Allergy is a disorder of the immune system often also referred to as atopy. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings S00-T14 - Injury (S00-S09 Head ( Superficial Injury of head ( Superficial injury of The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books In medicine a disorder is a functional abnormality or disturbance An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body Allergic reactions occur to environmental substances known as allergens; these reactions are acquired, predictable and rapid. See also Nature The natural environment, commonly referred to simply as the environment, is a terminology that is comprised of all living and An allergen is a nonparasitic Antigen capable of stimulating a Type-I hypersensitivity reaction in atopic individuals An acquired disorder is a Medical condition which develops post- Fetally in contrast with a Congenital disorder, which is present at Birth Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. Hypersensitivity (also called hypersensitivity reaction refers to undesirable (damaging discomfort-producing and sometimes fatal reactions produced by the normal immune system It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily In Biology, Immunoglobulin E ( IgE) is a class of Antibody (or Immunoglobulin " Isotype " that has only been found in Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Common allergic reactions include eczema, hives, hay fever, asthma, food allergies, and reactions to the venom of stinging insects such as wasps and bees. Eczema (from Greek έκζεμα) is a form of Dermatitis, or Inflammation of the Epidermis. Hay Fever is a comic play written by Noel Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are A food allergy is an adverse immune response to a food protein This article is about the class of Biotoxins For other uses see Venom (disambiguation and Venomous (disambiguation. Insects ( Class Insecta) are a major group of Arthropods and the most diverse group of Animals on the Earth with over a million described A wasp is any Insect of the order Hymenoptera and suborder Apocrita that is neither a Bee nor Ant. Bees are flying Insects closely related to Wasps and Ants Bees are a Monophyletic lineage within the superfamily Apoidea ^[1]

Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Hay Fever is a comic play written by Noel Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss In Biology a population is the collection of inter-breeding organisms of a particular Species; in Sociology A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Allergic conjunctivitis is inflammation of the Conjunctiva (the membrane covering the white part of the eye due to Allergy. Rhinorrhea, commonly known as a runny Nose, consists of an unusually significant amount of nasal discharge Allergies can play a major role in conditions such as asthma. Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions and potentially death. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals

A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of anti-histamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy. A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion Immunotherapy in medicine refers to an array of treatment strategies based upon the concept of modulating the Immune system to achieve a prophylactic and/or For medical purposes desensitization is a method to reduce or eliminate an organism's negative reaction to a substance or stimulus Targeted therapy is a type of Medication that blocks the growth of Cancer cells by interfering with specific targeted Molecules needed for Carcinogenesis

Classification and history

The concept "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods. Vienna ( in Wien; see also other names) is the Capital of Austria, and is also one of the nine States of Austria. Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents Clemens Peter Freiherr von Pirquet ( May 12[[ 874]]&ndash February 28[[ 929]] was an Austrian scientist and pediatrician best known for his contributions Dust is a general name for minute Solid particles with Diameters less than 500 micrometers. Pollen is a fine to coarse powder consisting of microgametophytes ( pollen grains) which produce the male Gametes (sperm cells of ^[2] Pirquet called this phenomenon "allergy" from the Greek words allos meaning "other" and ergon meaning "work". Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly ^[3] Historically, all forms of hypersensitivity were 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 the common link to a disordered activation of the immune system. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly 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. Philip George Houthem Gell ( 20 October 1914 – 3 May 2001) was an Immunologist working in postwar Britain Robert Royston Amos ("Robin" Coombs, ( January 9 1921 &ndash February 25 2006) was a British immunologist, co-discoverer Hypersensitivity (also called hypersensitivity reaction refers to undesirable (damaging discomfort-producing and sometimes fatal reactions produced by the normal immune system ^[4] With this new classification, the word "allergy" was restricted to only type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions.

