Rheumatoid arthritis (RA) is an autoimmune disease with chronic, symmetrical multisynovial arthritis and extra-articular lesions (subcutaneous nodules, pericarditis, pleurisy, pneumonia, peripheral neuritis, etc.) as the main clinical manifestations, and no specific diagnostic indication is known.
The prevalence of this disease in China varies from article to article, about 0.36%, with 5 million people affected and about 3 times more women than men. The clinical course varies, with about 15% of single episodes remitting, 25% of intermittent episodes, 50% of persistent episodes, and 10% of rapid progression to severe disease. The peak age of onset is 20-40 years old, and female patients are more likely to be 40-60 years old.
Etiology
1.Infection factors
A large amount of information proves that RA is related to EBV infection, but it is speculated that RA may not be caused by direct infection of the synovial membrane by EBV, but may be caused by EBV infection causing disorders in the regulation of the autoimmune system. Some scholars believe that Mycobacterium tuberculosis and Mycobacterium avium kinase infection are also related.
2. Genetic factors
If RA is entirely determined by genetic factors, identical twins should have a 100% chance of having the disease together, but in fact only 30%. This means that there is a genetic susceptibility to the disease, but its onset is the result of a combination of factors, and genetics only plays a role.
3. Immunological abnormalities
Clinical manifestations
1.Joint manifestations
Joint manifestations are the most important symptoms, with swelling and slightly red skin in the acute stage, and joint deformity in the progressive or late stage.
(1) “Target joints” of RA: proximal interphalangeal joints, metacarpophalangeal joints and wrist joints are called “target joints” of RA, and almost all patients are involved in at least one of these three groups of joints. A small number of patients whose first involvement is in other joints will soon invade these “target joints”.
(2) Other affected joints: elbow, knee, ankle, shoulder, etc.
(3) Morning stiffness: After the patient wakes up in the morning or after a period of inactivity, the diseased joint becomes stiff and movement is limited, affecting activities such as turning over, buttoning clothes, clenching fists, etc. The sensation disappears only after the limb is slowly moved. Morning stiffness is an early manifestation of rheumatoid arthritis. The duration of morning stiffness is defined as the time when the patient wakes up in the morning and feels a significant reduction in this sensation, and is divided into units of calculation. the duration of morning stiffness in RA patients often reaches more than 60 minutes. Generally speaking, the more severe the disease is during the active phase, the longer the duration of morning stiffness, which can last for several hours. Morning stiffness first occurs in the joints of the hands, which are stiff and uncomfortable and cannot make a fist, and later, as the disease progresses, stiffness in the joints of the whole body may appear. The duration of morning stiffness parallels the extent of the disease. When the disease is in remission, the duration of stiffness will be shortened or even disappear, so the duration of stiffness can be used as an indicator to observe the activity and severity of the disease.
(4) Pain: The most prominent symptom of this disease is pain. It is characterized as chronic and symmetrical. The joint pain is obvious at night, in the morning and when the joint starts to move, and the pain can be reduced after activity. Initially, it may manifest as wandering pain in the small joints of the fingers, wrists and toes.
(5) Swelling: uniform swelling around the joints, with a few redness.
(6) Activity impairment: Early joint swelling causes can be restored to normal. Later, joint movement is restricted and cannot be recovered. Continuing to develop, fibrous and bony fusion occurs in the joint and the joint movement function is completely lost. The activity disorder of the joint affects the overall activity function, such as the finger and wrist joint flexion and extension restrictions, can make the grip strength decreased, can not button, or even can not hold things; shoulder joint disorder can affect the lifting function, resulting in hair combing difficulties; knee joint disorder can affect the squatting function, walking difficulties; temporomandibular joint disorder can affect the open mouth and chewing function. Therefore, patients in the middle and late stages of the disease may affect or lose the ability to work, or even unable to take care of themselves.
(7) Joint deformity: late manifestation of the disease.
2, extra-articular manifestations: extra-articular manifestations are signs of severe RA disease or lesion activity, and all organs of the body can be involved, with various manifestations.
(1) rheumatoid nodules
Rheumatoid arthritis patients, such as the dorsal side of the elbow, finger joints, sacral prominence, occipital prominence, the emergence of small nodules, may be a granulomatous reaction after small vasculitis. 20-30% of patients have them, mostly reflecting the activity of the disease and accompanied by patients with severe disease.
(2)Rheumatoid vasculitis
(3)Others Pleurisy, pericarditis, lymph node enlargement, anemia, weight loss and hepatosplenomegaly
Laboratory tests
1. Anemia: Active RA may have anemia, which recovers as the disease improves. The number of white blood cells and platelets may be increased. However, attention should be paid to drug-related anemia caused by long-term use of NSAIDs and immunosuppressants.
