What Is Autoimmune Arthritis?

Autoimmune diseases refer to diseases caused by the body's own tissue damage caused by the body's immune response to autoantigens. The existence of autoantibodies and autoimmune diseases are not two equivalent concepts. Autoantibodies can exist in normal people without autoimmune diseases, especially the elderly, such as antithyroglobulin, thyroid epithelial cells, gastric parietal cells, and nuclear DNA Wait. Sometimes, damaged or changed antigenicity can trigger the production of autoantibodies. To determine the existence of autoimmune diseases generally need to be based on: the existence of an autoimmune reaction, the possibility of secondary immune response, the existence of other causes.

Autoimmune disease

Autoimmune disease

Autoimmune diseases refer to diseases caused by the body's own tissues caused by the immune response to autoantigens. Since Donath and Landsteiner proposed this concept, many diseases have been listed as

Immunodeficiency disease is a group of diseases caused by decreased or missing immune function caused by congenital hypoplasia or acquired impairment of the immune system.

The exact pathogenesis of autoimmune diseases is unknown and may be related to the following factors:

1. Loss of immune tolerance

The incidence of autoimmune diseases such as multiple sclerosis and type 1 diabetes has soared in developed countries in recent decades. In three recent studies published in Nature, researchers at the Broad Institute, Brigham Women's Hospital, Harvard University, MIT, and Yale University have described a molecular pathway that causes autoimmunity Sexual diseases, identify the culprit: salt. ^[1]

Autoimmune diseases can be divided into two categories:

(A) organ-specific autoimmune diseases

The pathological damage and dysfunction of tissues and organs is limited to an organ targeted by antibodies or sensitized lymphocytes. Mainly chronic chronic thyroiditis, hyperthyroidism, insulin-dependent diabetes, myasthenia gravis, chronic ulcerative colitis, malignant anemia with chronic atrophic gastritis, goodpasture syndrome, pemphigus vulgaris, Pemphigoid, primary biliary cirrhosis, multiple cerebrospinal sclerosis, acute idiopathic polyneuritis, etc., the common ones will be described separately in each system disease.

(Two) systemic autoimmune diseases

Due to the extensive deposition of antigen-antibody complexes on the walls of blood vessels and other causes of multiple organ damage throughout the body, it is called a systemic auto-epidemic. It is also commonly known as collagen disease or connective tissue disease, which is caused by the cell wall and interstitial cell-like necrotic inflammation caused by immune damage and subsequent proliferation of collagen fibers in multiple organs. In fact, no matter from the perspective of ultrastructure and biochemical metabolism, most of the collagen fibers have no primary changes. The following briefly describes several common systemic autoimmune diseases.

1. Systemic lupus erythematosus (SLE) is a relatively common systemic autoimmune disease. It has a variety of autoantibodies, mainly antinuclear antibodies, and extensive small arterial disease and multisystem involvement. Clinical manifestations are mainly fever, skin lesions (such as facial butterfly erythema) and damage to joints, kidneys, liver, serosal membranes, and reduction of whole blood cells. It is more common in young women. The ratio of male to female is 1: 6-9. The course of disease is repeated and the prognosis is poor.

Etiology and pathogenesis The etiology and pathogenesis of this disease are unknown. The current research mainly focuses on the following three aspects.

(1) Immune factors: A variety of autoantibodies are formed in the patient's body, suggesting that B-cell activity is the basis of the disease. The results of in vitro culture of peripheral blood B cells found that their proliferation ability was 8-10 times stronger than normal.

(2) Genetic factors: The relationship between genetic factors and the disease is:

There is a high (69%) consistency in homozygous twins,

The possibility of onset is significantly increased among family members of SLE patients,

SLe is related to HLA DR2 and DR3 in North American whites. This may be because the immune response gene (Ir) in the HLA D region has a regulatory effect on the extent of the immune response triggered by the antigen (including autoantigens).

(3) Others: Non-genetic factors also play a role in initiating autoimmune responses. These factors include: drugs: hydralazine hydrochloride, procainamide, etc. can cause SLE-like reactions. However, it often heals itself after drug withdrawal; Virus: Type C virus infection is found in spontaneous SLE-like disease in experimental animals NZB and NZB / WF1 mice, and virus antigen-antibody complexes can be detected in glomeruli . However, viral factors have not been fully confirmed in SLE disease; sex hormones have an important effect on the occurrence of SLE, androgen seems to have a protective effect, while estrogen seems to have a promoting effect, so the majority of patients are women, especially Occurs during the reproductive age, and the condition worsens during menstruation and pregnancy.