A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) - Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s. In Biology, Immunoglobulin E ( IgE) is a class of Antibody (or Immunoglobulin " Isotype " that has only been found in Dr is a Japanese scientist who discovered the antibody class IgE in 1966 ^[5]

Signs and symptoms

Many allergens, such as dust or pollen, are airborne particles. The skin is the outer covering of living tissue of an animal (or plant A rash is a change of the Skin which affects its color appearance or Texture. Eczema (from Greek έκζεμα) is a form of Dermatitis, or Inflammation of the Epidermis. Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease Bloating is any abnormal general Swelling, or increase in diameter of the abdominal area Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea In these cases, symptoms arise in areas in contact with air, such as eyes, nose and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, and itching and redness of the eyes. ^[6] Inhaled allergens can also lead to asthmatic symptoms, caused by narrowing of the airways (bronchoconstriction) and increased production of mucus in the lungs, shortness of breath (dyspnea), coughing and wheezing. Bronchoconstriction is the constriction of the airways in the Lungs due to the tightening of surrounding Smooth muscle, with consequent Coughing, Wheezing In vertebrates mucus is a slippery secretion produced by and covering Mucous membranes It is a viscous Colloid containing Antiseptic enzymes (such as lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from ^[7]

Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and antibiotics such as penicillin. Food is any substance usually composed primarily of Carbohydrates Fats water and/or Proteins that can be eaten or drunk by an Insect sting allergy is the term commonly given to the allergic response of an animal in response to the bite or sting of an Insect. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhoea, itchy skin, and swelling of the skin during hives. Angioedema ( BE: angiooedema) also known by its Eponym Quincke's edema, is the rapid swelling ( Edema) of the Dermis Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis. In humans the respiratory tract is the part of the Anatomy that has to do with the process of respiration. Rhinitis is the medical term describing irritation and inflammation of some internal areas of the Nose. ^[8] Insect stings, antibiotics, and certain medicines 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. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals Digestion is the breaking down of chemicals in the body into a form that can be absorbed In living organisms a respiratory system functions to allow Gas exchange. This is an article about the rock music band "Circulatory System" ^[9][10][11] Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma, and even death. The skin is the outer covering of living tissue of an animal (or plant Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. Death is the termination of the biological functions that define living Organisms It refers both to a specific This type of reaction can be triggered suddenly, or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, sometimes through a device known as the Epi-Pen auto-injector. EpiPen is a registered trademark for the most commonly used Autoinjector of Epinephrine (a The nature of anaphylaxis is such that the reaction can seem to be subsiding, but may recur throughout a prolonged period of time. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals ^[11]

Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema. LaTeX (ˈleɪtɛ Contact dermatitis is a term for a Skin reaction resulting from exposure to Allergens (allergic contact dermatitis or irritants (irritant contact dermatitis ^[12] Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema. A wheal or wheal response (also termed a welt) is a firm elevated rounded or flat topped generally pale red Papule or Plaque An itchy ^[13]

Cause

Risk factors for allergy can be placed in two general categories, namely host and environmental factors. In Biology, a host is an organism that harbors a Virus or Parasite, or a mutual or Commensal Symbiont, typically providing nourishment See also Nature The natural environment, commonly referred to simply as the environment, is a terminology that is comprised of all living and Host factors include heredity, sex, race, and age, with heredity being by far the most significant. Gender comprises a range of differences between men and women extending from the biological to the social The term race or racial group usually refers to the concept of categorizing Humans into Populations or groups on the basis of various sets There have been recent increases in the incidence of allergic disorders, however, that cannot be explained by genetic factors alone. The four main environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes. An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic Pollution is the introduction of contaminants into an environment that causes instability disorder harm or discomfort to the physical systems or living organisms they are in This article is primarily about the human diet For a discussion of animal diets see List of feeding behaviours. ^[14]

