Allergen Immunotherapy Scientific Presentation PDF

ALLERGEN IMMUNOTHERAPY SCIENTIFIC PRESENTATION Dr. Massa Saoud 2024 1  TRAINING GOALS − To increase your information about Allergies. − To understand terminology used in the disease....

ALLERGEN IMMUNOTHERAPY SCIENTIFIC PRESENTATION Dr. Massa Saoud 2024 1  TRAINING GOALS − To increase your information about Allergies. − To understand terminology used in the disease. 2  Content Allergy Treatment Allergen Types of Immunotherapy Allergies 3  Content Sublingual Our Products Immunotherapy Subcutaneous Guidelines Immunotherapy 4 DISEASES 5 ALLERGY The body’s immune response to foreign substances common in the environment, and triggers a reaction from the body’s immune response described as hypersensitivity (an exaggerated response). 6 Hypersensitivity: An inappropriate immune response to common, typically harmless antigens, manifesting as a continuum from minor (atopic dermatitis and rhinitis) to severe manifestations (anaphylaxis, anaphylactoid and asthma). 7 Types of Hypersensitivity: Type III Type I Type II Type IV hypersensitivity hypersensitivity hypersensitivity hypersensitivity (immune (immediate (cytotoxic (delayed-type): complex reaction): reaction): reaction): IgE antibodies, IgG and IgM antibodies, IgG, IgM, and IgA T-cells or macrophages This results in mast cell leading to the complement antibodies, are activated as a result of degranulation and release of system activation and cell results in complement system cytokine release, leading histamine and other mediators. damage or lysis. activation, which leads to to tissue damage. polymorphonuclear leukocytes (PMNs) chemotaxis and causing tissue damage. 8  Type I IgE-mediated allergy (Immediate Hypersensitivity): Onset: Rapid (minutes to hours). Mechanism: Involves IgE antibodies and the release of histamine and other inflammatory chemicals. Include: 1. Atopic diseases: which are an exaggerated IgE mediated immune responses (allergic: asthma, rhinitis, conjunctivitis, and dermatitis). 2. Allergic diseases: which are immune responses to foreign allergens (anaphylaxis, urticaria, angioedema, food, and drug allergies). 9  Prevalence IgE-mediated allergy (Immediate Hypersensitivity): The incidence of type I hypersensitivity is hard to predict as discrepancies occur in the assessment of the type of reaction. For instance, some document patients as having anaphylaxis reaction status-post milder symptoms, and others report anaphylaxis with a full-blown presentation. A study predicted that the frequency of an individual experiencing anaphylaxis is 1% to 2% worldwide, with the incidence increasing in the younger population. 10  Prevalence IgE-mediated allergy (Immediate Hypersensitivity): In general, the prevalence of atopic disorders, such as food allergies, allergic rhinitis, conjunctivitis, dermatitis, asthma has been on the rise and occurs in about 20-30% of the population. 11  European Research U.S. 0.3% of the population will About 1.21% to undergo episodes of 15.04% of the anaphylaxis in their lifetime population will experience anaphylaxis 12  Etiology Type I hypersensitivity occurs as a result of exposure to an antigen. There are various types of antigens that the host can be exposed to: Food allergies (nuts, eggs, soy, wheat, shellfish) Animal source (bee, wasp, cats, insects, rats) Environmental factors (dust mites, latex, pollen, mold) Atopic diseases (allergic asthma, allergic rhinitis, conjunctivitis, dermatitis) Medication-induced reactions (antibiotics) Systemic reaction to an allergen (hives)  Etiology The response to the antigen occurs in two stages: The Sensitization The Effect Stage The host experiences an asymptomatic contact The pre-sensitized host is re-introduced to the with the antigen antigen, which then leads to a type I anaphylactic or atopic immune response. 14  Pathophysiology Allergens {antigens} the sensitization phase Antibodies bind to the First time exposure: Antigen- Fc receptors presenting cells T-cells B-cells Mast cells (APCs) Signal for stimulation to produce IgE antibodies Allergens {antigens} Second exposure: Degranulation of the cells and release Mast cells + IgE of histamine, proteolytic enzymes, and antibodies other mediators Crosslinking 15 16 Symptoms 17 Symptoms Pulmonary Skin hives, Ocular allergic reactions, atopic Nasal allergic conjunctivitis eczema, or rhinitis or hay such as allergic flushing fever asthma 18  Risk Factors There are certain risk factors that increase the risk of allergic diseases, include: Geographical distribution Environmental risks (pollution or socioeconomic status) Being a child The “hygiene hypothesis” suggests that our modern Genetic predisposition (having a family history society practices of good hygiene and the lack of early exposure to many microbes or antigens may result in of asthma or allergies, such as hay fever, hives or failures of the immune system functionality. As such, the eczema) hypothesis suggests that early exposure to a diverse range Hygiene hypothesis of microorganisms and antigens may actually lead to overall decreased rates of allergies, asthma, and other immune disorders. 