1. Etiology and pathogenesis
The role of MHC-II antigen and various inflammatory mediators, cytokines and chemokines in the pathogenesis of RA has been studied in depth, but its pathogenesis is still unclear.
Environmental factors
No direct infectious factors have been proven to cause the disease, but it is currently believed that some infectious factors (possibly bacteria, mycoplasma and viruses) may influence the pathogenesis and progression of RA through certain pathways by the following mechanisms.
Activation of T cells and macrophages and release of cytokines.
activation of B cells to produce RA antibodies, B cells in the synovium may secrete inflammatory factors such as TNF-α, and B cells may act as antigen-presenting cells, providing co-stimulatory signals required for the proliferation and effects of CD4+ cell clones.
Some components of infectious factors and the body’s own antigens lead to autoimmunity through molecular mimicry.
Genetic susceptibility
Epidemiological investigations have shown that the development of RA is closely related to genetic factors. Family lineage surveys have found an 11% probability of RA occurring in first-degree relatives of RA pre-documented individuals. Investigation of twins showed that the probability of monozygotic twins having RA at the same time was 12-30%, while the probability of dizygotic twins having RA at the same time was only 4%. Studies conducted in many regions and countries have found that HLA-DR4 haplotypes are associated with the development of RA.
Immune disorders
Immune disorders are thought to be the main pathogenesis of RA and are characterized by infiltration of synovial joints by activated CD4+ T cells and MHC-II positive antigen presenting cells (APCs). Some specific components of synovial joint tissue or endogenous substances produced in the body may also be presented as autoantigens by APCs to activate CD4+ T cells and initiate a specific immune response, resulting in the corresponding arthritic symptoms. During the course of the disease, different T cell clones in the T cell pool are activated and proliferate due to the stimulation of different antigens in vivo and in vitro, and macrophages in the synovium are also activated by antigens, resulting in an increase in cytokines such as TNF-α, IL-l, IL-6, IL-8, etc., which contribute to the chronic inflammatory state of the synovium. TNF-α further destroys articular cartilage and bone, resulting in joint deformity. IL-1 is the main cytokine causing systemic symptoms of RA such as hypothermia, malaise, and increased protein synthesis in the acute phase, and is the main factor causing elevated C-reactive protein and blood sedimentation.
In addition, B cells activate and differentiate into plasma cells, which secrete large amounts of immunoglobulins. The immune complex formed by immunoglobulins and RF, activated by complement, can induce inflammation. excess Fas molecules or dysregulation of the ratio of Fas molecules to Fas ligands in RA patients can affect the normal apoptosis of synovial tissue cells and sustain the immune response to RA synovitis.
It can be seen that RA is the result of a combination of various factors such as genetic susceptibility factors, environmental factors and immune system dysregulation.
2.Pathology
The basic pathological change of RA is synovitis. In the acute stage, the synovium is exudative and cellular infiltrative. The subsynovial layer is dilated with small blood vessels, swollen endothelial cells, enlarged cell spaces, and interstitial edema and neutrophil infiltration. As the lesion becomes chronic, the synovium becomes hypertrophic and forms numerous villi-like protrusions into the joint cavity or into the cartilage and subchondral bone. This villi appears microscopically as a proliferation of synovial cell layers from 1 to 3 layers to 5 to 10 layers or more, most of which are type A cells with macrophage-like functions and fibroblast-like type B cells. There were a large number of lymphocytes in the subsynovial layer, which were diffusely distributed or aggregated into nodules, like lymphoid follicles. Most of them are CD4+ T cells, followed by B cells and plasma cells. There is also neovascularization and a large number of activated fibroblasts and subsequent formation of fibrous tissue.
The villi, also known as vascular opacities, are highly destructive and are the pathological basis for joint destruction, deformity, and dysfunction.
Vasculitis can occur in any tissue outside the joints of patients with rheumatoid arthritis. It involves medium and small arteries and/or veins with lymphocytic infiltration of the vessel wall, fibrin deposition, and hyperplasia of the intima, resulting in narrowing or blockage of the vessel lumen. Rheumatoid nodules are a manifestation of vasculitis and commonly occur in the subcutaneous tissue at the site of joint extension compression, but also in any visceral organ. The nodules are centered on fibrinoid necrotic tissue, surrounded by an infiltration of epithelioid cells arranged in a ring, and surrounded by granulation tissue. There is a large number of lymphocytes and plasma cells between the granulation tissue.
