Hubbry Logo
AllergenAllergenMain
Open search
Allergen
Community hub
Allergen
logo
7 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Allergen
Allergen
Allergen
View on Wikipedia
from Wikipedia

An allergen is an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response.

In technical terms, an allergen is an antigen that is capable of stimulating a type-I hypersensitivity reaction in atopic individuals through immunoglobulin E (IgE) responses.[1] Most humans mount significant immunoglobulin E responses only as a defense against parasitic infections. However, some individuals may respond to many common environmental antigens. In atopic individuals, non-parasitic antigens stimulate inappropriate IgE production, leading to type I hypersensitivity.[citation needed]

Sensitivities vary widely from one person (or from one animal) to another. A very broad range of substances can be allergens to sensitive individuals.

Examples

[edit]
SEM of miscellaneous plant pollens. Pollens are very common allergens.
The house dust mite, its feces and chitin are common allergens

Allergens can be found in a variety of sources, such as dust mite excretion, pollen, pet dander, or even royal jelly.[2] Food allergies are not as common as food sensitivity, but some foods such as peanuts (a legume), nuts, seafood and shellfish are the cause of serious allergies in many people.[3]

The United States Food and Drug Administration recognizes nine foods as major food allergens: peanuts, tree nuts, eggs, milk, shellfish, fish, wheat, soy, and most recently sesame,[4] as well as sulfites (chemical-based, often found in flavors and colors in foods) at 10ppm and over.[citation needed] In other countries, due to differences in the genetic profiles of their citizens and different levels of exposure to specific foods, the official allergen lists will vary. Canada recognizes all nine of the allergens recognized by the US as well as mustard.[5] The European Union additionally recognizes other gluten-containing cereals as well as celery and lupin.[6]

Another allergen is urushiol, a resin produced by poison ivy and poison oak, which causes the skin rash condition known as urushiol-induced contact dermatitis by changing a skin cell's configuration so that it is no longer recognized by the immune system as part of the body. Various trees and wood products such as paper, cardboard, MDF etc. can also cause mild to severe allergy symptoms through touch or inhalation of sawdust such as asthma and skin rash.[7]

An allergic reaction can be caused by any form of direct contact with the allergen—consuming food or drink one is sensitive to (ingestion), breathing in pollen, perfume or pet dander (inhalation), or brushing a body part against an allergy-causing plant (direct contact). Other common causes of serious allergy are wasp,[8] fire ant[9] and bee stings,[10] penicillin,[11] and latex.[12] An extremely serious form of an allergic reaction is called anaphylaxis.[13] One form of treatment is the administration of sterile epinephrine to the person experiencing anaphylaxis, which suppresses the body's overreaction to the allergen, and allows for the patient to be transported to a medical facility.[14]

Although allergic reactions typically require prior sensitization to a specific allergen, clinical symptoms can sometimes occur upon first exposure to a food or substance; this is explained by IgE cross-reactivity, where prior sensitization to structurally homologous proteins from other sources leads the immune system to recognize similar proteins in the new allergen as triggers, even though the affected individual has never previously consumed or contacted it.[15]

Common

[edit]
Common food allergens
Main article: List of allergens

In addition to foreign proteins found in foreign serum (from blood transfusions) and vaccines, common allergens include:

Seasonal

[edit]

Seasonal allergy symptoms are commonly experienced during specific parts of the year, usually during spring, summer or fall when certain trees or grasses pollinate. This depends on the kind of tree or grass. For instance, some trees such as oak, elm, and maple pollinate in the spring, while grasses such as Bermuda, timothy and orchard pollinate in the summer.

Grass allergy is generally linked to hay fever because their symptoms and causes are somehow similar to each other. Symptoms include rhinitis, which causes sneezing and a runny nose, as well as allergic conjunctivitis, which includes watering and itchy eyes.[18] Also an initial tickle on the roof of the mouth or in the back of the throat may be experienced.

Also, depending on the season, the symptoms may be more severe and people may experience coughing, wheezing, and irritability. A few people even become depressed, lose their appetite, or have problems sleeping.[19] Moreover, since the sinuses may also become congested, some people experience headaches.[20]

If both parents have had allergies in the past, there is a 66% chance for the individual to experience seasonal allergies, and the risk lowers to 60% if just one parent has had allergies.[21] The immune system also has strong influence on seasonal allergies, because it reacts differently to diverse allergens like pollen. When an allergen enters the body of an individual that is predisposed to allergies, it triggers an immune reaction and the production of antibodies. These allergen antibodies migrate to mast cells lining the nose, eyes, and lungs. When an allergen drifts into the nose more than once, mast cells release a slew of chemicals or histamines that irritate and inflame the moist membranes lining the nose and produce the symptoms of an allergic reaction: scratchy throat, itching, sneezing and watery eyes. Some symptoms that differentiate allergies from a cold include:[22]

  • No fever.
  • Mucous secretions are runny and clear.
  • Sneezes occurring in rapid and several sequences.
  • Itchy throat, ears and nose.
  • These symptoms usually last longer than 7–10 days.

Among seasonal allergies, there are some allergens that fuse together and produce a new type of allergy. For instance, grass pollen allergens cross-react with food allergy proteins in vegetables such as onion, lettuce, carrots, celery, and corn. Besides, the cousins of birch pollen allergens, like apples, grapes, peaches, celery, and apricots, produce severe itching in the ears and throat. The cypress pollen allergy brings a cross reactivity between diverse species like olive, privet, ash and Russian olive tree pollen allergens. In some rural areas, there is another form of seasonal grass allergy, combining airborne particles of pollen mixed with mold.[23] Recent research has suggested that humans might develop allergies as a defense to fight off parasites. According to Yale University Immunologist Ruslan Medzhitov, protease allergens cleave the same sensor proteins that evolved to detect proteases produced by the parasitic worms.[24] Additionally, a new report on seasonal allergies called "Extreme allergies and Global Warming", have found that many allergy triggers are worsening due to climate change. 16 states in the United States were named as "Allergen Hotspots" for large increases in allergenic tree pollen if global warming pollution keeps increasing. Therefore, researchers on this report claimed that global warming is bad news for millions of asthmatics in the United States whose asthma attacks are triggered by seasonal allergies.[25] Seasonal allergies are one of the main triggers for asthma, along with colds or flu, cigarette smoke and exercise. In Canada, for example, up to 75% of asthmatics also have seasonal allergies.[26]

Diagnosis

[edit]

Based on the symptoms seen on the patient, the answers given in terms of symptom evaluation and a physical exam, doctors can make a diagnosis to identify if the patient has a seasonal allergy. After performing the diagnosis, the doctor is able to tell the main cause of the allergic reaction and recommend the treatment to follow. Two tests have to be done in order to determine the cause: a blood test and a skin test. Allergists do skin tests in one of two ways: either dropping some purified liquid of the allergen onto the skin and pricking the area with a small needle; or injecting a small amount of allergen under the skin.[27]

Alternative tools are available to identify seasonal allergies, such as laboratory tests, imaging tests, and nasal endoscopy. In the laboratory tests, the doctor will take a nasal smear and it will be examined microscopically for factors that may indicate a cause: increased numbers of eosinophils (white blood cells), which indicates an allergic condition. If there is a high count of eosinophils, an allergic condition might be present.[28]

Another laboratory test is the blood test for IgE (immunoglobulin production), such as the radioallergosorbent test (RAST) or the more recent enzyme allergosorbent tests (EAST), implemented to detect high levels of allergen-specific IgE in response to particular allergens. Although blood tests are less accurate than the skin tests, they can be performed on patients unable to undergo skin testing. Imaging tests can be useful to detect sinusitis in people who have chronic rhinitis, and they can work when other test results are ambiguous. There is also nasal endoscopy, wherein a tube is inserted through the nose with a small camera to view the passageways and examine any irregularities in the nose structure. Endoscopy can be used for some cases of chronic or unresponsive seasonal rhinitis.[29]

