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Allergies, also known as allergic diseases, refer a number of conditions caused by the
hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
of the immune system to typically harmless substances in the environment. These diseases include hay fever,
food allergies A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressur ...
, atopic dermatitis,
allergic asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coug ...
, and
anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...
. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note:
food intolerances Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Fo ...
and food poisoning are separate conditions. Common allergens include pollen and certain foods. Metals and other substances may also cause such problems. Food, insect stings, 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
mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s or
basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
s 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 steroids and
antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
. In severe reactions, injectable adrenalin (epinephrine) is recommended.
Allergen immunotherapy Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for environmental allergies, such as insect bites, and asthma. Immunotherapy involves exposing people to larger and larger amounts of allergen in ...
, 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, about 6% of people have at least one food allergy, 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 Clemens Peter Freiherr von Pirquet (12 May 187428 February 1929) was an Austrian scientist and pediatrician best known for his contributions to the fields of bacteriology and immunology. Career Born in Vienna, he studied theology at the Universit ...
in 1906.


Signs and symptoms

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 lungs, shortness of breath, coughing, and wheezing. Aside from these ambient allergens, allergic reactions can result from foods,
insect stings Insect bites and stings occur when an insect is agitated and seeks to defend itself through its natural defense mechanisms, or when an insect seeks to feed off the bitten person. Some insects inject formic acid, which can cause an immediate skin ...
, and reactions to
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s like aspirin and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain,
bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pres ...
, vomiting, diarrhea,
itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
y skin, and hives. Food allergies rarely cause
respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
(asthmatic) reactions, or
rhinitis Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip. The inflammation is caused by viruses, bacteria, irrita ...
. 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 the digestive system, the
respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies ...
, and the circulatory system. Depending on the severity, anaphylaxis can include skin reactions, bronchoconstriction, swelling,
low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...
, coma, and
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. 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.


Skin

Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as
contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...
or eczema. Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "
weal The term ''weal'' may refer to: * Happiness, positive or pleasant emotions ranging from contentment to intense joy * Prosperity, the state of flourishing, thriving, good fortune or good social status * Wealth, abundance of valuable resources or m ...
and flare" reaction characteristic of hives and
angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...
. 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 Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
.


Cause

Risk factors for allergies can be placed in two broad categories, namely host and environmental factors. Host factors include heredity, sex,
race Race, RACE or "The Race" may refer to: * Race (biology), an informal taxonomic classification within a species, generally within a sub-species * Race (human categorization), classification of humans into groups based on physical traits, and/or s ...
, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and
dietary In nutrition, diet is the sum of food consumed by a person or other organism. The word diet often implies the use of specific intake of nutrition for health or weight-management reasons (with the two often being related). Although humans are o ...
changes.


Dust mites

Dust mite allergy, also known as house dust allergy, is a
sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of sti ...
and allergic reaction to the droppings of
house dust mite House dust mites (HDM, or simply dust mites) are various species of acariform mites belonging to the family Pyroglyphidae that are found in association with dust in dwellings. They are known for causing allergies. Biology Species The curren ...
s. The allergy is common and can trigger allergic reactions such as asthma, eczema, or
itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
ing. It is the manifestation of a
parasitosis A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitolo ...
. The mite's gut contains potent digestive enzymes (notably peptidase 1) that persist in their feces and are major inducers of allergic reactions such as wheezing. The mite's exoskeleton can also contribute to allergic reactions. Unlike scabies mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic.


