What does antihistamine treat?

Antihistamines are drugs which treat allergic rhinitis and other allergies. Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy. Typically people take antihistamines as an inexpensive, generic, over-the-counter drug with few side effects. As an alternative to taking an antihistamine, people who suffer from allergies can instead avoid the substance which irritates them. However, this is not always possible as some substances, such as pollen, are carried in the air, thus making allergic reactions caused by them generally unavoidable. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Doctors recommend that people talk to them before any longer term use of antihistamines.

Antihistamine

Although people typically use the word “antihistamine” to describe drugs for treating allergies, doctors and scientists use the term to describe a class of drug that opposes the activity of histamine receptors in the body. In this sense of the word, antihistamines are subclassified according to the histamine receptor that they act upon. The two largest classes of antihistamines are H-antihistamines and H-antihistamines. Antihistamines that target the histamine H-receptor are used to treat allergic reactions in the nose (e.g., itching, runny nose, and sneezing) as well as for insomnia. They are sometimes also used to treat motion sickness or vertigo caused by problems with the inner ear. Antihistamines that target the histamine H-receptor are used to treat gastric acid conditions (e.g., peptic ulcers and acid reflux). H-antihistamines work by binding to histamine H receptors in mast cells, smooth muscle, and endothelium in the body as well as in the tuberomammillary nucleus in the brain; H-antihistamines bind to histamine H receptors in the upper gastrointestinal tract, primarily in the stomach.

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

The vast majority of marketed H-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. Clinically, H-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H-antihistamines that readily cross the blood–brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e., histamine) binding at the H receptor.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Most studies of antihistamines reported on people who are younger, so the effects on people over age 65 are not as well understood. Older people are more likely to experience drowsiness from antihistamine use than younger people. Also, most of the research has been on white people and other ethnicities are not as represented in the research. The evidence does not report how antihistamines affect women differently than men. Different studies have reported on antihistamine use in children, with various studies finding evidence that certain antihistamines could be used by children 2 years of age, and other drugs being safer for younger or older children.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamine

Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors. Only a few currently marketed H-antihistamines are known to function as inverse agonists.

Histamine produces increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.

Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.

H-antihistamines refer to compounds that inhibit the activity of the H receptor. Since the H receptor exhibits constitutive activity, H-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H receptor and heightens the receptor's activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine's.

A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Examples of H antagonists include:

The H receptor inverse agonists include:

H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.

H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.

Examples include:

These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H-antihistamines have a stimulant and nootropic effect, whereas H-antihistamines appear to have an immunomodulatory role.

An H-antihistamine is a classification of drugs used to inhibit the action of histamine at the H receptor. H receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H receptors in the cerebral cortex. Consequently, unlike the H-antihistamines which are sedating, H-antihistamines have stimulant and cognition-modulating effects.

Examples of selective H-antihistamines include:

H-antihistamines inhibit the activity of the H receptor.

Examples:

Inhibit the action of histidine decarboxylase:

Mast cell stabilizers are drugs which prevent mast cell degranulation.

Currently most people who use an antihistamine to treat allergies use a second generation drug.

The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.

Antihistamines can vary greatly in cost. Some patients consult with their doctor about drug prices to make a decision about which antihistamine to choose. Many antihistamines are older and available in generic form. Others are newer, still under patent, and generally expensive. The newer drugs are not necessarily safer or more effective. Because so many antihistamines are available, patients can have conversations with their health care provider to choose the right drug for them.

The United States government removed two second generation antihistamines, terfenadine and astemizole, from the market based on evidence that they could cause heart problems.

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.

Antihistamines can alleviate some of the milder symptoms of an allergic reaction, but do not treat all symptoms of anaphylaxis. Antihistamines block the action of histamine, which causes blood vessels to dilate and become leaky to plasma proteins. Histamine also causes itchiness by acting on sensory nerve terminals. The most common antihistamine given for food allergies is diphenhydramine.

Food allergy

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 pressure. This typically occurs within minutes to several hours of exposure. When the symptoms are severe, it is known as anaphylaxis. A food intolerance and food poisoning are separate conditions, not due to an immune response.
Common foods involved include cow's milk, peanuts, eggs, shellfish, fish, tree nuts, soy, wheat, rice, and fruit. The common allergies vary depending on the country. Risk factors include a family history of allergies, vitamin D deficiency, obesity, and high levels of cleanliness. Allergies occur when immunoglobulin E (IgE), part of the body's immune system, binds to food molecules. A protein in the food is usually the problem. This triggers the release of inflammatory chemicals such as histamine. Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge.
Early exposure to potential allergens may be protective. Management primarily involves avoiding the food in question and having a plan if exposure occurs. This plan may include giving adrenaline (epinephrine) and wearing medical alert jewelry. The benefits of allergen immunotherapy for food allergies is unclear, thus is not recommended as of 2015. Some types of food allergies among children resolve with age, including that to milk, eggs, and soy; while others such as to nuts and shellfish typically do not.
In the developed world, about 4% to 8% of people have at least one food allergy. They are more common in children than adults and appear to be increasing in frequency. Male children appear to be more commonly affected than females. Some allergies more commonly develop early in life, while others typically develop in later life. In developed countries, a large proportion of people believe they have food allergies when they actually do not have them. The declaration of the presence of trace amounts of allergens in foods is mandatory only in Brazil.
Food allergies usually have a fast onset (from seconds to one hour) and may include:

In some cases, however, onset of symptoms may be delayed for hours.

Symptoms can vary. The amount of food needed to trigger a reaction also varies.

Serious danger regarding allergies can begin when the respiratory tract or blood circulation is affected. The former can be indicated through wheezing and cyanosis. Poor blood circulation leads to a weak pulse, pale skin and fainting.