Fungal

[edit]

In 1952 basidiospores were described as being possible airborne allergens[30] and were linked to asthma in 1969.[31] Basidiospores are the dominant airborne fungal allergens. Fungal allergies are associated with seasonal asthma.[32][33] They are considered to be a major source of airborne allergens.[34] The basidiospore family include mushrooms, rusts, smuts, brackets, and puffballs. The airborne spores from mushrooms reach levels comparable to those of mold and pollens. The levels of mushroom respiratory allergy are as high as 30% of those with allergic disorder, but it is believed to be less than 1% of food allergies.[35][36] Heavy rainfall (which increases fungal spore release) is associated with increased hospital admissions of children with asthma.[37] A study in New Zealand found that 22 percent of patients with respiratory allergic disorders tested positive for basidiospores allergies.[38] Mushroom spore allergies can cause either immediate allergic symptomatology or delayed allergic reactions. Those with asthma are more likely to have immediate allergic reactions and those with allergic rhinitis are more likely to have delayed allergic responses.[39] A study found that 27% of patients were allergic to basidiomycete mycelia extracts and 32% were allergic to basidiospore extracts, thus demonstrating the high incidence of fungal sensitisation in individuals with suspected allergies.[40] It has been found that out of basidiomycete caps, mycelia, and spore extracts, the spore extracts are the most reliable extract for diagnosing basidiomycete allergy.[41][42]

In Canada, 8% of children attending allergy clinics were found to be allergic to Ganoderma, a basidiospore.[43] Pleurotus ostreatus,[44] Cladosporium,[45] and Calvatia cyathiformis are significant airborne spores.[34] Other significant fungal allergens include Aspergillus and Alternaria-Penicillium families.[46] In India, Fomes pectinatus is a predominant air-borne allergen affecting up to 22% of patients with respiratory allergies.[47] Some fungal air-borne allergens such as Coprinus comatus are associated with worsening of eczematous skin lesions.[48] Children who are born during Autumn months (during fungal spore season) are more likely to develop asthmatic symptoms later in life.[49]

Treatment

[edit]

Treatment includes over-the-counter medications, antihistamines, nasal decongestants, allergy shots, and alternative medicine. In the case of nasal symptoms, antihistamines are normally the first option. They may be taken together with pseudoephedrine to help relieve a stuffy nose and they can stop the itching and sneezing. Over-the-counter options include clemastine. However, these antihistamines may cause extreme drowsiness, therefore, people are advised to not operate heavy machinery or drive while taking this kind of medication. Other side effects include dry mouth, blurred vision, constipation, difficulty with urination, confusion, and lightheadedness.[50] There is also a newer second generation of antihistamines that are generally classified as non-sedating antihistamines or anti-drowsy, which include cetirizine, loratadine, and fexofenadine.[51]

An example of nasal decongestants is pseudoephedrine and its side-effects include insomnia, restlessness, and difficulty urinating. Some other nasal sprays are available by prescription, including azelastine and ipratropium bromide. Some of their side-effects include drowsiness. For eye symptoms, it is important to first bathe the eyes with plain eyewash to reduce irritation. People should not wear contact lenses during episodes of conjunctivitis.

Allergen immunotherapy treatment involves administering doses of allergens to accustom the body to induce specific long-term tolerance.[52] Allergy immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous).[53][54] Immunotherapy contains a small amount of the substance that triggers the allergic reactions.[55]

Gradual introduction is also used for egg and milk allergies as a home-based therapy mainly for children.[56][57] Such methods cited in the UK involve the gradual introduction of the allergen in a cooked form where the protein allergenicity has been reduced to become less potent.[58][59][60] By reintroducing the allergen from a fully cooked, usually baked, state, research suggests that a tolerance can emerge to certain egg and milk allergies under the supervision of a dietitian or specialist.[61][62][56] The suitability of this treatment is debated between British and North American experts.[56]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Allergen

View on Grokipedia
from Grokipedia
An allergen is a typically innocuous , often a or , that elicits the production of (IgE) antibodies in genetically predisposed individuals, resulting in reactions upon re-exposure. These reactions occur when allergens cross-link IgE bound to high-affinity FcεRI receptors on mast cells and , triggering rapid and release of mediators like , which manifest as symptoms ranging from mild itching to . Allergens are ubiquitous in the environment and diet, with common sources including from like grasses and trees, house dust mites (Dermatophagoides species), animal dander, fungal spores, and foods such as , tree , eggs, , soy, , and , which account for the majority of clinically significant reactions. Empirical data indicate that these substances provoke allergies in a subset of the population due to Th2-biased immune responses, where initial sensitization leads to memory B-cell production of allergen-specific IgE, rather than tolerance as seen in non-atopic individuals. Food allergens, in particular, often retain stability through , enhancing their . Globally, IgE-mediated allergies impose a substantial burden, with allergic rhinitis affecting 10-30% of populations and food allergies impacting up to 10% of adults in some regions, though varies by geography and diagnostic criteria, often underestimated in self-reports versus challenge-proven cases. Rising incidence in industrialized areas suggests environmental factors like reduced microbial exposure may disrupt immune priming, favoring allergic sensitization over regulatory responses, though causal mechanisms remain under investigation beyond . Controversies persist regarding patterns, where structural similarities between allergens (e.g., profilins in and fruits) complicate and management, highlighting the need for over broad avoidance strategies.

Definition and Fundamentals

Core Definition

An allergen is a substance, typically a foreign protein or glycoprotein, that triggers an immunoglobulin E (IgE)-mediated immune response in sensitized individuals, resulting in an allergic reaction despite being harmless to most people. This response involves the immune system erroneously recognizing the allergen as a pathogen, leading to mast cell degranulation and release of mediators like histamine upon subsequent exposure. Allergens differ from general antigens, which elicit adaptive immunity for protection, by provoking a maladaptive Type I hypersensitivity characterized by rapid onset symptoms such as inflammation, itching, or anaphylaxis. The allergenic potential arises from specific structural features, including stability to or , ability to IgE on effector cells, and enzymatic activity that enhances uptake by antigen-presenting cells. Not all proteins are allergens; only those with epitopes capable of inducing Th2-biased responses in genetically susceptible hosts qualify, influenced by factors like dosage, route of exposure, and adjuvants in the environment. occurs during initial encounters, priming B cells to produce allergen-specific IgE that binds to high-affinity receptors (FcεRI) on and mast cells. While allergens are ubiquitous in nature—encompassing , animal , fungal spores, and food-derived peptides—their identification relies on empirical demonstration of IgE reactivity via prick tests or serum assays, rather than mere presence. varies by population, with up to 25% of industrialized societies affected by IgE-mediated , underscoring the role of modern hygiene and urbanization in altering .

Properties and Identification

Allergens are typically proteins or glycoproteins with molecular weights between 5 and 100 that elicit IgE-mediated reactions upon exposure in sensitized individuals. These molecules often exhibit physicochemical stability, including resistance to heat, acidic conditions, and enzymatic digestion by proteases such as , which enables their survival during environmental persistence or gastrointestinal transit. Such stability is frequently linked to structural features like bonds, repetitive motifs, or the ability to form oligomers and aggregates, particularly in plant-derived allergens. Certain allergens display intrinsic adjuvanticity, meaning they can directly stimulate innate immune pathways—such as activity that activates protease-activated receptors or lipid-binding that disrupts epithelial barriers—independent of their antigenic properties, thereby promoting Th2-skewed responses. Major allergens tend to be abundant in their sources and possess acidic isoelectric points ( 4–6), facilitating solubility and interaction with immune cells. While no universal defines allergenicity, common protein families across sources include prolamins (e.g., in cereals), expansins (e.g., in ), and (e.g., in foods), which share epitopes recognized by IgE. Identification of allergens involves extraction from source materials using buffers to preserve native structure, followed by fractionation techniques like gel filtration or ion-exchange chromatography to isolate protein fractions. Immunological confirmation employs assays such as with allergen-specific IgE from sensitized patients or release tests from to verify IgE-binding capacity. Structural elucidation relies on (e.g., tandem MS/MS) for peptide sequencing and , often combined with bioinformatics tools to predict allergenic potential based on to known allergens in databases like WHO/IUIS. For quantitative detection in complex matrices, such as foods, liquid chromatography- (LC-MS) provides specificity by targeting signature peptides, outperforming antibody-based methods in cases of processed or denatured samples. These methods ensure allergens are distinguished from non-immunogenic proteins by demonstrating both persistence and specific immunogenicity.

