Introduction to scleroderma

Introduction

scleroderma(scleroderma) is a connective tissue disease characterized by localized or diffuse skin and connective tissue fibrosis, sclerosis and atrophy. Its main features are fibrosis or hardening of the skin, synovium, skeletal muscle, blood vessels and esophagus. . 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 Serious, poor prognosis. The disease ranks second only to lupus erythematosus in connective tissue disease. The number of patients is more women, and the ratio of women to men is about 3:1. The age of onset is more common in 20 to 50 years old. Women of childbearing age are the most common, and children and the elderly can also develop the disease. It has been reported that miners and workers exposed to silicon have more patients with scleroderma.

Cause

(1) Causes of the disease

It is not clear, and it is summarized in the following aspects:

(1) Genetic factors According to some patients with a clear family history, the incidence of HLA-B8 in severe patients and 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.

(B) Infection factors Many patients often have acute infections before onset, including angina, tonsillitis, pneumonia, scarlet fever, measles, and sinusitis. Paramyxovirus-like inclusion bodies have been found in the patient's striated muscle and kidney.

(3) Patients with abnormal connective tissue metabolism show extensive connective tissue lesions, and the collagen content in the skin is significantly increased. There are more soluble collagen and unstable intermolecular side chains in the virus active skin lesions. The fibroblast culture of the patient showed a marked increase in the activity of collagen synthesis.

(4) Patients with vascular abnormalities often have Raynaud's phenomenon, which is not limited to the extremity, but also occurs 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 disease. Primary vascular disease, but because vascular disease is not seen in all patients, it is also considered that vascular disease is not the only pathogenic factor of this disease.

(5) Immune abnormalities 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 extract) can be detected in patients; the number of B cells in patients increases, and humoral immunity is significantly enhanced in the system. The positive rate of circulating immune complexes in patients with type is up to 50%. Most patients have hypergammaglobulinemia; some cases are often complicated by lupus erythematosus, dermatomyositis, rheumatoid arthritis, Sjogren's syndrome or Hashimoto's thyroiditis. At present, most people think that this disease may be an autoimmune disease caused by a chronic infection based on a certain genetic background.

(two) pathogenesis

Pathogenesis

(1) Theory of vascular injury: The 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, it has been suggested that SSc is the result of repeated damage of vascular endothelial cells. Endothelial cell damage causes changes in capillary permeability, and damage to the arterioles leads to platelet aggregation and endothelial cell proliferation. Endothelial cells are damaging to diversity, with swelling and hyperplasia, followed by thrombosis leading to narrowing of the lumen and tissue ischemia. These vascular lesions are found in many systemic blood vessels such as skin, skeletal muscle, digestive tract, lung, heart, kidney and brain. Although there are significant vascular lesions in the early stage of the disease, immunoglobulin, complement and immune complexes are rarely found in the blood vessel wall, so it is also indicated that endothelial damage is the basis of this disease.

(2) Immunology: The disease often coexists with autoimmune diseases such as systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, rheumatoid arthritis, etc., and idiopathic thrombocytopenia often occurs in the course of the disease. Purpura, autoimmune anemia, etc. There are a variety of autoantibodies in the serum, and there are often multi-cell strains of hypergammaglobulinemia, immune complexes, etc., suggesting autoimmune diseases. These autoantibodies include: Scl-70, also known as anti-local isomerase I antibody, anti-centromere antibody, anti-nucleolytic antibody (including different nucleolar components), anti-PM/SSc antibody, etc., the role of these autoantibodies The mechanism is not very clear, but its corresponding target antigen is an important component of nuclear metabolism, so it is suggested that the disease is caused by molecular simulation. T lymphocytes also have significant abnormalities in the circulation and tissues around the SSc. In the peripheral blood, T cells decrease, and the ratio of T helper lymphocytes to inhibitory T cells increases; the lymphocytes of the skin dermis are mainly T helper lymphocytes, and the locally isolated lymphocytes can stimulate the activation of skin fibroblasts. Cytokines. In short, there are obvious humoral immune abnormalities and cellular immune abnormalities in this disease.

(3) Abnormal fiber proliferation: The skin and internal organs of this disease are extensively fibrotic because the newly synthesized collagen replaces most or all of the subcutaneous tissue, thus tightening and hardening the skin. Certain subtypes of fibroblasts isolated from the skin of SSc patients can synthesize excess collagen (mainly type I and III), glycoproteins, etc. in culture. Experiments have also shown that local collagen breakdown is reduced. Current studies have shown that TGF-B (growth-transforming factor) not only directly stimulates but also secretes PDGF-β (platelet-derived growth factor) to indirectly stimulate the growth of fibroblasts.

2. The main pathological changes of pathological SSc are connective tissue inflammatory cell infiltration, intimal hyperplasia, vascular occlusion, fibrous tissue hyperplasia and sclerotic atrophy. In the early stage of skin lesions (inflammation), interstitial edema of the dermis, separation of collagen fibers, infiltration of lymphocytes around small blood vessels, edema of blood vessel walls, and breakage of elastic fibers. Thereafter, the infiltration of inflammatory cells around the blood vessels subsided, the collagen swollen, and the acidic mucopolysaccharides and collagen around the small blood vessel fibers increased. In the late stage (hardening period), collagen fibers are homogenized, collagen fibers bundles parallel to the epidermis are increased, collagen fibers are proliferated, and spread to the deep. The small vessel wall is thickened, the lumen becomes smaller, and even occluded. Continued changes in the late stage, leading to atrophy of the epidermis and appendages, calcium deposition, fascial muscle sclerosis and atrophy.

Visceral lesions are basically consistent with skin lesions. Multiple systemic sclerosis: smooth muscle (including esophageal muscle fiber bundle) showed uniform sclerosis and atrophy, extensive atrophy and fibrosis of intestinal wall muscle and myocardium; fibrin-like protein degeneration, inflammatory infiltration and collagen in endocardium and pericardium Hyperplasia; pulmonary interstitial and alveolar extensive fibrosis, and cystic changes; pulmonary arteriolar wall thickening, alveolar and microvascular basement membrane thickening; renal interlobular artery intimal hyperplasia, glomerular basement membrane thickening, fibrin Like necrosis. Severe glomerular sclerosis and renal cortical infarction can be seen; thyroid may also have interstitial atrophy and fibrosis (Figure 1, 2, 3).

3. The etiology and pathogenesis of Chinese medicine The main cause of this disease is 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 hinders Weiyang, evil hinders the veins, and causes the camp to be discordant, the blood is impassable, the advance is involved in 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, the liquid is difficult to lose, and it is concentrated; or the spleen and kidney are yang, and the turbidity can not be turbid. If the turbidity is blocked in the skin veins and the skin of the tendons is dying, the disease may occur.