2.Blood sedimentation: Blood sedimentation in active RA increases significantly and decreases with remission, and can be used as one of the indicators for judging the efficacy of treatment. However, blood sedimentation is not a specific indicator, and it can be increased when the disease is complicated by infection and tumor. Sometimes the blood sedimentation is not consistent with the disease activity.
3.C-reactive protein: C-reactive protein is one of the inflammatory reactive proteins, which is generally elevated in RA and is closely related to the disease.
4, rheumatoid factor (RF): with the development of the disease, RF titer increases, but RF is not a specific indicator, RF negative can not exclude the diagnosis of RA, other rheumatic diseases RF can also be positive.
5, polyclonal hyperglobulinemia: hyperglobulinemia response to the presence of humoral immune abnormalities, suggesting that the disease to chronic transformation, but also one of the causes of extra-articular lesions.
6, synovial fluid and synovial examination: help the diagnosis and differential diagnosis of wind-like off.
Radiological examination
X-rays are an important indicator for the diagnosis and staging of RA, and the staging of RA is often judged by both hands (plus other parts if necessary).
RA diagnosis
There are no specific indicators for the diagnosis of RA, and the correct diagnosis should be based on a comprehensive judgment of the entire disease and requires the exclusion of other non-RA joint diseases before the diagnosis can be confirmed.
1. Morning stiffness of at least one hour (lasting ≥ 6 weeks)
2, swelling of 3 or more joints (lasting ≥ 6 weeks)
3, swelling of the wrist, metacarpophalangeal joint or proximal interphalangeal joint (lasting ≥ 6 weeks)
4.Symmetrical arthrogryposis (lasting ≥6 weeks)
5.Subcutaneous nodules
6.X-ray changes of the hand
7, positive rheumatoid factor (titer > 1:32)
The diagnosis of rheumatoid arthritis can be confirmed by having 4 or more of the above 7 items. (Our rheumatoid arthritis disease is lighter than that of Americans, the first and second of the criteria are not fully consistent with our people, can refer to the implementation.)
Diagnostic criteria for active rheumatoid arthritis: The activity of the condition of rheumatoid arthritis is judged according to the following criteria
1. moderate pain in the rest room
2.Morning stiffness ≥ 1 hour
3.Swelling of 3 or more joints
4, joint pressure pain ≥ 5 joints
5.Blood sedimentation (Wei’s method ≥ 28mm/h)
Anyone who meets the above four items at the same time can be diagnosed as active rheumatoid arthritis.
The aim of treatment is to improve the prognosis of the disease, maintain the function of joints and organs, relieve the symptoms and improve the quality of life.
The principle of treatment is early diagnosis and early rational and combined use of drugs. The commonly used anti-rheumatic drugs are as follows.
1, non-steroidal anti-inflammatory drugs (NSAIDs): these drugs can inhibit the synthesis of prostaglandins and rapidly produce anti-inflammatory and analgesic effects, and have a better effect on relieving pain, but can not change the course of the disease. nSAIDs through the inhibition of cyclooxygenase (COX) activity, thereby inhibiting the final production of arachidonic acid prostacyclin, prostaglandins (PGE1, PGE2) and thromboxane A2 and other inflammatory mediators. The human body has two different isoforms of cyclooxygenase, COX-1 and COX-2. COX-1 is a normal component of the body. COX-2 is present at sites of inflammation and contributes to the release of inflammatory mediators, inducing an inflammatory response. Most existing NSAIDs selectively inhibit COX-2 and COX-1, and therefore have both anti-inflammatory, analgesic, and antipyretic effects, as well as inevitable gastrointestinal and other adverse effects. Common gastrointestinal reactions, including epigastric discomfort, dyspepsia, and even gastric mucosal ulceration, bleeding, and perforation. In addition, there are adverse effects on kidney function.
Currently commonly used drugs with non-selective effects on COX include: salicylic acid preparations: aspirin; indoleacetic acid derivatives: anti-inflammatory pain, acemetacin; phenylpropanoids: ibuprofen tablets, fenpropathrin (ibuprofen suction-release capsules); extirpated acids: futalin (diclofenac sodium extended-release tablets), australia wet gram tablets, etc.; xicam: inflammation and pain xicam, etc.;
Some new NSAIDs have highly selective inhibition of COX-2, which can reduce adverse effects. The main ones are.
Celecoxib (coxib) class: this class of drugs have celecoxib (celecoxib) and rofecoxib (rofecoxib) two kinds of drugs, the former by the Farmacia company and Pfizer Pharmaceutical Co., Ltd. production, trade name Celebrex (Celebrex), the latter by Merck Sharp & Dohme Pharmaceuticals production, trade name Wanluo (Vioxx). These two drugs have some differences in chemical structure, but the pharmacological mechanism and efficacy are more or less the same. Their analgesic and anti-inflammatory effects are obvious, and damage to the gastric mucosa is less likely to occur.
