Commonallergens includepollen, certain foods, metals, insect stings, and medications.[11][2] The development of allergies is due to genetic and environmental factors.[2] The mechanism of allergic reactions involvesimmunoglobulin E antibodies (IgE) binding to an allergen and then toa receptor onmast cells orbasophils, where they trigger the release of inflammatory chemicals such ashistamine.[16] Diagnosis is typically based on a person'smedical history.[3] Further testing of theskin or blood may be useful in certain cases.[3] Positive tests, however, may not necessarily mean there is a significant allergy to the substance in question.[17]
Early exposure of children to potential allergens may be protective.[5] Treatments for allergies include avoidance of known allergens and the use of medications such assteroids andantihistamines.[6] In severe reactions, injectableadrenaline (epinephrine) is recommended.[7]Allergen immunotherapy, which gradually exposes people to larger and larger amounts of allergen, is useful for some types of allergies such as hay fever and reactions to insect bites.[6] Its use in food allergies is unclear.[6]
Allergies are common.[10] In the developed world, about 20% of people are affected by allergic rhinitis,[18] food allergy affects 10% of adults and 8% of children,[19] and about 20% have or have had atopic dermatitis at some point in time.[20] Depending on the country, about 1–18% of people have asthma.[21][22] Anaphylaxis occurs in between 0.05–2% of people.[23] Rates of many allergic diseases appear to be increasing.[7][24][25] The word "allergy" was first used byClemens von Pirquet in 1906.[2]
Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as the eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes.[26] Inhaled allergens can also lead to increased production ofmucus in thelungs,shortness of breath, coughing, and wheezing.[27]
Aside from these ambient allergens, allergic reactions can result from foods,insect stings, and reactions to medications likeaspirin andantibiotics such aspenicillin. Symptoms of food allergy include abdominal pain,bloating, vomiting,diarrhea,itchy skin, andhives. Food allergies rarely causerespiratory (asthmatic) reactions, orrhinitis.[28] Insect stings, food,antibiotics, and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including thedigestive system, therespiratory system, and thecirculatory system.[29][30][31] Depending on the severity, anaphylaxis can include skin reactions,bronchoconstriction,swelling,low blood pressure, coma, and death. This type of reaction can be triggered suddenly, or the onset can be delayed. The nature of anaphylaxis is such that the reaction can seem to be subsiding but may recur throughout a period of time.[31]
Substances that come into contact with the skin, such aslatex, are also common causes of allergic reactions, known ascontact dermatitis or eczema.[32] Skin allergies frequently causerashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives andangioedema.[33]
With insect stings, a large local reaction may occur in the form of an area of skin redness greater than 10 cm in size that can last one to two days.[34] This reaction may also occur afterimmunotherapy.[35]
The way the body responds to foreign invaders on the molecular level is similar to how allergens are treated even on the skin. The skin forms an effective barrier to the entry of most allergens but this barrier cannot withstand everything that comes at it. A situation such as an insect sting can breach the barrier and injectallergen to the affected spot. When an allergen enters the epidermis or dermis, it triggers a localized allergic reaction which activates the mast cells in the skin resulting in an immediate increase in vascular permeability, leading to fluid leakage and swelling in the affected area.[36] Mast-cell activation also stimulates a skin lesion called the wheal-and-flare reaction.[37] This is when the release of chemicals from local nerve endings by a nerve axon reflex, causes thevasodilatations of surrounding cutaneous blood vessels, which causes redness of the surrounding skin.[37]
As a part of the allergy response, the body has developed a secondary response which in some individuals causes a more widespread and sustained edematous response.[36] This usually occurs about 8 hours after the allergen originally comes in contact with the skin. When an allergen is ingested, a dispersed form of wheal-and-flare reaction, known as urticaria or hives will appear when the allergen enters the bloodstream and eventually reaches the skin.[36][38] The way the skin reacts to different allergens gives allergists the upper hand and allows them to test for allergies by injecting a very small amount of an allergen into the skin.[36] Even though these injections are very small and local, they still pose the risk of causing systematic anaphylaxis.[36]
Risk factors for allergies can be placed in two broad categories, namelyhost andenvironmental factors.[39] Host factors includeheredity, sex,race, and age, with heredity being by far the most significant. However, there has been a recent increase in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure toinfectious diseases during early childhood,environmental pollution, allergen levels, anddietary changes.[40]