Autoantibodies and tissue damage mechanisms There are a variety of autoantibodies in patients with this disease. More than 95% of patients are positive for antinuclear antibodies, and anti-DNA (double-stranded, single-stranded), anti-histone, anti-RNA-non-histone, and anti-ribose may appear. Nucleoprotein (mainly Smith antigen), anti-granulocyte, anti-platelet, anti-smooth muscle and other antibodies, of which anti-double-stranded DNA and anti-Smith antigen are relatively specific, with positive rates of 60% and 30%, while in other connective tissues The positive rates of disease were all below 5%.

Antinuclear antibodies are not cytotoxic, but they can attack granulocytes that are degenerate or have damaged cell membranes. Once they contact the nucleus, they can swell the nucleus, become a homogeneous piece, and be squeezed out of the cell body to form lupus (LE ) Corpuscles, LE corpuscles have chemotaxis to neutrophils and macrophages, and can promote cell phagocytosis in the presence of complement. The cells that engulf the LE bodies are lupus cells. In tissues, LE bodies are round or oval, and hematoxylin is stained with blue during HE staining, so it is also called hematoxylin, which is mainly found in glomeruli or renal interstitial. Hematoxylin bodies are usually detectable in only 20% of patients, which is the characteristic basis for the diagnosis of SLE.

The tissue damage of SLE is related to the presence of autoantibodies. Most visceral lesions are mediated by immune complexes (type III allergy). Among them, the vascular and glomerular lesions caused by DNA-anti-DNA complexes are the second, followed by specificities. Sexual anti-erythrocytes, granulocytes, and platelet autoantibodies cause damage and lysis of the corresponding blood cells through type allergy, causing total anemia.

Lesions Acute necrotizing arterioles and arteritis are the basic lesions of the disease, which are present in almost all patients and involve all organs of the body. The active lesions are mainly cellulosic necrosis. In the chronic phase, vascular wall fibrosis is obvious, the lumen is narrow, lymphocyte infiltration with edema and increased stroma around the blood vessel. Sometimes the vascular adventitial fibroblasts have obvious proliferation, collagen fibers increase, and an onion skin-like structure is formed. The changes in the central spleen artery are most prominent. The use of immunohistochemical methods can confirm the presence of immunoglobulins, complements, fibrin, and DNA in the affected blood vessel walls, suggesting the involvement of the antigen-antibody complex mechanism.

(1) Kidney: Renal failure is the leading cause of death in SLE. Almost all patients with SLE have different degrees of renal damage. About 60% of the patients are mainly manifested by lupus nephritis. Common types are mesangial proliferative type (10% to 15%), and focal proliferative type (10% to 15%). ), Diffuse hyperplasia type (40% -50%) and membrane type (10% -20%). The lesions of various types of lupus nephritis are similar to the corresponding primary glomerulonephritis. There is often crossover between the various types of lesions. Therefore, the glomerular lesions are diverse, and the typical manifestations of sclerosing nephritis may occur in the later stages. The occurrence of nephritis lesions is mainly based on the deposition of immune complexes in the glomerulus, which can be located in the mesangial area, subendothelium and subepithelium. Among them, the deposition of a large number of immune complexes under the endothelium in diffuse proliferative lupus nephritis is a characteristic lesion in the acute phase of SLE. In diffuse proliferative and membranous cases, about half of the cases also have immune complex deposition on the interstitial and tubule basement membranes. Therefore, glomerular lesions and interstitial inflammation are very obvious in lupus nephritis. The appearance of hematoxylin bodies has clear diagnostic significance.