3.Clinical manifestations
The clinical manifestations of RA are diverse, ranging from major joint symptoms to extra-articular manifestations of multisystem involvement. A few patients may have high fever, malaise, general malaise, weight loss and other symptoms, and then gradually develop typical joint symptoms. A small number of patients have a more rapid onset, with multiple joint symptoms appearing within a few days.
Joints
The former is reversible after treatment, but the latter is difficult to reverse once it appears.
Morning stiffness
The stiffness of the diseased joints after waking up in the morning is called “morning stiffness” (it can also occur after a long period of immobility during the day), which is a glue-like sensation and is more significant if it lasts for at least one hour. Morning stiffness occurs in more than 95% of RA patients. The duration of morning stiffness is directly proportional to the degree of joint inflammation, and it is often used as one of the indicators to observe the activity of the disease, although it is highly subjective. Arthritis of other etiologies may also present with morning stiffness, but it is not as pronounced and persistent as in this disease.
Pain and pressure pain
Arthralgia is often the earliest symptom and is most often seen in the wrist, metacarpophalangeal, and proximal interphalangeal joints, followed by the toes, knees, ankles, elbows, and shoulders. The painful joints are often accompanied by pressure pain, and the skin of the affected joints appears brownish pigmentation.
Joint swelling
Mostly caused by fluid accumulation in the joint cavity or inflammation of the soft tissues around the joint, or swelling due to hypertrophy of the synovial membrane after chronic inflammation in long-standing cases. All affected joints can be swollen, and the common sites are the wrist, metacarpophalangeal joints, proximal interphalangeal joints, knees and other joints, which also tend to be symmetrical.
Joint deformity
The deformity is aggravated by the atrophy and spasm of the muscles around the joint. The most common advanced joint deformities are ankylosis of the wrist and elbow joints, subluxation of the metacarpophalangeal joints, ulnar deviation of the fingers, and “swan neck” and “boutonniere” patterns. In severe cases, the joints become fibrous or bony ankylosis and lose joint function, making life impossible.
Special joints
The small movable joints of the cervical spine and the surrounding tendon sheaths are involved, resulting in neck pain, limited movement, and sometimes even spinal cord compression due to subluxation of the cervical spine.
The shoulder and hip joints are surrounded by more tendons and other soft tissues, making it difficult to detect swelling. The most common symptoms are localized pain and limitation of movement, with the hip joint often showing pain in the hip and lower back.
The temporomandibular joint is present in 1/4 of patients with RA and presents early with increased pain with speech or chewing, and in severe cases with limited mouth opening.
Joint dysfunction joint swelling and pain and structural damage both cause joint mobility impairment.
The American College of Rheumatology classifies the degree to which life is affected by this disease into four levels.
Grade I: Able to perform daily life and all tasks as usual.
Grade II: can perform general daily living and certain occupational tasks, but participation in other project activities is limited.
Level III: able to perform general daily living but limited participation in some kind of occupational work or other project activities
Grade IV: limited ability to care for oneself in daily life and to participate in work.
Extra-articular manifestations
Rheumatoid nodules
They are more common extra-articular manifestations of the disease and can be seen in 20% to 30% of patients, mostly located in the subcutaneous part of the joint bulge and pressure areas, such as the forearm extension, near the elbow eminence, occipital and Achilles tendons. The nodules vary in size from a few millimeters to several centimeters in diameter, are hard, non-pressure, and symmetrically distributed. In addition, almost all organs such as the heart, lungs, and eyes can be involved. Their presence suggests the activity of the disease.
Rheumatoid vasculitis
Systemic vasculitis is rare in patients with RA. Small vasculitis under the fingernails or at the fingertips is observed on physical examination. The long-term prognosis of subclinical vasculitis is unclear.
Lung: Lung involvement is very common, with more males than females, and can sometimes be the first symptom.
Interstitial lung lesions: are the most common lung lesion, seen in approximately 30% of patients, with progressive shortness of breath and pulmonary insufficiency, and in a few cases, chronic fibrous alveolitis is associated with a poor prognosis. Abnormalities in lung function and lung imaging, especially high-resolution CT, are useful for early diagnosis.