(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 block the air, the blood flow is not smooth, and gradually the lungs, spleen and kidneys are involved, and the main cause is damp heat, cold coagulation, and collateral stagnation. Yin, yin and yang can be strained. Those who are damaged by the viscera are more dangerous.

symptom

1. Skin manifests early hand and finger swelling, but also involves the forearm, foot, lower limbs and face, but the lower limbs are less affected. The swelling period can last for weeks, months, or even longer. Edema can be concave or non-concave and can be accompanied by 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 three stages of edema, hardening 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 appears and the fingertip fat pad disappears. In patients with localized skin lesions, early edema occurs on the fingers, back of the hand and face, and then spreads to the upper extremities, neck, shoulders, etc., diffuse type is often first from the trunk, and then spread to the surrounding. This period can last for several months.

(2) Intensive phase: the skin thickens and becomes hard, fibrosis occurs, the fingers and the back of the hand are shiny and tight, the early skin can be red, the surface has waxy luster, no sweat, the hair is scarce, the skin is not easy to pinch. Start. 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 are shortened. An ulcer can occur. It can produce limited flexion and extension of the finger. The chest is tight and the skin of the affected area can be pigmented and hypopigmented. The hair is scarce. The skin changes can be limited to the fingers, toes, hands, feet and face. It can be extended to the front arm and can start from the chest back and expand to the periphery. Involves the upper arm, shoulders, abdomen and legs. The extent and severity of endothelial damage usually peaks at 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 skin lesions. The improved Rodnan skin thickness integration method is a simplified semi-quantitative skin scoring method. The specific method is: the examiner respectively picks up the skin of the following 17 parts: face, chest, abdomen, left and right upper arms, left and right forearms, left and right hands, left and right fingers, left and right thighs, left and right Calf, left and right feet. Each site was scored according to the scoring criteria: normal skin thickness was 0; skin mildening was 1 point; skin was thickened to 2 points; skin was extremely thickened to 3 points. Then add the points of these 17 parts. This method is more accurate and reliable, and can be used to clinically estimate the condition and conduct observational studies.

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 emotionally excited, the closure of the anterior capillary artery and arteriovenous shunt of the skin of the hand, the foot and the toe will cause changes in the skin's paleness and subsequent blemishes. After the end of the stimulation (warming), the vasospasm is relieved, and the skin turns into flushing, accompanied by numbness, burning, and tingling. It usually takes 10 to 15 minutes, and the finger (toe) becomes normal or 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, and most of them had no vascular structural changes or tissue ischemic damage (primary Raynaud's phenomenon). 50% of patients with Raynaud's phenomenon are primary. The typical primary Raynaud phenomenon begins in adolescents, more common in 20 to 40 years of age, and more women than men. Patients with primary Raynaud's phenomenon are basically normal in other aspects, and the symptoms appear in the fingers (toes), showing a symmetric distribution.

For doctors, the important question is to determine whether the Raynaud's phenomenon is the first symptom of primary or scleroderma. The identification of the two is shown in Table 2. If there is a phenomenon of Raynaud's phenomenon, it does not have depression, ulcer, gangrene, normal wrinkle capillary and erythrocyte sedimentation rate, negative anti-nuclear antibody, it is rarely scleroderma. If the acne vasospasm increases and/or decreases and disappears, it indicates that the patient has a connective tissue disease such as scleroderma.

(3) Renault phenomenon and scleroderma: 90% of patients with scleroderma have obvious Raynaud's phenomenon, and the appearance of Raynaud's phenomenon is an abnormal manifestation of vascular spasm and finger artery structure. Compared with normal people, patients with scleroderma have malnutrition and hyperthermia through temperature-regulated flow to the skin in a low temperature environment. Also in the warming of the environment, the reaction to relieve vasoconstriction and restore local blood flow is delayed.

3. Muscle, joint and bone disease

(1) Muscle lesions: Patients with scleroderma often show significant myalgia and muscle weakness, which may be the first non-specific symptoms of scleroderma. Muscle atrophy can also occur in the advanced stage. On the one hand, the skin is thickened and hardened to limit the motor function of the joint, resulting in muscle atrophy. Diffuse scleroderma can occur in any joint, but fingers, wrists, and elbow joints are more common. On the other hand, it is also associated with fibrosis that spreads from the tendon to the muscle. There is also the use of secondary medications such as corticosteroids and penicillamine. When scleroderma overlaps with polymyositis or dermatomyositis, the patient may have significant proximal muscle weakness and serum creatine phosphokinase (CPK) continues to increase. The electromyogram showed an increase in multiphase potential, a decrease in amplitude and duration, and no insertional stress and fibrillation. Muscle tissue biopsy showed inflammatory changes, inflammatory cell infiltration, muscle fiber degeneration, atrophy or fibrosis.

(2) Arthritis: Arthritis occurs in the joints of the fingers, wrists, knees, and ankles. Joint pain can also be a non-specific symptom of early occurrence of scleroderma. Patients often have more obvious joint pain and morning stiffness, which can involve the upper arm and lower leg muscles from the joint along the tendon. Pain increases in the wrist, ankle, elbow, and knee joints, and a rougher rubbing sound may occur due to fibrosis and inflammation of the tendon sheath and adjacent tissues. This rubbing sound is more common in diffuse scleroderma, suggesting a poor prognosis. About 29% of patients have erosive joint lesions.

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

4. Patients with scleroderma with 80% to 90% of digestive system lesions may experience digestive system involvement. It can also be the first symptom of scleroderma.

(1) Oropharynx: The opening is restricted, the oral mucosa is dry and hardened, the tongue nipple disappears, the tongue muscles atrophy, the tongue cannot protrude out of the mouth, and the periodontal disease causes the patient to have difficulty chewing, teeth falling off and malnutrition. Generally, the function of the upper pharynx is not affected, unless the pharyngeal muscle is involved, and there is myositis or neuromuscular disease. At this point, food into the esophagus through the mouth will have difficulty swallowing, the patient will cough when swallowing liquid food, nasal reflux, head and shoulder flexion can prompt 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 is often manifested by the patient's feeling of sticking in a certain part of the esophagus after swallowing solid food, which can be relieved after drinking water. Attenuated esophageal peristalsis can result in a feeling of fullness and acute food impaction.

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

Delayed evacuation due to solid food retention in the stomach exacerbates esophageal reflux and leads to fullness, nausea, and vomiting. 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, unconscious cough, 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 showed that the esophageal peristalsis was weakened or disappeared, the esophagus was dilated, and the lower third was visible. Endoscopy showed that the mucosa had different degrees of erosion and thinning. Histopathological examination showed that the esophageal smooth muscle atrophy was replaced by fibrous tissue, and the submucosa and mucosal lamina propria were fibrotic. Esophageal manometry 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: abnormal intestinal peristalsis due to intestinal wall fibrosis and smooth muscle atrophy. It usually manifests as recurrent episodes of mild abdominal pain, diarrhea, weight loss and malnutrition. Malnutrition and diarrhea are caused by obstruction of the intestinal contents and excessive absorption of bacteria. In severe cases, patients may experience chronic pseudo-obstruction, manifested as 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. Patients with scleroderma have decreased colonic tone, have few diarrhea, and have constipation, lower abdominal distension, and loose caulking. Due to the atrophy of the intestinal wall of patients with scleroderma, its characteristic 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 in innervation. This defect is similar to the ischemic damage of nerve tissue secondary to microangiopathy. Advanced gastrointestinal smooth muscle atrophy and fibrosis of the submucosa and myometrium have become major pathological changes. This neurological deficit and fibrosis together lead to irreversible dysfunction of the digestive tract.

