Allergy

Introduction

Ah, the colors of spring - green grass, yellow daffodils, blue skies and red eyes - red, itchy, watery eyes.

What is it?

An allergy is your body's reaction to a foreign substance--such as pollen or pet dander--that enters, or comes in contact with the body. It may be that pollen never bothered you before but over time, and with repeated exposures, your body grew overly sensitive to it, resulting in allergy symptoms such as sneezing and watery eyes. When foreign substances such as pollen cause allergic reactions, they are called allergens.

Allergens cause cells in your body to release chemicals known as mediators, which trigger allergy symptoms. These mediators include histamine and prostaglandins.

• Histamine is the mediator that stimulates mucus production and causes redness, swelling and inflammation.
• Prostaglandins are mediators that constrict airways and enlarge blood vessels.

The Mechanism of an Allergic Reaction

There are three stages to the allergic response: In the first stage, the immune system encounters the foreign substance and identifies it as an invader. It then primes the immune system to recognize this invader as an enemy that needs to be destroyed in future encounters. This stage is known as sensitization. The subsequent stages are mast cell activation, and prolonged immune activation.

STAGE 1- SENSITIZATION
The first time an allergen meets the immune system, no allergic reaction occurs. Instead, the immune system prepares itself for future encounters with the allergen. Scavenger cells called macrophages surround and break up the invading allergen. The macrophages then display the allergen fragments on their cell walls to specialized white blood cells, called T lymphocytes, which are the main orchestraters of the body's immune reaction. The T cells secrete a signaling chemical called interleukin-4, which activates other white blood cells known as B lymphocytes. These cells secrete antibodies specific for that particular allergen. These antibodies, called immunoglobulin E (IgE) receptors, are attached to cells in the immune system, called mast cells and basophils. Individuals prone to allergies are known to have abnormally high levels of IgE antibodies.

STAGE 2- MAST CELL ACTIVATION
Stage 2, or mast cell activation, represents a later encounter between the allergen and the immune system and usually occurs within minutes after the second exposure to an allergen. IgE antibodies on mast cells, constructed during the sensitization phase, recognize the allergen and bind to the invader. Once the allergen is bound to the receptor, granules in the mast cells release their contents.

The mast cell is destabilizing, releasing allergy-causing chemicals.

These contents, or mediators, are substances such as histamine, platelet-activating factor, prostaglandins, and leukotrienes. Mediators are what actually trigger the allergy attack. Histamine stimulates mucus production and causes redness, swelling, and inflammation. Prostaglandins constrict airways and enlarge blood vessels.

STAGE 3- LATE PHASE INFLAMMATORY RESPONSE
In Stage 3 tissue mast cells and neighboring cells produce chemical messengers that signal circulating basophils, eosinophils, and other cells to migrate into that tissue, to help fight the foreign material. These recruited immune cells secrete chemicals of their own that sustain inflammation, cause tissue damage, and recruit yet more immune cells. This phase occurs several hours after exposure and can last for hours and even days.

Once the mast cells have released histamine and other chemicals, these cause other immune system cells, called basophils, to prolong the reaction, damaging tissue.

What causes it?

The most common allergens include:

• pollens (tree, grass and weeds)
• molds
• house dust
• dust mites
• bee stings
• medications, both prescription and over-the-counter
• foods
• animals
• air pollutants

1. Seasonal allergies like hay fever are more common in the spring and fall when plant pollination begins. Trees and grass cause most symptoms in the spring, while ragweed is responsible for the majority of autumn symptoms.

2. Perennial allergies are usually year-round problems. Common triggers for perennial allergies include mold spores, pet dander and dust mites.

Who has it?

More than 50 million Americans have allergies. Allergic rhinitis (inflammation in the nasal area) is the most common allergic disease, affecting at least 20 to 25 percent of the population. Typically, symptoms first appear between ages two and three, peak during the early teens, show a smaller increase in early adulthood, then diminish with age.

Allergies are the 6th leading cause of chronic illness in the U.S. It has been estimated that allergies cost almost $6 billion annually in workplace productivity. Direct health care costs of allergic rhinitis are increasing each year. These costs include money spent on medication ($2.3 billion--including prescription and over-the-counter drugs), visits to the doctor's office (approximately 16.7 million office visits to health care providers each year are attributed to allergic rhinitis which all together costs $1.1 billion), and medical tests.

What are the risk factors?

Risk factors are characteristics that can predispose you to developing a condition. The following are two key risk factors for developing allergies:

1. A personal or family history of allergies.
2. Continued exposure to a known allergen. For example, if a person has a feather allergy and continues to sleep on a feather pillow, the likelihood of developing an allergic response is greater than if a foam pillow is used.

