An allergy is a specific type of exaggerated immune response where the body mistakenly identifies a ordinarily harmless substance (, like pollen, pet dander, or certain foods) as a threat and launches a defense against it.
Allergic diseases are the conditions that arise as a result of allergic reactions, such as hay fever, allergic conjunctivitis, allergic asthma, atopic dermatitis, Food allergy, and anaphylaxis. Symptoms of the above diseases may include red eyes, an itchy rash, sneeze, coughing, a rhinorrhea, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.
Common include pollen and certain foods. Metals and other substances may also cause such problems. Food, , and medications are common causes of severe reactions. Their development is due to both genetic and environmental factors. The underlying mechanism involves immunoglobulin E antibodies (IgE), part of the body's immune system, binding to an allergen and then to a receptor on or where it triggers the release of inflammatory chemicals such as histamine. Diagnosis is typically based on a person's medical history. Further testing of the skin or blood may be useful in certain cases. Positive tests, however, may not necessarily mean there is a significant allergy to the substance in question.
Early exposure of children to potential allergens may be protective. Treatments for allergies include avoidance of known allergens and the use of medications such as Corticosteroid and antihistamines. In severe reactions, injectable adrenaline (epinephrine) is recommended. 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. Its use in food allergies is unclear.
Allergies are common. In the developed world, about 20% of people are affected by allergic rhinitis, food allergy affects 10% of adults and 8% of children, and about 20% have or have had atopic dermatitis at some point in time. Depending on the country, about 1–18% of people have asthma. Anaphylaxis occurs in between 0.05–2% of people. Rates of many allergic diseases appear to be increasing. The word "allergy" was first used by Clemens von Pirquet in 1906.
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. Inhaled allergens can also lead to increased production of mucus in the , shortness of breath, coughing, and wheezing.
Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, skin, and Angioedema. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis. Insect stings, food, , and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system. Depending on the severity, anaphylaxis can include skin reactions, bronchoconstriction, edema, hypotension, 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.
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. This reaction may also occur after immunotherapy.
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 inject allergen 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. Mast-cell activation also stimulates a skin lesion called the wheal-and-flare reaction. This is when the release of chemicals from local nerve endings by a nerve axon reflex, causes the Vasodilation of surrounding cutaneous blood vessels, which causes redness of the surrounding skin.
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. 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. 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. Even though these injections are very small and local, they still pose the risk of causing systematic anaphylaxis.
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. The sensitivity is usually to proteins in the Egg white, rather than the yolk.
Milk allergy—distinct from lactose intolerance—are most common in children. Approximately 60% of milk-protein reactions are immunoglobulin E–mediated, with the remaining usually attributable to proctocolitis. 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.Sicherer 64 Lactose intolerance, a common reaction to milk, is not a form of allergy at all, but due to the absence of an enzyme in the digestive tract.
Those with tree nut allergies may be allergic to one or many tree nuts, including , pistachios, and . In addition, seeds, including sesame seeds and , contain oils in which protein is present, which may elicit an allergic reaction.
Allergens can be transferred from one food to another through genetic engineering; however, genetic modification can also remove allergens. Little research has been done on the natural variation of allergen concentrations in unmodified crops.
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. Anaphylactic reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but other mucous membrane exposures, such as dental procedures, can also produce systemic reactions.
Latex and banana sensitivity may cross-react. Furthermore, those with latex allergy may also have sensitivities to avocado, kiwifruit, and chestnut. These people often have perioral itching and local urticaria. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some other plant proteins.
Of these poisonous plants, sumac is the most virulent.
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 of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction. cited in
The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk. Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.
Ethnic group may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to human migration. It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of Caucasian race, Hispanic, Asian people, and African origins.
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).
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. Additionally, some loci show pleiotropic effects, linking them to both autoimmune and allergic conditions, including PRDM2, G3BP1, HBS1L, and POU2AF1. 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.
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. 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. 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. IL-13 is an immunoregulatory cytokine that is made mostly by activated T-helper 2 (Th2) cells. 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. IL-13 also suppresses macrophage function by reducing the release of pro-inflammatory cytokines and chemokines. 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.
The hygiene hypothesis was developed to explain the observation that hay fever and eczema, 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. 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. 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.
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. Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner. The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases. The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by caesarean section rather than vaginal birth.
Alterations in exposure to is another plausible explanation, at present, for the increase in Atopy. Endotoxin exposure reduces release of inflammatory such as TNF-α, interferon-gamma, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood. Certain microbe-sensing , known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.
and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies. Recent research has shown that some common parasites, such as intestinal worms (e.g., ), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite. This gives rise to a new slant on the hygiene hypothesis theory—that co-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.
In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in . However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms. Clinical trials have been initiated to test the effectiveness of helminthic therapy with certain worms in treating some allergies. It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.