5. Lung involvement in patients with scleroderma is very common, and often accompanied by cardiac involvement, is the main cause of death. The earliest symptom is shortness of breath after activity; the latter manifests as innocent dry cough. Chest pain is usually not caused by scleroderma, but by musculoskeletal pain, reflux esophagitis, pleurisy or pericarditis. Patients with scleroderma have pulmonary fibrosis and pulmonary vascular disease at the same time, but a pathological change is the main cause. Pulmonary interstitial fibrosis is more obvious in patients with diffuse scleroderma positive for anti-Sc1-70 antibody. Severe, pulmonary vascular disease and pulmonary hypertension are the main lung manifestations in patients with CREST syndrome. In patients with scleroderma, aspiration pneumonia caused by esophageal lesions, respiratory failure caused by respiratory muscle weakness, pulmonary hemorrhage, pleural reaction, pneumothorax, and right heart failure caused by pulmonary hypertension may also occur.

Approximately 80% of patients with specific and sensitive methods have abnormal lung function. Most lung lesions have no obvious clinical symptoms until the pulmonary fibrosis is aggravated and symptoms appear when pulmonary hypertension occurs. At this time, pulmonary function tests show restrictive ventilatory disorders, which may have a decrease in lung volume [eg, reduced forced vital capacity (FVC)] or a decrease in carbon monoxide diffusion, which may reflect impaired gas exchange function, by pulmonary interstitial fibrosis or Pulmonary vascular disease, if it falls below 40% of the predetermined value, or a rapid decline in carbon monoxide diffusion and/or a rapid decline in lung capacity suggests a poor prognosis.

Pulmonary interstitial fibrosis caused by neutrophiliculitis can be detected by CT and/or bronchoalveolar lavage. X-ray examination is relatively insensitive, but if there is an abnormality, it can show that the bilateral interstitial texture is enhanced, and there is a nodular change in the lower part of the lung parenchyma. When there is active alveolitis, a high-resolution CT examination may have a "hairy glass"-like change. Bronchoalveolar lavage fluid examination showed an increase in cells. Patients can present with significant dyspnea and reduced carbon monoxide diffusion. Pulmonary vascular disease with pulmonary hypertension is the most difficult problem in scleroderma control. It is often difficult to detect before severe irreversible pulmonary hypertension. Non-invasive detection using two-dimensional echocardiography helps early detection of the presence of pulmonary hypertension.

6. Heart disease 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, palpitations, chest discomfort, and corresponding clinical manifestations of pericarditis, congestive heart failure, pulmonary hypertension, and arrhythmia. The presence of 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. Simple pulmonary hypertension without pulmonary fibrosis is rare, almost only seen 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, so it is necessary to pay attention to the presence of ventricular diastolic function and pulmonary hypertension. Dyspnea after activity is secondary to lung damage in scleroderma. Palpitations, chest pain, or syncope can be caused by arrhythmia or pericardial disease. Echocardiography or ECG monitoring is helpful for diagnosis. An angina is available for angina to determine if there is coronary arteriosclerosis. Electrocardiogram examination can show abnormal cardiac conduction and arrhythmia, which is more valuable if combined with 24h ECG monitoring. The most common arrhythmia is ventricular premature contraction (pre-systolic). Atrial premature contraction (pre-contraction), supraventricular tachycardia, and atrioventricular or indoor conduction abnormalities are rare. In the advanced stage of diffuse scleroderma, the left ventricular ejection fraction may decrease. After the patient's exercise, radionuclide scans may be performed. 40% to 50% of patients may have abnormalities, and 15% of patients may have abnormalities during rest. Echocardiography revealed abnormalities in left and right ventricular function, especially left ventricular diastolic dysfunction. Shortness of breath after unexplained exercise may be an early manifestation of diastolic dysfunction.

Autopsy found that 30% to 70% of patients with scleroderma have fibrin or fibronectin pericarditis. 30% to 40% of patients have small or large pericardial effusions.

7. Renal involvement may occur in 75% of patients with renal disease. The main clinical manifestations are hypertension, proteinuria and azotemia. The most severe renal impairment in patients with scleroderma is rapidly developing hypertension and/or rapidly progressing renal failure, the scleroderma renal crisis (SRC).

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

(2) Proteinuria: Patients often have intermittent proteinuria and/or microscopic hematuria. A small number of patients present with a large number of proteinuria or nephrotic syndrome, sometimes proteinuria and hypertension and azotemia can be combined, such patients have a poor prognosis.

(3) azotemia: more than one-fourth of patients may have increased blood urea nitrogen and decreased creatinine clearance. In the presence of acute renal failure, elevated blood urea nitrogen may be more pronounced than serum creatinine, suggesting insufficient renal blood flow. If accompanied by malignant hypertension, the patient may present with oliguric renal failure. Renal failure in patients with scleroderma is not completely irreversible. After dialysis and appropriate medication, renal function can be restored in some patients. Common causes of kidney failure are stress conditions such as heart failure, infection, dehydration, and surgery. Patients with renal failure have a poor prognosis.

(4) Kidney crisis of scleroderma: 10% of patients with scleroderma may have kidney crisis, and 80% of them have a kidney crisis in the first 4 years of the disease. It usually occurs in winter. Patients with renal crisis may have sudden typical malignant hypertension, manifested as nervous system changes such as headache, decreased vision, convulsions, seizures, confusion, and even coma, as well as congestive heart failure and rapid progressive renal failure. . Patients often have diastolic blood pressure, and hypertensive encephalopathy can occur. With retinal edema, fundus hemorrhage and exudation, plasma renin activity increased. Patients can also have microangiopathic hemolytic anemia and thrombocytopenia, which is more common in patients with normal blood pressure. Renal crises often develop into oliguric renal failure within a few weeks. The incidence is reported to be 10% to 40%, most of which range from malignant hypertension to death in less than 3 months. However, patients with localized scleroderma with anti-central antibody positives do not have kidney crisis.

Risk factors for renal crisis in patients with scleroderma include: diffuse skin lesions, emerging unexplained anemia, and the presence of anti-RNA polymerase III antibodies. It has been suggested that the use of high doses of glucocorticoids and the use of small doses of cyclosporine A may promote the appearance of renal crisis. Non-malignant hypertension, abnormal urine tests, elevated 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. The degree of performance is related to the patient's personality characteristics and the care and care received, and has nothing to do with the condition.