19  Types of allergens Airborne Skin Food Medication Pollens Latex Fish Milk, Eggs Dander Wheat Cleaning products Mites Nuts Cosmetics Molds Pollens Fish 20  1 AIRBORNE ALLERGENS 21  1 Airborne Allergens are proteins or glycoproteins of a molecular weight between 5 and 100 kDa, released from volatile particles that are in suspension in the form of aerosols. Which in most cases are water soluble, capable of inducing IgE antibody production in genetically predisposed (atopic) individuals, will react abnormally and presenting symptoms that will depend on the type and intensity of the allergen load and the specific tissue where the interaction occurs Which are responsible for allergic rhinitis, conjunctivitis, and asthma, chronic diseases that could be seasonal or perennial, affect quality of life, and generate high healthcare costs. Larger particles > 10–20 µm are retained in the nose and Smaller particles 2 - 5 µm conjunctiva, causing reach more distal regions and therefore rhinoconjunctivitis. are capable of eliciting asthma symptoms 22 Airborne Allergens can be classified, according to their area of exposure, into indoor allergens (mites, epithelia, fungi, and pests) or outdoor allergens (pollens and fungal spores), as well as according to the time of exposure into being perennial or seasonal. Also it can be classified according to the frequency of recognition: Major allergens (> 50% of sensitized individuals). Minor allergens (< 50% of sensitized individuals). 23 Requirements for a substance to be considered a respiratory allergen: 1. To be present in the environment. 2. In sufficient quantities to induce sensitization. 3. Allergic sensitization is demonstrable by a skin test or by a specific IgE. 4. Produce symptoms after inhalation. 5. Molecular size of less than 100 kDa (mainly between 3 and 60 kDa). 6. Induction of T cell proliferation. 7. Usually intra- and interspecific cross-reactivity. 24 INDOOR ALLERGENS 25  Dust Mites Mites belong to the class Arachnida, subclass Acari, and order Astigmata. Microscopic arthropods that are about 300 µm long, blind, and photophobic, that exchange O2 and CO2 through their body surfaces, they select food that has been precomposed by fungi, their life cycle from an egg to an adult mite is about 30 days. There are two groups of dust mites, house dust mites (HDMs) and storage mites (SMs), that have been identified in household environments. 26 The most relevant families for allergenic purposes: Dermatophagoides Dermatophagoides Pyroglyphidae pteronyssinus farinae Euroglyphus mainei Glycyphagus Lepidoglyphus Glycyphagidae domesticus destructor - Echimyopodidae Blomia tropicalis - - Tyrophagus Acaridae putrescentiae Acarus siro - 27  Allergens from mites have a high sensitizing capacity, constituting through their frequency and ubiquity the main inner indoor pneumoallergen. The ideal habitat for Dermatophagoides is a domestic environment in areas with temperatures above 25◦C and a relative humidity higher than 75–80%, conditions that occur in homes in coastal areas. They grow in dust, accumulate in carpets, rugs, mattresses, pillows, and curtains, and feed on human flaking. They reach average concentrations of 100-500 mites per gram of dust, where concentrations above 100 mites/g of dust are considered to initiate allergic responses in sensitized individuals. At more than 1000 m above sea level and/or in arid environments, the Dermatophagoides population is drastically reduced until it disappears in situations of ambient humidity below 55%, which demonstrates their low resistance to desiccation. 28  The most important allergens of the mites are found in: Feces, each mite produces about 10–20 feces particles per day. Bodies, the diameter of particles ranges from 15 to 30 microns, so large enough to remain airborne for more than a few minutes. The most important allergens (groups 1 and 2) act as proteases, which in addition to inducing the production of specific IgEs are able to detach elements of the respiratory epithelium, making it more permeable to allergens and other irritating particles, acting as adjuvants in Th2 allergic inflammation and increasing bronchial hyperresponsiveness. 29  Pet Dander About 10% of the population in developed countries shows allergy to dogs and/or cats. Pet allergens are ubiquitous, acting as hidden “mines”, due to their presence in private and public places, the presence of these allergens has been demonstrated in the homes and automobiles of those who don’t have furry pets in concentrations sufficient to generate sensitization and even an allergy (established at 1 and 8 mcg/g of dust for Fel d1 (Cat) as well as 2 and 10 mcg/g for Can f1). It can float in the air for several days, and even after the pet is removed from the home, persist for months in the environment, making it a public health problem, because the higher the number of people with pets the greater levels of allergens transferred, increasing their load in common spaces. 