(2) Skin: About 40% of patients with SLE have obvious skin damage. The facial butterfly erythema is the most typical and can also involve the trunk and limbs. Under the microscope, the epidermis often has atrophy, hyperkeratosis, hair follicle keratin plug formation, basal cell liquefaction, edema at the junction of the epidermis and dermis, fibrous necrosis of the collagen fibers of the basement membrane, arteriolar wall, and dermis. There is lymphocytic infiltration. Immunofluorescence confirmed the deposition of IgG, IgM, and C3 at the junction of the dermis and epidermis, forming a granular or clump-like fluorescent band called "lupus band", which may be the antigen released by necrotic epithelial cells and the antinuclear antibodies dispersed in the blood circulation Immune complexes formed by autoantibodies. The presence of lupus bands has diagnostic significance for this disease.

(3) Heart: About half of the cases have heart involvement, and non-bacterial verrucous endocarditis or Libman-Sach endocarditis is the most typical. The characteristics are: the size is from 1mm to 3 ~ 4mm, the number is singular or multiple, and the distribution is very irregular, which can involve the intima or chordae before or after the valve. Under the microscope, the neoplasm is composed of fibrin and necrotic debris and inflammatory cells. The root matrix has cellulose-like necrosis, accompanied by infiltration of inflammatory cells, and later stage mechanization.

(4) Joints: More than 90% of cases have joint involvement in varying degrees. Synovial congestion and edema, with more mononuclear cells infiltration. Focal cellulosic necrosis can occur in the connective tissue immediately adjacent to the superficial part of the epithelium, but it rarely invades deep tissues such as articular cartilage, so it rarely causes joint deformities.

(5) Liver: Liver damage can occur in about 25% of cases, which is called lupus hepatitis. It can be manifested as typical lesions of chronic active hepatitis such as mononuclear cell infiltration in the manifold area and surrounding manifold areas, and debris-like necrosis of nearby liver cells. There can also be only a small number of scattered small focal necrosis and other minor lesions.

(6) Spleen: The volume is slightly increased, the capsule is thickened, and the follicular hyperplasia is quite common. There are many plasma cells in the red pulp, containing IgG and IgM. The most prominent change is fibrosis around the arterioles, forming an onion skin-like structure.

(7) Lymph nodes: Systemic lymph nodes are swollen to varying degrees and sinus endothelium is hyperplasia. Among them, more plasma cells and small blood vessels were observed in the same way as the spleen. 2. Sjgren syndrome is characterized by dry eyes and dry mouth, which is caused by immune damage to salivary and lacrimal glands. This disease can exist alone or concurrently with other autoimmune diseases, the most common of which are rheumatoid arthritis and SLE. The lesions mainly involve the salivary and lacrimal glands, and other exocrine glands including the respiratory and digestive tract glands can also be affected.

The histological lesions of salivary glands are mainly manifested by a large number of infiltrating inflammatory cells around the glandular ducts, mainly lymphocytes and plasma cells. Sometimes, lymphatic follicles can be formed and germinal centers formed. With glandular epithelial hyperplasia, causing lumen obstruction. The advanced acinar atrophy and fibrosis were replaced by adipose tissue. Individual cases of infiltrating lymphocytes form lymphoma-like structures. Oral mucosa dryness and ulceration due to the destruction of salivary glands.

Similar lesions of the lacrimal gland can cause dry corneal epithelium, inflammation, and ulcers. Respiratory and digestive tract involvement can lead to corresponding rhinitis, laryngitis, bronchitis, pneumonia, and atrophic gastritis. Interstitial nephritis can occur in the kidney, and a large number of mononuclear cells infiltrate the renal tubules, leading to renal tubular atrophy and fibrosis. Renal tubular acidosis and phosphate urine are common due to impaired renal tubular function.

Lymph nodes are enlarged and have proliferative changes, and there are many mitoses, so they are also called pseudolymphomas. It is worth mentioning that patients with this disease are 40 times more likely to develop malignant lymphoma than normal people.

Pathogenesis The pathogenesis of this disease is unclear. SLE and rheumatoid arthritis are often associated, suggesting that the occurrence of this disease is related to immune damage. The patient's B-cell function was excessive, manifested by polyclonal hyperglobulinemia and the formation of rheumatoid factor (RF), antinuclear antibodies, cryoglobulin, and anti-salivary gland antibodies. In recent years, two characteristic autoantibodies against ribonucleoprotein have been found, named anti-SS-B and SS-A, respectively. They have a high positive rate (60%, 70%) in this disease. The diagnosis is valuable. There was a large amount of B and T cell infiltration at the lesion, most of which were T helper cells, and some were T killer cells, suggesting that the cellular immune mechanism was also involved.