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

(3) Dry eyes and dry mouth: This is a common manifestation of patients with scleroderma. Small salivary gland biopsy showed fibrotic changes without lymphocyte infiltration specific to Sjogren's syndrome, and anti-SSA (Ro) antibodies and anti-SSB (La) antibodies were not detected in the vast majority of patients. It shows that the mucosal dryness of patients with scleroderma is different from that of Sjogren's syndrome.

(4) Neurological pathology: Scleroderma is not affected by central nervous system involvement. But it can involve peripheral nerves, such as trigeminal neuropathy and carpal tunnel syndrome. Neurological abnormalities are often secondary to microvascular disease. For example, the Raynaud phenomenon is associated with increased adrenergic neuroreactivity. Gastrointestinal manifestations are also associated with impaired cholinergic nerve function. It indicates 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, and the pathological manifestation is lymphocyte infiltration.

(6) Pregnancy: Patients with scleroderma often have irregular menstruation, so the pregnancy rate is lower than normal. The rates of spontaneous abortion, premature delivery, and low birth weight were higher than in the normal population. However, this does not mean that patients with scleroderma cannot 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. The incidence of malignant tumors in patients with scleroderma and malignant scleroderma is 2.1 times that of the same age group. Older patients and patients with positive anti-topoisomerase antibodies have an increased incidence of cancer. Patients can have lung cancer on the basis of pulmonary fibrosis, and there are reports of breast cancer.

10. CREST Syndrome This is a special symptom subtype of systemic sclerosis, which is mainly characterized by subcutaneous calcareous deposition, Raynaud's phenomenon, abnormal esophageal peristalsis, finger (toe) hardening and skin telangiectasia. Subcutaneous calcareous deposits can be found in 40% of patients. The 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 joints, such as the tendon sheath and the bursa. In fact, any part can appear.

The deposited calcium forms irregular, non-pressurized lumps ranging in diameter from a few millimeters to a few centimeters. The overlying skin can be normal, inflamed or ulcerated, and the skin from the rupture is like a white sputum, and the ruptured skin is easily infected. Patients with this syndrome have a significant Raynaud's phenomenon with an incidence of 100%. The patient's esophageal peristalsis is weakened and the same clinical symptoms as systemic sclerosis esophageal involvement may occur. Finger (toe) hardening, gradually extending from the distal end to the proximal end, local skin thickening, formation of sausage-like changes, sometimes accompanied by finger (toe) distal bone absorption. Skin telangiectasia can occur in the hands, nails, face, neck, chest, and back. The intrinsic progress is slow, the visceral involvement is lighter, and the prognosis is better. However, such patients may have pulmonary interstitial lesions and pulmonary hypertension, and may also be complicated by primary biliary cirrhosis.

diagnosis

1. The most common first symptoms of scleroderma are Raynaud's phenomenon, fatigue and skeletal muscle pain. These symptoms can persist for several months and are difficult to diagnose. These patients are often diagnosed as "undifferentiated connective tissue disease" (UCTD). However, such patients have the following characteristics for early diagnosis of scleroderma: Raynaud's phenomenon occurs in older patients, Raynaud's phenomenon is more serious, abnormal wrinkle capillary examination, scleroderma-related antinuclear antibody Positive (eg anti-topoisomerase or anti-centromere antibody). The first clue to the diagnosis of scleroderma usually is thickening of the skin, often starting with swelling of the fingers and hands. The diagnosis of systemic sclerosis is mainly based on the appearance of crust, Raynaud's phenomenon, visceral involvement and specific anti-nuclear antibodies.

Currently, the classification criteria for scleroderma developed by the American College of Rheumatology in 1980 is shown in Table 3. The standard has a sensitivity of 91% and a specificity of 99%. Systemic sclerosis can be diagnosed if one of the following major criteria or two minor criteria is available.

Main criteria: symmetry thickening, tightening and hardening of the proximal skin of the proximal hard skin such as the fingers, metacarpophagic or metatarsophalangeal joints.

Such changes can affect the limbs, face, neck and torso (chest and abdomen).

Secondary criteria:

(1) Hard finger: The above skin changes are limited to the fingers.

(2) Finger depressed scar or finger pad thinning: fingertip depression or finger pad tissue loss due to ischemia.

(3) Fibrosis of the basal fibrosis of the lungs: Patients with no primary pulmonary disease have a network, linear or nodular density increase at the bottom of both lungs, and may also be diffusely spotted or honeycomb.

2. CREST syndrome has five characteristic features: subcutaneous calcareous deposit, Raynaud's phenomenon, abnormal esophageal peristalsis, finger (toe) hardening and skin telangiectasia. Have 3 or more of the characteristic performance, plus anti-centromere antibody positive. The diagnosis can be determined.

Identification

(1) Localized scleroderma needs to be identified with the following diseases:

1. Early damage of plaque atrophy is of different sizes, skin-colored or blue-white, dimples or bulges, wrinkles on the surface, and hard to touch.

2. Atrophic sclerosing mossy skin lesions are lavender shiny flat papules, which vary in size and often aggregate, but do not fuse with each other. There are hair follicle horny plugs on the surface, sometimes blisters, and skin atrophy gradually occurs.

(2) Systemic sclerosis needs to be identified with the following diseases:

1. Adult scleredema: The skin lesions start from the head and neck to the shoulder and back, and the deep dermis is swollen and stiff. Local non-pigmentation, no atrophy and hair loss, and self-healing tendency.

2. Mixed connective tissue disease: The patient has mixed manifestations of systemic lupus erythematosus, scleroderma, dermatomyositis or polymyositis, including Raynaud's phenomenon, non-recessed edema of face and hands, and swollen fingers. , fever, non-destructive polyarthritis, muscle weakness or myalgia and other symptoms. Both leaching nuclear antigen (ENA) and RNP antibodies are highly titer positive.

3. Chemicals, poison-induced scleroderma-like syndrome exposure to chemicals such as polyvinyl chloride and benzene, as well as those who consume toxic oil or certain drugs and who receive silicone breast augmentation, may have a hard skin and a scleroderma Some other symptoms. However, these people have no typical scleroderma manifestations, no specific autoantibodies in the serum, stop contact, and the symptoms can gradually disappear, which is easy to distinguish from scleroderma.

complication

(1) joint damage;

(2) damage to the smooth muscle of the gastrointestinal tract;

(3) malnutrition;

(4) Myocardium forms fibrous tissue, which may cause permanent damage and/or functional deterioration;

(5) Kidney damage and/or renal dysfunction;

(6) The thyroid gland forms fibrous tissue.

treatment

1. Western medicine treatment has always been a difficult problem. Because of its wide spectrum of disease, clinical manifestations and severity, and different course of disease, it is difficult to evaluate the impact of treatment methods on the disease. Only after quantifying the lesions, can we find an objective evaluation method. These indicators include measurements of "thickness of the skin", "pulmonary function", "systolic function" and "kidney function".