A severe case of an allergic reaction, caused by symptoms affecting the respiratory tract and blood circulation, is called anaphylaxis. When symptoms are related to a drop in blood pressure, the person is said to be in anaphylactic shock. Anaphylaxis occurs when IgE antibodies are involved, and areas of the body that are not in direct contact with the food become affected and show symptoms. Those with asthma or an allergy to peanuts, tree nuts, or seafood are at greater risk for anaphylaxis.

Although sensitivity levels vary by country, the most common food allergies are allergies to milk, eggs, peanuts, tree nuts, seafood, shellfish, soy, and wheat. These are often referred to as "the big eight". Allergies to seeds — especially sesame — seem to be increasing in many countries. An example an allergy more common to a particular region is that to rice in East Asia where it forms a large part of the diet.

One of the most common food allergies is a sensitivity to peanuts, a member of the bean family. Peanut allergies may be severe, but children with peanut allergies sometimes outgrow them. Tree nuts, including cashews, Brazil nuts, hazelnuts, macadamia nuts, pecans, pistachios, pine nuts, coconuts, and walnuts, are also common allergens. Sufferers may be sensitive to one particular tree nut or to many different ones. Also, seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.

Egg allergies affect about one in 50 children but are frequently outgrown by children when they reach age five. Typically, the sensitivity is to proteins in the white, rather than the yolk.

Milk from cows, goats, or sheep is another common food allergen, and many sufferers are also unable to tolerate dairy products such as cheese. A small portion of children with a milk allergy, roughly 10%, have a reaction to beef. Beef contains a small amount of protein that is also present in cow's milk.

Seafood is one of the most common sources of food allergens; people may be allergic to proteins found in fish, crustaceans, or shellfish.

Other foods containing allergenic proteins include soy, wheat, fruits, vegetables, maize, spices, synthetic and natural colors, and chemical additives.

Balsam of Peru, which is in various foods, is in the "top five" allergens most commonly causing patch test reactions in people referred to dermatology clinics.

Sensitization can occur through the gastrointestinal tract, respiratory tract and possibly the skin. Damage to the skin in conditions such as eczema has been proposed as a risk factor for sensitization. An Institute of Medicine report says that food proteins contained in vaccines, such as gelatin, milk, or egg can cause sensitization (development of allergy) in vaccine recipients, to those food items.

Food allergies develop more easily in people with the atopic syndrome, a very common combination of diseases: allergic rhinitis and conjunctivitis, eczema, and asthma. The syndrome has a strong inherited component; a family history of allergic diseases can be indicative of the atopic syndrome.

Some children who are allergic to cow's milk protein also show a cross-sensitivity to soy-based products. Some infant formulas have their milk and soy proteins hydrolyzed, so when taken by infants, their immune systems do not recognize the allergen and they can safely consume the product. Hypoallergenic infant formulas can be based on proteins partially predigested to a less antigenic form. Other formulas, based on free amino acids, are the least antigenic and provide complete nutritional support in severe forms of milk allergy.

People with latex allergy often also develop allergies to bananas, kiwifruit, avocados, and some other foods.

Conditions caused by food allergies are classified into three groups according to the mechanism of the allergic response:Allergic reactions are hyperactive responses of the immune system to generally innocuous substances. When immune cells encounter the allergenic protein, IgE antibodies are produced; this is similar to the immune system's reaction to foreign pathogens. The IgE antibodies identify the allergenic proteins as harmful and initiate the allergic reaction. The harmful proteins are those that do not break down due to the strong bonds of the protein. IgE antibodies bind to a receptor on the surface of the protein, creating a tag, just as a virus or parasite becomes tagged. Why some proteins do not denature and subsequently trigger allergic reactions and hypersensitivity while others do is not entirely clear.

Hypersensitivities are categorized according to the parts of the immune system that are attacked and the amount of time it takes for the response to occur. The four types of hypersensitivity reaction are: type 1, immediate IgE-mediated; type 2, cytotoxic; type 3, immune complex-mediated; and type 4, delayed cell-mediated. The pathophysiology of allergic responses can be divided into two phases. The first is an acute response that occurs immediately after exposure to an allergen. 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.

Many food allergies are caused by hypersensitivities to particular proteins in different foods. Proteins have unique properties that allow them to become allergens, such as stabilizing forces in their tertiary and quaternary structures which prevent degradation during digestion. Many theoretically allergenic proteins cannot survive the destructive environment of the digestive tract, thus do not trigger hypersensitive reactions.

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 T2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These T2 cells interact with other lymphocytes called B cells, whose role is the 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 cells and basophils, 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 (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. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, the allergen, and the 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.

After the chemical mediators of the acute response subside, late-phase responses can often occur due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction. 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 T2 cells.

Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge.Skin-prick testing is easy to do and results are available in minutes. Different allergists may use different devices for testing. Some use a "bifurcated needle", which looks like a fork with two prongs. Others use a "multitest", which may look like a small board with several pins sticking out of it. In these tests, a tiny amount of the suspected allergen is put onto the skin or into a testing device, and the device is placed on the skin to prick, or break through, the top layer of skin. This puts a small amount of the allergen under the skin. A hive will form at any spot where the person is allergic. This test generally yields a positive or negative result. It is good for quickly learning if a person is allergic to a particular food or not, because it detects IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can, however, confirm an allergy in light of a patient's history of reactions to a particular food. Non-IgE-mediated allergies cannot be detected by this method.A CAP-RAST has greater specificity than RAST; it can show the amount of IgE present to each allergen. Researchers have been able to determine "predictive values" for certain foods, which can be compared to the RAST results. If a person's RAST score is higher than the predictive value for that food, over a 95% chance exists that patients will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food. Currently, predictive values are available for milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE-mediated allergies cannot be detected by this method. Other widely promoted tests such as the antigen leukocyte cellular antibody test and the food allergy profile are considered unproven methods, the use of which is not advised.Food challenges, especially double-blind, placebo-controlled food challenges, are the gold standard for diagnosis of food allergies, including most non-IgE-mediated reactions, but is rarely done. Blind food challenges involve packaging the suspected allergen into a capsule, giving it to the patient, and observing the patient for signs or symptoms of an allergic reaction.