30  In cat allergy Fel d1, about 95% of patients are sensitized to this secretoglobine which is present in perianal and sebaceous glands, as well as in saliva (particles of a size between 5 and 9 microns, and so can reach the distal bronchi and induce asthma alongside rhinitis symptoms). The sensitization profiles against dogs are more diverse and there is not a single predominant allergen. Can f1 and Can f2 are lipocalins that come from saliva and sebaceous glands. Pet allergens are carried by particles present in saliva, dander, urine, and hair. These particles, depending on their weight, are deposited on the floor and furniture or remain suspended in the air. These differences may be influenced, among other things, by the number of dogs, their size, the cleanliness of a home, age, hydration, and frequency as well as type of pet washing. 31  Cockroaches The prevalence of cockroach allergy ranges in the United States from 17 - 41%, while in Europe 25% of asthmatic children are sensitized to cockroaches. Cockroach allergy is an important risk factor for hospital admissions, emergency department visits, and asthma morbidity, exerting a greater impact on the latter than dust mites or pets. Come from dried remains of the Humid, dark, and cytoskeleton, temperate areas & secretions, eggs, and feed on plants, fecal matter, which can paper, tissues, become airborne and insect remains, cause perennial allergic and food. symptoms 32  Of the approximately 4000 species of cockroaches, the most frequently encountered in domestic environments and therefore of allergenic interest are Blatella germanica, Periplaneta americana, and Blatta orientalis. These allergens can remain in the environment for several months, carried in particles of a size of 70% predicted. 152 153 GINA Allergen-specific immunotherapy may be considered as add-on therapy for adults and children with asthma who have clinically significant sensitization to aeroallergens, including in those with allergic rhinitis. It involves the identification of clinically relevant allergens and the administration of extracts in precisely calculated doses to induce desensitization and/or tolerance. Allergen immunotherapy is currently the only intervention with both an immune modifying effect and long-term efficacy on the allergic response. There are two approaches: subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). 154  2 DEVELOPED BY EUFOREA EXPERT TEAMS BASED ON INTERNATIONAL GUIDELINES 155 156 157 158 159  3 ARIA 160 1. We suggest subcutaneous allergen immunotherapy in adults with seasonal (conditional recommendation | moderate quality evidence) and perennial allergic rhinitis due to house dust mites (conditional recommendation | low quality evidence). 2. In children with allergic rhinitis, we suggest subcutaneous immunotherapy (conditional recommendation | low quality evidence). 3. We suggest sublingual allergen immunotherapy in adults with rhinitis due to pollen (conditional recommendation | moderate quality evidence) or house dust mites (conditional recommendation | low quality evidence). 4. In children with allergic rhinitis due to pollens, we suggest sublingual allergen immunotherapy (conditional recommendation | moderate quality evidence). 161 1. In patients with allergic rhinitis and asthma, we suggest subcutaneous immunotherapy for treatment of asthma (conditional recommendation | moderate quality evidence). 2. In patients with allergic rhinitis and asthma, we suggest sublingual immunotherapy for treatment of asthma (conditional recommendation | low quality evidence). We present specific recommendations for: Prevention of allergy, allergic rhinitis, and/or asthma Reducing allergen exposure for treatment of allergic rhinitis and/or asthma Pharmacological treatment of allergic rhinitis Immunotherapy in allergic rhinitis Alternative and complementary treatment of allergic rhinitis Treatment of asthma in patients with concomitant allergic rhinitis 162  Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence 2020 163 164 165  4 EAACI 166 167 168 169 170 171 172 173 174  5 Australian society of Clinical immunology and allergy 175 Aeroallergen Immunotherapy In most patients who are allergic to aeroallergens, allergen immunotherapy reduces, allergic reactions to aeroallergens. The aims of AIT are to: Reduce symptom severity and medication use in allergic rhinitis and allergic asthma. This may lead to improvement of quality of life (QOL), improved functional capacity at work and school, reduced absenteeism and presenteeism, and reduced hospital admissions for asthma. Improve tolerance to allergen exposure. Possibly reduces the risk of new allergic sensitizations in patients. Possibly reduces the risk of asthma development in patients with allergic rhinoconjunctivitis. 