Nodular changes: The presence of single or multiple nodules in the lungs is a manifestation of rheumatoid nodules in the lungs. The nodules may sometimes liquefy and form cavities when coughed up.
Caplan’s syndrome: Patients with pneumoconiosis combined with RA are prone to develop a large number of pulmonary nodules, called Caplan’s syndrome, also known as rheumatoid pneumoconiosis. The clinical and chest X-ray manifestations resemble rheumatoid nodules in the lungs, which are numerous and large, and may appear suddenly with increased joint symptoms. Pathological examination of the nodules contains dust in the central necrotic area.
Pleurisy: seen in about 10% of patients. It is a small amount of pleural fluid unilaterally or bilaterally, or occasionally a large amount of pleural fluid. The pleural fluid is exudative and has a very low sugar content.
Pulmonary hypertension: partly due to intrapulmonary artery disease and partly due to interstitial lung disease.
Cardiac involvement
Cardiac involvement can occur in both acute and chronic RA patients, with pericarditis being the most common, most often seen in patients with positive RF and rheumatoid nodules, but most patients have no associated clinical manifestations. Small pericardial effusions are seen by echocardiography in approximately 30% of patients.
Gastrointestinal tract
Patients may have epigastric discomfort, stomach pain, nausea, poor appetite, or even black stools, mostly associated with the use of anti-rheumatic drugs, especially NSAIDs, and rarely caused by RA itself.
Renal: Vasculitis in this disease rarely involves the kidneys. Minor membranous nephropathy, glomerulonephritis, small intrarenal vasculitis, and amyloidosis (amyloidosis) of the kidneys have been reported occasionally.
Nervous system
Nerve compression is a common cause of neurological lesions in patients with RA. The peripheral neuropathy under compression correlates with the severity of synovitis in the corresponding joint. The most commonly involved nerves are the median nerve, ulnar nerve, and radial nerve. Neurological involvement can be diagnosed based on clinical symptoms and nerve localization, such as carpal tunnel syndrome due to compression of the median nerve at the wrist joint. As the inflammation decreases, the patient’s neuropathy gradually decreases, but sometimes surgical decompression is required. Spinal cord compression manifests as gradual onset of sensory abnormalities and loss of strength in both hands, with tendon reflexes mostly hyperactive and positive pathologic reflexes. Polyneuritis mononeuritis is caused by ischemic lesions of small vessels.
Hematologic system
The degree of anemia in patients with RA is usually related to the activity of the disease, especially to the degree of inflammation of the joints. anemia in RA patients is usually an orthocytic orthopigmented anemia, and in the presence of microcytic hypochromic anemia, the anemia can be caused by the lesion itself or by a small amount of prolonged bleeding from the gastrointestinal tract due to the administration of nonsteroidal anti-inflammatory drugs. disease (ACD) pathogenesis, the anemia can also improve after the patient’s inflammation is controlled. In patients with active RA, thrombocytosis is common, and the degree of increase is positively correlated with the number of joints with active synovitis and influenced by extra-articular manifestations; the mechanism of thrombocytosis is not well understood.
Felty’s syndrome is a combination of splenomegaly, neutropenia, and in some cases, anemia and thrombocytopenia in RA patients, not all of whom are in the active phase of arthritis.
Dry syndrome: About 30% to 40% of RA patients can develop this syndrome in all periods of the disease, and the prevalence of dry syndrome gradually increases with the prolongation of the disease. Dry mouth and dry eyes are the manifestations of this syndrome, but some patients do not have obvious symptoms, and dry angle, conjunctivitis and dry mouth must be confirmed through various examinations.
4.Check
Blood picture: There is mild to moderate anemia. Platelets may be increased in active patients. White blood cells and classification are mostly normal.
Inflammatory markers: Blood sedimentation and C-reactive protein (CRP) are often elevated and correlate with the activity of the disease.
Autoantibodies.
Detection of autoantibodies facilitates the differentiation of RA from other inflammatory arthritis such as psoriatic arthritis, reactive arthritis and degenerative arthritis. new antibodies are being discovered in RA, some of which are significantly more specific for diagnosis than RF and can appear early in the disease, such as anti-cyclic citrullinated peptide (CCP) antibodies, antiperinuclear factor (APF) antibodies, anti-keratin antibodies (AKA) and anti-Sa antibodies, etc.