(1) Principles of treatment:

1 Early diagnosis and early treatment are beneficial to prevent disease progression. The principle is vasodilation, anti-fibrosis, immunosuppression and immune regulation, but no specific drugs.

2 The treatment of scleroderma mainly focuses on three aspects: vascular abnormalities, immune abnormalities and fibrotic lesions.

(2) Treatment of vascular lesions: Since the Raynaud phenomenon is often a precursor to scleroderma, vascular abnormalities should be treated first. The treatment of Raynaud's phenomenon should control or reduce the occurrence of vasospasm caused by cold and mood swings, and prevent the occurrence of fingertip ischemic ulcers.

1 general treatment: patients do not smoke, so as not to cause vasospasm. Avoid using drugs that can aggravate your condition, such as beta-blockers. Use cotton gloves and thick socks to keep your hands and feet warm and wear more clothes to prevent the reflective effect caused by the cold stimulation of the trunk. The rotational movement of the upper arm is performed to promote blood circulation.

2 drugs for blood vessels and improving microcirculation: aspirin and dipyridamole (dipyridamole), which alter platelet function, have little effect.Ketochrome(Ketanserin) is a histamine antagonist that reduces the frequency and severity of Raynaud's onset and improves the prognosis of finger ulcers, but it is not effective in improving skin thickening or internal organ damage.Iloprost(Iloprost) is a prostacyclin analogue that is a new drug for the treatment of Raynaud's phenomenon and fingertip ulcer. The calcium channel blocker nitrendipine is an effective vasodilator. Angiotensin-converting enzyme inhibitors such as captopril and enalapril are effective in controlling hypertension and early renal insufficiency. The drugs that improve microcirculation are also Danshen andDextran40 (low molecular weight dextran injection) has a certain effect on skin hardening, joint stiffness and pain.

A.ColchicineIt can affect the delivery and secretion of procollagen through fibroblasts, but it has no obvious clinical effect. A mast cell stabilizer, ketotinic acid, prevents skin sclerosis in hard-skinned mice, but the double-blind trial in patients with SSc failed to show any effect.

B. Other drugs that improve microcirculation: such as intravenous infusion of urokinase, oral administration of tolazoline, oral administration of methyldopa, and troxerutin (Wei Nalutong) have certain curative effects.

C. Chinese medicine preparation: such as Danshen injection 250ml containing Danshen 16g, 1 time / d, intravenous drip, 1 course every 15 days, continuous or intermittent use 2 ~ 3 courses. At the same time, it can also be combined with oral vasculitis tablets (formerly known as Fuchun tablets). The main ingredients are frankincense, myrrh and turmeric. Each time 2.4 grams, 3 times / d, oral, when the patient is in the menstrual period, can be suspended In order to avoid causing excessive menstrual flow, continue to take after menstruation.

Application of alprostadil (prostaglandin E1), salvia miltiorrhiza injection and vasculitis tablets in combination with three drugs, 15 days for one course of treatment, interval 2 to 3 days and then the second course of treatment, sharing 2 to 3 courses, found The combination has a synergistic effect, which can reduce the skin hardening range, restore skin elasticity and tension, soften the skin, pinch wrinkles, open mouth and difficulty swallowing, Raynaud's phenomenon, fingernail ulcer, joint and organ involvement Symptoms have been significantly improved, and its efficacy is better than one of the drugs alone.

D. Surgical treatment: Digital sympathectomy is used to treat only 1 or 2 finger ischemia. Lumbar sympathectomy is used to treat the severe Raynaud's phenomenon in the lower extremities. Cervical sympathectomy is used to treat the upper limbs Reynolds phenomenon. However, it has been reported that these types of surgery have a short duration of action and are prone to recurrence, and are rarely used now.

(3) Immunomodulation therapy:

1 glucocorticoids and immunosuppressive drugs: Although glucocorticoids can not control the progression of the disease, but have a certain effect on arthritis, myositis, pericarditis, myocardial damage, inflammatory phase of pulmonary interstitial lesions. Combined with immunosuppressive drugs, it can improve the efficacy and reduce the amount of glucocorticoids.Prednisone30 ~ 40mg / d, after 1 month reduction, with 10 ~ 15mg / d maintenance with the improvement of clinical symptoms. Applying prednisone 20 to 30 mg per day to patients with skin edema can reduce edema. However, glucocorticoids cannot be used for a long time because it does not prevent the progression of the disease, and large doses can promote the occurrence of acute renal failure and induce kidney crisis. For patients with scleroderma with inflammatory myopathy or pericarditis.

Double-blind controlled treatment trials found that chlorpheniramine benzoate and fluorouracil were ineffective against SSc.MethotrexateAnd cyclosporine A (CsA) has a certain effect in a few human trials, but the renal toxicity of CsA limits its application.

2 Immunosuppressive drugs: The activated immune system plays an important role in vascular injury and fibrotic lesions in patients with systemic sclerosis, and its greatest damage effect may occur in the early stages of the disease. Therefore, it is believed that immunosuppressive drugs such as Chlorambucil, Fluorouracil (5-fluorouracil), Cyclophosphamide, and A should be used in patients with significant cellular and humoral immune abnormalities. Methotrexate,Azathioprine(Azathioprine),Cyclosporin A(Cyclosporin A), thioguanine (6-thioguanine), etc., but their exact long-term efficacy has yet to be further verified clinically. It has been reported that the combination of cyclophosphamide with glucocorticoids or plasmapheresis can improve dyspnea, improve efficacy, and reduce glucocorticoid dose. Some people think that cyclosporine A is helpful for the treatment of scleroderma, but its application is limited due to its nephrotoxic effect.

(4) Anti-fibrotic treatment (connective tissue formation inhibitor): Once fibrosis occurs, it is difficult to treat. Because there is currently no safe and effective method to remove overgrown insoluble cross-linked collagen fibers without damaging the structural scaffolds of organs or tissues. Some people advocate the use of anti-fibrotic treatment as early as possible in the early stages of the disease, but these drugs have a slow onset of action and generally advocate the use of immunosuppressive drugs in combination to improve the efficacy. For localized scleroderma, if there is no visceral damage, anti-fibrosis treatment may not be used. Commonly used connective tissue formation inhibitors are:

PenicillamineIt is an immunomodulatory drug. Because it can interfere with the cross-linking of collagen, it is widely used to treat SSc. It has a certain effect on inhibiting skin cirrhosis and visceral damage. It can be received orally 0.5~1.0g/d, and can be received in 1-3 years. Efficacy. Its efficacy is related to the course of the disease, the course of treatment and the total amount of the drug. A large sample retrospective study found that after 2 years of application, the thickened skin was significantly improved. Compared with the untreated group, the 5-year survival rate increased significantly. Re-evaluation of the drug several years later confirmed this conclusion. In addition, it was found that IFN-γ can down-regulate fibroblast proliferation and reduce collagen production.

