Allergic Rhinitis

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Posted by r2d2 03/07/2009 @ 06:08

Tags : allergic rhinitis, allergies, diseases, health

News headlines
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By Judith Moser, MD WARSAW, Poland -- June 11, 2009 -- Sublingual immunotherapy (SLIT) provides significant improvements in the quality of life of polysensitised patients with allergic rhinitis -- even when they are treated with only 1 extract,...
Merck Statement in Response to the FDA's June 12, 2009 ... - WELT ONLINE
Merck is confident in the efficacy and safety of SINGULAIR, a medicine that has been prescribed to tens of millions of patients with asthma and allergic rhinitis since its approval more than 11 years ago. "For the millions of people suffering from...
Fluticasone Furoate Nasal Spray Demonstrates Consistent Efficacy ... - DG News
By Judith Moser, MD WARSAW, Poland -- June 9, 2009 -- Fluticasone furoate nasal spray (FFNS) 110 mcg once daily showed a marked and consistent beneficial effect on individual nasal symptoms in a large patient population with seasonal allergic rhinitis,...
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Another study measured allergen-specific ige levels through baseline washings from the nasal mucosal of allergic rhinitis patients, she said. Researchers did a ragweed challenge using plain ragweed and ragweed plus diesel exhaust particles....
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Warsaw, Poland – June 9, 2009 – According to new data presented today for the first time, patients with seasonal allergic rhinitis (SAR) experienced greater relief of nasal symptoms and equivalent relief of ocular symptoms with NASONEX® (mometasone...
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It can also be used all year to aid the treatment of non-hayfever allergic rhinitis. Broch says he is thrilled to be able to offer a side effects-free solution to the problems affecting millions of hayfever and allergic rhinitis sufferers every year,...
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Allergy

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

Allergy is a disorder of the immune system often also referred to as atopy. Allergic reactions occur to environmental substances known as allergens; these reactions are acquired, predictable and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma, food allergies, and reactions to the venom of stinging insects such as wasps and bees.

Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions and potentially death.

A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of anti-histamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy.

The concept of "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods. Pirquet called this phenomenon "allergy" from the Greek words allos meaning "other" and ergon meaning "work". Historically, all forms of hypersensitivity were classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity. With this new classification, the word "allergy" was restricted to only type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions.

A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) - Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s.

Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as eyes, nose and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, and itching and redness of the eyes. Inhaled allergens can also lead to asthmatic symptoms, caused by narrowing of the airways (bronchoconstriction) and increased production of mucus in the lungs, shortness of breath (dyspnea), coughing and wheezing.

Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and swelling of the skin during hives. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis. Insect stings, antibiotics, and certain medicines produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system. Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma, and even death. This type of reaction can be triggered suddenly, or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, sometimes through a device known as the EpiPen auto-injector. The nature of anaphylaxis is such that the reaction can seem to be subsiding, but may recur throughout a prolonged period of time.

Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema. Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema.

Risk factors for allergy can be placed in two general categories, namely host and environmental factors. Host factors include heredity, sex, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.

Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins. Allergic parents are more likely to have allergic children, and their allergies are likely to be more severe than those from non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not.

The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk. Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10. Overall, boys have a higher risk of developing allergy than girls, although for some diseases, namely asthma in young adults, females are more likely to be affected. Sex differences tend to decrease in adulthood. Ethnicity may play a role in some allergies, however racial factors have been difficult to separate from environmental influences and changes due to migration. Interestingly, it has been suggested that different genetic loci are responsible for asthma, specifically, in people of Caucasian, Hispanic, Asian, and African origins.

According to the hygiene hypothesis, proposed by David P. Strachan, allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis stated that insufficient stimulation of the TH1 arm of the immune system lead to an overactive TH2 arm, which in turn led to allergic disease. In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when it is not exposed to this level the immune system will attack harmless antigens, and thus normally benign microbial objects, like pollen, will trigger an immune response.

The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were presumably exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that has been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.

Epidemiological data supports the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world. Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, presumably, cleaner. The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases. The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth.

International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.

Exposure to allergens, especially in early life, is an important risk factor for allergy. Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy. Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood. Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.

Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies. Recent research has shown that some common parasites, such as intestinal worms (e.g. hookworms), secrete chemicals into the gut wall (and hence the bloodstream) that suppress the immune system and prevent the body from attacking the parasite. This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that only functions correctly in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive. In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants. However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms. Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies. It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work. For more information on this topic, see Helminthic therapy.

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.

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 TH2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast 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, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.