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 called degranulation, during which they release histamine and other inflammatory chemical mediators (, , , and ) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucus secretion, nerve stimulation, and smooth muscle contraction.
This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. 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 the dermis.
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. Early and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions.
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. Annual Allergy test 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. 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.
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-blown Urticaria (called "wheal and flare") in more sensitive patients similar to a mosquito 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.
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). 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.
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 taken antihistamines in the last several days.
An allergy blood test is available through most laboratories. 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.
The test measures the concentration of specific IgE 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 explain cross-reactivity.
A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens. statistics, such as , 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.
Laboratory methods to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay (ELISA, or EIA), radioallergosorbent test (RAST), fluorescent enzyme immunoassay (FEIA),
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, including applied kinesiology (allergy testing through muscle relaxation), cytotoxicity testing, urine autoinjection, skin titration (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.
Fish oil supplementation during pregnancy is associated with a lower risk of food sensitivities. Probiotic supplements during pregnancy or infancy may help to prevent atopic dermatitis.
Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children and in asthma. The benefits may last for years after treatment is stopped. It is generally safe and effective for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insects.
To a lesser extent, the evidence also supports the use of sublingual immunotherapy for rhinitis and asthma. For seasonal allergies the benefit is small. In this form the allergen is given under the tongue and people often prefer it to injections. Immunotherapy is not recommended as a stand-alone treatment for asthma.
A review found no effectiveness of homeopathic treatments and no difference compared with placebo. 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.
According to the National Center for Complementary and Integrative Health, U.S., the evidence is relatively strong that saline nasal irrigation and butterbur are effective, when compared to other alternative medicine treatments, for which the scientific evidence is weak, negative, or nonexistent, such as honey, acupuncture, omega 3's, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora, or guduchi.
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 the Gut flora. Evidence has shown that exposure to food and fecal-oral route pathogens, such as hepatitis A, Toxoplasma gondii, and Helicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma. It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation. Important elements of newer hygiene hypotheses also include exposure to , exposure to pets and growing up on a farm.
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 by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity.
With this new classification, the word allergy, sometimes clarified as a true allergy, was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions involving IgE antibodies.
A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE). IgE was simultaneously discovered in 1966–67 by two independent groups: Ishizaka's team at the Children's Asthma Research Institute and Hospital in Denver, USA, and by Gunnar Johansson and Hans Bennich in Uppsala, Sweden.Johansson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin" Immunology 1967; 13:381–94. Their joint paper was published in April 1969.
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.
American College of Allergy Asthma and Immunology (ACAAI) and the American Academy of Allergy Asthma and Immunology (AAAAI) issued the Joint Task Force Report "Pearls and pitfalls of allergy diagnostic testing" in 2008, and is firm in its statement that the term RAST is now obsolete:
The updated version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receive Food and Drug Administration approval to quantitatively report to its detection limit of 0.1kU/L.
After completing medical school and graduating with a medical degree, a physician will undergo three years of training in internal medicine (to become an internist) or pediatrics (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the American Board of Pediatrics (ABP), the American Osteopathic Board of Pediatrics (AOBP), the American Board of Internal Medicine (ABIM), or the American 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.
In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. After obtaining postgraduate exams (MRCP or MRCPCH), a doctor works for several years as a specialist registrar before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by . A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK.
In 2006, the House 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.
Signs and symptoms
Swelling of the nasal mucous membrane (allergic rhinitis) runny nose, sneezing Allergic sinusitis Redness and of the conjunctiva (allergic conjunctivitis, watery) Sneezing, coughing, bronchoconstriction, wheeze and dyspnea, sometimes outright attacks of asthma, in severe cases the airway constricts due to swelling known as laryngeal edema Feeling of fullness, possibly pain, and impaired hearing due to the lack of eustachian tube drainage. , such as eczema and urticaria Abdominal pain, bloating, vomiting, diarrhea
Skin
Cause
Dust mites
Foods
Latex
Medications
Insect stings
Toxins interacting with proteins
Genetics
Hygiene hypothesis
Stress
Other environmental factors
Pathophysiology
Acute response
Late-phase response
Allergic contact dermatitis
Diagnosis
Skin prick testing
Patch testing
Blood testing
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Other testing
Differential diagnosis
Prevention
Management
Medication
Immunotherapy
Alternative medicine
Epidemiology
+ Allergic conditions: Statistics and epidemiology 3.3 million (about 5.5% of the populationBased on an estimated population of 60.6 million ) 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. 5.8 million (about 1% severe). Between 1999 and 2006, 48 deaths occurred in people ranging from five months to 85 years old. Unknown Unknown 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. 2.3 million (about 3.7%), prevalence has increased by 48.9% between 2001 and 2005.
Changing frequency
History
Diagnosis
Medical specialty
Research
See also
External links
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