In 1911, Noon & Freeman began experimenting with SAV (then called desensitization) for the treatment of hay fever, and it has been used for more than 90 years since then. terminology such as desensitization or hyposensitization and recommended the term allergenimmunotherapy. Over the past few decades, SAV has fallen into disfavor due to the potential for severe allergic reactions and the improved efficacy of inhaled glucocorticosteroids for asthma. In recent years, with the recognition of the limitations of the efficacy of inhaled glucocorticosteroids, the efficacy of SAV has been re-evaluated and its place in the treatment of allergic diseases has been re-affirmed by the WHO. Studies have shown that allergic diseases, including asthma, are caused by a combination of an imbalance in the Th1/Th2 ratio in the immune response and several other factors. Immunotherapy can interfere with the natural progression of type I allergic reactions by modulating the cellular and humoral immune responses in allergic diseases, as well as preventing the occurrence of allergic reactions to new allergens and the progression from allergic rhinitis to asthma.
SAV is by far the most direct method for the etiological treatment of allergic diseases, mainly for the prevention and treatment of type I allergic diseases such as allergic asthma, allergic rhinitis, hay fever, allergic skin disease and bee venom allergy. The European Academy of Allergy and Clinical Immunology (EAACI) summarized the research progress of SAV in recent years more comprehensively in 1988 and 1992, respectively, and affirmed that SAV has the dual significance of attack prevention and etiological treatment for allergic diseases such as allergic asthma and allergic rhinitis, and has long-lasting efficacy with few side effects. China has been treating allergic asthma, atopic dermatitis and allergic rhinitis with dust mites for more than 20 years in Shanghai, treating a total of 2 million people, with an efficiency rate of 70% in adults and up to 80% in children.
In 1997, the WHO Working Group on Allergen Immunotherapy met in Geneva and published the WHO position paper (Allergen immunotherapy: Therapeutic vaccines for allergic diseases), which became a global guideline for the treatment of allergic diseases. In 1997, the Berlin International Symposium on Allergic Reactions (IBSA) clarified the indications for SAV, the best time to start treatment and the duration of treatment. The Global Initiative for the Control of Asthma (GINA) has also included SAV in its treatment protocol. The use of standardized allergen preparations with high purity, high immunogenicity and low allergenicity, together with the improvement of treatment methods and the application of non-injectable routes, has gradually made SAV more effective and safer, and it has become one of the important measures in the current treatment of asthma in remission, taking its place in the current asthma treatment regimen based on anti-inflammatory drugs such as inhaled glucocorticoids and bronchial antispasmodics.
Looking forward to the 21st century, SAV will be studied around the following four areas.
(i) Allergen gene immunotherapy: Introducing trace amounts of allergen genes into the body through DNA vaccines to produce a durable immune response in the body;
(ii) recombinant allergen therapy: recombinant antigenic protein of allergens for immunotherapy by genetic engineering technology, which can provide material guarantee for commercialization of allergen vaccines;
③Research on surprise immunotherapy, oral or sublingual immunotherapy;
④Study on the feasibility of using interventional therapy for SAV in children with asthma at the early stage of atopy.
【Treatment objectives】.
(a) To change the course of allergic diseases such as allergic asthma and allergic rhinitis The standardized treatment of allergic diseases such as allergic asthma and allergic rhinitis should be combined with pharmacotherapy and SAV The symptoms of asthma patients can be controlled by pharmacotherapy, while SAV can change the evolution of asthma and improve the prognosis, such as preventing irreversible asthma by reducing sensitivity to allergens and reducing the airway inflammatory response the appearance of airway inflammatory damage, reducing asthma symptoms by inhibiting or eliminating airway inflammation, reducing the amount of medication used by asthma patients, and improving the quality of life of patients, thus improving the prognosis of allergic diseases such as allergic asthma and allergic rhinitis, and potentially enabling some asthma patients to be cured.