3 Rheumatoid arthritis Rheumatoid arthritis is a chronic systemic autoimmune disease. It mainly invades joints throughout the body, presenting multiple and symmetrical chronic proliferative synovitis, which causes the destruction of articular cartilage and joint capsule, and finally leads to joint ankylosing. In addition to joints, other organs or tissues of the body can also be affected, including subcutaneous tissue, heart, blood vessels, lungs, spleen, lymph nodes, eyes and serosa. The age of onset of this disease is mostly between 25 and 55 years old, and is also found in children. The incidence is 2 to 3 times higher in women than in men. The disease has a chronic course, and the lesions increase and relieve repeatedly alternately. Rheumatoid factor (RF) and its immune complexes are present in the plasma of most patients.

Pathological changes

(A) basic lesions

Rheumatoid arthritis is a systemic immune disease. In the joints and other affected organs and tissues, there is infiltration of lymphocytes, plasma cells, and macrophages, which are closely related to the immune response, and can be associated with lymphoid follicle formation. In addition, the disease mainly involves connective tissue, which belongs to collagen disease. Interstitial collagen fibers and blood vessels in the whole body can show cellulosic degeneration or necrosis (probably caused by the deposition of local immune complexes).

The formation of rheumatoid granuloma (rheumatoid granuloma) or rheumatoid nodule (rheumatoid nodule) is formed, which has certain characteristics. Under the microscope, the center of the nodule is a large piece of cellulose-like necrosis, with epithelial cells arranged in a grid-like or radial manner around the nucleus, and the periphery is proliferated with capillaries and fibroblasts, with the infiltration of the above-mentioned inflammatory cells. Finally, fibrosis occurs. Rheumatoid nodules mainly occur on the skin, followed by the heart, lungs, spleen, and serosa.

Vasculitis: It mainly occurs in small veins and arteries, of varying severity. A few severe cases have fibroid necrotizing arteritis, often accompanied by thrombosis.

(II) Lesions of various organs

1. Joint disease is the most common, mostly multiple and symmetrical, often involving small joints of the hands and feet, especially the proximal interphalangeal, metacarpophalangeal, and metatarsophalangeal joints, followed by the knee, ankle, wrist, elbow, hip, and spine And so on.

(1) Synovial lesions: In the early stage, the main lesions are in the synovium, which can be divided into acute and chronic phases. There is no clear boundary between the two.

In acute synovitis, joint swelling, hyperemia and edema of the synovium, focal necrosis and fibrous covering of the synovial tissue can be seen. Although neutrophil infiltration can be seen at this stage, lymphocytes and macrophages are the main ones. There is cloudy milky fluid in the joint cavity, or fibrin clots can be seen.

Chronic synovitis has more characteristic changes, manifested as:

There are a large number of lymphocytes, macrophages and plasma cells infiltration in the synovium, and lymph nodes can be formed. The germinal center can be seen in those with a longer course of disease.

Synovial cells proliferate actively and can form multiple layers, with multinucleated giant cells visible. The latter has a slightly basophilic cytoplasm, ranging from 2 to 12 nuclei, mostly in a flower-ring arrangement at the periphery of the cytoplasm. Under the electron microscope, the proliferating synovial cells were mainly type B (fibroblast-like cells), while multinucleated giant cells were similar in morphology to type A synovial cells (macrophage-like cells).

Synovial villous hyperplasia and vascular formation. Chronic inflammation of the synovium leads to the proliferation of new blood vessels and fibrous tissue. The synovium is irregularly thickened, and many villous protrusions are formed and extend to the joint cavity. The fluff diameter is about 1 ~ 2mm, and the length can reach 2cm. These nodules are often located at the ends of the villi. Vasculitis changes can be seen in the synovium, or focal necrosis, or small focal hemorrhage and hemosiderin deposition can be seen, and cellulose deposition can be seen on the synovial membrane and villus surface.

The inflammatory granulation tissue in the synovium expands to the edge of the articular cartilage, forming pannus, and gradually covers and destroys the articular cartilage.