Genetic basis

Allergic diseases are strongly familial: identical twins 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. Family denotes a group of People affiliated by consanguinity affinity or co-residence Twins are Offspring resulting from the same Pregnancy, either of the same or opposite Sex. Twins are Offspring resulting from the same Pregnancy, either of the same or opposite Sex. ^[15] Allergic parents are more likely to have allergic children,^[16] and their allergies are likely to be more severe than those from non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. Genealogy (from Greek: el γενεά el-Latn genea, "descent" and el λόγος el-Latn logos, "knowledge" is the study of The peanut, or Groundnut ( Arachis hypogaea) is a species in the Legume family Fabaceae native to South America, Mexico Ragweeds ( Ambrosia) also called bitterweeds and bloodweeds, are a Genus of flowering Plants from the sunflower It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not. An allergen is a nonparasitic Antigen capable of stimulating a Type-I hypersensitivity reaction in atopic individuals ^[16]

The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk. ^[17] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. ^[17] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10. ^[18] Overall, boys have a higher risk of developing allergy than girls,^[16] although for some diseases, namely asthma in young adults, females are more likely to be affected. ^[19] Sex differences tend to decrease in adulthood. ^[16] Ethnicity may play a role in some allergies, however racial factors have been difficult to separate from environmental influences and changes due to migration. ^[16] Interestingly, it has been suggested that different genetic loci are responsible for asthma, specifically, in people of Caucasian, Hispanic, Asian, and African origins. In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a The Caucasian race, sometimes the Caucasoid race, is a term of Racial classification, coined around 1800 by Johann Friedrich Blumenbach for the " Hispanic (hispano hispánico hispânico Hispānus adjective from ''Hispānia'', the Roman name for the Iberian Peninsula) is a term that historically Asian or Asiatic is a Demonym for people from Asia. However the use of the term varies by country and person often referring to people from a particular ^[20]

Environmental factors

International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined. is a process of social and economic change whereby a human group is transformed from a Pre-industrial society into an industrial one Agriculture refers to the production of goods through the growing of plants and fungi and the raising of domesticated Animals The study of agriculture Rural areas can be large and isolated (also referred to as "the country" and/or "the countryside over the course of time ^[21]

Exposure to allergens, especially in early life, is an important risk factor for allergy. A risk factor is a variable associated with an increased risk of Disease or Infection. Alterations in exposure to microorganisms is the most plausible explanation, at present, for the increase in atopic allergy. A microorganism (also spelled micro organism or micro-organism and also called a microbe) is an Organism that is Microscopic (usually Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body ^[14] Since children that live in large families or overcrowded households, or attend day care, have a reduced incidence of allergic disease, a relationship has been proposed between exposures to bacteria and viruses during childhood, and protection against the development of allergy, which has been called – the "hygiene hypothesis". The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable In Medicine, the hygiene Hypothesis states that a lack of early childhood exposure to infectious agents Symbiotic microorganisms (e ^[21] Exposure to endotoxin and other components of bacteria may reduce atopic diseases. Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. ^[22] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic Interferon-gamma ( IFN-γ) is a Dimerized soluble Cytokine that is the only member of the type II class of Interferons This interferon was originally Interleukin -10 (IL-10 or IL10 also known as human cytokine synthesis inhibitory factor (CSIF is an anti- Inflammatory Cytokine. For Il-12 see also Ilyushin Il-12 Interleukin 12 ( IL-12) is an Interleukin that is naturally produced by Dendritic Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products ^[23] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Toll-like receptors ( TLRs) are a class of single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from Microbes ^[24]