(B) Prevention of allergic diseases such as allergic asthma and allergic rhinitis 1. Early SAV for patients with allergic rhinitis can prevent further development of the disease to allergic asthma. According to statistics, only 5% of patients with allergic rhinitis develop allergic asthma after routine SAV, while 23-68% of those who do not undergo SAV develop allergic asthma.2. SAV can prevent asthma patients from developing allergic reactions to new allergens and improve the body’s tolerance to various allergens. The above points are especially important for children with asthma. Long years of clinical practice have confirmed that SAV is significantly more effective in children than adults with asthma. Long-term remission rates in children with asthma can be greatly improved by appropriate SAV, and children with allergic rhinitis can be prevented from developing allergic asthma. Children with atopic qualities can also be made much more tolerant to the corresponding allergens by SAV, and even benefit for life.
Indications and contraindications for desensitization therapy]
Most allergists believe that the indications for SAV should be the same as those for long-term prophylaxis, i.e., anti-inflammatory therapy in remission (including inhaled glucocorticoids or sodium cromoglycate, etc.) and SAV can be administered simultaneously. Adjuvant SAV can alter the natural course of I allergic diseases, including asthma. Since allergic asthma, allergic rhinitis and other allergic diseases have many triggers, especially many inhaled allergens are difficult to avoid, and complete avoidance of inhaled allergens is still difficult for most patients when living conditions in China are not perfect at present, SAV has a broader indication in China.
Patients with allergic asthma, allergic rhinitis and other allergic diseases should consider the following aspects before undergoing SAV.
(a) Determine the etiology of patients with bronchial asthma confirmed to be IgE-mediated and with defined allergens, especially those induced by some unavoidable allergens, should undergo SAV early. treatment is preceded by careful history taking, skin allergen testing, bronchial excitation testing, and measurement of allergen-specific IgE and allergen-specific T cells to clarify the allergens. SAV is not advocated in asthmatic patients with more than three completely unrelated allergens or with allergens that are difficult to identify, or with allergens that can be avoided.
(b) The course of the disease is advocated in the early stages of asthma, when irreversible airway damage has not yet occurred. sAV can alter its natural course, reduce chronic airway inflammation, and avoid irreversible airway damage. SAV is not recommended for patients with advanced asthma whose FEV1 values are still lower than 70% of the expected values after appropriate drug therapy, suggesting that irreversible airway damage already exists at this time.
(c) The severity of the asthma patient’s condition should be judged before formulating a treatment plan, and the suitability of SAV should be analyzed in conjunction with other factors, and the possible benefits as well as risks and complications of SAV should be fully considered. SAV should be considered in the following situations.
(1) Patients whose disease has progressed or progressed from allergic rhinitis to asthma despite treatment with allergen avoidance measures or application of appropriate medications.
(2) Those with allergic rhinitis, allergic rhinitis-asthma syndrome and allergic asthma requiring daily medication for symptom control.
(3) Patients with allergic rhinitis, allergic rhinitis asthma syndrome and allergic asthma requiring year-round use of preventive medication.
(4) Patients with asthma whose condition cannot be controlled by inhaled glucocorticoids and bronchial antispasmodics.
The use of SAV is not recommended in the following cases.
(1) Severe asthma. The more severe the asthma, the less effective the treatment.
(2) Those with combined chronic bronchitis and obstructive emphysema.
(3) Those with unstable disease. Because SAV has the potential to stimulate exacerbation of the disease.
(4) Age is more effective in children with asthma and allergic rhinitis asthma syndrome than in adults with asthma and adult allergic rhinitis asthma syndrome.
Because of the short duration of asthma in children, the absence of irreversible airway damage, and the underdeveloped and malleable immune system of children, SAV in early childhood has the potential to achieve a cure. The age of >5 years is generally advocated, but with the improvement of safety and the use of non-injection routes, it is not contraindicated in children younger than 5 years, but it should be performed under the guidance of an experienced physician and closely observed, and there should be resuscitation measures at the scene, and intravenous access can be established quickly, etc. Elderly patients with asthma are less effective. Since most elderly patients with asthma have had irreversible inflammatory damage to the airways or have developed irreversible pulmonary dysfunction, and the importance of IgE-mediated allergic reactions in the pathogenesis of elderly asthma has decreased. Together with the fact that elderly patients often have a combination of heart disease or hypertension, the use of epinephrine is limited in the event of an unexpected reaction to SAV. Therefore, the efficacy/safety ratio of elderly patients with asthma receiving SAV is poor and its use is not advocated.