Immunological Mechanisms

Type I Hypersensitivity Pathway

![Pollen grains, common triggers of Type I hypersensitivity][float-right]
represents an (IgE)-mediated immune response triggered by allergens, leading to rapid activation of and . This pathway underlies immediate allergic reactions, including hay fever, exacerbations, and , occurring within minutes of re-exposure to the sensitizing allergen. The process initiates with a phase upon first allergen encounter. Allergens, typically proteins from sources like or dust mites, are processed by antigen-presenting cells such as dendritic cells, which present peptides via class II to naive CD4+ T cells. This promotes differentiation into T helper 2 (Th2) cells, driven by cytokines including interleukin-4 (IL-4) from or prior exposures. Th2 cells then secrete IL-4 and IL-13, inducing B cell class-switch recombination to produce allergen-specific IgE antibodies. Circulating IgE binds with high affinity to FcεRI receptors on the surface of mast cells and , arming these effector cells for future encounters. Upon subsequent allergen exposure, multivalent allergens cross-link FcεRI-bound IgE molecules, initiating intracellular signaling. This involves by kinases such as Lyn and Syk, leading to calcium influx and . Mast cells release preformed mediators from granules, including , which binds H1 receptors to induce , increased , and smooth muscle contraction, manifesting as urticaria, , or . and chymase contribute to tissue remodeling and further . Concurrently, lipid mediators like leukotriene C4 and are synthesized de novo, amplifying bronchoconstriction and mucus secretion, particularly in airway allergies. Cytokines such as IL-5 recruit , while IL-4 and IL-13 sustain Th2 responses, transitioning to a late-phase reaction 4-12 hours post-exposure characterized by cellular infiltration and prolonged . This biphasic response explains the persistence of symptoms beyond initial . , though less abundant in tissues, contribute circulating mediators and amplify Th2 immunity via IL-4 release. Key mediators and their effects include: This pathway's evolutionary role includes defense against helminths, where IgE facilitates expulsion via similar effector mechanisms, though dysregulated responses to harmless environmental proteins yield pathology in modern settings.

Non-IgE Pathways and Variants

Allergic responses extend beyond IgE-mediated to include non-IgE pathways classified under Types II, III, and IV in the Gell and Coombs system, where allergens or haptens trigger antibody-independent or alternative antibody-driven mechanisms leading to . involves IgG or IgM antibodies binding to cell-bound allergens, activating complement or cytotoxic responses, as observed in some drug-induced hemolytic anemias or penicillin-related reactions, though environmental allergens rarely dominate this pathway. Type III reactions arise from immune complex deposition, precipitating complement activation and influx, typically in serum sickness-like responses to heterologous proteins or drugs rather than common allergens. Type IV, a delayed cell-mediated response, depends on T-lymphocyte activation following processing by antigen-presenting cells, resulting in cytokine-driven inflammation peaking 48-72 hours after exposure; prominent examples include from in jewelry or in , where low-molecular-weight allergens act as haptens sensitizing skin T-cells. In gastrointestinal contexts, non-IgE-mediated food allergies manifest as delayed symptoms like vomiting, diarrhea, or enteropathy, driven by T-cell infiltration, activation, and innate immune responses rather than , as in (FPIES) affecting infants post-cow's milk or soy ingestion. These disorders, including food protein-induced allergic proctocolitis and variants, lack specific biomarkers and rely on elimination diets for , with involving local shifts like elevated IL-9 but incompletely understood systemic mechanisms. Non-IgE anaphylaxis variants bypass IgE crosslinking via direct or activation, such as MRGPRX2 receptor agonism by certain drugs or peptides, or IgG-mediated platelet activation releasing mediators, explaining idiopathic or perioperative reactions indistinguishable from IgE-driven events. These pathways highlight allergens' capacity for diverse engagement, underscoring diagnostic challenges where prick tests fail and oral challenges or patch testing predominate.

Classification of Allergens

Inhalant and Airborne Allergens

Inhalant allergens encompass aeroallergens that enter the via , primarily eliciting responses such as and exacerbations. These include particles from biological sources that become airborne, with key examples comprising grains, mite-derived materials, animal , fungal spores, and insect fragments. to these allergens affects a substantial portion of the population, with studies indicating that over 40% of individuals with in the United States and Europe show IgE reactivity to inhalant sources. Airborne transmission facilitates widespread exposure, influenced by environmental factors like wind dispersal for pollens and indoor for mites. Pollen represents a primary seasonal allergen, derived from anemophilous including trees (e.g., , ), grasses (e.g., timothy), and weeds (e.g., ). Pollen grains, typically 10-100 micrometers in , release allergenic proteins upon rupture, with concentrations peaking during seasons—such as spring for trees and late summer for weeds in temperate regions. In the United States, pollen alone contributes to significant morbidity, with airborne levels exceeding 100 grains per cubic meter during peak bloom triggering symptoms in sensitized persons. patterns vary geographically; for instance, grass pollen dominates in , while tree pollens like are prevalent in northern latitudes. House dust mites, particularly species Dermatophagoides pteronyssinus and D. farinae, constitute major perennial indoor allergens, with potent proteins concentrated in fecal pellets (10-40 micrometers) that aerosolize during disturbances like bedding agitation. These mites flourish in environments with relative humidity above 70% and temperatures of 20-25°C, leading to higher allergen levels in humid climates or poorly ventilated homes. Exposure metrics show Der p 1 (a key mite allergen) concentrations often surpassing 10 micrograms per gram of in infested dwellings, correlating with risk in children. In population studies, dust mite ranks among the most common triggers, affecting up to 50% of asthmatic patients in urban settings. Animal allergens, shed from , , or of pets like (Fel d 1 from salivary proteins) and (Can f 1 from ), persist in indoor air and on surfaces for months due to their small size (submicrometer fragments). Cat allergens, for example, can remain airborne for over 24 hours post-disturbance, with sensitized individuals reacting at exposures as low as 1-2 nanograms per cubic meter. Dog allergens show broader but lower potency compared to . Prevalence of pet-related sensitization reaches 20-30% in allergic populations, exacerbating both and independently of visible pet presence via transported allergens on clothing. Fungal spores from molds such as and serve as ubiquitous airborne allergens, with spores (2-10 micrometers) dispersing indoors from damp areas or outdoors via wind. Indoor mold growth, promoted by or high humidity, yields allergen concentrations that correlate with hospitalizations, particularly in children, where Alternaria sensitivity doubles exacerbation risk. Outdoor spores peak in humid, warm conditions, contributing to seasonal flares. Cockroach allergens, mainly from Blattella germanica , predominate in urban environments, with sensitization rates exceeding 60% among inner-city asthmatic children, linked to fecal residues becoming airborne in dust. Cross-sensitization and co-exposure complicate clinical patterns, as seen in pollen-food syndromes where proteins (e.g., birch profilin) mimic food epitopes. Diagnostic skin prick tests or serum IgE assays target these sources, revealing regional variations; for example, dust mites dominate in subtropical , while pollens prevail in temperate zones. Mitigation strategies emphasize source control, such as filtration for airborne particles and dehumidification for mites, reducing exposure by 50-80% in controlled studies. Overall, allergens drive a significant burden, with prevalence at 10-30% globally, often comorbid with in 20-40% of cases attributable to these triggers.