The best method for diagnosing food allergy is to be assessed by an allergist. The allergist will review the patient's history and the symptoms or reactions that have been noted after food ingestion. If the allergist feels the symptoms or reactions are consistent with food allergy, he/she will perform allergy tests. Additional diagnostic tools for evaluation of eosinophilic or non-IgE mediated reactions include endoscopy, colonoscopy, and biopsy.

Important differential diagnoses are:

Breastfeeding for more than four months may prevent atopic dermatitis, cow's milk allergy, and wheezing in early childhood. Early exposure to potential allergens may be protective. Specifically, early exposure to eggs and peanuts reduces the risk of allergies to these. Guidelines suggest introducing peanuts as early as 4-6 months and include precautionary measures for high-risk infants. The former guidelines, advised delaying the introduction of peanuts, are now thought to have contributed to the increase in peanut allergy seen recently.

To avoid an allergic reaction, a strict diet can be followed. It is difficult to determine the amount of allergenic food required to elicit a reaction, so complete avoidance should be attempted. In some cases, hypersensitive reactions can be triggered by exposures to allergens through skin contact, inhalation, kissing, participation in sports, blood transfusions, cosmetics, and alcohol.

Allergic reactions to airborne particles or vapors of known food allergens have been reported as an occupational consequence of people working in the food industry, but can also take place in home situations, restaurants, or confined spaces such as airplanes. According to two reviews, respiratory symptoms are common, but in some cases there has been progression to anaphylaxis. The most frequent reported cases of reactions by inhalation of allergenic foods were due to peanut, seafood, legumes, tree nut, and cow's milk. Steam rising from cooking of lentils, green beans, chickpeas and fish has been well documented as triggering reactions, including anaphylactic reactions. One review mentioned case study examples of allergic responses to other foods, including examples in which oral consumption of the food is tolerated.

The mainstay of treatment for food allergy is total avoidance of the foods identified as allergens. An allergen can enter the body by consuming a food containing the allergen, and can also be ingested by touching any surfaces that may have come into contact with the allergen, then touching the eyes or nose. For people who are extremely sensitive, avoidance includes avoiding touching or inhaling the problematic food. Total avoidance is complicated because the declaration of the presence of trace amounts of allergens in foods is not mandatory (see regulation of labelling).

If the food is accidentally ingested and a systemic reaction (anaphylaxis) occurs, then epinephrine should be used. A second dose of epinephrine may be required for severe reactions. The person should then be transported to the emergency room, where additional treatment can be given. Other treatments include antihistamines and steroids.

Epinephrine (adrenaline) is the first-line treatment for severe allergic reactions (anaphylaxis). If administered in a timely manner, epinephrine can reverse its effects. Epinephrine relieves airway swelling and obstruction, and improves blood circulation; blood vessels are tightened and heart rate is increased, improving circulation to body organs. Epinephrine is available by prescription in an autoinjector.

Antihistamines can alleviate some of the milder symptoms of an allergic reaction, but do not treat all symptoms of anaphylaxis. Antihistamines block the action of histamine, which causes blood vessels to dilate and become leaky to plasma proteins. Histamine also causes itchiness by acting on sensory nerve terminals. The most common antihistamine given for food allergies is diphenhydramine.

Glucocorticoid steroids are used to calm down the immune system cells that are attacked by the chemicals released during an allergic reaction. This treatment in the form of a nasal spray should not be used to treat anaphylaxis, for it only relieves symptoms in the area in which the steroid is in contact. Another reason steroids should not be used is the delay in reducing inflammation. Steroids can also be taken orally or through injection, by which every part of the body can be reached and treated, but a long time is usually needed for these to take effect.

The most common food allergens account for about 90% of all allergic reactions; in adults they include shellfish, peanuts, tree nuts, fish, and egg. In children, they include milk, eggs, peanuts, and tree nuts. Six to 8% of children under the age of three have food allergies and nearly 4% of adults have food allergies.

For reasons not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations recently. One possible explanation for this is the "old friends" hypothesis which suggests that non disease causing organisms, such as helminths, could protect against allergy. Therefore, reduced exposure to these organisms, particularly in developed countries, could have contributed towards the increase.

In the United States, food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. A similar prevalence is found in Canada.

About 75% of children who have allergies to milk protein are able to tolerate baked-in milk products, i.e., muffins, cookies, cake, and hydrolyzed formulas.

About 50% of children with allergies to milk, egg, soy, peanuts, tree nuts, and wheat will outgrow their allergy by the age of 6. Those who are still allergic by the age of 12 or so have less than an 8% chance of outgrowing the allergy.

Peanut and tree nut allergies are less likely to be outgrown, although evidence now shows that about 20% of those with peanut allergies and 9% of those with tree nut allergies will outgrow them.

In Japan, allergy to buckwheat flour, used for soba noodles, is more common than peanuts, tree nuts or foods made from soy beans.

In the United States, an estimated 12 million people have food allergies. Food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. The prevalence of food allergies is rising. Food allergies cause roughly 30,000 emergency room visits and 150 deaths per year.