(v) SAV is contraindicated when the following physical conditions are present.
(1) Pregnant women. There is no evidence of teratogenic effects of SAV, but initiation of SAV is generally not advocated in patients with combined pregnancy, but it is not necessary to discontinue the drug if SAV has been performed before pregnancy.
(2) Patients with combined severe autoimmune disease or malignancy. It is contraindicated in patients with collagenous diseases, autoimmune diseases, lymphoid tissue proliferative diseases and other more serious immune diseases to avoid aggravation; use with caution in patients with combined severe atopic dermatitis.
(3) Contraindicated in patients with combined hypertension, coronary artery disease and other conditions that should not be treated with epinephrine. Because SAV may cause systemic allergic reactions or even anaphylaxis, such patients cannot be treated with epinephrine for first aid, making the risk much higher. Those treated with beta-blockers should also not receive SAV.
(4) Lack of compliance is contraindicated in patients. Successful immunotherapy requires the patient to cooperate with the physician, to receive long-term and regular treatment, and to complete the course of treatment. if the patient lacks cooperation or has serious psychological disorders, SAV should not be performed. in summary, the indications and contraindications for performing SAV should be strictly mastered, and the ratio of efficacy to side effects should be comprehensively evaluated to select suitable patients to achieve the best treatment effect and to avoid serious side effects. Various treatment options regarding desensitization therapy can be referred to the extended reading.
(VI) Treatment options
1.Rapid desensitization injection This method is to reach the maintenance amount in a short time, after starting the treatment, the antigen is injected 2~4 times a day and the dose of antigen is multiplied, that is, 0.1, 0.2, 0.4, 0.8ml, and the concentration is changed in about two days, and then it is changed to once every one or two weeks after the concentration of antigen has reached the maintenance amount. Patients who choose this method need to be hospitalized. The use of rapid desensitization injections is effective and convenient for the patient, but certain local and systemic reactions often occur. Such as the appearance of rhinitis symptoms, chest tightness, asthma, etc. There is a maintenance volume mentioned here, and there is actually a maintenance concentration, both of which refer to the degree that the patient can tolerate, that is, the maximum dose and concentration that the patient will not have local or systemic reactions.
2, perennial hyposensitization injections choose perennial hyposensitization injections for allergic rhinitis, safety is guaranteed, there is generally no systemic reaction, the efficacy is durable and stable, but it will take a long time, patients need to adhere to the treatment. To use this method, after the starting concentration is determined at the beginning, the injection will start from 0.1ml, and the initial injection will be given once every two or three days, in increments of one at a time, with ten days as a course of treatment, and one concentration will be used for one course of treatment. Generally speaking, the concentration of the first course of treatment is 1:106 to 1:108, and then it will be increased according to the course of treatment, and finally reach the maintenance concentration and maintenance amount. The number of injections is gradually reduced, from once every two or three days at the beginning to once a week to once every two weeks or a month, etc., depending on the patient’s condition. It is often necessary to adhere to two to three years.
This method is mainly for seasonal allergic rhinitis, which is injected three months before the pollen period, so that the pollen period can reach sufficient concentration to effectively prevent and control allergic rhinitis. The injections can be stopped after the pollen period.
How is desensitization performed?