(2) Articular cartilage changes: Acute synovitis can subside without involving articular cartilage, but when inflammation recurs and becomes chronic, articular cartilage is almost necessarily damaged. The earliest manifestation was that the metachromaticity of the matrix weakened or disappeared, which was confirmed by staining with toluidine blue. Vascular crests formed at the edges of articular cartilage directly erode and damage articular cartilage, and cartilage erosion and small focal necrosis can be seen at the interface between the two. As the vascular crest gradually extended and covered the entire articular cartilage surface, the articular cartilage was severely damaged and eventually replaced by the vascular crest.

Chronic chronic inflammation and recurrent episodes, synovial membrane proliferation, fibrous tissue accumulation, fibrous exudates in the joint cavity, and continuous mechanization and scarring, narrowing the joint cavity, at the same time, the articular cartilage is destroyed and replaced by vascular crests. Fibrous adhesions occur on the two articular surfaces, forming fibrous joint ankylosis, which can eventually develop into bony joint ankylosis. Due to muscle spasms and tendon relaxation around the joints, joint dislocation or subluxation can be caused, and joint deformities are aggravated.

(3) Changes in joint adjacent tissues:

Chronic rheumatoid arthritis can cause bone tissue absorption and osteoporosis near the joints and bone destruction under the joint cartilage. Sometimes small capsule cavities can be seen, and occasionally the nearby cortex is eroded and damaged, which can lead to pathological fractures. These changes are related to bone resorption by osteoclasts and macrophages, long-term application of corticosteroids, and the spread of arthritis.

The tendons, ligaments and muscles around the joint are often affected, with focal lymphocytes, plasma cells, and macrophages infiltration, and occasionally rheumatoid nodules. Muscle atrophy.

Draining lymph nodes of joint lesions are enlarged, lymphoid tissues are proliferated, germinal centers are obvious, and rheumatoid granulomas are occasionally formed.

2. Rheumatoid disease changes other than joints are not common, and are often associated with those with significant active joint disease.

(1) Subcutaneous nodules: It is the most common in rheumatoid diseases other than joints. It is found in about 20% to 25% of cases. It is mostly located near the joints, and it is most common in bone protrusion and compression sites such as the olecranon process. Single or multiple, ranging from a few millimeters to 2cm in size, hard and no tenderness. The macroscopic view was gray-white, with a yellow-colored necrotic area in the center, and a typical rheumatoid granulomatous change was seen under the microscope. Subcutaneous nodules exist for a long time and can persist for months or years.

(2) Heart and lung lesions: Rheumatoid granulomatosis, vasculitis and infiltration of lymphocytes, plasma cells, and macrophages can appear in many organs and tissues, but are more common in the heart (endocardium, myocardium, and Epicardial) and lungs, eventually leading to focal or diffuse interstitial fibrosis of the heart and lungs. Occasionally causes heart valve deformation and insufficiency. Serous membrane involvement causes fibrous pericarditis and pleurisy, and finally causes extensive thickening and adhesion of the pericardium and pleura.

3, vascular disease: occasional acute fibroid necrotizing arteritis, often accompanied by thrombosis and infarction of the corresponding tissue. The aorta can also be affected.

Etiology and pathogenesis

At present, this disease is generally considered to be an autoimmune disease. The initiating factor is unknown. It may be that infectious factors (such as viruses, mycoplasma, or bacteria) enter the human body, and some of the components (such as oligosaccharides or sugars) Peptide fragments) are taken up by synovial cells in the joints and combined into proteoglycans synthesized by synovial cells, making their structure changed and antigenic. This kind of autoantigen can not only make the body produce antibodies (IgG), but also cause the Fc fragment structure of the IgG molecule to change, forming new antigenic determinants, thereby stimulating the formation of another antibody, rheumatoid factor (RF).

The most important component of RF in serum is IgM, and there are also IgG, IgA, and IgE. IgM type RF is found in about 85% to 95% of rheumatoid arthritis patients and is an important indicator for clinical diagnosis. The immune complexes formed by RF and IgG of various immunoglobulin types are present in the blood circulation. RF and immunoglobulins can be synthesized in the joints and combined to form immune complexes. RF-IgG complexes can also be deposited in local tissues in the circulation, which is closely related to the occurrence of joints and extra-articular organs and tissue lesions. The RF-IgG complex in the synovial joint can fix and activate complement, produce C3a and C5a, and attract neutrophils and monocytes to exudate.