Foods

A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow's
milk Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digest solid food. Immune factors and immune-modula ...
,
soy The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu and ...
,
eggs Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especial ...
,
wheat Wheat is a grass widely cultivated for its seed, a cereal grain that is a worldwide staple food. The many species of wheat together make up the genus ''Triticum'' ; the most widely grown is common wheat (''T. aestivum''). The archaeologi ...
, peanuts,
tree nuts A nut is a fruit consisting of a hard or tough nutshell protecting a kernel which is usually edible. In general usage and in a culinary sense, a wide variety of dry seeds are called nuts, but in a botanical context "nut" implies that the shell ...
,
fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of ...
, and shellfish. Other
food allergies A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressur ...
, affecting less than 1 person per 10,000 population, may be considered "rare". The use of hydrolyzed milk baby formula versus standard milk baby formula does not appear to affect the risk. The most common food allergy in the US population is a sensitivity to crustacea. Although peanut 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. 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 white, rather than the yolk. Milk-protein allergies are most common in children. Approximately 60% of milk-protein reactions are immunoglobulin E-mediated, with the remaining usually attributable to inflammation of the colon. 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. Beef contains small amounts of proteins that are present in greater abundance in cow's milk.
Lactose intolerance Lactose intolerance is a common condition caused by a decreased ability to digest lactose, a sugar found in dairy products. Those affected vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pai ...
, a common reaction to milk, is not a form of allergy at all, but due to the absence of an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
in the
digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
. Those with tree nut allergies may be allergic to one or to many tree nuts, including pecans,
pistachios The pistachio (, ''Pistacia vera''), a member of the cashew family, is a small tree originating from Central Asia and the Middle East. The tree produces seeds that are widely consumed as food. ''Pistacia vera'' is often confused with other spe ...
,
pine nut Pine nuts, also called piñón (), pinoli (), pignoli or chilgoza (), are the edible seeds of pines (family Pinaceae, genus ''Pinus''). According to the Food and Agriculture Organization, only 29 species provide edible nuts, while 20 are trad ...
s, and
walnut A walnut is the edible seed of a drupe of any tree of the genus ''Juglans'' (family Juglandaceae), particularly the Persian or English walnut, '' Juglans regia''. Although culinarily considered a "nut" and used as such, it is not a true ...
s. In addition, seeds, including
sesame seeds Sesame ( or ; ''Sesamum indicum'') is a flowering plant in the genus '' Sesamum'', also called benne. Numerous wild relatives occur in Africa and a smaller number in India. It is widely naturalized in tropical regions around the world and is cu ...
and poppy seeds, 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.


Latex

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. 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 Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but other mucosal 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 In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on t ...
itching and local
urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...
. 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.


Medications

About 10% of people report that they are allergic to penicillin; however, 90% turn out not to be. Serious allergies only occur in about 0.03%.


Insect stings

Typically,
insects Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of j ...
which generate allergic responses are either stinging insects ( wasps, bees, hornets and
ants Ants are Eusociality, eusocial insects of the Family (biology), family Formicidae and, along with the related wasps and bees, belong to the Taxonomy (biology), order Hymenoptera. Ants evolved from Vespoidea, vespoid wasp ancestors in the Creta ...
) or biting insects (
mosquitoes Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small Diptera, flies within the family Culicidae (from the Latin ''culex'' meaning "gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish ...
,
ticks Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...
). Stinging insects inject venom into their victims, whilst biting insects normally introduce anti-coagulants.


Toxins interacting with proteins

Another non-food protein reaction,
urushiol-induced contact dermatitis Urushiol-induced contact dermatitis (also called Toxicodendron dermatitis or Rhus dermatitis) is a type of allergic contact dermatitis caused by the oil urushiol found in various plants, most notably species of the genus '' Toxicodendron'': pois ...
, originates after contact with poison ivy, eastern poison oak, western poison oak, or
poison sumac ''Toxicodendron vernix'', commonly known as poison sumac, or swamp-sumach, is a woody shrub or small tree growing to 9 metres (30 feet) tall. It was previously known as ''Rhus vernix''. This plant is also known as thunderwood, particul ...
. Urushiol, which is not itself a protein, acts as a
hapten In immunology, haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself (in general, only large molecules, i ...
and chemically reacts with, binds to, and changes the shape of
integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...
s on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response. Of these poisonous plants, sumac is the most virulent. The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling,
papule A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
s, vesicles, blisters, and streaking. Estimates vary on the percentage of the population that will have an immune system response. Approximately 25 percent of the population will have a strong allergic response to urushiol. In general, approximately 80 percent to 90 percent 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.