Xicam: meloxicam (meloxicam). For the German Boehringer Ingelheim pharmaceutical production, trade name Mobic (Mobic), there are now a number of domestic generic products.
In recent years, there are also some non-steroidal anti-inflammatory drugs, such as nimesulide (Provera), nabumetone (Relifen), etc., because the COX-2/COX-1 ratio measured in vitro is very low, so they all call themselves selective COX-2 inhibitors.
Why can’t rheumatic diseases be treated with only NSAIDs? (From “What about 300 rheumatic diseases?” edited by Professor Tang Fulin, Director of the Chinese Society of Rheumatology)
Early rational and regular use of NSAIDs can often reduce joint and muscle pain and achieve good results. However, this does not mean that the use of NSAIDs alone is sufficient for the treatment of the disease. Because the mechanism of action of NSAIDs is only to suppress inflammation and reduce pain by controlling the production of inflammatory mediators, it does not control the disease process itself. For example, in rheumatoid arthritis, it does not control the development of joint lesions and many other extra-articular manifestations. If not supplemented with other medications in a timely manner, the joint lesions can often progress to fusion and complete loss of function. The progression of the disease can also lead to irreversible damage to other organs and systems in the body. Therefore, for progressive rheumatic diseases, our focus should not be limited to controlling symptoms, but should actively stop the development of the disease process.
2, improve the condition of anti-rheumatic drugs (DMARDs): can alleviate the disease to a certain extent or stop the progression of the disease. Including slow-acting drugs and immunosuppressants. Methotrexate (MTX) has become the gold standard for evaluating the treatment of rheumatoid DMARDs because it is the most widely used clinically, its efficacy is certain, and its toxic side effects are relatively mild.
① Slow-acting drugs (SAARDs): have some control effect on the disease but slow onset of action, requiring weeks or months before the slow onset of action. The common ones are antimalarials (hydroxychloroquine and chloroquine), salazosulfapyridine, gold agents, penicillamine, etc.
② Immunosuppressants: These drugs were initially used to treat tumors and later in organ transplants to suppress the host’s immune system. They produce immunosuppressive effects through different pathways, and although the side effects are more frequent and severe, they have a great effect on improving the prognosis of the disease. The common ones are methotrexate (MTX), cyclophosphamide (CTX), azathioprine (AZA), cyclosporine (CyC), Erofloxacin and primaquine, which are the second-line drugs for rheumatic diseases.
Phytopharmaceuticals with certain alleviating effects: they are anti-rheumatic slow-acting phytopharmaceuticals derived from plants, partially purified and proven to be effective through rigorous clinical trials. in the early 80s, it has been confirmed that Leigongteng polysaccharide and Qingtengine are effective in rheumatic diseases such as RA, and in the 90s, it was also confirmed that total glucoside of peony has better efficacy. Botanicals are welcomed by patients because they are considered to be less toxic and can enhance the effect of “western drugs” or reduce the adverse effects of “western drugs”.
3.Hormones: Synthetic glucocorticoids, representing drugs such as prednisone, hydrocortisone and methylprednisolone. The effect of glucocorticoids on the body varies according to the dose, and only the supraphysiological amount has pharmacological effects such as anti-inflammation, immune suppression, anti-shock, anti-toxicity, anti-allergy and adjustment of the blood system. It can rapidly eliminate joint swelling and reduce painful morning stiffness, and has been widely used clinically. It is an important drug in the treatment of rheumatic diseases, but it does not stop the destruction of joints and does not improve the development of lesions. Please note: Many wandering doctors under the banner of “ancestral secret recipes” add hormones to traditional Chinese medicine as the so-called “secret recipes”, and due to the powerful effect of hormones in improving symptoms, many patients taking the “secret recipes” are often unable to find out immediately. Because of the powerful effect of hormones in improving symptoms, many patients taking the “secret formula” often cannot immediately discover the fraud, which brings serious consequences to patients’ health and even endangers their lives.
There are two clinical causes of glucocorticoid side effects, one is long-term heavy use and the other is inappropriate discontinuation of the drug. Long-term use of glucocorticosteroids can cause a series of acute cortical insufficiency manifestations if the drug is stopped too quickly.
The side effects of hormones include.
1) Disorders of water, salt, sugar, protein and fat, mineral metabolism: manifested as centripetal obesity, commonly known as full moon face, buffalo back, acne, hirsutism, hyperglycemia, hypertension, hyperlipidemia, edema, diabetes, etc.