Neutrophils, monocytes, and synoviocytes (type A cells), after engulfing the immune complex, are activated and synthesize and release lysosomal enzymes, including neutral proteases, collagenases, and various media such as Prostaglandins, leukotrienes, IL-1, etc., cause destruction of synovium and articular cartilage. IL-1 is the main mediator of rheumatoid arthritis and is produced by activated macrophages and synovial cells. IL-1 enables synovial cells and chondrocytes to synthesize and release collagenase and other proteolytic enzymes, and inhibits chondrocytes from synthesizing proteoglycans, which itself is an osteoclast activating factor.

Not only RF, various immunoglobulins and complements in the synovium, but also immunofluorescence and tissue culture also show that they can be produced by B cells and plasma cells in the synovium. Even when the initiating factors (such as infectious factors) no longer exist, RF is still generated, resulting in repeated episodes of inflammatory lesions and chronic inflammation.

The research results show that in addition to the humoral immune factors mentioned above, the disease is also closely related to cellular immunity. As synovial lesions became chronic, T cells and plasma cells increased significantly, mainly T4 helper cells. T4 works synergistically with B cells, participates in RF and immunoglobulin synthesis, increases HLA-DR positive macrophages and dendritic cells in the synovium, interacts with T4, and is also related to the immune mechanism that causes joint damage.

Regarding the relationship between infectious agents and the disease, the role of EB virus infection has been noticed in recent years. Approximately 65% to 93% of rheumatoid arthritis patients have EB virus core antibodies in their sera, while other arthritis patients only have 10% to 29%. In addition, B cells from cell culture of patients with this disease have been transformed by EB virus. Can generate RF.

4 Scleroderma, also known as progressive systemic sclerosis, is characterized by excessive fibrosis of interstitial tissue in many organs throughout the body. More than 95% of patients have skin involvement; however, striated muscle and many organs (gastrointestinal tract, lung, kidney, heart, etc.) are the main damage of this disease. Those with severe lesions can cause organ failure and threaten life.

Etiology and pathogenesis The etiology of this disease is unknown, and its incidence may be related to the following factors:

(1) Increased collagen synthesis: In vitro culture confirmed that patients 'fibroblasts' ability to synthesize collagen is significantly higher than that of normal people, and the synthesis exceeds degradation, resulting in the accumulation of a large amount of collagen fibers;

(2) Type IV allergic reactions: T cell infiltration in skin lesions, secreted lymphokines and factors that stimulate macrophages can stimulate fibroblasts to synthesize collagen in large amounts;

(3) Autoantibodies: 50% of patients have mild hypergammaglobulinemia and a variety of autoantibodies, including RF, anti-smooth muscle antibodies, antinuclear antibodies, etc., which may be due to the deposition of antigen-antibody immune complexes or endothelial cytotoxicity. Effect, causing damage to small blood vessel endothelial cells, thrombosis, fibrosis of the wall of the tube, narrowing of the lumen, leading to tissue hypoxia and causing fibrous interstitial hyperplasia.

Lesion

(1) Skin: The lesion begins at the fingertips and develops concentrically, involving the forearm, shoulders, neck, and face, and restricting joint movements. Early affected skin is edema and tough. Microscopically, the main manifestations are infiltration of lymphocytes around small blood vessels, swelling of capillary endothelial cells, thickening of the basement membrane, partial obstruction of the lumen, interstitial edema, swelling of collagen fibers, and enhanced eosinophilia. With the development of lesions, collagen fibers in the dermis increased significantly, and tightly combined with the subcutaneous tissue, the epidermal atrophy flattened, melanin increased, the adenoid process and appendage atrophy disappeared, small blood vessels thickened, and hyaline changes. In the later stage, the fingers are thin and claw-shaped, the joints are restricted in motion, and sometimes the finger tip is necrotic or even detached, and the facial expression is pseudomask-like.

(2) Gastrointestinal tract: About 1/2 of the patients are affected by the digestive tract, the epithelium of the mucosa is atrophied, the lamina propria, submucosa and muscle are replaced by a large number of collagen fibers, and mononuclear cells infiltrate the perivascular area. The lesions were most severe in the 2/3 segment below the esophagus, with narrow lumen and lack of elasticity. The small intestine and colon can also be affected. Symptoms such as dysphagia and indigestion appear clinically.