Whether rates of food allergy is increasing or not, food allergy awareness has definitely increased, with impacts on the quality of life for children, their parents and their immediate caregivers. In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 causes people to be reminded of allergy problems every time they handle a food package, and restaurants have added allergen warnings to menus. The Culinary Institute of America, a premier school for chef training, has courses in allergen-free cooking and a separate teaching kitchen. School systems have protocols about what foods can be brought into the school. Despite all these precautions, people with serious allergies are aware that accidental exposure can easily occur at other peoples' houses, at school or in restaurants. Food fear has a significant impact on quality of life. Finally, for children with allergies, their quality of life is also affected by actions of their peers. There is an increased occurrence of bullying, which can include threats or acts of deliberately being touched with foods they need to avoid, also having their allergen-free food deliberately contaminated. In the 2018 animated/live action movie "Peter Rabbit," rabbits used blackberries to deliberately induce an anaphylactic allergy response in a farmer who is trying to protect his garden. After many public protests, Sony Pictures and the director apologized for making light of food allergies.

In response to the risk that certain foods pose to those with food allergies, some countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain major allergens or byproducts of major allergens among the ingredients intentionally added to foods. Nevertheless, there are no labeling laws to mandatory declare the presence of trace amounts in the final product as a consequence of cross-contamination, except in Brazil.

In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) requires companies to disclose on the label whether a packaged food product contains any of these eight major food allergens, added intentionally: cow's milk, peanuts, eggs, shellfish, fish, tree nuts, soy and wheat. This list originated in 1999 from the World Health Organisation Codex Alimentarius Commission. To meet FALCPA labeling requirements, if an ingredient is derived from one of the required-label allergens, then it must either have its "food sourced name" in parentheses, for example "Casein (milk)," or as an alternative, there must be a statement separate but adjacent to the ingredients list: "Contains milk" (and any other of the allergens with mandatory labeling). The European Union requires listing for those eight major allergens plus molluscs, celery, mustard, lupin, sesame and sulfites.

FALCPA applies to packaged foods regulated by the FDA, which does not include poultry, most meats, certain egg products, and most alcoholic beverages. However, some meat, poultry, and egg processed products may contain allergenic ingredients. These products are regulated by the Food Safety and Inspection Service (FSIS), which requires that any ingredient be declared in the labeling only by its common or usual name. Neither the identification of the source of a specific ingredient in a parenthetical statement nor the use of statements to alert for the presence of specific ingredients, like "Contains: milk", are mandatory according to FSIS. FALCPA also does not apply to food prepared in restaurants. The EU Food Information for Consumers Regulation 1169/2011 – requires food businesses to provide allergy information on food sold unpackaged, for example, in catering outlets, deli counters, bakeries and sandwich bars.

In the United States, there is no federal mandate to address the presence of allergens in drug products. FALCPA does not apply to medicines nor to cosmetics.

The value of allergen labeling other than for intentional ingredients is controversial. This concerns labeling for ingredients present unintentionally as a consequence of cross-contact or cross-contamination at any point along the food chain (during raw material transportation, storage or handling, due to shared equipment for processing and packaging, etc.). Experts in this field propose that if allergen labeling is to be useful to consumers, and healthcare professionals who advise and treat those consumers, ideally there should be agreement on which foods require labeling, threshold quantities below which labeling may be of no purpose, and validation of allergen detection methods to test and potentially recall foods that were deliberately or inadvertently contaminated.

Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed precautionary allergen labeling (PAL), also known as “may contain” statements, for possible, inadvertent, trace amount, cross-contamination during production. PAL labeling can be confusing to consumers, especially as there can be many variations on the wording of the warning. PAL is regulated only in Switzerland, Japan, Argentina, and South Africa. Argentina decided to prohibit precautionary allergen labeling since 2010, and instead puts the onus on the manufacturer to control the manufacturing process and label only those allergenic ingredients known to be in the products. South Africa does not permit the use of PAL, except when manufacturers demonstrate the potential presence of allergen due to cross-contamination through a documented risk assessment and despite adherence to Good Manufacturing Practice. In Australia and New Zealand there is a recommendation that PAL be replaced by guidance from VITAL 2.0 (Vital Incidental Trace Allergen Labeling). A review identified "the eliciting dose for an allergic reaction in 1% of the population" as ED01. This threshold reference dose for foods (such as cow's milk, egg, peanut and other proteins) will provide food manufacturers with guidance for developing precautionary labeling and give consumers a better idea of might be accidentally in a food product beyond "may contain." VITAL 2.0 was developed by the Allergen Bureau, a food industry sponsored, non-government organization. The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected to publish such before 2024.

In Brazil since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the Good Manufacturing Practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts. These allergens include wheat, rye, barley, oats and their hybrids, crustaceans, eggs, fish, peanuts, soybean, milk of all species of mammalians, almonds, hazelnuts, cashew nuts, Brazil nuts, macadamia nuts, walnuts, pecan nuts, pistaches, pine nuts, and chestnuts.

There are concerns that genetically modified foods, also described as foods sourced from genetically modified organisms (GMO), could be responsible for allergic reactions, and that the widespread acceptance of GMO foods may be responsible for what is a real or perceived increase in the percentage of people with allergies. There is a scientific consensus that available food derived from GM crops poses no greater risk to human health than conventional food. A 2016 U.S. National Academy of Sciences report concluded that there is no relationship between consumption of GM foods and the increase in prevalence of food allergies.

One concern is that genetic engineering could make an allergy-provoking food more allergic, meaning that smaller portions would suffice to set off a reaction. Of the food currently in widespread GMO use, only soybeans are identified as a common allergen. However, for the soybean proteins known to trigger allergic reactions, there is more variation from strain to strain than between those and the GMO varieties. Another concern is that genes transferred from one species to another could introduce an allergen in a food not thought of as particularly allergenic. Research on an attempt to enhance the quality of soybean protein by adding genes from Brazil nuts was terminated when human volunteers known to have tree nut allergy reacted to the modified soybeans.