Ingestant and Food Allergens

Ingestant allergens encompass substances ingested orally that elicit IgE-mediated hypersensitivity reactions, primarily proteins from foods that survive digestion and interact with mucosal immune cells in the gastrointestinal tract. These differ from inhalant or contact allergens by their route of exposure, often leading to systemic symptoms ranging from gastrointestinal distress to anaphylaxis upon consumption. The U.S. designates nine major allergens responsible for approximately 90% of allergic reactions: , eggs, , crustacean , tree nuts, , , soybeans, and , with added to the list in via the FASTER Act and recent 2025 guidance clarifying definitions for eggs and while excluding . In children, the most prevalent include cow's (affecting about 2-3% in early childhood), eggs, and , while adults more commonly react to (2.9%), (1.9%), (1.8%), and tree nuts (1.7%). Epidemiological data indicate food allergy affects roughly 8% of U.S. children and 10% of adults, with IgE-mediated cases comprising over 10% of the population when accounting for multiple sensitizations, though self-reported figures may inflate due to inclusion of intolerances. Prevalence has risen, with U.S. childhood rates at 5.8% (about 4 million children under 18) as of 2021, disproportionately impacting non-Hispanic Black children and showing faster increases in certain demographics. Globally, common allergens overlap but vary regionally, such as higher and soy sensitivity in alongside universal triggers like and . Certain ingestants pose higher anaphylaxis risks, with and tree nuts implicated in severe reactions due to potent, heat-stable proteins like Ara h 2 in that resist processing. occurs, as in the lipid transfer protein syndrome in Mediterranean regions linking fruits, nuts, and vegetables, or associating ingested pollens with fresh produce via homologous proteins. Processing methods, such as cooking, can attenuate allergenicity for labile proteins in or but exacerbate others through neoallergens formed via Maillard reactions in baked goods.

Contact and Injectable Allergens

Contact allergens primarily elicit , a delayed-type ( reaction mediated by T cells rather than IgE antibodies, occurring upon direct exposure to hapten-like substances that penetrate the and bind to proteins to form complete antigens. Common examples include metals such as (affecting up to 17% of the general population in patch testing studies), , and chromate; fragrances like and components of the fragrance mix; preservatives such as ; rubber accelerators like thiurams and carbamates; and plant-derived oleoresins from (containing ). These allergens often require prior through repeated exposure, with elicitation occurring at lower concentrations than induction, and reactions manifesting 24-72 hours post-contact as eczematous eruptions. Injectable allergens, or injectants, refer to substances introduced parenterally, most notably venoms from insects such as (Apis mellifera), wasps ( species), and fire ants (Solenopsis invicta), which trigger IgE-mediated reactions ranging from local swelling to systemic . venom contains major allergens including (Api m 1, comprising 10-14% of dry venom weight), (Api m 2), and melittin, while vespid venoms feature antigen 5 (Ves v 5) as a dominant allergen responsible for up to 80% of IgE reactivity in sensitized patients. In the United States, stings cause approximately 40-100 deaths annually from , with injection volumes typically 50-140 μg for honeybees and less for vespids. Other injectants include certain parenteral drugs like penicillin derivatives or , but insect venoms predominate in clinical significance due to their potent multi-allergen composition and potential for life-threatening responses upon natural . often involves testing with standardized extracts at concentrations of 0.01-1 μg/mL, confirming sensitization in 60-80% of systemically reacting individuals.

Epidemiology

Allergic diseases, triggered by exposure to various allergens, affect an estimated 10–30% of the global population, with allergic rhinitis impacting 10–30% worldwide and sensitization to environmental proteins observed in up to 40% of individuals in some regions. In 2021, global prevalence reached 260 million cases of asthma and 129 million cases of atopic dermatitis, reflecting a 20% increase in the latter since 1990 according to Global Burden of Disease analyses.00003-7/abstract) Food allergies, often involving ingestant allergens like peanuts or milk, have a worldwide prevalence of approximately 4% in children and 1% in adults. In the United States, 31.8% of the population reports any allergy, including 25.7% with seasonal allergies to airborne allergens such as pollen, 7.3% with eczema linked to contact or inhalant allergens, and 6.2% with food allergies. Prevalence varies by allergen type and region, with higher rates in industrialized nations for inhalant allergens like house dust mites and , where incidence averaged 1,155.77 per 100,000 population globally in recent estimates, exceeding this in 96 countries. Children bear a disproportionate burden, with oral challenge-proven allergies exceeding 10% in some cohorts, particularly for common triggers like eggs and . Atopic dermatitis and urticaria cases have risen steadily, reaching 129 million and contributing to ongoing morbidity, though disability-adjusted life years (DALYs) for declined from 6.9 million in 1990 to 4.6 million in 2021, possibly due to improved management amid rising case numbers.00049-3/fulltext) Trends indicate a marked increase in allergic prevalence over the past five decades, particularly in industrialized countries, with sensitization rates and overall allergy incidence continuing to rise. Food allergy prevalence has doubled among U.S. children from 2000 to 2018, while probable food allergy in those under 20 years in more than doubled from 0.96% in 2008 to higher rates by 2018.00163-4/fulltext) and atopic dermatitis have shown global increases in both prevalence and incidence cases since 1990, with allergic conditions rising dramatically even in developing regions, from rates as low as 1% to 20% for . Hospital visits for food allergies in the U.S. tripled from 1993 to 2006, underscoring the escalating burden. These patterns persist despite diagnostic advancements, as evidenced by rising confirmed incidence in population-based studies.

Demographic and Environmental Risk Factors

Familial history of represents the strongest demographic risk factor for allergic diseases, with twin studies estimating heritability at approximately 75% for and genetic accounting for up to 85% of shared variance across atopic conditions. atopy predicts clinical manifestations more strongly than parental history alone in . Loss-of-function mutations in the (FLG) gene confer the most significant single genetic risk for , though most cases arise from polygenic interactions rather than monogenic causes. Allergic disease prevalence varies by age, with food allergies and eczema peaking in infancy and before declining in adulthood, while seasonal allergies remain stable at around 24.7% across ages in U.S. data from 2018–2020. Sex differences emerge developmentally: males exhibit higher rates of childhood and , but females face elevated risks for non-allergic and between ages 20 and 44. , self-reports indicate higher prevalence among Asian (10.5%), (10.5%), and (10.5%) individuals compared to (9.5%), with faster rises in childhood prevalence among (2.1% per decade) and (1.2% per decade) populations from 1997–2018. Lower correlates with increased risk, potentially due to compounded exposures rather than affluence alone. Environmental factors modulate genetic predispositions through early-life exposures, as evidenced by the , which posits that reduced microbial diversity from , antibiotics, and excessive sanitation elevates risk by impairing . Cohort studies confirm protective effects from rural living and early pet exposure, with lower sensitization rates among children in microbe-rich environments, though this holds primarily for IgE-mediated and weakens for non-IgE pathways. International migration from low- to high-income countries doubles incidence in offspring, attributed to shifts in and allergen exposure. Indoor pollutants like , tobacco smoke, and pet dander heighten onset, while outdoor factors such as and particulate matter exacerbate sensitization via epithelial barrier disruption. Rising CO2 levels enhance allergenicity in grasses and weeds, extending seasons and potency, as documented in controlled exposure studies. Early antibiotic use and cesarean delivery further disrupt , increasing odds by 20–30% in longitudinal cohorts. These modifiable risks underscore causal pathways from environmental perturbations to dysregulated Th2 immunity, independent of genetic loading.