2) Medically induced adrenocortical insufficiency: long-term high-dose hormone use can cause a decrease in endogenous glucocorticoid secretion. If the drug is suddenly stopped, nausea, vomiting, hypoglycemia, hyponatremia, hyperkalemia, cardiac arrhythmia, hypotension and other withdrawal reactions can occur. The way to prevent this is to withdraw the drug gradually and reasonably.
3) Weaken the body’s resistance. Induces and aggravates infection.
4) Inducing and aggravating ulcers: peptic ulcers are one of the common side effects.
5) Osteoporosis and spontaneous fractures.
6) Aseptic osteonecrosis: About 5% of patients receiving high doses of corticosteroids can develop aseptic osteonecrosis within 1 month to several years, most often in the bilateral femoral head.
7) Susceptibility to menstrual cycle disorders.
Introduction of several common representative disease-relieving antirheumatic drugs (DMARDs)
Methotrexate (MTX)
Overview】This product is an anti-folate antineoplastic drug. It acts selectively in the S stage. 1965 was the first year that female choriocapillary epithelial carcinoma could be cured by MTX, which aroused interest in chemotherapy research. Another development was the application of formyltetrahydrofolate (CF) to rescue the MTX toxicity technique after which a larger increase in MTX dose could be used to treat some osteogenic sarcomas and head and neck tumors that are insensitive to low doses of MTX without severely damaging normal tissues, and it also treats psoriasis and certain immune diseases. After methotrexate, the addition of calcium formyl tetrahydrofolate can provide tetrahydrofolate coenzyme directly to cells, avoiding the inhibitory effect of methotrexate to reduce its cytotoxic effect.
Mechanism of action】 Mainly through the inhibition of dihydrofolate reductase to hinder the synthesis of tumor cell DNA, and inhibit the growth and reproduction of tumor cells.
Indications】It is used for acute leukemia, especially acute lymphoblastic leukemia, choriocapillary epithelial carcinoma and malignant staphyloma, etc. The effect is better. It is also effective for head and neck tumors, breast cancer, linguopharyngeal cancer, bladder cancer, testicular tumors, lung cancer and pelvic tumors.
Toxic reactions】 MTX can cause severe mucosal reactions, such as stomatitis, ulcerative gastritis, hemorrhagic enteritis, and sometimes intestinal perforation and death; there are also bone marrow suppression, such as granulocytopenia, thrombocytopenia, anemia, and a decrease in complete blood picture, which is related to the dose and dosing regimen used. Repeated application of low dose MTX can cause fatty liver and cirrhosis; high dose MTX can cause nephrotoxicity; it can also cause sperm and egg defects, teratogenic fetuses in pregnant women, delayed menstruation and reduced reproductive function in a few patients.
Methotrexate in the field of rheumatology and immunology
MTX was introduced in 1946 for the treatment of childhood leukemia and was approved by the FDA in 1971 for the treatment of psoriasis and in 1988 for the treatment of active rheumatoid arthritis. Methotrexate has been accepted by rheumatologists worldwide for more than 10 years and has proven to be a very effective, fast-acting, well-tolerated antirheumatic drug with a satisfactory benefit/toxicity ratio. In recent years, methotrexate has also been used in the treatment of other rheumatic diseases such as dermatomyositis, systemic lupus erythematosus, vasculitis, and dry syndrome with satisfactory results, and its role in the treatment of rheumatic and other autoimmune diseases continues to be explored.
Dosing method
Generally, using pulse therapy, oral administration of 7.5-20mg/w for 6-8 weeks can result in significant reduction of RA. Intravenous shock therapy can be tried for severe RA complicated by vasculitis.
Precautions
Free MTX is its active form. Salicylic acid, sulfadiazine, phenobarbital, and chloramphenicol can compete with MTX to bind plasma proteins, thereby increasing the concentration of free MTX; and propofol, salicylic acid, and protamine can reduce renal tubular excretion of MTX, which can increase MTX toxicity if combined with them. Formyl tetrahydrofolate should be given in high-dose shock therapy or in the presence of serious complications to overcome MTX-induced impaired folate metabolism and bone marrow toxicity.
Monitoring of side effects
Check blood and urine routine monthly; check liver and kidney function every 3 months.
Antimalarials (chloroquine/hydroxychloroquine)
Chloroquine, an antimalarial drug, was originally used for the treatment of malaria and has been used since 1951 for the treatment of rheumatoid arthritis. Clinically, quinine phosphate (chloroquine) and hydroxychloroquine (HCQ) are the most commonly used. In general, the side effects of chloroquine are more common and obvious than those of hydroxychloroquine, but the effect of chloroquine is faster, usually 4 weeks after administration, while the effect of hydroxychloroquine is relatively slow, starting to take effect only after 6 weeks of administration, and the obvious effect can be seen only after 3 to 6 months. Currently, hydroxychloroquine is the main antimalarial drug used for anti-rheumatic purposes in the world.