At present, prior to a new GMO food receiving government approval, certain criteria need to be met. These include: Is the donor species known to be allergenic? Does the amino acid sequence of the transferred proteins resemble the sequence of known allergenic proteins? Are the transferred proteins resistant to digestion - a trait shared by many allergenic proteins? Genes approved for animal use can be restricted from human consumption due to potential for allergic reactions. In 1998 Starlink brand corn restricted to animals was detected in was found in the human food supply, leading to first a voluntary and then a FDA mandated recall. There are requirements in some countries and recommendations in others that all foods containing GMO ingredients be so labeled, and that there be a post-launch monitoring system to report adverse effects (much there exists in some countries for drug and dietary supplement reporting). According to a 2015 report from the Center for Food Safety, 64 countries require labeling of GMO products in the marketplace.

A number of desensitization techniques are being studied. Areas of research include anti-IgE antibody (omalizumab), specific oral tolerance induction (SOTI, also known as OIT for oral immunotherapy), and sublingual immunotherapy (SLIT). The benefits of allergen immunotherapy for food allergies is unclear, thus is not recommended as of 2015.

There is research on the effects of increasing intake of polyunsaturated fatty acids (PUFAs) during pregnancy, lactation, via infant formula and in early childhood on the subsequent risk of developing food allergies during infancy and childhood. From two reviews, maternal intake of omega-3, long-chain fatty acids during pregnancy appeared to reduce the risks of medically diagnosed IgE-mediated allergy, eczema and food allergy per parental reporting in the first 12 months of life, but the effects were not all sustained past 12 months. The reviews characterized the literature's evidence as inconsistent and limited. Results when breastfeeding mothers were consuming a diet high in PUFAs were inconclusive. For infants, supplementing their diet with oils high in PUFAs did not affect the risks of food allergies, eczema or asthma either as infants or into childhood.

There is research on probiotics, prebiotics and the combination of the two (synbiotics) as a means of treating or preventing infant and child allergies. From reviews, there appears to be a treatment benefit for eczema, but not asthma, wheezing or rhinoconjunctivitis. The evidence was not consistent for preventing food allergies and this approach cannot yet be recommended.

Antihistamines, which are commonly used to treat allergy symptoms, interfere with skin tests, as they can prevent the skin from reacting to the allergens being tested. People who take an antihistamine need either to choose a different form of allergy test or to stop taking the antihistimine temporarily before the test. The period of time needed can range from a day or two to 10 days or longer, depending on the specific medication. Some medications not primarily used as antihistamines, including tricyclic antidepressants,
phenothiazine-based antipsychotics, and several kinds of medications used for gastrointestinal disorders, can similarly interfere with skin tests.

Skin allergy test

Skin allergy testing or Skin prick test is a method for medical diagnosis of allergies that attempts to provoke a small, controlled, allergic response.

A microscopic amount of an allergen is introduced to a patient's skin by various means:

If an immuno-response is seen in the form of a rash, urticaria (hives), or "(worse)" anaphylaxis it can be concluded that the patient has a hypersensitivity (or allergy) to that allergen. Further testing can be done to identify the particular allergen.

The "skin scratch test" as it is called, is not very commonly used due to increased likelihood of infection. On the other hand, the "skin scrape test" is painless, does not leave residual pigmentation and does not have a risk of infection, since it is limited to the superficial layer of the skin.

Some allergies are identified in a few minutes but others may take several days. In all cases where the test is positive, the skin will become raised, red and appear itchy. The results are recorded - larger wheals indicating that the subject is more sensitive to that particular allergen. A negative test does not conclusively rule out an allergy; occasionally, the concentration needs to be adjusted, or the body fails to elicit a response.

In the prick, scratch and scrape tests, a few drops of the purified allergen are gently pricked on to the skin surface, usually the forearm. This test is usually done in order to identify allergies to pet dander, dust, pollen, foods or dust mites. Intradermal injections are done by injecting a small amount of allergen just beneath the skin surface. The test is done to assess allergies to drugs like penicillin or bee venom.
To ensure that the skin is reacting in the way it is supposed to, all skin allergy tests are also performed with proven allergens like histamine or glycerin. The majority of people do react to histamine and do not react to glycerin. If the skin does not react appropriately to these allergens then it most likely will not react to the other allergens. These results are interpreted as falsely negative.

The patch test simply uses a large patch which has different allergens on it. The patch is applied onto the skin, usually on the back. The allergens on the patch include latex, medications, preservatives, hair dyes, fragrances, resins and various metals.

Also called an "intradermal test", this skin end point titration (SET) uses intradermal injection of allergens at increasing concentrations to measure allergic response. To prevent a severe allergic reaction, the test is started with a very dilute solution. After 10 minutes, the injection site is measured to look for growth of wheal, a small swelling of the skin. Two millimeters of growth in 10 minutes is considered positive. If 2 mm of growth is noted, then a second injection at a higher concentration is given to confirm the response. The end point is the concentration of antigen that causes an increase in the size of the wheal followed by confirmatory whealing. If the wheal grows larger than 13 mm, then no further injection are given since this is considered a major reaction.

There are no major preparations required for skin testing. At the first consult, the subject's medical history is obtained and physical examination is performed. All consumers should bring a list of their medications because some may interfere with the testing. Other medications may increase the chance of a severe allergic reaction. Medications that commonly interfere with skin testing include the following:Consumers who undergo skin testing should know that anaphylaxis can occur anytime. So if any of the following symptoms are experienced, a physician consultation is recommended immediately:Even though skin testing may seem to be a benign procedure, it does have some risks, including swollen red bumps (hives) which may occur after the test. The hives usually disappear in a few hours after the test. In rare cases they can persist for a day or two. These hives may be itchy and are best treated by applying an over the counter hydrocortisone cream.
In very rare cases one may develop a full blown allergic reaction. Physicians who perform skin test always have equipment and medications available in case an anaphylaxis reaction occurs. This is the main reason why consumers should not get skin testing performed at corner stores or by people who have no medical training.