What are the symptoms?

Most allergens enter the body through the respiratory system (nose, pharynx, larynx, trachea, bronchi and lungs). Allergen stimulation in the upper respiratory system can result in:

• sneezing
• runny nose
• nasal congestion
• scratchy throat
• post-nasal drip
• itchy eyes and nose
• watery eyes

• dry or irritated throat
• snoring
• pain or darkness around eyes
• mouth breathing
• headaches
• ear aches
• altered hearing, taste, or smell
• sleep disturbances

• chest tightening
• wheezing
• trouble breathing
• coughing

• nausea
• vomiting
• diarrhea

Anaphylaxis, the most severe allergic reaction, results when an allergen causes a reaction in the circulatory system (blood, heart and chest). During anaphylaxis, blood vessels relax and lose fluid. This causes blood pressure to drop, which can make you dizzy. The fluid also leaks into surrounding tissues, causing them to swell. If the swelling is severe, it can restrict your airways, making it impossible to breathe.

How is it treated?

The main goals for treating allergic rhinitis are to minimize or prevent allergy symptoms and help allergy sufferers maintain normal daily activities and lifestyles.

The most effective treatment for allergies is to avoid what is causing the symptoms. If this is not possible, then medication selection should be based on the symptoms the individual is experiencing.

Generally speaking, if you have nasal congestion, an oral or nasal spray decongestant should be used. For symptoms such as runny nose, sneezing, or itchy/watery eyes, an antihistamine should be used. A combination of these medications can be used if you have both symptoms. For patients experiencing seasonal allergic rhinitis, treatment should be started 10-14 days before the allergy season when symptoms are expected to appear and should be continued for 2-3 weeks after the end of the allergy season to alleviate persistent symptoms.

Most physicians try to follow a stepwise approach to treating allergies based on the severity and frequency of allergy symptoms:

For Mild, Infrequent Allergic Rhinitis Symptoms:

For allergy symptoms such as a runny nose, watery/itchy eyes, or sneezing that occur infrequently, most individuals can be treated sucessfully with an oral non-sedating antihistamine such as loratadine (Claritin), desloratadine (Clarinex), fexofenadine (Allegra), cetirizine (Zyrtec), levocetirizine (Xyzal) or or an antihistamine nasal spray such as azelastine (Astelin) to be taken on an as needed basis when allergy symptoms arise. Another option may be to try to prevent allergy symptoms before the anticipated allergen exposure by using cromolyn (Nasalcrom) nasal spray prior to exposure to the allergen. Cromolyn nasal spray is also recommended for kids. Cromolyn (Nasalcrom) nasal spray, loratadine (Claritin), and cetirizine (Zyrtec) are products that are available over-the-counter without a prescription.

For infrequent nasal decongestion, over-the-counter oral decongestants such as psuedoephedrine (available behind the pharmacy counter without a prescription) or nasal spray decongestants such as phenylephrine (Neo-Synephrine products) or oxymetolazone (Afrin products) can be tried. Nasal spray decongestants will provide quicker relief but oral decongestants may provide longer relief of congestion. These products should be used on an as needed basis for no longer than 3 to 5 days.

For Persistent, Mild-to-Moderate Allergic Rhinitis Symptoms:

Treatment options include oral non-sedating antihistamines as listed above but taken on a daily basis. For individuals who have nasal congestion along with a runny nose, itchy/watery eyes, or sneezing, a combination non-sedating antihistamine/decongestant product can be tried such as Claritin-D, Allegra-D, or Zyrtec-D. Nasal corticosteroids such as beclomethasone (Beconase, Vancenase), budesonide (Rhinocort), flunisolide (Nasalide, Nasarel), fluticasone (Flonase), triamcinolone (Nasacort), or mometasone (Nasonex) may also be tried as separate therapy or added to antihistamines and decongestants. For children with persistent, mild-to-moderate allergy symptoms, cromolyn (Nasalcrom) nasal spray or an oral non-sedating antihistamine approved for use in children may be tried.

For Severe Allergic Rhinitis Symptoms:

For patients with severe allergy symptoms, nasal corticosteroids will most likely be needed along with a non-sedating antihistamine (with or without a decongestant). Cromolyn (Nasalcrom) nasal spray should be used in children. If needed, a short course (meaning 3 to 10 days) of oral corticosteroids can be used. For individuals with severe allergies, referral to an allergy/immunolgy specialist or an "ear, nose, and throat" allergy specialist is recommended.