Dust mite allergy, also known as house dust allergy, is asensitization and allergic reaction to the droppings ofhouse dust mites. The allergy is common[41][42] and can trigger allergic reactions such as asthma,eczema, oritching. The mite's gut contains potent digestive enzymes (notablypeptidase 1) that persist in their feces and are major inducers of allergic reactions such aswheezing. The mite's exoskeleton can also contribute to allergic reactions. Unlikescabies mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic.[43]
A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow's milk,soy, eggs, wheat, peanuts,tree nuts, fish, and shellfish.[44] Other food allergies, affecting less than 1 person per 10,000 population, may be considered "rare".[45] The most common food allergy in the US population is a sensitivity tocrustacea.[45] Althoughpeanut allergies are notorious for their severity, peanut allergies are not the most common food allergy in adults or children. Severe or life-threatening reactions may be triggered by other allergens and are more common when combined with asthma.[44]
Rates of allergies differ between adults and children. Children can sometimes outgrow peanut allergies.Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.[46] The sensitivity is usually to proteins in thewhite, rather than theyolk.[47]
Milk-protein allergies—distinct fromlactose intolerance—are most common in children.[48] Approximately 60% of milk-protein reactions areimmunoglobulin E–mediated, with the remaining usually attributable toinflammation of the colon.[49] Some people are unable to tolerate milk from goats or sheep as well as from cows, and many are also unable to tolerate dairy products such as cheese. Roughly 10% of children with a milk allergy will have a reaction to beef.[50] Lactose intolerance, a common reaction to milk, is not a form of allergy at all, but due to the absence of anenzyme in thedigestive tract.[51]
Allergens can be transferred from one food to another throughgenetic engineering; however, genetic modification can also remove allergens. Little research has been done on the natural variation of allergen concentrations in unmodified crops.[52][53]
Latex can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, 1 in 800 surgical patients (0.125 percent) reported latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins.[54]
The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48–96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.[54]Anaphylactic reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but othermucosal exposures, such as dental procedures, can also produce systemic reactions.[54]
Latex and banana sensitivity may cross-react. Furthermore, those with latex allergy may also have sensitivities toavocado, kiwifruit, and chestnut.[55] These people often haveperioral itching and localurticaria. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana,avocado,kiwifruit, andchestnut occurs because latex proteins are structurallyhomologous with some other plant proteins.[54]
About 10% of people report that they are allergic topenicillin; however, of that 10%, 90% turn out not to be.[56] Serious allergies only occur in about 0.03%.[56]
Of these poisonous plants, sumac is the most virulent.[59][60] The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling,papules,vesicles,blisters, and streaking.[61]
Estimates vary on the population fraction that will have an immune system response. Approximately 25% of the population will have a strong allergic response to urushiol. In general, approximately 80–90% of adults will develop a rash if they are exposed to 0.0050 mg (7.7×10−5 gr) of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.[62]
Allergic diseases are stronglyfamilial;identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time innon-identical twins.[63] Allergic parents are more likely to have allergic children[64] and those children's allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent alonggenealogies; parents who are allergic to peanuts may have children who are allergic toragweed. The likelihood of developing allergies isinherited and related to an irregularity in the immune system, but the specificallergen is not.[64]
The risk of allergicsensitization and the development of allergies varies with age, with young children most at risk.[65] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.[65] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.[66]
Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due tomigration.[64] It has been suggested that differentgenetic loci are responsible for asthma, to be specific, in people ofEuropean,Hispanic,Asian, andAfrican origins.[67]
Researchers have worked to characterize genes involved in inflammation and the maintenance of mucosal integrity. The identified genes associated with allergic disease severity, progression, and development primarily function in four areas: regulating inflammatory responses (IFN-α,TLR-1,IL-13,IL-4, IL-5, HLA-G, iNOS), maintaining vascular endothelium and mucosal lining (FLG, PLAUR, CTNNA3, PDCH1, COL29A1), mediating immune cell function (PHF11, H1R, HDC, TSLP, STAT6, RERE, PPP2R3C), and influencing susceptibility to allergic sensitization (e.g., ORMDL3, CHI3L1).[68]