Rheumatoid factor: It can be classified as IgM, IgG and IgA type RF. in routine clinical work mainly detects IgM type RF, which is found in about 70% of patients’ sera, and its titer is generally proportional to the activity and severity of the disease. However, RF is not a specific antibody for RA, even in 5% of normal people can also appear low titers of RF, so RF-positive people must be combined with clinical manifestations in order to diagnose the disease.
Anti-keratin antibodies: The spectrum includes antiperinuclear factor (APF) antibodies, anti-keratin antibodies (AKA), anti-polykeratin microfilament protein antibodies (AFA) and anti-cyclic citrullinated peptide (CCP) antibodies. The target antigen of this group of antibodies is polykeratin microfilament protein (filaggrin) of the cellular matrix, and cyclic citrullinated peptide is the major component of this antigen. Therefore, anti-CCP antibodies have been commonly used in clinical practice because of their high sensitivity and specificity for the diagnosis of RA in this antibody spectrum. These antibodies help in the early diagnosis of RA, especially in patients with negative serum RF and atypical clinical symptoms. Since their epitopes all contain citrulline, they are called citrulline-associated autoimmune system, and this system may play a role in the pathogenesis and development of RA.
Immune complexes and complement: Various types of immune complexes are present in the serum of 70% of patients, especially in active and RF-positive patients. Serum complement is elevated in both the acute and active phases, with hypocomplementemia occurring only in a minority of those with vasculitis.
Synovial fluid: The synovial fluid in the joint cavity of a normal person does not exceed 3.5 ml. in the presence of inflammation in the joint, the synovial fluid has an increased number of leukocytes, up to 2000 × 106/L to 75,000 × 106/L, with a predominance of neutrophils, its poor viscosity and low glucose content (lower than blood glucose).
Imaging of joints.
X-ray plain film: It is important for the diagnosis of RA, staging of joint lesions, and monitoring of lesion evolution. At least X-rays of the finger and wrist joints should be taken at the initial diagnosis. Early stage, swollen shadow of soft tissues around the joint and osteoporosis at the joint end (stage I); then narrowing of the joint space (stage II); worm-like changes on the joint surface (stage III); late stage, joint subluxation and fibrous and bony ankylosis after joint destruction (stage IV). The diagnosis should be bone erosion or definite limited or significant decalcification of the proximal aspect of the involved joint.
Other: including digital imaging of joint X-ray, CT and MRI, which are helpful in diagnosing early RA. MRI can show early lesions of joint soft tissues, such as synovial edema and bone marrow edema, which is a precursor of bone destruction lesions, etc. CT can show bone destruction that is not yet visible on X-ray films, but it cannot be commonly used in daily clinical practice because it requires certain conditions.
Biopsy of rheumatoid nodules: its typical pathological changes can help the diagnosis of this disease.
5.Diagnosis
The current diagnosis of RA still follows the ACR 1987 revised classification criteria.
Intra-articular or peripheral morning stiffness lasting at least 1 hour.
Soft tissue swelling or effusion in at least 3 joint areas at the same time.
Swelling in at least 1 of the wrist, metacarpophalangeal, and proximal interphalangeal joint regions.
Symmetrical arthritis.
The presence of rheumatoid nodules.
Positive serum RF (no more than 5% of the normal population positive by the method used).
Radiographic changes (at least osteoporosis and joint space narrowing).
The diagnosis of RA is made when four of the above seven items are met (the duration of disease in items I-IV lasts at least 6 weeks).
The above classification criteria are not only applicable to the selection of cases for large-scale epidemiological investigation and drug validation, but also used as diagnostic criteria in clinical medical work, but some early or atypical patients are easily missed, mainly for the following reasons: First, most of the early RA only has the manifestation of arthritis, lacking imaging support. Second, RF is not a specific antibody for RA, and 20% to 30% of RA patients are negative for RF. Furthermore, many other diseases also manifest as arthritis in early stages.
RA is a heterogeneous disease that can be slow or rapid in onset, monoarticular or polyarticular, with arthritic symptoms or extra-articular manifestations, or even with non-articular symptoms such as bursitis. The course of the disease may be self-limiting, i.e., one episode resolves on its own and no more episodes occur; most of the episodes are intermittent or continue to develop with mild or severe fluctuations; a few are progressive and “malignant”. Special care should be taken in early diagnosis to avoid over-diagnosis and over-medication, and not to delay treatment.