Genetics

Allergic diseases are strongly familial:
identical twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in
non-identical twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
. Allergic parents are more likely to have allergic children, 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 along
genealogies Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kins ...
; parents who are allergic to peanuts may have children who are allergic to
ragweed Ragweeds are flowering plants in the genus ''Ambrosia'' in the aster family, Asteraceae. They are distributed in the tropical and subtropical regions of the Americas, especially North America,inherited and related to an irregularity in the immune system, but the specific allergen is not. The risk of allergic
sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of sti ...
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. Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to
migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
. It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.


Hygiene hypothesis

Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
and
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es elicit a TH1-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. 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. 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. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. 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.


Stress

Chronic
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of
interleukin 12 Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B- lymphoblastoid cells ( NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. ...
by both the autonomic nervous system and the
hypothalamic–pituitary–adrenal axis The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a ...
. Stress management in highly susceptible individuals may improve symptoms.


Other environmental factors

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 Urban means "related to a city". In that sense, the term may refer to: * Urban area, geographical area distinct from rural areas * Urban culture, the culture of towns and cities Urban may also refer to: General * Urban (name), a list of people ...
populations versus rural populations, although these differences are becoming less defined. 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". Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy. Endotoxin exposure reduces release of inflammatory
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s such as TNF-α,
IFNγ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...
, interleukin-10, and
interleukin-12 Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B- lymphoblastoid cells ( NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. ...
from white blood cells ( leukocytes) that circulate in the blood. Certain microbe-sensing
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes. Gutworms 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 Chlorination may refer to: * Chlorination reaction In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transform ...
and purification of drinking water supplies. Recent research has shown that some common parasites, such as
intestinal worms An intestinal parasite infection is a condition in which a parasite infects the gastro-intestinal tract of humans and other animals. Such parasites can live anywhere in the body, but most prefer the intestinal wall. Routes of exposure and infe ...
(e.g., hookworms), 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 In biology, coevolution occurs when two or more species reciprocally affect each other's evolution through the process of natural selection. The term sometimes is used for two traits in the same species affecting each other's evolution, as well ...
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 infants. 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 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. For more information on this topic, see Helminthic therapy.


Pathophysiology


Acute response

In the initial stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional antigen-presenting cell causes a response in a type of immune cell called a TH2 lymphocyte, a subset of
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s that produce a
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
called
interleukin-4 The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 ...
(IL-4). These TH2 cells interact with other lymphocytes called B 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 of Fc receptor called FcεRI) on the surface of other kinds of immune cells called
mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s and
basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
s, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen. 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 (
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s,
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s,
leukotriene Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes ...
s, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as
vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...
, mucous secretion, nerve stimulation, and smooth muscle contraction. This results in
rhinorrhea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies ( hay fever) or certain viral infections, such as the common cold or CO ...
, 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.


Late-phase response

After the chemical mediators of the acute response subside, late-phase responses can often occur. This is due to the migration of other leukocytes such as
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s, lymphocytes,
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
s, and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction. 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.


Allergic contact dermatitis

Although
allergic contact dermatitis Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD). Although less common than ICD, ACD is ...
is termed an "allergic" reaction (which usually refers to type I hypersensitivity), its pathophysiology involves a reaction that more correctly corresponds to a
type IV hypersensitivity Type IV hypersensitivity, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not humoral (not antibody-mediated) but rather is a type of cell-med ...
reaction. In type IV hypersensitivity, there is activation of certain types of
T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
(CD8+) that destroy target cells on contact, as well as activated macrophages that produce hydrolytic
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s.


Diagnosis

Effective management of allergic diseases relies on the ability to make an accurate diagnosis. Allergy testing can help confirm or rule out allergies.NICE Diagnosis and assessment of food allergy in children and young people in primary care and community settings, 2011 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. To assess the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test, or an allergy blood test. Both methods are recommended, and they have similar diagnostic value. 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 testing 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.