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 and purification of drinking water supplies. Chlorination is the process of adding the element Chlorine to Water as a method of Water purification to make it fit for human consumption as ^[25] Recent research has shown that some common parasites, such as intestinal worms (e. Parasitism is a type of symbiotic relationship between Organisms of different Species. Intestinal worms, (such as threadworms and pinworms) are parasites, and usually live in the Small intestine, where they mate and live 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. The hookworm is a parasitic Nematode worm that lives in the Small intestine of its host which may be a Mammal such as a Dog, An immunosuppressant is a substance that performs Immunosuppression of the Immune system. ^[26] This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that only functions correctly in the presence of the parasites. In a broad sense biological co-evolution is "the change of a biological object triggered by the change of a related object" Without them, the immune system becomes unbalanced and oversensitive. ^[27] In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants. The gut flora are the Microorganisms that normally live in the Digestive tract and can perform a number of useful functions for their hosts ^[28] 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. China ( Wade-Giles ( Mandarin) Chung¹kuo² is a cultural region, an ancient Civilization, and depending on perspective a National NOTE This intro is the result of careful NPOV work Please do not make potentially controversial edits to it without first discussing on the talk page ^[21] Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies. ^[29] It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work. This article is about the biological phenomenon for other uses see Symbiosis (disambiguation The term symbiosis (from the Greek ^[29] For more information on this topic, see Helminthic therapy. Helminthic therapy is the treatment of Autoimmune diseases and Immune disorders by means of deliberate infestation with a Helminth or with the ova of a helminth

Pathophysiology

The pathophysiology of allergic responses can be divided into two phases. Pathophysiology is the study of the disturbance of normal Mechanical, Physical, and Biochemical functions either caused by a Disease, or resulting The first is an acute response that occurs immediately after exposure to an allergen. In Medicine, an acute disease is a disease with either or both of a rapid onset a short course (as opposed to a chronic course This phase can either subside or progress into a "late phase reaction" which can substantially prolong the symptoms of a response, and result in tissue damage.

Acute response

Degranulation process in allergy. 1 - antigen; 2 - IgE antibody; 3 - FcεRI receptor; 4 - preformed mediators (histamine, proteases, chemokines, heparine); 5 - granules; 6 - mast cell; 7 - newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF)

In the early stages of allergy, a type I hypersensitivity reaction against an allergen, encountered for the first time, causes a response in a type of immune cell called a T_H2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Interleukin-4, abbreviated IL-4, is a Cytokine that induces differentiation of naive helper T cells ( Th0 cells to Th2 cells Upon activation by These T_H2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by 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 cells and basophils, which are both involved in the acute inflammatory response. An Fc receptor is a protein found on the surface of certain cells - including Natural killer cells Macrophages Neutrophils and Mast cells - that FcεRI, or Fc epsilon RI, is the high- Affinity receptor for Immunoglobulin E (IgE an Antibody Isotype involved in A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin The IgE-coated cells, at this stage are sensitized to the allergen. ^[14]

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 (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction. Degranulation is a cellular process that releases Antimicrobial Cytotoxic molecules from secretory vesicles called granules found inside Histamine is a Biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a Neurotransmitter Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body A nerve is an enclosed cable-like bundle of peripheral Axons (the long slender projections of Neurons. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Rhinorrhea, commonly known as a runny Nose, consists of an unusually significant amount of nasal discharge Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis. The dermis is a layer of Skin beneath the epidermis that consists of Connective tissue, and cushions the body from stress and strain ^[14]

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 neutrophils, lymphocytes, eosinophils and macrophages to the initial site. Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Eosinophil granulocytes, usually called eosinophils (or less commonly acidophils) are White blood cells that are one of the Immune System components Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that The reaction is usually seen 2-24 hours after the original reaction. ^[30] Cytokines from mast cells may also 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 T_H2 cells. Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are ^[31]

Diagnosis

An allergy testing machine being operated in the diagnostic immunology lab at Lackland Air Force Base

Before a diagnosis of allergic disease can be confirmed, the other possible causes of the presenting symptoms should be carefully considered. Lackland Air Force Base is a base of the United States Air Force operated by the Air Education and Training Command ( AETC) ^[32] Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis. Vasomotor rhinitis is a form of Rhinitis that is not related to allergic reactions but which is characterized by some of the same symptoms such as a chronic Illness (sometimes referred to as ill-health or ail) can be defined as a state of poor Health. ^[33] 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.