Other allergy therapies include ipratropium nasal (Atrovent), a nasal spray sometimes used for individuals who have a runny nose from allergies. Older antihistamines such as diphenhydramine (Benadryl), brompheniramine (Brovex), chlorpheniramine (Chlor-Trimetron), and clemastine (Tavist) are also available and can be used to treat allergy symptoms like runny nose, itchy/watery eyes, and sneezing, but these older antihistamines can cause drowsiness and sedation more so than the newer non-sedating antihistamines.

Immunotherapy may also be considered but it is expensive, has certain risks, and requires a significant time commitment by the individual suffering from allergies. Immunotherapy is a series of injections where gradually increasing doses of antigens (substances that are responsible for triggering an allergic response) are injected into the patient in hopes to build tolerance to the allergen.

To learn more about the individual drugs used to treat allergies, click on the drug links below.

Helping Yourself

Although it may require extra effort, avoiding allergens can be an inexpensive and effective way to control allergies. You can avoid allergens in the following ways:

• Monitor pollen counts by reading the newspapers, watching the news or by exploring the World Wide Web. Remain indoors when counts are particularly high.
• Use air conditioning rather than opening windows in your car, home and office, especially when pollen counts are high.
• Limit dust mite exposure by using allergy-proof casings on pillows and mattresses and by frequently laundering bed linens and pillows.
• If pets are the target allergen and complete removal is not an option, vacuum carpets and furniture often to remove dander. Restrict the pet's access to your bedroom or sleeping area.

What is on the horizon?

Doctors and patients have become concerned with the possibility of decreases in bone health that have been reported with inhaled corticosteroid use. This has lead to increased use of other agents in this class including the leukotriene inhibitors such as Montelukast (Singulair). Combination products including both a second generation antihistamine and leukotriene modifying agent are under active investigation.

On another research front, investigators are currently recruiting participants for a study looking at the effect allergic rhinitis, and its treatment, may have on driving ability. Although this may sound insignificant, the results of this study may help guide the development of future drugs and treatments for allergic rhinitis.

Researchers recently identified a protein in mice, called RGS13, which suppresses allergic reactions, including the very severe form of anaphylaxis. RGS13 has also been identified in a certain number of human cells, making it a possible target for developing new drugs to treat and prevent allergic reactions. Through current and future research, doctors hope to identify a correlation between abnormal expression of this protein and specific allergic diseases.

Finally, scientists are using x-ray crystallography to map the three-dimensional structure of a receptor molecule that plays a key role in triggering the symptoms of asthma and allergies. This finding not only advances our understanding of these diseases, but paves the way for a new class of anti-allergy drugs. Scientists are also continuing investigation of DNA vaccines for allergic diseases.

References

National Institute of Allergy and Infectious Diseases. Allergy Statistics. Available at: http://www.niaid.nih.gov/factsheets/allergystat.htm. Accessed April 2006.

Long A, McFadden C, DeVine D, et al. Management of Allergic and Nonallergic Rhinitis (Evidence Report/Technology Assessment No. 54 (Prepared by New England Medical Center Evidence-based Practice Center under Contract No. 290-97-0019). AHRQ Pub. No. 02-E024. Rockville, MD: Agency for Healthcare Research and Quality. May 2002.

American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Available at: http://www.theallergyreport.com/. Accessed January 2008.

May JR. Allergic Rhinitis. In: Pharmacotherapy, A Pathophysiologic Approach. 6th ed. Dipiro JT, Talbert RL, Yee GC, et al. eds. McGraw-Hill. New York. 2005, pages 1729-1739.

AllerDays: Relief Info Plus:Why Do I Feel Like This?: What Are Allergies? Available at: http://www.allerdays.com/whatare.html#mechanics

Canadian Medical Association. Assessing and Treating Rhinitis, A Practical Guide for Canadian Physicians. Available at: http://www.cma.ca/cpgs/rhinitis

Fireman P. Treatment strategies designed to minimize medical complications of allergic rhinitis. American Journal of Rhinology 1997;11(2):95-102

Hulisz D, Fillwock L. Management of allergic rhinitis. U.S. Pharmacist 1996; 21(7):49-60.

Jardieu P, Shields R, Nakamura G. http://www.accessexcellence.org/LC/ss/BkgndPaper_Current_Seminar.html

National Institute of Allergy and Infectious Diseases. Allergic Diseases. Available at: http://www3.niaid.nih.gov/. Accessed January 2008.

Wilson, L. Focus On. . . The Etiology of Allergy. Available at: http://pharminfo.com/pubs/msb/allergy_et.html

U.S. Food and Drug Administration Website. URL:http://www.fda.gov. Accessed January 2008.

Xyzal. Full Prescribing Information. www.xyzal.com (Accessed January 2008).

Allergy Health Condition Last Updated: January 2008

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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