(3) Renal: The interlobular arteriolar lesions are the most prominent, manifested by endometrial mucoid degeneration, accompanied by endothelial cell proliferation and subsequent wall fibrosis and markedly narrowed lumen, and in some cases, arteriolar fibroid necrosis. Hypertension may occur clinically, and it is difficult to distinguish it from malignant hypertensive nephropathy. Approximately 50% of patients die from renal failure.

(4) Lungs: diffuse interstitial fibrosis, alveolar dilatation, rupture of the alveolar septum, and the formation of a cystic cavity. This disease is one of the important causes of honeycomb lungs.

5. Nodular polyarteritis Nodosa polyarteritis (polyarteritis nodosa) is a disease of the systemic arterial system, manifested as necrotic inflammation of the small and medium arterial walls. The majority of patients are young people, and sometimes they can occur in children and the elderly, and the ratio of male to female is 2 to 3: 1.

The small and medium arteries of all diseased systems or organs can be affected, with kidney (85%), heart (75%), liver (65%), and digestive tract (50%) being the most common. In addition, the pancreas, testes, skeletal muscles, nervous system, and skin can also be affected.

The lesions are mostly segmental, with the bifurcation being the most common. From the inside view, small white nodules with a diameter of about 2 to 4 mm formed at the lesion, and the appearance of the vessel wall between the nodules was normal. Microscopically, the acute phase is manifested as acute necrotic inflammation. The lesions start from the inner layer of the intima and the middle layer and extend to the whole layer of the tube wall and around the outer membrane. The fibrous necrosis is quite significant. The infiltration with inflammatory cells is especially acidophilic and There are many neutrophils, followed by thrombosis. Subsequent advances were fibrous hyperplasia, tube wall thickening, mechanized occlusion of the lumen, and significant fibrosis around the arteries. It is worth noting that early inflammatory necrosis changes and later collagenization can coexist. The main consequences of the lesion are ischemic damage and infarction formation.

The disease is widely distributed and the clinical manifestations are varied. Patients often have symptoms of low fever, fatigue, increased granulocytes, and multisystem involvement, such as hematuria, renal failure, hypertension, abdominal pain, diarrhea, black stool and peripheral neuritis. The course of disease varies, and 55% of patients survive after immunosuppressive treatment.

The etiology and pathogenesis are unknown. Animal experiments suggest that humoral factors play an important role in the occurrence of this disease. Immunofluorescence technology confirmed that human nodular polyarteritis has vascular wall immunoglobulins and complements, and some have HBsAg. About 50% of patients have positive serum HBsAg or anti-HBs.

6. Wegener's granulomatosisWegener's granulomatosis is a rare disease with the following characteristics:

Acute necrotizing vasculitis of small blood vessels can involve the blood vessels of various organs. The respiratory tract, kidney, and spleen are most commonly affected. Presented as fibroid necrosis of the arterioles and venule walls, with diffuse neutral and eosinophil infiltration;

Granulomatous necrotic lesions of the respiratory tract can affect the mouth, nasal cavity, paranasal sinuses, throat, trachea, bronchi and lungs. The lesion is a granuloma composed of a large number of accumulated mononuclear macrophages, lymphocytes and a small number of multinucleated giant cells, epithelioid cells, and fibroblasts, and the center can be trapped into pieces of coagulative necrosis. Obvious lumps often form on the naked eye, and ulcers form on the surface due to necrosis and ulceration;

Necrotizing glomerulonephritis, manifested as fibrous necrosis with segmental capillary loops, and thrombosis, which can develop rapidly if untreated, on the basis of focal or diffuse proliferative glomerulonephritis. Progressive nephritis, with a dangerous course and progressive renal failure.

The etiology of this disease is unknown, due to obvious vasculitis, and immunoglobulin and complement can be detected locally, suggesting that its pathogenesis is related to type III allergies. However, granuloma and necrotic lesions in the respiratory tract also suggest that it may be related to type allergies. Most of the clinical application of cytotoxic drugs can alleviate the disease.