Skin prick testing

Skin test A skin test is a medical test in which a substance is injected into the skin. Examples * Casoni test * Corneometry * Dick test * Fernandez reaction * Frei test * Hair perforation test * Kveim test * Leishmanin skin test * Lepromin * Patch t ...
ing 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 their extracts (''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 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-blown hive (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. 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 Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
in the last several days.


Patch testing

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 or
contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...
. 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.


Blood testing

An allergy blood 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 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. The test measures the concentration of specific IgE 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 explain
cross-reactivity Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a c ...
. A low total IgE level is not adequate to rule out
sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of sti ...
to commonly inhaled allergens.
Statistical methods Statistics (from German: ''Statistik'', "description of a state, a country") is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of data. In applying statistics to a scientific, industria ...
, such as ROC 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. Laboratory methods to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay (ELISA, or EIA), radioallergosorbent test (RAST) and fluorescent enzyme immunoassay (FEIA).


Other testing

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 an
allergist An allergist is a physician specially trained to manage and treat allergies, asthma and the other allergic diseases. They may also be called immunologists. Becoming an allergist Becoming an allergist/immunologist requires completion of at lea ...
. 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 Titration (also known as titrimetry and volumetric analysis) is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte (a substance to be analyzed). A reagent, termed the ''titrant'' ...
(Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.


Differential diagnosis

Before a diagnosis of allergic disease can be confirmed, other plausible causes of the presenting symptoms should be considered.
Vasomotor rhinitis Nonallergic rhinitis is rhinitis—inflammation of the inner part of the nose—not caused by an allergy. Nonallergic rhinitis displays symptoms including chronic sneezing or having a congested, drippy nose, without an identified allergic reaction ...
, for example, is one of many illnesses that share symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis. Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.


Prevention

Giving peanut products early may decrease the risk of allergies while only
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
during at least the first few months of life may decrease the risk of dermatitis. There is no good evidence that a mother's diet during
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
or breastfeeding affects the risk of allergies, nor is there evidence that delayed introduction of certain foods is useful. Early exposure to potential allergens may actually be protective. Fish oil supplementation during pregnancy is associated with a lower risk. Probiotic supplements during pregnancy or infancy may help to prevent atopic dermatitis.


Management

Management of allergies typically involves avoiding the allergy trigger and taking medications to improve the symptoms.
Allergen immunotherapy Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for environmental allergies, such as insect bites, and asthma. Immunotherapy involves exposing people to larger and larger amounts of allergen in ...
may be useful for some types of allergies.


Medication

Several medications may be used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine (adrenaline), mast cell stabilizers, and antileukotriene agents are common treatments of allergic diseases.
Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...
s,
decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter ...
s, and other compounds thought to impair
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
chemotaxis are also commonly used. Although rare, the severity of anaphylaxis often requires epinephrine injection, and where medical care is unavailable, a device known as an epinephrine autoinjector may be used.


Immunotherapy

Allergen
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
is useful for environmental allergies, allergies to insect bites, and asthma. Its benefit for food allergies is unclear and thus not recommended. Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system's response. 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.


Alternative medicine

An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases, but evidence does not show effectiveness. 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 The National Center for Complementary and Integrative Health (NCCIH) is a United States government agency which explores complementary and alternative medicine (CAM). It was initially created in 1991 as the Office of Alternative Medicine (OAM), ...
, U.S., the evidence is relatively strong that saline nasal irrigation and
butterbur ''Petasites'' is a genus of flowering plants in the sunflower family, Asteraceae, that are commonly referred to as butterburs and coltsfoots.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.


Epidemiology

The allergic diseases—hay fever and asthma—have increased in the Western world over the past 2–3 decades. 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, although some suggest that a steady rise in sensitization has been occurring since the 1920s. The number of new cases per year of atopy in developing countries has, in general, remained much lower.