Skin testing

Skin Testing

For assessing the presence of allergen-specific IgE antibodies, allergy skin testing is preferred over blood allergy tests because it is more sensitive and specific, simpler to use, and less expensive. ^[34] Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny puncture or pricks made into the patient's skin. Skin allergy testing is a method for medical diagnosis of allergies that attempts to provoke a small controlled allergic response Small amounts of suspected allergens and/or their extracts (pollen, grass, mite proteins, peanut extract, etc. ) 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. HIVE is an abstract game Programming library. It is designed to be simple and easy to understand 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. ^[35] 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. ^[36]

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 not avoided antihistamines for several days. A histamine antagonist is an agent which serves to inhibit the release or action of Histamine.

Blood testing

Various blood allergy testing methods are also available for detecting allergy to specific substances. This kind of testing measures a "total IgE level" - an estimate of IgE contained within the patient's serum. Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended This can be determined through the use of radiometric and colormetric immunoassays. In Optics, radiometry is the field that studies the Measurement of Electromagnetic radiation, including Visible light. Colorimetry or Colourimetry can refer to the quantitative study of Color perception An immunoassay is a Biochemical test that measures the Concentration of a substance in a biological liquid typically serum or Urine, using the Radiometric assays include the radioallergosorbent test (RAST) test method, which uses IgE-binding (anti-IgE) antibodies labeled with radioactive isotopes for quantifying the levels of IgE antibody in the blood. A RAST test (short for radioallergosorbent test) is a blood test used to determine what a person is allergic to A radionuclide is an Atom with an unstable nucleus, which is a nucleus characterized by excess energy which is available to be imparted either to a newly-created ^[34] Other newer methods use colorimetric or fluorometric technology in the place of radioactive isotopes. Some "screening" test methods are intended to provide qualitative test results, giving a "yes" or "no" answer in patients with suspected allergic sensitization. One such method has a sensitivity of about 70. 8% and a positive predictive value of 72. 6% according to a large study. ^[37]

A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens. ^[38] Statistical methods, such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. Statistics is a mathematical science pertaining to the collection analysis interpretation or explanation and presentation of Data. In Signal detection theory, a receiver operating characteristic ( ROC) or simply ROC curve, is a graphical plot of the sensitivity These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with specific allergy tests for a carefully chosen allergens is often warranted.

Treatment

There have been enormous improvements in the medical treatments used to treat allergic conditions. With respect to anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin diseases, advances have included the identification of food proteins to which IgE binding is associated with severe reactions and development of low-allergen foods, improvements in skin prick test predictions; evaluation of the atopy patch test; in wasp sting outcomes predictions and a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases. Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body ^[39]

Traditionally treatment and management of allergies involved simply avoiding the allergen in question or otherwise reducing exposure. For instance, people with cat allergies were encouraged to avoid them. While avoidance may help to reduce symptoms and avoid life-threatening anaphylaxis, it is difficult to achieve for those with pollen or similar air-borne allergies. Strict avoidance still has a role in management though, and is often used in managing food allergies.

Pharmacotherapy

Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks These include antihistamines, cortisone, dexamethasone, hydrocortisone, epinephrine (adrenaline), theophylline and cromolyn sodium. A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. Cortisone (ˈkɔrtɨsoʊn or /ˈkɔrtɨzoʊn/ (ˈkôrtəˌsōn or -zōn (17-hydroxy-11-dehydrocorticosterone is a Steroid Hormone. Dexamethasone is a potent synthetic member of the glucocorticoid class of Steroid Hormones It acts as an Anti-inflammatory and immunosuppressant Cortisol is a Corticosteroid Hormone produced by the Adrenal gland (in the Zona fasciculata of the Adrenal cortex) Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response Montelukast (trade name Singulair) is a Leukotriene receptor antagonist (LTRA used for the maintenance treatment of Asthma and to relieve symptoms of seasonal Zafirlukast is an oral Leukotriene receptor antagonist Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. A receptor is cholinergic if it uses Acetylcholine as its Neurotransmitter. A decongestant is a broad class of Medications used to relieve Nasal congestion. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements These drugs help to alleviate the symptoms of allergy, and are imperative in the recovery of acute anaphylaxis, but play little role in chronic treatment of allergic disorders.

