infiltration around small blood vessels between collagen fibers and dermis, mainly T cells, late stage, collagen fibers in dermis and subcutaneous tissue, dermis Significant thickening, collagen swelling, fibrosis, destruction of elastic fibers, thickening of the vessel wall, narrowing of the lumen, and even occlusion. Later, the epidermis, skin appendages and sebaceous glands atrophy, sweat glands are reduced, and the deep and subcutaneous tissue of the dermis is calcium.

(2) Renal pathological examination: Under the light microscope, the characteristic small arcuate artery and interlobular artery can be seen, which is characterized by intimal thickening with endothelial cell hyperplasia, which is "onion skin"-like change. In severe cases, it can partially or completely block blood vessels. Cavity, glomeruli often show ischemic changes, capillary atrophy, thickened blood vessel wall, wrinkles, and even necrosis, tubular atrophy, renal interstitial fibrosis.

Immunofluorescence revealed fibrinogen in the vessel wall, immunoglobulins, mainly IgM and complement C3 deposition.

Electron microscopy showed glomerular mesangial hyperplasia and epithelial cell foot process fusion, granular deposition of small arterial endothelium, glomerular basement membrane division, thickening, wrinkling, and interlobular arterial fibrinogen deposition.

5. X-ray inspection

The texture of the two lungs is enhanced, or there is a small cystic change, and there may be a reticular-nodular change in the lower lobe. The esophagus, gastrointestinal tract peristalsis is weakened or disappeared, the lower end is narrowed, the proximal side is widened, and the small intestine peristalsis is also reduced. The lateral small intestine is dilated, the colonic pocket can change in a spherical shape, the finger bone is absorbed, and there is calcium salt deposition in the soft tissue.

Diagnosis of scleroderma

diagnosis

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Differential diagnosis

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