After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. 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 TH2 cells.

Before a diagnosis of allergic disease can be confirmed, the other possible causes of the presenting symptoms should be carefully considered. Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis. Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.

For assessing the presence of allergen-specific IgE antibodies, allergy skin testing is preferred over blood allergy tests because it is more sensitive and specific, simpler to use, and less expensive. Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny puncture or pricks made into the patient's skin. Small amounts of suspected allergens and/or their extracts (pollen, grass, mite proteins, peanut extract, etc.) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A small plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected "intradermally" into the patient's skin, with a needle and syringe. Common areas for testing include the inside forearm and the back. If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blown hive (called "wheal and flare") in more sensitive patients. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/- meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature. Some patients may believe they have determined their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy.

If a serious life threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has taken antihistamines sometime the last several days.

Various blood allergy testing methods are also available for detecting allergy to specific substances. This kind of testing measures a "total IgE level" - an estimate of IgE contained within the patient's serum. This can be determined through the use of radiometric and colormetric immunoassays. Radiometric assays include the radioallergosorbent test (RAST) test method, which uses IgE-binding (anti-IgE) antibodies labeled with radioactive isotopes for quantifying the levels of IgE antibody in the blood. Other newer methods use colorimetric or fluorometric technology in the place of radioactive isotopes. Some "screening" test methods are intended to provide qualitative test results, giving a "yes" or "no" answer in patients with suspected allergic sensitization. One such method has a sensitivity of about 70.8% and a positive predictive value of 72.6% according to a large study.

A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens. Statistical methods, such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with specific allergy tests for a carefully chosen allergens is often warranted.

There have been enormous improvements in the medical treatments used to treat allergic conditions. With respect to anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin diseases, advances have included the identification of food proteins to which IgE binding is associated with severe reactions and development of low-allergen foods, improvements in skin prick test predictions; evaluation of the atopy patch test; in wasp sting outcomes predictions and a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.

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

Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, cortisone, dexamethasone, hydrocortisone, epinephrine (adrenaline), theophylline and cromolyn sodium. Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. These drugs help to alleviate the symptoms of allergy, and are imperative in the recovery of acute anaphylaxis, but play little role in chronic treatment of allergic disorders.

Desensitization or hyposensitization is a treatment in which the patient is gradually vaccinated with progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG antibody production, to block excessive IgE production seen in atopys. In a sense, the person builds up immunity to increasing amounts of the allergen in question. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the development of new allergy. Meta-analyses have also confirmed efficacy of the treatment in allergic rhinitis in children and in asthma. A review by the Mayo Clinic in Rochester confirmed the safety and efficacy of allergen immunotherapy for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insect based on numerous well-designed scientific studies. Additionally, national and international guidelines confirm the clinical efficacy of injection immunotherapy in rhinitis and asthma, as well as the safety, provided that recommendations are followed.

A second form of immunotherapy involves the intravenous injection of monoclonal anti-IgE antibodies. These bind to free and B-cell associated IgE; signalling their destruction. They do not bind to IgE already bound to the Fc receptor on basophils and mast cells, as this would stimulate the allergic inflammatory response. The first agent of this class is Omalizumab. While this form of immunotherapy is very effective in treating several types of atopy, it should not be used in treating the majority of people with food allergies.

A third type, Sublingual immunotherapy, is an orally-administered therapy which takes advantage of oral immune tolerance to non-pathogenic antigens such as foods and resident bacteria. This therapy currently accounts for 40 percent of allergy treatment in Europe. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by doctors who treat allergy.

Allergy shot treatment is the closest thing to a ‘cure’ for allergic symptoms. This therapy requires a long-term commitment.

An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favouring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but again is not approved by the U.S. Food and Drug Administration or of proven effectiveness.

In alternative medicine, a number of allergy treatments are described by its practitioners, particularly naturopathic, herbal medicine, homeopathy, traditional Chinese medicine and applied kinesiology. Systematic literature searches conducted by the Mayo Clinic through 2006, involving hundreds of articles studying multiple conditions, including asthma and upper respiratory tract infection showed no effectiveness of any alternative treatments, and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of alternative treatments.

Many diseases related to inflammation such as type 1 diabetes, rheumatoid arthritis and allergic diseases—hay fever and asthma—have increased in the Western world over the past 2-3 decades. Rapid increases in allergic asthma and other atopic disorders in industrialized nations probably began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s, although some suggest that a steady rise in sensitization has been occurring since the 1920s. The incidence of atopy in developing countries has generally remained much lower.