Multiple studies have investigated the genetic profiles of individuals with predispositions to and experiences of allergic diseases, revealing a complex polygenic architecture. Specific genetic loci, such as MIIP, CXCR4, SCML4, CYP1B1, ICOS, and LINC00824, have been directly associated with allergic disorders.[68] Additionally, some loci show pleiotropic effects, linking them to both autoimmune and allergic conditions, including PRDM2, G3BP1, HBS1L, and POU2AF1.[68] These genes engage in shared inflammatory pathways across various epithelial tissues—such as the skin, esophagus, vagina, and lung—highlighting common genetic factors that contribute to the pathogenesis of asthma and other allergic diseases.[68]
In atopic patients, transcriptome studies have identified IL-13-related pathways as key for eosinophilic airway inflammation and remodeling. That causes the body to experience the type of airflow restriction of allergic asthma.[68] Expression of genes was quite variable: genes associated with inflammation were found almost exclusively in superficial airways, while genes related to airway remodeling were mainly present in endobronchial biopsy specimens.[68] This enhanced gene profile was similar across multiple sample sizes – nasal brushing, sputum, endobronchial brushing – demonstrating the importance of eosinophilic inflammation, mast cell degranulation and group 3 innate lymphoid cells in severe adult-onset asthma.[68] IL-13 is an immunoregulatory cytokine that is made mostly by activated T-helper 2 (Th2) cells.[69] It is an important cytokine for many steps in B-cell maturation and differentiation, since it increases CD23 and MHC class II molecules, and aids in B-cell isotype switching to IgE.[68][69] IL-13 also suppresses macrophage function by reducing the release of pro-inflammatory cytokines and chemokines.[69][70] The more striking thing is that IL-13 is the prime mover in allergen-induced asthma via pathways that are independent of IgE and eosinophils.[69]
Allergic diseases are caused by inappropriate immunological responses to harmlessantigens driven by aTH2-mediated immune response. Many bacteria and viruses elicit aTH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease.[71] In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens, and thus normally benign microbial objects—like pollen—will trigger an immune response.[72]
The hygiene hypothesis was developed to explain the observation thathay fever andeczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child.[73] It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries.[74] The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.[75]
Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world, and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[76] Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[77] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[78] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth bycaesarean section rather than vaginal birth.[79][80]
Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.[82] Historically, the trees planted in urban areas were predominantly male to prevent litter from seeds and fruits, but the high ratio of male trees causes high pollen counts, a phenomenon that horticulturist Tom Ogren has called "botanical sexism".[83]
Parasitic worms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routinechlorination and purification of drinking water supplies.[86] Recent research has shown that some common parasites, such as intestinal worms (e.g.,hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) thatsuppress the immune system and prevent the body from attacking the parasite.[87] This gives rise to a new slant on the hygiene hypothesis theory—thatco-evolution of humans and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive.[88]
In particular, research suggests that allergies may coincide with the delayed establishment ofgut flora ininfants.[89] However, the research to support this theory is conflicting, with some studies performed in China andEthiopia showing an increase in allergy in people infected with intestinal worms.[82] Clinical trials have been initiated to test the effectiveness ofhelminthic therapy with certain worms in treating some allergies.[90] It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspectedsymbiosis is at work.[90]
Degranulation process in allergy. Second exposure to allergen.1 – antigen;2 – IgE antibody;3 – FcεRI receptor;4 – preformed mediators (histamine, proteases, chemokines, heparin);5 –granules;6 –mast cell;7 – newly formed mediators (prostaglandins, leukotrienes, thromboxanes,PAF).
In the initial stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professionalantigen-presenting cell causes a response in a type of immune cell called aTH2 lymphocyte, a subset ofT cells that produce acytokine calledinterleukin-4 (IL-4). These TH2 cells interact with otherlymphocytes calledB cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind ofFc receptor calledFcεRI) on the surface of other kinds of immune cells calledmast cells andbasophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen.[40]
If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule and activates the sensitized cell. Activated mast cells and basophils undergo a process calleddegranulation, during which they releasehistamine and other inflammatory chemical mediators (cytokines,interleukins,leukotrienes, andprostaglandins) from theirgranules into the surrounding tissue causing several systemic effects, such asvasodilation,mucous secretion,nerve stimulation, andsmooth muscle contraction.