Immunotherapy

Desensitization or hyposensitization is a treatment in which the patient is gradually vaccinated with progressively larger doses of the allergen in question. Hyposensitization (or allergy desensitization) is a form of Immunotherapy in which the patient is Vaccinated with progressively larger doses of an Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG antibody production, to block excessive IgE production seen in atopys. Immunoglobulin G ( IgG) is a Monomeric Immunoglobulin, built of two heavy chains γ and two light chains. In a sense, the person builds up immunity to increasing amounts of the allergen in question. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the development of new allergy. ^[40] Meta-analyses have also confirmed efficacy of the treatment in allergic rhinitis in children and in asthma. A review by the Mayo Clinic in Rochester confirmed the safety and efficacy of allergen immunotherapy for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insect based on numerous well-designed scientific studies. ^[41] Additionally, national and international guidelines confirm the clinical efficacy of injection immunotherapy in rhinitis and asthma, as well as the safety, provided that recommendations are followed. ^[42]

A second form of immunotherapy involves the intravenous injection of monoclonal anti-IgE antibodies. Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell These bind to free and B-cell associated IgE; signalling their destruction. They do not bind to IgE already bound to the Fc receptor on basophils and mast cells, as this would stimulate the allergic inflammatory response. The first agent of this class is Omalizumab. Omalizumab (marketed under the name Xolair) is a Monoclonal antibody made by Genentech / Novartis and used mainly in Allergy -related While this form of immunotherapy is very effective in treating several types of atopy, it should not be used in treating the majority of people with food allergies.

A third type, Sublingual immunotherapy, is an orally-administered therapy which takes advantage of oral immune tolerance to non-pathogenic antigens such as foods and resident bacteria. Sublingual Immunotherapy is method of Allergy treatment that uses an Allergen solution given under the Tongue, which over the course of treatment reduces Immune or immunological tolerance is the process by which the Immune system does not attack an Antigen. This therapy currently accounts for 40 percent of allergy treatment in Europe. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by doctors who treat allergy.

Unproven or ineffective treatments

An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. Enzyme potentiated desensitization, or EPD is a treatment for allergies developed in the 1960s by Dr ^[43] EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favouring desensitization, or down-regulation, rather than sensitization. Glucuronidases are Enzymes that separate Glucuronic acid molecules from other molecules by cutting Glycosidic bonds They are thus classified as Glycoside EPD has also been tried for the treatment of autoimmune diseases but again is not FDA approved or of proven effectiveness. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues ^[43]

In alternative medicine, a number of allergy treatments are described by its practitioners, particularly naturopathic, herbal medicine, homeopathy, traditional Chinese medicine and kinesiology. The term alternative medicine, as used in the modern western world encompasses any healing practice "that does not fall within the realm of conventional Medicine. Naturopathic medicine (also known as naturopathy, or natural medicine) is a Complementary and alternative medicine which emphasizes the body's intrinsic Herbalism is a traditional Medicinal or Folk medicine practice based on the use of Plants and Plant extracts Herbalism is also known as This article has been the subject of edit wars and has been placed on probation Traditional Chinese medicine (also known as TCM,) includes a range of traditional medical practices originating in China. Kinesiology, also known as Human Kinetics, is the science of human movement Systematic literature searches conducted by the Mayo Clinic through 2006, involving hundreds of articles studying multiple conditions, including asthma and upper respiratory tract infection showed no effectiveness of any alternative 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 alternative treatments. ^[44]