Although genetic factors fundamentally govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. Several hypotheses have been identified to explain this increased prevalence; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise. The hygiene hypothesis maintains that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from TH1 type responses, leading to unrestrained TH2 responses that allow for an increase in allergy.

Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, Toxoplasma gondii, and Helicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma. It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation. Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.

In the United States physicians who hold certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and an evaluation process, including a secure, proctored examination to demonstrate the knowledge, skills, and experience to the provision of patient care in allergy and immunology. An allergist-immunologist is a physician specially trained to manage and treat asthma and the other allergic diseases. Becoming an allergist-immunologist requires completion of at least nine years of training. After completing medical school and graduating with a medical degree, a physician will then undergo three years of training in internal medicine (to become an internist) or pediatrics (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the American Board of Pediatrics (ABP) or the American Board of Internal Medicine (ABIM). Internists or pediatricians who wish to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy-immunology training program. Allergist-immunologists who are listed as ABAI-certified have successfully passed the certifying examination of the American Board of Allergy and Immunology (ABAI), following their fellowship.

In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. After obtaining postgraduate exams (MRCP or MRCPCH respectively) a doctor works as several years as a specialist registrar before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by immunologists. A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK. In 2006, the House of Lords convened a subcommittee that reported in 2007. It concluded likewise that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several other recommendations.

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Rhinitis

Pollen grains from a variety of common plants can cause hay fever.

Rhinitis, commonly known as a runny nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or irritants. The inflammation results in the generating of excessive amounts of mucus, commonly producing the aforementioned runny nose, as well as nasal congestion and post-nasal drip. According to recent studies completed in the United States, more than 50 million Americans are current sufferers. Rhinitis has also been found to adversely affect more than just the nose, throat, and eyes. It has been associated with sleeping problems, ear conditions, and even learning problems. Rhinitis is caused by an increase in histamine. This increase is most often caused by airborne allergens. These allergens may affect an individual's nose, throat, or eyes and cause an increase in fluid production within these areas.

Rhinitis is categorized into three types: infective rhinitis includes acute and chronic bacterial infections; Nonallergic (vasomotor) rhinitis includes autonomic, hormonal, drug-induced, atrophic, and gustatory rhinitis, as well as Rhinitis medicamentosa; allergic rhinitis, the most common of the three, is an allergic reaction triggered by pollen, mold, animal dander, dust and other similar inhaled allergens.

Vasomotor rhinitis is also known as non-allergenic rhinitis, because it often has the same symptoms as allergies, but has different causes. Whereas allergenic rhinitis conditions (such as hayfever) are the result of the immune system overreacting to environmental irritants (pollen, etc), vasomotor rhinitis is believed to be caused by oversensitive or excessive blood vessels in the nasal membrane. These blood vessels (which are controlled in turn by the autonomic nervous system) contract or dilate in order to regulate mucus flow and congestion. But in the vasomotor rhinitis sufferer, oversensitive or excessive blood vessel dilation or contraction causes an overreaction to such stimuli as changes in weather, temperature, or barometric pressure, chemical irritants such as smoke, ozone, pollution, perfumes, and aerosol sprays, psychological stress and emotional shocks, certain types of medications, alcohol, and even spicy food. Thus, while a normal person's nose may run on a very cold day, a vasomotor rhinitis sufferer's nose may start running (or go completely dry) simply by walking into a slightly colder (or slightly warmer) room, or from eating food that is slightly warmer or cooler than room temperature. While a normal person may tolerate a certain degree of cigarette smoke, the vasomotor rhinitis sufferer may experience significant discomfort from the same level of smoke, etc.

The pathology of vasomotor rhinitis is in fact not very well-understood and more research is needed. Vasomotor rhinitis appears to be significantly more common in women than men, leading some researchers to believe hormones to play a role. In general, age of onset occurs after 20 years of age, in contrast to allergic rhinitis which generally appears before age 20. Individuals suffering from vasomotor rhinitis typically experience symptoms year-round, though symptoms may exacerbate in the spring and fall when rapid weather changes are more common.

Many patients can be subject to vasomotor rhinitis and allergic rhinitis simultaneously. Vasomotor rhinitis is a common condition that often goes unrecognized/underrecognized, especially in women. An estimated 17 million United States citizens have vasomotor rhinitis.

