Introduction to rheumatoid arthritis (RA)

Introduction: The cause of rheumatoid arthritis is still not very clear. Most of them are considered to be autoimmune diseases of the human body. They can also be regarded as a chronic syndrome, which is characterized by non-specific inflammation of the peripheral joints. At this time, the diseased joint and its surrounding tissues are progressively destroyed, and the synovitis is persistent and recurrent, which may lead to destruction of cartilage and bone in the joint, joint dysfunction, and even disability. Vasculitis lesions involve various organs of the body, so this disease is also known as rheumatoid disease. The incidence of rheumatoid arthritis is higher in women than in men, and women are 2 to 3 times more likely than men; the incidence rate in European and American countries is significantly higher than that in Chinese. Causes: 1. The cause of the disease is not completely clear. Rheumatoid arthritis is a disease that is closely related to factors such as the environment, cells, viruses, genetics, sex hormones, and neuropsychiatric states. (1) Bacterial factors Experimental studies have shown that group A streptococci and peptidoglycan may be a persistent stimulator of RA, and group A streptococci have long-lasting antigens in the body, stimulating the body to produce antibodies. , caused by immunopathological damage. The arthritis animal model produced by Mycoplasma is similar to human RA, but does not produce rheumatoid factor (RF) specific to human RA. Bacterial or bacterial antigenic material has never been found in the synovial fluid and synovial tissue of RA patients, suggesting that bacteria may be involved in the onset of RA, but lacks direct evidence. (2) Viral factors The relationship between RA and viruses, especially EB virus, is one of the issues that scholars at home and abroad pay attention to. Studies have shown that arthritis caused by EB virus infection is different from RA, and RA patients have strong reactivity with EB virus than normal people. There is a persistently high level of anti-EBV-membrane antigen antibody in serum and synovial fluid of RA patients, but so far no Epstein-Barr virus nuclear antigen or capsid antigen antibody has been found in the serum of RA patients. (3) Genetic factors The incidence of this disease is high in some families. In the population survey, human leukocyte antigen (HLA)-DR4 was found to be associated with RF-positive patients. HLA studies have found that DW4 is associated with the pathogenesis of RA. 70% of patients are HLA-DW4 positive, and patients have susceptibility genes at this point, so inheritance may play an important role in the pathogenesis. (4) Sex hormone studies have shown that the incidence of RA is between 1:2 and 4, the condition of pregnancy is reduced, and the incidence of contraceptives is reduced. Animal models show that LEW/n females have high sensitivity to arthritis and low male incidence. After male rats are treated with castration or treated with β-estradiol, arthritis occurs in the same way as female mice, indicating that sex hormones are in RA. It plays a role in the onset. Cold, damp, fatigue, malnutrition, trauma, mental factors, etc., are often the predisposing factors of this disease, but most patients often have no obvious incentives before. (B) The pathogenesis of pathogenesis has not been fully defined, and it is considered that RA is an autoimmune disease that has been widely recognized. Those with HLA-DR4 and DW4 antigens have high sensitivity to external environmental conditions, viruses, bacteria, neuropsychiatric and endocrine factors. When invading the body, they change the HLA antigenic determinant to make HLA Nuclear cells become targets of immunosuppression. Since the HLA gene produces a property that can carry a T cell antigen receptor and an immune-related antigen, when an external stimulating factor is recognized by a macrophage, T cell activation and release of a series of immune media are generated, thereby generating an immune response. Intercellular interactions result in excessive activation of B cells and plasma cells to produce a large number of immunoglobulins and rheumatoid factors (RF), resulting in the formation of immune complexes and deposition on synovial tissue, simultaneously activating complement and producing multiple allergies. Toxins (C3a and C5a chemokines). Local factors such as IL-1, tumor necrosis factor a, and leukotriene B4 produced by monocytes and macrophages can stimulate my nucleated leukocytes to migrate into the synovium. Local angiogenesis of prostaglandin E2 can also promote the entry of inflammatory cells into the inflammatory site, phagocytose immune complexes and release lysosomes, including neutral proteases and collagenases, destroy collagen elastic fibers, and make the synovial surface and articular cartilage damage. RF can also be seen in the flash cells of the lubricated membrane, the proliferating lymphoid follicles and the synovial cells, and the IgG-RF complex can also be seen. Therefore, even if the infection factor does not exist, RF can be continuously generated, causing the onset of the lesion. Become a chronic inflammation. The RF synovium is characterized by the presence of several products secreted by active lymphocytes, macrophages, and other cells. These cellular active substances include a variety of factors: T lymphocytes secrete such as interleukin II (IL-2), IL-6. , granulocyte-macrophage stimulating factor (GM-CSF), tumor necrosis factor a, variant growth factor β: factors derived from activated macrophages include IL-1, tumor necrosis factor a, IL-6, GM-CSF Macrophage CSF, platelet-derived growth factor: Active substances secreted by other cells in the synovium (fibroblasts and endogenous cells) include IL-1, IL-6, GM-CSF and macrophage CSF. These cellular active substances can account for many of the characteristics of rheumatoid synovitis, including inflammation of the synovial tissue, proliferation of the synovium, damage to cartilage and bone, and the whole body of RA. The cellular active substances IL-1 and tumor necrosis factor activate activated chondrocytes and produce collagenase and proteolytic enzymes to destroy local cartilage. RF includes IgG, IgA, and IgM, and plays an important role in the occurrence of systemic diseases. IgG-RF itself has both antigen and antibody binding sites, and can form diploids or multimers by itself. The immune complex containing IgG is deposited in the synovial tissue, which stimulates the synovial membrane to produce IgM0 and IgA type RA. IgG-RF, in turn, binds to an immune complex containing IgG, which has a greater ability to activate complement than a simple IgG-containing immune complex. 1. Joint lesions (1) Changes in synovial membrane: joint lesions begin with synovial membrane, synovial congestion, edema. The synovial membrane near the edge of the cartilage is most pronounced. There is fibrin exudate covering on the surface of the synovial membrane. The synovial membrane has lymphocytes, plasma cells and a small amount of multinucleated granulocyte infiltration. Cells infiltrated in the lower layer of the synovial membrane form a "lymphoid nodule", some of which accumulate around small blood vessels. The surface cells of the synovial membrane proliferate in a fence-like shape, and the surface villi proliferate. In the late stage, most of the infiltrating cells are plasma cells, and there is exudate in the joint cavity. (2) Granuloma formation: After the acute inflammation subsides, the oozing waves are gradually absorbed. Fibroblasts proliferate around the capillaries at the site of cell infiltration. The synovial cells are columnar and arranged in a fence, and the synovial membrane is thickened and fluffy. The blood vessels in the synovial membrane proliferate, and the blood vessels in the synovium increase, which is a granuloma, which adheres to the cartilage and invades the cartilage. There are lysosomal vacuoles in the endothelium cells; there are plasma cells around the blood vessels, and "rheumatoid cells" are found in the synovium. (3) Changes in articular cartilage and subchondral bone: As the granulation tissue of the granulation tissue, which is caused by the synovial membrane, intrudes into the cartilage, it gradually spreads to the central part of the cartilage, blocking the cartilage from absorbing nutrients from the synovial fluid, and the cartilage is gradually absorbed. At the same time, due to the release of protein degrading enzymes and collagenase in the lysosome, the cartilage matrix is destroyed and dissolved, resulting in extensive destruction of the articular cartilage, narrowing of the joint space, rough joint surface, adhesion formation after vasospasm, and fibrous tissue proliferation. Extensive adhesions are formed in the joint cavity, which significantly restricts joint function and forms fibrous rigidity. After most of the articular cartilage surface is absorbed, the large area of the subchondral bone breaks and grows at the same time, forming new bone between the bone ends, and causing the joint bone tough. Due to long-term repeated fluid accumulation in the joint, the joint capsule and its surrounding ligaments are pulled and prolonged and relaxed. In addition, the destruction of the articular surface and the bone end narrows the joint space and makes the joint ligament more relaxed. Due to joint inflammation and cartilage surface damage, patients are often in a forced position due to pain. Protective muscles occur in the muscles around the joints. Muscles, tendons, ligaments, and fascia around the joints are also invaded by the lesions, and even rupture, eventually leading to dislocation of the joint or deformity of the bone. 2. Extra-articular manifestations (1) Rheumatoid subcutaneous nodules: Rheumatoid subcutaneous nodules are reliable evidence for the diagnosis of rheumatoid arthritis, nodules are granulomatous changes, and the central necrotic area contains IgG and RF immune complexes. Surrounded by fibroblasts, lymphocytes and monocytes, it eventually becomes dense connective tissue. (2) tendon and tendon sheath, bursitis inflammation: tendon and tenosynovitis are common in the hands and feet, tendon and sheath have lymphocytes, monocytes, plasma cells infiltration. In severe cases, the nodules on the palate can be touched, and the tendons can be broken and adhered, which is the cause of the deformity of the surrounding joints. The bursitis is more common with Achilles bursitis, and localized synovitis often forms at the tendon attachment, which may even cause local bone hyperplasia or defect. Bursitis may also occur in the axilla, forming a popliteal cyst. Symptoms: The onset is slow, and there are several prodromal symptoms such as fatigue, weight loss, poor appetite, low fever, and tingling in the hands and feet. First, joint symptoms: (A) morning stiffness: the first symptom of the joint, often appear before joint pain. The joint stiffness is painful when it starts to move, and the morning stiffness is reduced or disappeared when the joint activity increases. The joint morning stiffness is obvious in the morning and relieves in the afternoon. (B) joint swelling and pain: more symmetry, often invaded and metacarpophalangeal joints, wrist joints, shoulder joints, interphalangeal joints, ankle joints and knee joints. Joint redness, swelling, heat, pain, and movement disorders. (3) Malformation: In the later cases, the metacarpophalangeal joint flexion and ulnar deviation are generally present; if it occurs on the toes, the appearance of the claw-toe deformity appears. Second, extra-articular manifestations: is part of the systemic manifestations of rheumatoid arthritis or its complications. The joint disease of this disease can be disabling, but it will not kill. Extra-articular manifestations are often the cause of death from this disease. (A) rheumatoid nodules: seen in 15 to 20% of patients, more common in the forearm often under pressure on the extension side, such as the ulnar side and the olecranon. A soft amorphous knot is attached under the skin or a rubber-like knot fixed to the periosteum. Subcutaneous rheumatoid nodules are more common in patients with strong serum rheumatoid factor. (B) rheumatoid vasculitis: rheumatoid vasculitis is the basic disease of this disease, in addition to the joints and tissues around the joints, vasculitis can occur elsewhere in the body. It is characterized by distal vasculitis, skin ulcers, peripheral neuropathy, pericarditis, visceral arteritis such as heart, lung, intestine, spleen, pancreas, kidney, lymph nodes and testicles. (C) rheumatic heart disease: cardiac involvement, myocardial, valvular or aortic root rheumatoid granuloma formation, or myocardial, endocardial and annulus lymphocytes infiltration or fibrosis. (D) rheumatoid lung disease: chronic fibrosis pneumonia is more common, pulmonary fibroin-like necrosis and mononuclear cell infiltration, fever, dyspnea, cough and chest pain. (5) Kidney damage. (6) Ocular manifestations: Uveitis is a common disease of juvenile rheumatoid arthritis, which often causes keratitis in human rheumatoid arthritis. (7) Felty syndrome: It is a serious rheumatoid arthritis, which often causes splenomegaly, neutropenia, high positive rate of serum rheumatoid factor, and positive antinuclear antibody. (8) Sjogren's syndrome: It is a chronic inflammatory autoimmune disease. It mainly invades the lacrimal gland and the size of the salivary gland, resulting in the reduction or lack of gland destruction and secretion. The clinical manifestations are dryness syndrome mainly composed of the eye and oral mucosa. (9) Digestive tract damage. Diagnosis: The diagnosis of typical cases is generally not difficult, but in the early stage, especially when the beginning of single arthritis and X-ray changes are not obvious, follow-up observation can be confirmed. Internationally, the American College of Rheumatology 1985 diagnostic criteria were adopted. The standard was revised in 1987 to remove the damage examination and the poor specificity of joint pain and tenderness. The requirements for morning stiffness and joint swelling are more stringent. 1. Typical rheumatoid arthritis This type of diagnosis requires 7 of the following criteria, of which standard 1 to 5 joint symptoms or signs must last at least 6 weeks. Read more...