Anti-rheumatic mechanism.
Although antimalarials have been used for antirheumatic treatment for more than 100 years, the exact antirheumatic mechanism has not been completely clarified. Traditionally, it is believed that
1. Interfere with the synthesis of DNA and RNA and inhibit antigen-antibody binding.
2. Inhibition of lymphocyte response to mitogen.
3. Inhibit chemotaxis and phagocytosis of neutrophils.
4. Stabilize the lysosomal membrane, inhibit the synthesis of PGE2, leukotriene, collagenase, etc.,, and have anti-inflammatory and anti-swelling effects.
Dosage and Administration
Chloroquine is administered orally 250mg daily and gradually reduced to 250mg twice a week after achieving efficacy (usually 2-4 months).
Hydroxychloroquine, 200mg twice a day. after 6 months, change to 200mg twice a week.
Clinical Applications
Mainly used for lupus erythematosus, rheumatoid arthritis. Also used for dry syndrome, rheumatic polymyalgia.
Toxic and side effects and treatment
Precautions for chloroquine.
1. This product has damage to cornea and retina, therefore, before long-term treatment with this product, a detailed eye examination should be made to exclude the original lesion, and patients over 60 years old should be examined diligently to prevent visual function impairment. Long-term maintenance dose of 0.25g per day or less is appropriate, and the course of treatment should not exceed 1 year.
2.After taking the drug, there may be reactions such as loss of appetite, nausea and vomiting, diarrhea, etc.; skin itching, purpura, hair loss, hair whitening, eczema and exfoliative dermatitis, psoriasis; heavy head, headache, dizziness, tinnitus, vertigo, lethargy, sleep disorders, mental confusion, reduced visual field, corneal and retinal degeneration, etc.
3.Sometimes leukopenia is seen, and should be discontinued if reduced to below 4000.
4.This product does not contract the uterus, but may cause fetal deafness, hydrocephalus, limb defects, so pregnant women should not use.
5.For a few patients, it may cause arrhythmia, and in serious cases, it may lead to As syndrome, which deserves attention and may lead to death if not rescued in time.
Monitoring of side effects
Ophthalmic examination should be done every 3 months for chloroquine and every 6 months for hydroxychloroquine. Ophthalmologic examination should include visual field, visual acuity, color discrimination, fundus examination, etc. Blood tests should be done monthly.
Salicylazosulfapyridine (SASP)
Salicylazosulfapyridine (SASP or SSZ, also known as sulfasalazine) is an azo compound consisting of 5-aminosalicylic acid and sulfapyridine, which has both the anti-rheumatic effect of salicylic acid and the antibacterial effect of sulfonamides. It was originally used mainly for acute and chronic ulcerative colitis and segmental enteritis, and since 1978, it has gradually become one of the most popular slow-acting antirheumatic drugs, used not only for the treatment of rheumatoid arthritis but also for the treatment of seronegative spondyloarthropathies such as ankylosing spondylitis.
Mechanism of action
1.Antibacterial effect
Although the relationship between rheumatoid arthritis and infection has not been confirmed, the role played by certain bacterial infections of the intestinal tract (such as Klebsiella, Shigella) in the pathogenic process of ankylosing spondylitis and Ritter syndrome has been noted.
2. Immunomodulatory effects.
Inhibit the synthesis of rheumatoid factor and mitogen-induced lymphocyte proliferation. Large doses can also inhibit the activity of natural killer cells.
3.Anti-inflammatory effect
Mainly through the inhibition of thromboxane synthase and lipoxygenase pathway, inhibition of neutrophil chemotaxis and lysozyme activity, as well as IgE-mediated mast cell degranulation effect.
4.Affect folic acid metabolism
Inhibits both the absorption and metabolism of folic acid.
Clinical applications
1.Rheumatoid arthritis (RA)
In 1992, Felson et al. did a meta-analysis of published clinical trials of slow-acting antirheumatic drugs, and the results showed that the efficacy of sulfadoxine-pyridine was less than that of methotrexate (MTX) and better than that of antimalarials. The combination of salazosulfapyridine and methotrexate can increase the efficacy without increasing the side effects; the combination of salazosulfapyridine and antimalarials is not better than salazosulfapyridine alone, so it is not accepted.