Historical Context

Pre-20th Century Observations

![Misc_pollen.jpg][float-right] Ancient civilizations documented symptoms resembling allergic reactions, though without modern immunological understanding. In , circa 3640–3300 BC, reportedly died from a wasp sting, marking the earliest recorded anaphylactic-like event. (c. 460–370 BC) described conditions akin to and eczema, attributing respiratory distress to imbalances in bodily humors such as , and noted that certain foods could provoke adverse symptoms or even fatal reactions in susceptible individuals. Similar asthma-like accounts appear in texts from ancient , , and , often linked to environmental irritants without identifying specific triggers. During the medieval period, Arabic physicians advanced observations of seasonal . Rhazes (Al-Razi, 865–925 AD) provided the first detailed description of "rose fever," a seasonal triggered by odors, in his El Hawi, distinguishing it from infectious colds. These accounts, while innovative for their time, reflected humoral theory rather than recognition of extrinsic allergens, and evidence for widespread allergic prevalence remains suggestive rather than conclusive. By the , European texts occasionally referenced "summer colds" or pollen-related irritations, but systematic attribution to specific substances was absent. In the , isolated case reports emerged of to foods and inhalants; for instance, Jean Baptiste van Helmont documented asthmatic reactions to ingested substances. By the late , seasonal gained recognition in , with physicians observing patterns tied to hay harvest or floral blooms, leading to the term "hay fever" supplanting "rose cold." John Bostock's 1819 clinical description of his own paroxysmal sneezing, lacrimation, and nasal discharge in summer—termed "periodic " or hay fever—provided the first systematic account, estimating only about 100 known cases in at the time, suggesting rarity or underreporting. These pre-20th century observations laid groundwork for later causal identification but often misattributed symptoms to miasmas, climate, or nervous debility rather than allergenic proteins.

Modern Discoveries and Milestones

In 1911, Leonard Noon and John Freeman pioneered subcutaneous by administering graduated doses of grass pollen extract to hay fever patients, marking the first targeted treatment for allergen . This approach demonstrated desensitization through repeated exposure, laying the foundation for modern specific protocols applied to various allergens.31214-X/fulltext) The 1960s brought pivotal insights into allergen sources and mechanisms. In 1967, Rob Voorhorst and colleagues identified the Dermatophagoides pteronyssinus as the primary allergen in house dust, linking mite fecal pellets to perennial and symptoms previously attributed vaguely to "dust."48153-X/pdf) Concurrently, Kimishige and Teruko Ishizaka discovered (IgE) in 1966–1967, isolating the reaginic antibody responsible for immediate reactions via passive transfer experiments and gel filtration chromatography. This breakthrough elucidated the immunological basis of type I allergies, shifting research toward IgE-mediated pathways.30165-8/fulltext) Advancing into molecular identification, the late 1980s saw the and expression of the first allergen , Der p 1 from house dust mites, by Thomas et al. in 1988, enabling recombinant production and detailed structural analysis of allergenic proteins. This facilitated component-resolved diagnostics, allowing precise IgE profiling against individual allergen molecules rather than crude extracts, improving diagnostic accuracy and personalized therapy by the 2000s. Subsequent milestones include the establishment of the WHO/IUIS Allergen Database in the , standardizing allergen designations based on biochemical and immunological criteria.

Diagnosis

Clinical Testing Methods

Skin prick testing (SPT) serves as the primary method for detecting IgE-mediated sensitization to , , and certain drug allergens, involving the application of standardized allergen extracts to the followed by a superficial prick with a lancet or needle, with reactions assessed after 15-20 minutes via wheal and flare measurement. A positive result is typically defined as a wheal at least 3 mm larger than the negative saline control, alongside a positive control for skin reactivity; this approach demonstrates high sensitivity (85-94%) and specificity (79-87%) for common inhalants like and dust mites, though false positives can arise from or non-standardized extracts. SPT is preferred over alternatives due to its cost-effectiveness, rapidity, and correlation with clinical challenges, but requires discontinuation of antihistamines for 5-7 days and is contraindicated in patients with extensive skin or recent severe reactions. Serum-specific IgE (sIgE) testing provides an complement or alternative to SPT, quantifying allergen-bound IgE antibodies via immunoassays such as ImmunoCAP, with results reported in kUA/L and thresholds often starting at 0.35 kUA/L indicating . It is indicated when SPT is infeasible, such as in dermatographism, ongoing use, or severe eczema, offering safety without reaction risk but lower sensitivity (70-75% average) compared to SPT for many allergens and higher costs; predictive values vary by allergen, with higher levels to increased clinical risk for foods like but requiring history as does not equate to . Intradermal testing, injecting dilute extracts subcutaneously, may follow negative SPT in select cases like or allergies but risks more false positives and systemic reactions, limiting its routine use. Provocation challenges confirm clinical allergy when sensitization tests are equivocal, with oral food challenges (OFC) as the gold standard for ingestants, involving graded supervised ingestion under medical monitoring to observe objective symptoms like urticaria or . Bronchial or nasal challenges assess inhalant reactivity via or symptom scoring post-exposure, while supervised insect stings evaluate venom hypersensitivity; these carry risks of severe , necessitating emergency preparedness, and are reserved for ambiguous cases due to their resource intensity. For non-IgE-mediated contact allergens causing , patch testing applies diluted haptens via adhesive chambers to the back for 48 hours, with readings at 48-96 hours identifying delayed via or vesicles, using standardized series like TRUE Test for common culprits such as or fragrances. All methods detect rather than proven , with negative SPT or sIgE offering high negative predictive value (often >95% for ruling out ) but low positive predictive value necessitating clinical integration; guidelines from organizations like AAAAI emphasize allergist oversight to avoid overinterpretation, as up to 50-60% of positive tests may lack symptoms. Component-resolved diagnostics, analyzing IgE to specific allergen proteins, enhance specificity for foods but remain adjunctive, not replacing challenges for confirmation.

Interpretation and Limitations

Interpretation of diagnostic tests for allergens, such as skin prick tests (SPT), serum-specific IgE assays, and patch tests, primarily assesses rather than confirming clinical , which requires reproducible symptoms upon allergen exposure. In SPT, a positive result is typically defined by a wheal at least 3 mm larger than the negative control after 15-20 minutes, indicating IgE-mediated to inhalant or allergens, though wheal size correlates imperfectly with symptom severity. Serum IgE tests quantify allergen-specific antibodies, with levels above 0.35 kU/L often considered positive, but higher thresholds (e.g., >0.7 kU/L for foods) improve predictive value for clinical reactivity. Patch tests for contact allergens evaluate delayed via graded reactions (e.g., + to ++ based on and vesicles at 48-96 hours), but relevance demands history of exposure and dermatitis resolution upon avoidance. Across methods, results must integrate with patient history, as isolated positives reflect immune recognition without guaranteeing symptomatic responses. Limitations include variable diagnostic accuracy, with SPT showing pooled sensitivity of 88% and specificity of 77% for allergic rhinitis but lower specificity (around 50%) for food allergies, leading to frequent false positives where sensitization exists without symptoms. Serum IgE tests exhibit sensitivity of 60-95% and specificity of 30-95%, influenced by assay variability and cross-reactivity, often overestimating allergy in low-prevalence settings. False negatives in SPT arise from antihistamine use, dermographism, or extract potency issues, while patch tests suffer from technique errors, insufficient allergen concentrations, or immunosuppressive therapies, yielding moderate accuracy where positives do not always correlate with clinical relevance. No in vitro or skin test serves as a standalone gold standard; double-blind oral challenges remain confirmatory but carry anaphylaxis risk (up to 3% in supervised settings), restricting their use. Confounders like age, atopy, and environmental factors further complicate interpretation, underscoring the need for specialist oversight to avoid misdiagnosis.