This results inrhinorrhea, itchiness,dyspnea, andanaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis) or localized to specific body systems. Asthma is localized to the respiratory system and eczema is localized to thedermis.[40]
After the chemical mediators of the acute response subside, late-phase responses can often occur. This is due to the migration of otherleukocytes such asneutrophils,lymphocytes,eosinophils, andmacrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction.[91] Cytokines from mast cells may play a role in the persistence of long-term effects. Late-phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils and are still dependent on activity of TH2 cells.[92]
Althoughallergic contact dermatitis is termed an "allergic" reaction (which usually refers to type I hypersensitivity), its pathophysiology involves a reaction that more correctly corresponds to atype IV hypersensitivity reaction.[93] In type IV hypersensitivity, there is activation of certain types ofT cells (CD8+) that destroy target cells on contact, as well as activatedmacrophages that producehydrolyticenzymes.[94]
An allergy testing machine being operated in a diagnostic immunology lab
Effective management of allergic diseases relies on the ability to make an accurate diagnosis.[95] Allergy testing can help confirm or rule out allergies.[96][97] Correct diagnosis, counseling, and avoidance advice based on valid allergy test results reduce the incidence of symptoms and need for medications, and improve quality of life.[96] To assess the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test, or an allergyblood test. Both methods are recommended, and they have similar diagnostic value.[97][98]
Skin prick tests and blood tests are equally cost-effective, and health economic evidence shows that both tests were cost-effective compared with no test.[96] Early and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions.[99]
Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed to improve health and quality of life. Annualtesting is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown, and the testing interval is extended to 2–3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish.[97] Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.[100]
Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny punctures or pricks made into the patient's skin. Tiny amounts of suspected allergens and/or theirextracts (e.g., pollen, grass, mite proteins, peanut extract) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A negative and positive control are also included for comparison (eg, negative is saline or glycerin; positive is histamine). A small plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected "intradermally" into the patient's skin, with a needle and syringe. Common areas for testing include the inside forearm and the back.
If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blownhive (called "wheal and flare") in more sensitive patients similar to amosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/− meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature.[101]
In general, a positive response is interpreted when the wheal of an antigen is ≥3mm larger than the wheal of the negative control (eg, saline or glycerin).[102] Some patients may believe they have determined their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy.[103]
If a serious life-threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has takenantihistamines in the last several days.
Patch testing is a method used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed reactions. It is used to help ascertain the cause of skin contact allergy orcontact dermatitis. Adhesive patches, usually treated with several common allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, usually at 48 hours after application of the patch, and again two or three days later.
An allergyblood test is quick and simple and can be ordered by a licensed health care provider (e.g., an allergy specialist) or general practitioner. Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity, and pregnancy. Adults and children of any age can get an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often gentler than several skin pricks.
An allergy blood test is available through mostlaboratories. A sample of the patient's blood is sent to a laboratory for analysis, and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are very safe since the person is not exposed to any allergens during the testing procedure. After the onset of anaphylaxis or a severe allergic reaction, guidelines recommend emergency departments obtain a time-sensitive blood test to determine blood tryptase levels and assess for mast cell activation.[104]
The test measures the concentration of specificIgE antibodies in the blood.Quantitative IgE test results increase the possibility of ranking how different substances may affect symptoms. A rule of thumb is that the higher the IgE antibody value, the greater the likelihood of symptoms. Allergens found at low levels that today do not result in symptoms cannot help predict future symptom development. The quantitative allergy blood result can help determine what a patient is allergic to, help predict and follow the disease development, estimate the risk of a severe reaction, and explaincross-reactivity.[105][106]
A low total IgE level is not adequate to rule outsensitization to commonly inhaled allergens.[107]Statistical methods, such asROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted.
Challenge testing: Challenge testing is when tiny amounts of a suspected allergen are introduced to the body orally, through inhalation, or via other routes. Except for testing food and medication allergies, challenges are rarely performed. When this type of testing is chosen, it must be closely supervised by anallergist.
Elimination/challenge tests: This testing method is used most often with foods or medicines. A patient with a suspected allergen is instructed to modify his diet to totally avoid that allergen for a set time. If the patient experiences significant improvement, he may then be "challenged" by reintroducing the allergen, to see if symptoms are reproduced.
Unreliable tests: There are other types of allergy testing methods that are unreliable, includingapplied kinesiology (allergy testing through muscle relaxation),cytotoxicity testing, urine autoinjection, skintitration (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.[112]
Before a diagnosis of allergic disease can be confirmed, other plausible causes of the presenting symptoms must be considered.[113]Vasomotor rhinitis, for example, is one of many illnesses that share symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.[114] Once a diagnosis ofasthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.