2.Ankylosing spondylitis
Sulfasalazine has been used for the treatment of ankylosing spondylitis since the 1980s, and is the drug of choice for the treatment of ankylosing spondylitis. A large number of clinical studies at home and abroad have proved that the efficacy of salazosulfapyridine in the treatment of ankylosing spondylitis increases with the prolongation of the medication, with a medication efficiency of 71% for six months, 85% for one year and 90% for two years.
3.Wright’s syndrome
4.Ulcerative colitis and clonorchiasis
Adverse reactions
1.Gastrointestinal reactions
20% of patients have gastrointestinal reactions, mainly including decreased appetite, nausea, vomiting, etc.
2, a small number of allergic rash, toxic hepatitis, pneumonia, granulocytopenia, individual aplastic anemia (bone marrow suppression), once it appears, must immediately stop the drug. Check the blood picture monthly and monitor closely.
3. Some men develop reversible sperm count reduction, which can be recovered after stopping the drug. Men who plan to have children in the near future should avoid taking it. Some patients may experience headache, general discomfort, and anemia.
Monitoring of side effects
Blood and urine routine once a month. Liver function is checked every 3 months.
Radix Rehmanniae
This product is the root of the plant of the family Weimaraceae, and its leaves, flowers and fruits can be used as medicine. Its function is to dispel wind and dampness, relieve inflammation and pain, detoxify and kill insects. It contains a variety of active substances, such as alkaloids, diterpenes, triterpenes and glycosides, and the most used one at present is Radix et Rhizoma polysaccharide.
Pharmacological effects
1, immunosuppressive effect: inhibit humoral immunity and lymphocyte transformation, less effect on non-specific organism immune defense function. The small dose of Radix et Rhizoma can enhance the activity of spleen NK cells in mice, while the large dose has an inhibitory effect.
2, anti-inflammatory effect: Lei Gong Deng has obvious anti-inflammatory effect, can inhibit the increase of capillary permeability caused by xylene and histamine in mice, and inhibit the formation of swelling and granuloma caused by inflammatory substances in rats.
3.Anti-tumor effect: Radix et Rhizoma hydroxylactone has high anti-tumor activity.
Clinical applications
1.Rheumatoid arthritis (RA)
The treatment of RA has a history of more than 20 years in China, with positive efficacy, rapid onset of action and an efficiency of 80% to 90%.
2, ankylosing spondylitis (AS)
The efficacy of tretinoin in the treatment of AS is no less than that of salbutamol, but AS patients are relatively young, and its side effects on the gonads should be noted.
3.Other connective tissue diseases
4.Renal diseases
5.Other autoimmune diseases
Side effects
1.Reproductive system
The most significant side effect of tretinoin in treatment is its effect on the reproductive system. More than 50% of women of childbearing age develop amenorrhea after six months of taking Radix Polygonatum Tablets. However, if the drug is continued after menopause, it can lead to irreversible amenorrhea, a decrease in estrogen levels in the patient’s blood, and early menopause. Amenorrhea is significantly associated with the total amount of tretinoin used, with the site of action being in the ovaries. There is also a significant correlation between amenorrhea and the age of the patient, with women over 40 years of age, even short-term use of the drug can lead to amenorrhea and it is not easily recovered after discontinuation of the drug. In adult men, sperm concentration and viability have reached the level of infertility after 2 months of taking Radix Polygonatum Tablets and recovered after 2 months of discontinuation. The effect on sexual function is not obvious.
2.Digestive system
The most common side effects of Leigongteng are digestive symptoms, including loss of appetite, nausea and vomiting, heartburn, abdominal pain, diarrhea, and occasionally upper gastrointestinal bleeding. About 10%-15% of patients have elevated serum transaminases, which mostly appear 1 month after the drug is used, and can return to normal after stopping the drug and liver-protective treatment.
3.Skin and mucous membrane
The rash will subside on its own with symptomatic treatment in mild cases, and will be discontinued in severe cases. Stomatitis and mucosal ulcers are less symptomatic and have no effect on treatment. Pigmentation.
4.Hematological system and others
Reglanto has an inhibitory effect on bone marrow, mainly manifested as a decrease in white blood cells, platelets and red blood cells, with granulocytopenia being the most common, and generally recovering only after discontinuation of the drug. Occasionally, palpitations, shortness of breath and arrhythmias may occur.
Monitoring of side effects
Blood and urine routine every 3 months. Liver function is checked every 6 months.