Management and Treatment

Primary Prevention and Avoidance

Early introduction of common allergenic foods represents the most evidence-based primary prevention strategy for food allergies in high-risk infants, those with severe eczema or by 4-6 months of age. The Learning Early About (LEAP) , involving 640 infants, demonstrated that regular consumption of peanut products from 4 to 11 months of age reduced the prevalence of at 5 years by 81% (1.9% in the consumption group versus 13.7% in the avoidance group), with absolute risk reduction of 11.8%. Long-term follow-up in the LEAP-On extension confirmed sustained protection, with rates remaining at 3.2% in the early introduction group versus 17.2% in the avoidance group after 12 months of consumption. Guidelines from organizations such as the National Institute of Allergy and Infectious Diseases recommend this approach, shifting from prior avoidance recommendations that lacked empirical support and potentially increased risk. Similar, though less definitive, evidence supports early egg introduction around 6 months to mitigate , based on trials showing reduced . In contrast, allergen avoidance measures during , , or early infancy do not prevent atopic development and may counterproductive for foods like . Systematic reviews of nutritional interventions conclude that maternal dietary restrictions provide no benefit in reducing incidence in offspring. For aeroallergens, primary prevention through environmental control yields inconsistent results; meta-analyses of avoidance in high-risk families, including encasings and acaricides, show no significant reduction in or rates. A 2024 meta-analysis of 35 trials involving 2,419 patients with mite-sensitive found no overall improvement in symptoms or function from avoidance strategies, though subgroup analyses hinted at potential benefits from high-efficiency particulate air filtration in specific nocturnal settings. Other interventions, such as exclusive breastfeeding for 3-4 months, offer limited protection against eczema (risk ratio 0.72) but fail to consistently prevent food allergies or asthma per cohort studies and reviews. Probiotic supplementation in pregnancy or infancy shows no reliable effect on primary prevention across meta-analyses, with benefits confined to specific strains and outcomes like atopic dermatitis in select subgroups. Avoidance of tobacco smoke exposure remains a general recommendation, as prenatal or postnatal exposure increases allergy risk by 20-30% in observational data, though not allergen-specific. Overall, primary prevention efficacy remains strongest for targeted early oral exposure to foods, underscoring a causal role for tolerance induction over blanket avoidance.

Symptomatic and Acute Interventions

Symptomatic interventions for mild to moderate allergic reactions, such as those triggered by airborne allergens like or mites, primarily involve pharmacologic agents targeting histamine-mediated effects. Oral second- and third-generation H1-antihistamines, including , loratadine, and fexofenadine, effectively alleviate symptoms like sneezing, itching, and in , with evidence from randomized trials showing symptom reduction comparable to in short-term use for seasonal allergies. Intranasal corticosteroids, such as fluticasone or mometasone, represent the most effective monotherapy for persistent symptoms impacting , outperforming antihistamines in controlling and based on meta-analyses of clinical trials. Decongestants like provide adjunctive relief for nasal obstruction but carry risks of and are not recommended for prolonged use. For acute severe reactions, including from food allergens like or insect stings, intramuscular epinephrine remains the cornerstone intervention, administered at a dose of 0.01 mg/kg (maximum 0.5 mg) into the anterolateral as soon as symptoms such as airway compromise or manifest. Guidelines emphasize prompt delivery via devices like EpiPen to reverse and , with repeat dosing every 5-15 minutes if needed until improvement occurs, supported by observational data showing reduced mortality when given early. Following epinephrine, adjunctive therapies include antihistamines for histamine-driven symptoms like urticaria and systemic corticosteroids (e.g., 1-2 mg/kg IV) to potentially mitigate prolonged effects, though randomized evidence indicates corticosteroids do not prevent biphasic reactions and lack a proven acute benefit. Supportive measures, such as supplemental oxygen, fluid resuscitation, and bronchodilators for wheezing, address secondary manifestations in settings. Patients with known severe risks should carry epinephrine s, with prescription rates increasing post-2023 updates recommending devices for children as young as 7.5 kg.

Disease-Modifying Therapies

Allergen immunotherapy (AIT), also known as desensitization, represents the primary disease-modifying treatment for IgE-mediated allergic s, inducing long-term rather than merely suppressing symptoms. Unlike pharmacotherapies that provide temporary relief, AIT alters the underlying allergic response by shifting T-helper 2 (Th2)-dominated immunity toward regulatory T cells and Th1 responses, reducing allergen-specific IgE and increasing IgG4 antibodies. Clinical guidelines from regulatory bodies, such as the , endorse AIT for allergens and venoms due to its capacity to prevent progression, including new sensitizations and onset in patients. Subcutaneous immunotherapy (SCIT), administered via injections, has served as the historical standard since the early , with meta-analyses confirming its in reducing symptoms and use for and by 30-40% over in randomized controlled trials. A typical course involves an up-dosing phase over 6-8 weeks followed by maintenance doses for 3-5 years, yielding sustained benefits persisting 7-12 years post-treatment in real-world studies. Sublingual immunotherapy (SLIT), involving allergen extracts held under the , offers comparable to SCIT for grass and house dust mite allergies, with network meta-analyses ranking certain SLIT formulations highly for symptom score reductions in . SLIT demonstrates a superior profile, with systemic reactions occurring in under 0.2% of doses versus 0.7-4% for SCIT, though local oral reactions affect up to 75% of SLIT users initially. For venom allergies, AIT achieves near-complete protection against , with success rates exceeding 90% after 5 years of SCIT, as evidenced by long-term cohort data. Emerging applications include oral immunotherapy (OIT) for allergens like , where FDA-approved products such as Palforzia (peanut allergen extract) induce desensitization in 67% of children after 12 months, though sustained unresponsiveness remains limited to 10-20% without ongoing exposure. Biologics like , an anti-IgE , serve as adjuncts in severe cases but do not confer the tolerance induced by AIT, functioning primarily to enable safer AIT initiation rather than standalone disease modification. Overall, AIT's disease-modifying effects are supported by systematic reviews, though patient adherence (around 60-70% completion rates) and cost-effectiveness vary by formulation and allergen.

Debates and Controversies

Hygiene Hypothesis and Microbial Exposure

The posits that reduced exposure to diverse microorganisms in contributes to the rising prevalence of allergic diseases by impairing the development of . Originally formulated by epidemiologist David Strachan in 1989, the hypothesis arose from observations in a British showing an inverse relationship between sibship size—serving as a proxy for early infections—and hay fever incidence, suggesting that fewer opportunities for microbial transmission in smaller families or cleaner environments heightened allergy risk. Subsequent refinements, such as the "old friends" hypothesis, emphasize that exposure to specific commensal microbes, helminths, and environmental bacteria—rather than pathogenic infections alone—trains the to distinguish harmless antigens from threats, thereby preventing aberrant Th2-dominated responses characteristic of allergies. Empirical support derives primarily from longitudinal cohort studies linking early-life microbial diversity to lower rates. For instance, multiple European farm studies, including the Protection Against : Study in Rural Environments () cohort initiated in 2006, demonstrate that children raised on traditional dairy farms with animal contact and unprocessed hay exhibit 30-50% reduced odds of , hay fever, and compared to urban or non-farm rural peers, attributable to higher inhalation and ingestion of endotoxin-rich dust and diverse . Similarly, a 2011 New England Journal of Medicine analysis of over 1,000 children across European regions found farm-reared individuals exposed to greater microbial variety in house dust had significantly lower prevalence (odds ratio 0.4), with protection mediated by signaling from bacterial components rather than broad levels. Gut analyses corroborate this, revealing that vaginally delivered infants with early and pet exposure develop more diverse by age 1, correlating with diminished atopic sensitization; antibiotic use in infancy, disrupting this diversity, elevates risk by up to 1.5-fold in meta-analyses. Mechanistically, microbial exposure promotes regulatory T-cell differentiation and IL-10 production, countering IgE-mediated ; murine models confirm that neonatal administration of farm-like microbial extracts prevents allergen-induced airway via epigenetic modulation of Th2 genes. However, limitations persist: the does not uniformly explain all allergies, as certain viral infections (e.g., ) exacerbate rather than protect, and urban green space exposure yields inconsistent benefits without the microbial richness of farms. Critics argue the term "hygiene" misleadingly implies excessive cleanliness as causal, ignoring confounders like or , and randomized trials of yield mixed results, with only specific strains (e.g., Lactobacillus rhamnosus GG) showing modest prevention in high-risk cohorts up to age 5. Overall, while causal evidence favors targeted microbial interventions over generalized "dirtiness," the underscores the immune system's evolutionary calibration to pre-industrial microbial loads, challenging blanket sanitization without nuanced application.