1 penicillamineD-penicillamine): Penicillamine has two effects in the treatment of scleroderma: First, it affects the biosynthesis of collagen, because there are many aldehyde groups on the collagen molecule, and the aldehyde groups of adjacent collagen molecules condense, causing the interaction between the collagen chains. Linked to form collagen fibers. Penicillamine can bind to these aldehyde groups, block the cross-linking between collagen chains, thereby inhibiting the maturation and stability of new collagen, and activate collagenase to degrade the formed collagen fibers and reduce soluble collagen to insoluble. Transformation of collagen. Second, penicillamine has an immunosuppressive effect and inhibits the activity of T lymphocytes in vitro. Steen in the United States and 1982 reported the results of a controlled study of penicillamine in 152 patients and 73 patients with scleroderma. They found that skin sclerosis was significantly improved after 2 years of treatment. The 5-year survival rate was significantly higher than that of the control. Group, up to 80%. Another scholar has conducted 15 years of treatment observations and reported similar results.

The use of penicillamine should start from a small dose, gradually increase the amount, start 250mg per day, after every 2 to 4 weeks, the daily dose is increased by 125mg, until 750 ~ 1000mg / d, generally maintain a daily dose of 500 ~ 1000mg, for the most The best absorption effect should be taken 1 hour before the meal or 2 hours after the meal, and the drug is used for 2 to 3 years. The effect is better. It can improve the skin thickening, hardening and nutritional status, and also reduce the incidence of lung and other organ involvement, and improve the survival rate. Common side effects of penicillamine are myelosuppression, kidney damage, oral ulcers, loss of appetite, rash, and fever. During the medication, the patient should have regular blood and urine tests every month.

2α- and γ-interferon: α- and γ-interferon inhibit collagen synthesis and proliferation of skin and synovial fibroblasts in vitro. As a collagen synthesis inhibitor, γ-interferon is more potent than α-interferon, but γ-interferon can cause macrophage activation in vitro, expression of MHC class II antigen in fibroblasts and endothelial cells, and increase IL- Expression of receptors for 2R and IgG Fc and increased expression of intracellular adhesion molecule (ICAM)-1 in endothelial cells. It has been reported that 19 patients with scleroderma have been treated with interferon for 3 years, and the synthesis of type I collagen is significantly reduced. However, its long-term efficacy still needs further verification.

3Colchicine(Colchicine): Colchicine treats scleroderma by affecting collagen metabolism. On the one hand, it can inhibit the production of collagen by destroying the formation of microtubules in the fibroblast skeleton; on the other hand, it prevents the accumulation of collagen by increasing the activity of collagenase. The dosage is 0.5-1.5mg per day for 3 months to several years, which has certain curative effect on Raynaud's phenomenon, skin sclerosis and esophageal lesions. The main side effects are abdominal pain, diarrhea, alopecia, gonadal inhibition, nausea, vomiting and the like. For example, diarrhea can be reduced or given galactosidase (β-galactosidase) to relieve symptoms.

4 Asiaticoside: This is an active ingredient extracted from Centella asiatica, and the foreign name is Madecassol. It inhibits the proliferation and activity of fibroblasts, inhibits the matrix and fiber components of connective tissue, and softens connective tissue. Usage is 20 ~ 40mg per day, divided into oral, or 20mg intramuscular injection, 2 to 3 times a week, medication 1 to 3 months effective, can eliminate tissue edema, soften the hardened skin, relieve joint pain, promote The ulcer heals.

(5) Treatment of internal organ involvement:

1 pulmonary lesions: pulmonary interstitial fibrosis and pulmonary hypertension are still one of the main causes of systemic sclerosis.

A. Pulmonary interstitial fibrosis: glucocorticoids andCyclophosphamideCombination therapy can improve lung function. Thirty patients with pulmonary alveolitis confirmed by pulmonary biopsy were treated with grouped control. One group received large doses of prednisone (60 mg/d), and the amount was reduced after 1 month. The other group was injected with small dose. Nisson (20mg / every other day), combined with cyclophosphamide treatment. After 1 year of follow-up, it was found that half of the patients in the two groups responded to treatment, with a manifestation of forced vital capacity (FVC) or carbon monoxide diffusion function (DLCO) improved by 15% compared with pre-treatment. However, in some patients treated with high-dose prednisone, renal failure occurred several years later. High dose hormonal therapies are currently not advocated. Immunosuppressive drugs combined with plasmapheresis can improve lung function. In addition, pulmonary fibrosis can also be controlled by maintaining treatment with penicillamine for a certain period of time. Once extensive lung disease and fibrosis occur, treatment often makes it difficult to significantly improve lung function. If treatment can stabilize the lesion, it is the best response to treatment, and should not be considered as treatment ineffective.

B. Pulmonary vascular disease: Pulmonary vascular disease includes two aspects: one is reversible pulmonary vasoconstriction and the other is irreversible occlusive disease. The latter is difficult to treat any vasodilator. There are short-term observations that verapamil, hydralazine, ketochrome and nifedipine are effective in the treatment of pulmonary vasculopathy. Mid-term observations suggest that nifedipine and Kaibotong are more effective. It has been reported that continuous intravenous application of PGE1 for 24h has a therapeutic effect on severe primary pulmonary hypertension, and the therapeutic effect of prostacyclin is also under observation. Some people advocate that the cardioprostacyclin treatment for 5 days every 4 to 8 weeks can maintain the stability of the pulmonary artery. The continuous intravenous application of cyclacycline for 24 hours may have a certain effect on advanced lung disease. However, its potential complication is that it may aggravate the lack of cardiac output due to decreased systemic vascular resistance. Oxygen therapy can temporarily relieve symptoms and improve pulmonary vascular resistance in patients with hypoxemia and pulmonary hypertension. It has been reported that Warfarin treatment can increase the survival rate of patients with primary pulmonary hypertension.

2 Kidney disease: Kidney disease is still the most serious complication of life in patients with scleroderma in some cases. A good prognosis can still be achieved if early and reasonable treatment is available. The most characteristic renal manifestations in patients with scleroderma are acute or subacute hypertensive renal crisis. High-dose glucocorticoid therapy can increase the risk of renal crisis in patients with scleroderma. Therefore, the daily dose of prednisone is preferably not more than 20 mg. Patients with hypertension should control blood pressure, properly reduce blood pressure, avoid sharp blood volume changes, and maintain renal perfusion pressure. A higher dose of angiotensin converting enzyme inhibitor, such as Kaibotong, enalapril or quinopril, can be used to control blood pressure. Calcium channel blockers or doxazosin may also be used to reduce systolic and diastolic blood pressure by 2.68 kPa (20 mmHg) within the first 48 hours, and finally maintain diastolic blood pressure at 10.66 to 12 kPa (80 to 90 mmHg). . Intravenous infusion of prostacyclin contributes to the treatment of microvascular damage and does not aggravate high blood pressure. Renal biopsy helps to determine the diagnosis, estimate the extent of the injury, and eliminate the presence of concurrent glomerulonephritis. Hemodialysis, peritoneal dialysis, or kidney transplantation may be used for irreversible renal crisis or slow end-stage renal failure. Sometimes the acute renal crisis can be restored after treatment, and can be maintained for more than 2 years, and can stop dialysis treatment. It has been reported that after the treatment of renal crisis, skin sclerosis is also reduced, especially those who are treated by dialysis, which may be due to the elimination or inactivation of the immune medium in the circulation, or may be a natural improvement of the disease.