When an allergen such as pollen or dust is inhaled by a person with a sensitized immune system, it triggers antibody production. These antibodies mostly bind to mast cells, which contain histamine. When the mast cells are stimulated by pollen and dust, histamine (and other chemicals) are released. This causes itching, swelling, and mucus production. Symptoms vary in severity from person to person. Very sensitive individuals can experience hives or other rashes. Particulate matter in polluted air and chemicals such as chlorine and detergents, which can normally be tolerated, can greatly aggravate the condition.

Sufferers might also find that cross-reactivity occurs. For example, someone allergic to birch pollen may also find that they have an allergic reaction to the skin of apples or potatoes. A clear sign of this is the occurrence of an itchy throat after eating an apple or sneezing when peeling potatoes or apples. This occurs because of similarities in the proteins of the pollen and the food. There are many cross-reacting substances.

Some disorders may be associated with allergies: Comorbidities include eczema, asthma, depression and migraine.

Allergy testing may reveal the specific allergens a person is sensitive to. Skin testing is the most common method of allergy testing. This may include intradermal, scratch, patch, or other tests. Less commonly, the suspected allergen is dissolved and dropped onto the lower eyelid as a means of testing for allergies. (This test should only be done by a physician, never the patient, since it can be harmful if done improperly). In some individuals who cannot undergo skin testing (as determined by the doctor), the RAST blood test may be helpful in determining specific allergen sensitivity.

In addition to individual sensitivity and geographic differences in local plant populations, the amount of pollen in the air can be a factor in whether hay fever symptoms develop. Hot, dry, windy days are more likely to have increased amounts of pollen in the air than cool, damp, rainy days when most pollen is washed to the ground.

The time of year at which hay fever symptoms manifest themselves varies greatly depending on the types of pollen to which an allergic reaction is produced. The pollen count, in general, is highest from mid-spring to early summer. As most pollens are produced at fixed periods in the year, a long-term hay fever sufferer may also be able to anticipate when the symptoms are most likely to begin and end, although this may be complicated by an allergy to dust particles.

The goal of rhinitis treatment is to reduce the symptoms caused by the inflammation of affected tissues. In cases of allergic rhinitis, the most effective way to decrease allergic symptoms is to completely avoid the allergen. Vasomotor rhinitis can be brought under a measure of control through avoidance of irritants, though many irritants, such as weather changes, are uncontrollable.

Allergic rhinitis can typically be treated much like any other allergic condition.

Eliminating exposure to allergins is the most effective preventive measure, but requires consistent effort.

Many people with pollen allergies reduce their exposure by remaining indoors during hay fever season, particularly in the morning and evening, when outdoor pollen levels are at their highest. Closing all the windows and doors prevents wind-borne pollen from entering the home or office. When traveling in a vehicle, closing all the windows reduces exposure. Air conditioners are reasonably effective filters, and special pollen filters can be fitted to both home and vehicle air conditioning systems.

Because many allergins clings to clothing, skin, and hair, regular cleaning reduces exposure and therefore symptoms. Many people bathe before sleeping, to minimize their exposure to potential allergins that could have stuck to their bodies during the day. Some people use nasal irrigation to physically remove contaminants from their noses.

Frequently cleaning floors and washing bedding can significantly reduce local irritants such as dust, as well as those tracked in by family, pets and visitors.

Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, cortisone, dexamethasone, hydrocortisone, epinephrine (adrenaline), theophylline and cromolyn sodium. Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. One antihistamine, Azelastine (Astelin), is available as a nasal spray.

More severe cases of allergic rhinitis require immunotherapy (allergy shots) or removal of tissue in the nose (e.g., nasal polyps) or sinuses.

Many allergy medications can have unpleasant side-effects, most notably drowsiness; more serious side-effects such as asthma, sinusitis, and even nasal polyps have also been reported however.

A case-control study found "symptomatic allergic rhinitis and rhinitis medication use are associated with a significantly increased risk of unexpectedly dropping a grade in summer examinations".

Systemic Glucocorticoids such as Triamcinolone or Prednisone are effective at reducing nasal inflammation, but their use is limited by their short duration of effect and the side effects of prolonged steroid therapy. Steroid nasal sprays are effective and safe, and may be effective without oral antihistamines. These medications include, in order of potency: beclomethasone (Beconase), budesonide (Rhinocort), flunisolide (Syntaris), mometasone (Nasonex), fluticasone (Flonase, Flixonase), triamcinolone (Nasacort AQ). They take several days to act and so need be taken continually for several weeks as their therapeutic effect builds up with time.

Topical decongestants: may also be helpful in reducing symptoms such as nasal congestion, but should not be used for long periods as stopping them after protracted use can lead to a rebound nasal congestion (Rhinitis medicamentosa).