Explanations for Increasing Incidence

The incidence of allergic diseases has risen markedly in recent decades, particularly in industrialized nations, with food allergy prevalence among children in the United States increasing by 50% between 1997 and 2011, and by another 50% between 2007 and 2021. This trend extends to asthma, eczema, and other atopic conditions, with global rates of asthma varying from 1% to 20% across regions, including rapid increases in developing countries. Genetic factors alone cannot account for such swift changes, as human genome evolution occurs over much longer timescales; instead, environmental influences interacting with genetic predispositions are implicated. The , first proposed by Strachan in , posits that reduced early-life exposure to diverse microbes and infections—due to improved sanitation, smaller family sizes, , and fewer farm environments—disrupts development, favoring a Th2-biased response that promotes allergic over tolerance. Supporting evidence includes epidemiological studies showing lower rates among children in larger families, those raised on farms with contact, or in settings with higher parasitic or bacterial exposures, such as daycare attendance correlating with reduced in some cohorts. Animal models and human trials further demonstrate that early microbial diversity, particularly from species like Bifidobacterium and Lactobacillus, fosters regulatory T-cell activity that mitigates allergic inflammation. However, the hypothesis faces nuances; for instance, certain viral infections like can exacerbate allergies in predisposed individuals, suggesting that not all microbial exposures are protective and that timing and type matter. Alterations in the gut microbiome, often termed , contribute via mechanisms linked to the , including overuse, cesarean deliveries, and formula feeding, which reduce beneficial and impair oral tolerance to allergens. Peer-reviewed analyses indicate that low microbial diversity in infancy correlates with higher risks of food allergies and eczema, with interventions like showing mixed but promising results in preventing when administered perinatally. Dietary shifts toward processed, low-fiber Western diets further diminish short-chain fatty acid production by gut , which normally suppresses allergic responses; conversely, high-fat or obese states may amplify Th2 cytokines. Environmental pollutants and exacerbate incidence by enhancing allergen potency and exposure duration. Rising CO2 levels and warmer temperatures have extended seasons by up to three weeks in some regions since the 1990s, increasing aeroallergen concentrations and in syndromes like pollen-food . particles, for example, act as adjuvants that penetrate mucosal barriers and boost IgE production, with linking higher PM2.5 exposure to elevated hospitalizations. , prevalent in modern indoor lifestyles, may also play a role by impairing regulatory immune pathways, though supplementation trials yield inconsistent prevention outcomes. Overall, these factors interact multifactorially, with no single cause dominating, and ongoing research emphasizes early-life windows for intervention to curb the trajectory.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5406225/
  2. https://www.ncbi.nlm.nih.gov/books/NBK10756/
  3. https://www.ncbi.nlm.nih.gov/books/NBK27112/
  4. https://www.ncbi.nlm.nih.gov/books/NBK27117/
  5. https://pubmed.ncbi.nlm.nih.gov/31690370/
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC11250430/
  7. https://www.ncbi.nlm.nih.gov/books/NBK545237/
  8. https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2021.769728/full
  9. https://www.aaaai.org/about/news/for-media/allergy-statistics
  10. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2720064
  11. https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-025-03518-y
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC10959674/
  13. https://www.sciencedirect.com/topics/medicine-and-dentistry/allergen
  14. https://www.frontiersin.org/research-topics/19838/what-makes-an-allergen-an-allergen/magazine
  15. https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/allergy
  16. https://www.aaaai.org/tools-for-the-public/allergy%2C-asthma-immunology-glossary/allergen-defined
  17. https://www.niehs.nih.gov/health/topics/agents/allergens
  18. https://www.mayoclinic.org/diseases-conditions/allergies/symptoms-causes/syc-20351497
  19. https://www.sciencedirect.com/science/article/pii/S1043452620300140
  20. https://www.jacionline.org/article/S0091-6749%2804%2902678-8/fulltext
  21. https://www.uptodate.com/contents/molecular-features-of-food-allergens
  22. https://pubmed.ncbi.nlm.nih.gov/25989479/
  23. https://www.sciencedirect.com/science/article/pii/S0889856122004660
  24. https://www.tandfonline.com/doi/abs/10.1080/02652030310001620423
  25. https://www.sciencedirect.com/science/article/abs/pii/S0889157524009402
  26. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pmic.202200427
  27. https://pmc.ncbi.nlm.nih.gov/articles/PMC12191692/
  28. https://www.ncbi.nlm.nih.gov/books/NBK560561/
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC9841766/
  30. https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/overview-of-allergic-and-atopic-disorders
  31. https://www.ncbi.nlm.nih.gov/books/NBK562228/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC8721028/
  33. https://aacijournal.biomedcentral.com/articles/10.1186/s13223-024-00933-4
  34. https://www.mdpi.com/2624-5647/6/2/33
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC12350582/
  36. https://www.jacionline.org/article/S0091-6749%2821%2900230-X/fulltext
  37. https://www.jaci-inpractice.org/article/S2213-2198%2824%2900193-4/abstract
  38. https://asthmarp.biomedcentral.com/articles/10.1186/s40733-015-0008-0
  39. https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2023.1173540/full
  40. https://pmc.ncbi.nlm.nih.gov/articles/PMC12258866/
  41. https://www.sciencedirect.com/science/article/pii/S1939455123001278
  42. https://pmc.ncbi.nlm.nih.gov/articles/PMC3939690/
  43. https://www.lung.org/clean-air/indoor-air/indoor-air-pollutants/pet-dander
  44. https://www.epa.gov/indoor-air-quality-iaq/biological-pollutants-impact-indoor-air-quality
  45. https://aafa.org/allergies/prevent-allergies/control-indoor-allergens/
  46. https://www.sciencedirect.com/science/article/pii/S1323893024000893
  47. https://karger.com/iaa/article/186/5/445/915991/Investigation-and-Analysis-of-Inhalant-Allergens
  48. https://jamanetwork.com/journals/jama/fullarticle/419320
  49. https://www.jacionline.org/article/S0091-6749%2801%2962488-6/fulltext
  50. https://www.ncbi.nlm.nih.gov/books/NBK482187/
  51. https://pmc.ncbi.nlm.nih.gov/articles/PMC7883751/
  52. https://www.fda.gov/food/nutrition-food-labeling-and-critical-foods/food-allergies
  53. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-questions-and-answers-regarding-food-allergen-labeling-edition-5
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC4254585/
  55. https://www.niaid.nih.gov/diseases-conditions/food-allergy
  56. https://aafa.org/wp-content/uploads/2025/04/aafa-allergy-facts-and-figures.pdf
  57. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1373110/full
  58. https://www.jacionline.org/article/s0091-6749%2813%2901836-8/fulltext
  59. https://www.ncbi.nlm.nih.gov/books/NBK435944/