People who have severe, generalized skin disease or an acute skin infection should not undergo skin testing, as one needs uninvolved skin for testing. Also, skin testing should be avoided for people at a heightened risk of anaphylactic shock, including people who are known to be highly sensitive to even the smallest amount of allergen.

Besides skin tests, there are blood tests which measure a specific antibody in the blood. The IgE antibody plays a vital role in allergies but its levels in blood do not always correlate with the allergic reaction.

There are many alternative health care practitioners who perform a variety of provocation neutralization tests, but the vast majority of these tests have no validity and have never been proven to work scientifically.

The immediate symptoms of this type are treated with antihistamines, epinephrine and airway support. Taking antihistamines prior to exercise may be effective. Ketotifen is acknowledged to stabilise mast cells and prevent histamine release, and has been effective in treating this hives disorder. Avoiding exercise or foods that cause the mentioned symptoms is very important. In particular circumstances, tolerance can be brought on by regular exercise, but this must be under medical supervision.

Hives

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. They may also burn or sting. Often the patches of rash move around. Typically they last a few days and do not leave any long-lasting skin changes. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.
Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food. Psychological stress, cold temperature, or vibration may also be a trigger. In half of cases the cause remains unknown. Risk factors include having conditions such as hay fever or asthma. Diagnosis is typically based on the appearance. Patch testing may be useful to determine the allergy.
Prevention is by avoiding whatever it is that causes the condition. Treatment is typically with antihistamines such as diphenhydramine and ranitidine. In severe cases, corticosteroids or leukotriene inhibitors may also be used. Keeping the environmental temperature cool is also useful. For cases that last more than six weeks immunosuppressants such as ciclosporin may be used.
About 20% of people are affected. Cases of short duration occur equally in males and females while cases of long duration are more common in females. Cases of short duration are more common among children while cases of long duration are more common among those who are middle aged. Hives have been described at least since the time of Hippocrates. The term urticaria is from the Latin "urtica" meaning "nettle".
Welts (raised areas surrounded by a red base) from hives can appear anywhere on the surface of the skin. Whether the trigger is allergic or not, a complex release of inflammatory mediators, including histamine from cutaneous mast cells, results in fluid leakage from superficial blood vessels. Welts may be pinpoint in size, or several inches in diameter.

Angioedema is a related condition (also from allergic and nonallergic causes), though fluid leakage is from much deeper blood vessels in the subcutaneous or submucosal layers. Individual hives that are painful, last more than 24 hours, or leave a bruise as they heal are more likely to be a more serious condition called urticarial vasculitis. Hives caused by stroking the skin (often linear in appearance) are due to a benign condition called dermatographic urticaria.

Hives can also be classified by the purported causative agent. Many different substances in the environment may cause hives, including medications, food and physical agents. In perhaps more than 50% of people with chronic hives of unknown cause, it is due to an autoimmune reaction.

Drugs that have caused allergic reactions evidenced as hives include codeine, sulphate of morphia, dextroamphetamine, aspirin, ibuprofen, penicillin, clotrimazole, trichazole, sulfonamides, anticonvulsants, cefaclor, piracetam, vaccines, and antidiabetic drugs. The antidiabetic sulphonylurea glimepiride, in particular, has been documented to induce allergic reactions manifesting as hives. Drug-induced hives has been known to have an effect on severe cardiorespiratory failure.

The most common food allergies in adults are shellfish and nuts. The most common food allergies in children are shellfish, nuts, eggs, wheat, and soy. One study showed Balsam of Peru, which is in many processed foods, to be the most common cause of immediate contact urticaria. A less common cause is exposure to certain bacteria, such as "Streptococcus" species or possibly "Helicobacter pylori".

Hives including chronic spontaneous hives can be a complication and symptom of a parasitic infection, such as blastocystosis and strongyloidiasis among others.

The rash that develops from poison ivy, poison oak, and poison sumac contact is commonly mistaken for urticaria. This rash is caused by contact with urushiol and results in a form of contact dermatitis called urushiol-induced contact dermatitis. Urushiol is spread by contact, but can be washed off with a strong grease- or oil-dissolving detergent and cool water and rubbing ointments.

Dermatographic urticaria (also known as dermatographism or "skin writing") is marked by the appearance of weals or welts on the skin as a result of scratching or firm stroking of the skin. Seen in 4–5% of the population, it is one of the most common types of urticaria, in which the skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped.

The skin reaction usually becomes evident soon after the scratching, and disappears within 30 minutes. Dermatographism is the most common form of a subset of chronic hives, acknowledged as "physical hives".

It stands in contrast to the linear reddening that does not itch seen in healthy people who are scratched. In most cases, the cause is unknown, although it may be preceded by a viral infection, antibiotic therapy, or emotional upset. Dermographism is diagnosed by taking a tongue blade and drawing it over the skin of the arm or back. The hives should develop within a few minutes. Unless the skin is highly sensitive and reacts continually, treatment is not needed. Taking antihistamines can reduce the response in cases that are annoying to the patient.

This type of hives can occur right away, precisely after a pressure stimulus or as a deferred response to sustained pressure being enforced to the skin. In the deferred form, the hives only appear after about six hours from the initial application of pressure to the skin. Under normal circumstances, these hives are not the same as those witnessed with most urticariae. Instead, the protrusion in the affected areas is typically more spread out. The hives may last from eight hours to three days. The source of the pressure on the skin can happen from tight fitted clothing, belts, clothing with tough straps, walking, leaning against an object, standing, sitting on a hard surface, etc. The areas of the body most commonly affected are the hands, feet, trunk, abdomen, buttocks, legs and face. Although this appears to be very similar to dermatographism, the cardinal difference is that the swelled skin areas do not become visible quickly and tend to last much longer. This form of the skin disease is, however, rare.

Cholinergic urticaria (CU) is one of the physical urticaria which is provoked during sweating events such as exercise, bathing, staying in a heated environment, or emotional stress. The hives produced are typically smaller than classic hives and are generally shorter-lasting.