Sublingual desensitization Sublingual desensitization therapy is currently only available for patients with dust mite and house dust mite allergies. The method is safer to use and the patient complies with the method. It is administered at different maintenance doses depending on age. It is easy to use with drops under the tongue for 1-3 minutes at a relatively fixed time each day. The incremental phase of the dose is divided into #1, #2, and #3. Maintenance doses are divided into #4 and #5. Generally, those under 14 years of age are maintained with No. 4 and those over 14 years of age are maintained with No. 5. For dust mite induced allergic rhinitis, allergic asthma, allergic conjunctivitis, allergic rash, allergic urticaria, allergic conjunctivitis, etc. Patients also have altered immunological indices in vivo before and after sublingual dust mite immunotherapy. Due to the thin tissue of the sublingual mucosa, these Langerhans cells located on the surface of the mucosa will trap the signal of the presence of allergens when they come in contact with antigens, and the allergen vaccine can be rapidly absorbed, thus initiating a desensitization reaction. This includes an increase in serum IgG4 levels and an improvement in the Th2/Th1 cell ratio.
Because it is administered sublingually, it usually does not produce serious adverse reactions such as anaphylaxis. Very few patients occasionally have a mild rash or mild diarrhea, which can be recovered by stopping treatment or reducing the dose. The mechanism of sublingual desensitization therapy is because the sublingual mucosa has a very large number of Langerhans cells, which process and convert them into mite peptide information by absorbing minute amounts of dust mite allergens, and prevent the occurrence of allergic reactions by presenting them to Th0 cells, which convert Th0 cells to Th1 cells. Acupoint Desensitization Patch Desensitization Patch is a special patch for the treatment of allergic rhinitis and other allergic reactive diseases. The product integrates traditional meridian science and modern immune theory, while using advanced nano-liposome-containing drug encapsulation technology, which provides a more scientific, effective, convenient and painless option for the desensitization treatment of allergic rhinitis and other allergic diseases from the technical point of view of transdermal absorption pathway.
”Nano desensitization therapy” is based on the principle of “injection desensitization”, and changes the route of drug delivery to enter the body through transdermal penetration. Tio2(titanium dioxide) nanocrystals can effectively decompose the organic matter in the dry allergen powder under the catalyst of light and far infrared rays, and produce free small molecule antigen; at the same time, Tio2(titanium dioxide) nanocrystals can decompose the skin keratin layer protein under the catalyst of light, and make the epithelial tissue At the same time, Tio2 (titanium dioxide) nanocrystals under photocatalysis can break down the skin keratin layer protein, so that the epithelial tissue gap increases, which is conducive to promoting small molecule antigen continuous and maximum penetration of skin into the body. The body gradually develops immune tolerance under the long-term continuous stimulation of these antigens and does not react to further exposure to allergens. The total course of subcutaneous desensitization treatment takes 2 to 3 years. Desensitization therapy is divided into two parts: initiation therapy and maintenance therapy.
【Initiation treatment】is 15-17 weeks.
The way: you need to come to the hospital once a week for subcutaneous injection, and the injection dose is gradually increased every week to induce the body to build up tolerance mechanism to mites.
Maintenance treatment] is injected every 6-8 weeks to consolidate the efficacy of previous treatment.
The way: pediatric experts from Shenzhen Far Eastern Women’s and Children’s Hospital point out that after each injection, you need to take a 30-minute break at the desensitization center and have your lung function and heartbeat and breathing checked by medical staff before and after each treatment to ensure that your physical condition is acceptable for treatment and to adjust your medication. Desensitization desensitization treatment standardized treatment is safe and reliable the fastest growing desensitization treatment (i.e. specific immunotherapy or immunotherapy) method in the world, in line with the rationalized treatment plan of symptomatic + causative treatment recommended by the World Health Organization. Both the symptoms and the root cause: fundamental treatment of allergic diseases, with significant effect and complete desensitization; overcoming the limitations of traditional hormonal chemical drugs that only treat the symptoms when the disease is onset, treating the symptoms but not the root cause, and with the prolongation of taking time, with varying degrees of adverse reactions may produce a certain degree of drug resistance. High safety: Globally, no serious side effects have occurred in 30 years of use, which maximizes the safety of long-term medication for desensitization therapy; avoids the serious systemic adverse reactions (including anaphylaxis and even death) that may be caused by injectable desensitization therapy, thus reducing the psychological burden of health care workers and patients.