  60. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC3276771/
  62. https://www.annallergy.org/article/S1081-1206%2822%2900212-5/fulltext
  63. https://www.fda.gov/cosmetics/cosmetic-ingredients/allergens-cosmetics
  64. https://pmc.ncbi.nlm.nih.gov/articles/PMC10580978/
  65. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00077/full
  66. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/hymenoptera-venom
  67. https://pmc.ncbi.nlm.nih.gov/articles/PMC5647953/
  68. https://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2005.00963.x
  69. https://acaai.org/allergies/allergies-101/facts-stats/
  70. https://www.cdc.gov/nchs/fastats/allergies.htm
  71. https://www.northwell.edu/news/the-latest/why-allergies-are-on-the-rise
  72. https://pubmed.ncbi.nlm.nih.gov/37431853/
  73. https://pmc.ncbi.nlm.nih.gov/articles/PMC9993206/
  74. https://www.bbc.com/future/article/20201023-food-allergies-why-nut-dairy-and-food-allergy-are-rising
  75. https://www.sciencedirect.com/science/article/pii/S0362028X24002084
  76. https://www.jacionline.org/article/S0091-6749%2819%2932606-5/pdf
  77. https://www.sciencedirect.com/science/article/abs/pii/S0091674998701642
  78. https://aacijournal.biomedcentral.com/articles/10.1186/s13223-016-0158-5
  79. https://www.cdc.gov/nchs/data/databriefs/db460.pdf
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC4669616/
  81. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2806015
  82. https://www.foodallergy.org/resources/facts-and-statistics
  83. https://pubmed.ncbi.nlm.nih.gov/40836867/
  84. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.637087/full
  85. https://pmc.ncbi.nlm.nih.gov/articles/PMC4918254/
  86. https://pmc.ncbi.nlm.nih.gov/articles/PMC10084123/
  87. https://pmc.ncbi.nlm.nih.gov/articles/PMC8391414/
  88. https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2023.1063982/full
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC8453757/
  90. https://www.thelancet.com/article/S2352-3964%2816%2930146-3/fulltext
  91. https://www.achooallergy.com/blog/learning/a-history-of-allergies-and-asthma-part-one-the-ancients-perspective/
  92. https://link.springer.com/chapter/10.1007/978-4-431-98349-1_1
  93. https://www.redsneakers.org/blog-posts/historical-footprints-of-food-allergies
  94. https://www.nationalgeographic.com/science/article/partner-content-brief-history-of-allergies
  95. https://www.achooallergy.com/blog/learning/a-history-of-allergies-and-asthma-part-two-the-middle-ages-and-the-renaissance/
  96. https://aai.org.tr/pdf.php?id=90
  97. https://pubmed.ncbi.nlm.nih.gov/24925380/
  98. https://www.sciencedirect.com/science/article/pii/S1323893016301137
  99. https://www.achooallergy.com/blog/learning/a-history-of-allergies-part-three-the-16th-century-to-the-20th-century/
  100. https://www.sciencedirect.com/science/article/pii/S1879729623001230
  101. https://pmc.ncbi.nlm.nih.gov/articles/PMC3110966/
  102. https://www.jacionline.org/article/s0091-6749%2815%2900584-9/fulltext
  103. https://www.nature.com/articles/s41577-022-00786-1
  104. https://pubmed.ncbi.nlm.nih.gov/30287256/
  105. https://pmc.ncbi.nlm.nih.gov/articles/PMC6770348/
  106. https://pmc.ncbi.nlm.nih.gov/articles/PMC7756543/
  107. https://www.aaaai.org/tools-for-the-public/conditions-library/allergies/allergy-testing
  108. https://pmc.ncbi.nlm.nih.gov/articles/PMC3565910/
  109. https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/allergydiagnostictesting.pdf
  110. https://pmc.ncbi.nlm.nih.gov/articles/PMC8346756/
  111. https://www.niaid.nih.gov/diseases-conditions/diagnosing-food-allergy
  112. https://dermnetnz.org/topics/patch-tests
  113. https://www.aafp.org/pubs/afp/issues/2018/0701/p34.html
  114. https://www.ncbi.nlm.nih.gov/books/NBK537020/
  115. https://www.ccjm.org/content/ccjom/78/9/585.full.pdf
  116. https://pmc.ncbi.nlm.nih.gov/articles/PMC2958195/
  117. https://www.foodallergy.org/resources/skin-prick-tests
  118. https://pmc.ncbi.nlm.nih.gov/articles/PMC4848807/
  119. https://www.uptodate.com/contents/diagnostic-evaluation-of-ige-mediated-food-allergy/print
  120. https://publications.ersnet.org/content/breathe/3/4/345
  121. https://www.healio.com/news/allergy-asthma/20240620/qa-allergy-test-interpretations-require-caution
  122. https://www.nejm.org/doi/full/10.1056/NEJMoa1414850
  123. https://www.nih.gov/news-events/news-releases/introducing-peanut-infancy-prevents-peanut-allergy-into-adolescence
  124. https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2024-070516/204636/Guidelines-for-Early-Food-Introduction-and
  125. https://pmc.ncbi.nlm.nih.gov/articles/PMC10359645/
  126. https://pmc.ncbi.nlm.nih.gov/articles/PMC7305068/
  127. https://pubmed.ncbi.nlm.nih.gov/38966606/
  128. https://pmc.ncbi.nlm.nih.gov/articles/PMC7757062/
  129. https://aacijournal.biomedcentral.com/articles/10.1186/1710-1492-3-4-105
  130. https://aacijournal.biomedcentral.com/articles/10.1186/s13223-019-0375-9
  131. https://www.aafp.org/pubs/afp/issues/2015/1201/p985.html
  132. https://pmc.ncbi.nlm.nih.gov/articles/PMC7066682/
  133. https://pmc.ncbi.nlm.nih.gov/articles/PMC10185359/
  134. https://pmc.ncbi.nlm.nih.gov/articles/PMC8139870/
  135. https://www.aaaai.org/Aaaai/media/Media-Library-PDFs/Allergist%2520Resources/Statements%2520and%2520Practice%2520Parameters/Anaphylaxis-Practice-Paramaters-2023.pdf
  136. https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/
  137. https://www.aaaai.org/allergist-resources/ask-the-expert/answers/old-ask-the-experts/corticosteroids-anaphylaxis
  138. https://emedicine.medscape.com/article/135065-treatment
  139. https://pmc.ncbi.nlm.nih.gov/articles/PMC8236874/
  140. https://pubmed.ncbi.nlm.nih.gov/35416072/
  141. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-development-products-specific-immunotherapy-treatment-allergic-diseases_en.pdf
  142. https://pmc.ncbi.nlm.nih.gov/articles/PMC12507858/
  143. https://www.jacionline.org/article/S0091-6749%2823%2900284-1/fulltext
  144. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1144816/full
  145. https://www.tandfonline.com/doi/full/10.1080/02770903.2024.2391441
  146. https://link.springer.com/article/10.1007/s40521-024-00377-6
  147. https://www.ncbi.nlm.nih.gov/books/NBK535367/
  148. https://www.jacionline.org/article/S0091-6749%2822%2901117-4/fulltext
  149. https://pmc.ncbi.nlm.nih.gov/articles/PMC12176734/
  150. https://core.ac.uk/download/pdf/13115613.pdf
  151. https://pmc.ncbi.nlm.nih.gov/articles/PMC9731379/
  152. https://pmc.ncbi.nlm.nih.gov/articles/PMC8044987/
  153. https://www.nejm.org/doi/full/10.1056/NEJMoa1007302
  154. https://www.nature.com/articles/s41577-020-00420-y
  155. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.635935/full
  156. https://pmc.ncbi.nlm.nih.gov/articles/PMC4966430/
  157. https://www.pnas.org/doi/10.1073/pnas.1700688114
  158. https://www.jacionline.org/article/S0091-6749%2815%2900721-6/fulltext
  159. https://pmc.ncbi.nlm.nih.gov/articles/PMC2841828/
  160. https://publichealth.jhu.edu/2022/is-the-hygiene-hypothesis-true
  161. https://www.usatoday.com/story/graphics/2025/04/28/worse-allergy-season-2025-spring-warmups/83253697007/
  162. https://www.sciencedirect.com/science/article/pii/S2213219825002120
  163. https://www.science.org/doi/10.1126/scitranslmed.add2563
Add your contribution
Related Hubs
User Avatar
No comments yet.