Multiple subtypes have been elucidated, each of which require distinct treatment.

The cold type of urticaria is caused by exposure of the skin to extreme cold, damp and windy conditions; it occurs in two forms. The rare form is hereditary and becomes evident as hives all over the body 9 to 18 hours after cold exposure. The common form of cold urticaria demonstrates itself with the rapid onset of hives on the face, neck, or hands after exposure to cold. Cold urticaria is common and lasts for an average of five to six years. The population most affected is young adults, between 18 and 25 years old. Many people with the condition also suffer from dermographism and cholinergic hives.

Severe reactions can be seen with exposure to cold water; swimming in cold water is the most common cause of a severe reaction. This can cause a massive discharge of histamine, resulting in low blood pressure, fainting, shock and even loss of life. Cold urticaria is diagnosed by dabbing an ice cube against the skin of the forearm for 1 to 5 minutes. A distinct hive should develop if a patient suffers cold urticaria. This is different from the normal redness that can be seen in people without cold urticaria. Patients with cold urticaria need to learn to protect themselves from a hasty drop in body temperature. Regular antihistamines are not generally efficacious. One particular antihistamine, cyproheptadine (Periactin), has been found to be useful. The tricyclic antidepressant doxepin has also been found to be an effective blocking agent of histamine discharge. Finally, a medication named ketotifen, which keeps mast cells from discharging histamine, has also been employed with widespread success.

This form of the disease occurs on areas of the skin exposed to the sun; the condition becomes evident within minutes of exposure.

This type of urticaria is also termed rare, and occurs upon contact with water. The response is not temperature-dependent and the skin appears similar to cholinergic form of the disease. The appearance of hives is within one to 15 minutes of contact with the water, and can last from 10 minutes to two hours. This kind of hives do not seem to be stimulated by histamine discharge like the other physical hives. Most researchers believe this condition is actually skin sensitivity to additives in the water, such as chlorine. Water urticaria is diagnosed by dabbing tap water and distilled water to the skin and observing the gradual response. Aquagenic urticaria is treated with capsaicin (Zostrix) administered to the chafed skin. This is the same treatment used for shingles. Antihistamines are of questionable benefit in this instance, since histamine is not the causative factor.

Chizzola maculae is a very specific skin lesion due to fluoride exposure. The size of a coin, these lesions may resemble small blue bruises or be wholly pink. Doctors George Waldbott and V. A. Cecilioni named the lesions after a town in Italy, where they were common in young women and children. According to Waldbott, chizzola maculae are early symptoms of fluoride intoxication.

The condition was first distinguished in 1980. People with exercise urticaria (EU) experience hives, itchiness, shortness of breath and low blood pressure five to 30 minutes after beginning exercise. These symptoms can progress to shock and even sudden death. Jogging is the most common exercise to cause EU, but it is not induced by a hot shower, fever, or with fretfulness. This differentiates EU from cholinergic urticaria.

EU sometimes occurs only when someone exercises within 30 minutes of eating particular foods, such as wheat or shellfish. For these individuals, exercising alone or eating the injuring food without exercising produces no symptoms. EU can be diagnosed by having the patient exercise and then observing the symptoms. This method must be used with caution and only with the appropriate resuscitative measures at hand. EU can be differentiated from cholinergic urticaria by the hot water immersion test. In this test, the patient is immersed in water at 43 °C (109.4 °F). Someone with EU will not develop hives, while a person with cholinergic urticaria will develop the characteristic small hives, especially on the neck and chest.

The immediate symptoms of this type are treated with antihistamines, epinephrine and airway support. Taking antihistamines prior to exercise may be effective. Ketotifen is acknowledged to stabilise mast cells and prevent histamine release, and has been effective in treating this hives disorder. Avoiding exercise or foods that cause the mentioned symptoms is very important. In particular circumstances, tolerance can be brought on by regular exercise, but this must be under medical supervision.

The skin lesions of urticarial disease are caused by an inflammatory reaction in the skin, causing leakage of capillaries in the dermis, and resulting in an edema which persists until the interstitial fluid is absorbed into the surrounding cells.

Hives is caused by the release of histamine and other mediators of inflammation (cytokines) from cells in the skin. This process can be the result of an allergic or nonallergic reaction, differing in the eliciting mechanism of histamine release.

Histamine and other proinflammatory substances are released from mast cells in the skin and tissues in response to the binding of allergen-bound IgE antibodies to high-affinity cell surface receptors. Basophils and other inflammatory cells are also seen to release histamine and other mediators, and are thought to play an important role, especially in chronic urticarial diseases.

Over half of all cases of chronic idiopathic hives are the result of an autoimmune trigger. Roughly 50% of patients with chronic urticaria spontaneously develop autoantibodies directed at the receptor FcεRI located on skin mast cells. Chronic stimulation of this receptor leads to chronic hives. Patients often have other autoimmune conditions, such as autoimmune thyroiditis, celiac disease, type 1 diabetes, rheumatoid arthritis, Sjögren's syndrome or systemic lupus erythematosus.

Hive-like rashes commonly accompany viral illnesses, such as the common cold. They usually appear three to five days after the cold has started, and may even appear a few days after the cold has resolved.

Mechanisms other than allergen-antibody interactions are known to cause histamine release from mast cells. Many drugs, for example morphine, can induce direct histamine release not involving any immunoglobulin molecule. Also, a diverse group of signaling substances, called neuropeptides, have been found to be involved in emotionally induced hives. Dominantly inherited cutaneous and neurocutaneous porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been associated with solar urticaria. The occurrence of drug-induced solar urticaria may be associated with porphyrias. This may be caused by IgG binding, not IgE.

This is termed scombroid food poisoning. Ingestion of free histamine released by bacterial decay in fish flesh may result in a rapid-onset, allergic-type symptom complex which includes hives. However, the hives produced by scombroid is reported not to include wheals.

