Introduction to scleroderma

Introduction Scleroderma is a connective tissue disease characterized by localized or diffuse skin and visceral connective tissue fibrosis, sclerosis and atrophy. Its main features are skin, synovium, skeletal muscle, blood vessels and esophagus. Fibrosis 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 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. Etiology (1) The cause of the disease is still unclear, and it is summarized in the following aspects: (1) Genetic factors According to some patients, there is 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. 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. (B) pathogenesis 1. Pathogenesis (1) vascular injury theory: 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 organ. 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. Symptoms 1. Skin manifestations of early hand, finger swelling, but also involving the forearm, feet, lower limbs and face, but lower limb involvement. 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. Measurement of skin involvement: Regular testing of the extent and extent of affected skin will help to 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. Raynaud's 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: Renault phenomenon is divided into two categories: primary (idiotypic) Raynaud's phenomenon, also known as Raynaud's disease (Raynauds) Read more...