3 heart disease: Some studies have suggested that repeated coronary artery spasm can cause cardiac fibrosis changes. Nicardipine, dipyridamole and Kaibotong can improve myocardial perfusion, and long-term application can reduce or prevent the occurrence of cardiac insufficiency. Because angiotensin II can also cause cardiac hypertrophy, and stimulate interstitial fibrosis by stimulating collagen synthesis, myocardial contractility and elasticity are reduced. Therefore, angiotensin II receptor antagonists can be used to treat cardiac complications of systemic sclerosis.

4 Gastrointestinal lesions: For patients with esophageal peristalsis and reflux esophagitis, do not eat too much at one time and avoid lying flat after meals. Use proton pump inhibitors, such as Omeprazole, 20mg twice daily, orally, to relieve symptoms. Drugs that increase esophageal peristalsis, such as Metaclopramide, can also be used. These drugs increase the lower esophageal sphincter tone and promote esophageal emptying, thereby reducing esophageal reflux. Intestinal peristalsis can be attenuated with long-acting somatostatin analogues, acetic acidOctreotide(Octreotide acetate) treatment, or with motilin stimulant, erythromycin (Erythromycin) treatment. Intestinal dysfunction can be treated with effective antibiotics. Nutritional supplements are given to patients with malabsorption of the small intestine, including vitamins, foods with low residue, and medium chain triacylglycerol. Patients with constipation should consume more foods rich in cellulose.

5 joints, muscle lesions: treatment of musculoskeletal involvement: non-steroidal anti-inflammatory drugs can be used for common joint and tendon sheath involvement, but the curative effect is worse than other connective tissue diseases. In the early stage of SSc, tenosynovitis caused by tenosynovitis is very painful. It also limits the movement of the joints, sometimes requiring the addition of small doses of hydrocortisone (cortisol) hormones or analgesics. For patients with tenosynovitis, early physical exercise combined with physical therapy is very important. Because this treatment is very painful, sometimes analgesics are needed to help the patient participate in the maximum amount of activity. Carpal tunnel syndrome often occurs in the early stage of SSc. It is effective in treating the wrist with a static clip. Sometimes it can be treated with local cortisol. The cortisol can be used to treat myositis. Low-dose glucocorticoid can effectively control joints and muscles. Inflammation and pain, for inflammatory myopathy (unlike polymyositis), can be used alone with glucocorticoids or with immunosuppressive agents such as methotrexate and azathioprine.

6 symptomatic treatment of skin: the skin should be less exposed to water, use emollients containing lanolin to keep the skin moisturized. Those with more telangiectasia can be treated with laser. Treatment of subcutaneous calcareous deposits with Probecid or Calcium disodium edetate (EDTA) can dissolve and prevent subcutaneous calcareous deposition. At present, it is considered that the treatment with diltiazem is also effective. If there is local ulcer on the skin, pay attention to prevent infection and anti-inflammatory treatment.

7 treatment of Raynaud's phenomenon: smoking cessation, avoiding cold, paying attention to body warmth and biofeedback exercise is effective in preventing Raynaud's phenomenon; vasodilator should be used when symptoms are severe or combined with finger ulcers, especially recommended for calcium channel blockers - Nikol Ground level. Since nitrendipine can relax vascular smooth muscle, it was found to be very effective in reducing the frequency and severity of Raynaud's phenomenon in a double-blind controlled trial.

Treatment of fingertip ulcers can soak fingers in disinfectant; seal the ulcer with antibiotic ointment and then apply bandages, infected ulcers should be taken orally; for large non-infected ulcers, wear closed ends; for deep infections, cope tissue should be treated Surgical debridement is performed, and antibiotics are given intravenously. If it is ineffective, surgical resection is feasible.

2. Chinese medicine treatment

(1) Syndrome Differentiation: The disease is characterized by cold coagulation, damp heat, blood stasis, phlegm obstruction, and venous obstruction; the lung, spleen and kidney are yang deficiency and qi deficiency; the virtual syndrome is the main manifestation.

1 cold evil obstruction, lung defense does not declare:

Main symptoms: cold limbs, cold hands and feet, white and purple, facial or skin swelling without heat, and gradually hard, or cough, fever, aversion to cold, chest tightness, shortness of breath, thin white tongue, weak pulse or sputum.

Governing Law: qi and Xuanfei, Tongmai and cold.

Recipe: Huangqi Guizhi Wuwu Decoction and Mahuang Fuzi Xixin Decoction.

Astragalus 25g, white peony 25g, cassia twig 15g, ramie yellow 15g, gun aconite 15g, pangolin 15g, ginger 15g, jujube 10, asarum 3g, Wang does not stay 10g.

Addition and subtraction: when the skin edema, add white mustard 15g, soil glutinous rice 25g, Zhejiang Fritillaria 15g; when the skin becomes hard, add saponin 15g, soil mites 15g, silkworm 15g, locust skin 15g.

2 cold coagulation, spleen and kidney yang deficiency:

Main symptoms: the limbs are cold, the skin of the hands and feet becomes white and purple, the skin of the face or the extremities becomes hard and thin, accompanied by fatigue, dizziness, backache, bloating or swallowing. The tongue is pale, the fur is white, and the pulse is fine. Or late.

Governing Law: warming kidney and dispelling cold, strengthening the spleen and turbid, promoting blood circulation and collaterals.

Recipe: Yang and Tang add flavor.

Rehmannia 25g, white mustard 15g, antler gum 15g, cinnamon 15g, pangolin 15g, Wang does not leave 15g, saponin 15g, gun ginger charcoal 15g, ricin yellow 10g, licorice 15g.

Addition and subtraction: skin hardening can add water 蛭 10g, soil mites 15g; skin muscle atrophy plus jaundice 25g, cassia twig 15g, locust skin 15g, leeches 10g.

3 phlegm and blood stasis:

Main symptoms: hard skin, stubborn skin, numbness, dizziness, heavy body, acid and sinking, fixed facial expression, unpleasant swallowing or chest tightness, cough, or skin nails, nail depression, fingertip ulcer, tongue and greasy, The pulse is sinking or slippery.

Governing Law: 祛痰 blood circulation and collaterals.

Recipe: Siwu Decoction and Guitang Decoction.