Saltwater sprays, rinses or steam: this removes dust, secretions and allergenic molecules from the mucosa, as they are all instant water soluble. A suitable solution is 2-3 spoonful of salt dissolved in one litre of lukewarm water.

A large number of over-the-counter treatments are sold without FDA approval, including herbs like eyebright (Euphrasia officinalis), nettle (Urtica dioica), and bayberry (Myrica cerifera), which have not been shown to reduce the symptoms of nasal-pharynx congestion. In addition, feverfew (Tanacetum parthenium) and turmeric (Curcuma longa) has been shown to inhibit phospholipase A2, the enzyme which releases the inflammatory precursor arachidonic acid from the bi-layer membrane of mast cells (the main cells which respond to respiratory allergens and lead to inflammation) but this is only in test tubes and it is not established as anti-inflammatory in humans.

It has been claimed that homeopathy provides relief free of side-effects. However, this is strongly disputed by the medical profession on the grounds that there is no valid evidence to support this claim.

Therapeutic efficacy of complementary-alternative treatments for rhinitis and asthma is not supported by currently available evidence.

Nevertheless, there have been some attempts with controlled trials to show that acupuncture is more effective than antihistamine drugs in treatment of hay fever. Complementary-alternative medicines such as acupuncture are extensively offered in the treatment of allergic rhinitis by non-physicians but evidence-based recommendations are lacking. The methodology of clinical trials with complementary-alternative medicine is frequently inadequate. Meta-analyses provides no clear evidence for the efficacy of acupuncture in rhinitis (or asthma). Currently, evidence-based recommendations for acupuncture or homeopathy cannot be made in the treatment of allergic rhinitis.

Eating locally produced unfiltered honey is believed by many to be a treatment for hayfever, supposedly by introducing manageable amounts of pollen to the body. Clinical studies have not provided any evidence for this belief.

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Immunoglobulin E

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

In biology, Immunoglobulin E (IgE) is a class of antibody (or immunoglobulin "isotype") that has only been found in mammals. It plays an important role in allergy, and is especially associated with type 1 hypersensitivity. IgE has also been implicated in immune system responses to most parasitic worms like Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica, and may be important during immune defense against certain protozoan parasites such as Plasmodium falciparum.

Although IgE is typically the least abundant isotype - blood serum IgE levels in a normal ("non-atopic") individual are only 0.05% of the IgG concentration, compared to 10 mg/ml for the IgGs (the isotypes responsible for most of the classical adaptive immune response) - it is capable of triggering the most powerful immune reactions.

IgE was discovered in 1966 by the Japanese scientist couple Teruka and Kimishige Ishizaka.

IgE can upregulate the expression of both Fcε receptors. FcεRI is expressed only on mast cells and/or basophils in both mice and humans. Aggregation of antigens and binding of IgE to the FcεRI on mast cells causes degranulation and the release of mediators from the cells, while basophils cross-linked with IgE release type 2 cytokines like interleukin-4 (IL-4) and interleukin-13 (IL-13) and other inflammatory mediators. The low affinity receptor (FcεRII) is always expressed on B cells, but its expression can be induced on the surfaces of macrophages, eosinophils, platelets and some T cells by IL-4.

There is much speculation into what physiological benefits IgE contributes, and so far, circumstantial evidence in animal models and statistical population trends have hinted that IgE may be beneficial in fighting gut parasites such as Schistosoma mansoni, but this has not been conclusively proven in humans.

Although it is not yet well understood, IgE may play an important role in the immune system’s recognition of cancer, in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. Of course, if this were the case, anti-IgE treatments such as omalizumab might have some undesirable side effects.

Atopic individuals can have up to 10 times the normal level of IgE in their blood (as do sufferers of hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood - recent research has shown that IgE production can occur locally in the nasal mucosa, without the involvement of lymphoid tissue.

IgE that can specifically recognise an "allergen" (typically this is a protein, such as dust mite DerP1, cat FelD1, grass or ragweed pollen, etc.) has a unique long-lived interaction with its high affinity receptor, FcεRI, so that basophils and mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine, leukotrienes and certain interleukins, which cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis and increased vascular permeability, ostensibly to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis. Although the mechanisms of each response are fairly well understood, why some allergics develop such drastic sensitivities when others merely get a runny nose is still one of science's hot topics. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cells is thought to involve the "low affinity" receptor, FcεRII or CD23. CD23 may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells expressing CD23 are able to present allergen to (and stimulate) specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies.