Giving peanut products early in childhood may decrease the risk of allergies, and onlybreastfeeding during at least the first few months of life may decrease the risk of allergicdermatitis.[115][116] There is little evidence that a mother's diet during pregnancy or breastfeeding affects the risk of allergies,[115] although there has been some research to show that irregular cow's milk exposure might increase the risk of cow's milk allergy.[117] There is some evidence that delayed introduction of certain foods is useful,[115] and that early exposure to potential allergens may actually be protective.[5]
According to recent studies from pediatric professionals in the U.K. and North Carolina, they suggest that early exposure to peanut products has greatly reducedpeanut allergies among young children in the U.S. Following milestone research from a decade ago, the studies found that pediatric guidelines from 2015 and 2017 were revised to encourage introducing peanuts to high risk infants from the early ages of 4 to 6 months. Researchers who looked into the collected data found a 43% drop in the frequent occurrence of peanut allergies. Which prevented an estimated 40,000 cases and resulted in a noticeable decline in overall food allergy cases. While this is notable, some pediatric experts want to ensure that caution is still provided to the public about the real-world implementation of guidelines since there are potential inconsistencies and limitations. These findings focus on the benefits and risks of early allergen introductions to hopefully slow the rise of food allergies.[118]
Fish oil supplementation during pregnancy is associated with a lower risk of food sensitivities.[116] Probiotic supplements during pregnancy or infancy may help to prevent atopic dermatitis.[119][120]
Management of allergies typically involves avoiding the allergy trigger and taking medications to improve the symptoms.[6]Allergen immunotherapy may be useful for some types of allergies.[6]
Allergenimmunotherapy is useful for environmental allergies, allergies to insect bites, and asthma.[6][122] Its benefit for food allergies is unclear and thus not recommended.[6] Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system's response.[6]
Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children[123][124] and in asthma.[122] The benefits may last for years after treatment is stopped.[125] It is generally safe and effective for allergic rhinitis andconjunctivitis, allergic forms of asthma, and stinging insects.[126]
To a lesser extent, the evidence also supports the use ofsublingual immunotherapy for rhinitis and asthma.[125] For seasonal allergies the benefit is small.[127] In this form the allergen is given under the tongue and people often prefer it to injections.[125] Immunotherapy is not recommended as a stand-alone treatment for asthma.[125]
An experimental treatment,enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective.[128] EPD uses dilutions of allergen and an enzyme,beta-glucuronidase, to whichT-regulatory lymphocytes are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment ofautoimmune diseases, but evidence does not show effectiveness.[128]
A review found no effectiveness ofhomeopathic treatments and no difference compared withplacebo. The authors concluded that based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.[129]
The allergic diseases—hay fever and asthma—have increased in the Western world over the past 2–3 decades.[132] Increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s,[133] although some suggest that a steady rise in sensitization has been occurring since the 1920s.[134] The number of new cases per year ofatopy in developing countries has, in general, remained much lower.[133]
10 million have allergic asthma (about 3% of the population). The prevalence of asthma increased 75% from 1980 to 1994. Asthma prevalence is 39% higher in African Americans than inEuropeans.[139]
5.7 million (about 9.4%). In six- and seven-year-olds asthma increased from 18.4% to 20.9% over five years, during the same time the rate decreased from 31% to 24.7% in 13- to 14-year-olds.
Atopic eczema
About 9% of the population. Between 1960 and 1990, prevalence has increased from 3% to 10% in children.[140]
5.8 million (about 1% severe).
Anaphylaxis
At least 40 deaths per year due to insect venom. About 400 deaths due to penicillin anaphylaxis. About 220 cases of anaphylaxis and 3 deaths per year are due to latex allergy.[141] An estimated 150 people die annually from anaphylaxis due to food allergy.[142]
Between 1999 and 2006, 48 deaths occurred in people ranging from five months to 85 years old.
Insect venom
Around 15% of adults have mild, localized allergic reactions. Systemic reactions occur in 3% of adults and less than 1% of children.[143]
Unknown
Drug allergies
Anaphylactic reactions to penicillin cause 400 deaths per year.
Unknown
Food allergies
7.6% of children and 10.8% of adults.[144] Peanut and/or tree nut (e.g.walnut) allergy affects about three million Americans, or 1.1% of the population.[142]
5–7% of infants and 1–2% of adults. A 117.3% increase in peanut allergies was observed from 2001 to 2005, an estimated 25,700 people in England are affected.