White peony total glucoside (Pafolin)
White peony is the dried root of Paeonia lactiflora, a plant of the buttercup family, is a traditional Chinese medicine in China. The “Compendium of Materia Medica” classifies white peony as a blood nourishing herb with the effects of nourishing blood, softening the liver, astringing yin, collecting sweat, slowing down pain, etc. It is also an important grouping in prescriptions for the treatment of acute and chronic hepatitis and liver cirrhosis. In Chinese medicine prescriptions and Japanese Chinese clinical prescriptions, prescriptions containing Paeonia lactiflora account for about 30% of the total, and have been highly valued by medical practitioners throughout the ages. Paflum capsule is made by Professor Xu Shuyun, Vice Chairman of the Chinese Pharmacological Society and Chairman of the Clinical Pharmacology Base Committee, and dozens of researchers from the Institute of Clinical Pharmacology of Anhui Medical University, after nearly 20 years of research, using modern technology to extract the effective part of Paeonia lactiflora total glycosides. Its main glycoside complexes are paeoniflorin, hydroxyl paeoniflorin, paeoniflorin endoside, and benzoyl paeoniflorin, which can treat autoimmune diseases such as rheumatoid arthritis (RA) by anti-inflammatory and regulating immune function. It is the only new class II western drug of Chinese medicine origin in China.
Pharmacological effects
I. Anti-inflammatory effects
a. Selectively inhibit the production of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in arthritic rats.
b. Significantly reduced fibrin exudation and inflammatory cell infiltration in the ankle joint of arthritic rats.
c. Inhibit the secretion of PGE2, NO, TNFα and IL-1 in AA rat synovial cells and inhibit the proliferation of rat synovial fibroblasts .
d. Protective effect on the liver
II. Immunomodulatory effects
It has a regulatory effect on both cellular and humoral immunity abnormalities. Experimentally, total glucoside of Paeonia lactiflora has a modulating effect on immune abnormalities in adjuvant arthritis and cyclophosphamide-induced cellular and humoral immune depression in rats, which can transform the immune function to normal. In patients with rheumatoid arthritis, total peony glycosides inhibited IL-1 production by monocytes and promoted normalization of IL-2 and IL-2 receptors. Total peony glycosides can return the lower Ts cell count to normal in rheumatoid off patients. (From “Practical Clinical Rheumatology”, edited by Wu Donghai and Wang Guochun, Title V, Chapter 5, Immunobiological Treatment of Rheumatic Diseases)
Third, the effect on free radicals
The anti-arthritic effect of total glucoside of Paeonia lactiflora is related to its reduction of lipid peroxidation and restoration of antioxidant enzyme activity.
Toxicity studies
1. Acute toxicity studies have shown that oral administration of TGP is safe. The LD50 of mice injected intravenously and intraperitoneally were 159 mg/kg and 230 mg/kg, respectively, and no obvious poisoning symptoms and no death were observed with gastric feeding of TGP >2500 mg/kg.
2. Chronic toxicological studies showed that TGP was not toxic to all important organs. Rats and dogs were given three different doses of TGP (50, 1000 and 2000 mg/kg per day by gastric feeding, equivalent to 5-200 times the highest adult dose) for 30 and 90 days without significant toxic damage, indicating that the drug has low toxicity and a large safety range.
3. The triptan test was negative (carcinogenic, mutagenic and teratogenic). The experimental study of reproductive toxicity found that total peony glucoside was still not teratogenic at doses as high as 2160mg.
Treatment of rheumatoid arthritis
Why is it important for patients with rheumatoid arthritis to have early and reasonable treatment? If reasonable treatment is not administered.
60% disability rate in 5-10 years; 90% disability rate in 30 years
With extra-articular involvement: 50% mortality rate
70% of patients develop arthrosis within 3 years
Early use of disease-modifying drugs (slow-acting drugs) can control disease progression and reduce disability.
Early diagnosis is a prerequisite for early treatment, and only early diagnosis and treatment can reduce the rate of disability and death.
From the Chinese Journal of Rheumatology, August 2001, Bone and Joint Diseases
In some studies conducted over a 10-year period, it was found that nearly 50% of patients developed joint space narrowing and/or bone erosion within the first 2 years of the disease, and during the 10-year observation period, at least 50% of those who were originally able to work became disabled (unable to work or could only do less or lighter work).
The disease itself is not curable, and false and exaggerated propaganda should not be listened to. The main goals of treatment are ① to relieve pain; ② to reduce inflammation; ③ to reduce unnecessary adverse reactions; ④ to protect muscle and joint function; ⑤ to restore a comfortable and creative life as much as possible.
Treatment regimens should be individualized and tailored to the patient’s condition. pincus proposed new strategies for the treatment of rheumatoid arthritis in the nineties: early detection of patients with progressive or aggressive disease; early treatment; and the use of new drugs in combination with long-term (5-10 years) observation of outcomes. Therefore, early treatment, regular use of drugs, combination of drugs, and long-term adherence are the most critical principles in the treatment of P. aeruginosa. Internationally, many experts believe that patients with P. aeruginosa need lifelong medication.