Chronic idiopathic hives has been anecdotally linked to stress since the 1940s. A large body of evidence demonstrates an association between this condition and both poor emotional well-being and reduced health-related quality of life. A link between stress and this condition has also been shown. A recent study has demonstrated an association between stressful life events (e.g. bereavement, divorce, etc.) and chronic idiopathic urticaria and also an association between post-traumatic stress and chronic idiopathic hives.

The cause of chronic hives can rarely be determined. In some cases regular extensive allergy testing over a long period of time is requested in hopes of getting new insight. No evidence shows regular allergy testing results in identification of a problem or relief for people with chronic hives. Regular allergy testing for people with chronic hives is not recommended.Acute and chronic hives are visually indistinguishable.

Angioedema is similar to hives, but in angioedema, the swelling occurs in a lower layer of the dermis than in hives, as well as in the subcutis. This swelling can occur around the mouth, eyes, in the throat, in the abdomen, or in other locations. Hives and angioedema sometimes occur together in response to an allergen, and is a concern in severe cases, as angioedema of the throat can be fatal.

This very rare form of angioedema develops in response to contact with vibration. In vibratory angioedema, symptoms develop within two to five minutes after contact with a vibrating object, and abate after about an hour. Patients with this disorder do not suffer from dermographism or pressure urticaria. Vibratory angioedema is diagnosed by holding a vibrating device such as a laboratory vortex machine against the forearm for four minutes. Speedy swelling of the whole forearm extending into the upper arm is also noted later. The principal treatment is avoidance of vibratory stimulants. Antihistamines have also been proven helpful.

The mainstay of therapy for both acute and chronic hives is patient education, avoiding triggers and using antihistamines.

Chronic hives can be difficult to treat and lead to significant disability. Unlike the acute form, 50–80% of people with chronic hives have no identifiable triggers. But 50% of people with chronic hives will experience remission within 1 year. Overall, treatment is geared towards symptomatic management. Individuals with chronic hives may need other medications in addition to antihistamines to control symptoms. Patients who experience hives with angioedema require emergency treatment as this is a life-threatening condition.

Treatment guidelines for the management of chronic hives have been published. According to the 2014 American practice parameters, treatment involves a step wise approach. Step 1 consists of second generation, H1 receptor blocking antihistamines. Systemic glucocorticoids can also be used for episodes of severe disease but should not be used for long term due to their long list of side effects. Step 2 consists of increasing the dose of the current antihistamine, adding other antihistamines, or adding a leukotriene receptor antagonist such as montelukast. Step 3 consists of adding or replacing the current treatment with hydroxyzine or doxepin. If the individual doesn't respond to steps 1–3 then they are considered to have refractory symptoms. At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other medications like omalizumab can be used. These options are explained in more detail below.

Non-sedating antihistamines that block the histamine H1 receptors are the first line of therapy. First generation antihistamines such as diphenhydramine or hydroxyzine block both central and peripheral H1 receptors and can be sedating. Second generation antihistamines such as loratadine, cetirizine, or desloratadine selectively antagonize the peripheral H1 receptors and are less sedating, less anticholinergic, and generally preferred over the first generation antihistamines.
People who don’t respond to the maximum dose of H1 antihistamines may benefit from increasing the dose, then to switching to another non-sedating antihistamine, then to adding a leukotriene antagonist, then to using an older antihistamine, then to using systemic steroids and finally to using ciclosporin or omalizumab.

H2-receptor antagonists are sometimes used in addition to H1-antagonists to treat urticaria, but there is limited evidence for their efficacy.

Oral glucocorticoids are effective in controlling symptoms of chronic hives however they have an extensive list of adverse effects such as adrenal suppression, weight gain, osteoporosis, hyperglycemia, etc. Therefore, their use should be limited to a couple of weeks. In addition, one study found that systemic glucocorticoids combined with antihistamines did not hasten the time to symptom control compared with antihistamines alone.

Leukotrienes are released from mast cells along with histamine. The medications, montelukast and zafirlukast block leukotriene receptors and can be used as add on treatment or in isolation for patients with CU. It is important to note that these medications may be more beneficial for patients with NSAID induced CU.

Other options for refractory symptoms of chronic hives include anti-inflammatory medications, omalizumab, and immunosuppressants.
Potential anti-inflammatory agents include dapsone, sulfasalazine, and hydroxychloroquine. Dapsone is a sulfone antimicrobial agent and is thought to suppress prostaglandin and leukotriene activity. It is helpful in therapy-refractory cases and is contraindicated in patients with G6PD deficiency. Sulfasalazine, a 5-ASA derivative, is thought to alter adenosine release and inhibit IgE mediated mast cell degranulation, Sulfasalazine is a good option for people with anemia who cannot take dapsone. Hydroxychloroquine is an antimalarial agent that suppresses T lymphocytes. It has a low cost however it takes longer than dapsone or sulfasalazine to work.

Omalizumab was approved by the FDA in 2014 for patients 12 years old and above with chronic hives. It is a monoclonal antibody directed against IgE. Significant improvement in pruritus and quality of life was observed in a phase III, multicenter, randomized control trial.
Immunosuppressants used for CU include cyclosporine, tacrolimus, sirolimus, and mycophenolate. Calcineurin inhibitors, such as cyclosporine and tacrolimus, inhibit cell responsiveness to mast cell products and inhibit T cell activity. They are preferred by some experts to treat severe symptoms. Sirolimus and mycophenolate have less evidence for their use in the treatment of chronic hives but reports have shown them to be efficacious. Immunosuppressants are generally reserved as the last line of therapy for severe cases due to their potential for serious adverse effects.

Afamelanotide is being studied as a hives treatment.

Opioid antagonists such as naltrexone have tentative evidence to support their use.