Pinellia 15g, dried tangerine peel 15g, glutinous rice 15g, licorice 15g, gallbladder 15g, medlar 15g, glutinous 15g, windproof 15g, Atractylodes 15g, ginger juice 15ml, bamboo leaching 15g, spatholobus 25g, pangolin 15g, Wang does not stay Line 15g, saponin 10g, Angelica 15g.

Addition and subtraction: turbidity plus white mustard 15g, leeches 10g, silkworm 15g; qi deficiency plus jaundice 25g, Codonopsis 15g, cassia twig 15g; bloody sputum plus peach kernel, safflower each 15g, trigon 15g, sputum 15g .

4 qi and blood deficiency, the context of glory:

Main symptoms: thin skin, thin skin, thin skin, loss of facial expression, wrong skin, hair loss, thin nose, shortness of breath, shortness of breath, cough, fatigue, less bloating, weak limbs, less tongue and less moss, pulse Shen Fine or addicted.

Governing Law: qi and nourishing blood and collaterals. Recipe Shiquan Dabu Tang addition and subtraction.

Ginseng 15g, 茯苓15g, Atractylodes 15g, Zhigancao 15g, Rehmannia 20g, Chuanxiong 15g, Angelica 15g, Angelica 20g, Astragalus 25g, Cinnamon 15g, Pangolin 15g, Wang does not leave 15g, Earthworm 15g.

Addition and subtraction: joint pain is even more with spatholobus 30g.

5 wet heat damage Yang:

Main symptoms: swollen hands and metacarpophalangeal joints, skin color red, showing dachshund-like finger, with mouth bitter mouth dry to drink water, aversion to cold, pale tongue or white moist, slow pulse or sputum.

Governing Law: dampness and heat, and blood circulation.

Recipe: Xuanqi Tanghe Siwu Decoction.

Raw glutinous rice 20g, fried atractylodes 10g, wood anti-self 6g, almond 10g, talc 10g, forsythia 15g, Pinellia 10g, angelica 15g, motherwort 15g, Chuanxiong 15g, red peony 15g, safflower 15g, hematoxylin 15g, scorpion 10g .

Addition and subtraction: joint swelling is more than 15g; the pain is even more than the green wind vine 20g.

(2) Comprehensive treatment:

1 Chinese patent medicine: Xiaoshuan oral liquid, Danggui pill, still Shaodan, Kunming Shanhaiqi tablets, Danshen injection, Mailuoning injection, vasculitis tablets, Tripterygium wilfordii tablets, blood stasis granules, refers to the sputum pills .

2 single prescription:

A. Guangdi dragon, aphids, earthworms, and black-snake snakes are all fine, and each time 3g is served with decoction or warm water.

B. Asian saponins (snow tablet), 54 ~ 72mg / d, 3 times orally, for 6 to 12 months.

C. External phlegm method: soft skin phlegm prescription: 25g of sclerotium, 15g of white mustard, 15g of white peony, 15g of scallop, seaweed 20g, kelp 20g, 炙山甲15g, safflower 30g, solo 15g, Sichuan 15g of pepper, 15g of Chuanxiong, 15g of dew hive, 6g of borneol, 15g of saponin. The medicine is researched into fine powder, 500ml of white wine and 0.5kg of fine salt, mixed and evenly mixed, put into the gauze bag, steamed the medicine bag for 45min, and then taken out with a dry towel pad, rubbed on the hardened skin, so as not to burn the skin. For degree. Each time half an hour, 2 times / d, 1 medicine bag can be used for 10 days.

D. External coating method: Red spirit wine prescription: raw angelica 60g, safflower 30g, pepper 30g, cinnamon 60g, camphor 15g, asarum 15g, dried ginger 30g. Apply medicinal 50% alcohol 1000ml, soak for 7 days, and apply twice a day for 10 minutes.

E. Acupuncture Therapy: Acupuncture can be taken according to the symptoms.

3. Recovery

(1) Purpose and principle: The purpose of rehabilitation is to relieve pain, maintain muscle and joint function, prevent deformity, and improve patient self-care ability. The course of the disease is long, and most patients progress slowly. Therefore, the patient's condition and general condition should be known before treatment, and a long-term rehabilitation plan should be formulated. Step by step, no acute rehabilitation should be performed during the acute progression.

(2) Method:

1 systemic treatment: see the "Treatment" section.

2 thermotherapy: warm the bag to 70 ~ 80 ° C in hot water, and then wrapped in a towel placed on the affected area. Other heat treatments, mud treatments, steam baths, spa baths and wax treatments can alleviate the discomfort of hard skin and prevent joint disability.

3 body position therapy: maintain a good position, try to be in the functional position, prevent the internal rotation of the shoulder joint, elbow flexion, forearm pronation, wrist flexion, finger flexion, lower extremity hip external rotation, knee extension, ankle joint Turning, sagging and other postures and postures. Take the supine position while sleeping, the head is facing in the front direction, the shoulder strap is extended as far as possible, the shoulder joint is abducted and externally rotated, and a towel roll is placed between the upper arm and the trunk to prevent the shoulder joint from receiving the internal rotation and the elbow joint is kept in the extension. Position, the upper limb is placed on the soft pillow, the height of the hand should exceed the position of the heart, and the knee joint is straightened to avoid buckling deformity.

4 joint training method: including passive movement, active movement, auxiliary active movement, for the joint that has contracted, should be added active traction, free traction, continuous traction. Pay attention to the training: A. Determine the location where the external force is applied; B. Take full consideration of the fixed position and method of the patient's limb during passive exercise; C. Gradually increase the weight and continue to exert force in the restricted position to maintain And expand the degree of activity, and then gradually reduce the force to fully relax; D. Beginning of the red swelling period, the intensity should be reduced; E. The technique should not be rough, generally should be carried out in the painless range.

5 Infrared treatment: can improve local blood circulation, relieve muscle tension, and have a certain relief effect on hard skin.

6 Chinese medicine fumigation treatment: see the "treatment" section.

The above content is for reference only, please consult the relevant physician or relevant medical institution if necessary.

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 are exposed to 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: At present, most people think that the disease is likely to be an autoimmune disease caused by genetic factors and persistent chronic infection. Some cases often overlap with systemic lupus erythematosus, Hashimoto's thyroiditis, rheumatoid arthritis, and Sjogren's syndrome. Therefore, the above risk factors should be noted.

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 intralesional injection. 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.

(3) Level 3 prevention:

1 Progressive systemic scleroderma progresses slowly, and some have a tendency to relieve themselves. Do not stop or give up treatment easily.

2 pay attention to exercise, reasonable life rules, avoid emotional stimuli and changes.

3 At present, there is no specific drug to treat this disease. In the whole course of disease, it should actively cooperate with traditional Chinese medicine therapy, and the control of the disease is very important.

4 patients with Raynaud's phenomenon should pay attention to heat preservation to avoid cold stimulation.

5 No smoking.