IgE may be an important target in treatments for allergy and asthma.

Currently, severe allergy and asthma is usually treated with drugs (like anti-histamines) that damp down the late stages of inflammation and relax airway smooth muscle. Unfortunately, these treatments are fairly broad in their action, and so many have unpleasant side effects; they may also inhibit important protective responses.

In 2002, researchers at The Randall Division of Cell and Molecular Biophysics determined the structure of IgE. Understanding of this structure (which is atypical of other isotypes in that it is highly bent and asymmetric), and of the interaction of IgE with receptor FcεRI will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor interaction. A new treatment, omalizumab, a monoclonal antibody, recognises IgE not bound to its receptor and is used to neutralise or mop-up existing IgE and prevent it from binding to cells. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit IgE binding to its receptor.

In 1975 Robert N. Hamburger, M.D. published "Peptide Inhibition of the P-K Reaction" based on blocking up to 89% of the IgE receptors on mast cells by the pentapeptide representing amino acids 320 to 324 on the epsilon chain of IgE.

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Bepotastine

Bepotastine.png

Bepotastine (INN, sold under the brand name Talion) is an antihistamine.

Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name TALION. TALION was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine for ophthalmic use.

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Mometasone furoate

Mometasone furoate.png

Mometasone furoate (also referred to as mometasone) is a moderately potent glucocorticoid steroid used in the treatment of inflammatory skin disorders (such as eczema and psoriasis), allergic rhinitis (such as hay fever), and asthma for patients unresponsive to less potent corticosteroids. In terms of steroid strength, it is more potent than hydrocortisone, and less potent than dexamethasone.

Schering-Plough markets the medication under the following brand names; Elocon (Elocom) as a cream or ointment for skin conditions, Nasonex as a nasal spray for upper respiratory conditions such as nasal sinus inflammation, Asmanex Twisthaler as a dry powder inhaler (DPI) for lower respiratory conditions.

Generic Mometasone cream is available in the United States, manufactured by Taro Pharmaceuticals of Canada (distributed in the USA by such companies as Clay-Park Labs, Perrigo Company). Nasonex is not available as a generic in the USA (its patent won't run out until at least 2014), nor is Asmanex Twisthaler (its patent won't run out until at least 2012).

Nasonex is known in the U.S. for a series of television ads featuring an animated bee which is voiced by the Spanish actor Antonio Banderas.

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Allergic inflammation

Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease .

The early phase of the allergic reaction typically occurs within minutes, or even seconds, following allergen exposure and is also commonly referred to as the immediate allergic reaction or as a Type I allergic reaction . The reaction is caused by the release of histamine and mast cell granule proteins by a process called degranulation, as well as the production of leukotrienes, prostaglandins and cytokines, by mast cells following the cross-linking of allergen specific IgE molecules bound to mast cell FcεRI receptors . These mediators affect nerve cells causing itching , smooth muscle cells causing contraction (leading to the airway narrowing seen in allergic asthma) , goblet cells causing mucus production , and endothelial cells causing vasodilatation and edema .

The late phase reaction is also sometimes called the Type IV allergic reaction or delayed type hypersensitivity and may take as long as 6 – 12 hours to fully develop following an encounter with allergen . The products of the early phase reaction include chemokines and molecules that act on endothelial cells and cause them to express Intercellular adhesion molecule (such as vascular cell adhesion molecule and selectins), which together result in the recruitment and activation of leukocytes from the blood into the site of the allergic reaction . Typically, the infiltrating cells observed in allergic reactions contain a high proportion of lymphocytes, and especially, of eosinophils. The recruited eosinophils will degranulate releasing a number of cytotoxic molecules (including Major Basic Protein and eosinophil peroxidase) as well as produce a number of cytokines such as IL-5 . The recruited T-cells are typically of the Th2 variety and the cytokines they produce lead to further recruitment of mast cells and eosinophils, and in plasma cell isotype switching to IgE which will bind to the mast cell FcεRI receptors and prime the individual for further allergic responses.

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Mast cell stabilizer

Nedocromil

Mast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and so prevent the release of histamine and related mediators. One suspected pharmacodynamic mechanism is the blocking of IgE-regulated calcium channels. Without intracellular calcium, the histamine vesicles cannot fuse to the cell membrane and degranulate.

As inhalers they are used to treat asthma, as nasal sprays to treat hay fever (allergic rhinitis) and as eye drops for allergic conjunctivitis. Finally in oral form they are used to treat the rare condition of mastocytosis.

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Source : Wikipedia