Drug treatment plan
Drug therapy for RA usually includes non-steroidal anti-inflammatory drugs (NSAIDs), disease-relieving anti-rheumatic drugs (DMARDs) and glucocorticoids. As the understanding of the disease continues to evolve, the treatment strategy for rheumatic diseases is also changing. Whereas a decade or so ago combination therapy was considered unconventional for severe rheumatoid arthritis only, now almost all rheumatologists are applying combination therapy. This shift in perception is due in part to advances in three areas.
① Early epidemiologic studies suggested that most patients with rheumatoid arthritis have a prolonged and persistent disease that responds poorly to therapeutic agents and has a poor long-term prognosis, leading to joint deformity, impaired function, and a shortened life span. Moreover, most joint erosion occurs within the first 1 to 2 years. Drug therapy can delay the progression of the disease, but generally cannot restore the damaged joint, so aggressive defensive therapy is advocated before the joint is destroyed;
②Studies have shown that a single palliative drug can only bring about remission in less than 2% of patients; continuous application of palliative drugs can indeed slow down the progression of the disease; nowadays, drugs such as hydroxychloroquine, salazosulfapyridine and methotrexate have better efficacy/toxicity ratios, especially methotrexate has good long-term efficacy, low toxicity and is well tolerated by patients. In the treatment of hypertension, tumors and other diseases, it has become almost customary to apply multiple drugs simultaneously when the efficacy of one drug is unsatisfactory. In contrast, rheumatoid patients rarely have complete remission, and many patients should receive combination therapy;
③In recent years several long-term (5-10 years) clinical observation results show that although disease activity including joint pain, joint swelling, blood sedimentation, morning stiffness and grip strength have improved, radiological examination shows that the disease is still progressing. This suggests that partial control of inflammation does not control the progression of radiological changes and that aggressive combination therapy should be used.
Appendix: American College of Rheumatology 2002 edition of rheumatoid arthritis treatment guidelines
The American College of Rheumatology (ACR) has published in its prestigious journal Arthritis Rheum the 2002 edition of its newly revised guidelines for the treatment of RA, which state that the ultimate goal of RA treatment is to prevent and control joint destruction, prevent loss of function, and reduce pain. Prior to treatment, the patient’s initial condition should be evaluated by documenting symptoms of disease activity, functional status, objective evidence of disease activity, mechanical joint damage, extra-articular manifestations, and imaging damage.
Disease activity should also be evaluated. A prolonged period of morning stiffness and fatigue and a joint examination that reveals active synovitis suggest disease activity. Sometimes, joint examination alone is not sufficient to reflect disease activity and joint destruction, and regular monitoring of ESR and CRP levels, examination of joint functional status, and imaging of affected joints should be performed.
Treatment of RA includes non-pharmacological and pharmacological treatments. Non-pharmacologic treatment includes patient education and instruction in moderate activity that does not exacerbate fatigue or joint symptoms, and pharmacologic treatment for RA typically includes non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and glucocorticoids.
NSAIDs with analgesic and anti-inflammatory properties are the initial drugs used to treat RA, but do not alter the course of the disease or joint destruction and, therefore, cannot be used alone for RA treatment. Although NSAID-related gastrointestinal symptoms can be treated with H2 receptor antagonists, routine application of H2 receptor antagonists is not recommended to prevent NSAID-induced gastrointestinal disorders.
Since DMARD has been shown to improve disease and delay bone and joint destruction (confirmed by imaging), any patient diagnosed with RA who has progressive joint pain, significant morning stiffness or fatigue, active synovitis, persistently elevated ESR and CRP levels, or imaging-confirmed bone and joint destruction should be started within 3 months of diagnosis, regardless of whether NSAID use provides adequate symptomatic relief. DMARD therapy should be initiated. New treatment guidelines recommend DMARD combination therapy.
Efficacy evaluation
The following indicators are commonly used for efficacy evaluation in China: rest pain, morning stiffness, grip strength, number and index of painful joints, number and index of swollen joints, ability to perform daily activities, physician’s evaluation, patient’s evaluation, blood sedimentation, CRP and rheumatoid factor. Generally, a few of the major indicators are selected for a comprehensive evaluation of the efficacy.
American College of Rheumatology (ACR) Clinical Remission Criteria.
Five of the following six indicators are required and must last for more than 2 months, while excluding active vasculitis, pericarditis, pleurisy, myositis and recent unexplained weight loss or fever;
1. Morning stiffness of no more than 15 minutes
2. No weakness
3. No joint pressure pain
4. No joint pain or pain with activity
5. No swelling of joint soft tissue or tendon sheath
6. Blood sedimentation <30min/h (female) or 20min/h (male).