Multiple allergies (Asthma, eczema and allergic rhinitis together)
Unknown
2.3 million (about 3.7%), prevalence has increased by 48.9% between 2001 and 2005.[145]
Although genetic factors govern susceptibility to atopic disease, increases inatopy have occurred within too short a period to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes.[133] Several hypotheses have been identified to explain this increased rate. Increased exposure to perennial allergens may be due to housing changes and increased time spent indoors, and a decreased activation of a common immune control mechanism may be caused by changes in cleanliness[146] or hygiene, and exacerbated by dietary changes, obesity, and decline in physical exercise.[132] Thehygiene hypothesis maintains[147] that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away fromTH1 type responses, leading to unrestrained TH2 responses that allow for an increase in allergy.[88][148]
Changes in rates and types of infection alone, however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of thegastrointestinal microbial environment. Evidence has shown that exposure to food andfecal-oral pathogens, such ashepatitis A,Toxoplasma gondii, andHelicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%,[149] and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma.[150] It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation.[151] Important elements of newer hygiene hypotheses also include exposure toendotoxins, exposure to pets and growing up on a farm.[151]
Some symptoms attributable to allergic diseases are mentioned in ancient sources.[152] Particularly, three members of the RomanJulio-Claudian dynasty (Augustus,Claudius andBritannicus) are suspected to have a family history ofatopy.[152][153] The concept of "allergy" was originally introduced in 1906 by theViennesepediatricianClemens von Pirquet, after he noticed that patients who had received injections of horse serum or smallpox vaccine usually had quicker, more severe reactions to second injections.[154] Pirquet called this phenomenon "allergy" from theAncient Greek wordsἄλλοςallos meaning "other" andἔργονergon meaning "work".[155]
All forms of hypersensitivity used to be classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with a common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed byPhilip Gell andRobin Coombs that described four types ofhypersensitivity reactions, known as Type I to Type IV hypersensitivity.[156]
With this new classification, the wordallergy, sometimes clarified as atrue allergy, was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions involving IgE antibodies.[157]
A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeledimmunoglobulin E (IgE). IgE was simultaneously discovered in 1966–67 by two independent groups:[158]Ishizaka's team at the Children's Asthma Research Institute and Hospital in Denver, USA,[159] and by Gunnar Johansson and Hans Bennich in Uppsala, Sweden.[160] Their joint paper was published in April 1969.[161]
Radiometric assays include theradioallergosorbent test (RAST test) method, which uses IgE-binding (anti-IgE) antibodies labeled withradioactive isotopes for quantifying the levels of IgE antibody in the blood.[162]
The RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which uses the newer fluorescence-labeled technology.[163]
The term RAST became a colloquialism for all varieties of (in vitro allergy) tests. This is unfortunate because it is well recognized that there are well-performing tests and some that do not perform so well, yet they are all called RASTs, making it difficult to distinguish which is which. For these reasons, it is now recommended that use of RAST as a generic descriptor of these tests be abandoned.[17]
The updated version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receiveFood and Drug Administration approval to quantitatively report to its detection limit of 0.1kU/L.[163]
The medical speciality that studies, diagnoses and treats diseases caused by allergies is called allergology.[164]An allergist is a physician specially trained to manage and treat allergies, asthma, and the other allergic diseases. In the United States physicians holding certification by theAmerican Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and evaluation process, including a proctored examination to demonstrate knowledge, skills, and experience in patient care in allergy and immunology.[165] Becoming an allergist/immunologist requires completion of at least nine years of training.
After completing medical school and graduating with a medical degree, a physician will undergo three years of training ininternal medicine (to become an internist) orpediatrics (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either theAmerican Board of Pediatrics (ABP), theAmerican Osteopathic Board of Pediatrics (AOBP), theAmerican Board of Internal Medicine (ABIM), or theAmerican Osteopathic Board of Internal Medicine (AOBIM). Internists or pediatricians wishing to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy/immunology training program. Allergist/immunologists listed as ABAI-certified have successfully passed the certifying examination of the ABAI following their fellowship.[166]
In 2006, theHouse of Lords convened a subcommittee. It concluded likewise in 2007 that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several recommendations.[168]
Low-allergen foods are being developed, as are improvements in skin prick test predictions; evaluation of the atopy patch test, wasp sting outcomes predictions, a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.[169]
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