Epidemiology

Many diseases related to inflammation such as type 1 diabetes, rheumatoid arthritis and allergic diseases—hay fever and asthma—have increased in the Western world over the past 2-3 decades. Diabetes mellitus type 1 (Type 1 diabetes Type I diabetes T1D T1DM IDDM juvenile diabetes is a form of Diabetes mellitus. Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where The term Western world, the West or the Occident ( Latin: occidens -sunset -west as distinct from the Orient) can have multiple meanings ^[45] Rapid increases in allergic asthma and other atopic disorders in industrialized nations probably began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s,^[46] although some suggest that a steady rise in sensitization has been occurring since the 1920s. ^[47] The incidence of atopy in developing countries has generally remained much lower. ^[46]

Although genetic factors fundamentally govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. ^[46] Several hypotheses have been identified to explain this increased prevalence; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise. ^[45] The hygiene hypothesis maintains^[57] that high living standards and hygienic conditions exposes children to fewer infections. In Medicine, the hygiene Hypothesis states that a lack of early childhood exposure to infectious agents Symbiotic microorganisms (e It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from T_H1 type responses, leading to unrestrained T_H2 responses that allow for an increase in allergy. ^[58][59]

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 (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%,^[60] and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma. The fecal-oral route (or alternatively the oral-fecal route or orofecal route) is a way Disease can be passed when fecal particles from one Hepatitis A, (formerly known as infectious hepatitis) is an acute Infectious disease of the Liver caused by Hepatitis A virus which is Toxoplasma gondii is a species of parasitic Protozoa in the Genus Toxoplasma. Helicobacter pylori ( is a Gram-negative, microaerophilic Bacterium that inhabits various areas of the stomach and Duodenum. ^[61] It is speculated that these infections exert their effect by critically altering T_H1/T_H2 regulation. ^[62] Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm. Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. ^[62]

Medical specialty

In the United States physicians who hold certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and an evaluation process, including a secure, proctored examination to demonstrate the knowledge, skills, and experience to the provision of patient care in allergy and immunology. The United States of America —commonly referred to as the ^[63] An allergist-immunologist is a physician specially trained to manage and treat asthma and the other allergic diseases. 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 then 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) or the American Board of Internal Medicine (ABIM). Internists or pediatricians who wish 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 who are listed as ABAI-certified have successfully passed the certifying examination of the American Board of Allergy and Immunology (ABAI), following their fellowship. ^[64]

In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Internal medicine is the medical specialty concerned with the diagnosis management and nonsurgical treatment of unusual or serious diseases Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents After obtaining postgraduate exams (MRCP or MRCPCH respectively) a doctor works as several years as a specialist registrar before qualifying for the General Medical Council specialist register. Membership of the Royal Colleges of Physicians (MRCP(UK is a postgraduate medical diploma A specialist registrar or SpR is a doctor in the United Kingdom who is receiving advanced training in a specialist field of Medicine in order eventually The General Medical Council (the GMC) is the regulator of the medical profession in the United Kingdom. Allergy services may also be delivered by immunologists. Immunology is a broad branch of biomedical Science that covers the study of all aspects of the Immune system in all Organisms It deals with A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK. The Royal College of Physicians of London was the first medical institution in England to receive a Royal Charter ^[65] In 2006, the House of Lords convened a subcommittee that reported in 2007. The House of Lords is the second house of the Parliament of the United Kingdom and is also commonly referred to as "the Lords" It concluded likewise that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several other recommendations. ^[66]

See also

• Allergic inflammation
• Allergen
• Hypersensitivity
• Hypoallergenic
• Multiple chemical sensitivity (MCS)
• Urticaria
• Immunoglobulin
• IgE

References

External links

• American College of Allergy, Asthma and Immunology
• American Academy of Allergy, Asthma & Immunology
• Asthma and Allergy Foundation of America – patient advocacy organization
• Allergy & Asthma Network Mothers of Asthmatics
• American Board of Allergy and Immunology – ABAI establishes qualifications and examines physicians to become recognized specialists in allergy and immunology in the U. S.
• Alert4allergy.org - Food allergy alert service - free for UK residents