6.Differential diagnosis
Osteoarthritis
It is a degenerative osteoarthropathy, which is mostly seen in people over 50 years old. It mainly involves the knee, spine and other weight-bearing joints. Joint pain is aggravated by activity, and there may be joint swelling and fluid accumulation. It is often misdiagnosed as RA, especially in the distal interphalangeal joint with Heberden’s nodes and the proximal phalangeal joint with Bouchard’s nodes, and as synovitis.OA is usually painless and most patients have normal sedimentation and negative or low titer RF.X-rays show joint space narrowing, labral hyperplasia or warts on the joint edges.
Ankylosing spondylitis
The main invasion of the spine, when the peripheral joints are involved, especially the knee, ankle, hip as the first symptoms, need to be distinguished from RA. There may be a family history, and more than 90% of patients are HLA-B27 positive. Serum RF is negative.
Psoriatic arthritis
This disease occurs several years after cutaneous psoriasis, and 30% to 50% of patients present with symmetric polyarthritis, which is very similar to RA. The difference is that the disease is more pronounced in the distal phalangeal joints and manifests itself as attachment telangiectasia and phalangitis of these joints. There may also be sacroiliac arthritis and spondylitis, and the serum is RF and mostly negative.
Systemic lupus erythematosus
However, the joint lesions are less severe than those of RA and are generally non-erosive, and the extra-articular systemic symptoms such as pteroidal erythema, alopecia, and proteinuria are more prominent. Serum ANA, anti-double-stranded DNA (dsDNA) antibodies and many other autoantibodies are positive.
Arthritis of other etiologies
Arthritis of rheumatic fever, reactive arthritis after intestinal infection or tuberculosis infection, all have their own primary pathogenic features.
7.Treatment
Since the etiology and pathogenesis of this disease are not fully understood, there is a lack of effective clinical measures to cure and prevent this disease. To reduce joint symptoms, delay the progression of the disease, prevent and reduce joint destruction, protect joint function, and maximize the quality of life of patients are the current treatment goals. In order to achieve these goals, early diagnosis and early treatment are extremely important.
Treatment measures include: general treatment, drug therapy, surgical treatment, immune purification, and functional exercise, among which drug therapy is the most important.
General treatment
Includes rest, joint braking (acute phase), joint functional exercise (recovery phase), physical therapy, etc. Bed rest is only suitable for patients in the acute stage, fever and internal organ involvement.
Drug therapy
According to the drug properties, the commonly used drugs for the treatment of RA are divided into four major categories, namely non-steroidal anti-inflammatory drugs (NSAID), disease-modifying anti-rheumatic drugs (DMARD), glucocorticoids (glucocorticoid) and botanicals.
Non-steroidal anti-inflammatory drugs
NSAIDs have analgesic and anti-swelling effects, and are commonly used to improve the symptoms of arthritis, but they cannot control the disease (see the general discussion for the mechanism of action), and must be taken together with disease-modifying antirheumatic drugs.
The doses of commonly used NSAIDs are as follows.
Regardless of the choice of NSAID, there will be gastrointestinal adverse reactions, the use of which must be noted, the dose should be individualized; only in a NSAID full dose after 1 to 2 weeks of ineffective use before changing to another; should avoid two or more NSAIDs taken at the same time, because their efficacy does not superimpose, and the increase in adverse reactions; the elderly should choose NSAID drugs with a short half-life, for the For the elderly with a history of ulcer, it is advisable to take selective COX-2 inhibitors to reduce the adverse effects in the gastrointestinal tract.
Celecoxib: daily dose of 200-400 mg in 1 to 2 doses, prohibited for those with sulfonamide allergy.
Meloxicam: daily dose of 7.5 to 15 mg in 1 to 2 divided doses.
Diclofenac: daily dose of 75-150mg in 2 divided doses
Indomethacin: daily dose of 75 to 100 mg in 3 doses, with more gastrointestinal reactions than the above 3 drugs; of similar structure are sulforaphane and acemetacin
Naproxen: daily dose of 0.5 to 1.0g, divided into 2 doses
Ibuprofen: the daily dose is 1.2 to 3.2g, divided into 3 to 4 doses.
Condition-modifying anti-rheumatic drugs
These drugs are slower to work than NSAIDs, and it takes about 1 to 6 months for the clinical symptoms to improve and delay the progression of the disease. It is generally believed that DMARD should be used in all cases of RA with a clear diagnosis, and the choice of drugs and the application of the program depends on the activity, severity and progression of the patient’s disease. Methotrexate (MTX) is generally preferred and used as the basic drug for combination therapy, based on a combination of clinical studies on efficacy and cost. Those with more than 20 joints involved, joint bone destruction within 2 years of disease onset, persistently high RF titers, and extra-articular symptoms should be treated with a combination DMARD regimen as early as possible. Each DMARD has its own different mechanism of action and adverse effects, which need to be carefully monitored when applied. The commonly used drugs in this class are detailed as follows.
Gold preparation: There are two types of dosage forms, injectable and oral. The commonly used injection is gold sodium thiomalate, injected intramuscularly once a week, starting from the smallest dose, gradually increased to 50mg each time, to be effective after the injection interval can be extended, now rarely used. Oral gold novocaine (auranofin), the daily dose of 6mg, divided into two oral, 3 months after the effect. Oral gold preparation has few adverse effects and is suitable for early or mild patients.
Penicillamine: the starting dose is 125mg, 2-3 times daily, without adverse reactions, the dose is doubled after every 2-4 weeks to 500-750rag daily, and then reduced to maintain after the symptoms improve. Adverse reactions are more frequent and include gastrointestinal reactions, bone marrow suppression, rash, mouth odor, and liver and kidney damage.
Azathioprine: Inhibits cell synthesis and function. The daily oral dose is 100mg, which can be changed to 50mg for maintenance after stabilization. Blood picture and liver and kidney function need to be monitored during the dosing period.
Cyclosporine: It is an immunosuppressant for the treatment of this disease in recent years, and the daily dose is every 3-5mg/kg, divided into 1 or 2 oral doses. Its prominent adverse reactions are the rise of blood creatinine and blood pressure, which should be closely monitored during the drug administration.
MTX: This drug inhibits intracellular dihydrofolate reductase, which inhibits purine synthesis and has anti-inflammatory effects. The weekly dose is 7.5~25mg, mainly taken orally (within 1 day), but can also be injected or myostatinized. 4~6 weeks for effect, at least 6 months for treatment. Adverse reactions include liver damage, gastrointestinal reactions, bone marrow suppression and corneal erosion, which can be recovered after discontinuation of the drug.
Sulfasalazine: The dose is 2-3g per day, divided into two doses, starting from a small dose, which will reduce adverse reactions, and is prohibited for those who are allergic to sulfonamide.
Leflunomide (1eflunomide): It mainly inhibits dihydroorotic acid dehydrogenase, which synthesizes pyrimidines, and inhibits the growth of activated lymphocytes. It is administered as 50 mg once daily and 10-20 mg once daily after 3 days.
Hydroxychloroquine and chloroquine: The former is 0.2-0.4g daily, divided into two doses. The latter 0.25g daily in 1 dose. Long-term use of chloroquine may lead to blind spots and “bull’s eye”-like changes in the fundus of the eyes, so fundus testing is recommended every 6 to 12 months.
Biological agents and immunotherapy: Biological agents such as TNF-α antagonists, IL-1 antagonists, CD20 monoclonal antibodies, cytotoxic T cell activation antigen-4 (CTLA-4) antibodies, etc., have been gradually used in recent years at home and abroad, and clinical trials suggest that they have clinical trials suggest that they have anti-inflammatory and prevent bone destruction effects. In order to increase the efficacy and reduce the adverse effects, it is advisable to combine this type of biological agents with MTX. The main side effects include local rash at the injection site, infection (especially tuberculosis infection), increased prevalence of lymphatic system tumors with long-term use, and transient autoimmune diseases and autoantibodies induced by TNF-α monoclonal antibody. Further research is needed on their long-term efficacy, duration, relapse and side effects after discontinuation of the drug.
Immunotherapy includes oral induction of immune tolerance and minocycline analogues, the efficacy of which is to be determined. Immunotherapy also includes plasma replacement and immunosorbent therapy with the main purpose of removing abnormal immunoglobulins from plasma, and is only used in some refractory and severe patients.
Other DMARD.
Glucocorticoids
This drug has a powerful anti-inflammatory effect, in the acute attack of arthritis can be given short-acting hormone, the dose of which is adjusted according to the severity of the disease, generally should not exceed prednisone 10mg per day, can make arthritis symptoms get rapid and obvious relief, improve joint function. Patients with systemic symptoms such as heart, lung, eye and nervous system involvement can be given 30-40 mg of prednisone daily, and the dose is reduced to 10 mg daily or less after the symptoms are controlled. However, since it cannot cure the disease, the symptoms will recur after stopping the drug. The dependence caused by long-term use of glucocorticoids makes it difficult to stop the drug and many adverse effects can occur. Hormone injections in the joint cavity are beneficial in reducing the symptoms of arthritis and improving joint function. However, they should not be given more than three times in a year. Excessive joint cavity punctures can lead to steroid crystalloid arthritis in addition to complications of infection.
Botanical preparations
Frequently available botanical preparations include.
Radix polygoni, which has lymphatic and monocyte inhibition and anti-inflammatory effects. Dosage: 30-60 mg/d in 3 doses. Adverse effects include toxicity to the gonads, decreased menstruation, menopause, decreased sperm vitality and number, skin pigmentation, thinning and softening of nails, liver damage, gastrointestinal reactions, etc.
Cytisine: Cytisine 60mg orally before meals, three times daily. Common adverse reactions include allergic reactions such as skin pruritus and rash, and leukopenia in a few patients.
Total Paeoniflorin: The commonly used dose is 0.6g, 2 to 3 times daily. Its adverse reactions include increased frequency of stools, mild abdominal pain, and poor appetite.
Surgical treatment
The former is suitable for more advanced joints with deformity and loss of function. Synovectomy can provide some relief, but the disease tends to recur when the synovial membrane proliferates again, so DMARD must be applied at the same time.
Immunopurification
Patients with rheumatoid arthritis often have high titers of autoantibodies, large amounts of circulating immune complexes, and high immunoglobulins in their blood. Therefore, in addition to drug therapy, immunopurification therapy can be used to quickly remove immune complexes and excessive immunoglobulins and autoantibodies from the plasma. If there are too many immunoreactive lymphocytes, individual nuclei clearance therapy can also be used, thus improving the function of T, B cells and macrophages and natural killer cells, and reducing blood viscosity to improve symptoms while increasing the efficacy of drug therapy. Immunopurification therapies commonly used today include plasma replacement, immunosorbent and lymphocyte/monocyte removal. The pathological components being replaced can be lymphocytes, granulocytes, immunoglobulins or plasma. The application of this method needs to be combined with drug therapy.
Functional Exercise
It is important to emphasize that functional exercise is an important way to restore and maintain joint function in patients with rheumatoid arthritis. Generally speaking, during the acute period when joint swelling and pain are obvious, joint activity should be appropriately limited. However, once the swelling and pain improve, functional activities should be performed without increasing the patient’s pain. For those without obvious joint swelling and pain but with reversible joint movement limitation, they should be encouraged to perform formal functional exercises. In hospitals where available, this should be done under the guidance of rheumatologists and rehabilitation specialists.
Prognosis
Most patients with RA have a prolonged disease course, with a high disability rate in the early 2-3 years of the disease course, and joint destruction up to 70% within 3 years if timely diagnosis and early and reasonable treatment are not provided. Active and correct treatment can lead to remission in more than 50% to 80% of RA patients. Only a minority (10%) can resolve on their own after a short-term episode without sequelae. There is no accurate predictor of prognosis, but possible factors include: males have a better prognosis than females; those with late onset have a better prognosis than those with early onset; the number of joints involved at onset, or the number of metatarsophalangeal joints involved, or the number of joints involved in the course of the disease is greater than 20 has a poor prognosis; persistent high titers of RF, persistent increased sedimentation, increased C-reactive protein, and increased blood eosinophilia all suggest a poor prognosis; there are severe systemic symptoms, fever, anemia, malaise and extra-articular manifestations (rheumatoid nodules, sclerositis, interstitial lung disease, pericardial disease, systemic vasculitis and other visceral injuries), often have a poor prognosis. In addition, the early or late treatment and the appropriateness of the treatment plan have an important impact on the prognosis. The main causes of death associated with this disease are: visceral vasculitis, infection and amyloidosis.