176 AIT may be considered as a therapeutic option only when all of the following criteria are met. The patient: Has an allergic disorder that has been shown to benefit from AIT. Has clinical evidence of a relationship between allergen exposure and symptoms. Has specific IgE to the relevant allergenic trigger (shown by blood sIgE test or SPT). Is able to give informed consent and a commitment to adhere to treatment course (for child parent/guardian). Has no absolute contraindications to AIT. Has allergic disease for which a commercially manufactured allergen extract suitable for AIT is available. Is unable (e.g. occupational or social exposures) or unwilling (e.g. pets) to avoid exposure. Other selection criteria: Children over five years of age (current recommendation; related partly to patient acceptability and partly to trials showing benefit in patients five years and older), but this is not an absolute limitation. Allergic disease is impacting significantly on QOL. Medication is inadequately effective to control symptoms, poorly tolerated, or patient wants to reduce medication use. Likelihood of greater adherence to supervised AIT than medication 177  5 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE– and Institute of Medicine–based recommendations 178 179 180 181 182  Should allergen immunotherapy be used for atopic dermatitis? What is the best evidence regarding the benefits and harms of allergen immunotherapy (AIT) to treat AD, and in whom should it be used? Recommendation: In patients with moderate-severe atopic dermatitis refractory, intolerant, or unable to use mid-potency topical treatment (adding allergen immunotherapy to standard topical treatment over not adding). conditional recommendation, moderate-certainty evidence. 183  6 American Academy of Dermatology Association 184 Allergen immunotherapies have been used in the treatment of asthma and allergic rhinitis and are now being tested for atopic dermatitis AD management. Preliminary studies on sublingual immunotherapy for dust mites demonstrated modest positive results, which may be more evident in those with milder AD. A series of small prospective studies on injection immunotherapy for HDM also had positive results. 185  7 APJAI 186  Allergen-specific immunotherapy is a potentially effective treatment modality for IgE-mediated AD. A subcutaneous administration using house-dust mites is most commonly employed for ASIT in AD. It can be administered sublingually or subcutaneously. Some studies have shown that ASIT can reduce the disease’s severity and improve the quality of life of patients with AD. ASIT therapy should be conducted under specialists’ care. 187  5 KAAACI Guidelines for Allergen Immunotherapy: 188  AIT is indicated for patients with allergic rhinitis (with or without allergic asthma or conjunctivitis) who are sensitized to clinically relevant allergens and have moderate to severe symptoms despite appropriate pharmacological treatment (High). Treatment effects of AIT are proven in target allergens, including pollens, HDM, Hymenoptera venom, furry pet animals, cockroaches, and mold (e.g., Alternaria, Cladosporium) (High). Major allergens in Korea consist of HDM, pollens (birch, oak, mugwort, ragweed, Japanese hop, grass), and furry pet animals (Very low). The selection of target allergens for AIT should be based on allergen exposure and subsequent symptoms and the results of skin prick test, sIgE levels or both (High). The target allergen for AIT should be confined to a single or minimal number of allergens with clinical relevance (Very low). Among pollens with cross-reactivity to each other, one pollen in the same genus or subfamily can be chosen as a target allergen for immunotherapy (Moderate). The concentration of each constituent allergen must be equal to or larger than that proven to be therapeutically effective. If the target maintenance dose cannot be tolerated, a lower dose, referred to as the maintenance dose, may provide clinical benefits (High) 189  AIT in children can prevent new allergen sensitization and reduce the occurrence of future allergic diseases, such as asthma in rhinitis patients (High). As with adults, AIT in children is most effective. SCIT or SLIT is recommended for allergic rhinitis, asthma, and bee venom allergy. Allergens mainly used for AIT are HDM, pollen, bee venom, and pet dander, which are similar to those of adults (High). For safety reasons, pediatric AIT is recommended for those aged 5 years or older. If AIT is performed in children younger than this, SLIT may be considered because injection therapy may be difficult (High). Since both SCIT and SLIT are equally effective in children, the choice depends on the preference, cost, and compliance of the patient or caregiver (High) 190 SUMMARY 191 192  Use our editable graphic resources... You can easily resize these resources without losing quality. To change the color, just ungroup the resource and click on the object you want to change. Then, click on the paint bucket and select the color you want. Group the resource again when you’re done. 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