Changing frequency

Although genetic factors govern susceptibility to atopic disease, increases in atopy have occurred within too short a period to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. 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 or hygiene, and exacerbated by dietary changes, obesity, and decline in physical exercise. The hygiene hypothesis maintains 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 from TH1 type responses, leading to unrestrained TH2 responses that allow for an increase in allergy. 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 gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, '' Toxoplasma gondii'', and ''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'' (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
endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
s, exposure to
pet A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence ...
s and growing up on a farm.


History

Some symptoms attributable to allergic diseases are mentioned in ancient sources. Particularly, three members of the Roman Julio-Claudian dynasty (
Augustus Caesar Augustus (born Gaius Octavius; 23 September 63 BC – 19 August AD 14), also known as Octavian, was the first Roman emperor; he reigned from 27 BC until his death in AD 14. He is known for being the founder of the Roman Pr ...
, Claudius and Britannicus) are suspected to have a family history of atopy. The concept of "allergy" was originally introduced in 1906 by the Viennese pediatrician
Clemens von Pirquet Clemens Peter Freiherr von Pirquet (12 May 187428 February 1929) was an Austrian scientist and pediatrician best known for his contributions to the fields of bacteriology and immunology. Career Born in Vienna, he studied theology at the Universit ...
, after he noticed that patients who had received injections of horse serum or smallpox vaccine usually had quicker, more severe reactions to second injections. Pirquet called this phenomenon "allergy" from the
Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic p ...
words ἄλλος ''allos'' meaning "other" and ἔργον ''ergon'' meaning "work". 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 A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
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. Their joint paper was published in April 1969.


Diagnosis

Radiometric assays include the radioallergosorbent test (RAST test) method, which uses IgE-binding (anti-IgE) antibodies labeled with
radioactive isotope A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...
s for quantifying the levels of IgE antibody in the blood. Other, newer methods use colorimetric or fluorescence-labeled technology in the place of radioactive isotopes. 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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
approval to quantitatively report to its detection limit of 0.1kU/L.


Medical specialty

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 the American 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. 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 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 The American Board of Pediatrics (ABP) was founded in 1933. It is one of the 24 certifying boards of the American Board of Medical Specialties (ABMS). The ABP is an independent and nonprofit organization. The ABP's mission is to advance child hea ...
(ABP), the American Osteopathic Board of Pediatrics (AOBP), the
American Board of Internal Medicine The American Board of Internal Medicine (ABIM) is a 501(c)(3) nonprofit, self-appointed physician-evaluation organization that certifies physicians practicing internal medicine and its subspecialties. The American Board of Internal Medicine is n ...
(ABIM), or the
American Osteopathic Board of Internal Medicine The American Osteopathic Board of Internal Medicine (AOBIM) is an organization that provides board certification to qualified Doctors of Osteopathic Medicine (D.O.) who specialize in the prevention, diagnosis, and treatment of disease in adults ...
(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 A specialist registrar (SpR) is a doctor in the United Kingdom or the Republic of Ireland who is receiving advanced training in a specialist field of medicine in order to become a consultant in that specialty. After graduation from medical school ...
before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by immunologists. A 2003
Royal College of Physicians The Royal College of Physicians (RCP) is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of physicians by examination. Founded by royal charter from King Henry VIII in 1 ...
report presented a case for improvement of what were felt to be inadequate allergy services in the UK.Royal College of Physicians (2003). ''Allergy: the unmet need''. London: Royal College of Physicians.
PDF version
(1.03 MB)
In 2006, the
House of Lords The House of Lords, also known as the House of Peers, is the upper house of the Parliament of the United Kingdom. Membership is by appointment, heredity or official function. Like the House of Commons, it meets in the Palace of Westminste ...
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.


Research

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.


See also

* List of allergens * Allergic shiner * Histamine intolerance * Oral allergy syndrome


References


External links

* *
Types of Pollen Allergies
{{Authority control Effects of external causes Immunology Respiratory diseases Immune system Immune system disorders Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate