Medications for Allergy

An adverse reaction to milk and milk products is not uncommon, especially in children, and results in a variety of symptoms. The most frequent reactions are in the skin, where eczema, hives, and angioedema (tissue swelling) may occur and in the gastrointestinal tract with abdominal bloating, pain, gas, diarrhea, constipation, nausea, vomiting, and occasionally blood loss in the stool (occult blood). In some people, upper respiratory tract symptoms and asthma may be caused or made worse when they consume milk or milk products.

Occult blood loss associated with cow’s milk allergy can cause iron-deficiency anemia, especially in children, because blood is the most important source of iron in the body. Another effect of cow’s milk allergy currently being investigated in children is an inability to fall asleep and restless, disturbed sleep. In an infant, inadequate growth and weight gain (failure to thrive) may be a result of milk allergy. The allergic reaction results in inflammation in the intestines, and absorption of nutrients may be impaired as a result of damage to the transport mechanisms in the intestinal cells. Transport mechanisms are processes that transport nutrients from the intestines into blood circulation.

The diagnosis of milk allergy is not a simple matter. Although any adverse reaction a person has after drinking milk is often ascribed to “milk allergy,” when the symptoms are in the gastrointestinal tract the problem may be lactose intolerance, not an immunologically mediated allergy to milk proteins.

♦ Milk allergy is caused by an immune reaction against milk proteins; more than 25 distinct proteins are identifiable; any number of these may trigger an immune response.

♦ Lactose intolerance is due to the body’s inability to produce enough of the digestive enzyme, called lactase, which splits lactose into its constituent mono-saccharides (single sugars), glucose and galactose.

What Causes Milk Allergy?

Milk-Free Diet

People who have a known allergy to cow’s milk proteins or are unable to tolerate lactose need to eliminate the following from their diet:

♦ All milk and milk-containing foods, including liquid and evaporated milks

♦ Fermented milks (yogurt, buttermilk)

♦ All cheeses (hard cheeses, cottage cheese, cream cheese)

♦ Ice cream and ice milk

♦ Any foods containing milk solids such as cream, butter, and margarines containing whey

♦ All foods or beverages containing components of milk such as casein, whey, lactoglobulin, and hydrolysates of these (Table Table label-reading guidelines for a milk-free diet)

Table Label-reading guidelines for a milk-free diet

Terms Indicating the Presence of Cow’s Milk Components Butter
Butter fat	Acidophilus milk	Hydrolyzed casein
Butter-flavored oil	Lactaid milk	Ammonium caseinate
Butter solids	Lacteeze milk	Calcium caseinate
Whipped butter	Condensed milk	Potassium caseinate
Artificial butter flavor	Evaporated milk	Sodium caseinate
Natural butter flavor	Cultured milk	Rennet casein
Buttermilk	Milk solids	Whey
Buttermilk solids	Malted milk	Whey protein
Cheese	Milk powder	Whey powder
Cottage cheese	Cream	Sweet dairy whey
Processed cheese	Whipped cream	Whey hydrolysate
Cream cheese	Half-and-half	Hydrolyzed whey
Feta	Light cream	Delactosed whey
Ricotta	Ice cream	Demineralized whey
Quark	Ice milk	Lactose
Curd	Sherbet	Lactulose
Homogenized; 1%; 2%; skim; whole; low-fat; non-fat milk	Yogurt Casein	Lactoglobulin
	Casein hydrolysate	Lactalbumin

Ingredients That May Contain Milk Proteins

Brown sugar flavoring	Margarine	Simplesse
Caramel flavor	Chocolate	High-protein flour
Natural flavor

Note: Lactic acid, lactate, and lactylate do not contain milk and do not need to be eliminated from the diet.

Alternate Sources of Nutrients

Substitutes for Milk in Meals and Recipes

Feeding the Milk-Allergic Infant

Mother’s Milk

Without question, the best nutrition for the newborn baby and young infant is its own mother’s breast milk. A baby will never be allergic to its mother’s milk, but may react to allergenic proteins that get into to her milk from her diet. If the baby is showing signs of allergy, and is being exclusively breast-fed, then the mother’s diet must be checked for the presence of allergenic foods to which her baby is reacting. Eggs and milk are the most common allergenic foods that seem to cause symptoms at this early life stage. The mother should avoid these, and any other foods suspected to be causing a reaction in her infant, for at least four weeks to determine if these foods are the cause of the baby’s symptoms. Reintroducing the foods into the mother’s diet and monitoring the baby’s response is a good way to identify the foods that are causing the baby’s problems.

If the breast-fed baby is lactose-intolerant (usually a temporary condition following intestinal infection at this age), the mother can continue to breastfeed, or pump her milk and treat it with lactase enzyme, until the baby’s symptoms go away. Details concerning feeding the lactose-intolerant infant are provided in the section “Lactose Intolerance,” later in this chapter. There is no point in the mother eliminating milk and milk products from her diet to treat lactose intolerance in her baby, because her milk will contain 6% lactose (6 milliliters lactose in 100 milliliters liquid) regardless of whether or not she consumes milk and milk products.

Milk-Free Formulas

Soy-based formulas may be tolerated by milk-allergic infants. However, about 50% of babies with milk allergy seem to develop an allergy to soy also. In these cases, protein hydrolysate formulas are the best alternative. Protein hydrolysate formulas including the extensively hydrolyzed casein formulas (such as Alimentum, Enfalac Nutramigen, Enfalac Pregestimil) or extensively hydrolyzed whey formulas (such as Profylac), in which the proteins have been broken down into their constituent amino acids and peptides too small to be allergenic, are usually tolerated by the milk-allergic infant. The biggest disadvantage of these formulas is their high cost.

Partially hydrolyzed milk-based formulas such as partially hydrolyzed whey (for example, GoodStart) are not suitable for an infant with suspected or diagnosed hypersensitivity to cow’s milk protein. Babies whose symptoms don’t go away when they’re on the extensively hydrolyzed casein formulas might tolerate an “elemental” amino acid formula such as Neocate. Children should be encouraged to continue on hydrolysate or amino acid formula (or soy-based formula if a soy protein allergy or intolerance has been ruled out) as long as it is acceptable. After the age of 12 months, when they are eating a good range of solid foods, milk-allergic children may do well on milk substitutes (e.g., fortified soy or rice milks) and other calcium-fortified foods, if allergy to these foods is not suspected.

Table The milk-free diet: foods allowed and foods restricted lists the foods allowed and foods restricted in a milk-free diet.

♦ About 50% of babies with IgE-mediated cow’s milk allergy develop an allergy to soy.

♦ In addition, soy can cause a non-lgE-mediated response (intolerance) that is separate and distinct from allergy. The effects are localized in the digestive tract, with symptoms such as colicky pain, abdominal bloating, gas, and diarrhea. This is sometimes referred to as soy enteropathy.

Lactose Intolerance

Distinguishing Between Milk Allergy and Lactose Intolerance

It is frequently very difficult to distinguish milk allergy from lactose intolerance on the basis of clinical symptoms alone, because some of the symptoms, such as abdominal pain, diarrhea, nausea, vomiting, gas, and bloating, are common to both conditions. However, milk allergy often results in symptoms in other organs, such as the upper respiratory tract (for example, a stuffy, runny nose), pain, itching, fluid drainage from the ears, or skin reactions (such as eczema or hives), and lactose intolerance does not.

Because secondary lactase deficiency is a consequence of inflammation in the digestive tract, the intestinal inflammation caused by milk allergy can sometimes result in lactase deficiency. Thus, both milk allergy and lactose intolerance can exist together. Because milk is the only source of lactose in the normal diet, eliminating milk from the diet will cure both conditions, but it will not distinguish which condition caused the symptoms. It is important to determine which condition is causing the problem: Milk and milk products are a significant source of nutrients, especially for infants and young children, and they should not be eliminated from the diet unless it is absolutely necessary to do so. Furthermore, eliminating milk entirely is not easy, because so many different foods, such as baked goods, soups, salad dressings, gravies, desserts, and so on, contain milk. Not being able to eat these foods can make meal planning very difficult.

Laboratory Tests for Lactose Intolerance

There are a number of laboratory tests that can identify lactose intolerance:

The fecal reducing sugar test is considered by many clinicians as very reliable. After the patient takes a drink containing lactose, the feces are collected and Fehling’s solution is added. The presence of lactose is indicated by a change in color, from blue to red. The lactose “reduces” the chemical in the solution. Thus, a change in color indicates that a deficiency of lactase has led to undigested lactose being excreted in the feces.

The hydrogen breath test is a common test for lactose intolerance. In this test the patient drinks a given quantity of lactose and after a prescribed interval, a breath sample is analyzed for the presence of hydrogen. If hydrogen is detected, it indicates that bacteria in the digestive tract have acted on undigested lactose and produced hydrogen as one of their metabolic by-products. Unfortunately, this test is not specific for lactase deficiency, because any sugar remaining in the digestive tract will be metabolized by bacteria with the production of hydrogen. Undigested sucrose, maltose, or a starch will give a similar result.

The blood glucose test involves measuring the level of glucose in the blood after the patient takes a drink containing 50 grams of lactose. An increase in blood glucose indicates that lactose has been broken down to glucose and galactose, the levels of which rise in the blood when the body is producing enough lactase. Measuring the level of galactose would be equally informative. If there is no increase in the level of glucose in the blood, lactose intolerance is confirmed.

If the feces collected after the above lactose drink are acidic, with a pH of 6 or lower (the fecal pH test), it indicates that microorganisms in the large bowel have fermented the undigested lactose. The microbial activity results in the production of acids, which lower the pH of the stool. Thus, the diagnosis of lactose intolerance is further reinforced.

Management of Lactose Intolerance

Lactase deficiency is easier to manage than cow’s milk protein allergy, because any milk or milk product free from lactose can be consumed without gastrointestinal symptoms. Lactose-free milk is available as products such as Lacteeze or Lactaid. Alternatively, a commercial form of lactase (sold as Lactaid liquid) can be added to any milk before consumption. After 24 hours in the fridge, the lactose is split into its two component sugars, glucose and galactose, which the body can absorb and use without harm. All of the nutrients and proteins in milk are thus available to the body, and there will be no risk of nutritional deficiency as a result of long-time avoidance of milk.

It is more difficult to avoid lactose in prepared foods; anything containing milk or milk solids is likely to contain lactose also. Some people find that they can consume lactose-containing foods without a problem if they take Lactaid in the form of a tablet before eating those foods.

Lactose intolerance is dose-related. Usually the epithelial cells of the digestive tract are producing a limited amount of the enzyme lactase, and the body can process small doses of foods containing lactose. Problems occur when the amount of lactose in the food exceeds the capacity of the enzyme to digest it. The important thing is to determine tolerance levels. By remaining within one’s own limits, a person should not have symptoms. Most people who are lactose-intolerant can drink a 6-ounce glass of milk without symptoms, but will experience abdominal discomfort if they exceed this amount.

When lactose intolerance has been diagnosed, the degree of lactase deficiency can be assessed by having the patient take increasing quantities of lactose in a variety of dairy products (Table Levels of lactose in normal serving sizes of common foods and beverages). Most lactase-deficient people can process the lactose in one glass of milk, which is about 11 grams of lactose. But taking several types of milk and dairy products in a 24-hour period would exceed their enzyme’s capacity to break down lactose and digestive tract symptoms would result.

Table Levels of lactose in normal serving sizes of common foods and beverages

Product	Serving Size	Lactose (grams)
Sweetened condensed milk	125 mL( ½ cup)	15
Evaporated milk	125 mL(1/2 cup)	12
Whole milk	250 mL(1 cup)	11
2% milk	250 mL(1 cup)	11
1% milk	250 mL(1 cup)	11
Skim milk	250 mL(1 cup)	11
Buttermilk	250 mL(1 cup)	10
Ice milk	125 mL(1/2 cup)	9
Ice cream	125 mL(1/2 cup)	6
Half-and-half light cream	125 mL(1/2 cup)	5
Yogurt, low-fat	250 mL(1 cup)	5
Sour cream	125 mL(1/2 cup)	4
Cottage cheese, creamed	125 mL(1/2 cup)	3
Whipping cream	125 mL(1/2 cup)	3
Cottage cheese, uncreamed	125 mL(1/2 cup)	2
Sherbet, orange	125 mL(1/2 cup)	2
American (jack) cheese	30 g (1 oz)	2
Swiss cheese	30 g (1 oz)	1
Blue cheese	30 g (1 oz)	1
Cheddar cheese	30 g (1 oz)	1
Parmesan cheese 3	9 (1 oz)	1
Cream cheese (e.g., Philadelphia)	30 g (1 oz)	1
Lactaid milk	125 mL(1/2 cup)	0.025
Butter	5mL(1 tsp)	trace

Feeding the lactose-intolerant baby

The Breast-Fed Baby

A breast-fed baby will ingest significant quantities of lactose in mother’s milk. The lactose composition of her milk will remain constant regardless of whether or not the mother consumes milk and dairy products.

♦ If the lactose intolerance is secondary to a gastrointestinal tract infection or other condition that is expected to be temporary some authorities advise continuing breast feeding and expect the diarrhea to gradually go away as the underlying inflammation disappears.

♦ Some authorities recommend placing a few drops of Lactaid directly into the baby’s mouth before each feeding. This may provide enough of the enzyme to break down the lactose in mother’s milk, and so reduce or eliminate the baby’s digestive tract symptoms.

♦ Alternatively the mother can pump her breast milk and treat the milk with Lactaid drops (4 drops per 250 millimeters of milk) and allow the enzyme to act for 24 hours in the fridge. The baby is fed the lactose-free milk the next day. This is continued until the diarrhea stops, when the baby can be gradually put back to the breast.

The Formula-Fed Baby

Infant formulas that are lactose-free can be given to a lactose-intolerant infant. If the baby is not allergic to milk, the milk-based formula Lacto-Free (Mead Johnson) or Similac LF (Ross), which are free from lactose, are suitable. If the infant is allergic to cow’s milk proteins, but tolerates soy, soy-based formulas such as Prosobee (Mead Johnson), Alsoy (Nestle), or Isomil (Ross) may be suitable. Infants who are allergic to both cow’s milk and soy proteins may tolerate a casein hydrolysate formula such as Alimentum (Ross), Nutramigen (Mead Johnson), or Pregestimil (Mead Johnson). All of these formulas are free from lactose.

Managing Lactose Intolerance

Lactose Restrictions

♦ Assume that foods, medications, and beverages containing milk and milk solids contain lactose, unless they are labelled “lactose-free.”

♦ Avoid products labelled as containing lactose, milk, milk solids, milk powder, cheese and cheese flavor, curd, whey, cream, butter, and margarine containing milk solids.

♦ Products containing lactic acid, lactalbumin, lactate, and casein do not contain lactose and can be consumed.

Acidophilus milk has had a bacterium called Lactobacillus acidophilus added to it. These bacteria do not break down lactose to any great extent, so lactose-intolerant people would not be able to tolerate this milk.

Milk and Milk Products Suitable for a Lactose-Restricted Diet

♦ Adding the enzyme lactase (commercially available as Lactaid) to liquid milk, and allowing the enzyme to act for a minimum of 24 hours in the refrigerator, will make it digestible. No milk substitutes are then necessary. The amount of the enzyme that needs to be added will depend on the degree of lactase deficiency. Follow the instructions that are provided with the product.

15 drops in 1 liter of milk will render it 99% lactose free. 10 drops reduces the lactose to 90%. 5 drops will provide a milk that is 70% lactose-free.

♦ Lactaid tablets may be taken before eating or drinking lactose-containing products and may be sufficient to break down the amount of lactose consumed in the following meal.

♦ Lactaid milk and Lacteeze milk, which are 99% lactose-free, are available in the dairy section of grocery stores. These are tolerated by lactose-deficient people, but they are more expensive than regular milk.

♦ Hard, fermented cheeses may be tolerated because most of the lactose is removed with the whey during their manufacture.

♦ Although butter and regular margarines contain a small amount of lactose (in whey), they are usually tolerated because the level of lactose is so low and these products are eaten in small quantities.

♦ Fermented milks such as yogurt and buttermilk may be tolerated because the level of lactose in these products is reduced (but not completely eliminated) by bacterial enzymes. Mixing Lactaid drops in the yogurt in the doses indicated above, and refrigerating the product for 24 hours, may make it acceptable for someone who is severely lactose-intolerant.

The Lactose-Free Diet

Ideas for Milk Substitutes on a Lactose-Reduced Diet

Beverages

Lactaid Milk and Lactaid Hot Chocolate

Combine 1 tbsp (15 mL) of pure cocoa with 1 tbsp sugar. Mix in 1 tbsp cold water until smooth. Stir in 1 cup of hot Lactaid milk.

Fruit and Vegetable Juices

All pure vegetable and fruit juices without added ingredients

Coffee and Tea

Clear coffee, tea, and herbal tea In place of milk, add Lactaid milk Rich’s Coffee Rich

Soy beverages (SoGood, SoNice) without milk-derived additives

Others

Soft drinks and mineral water

Alcoholic beverages except cream-based liqueurs

Liquid Meal Replacers

Liquid nutritional supplements containing casein, but free from whey, such as Boost, Enercal, Ensure, Resource

Soup

For a soup base:

Clear stock

Clear broth or bouillon

Defatted meat drippings

Tomato or vegetable juice Read labels on canned stock based soups, and avoid milk or cream-based soups.

Desserts

All desserts and baked goods made without milk or milk products, for example: Angel food cakes Gelatin fruit desserts (Jello) Rice Dream dessert Milk-free soy ice desserts Fruit ices Popsicles Fresh, frozen, or canned fruit

Sorbet made in a food processor

1 banana

A dash of lemon juice

1 to 1 ½ cups of frozen berries

Add sugar or Sugar Twin to taste

Condiments and Snacks

Salt and pepper

Tabasco, Worcestershire sauce, soy sauce

Ketchup, mustard, relish, pickles

Air-popped popcorn

Potato chips

Tortilla or nacho chips and salsa

Hard and gelatin candy in moderation

Avoid milk chocolate and candies made with restricted ingredients, such as Toffee Caramels Chocolates

Dining in Restaurants

♦ Dining in regular restaurants should pose no difficulty as many milk-free foods are included on all restaurant menus

♦ Check with the server to ensure that the dish is milk-free

♦ Most fast-food restaurants will have lists of the ingredients in all their menu items; avoid those that contain milk or its derivative.

♦ Avoid all cream-based sauces and dressings; request dishes without added sauces.



When symptoms of allergic rhinitis require continuous therapy, intranasal corticosteroids are the most effective agents available for nasal symptoms and are more potent than oral antihistamines. Corticosteroids inhibit both the early-phase (cytokine release) and late-phase (migration of mast cells, basophils and eosinophils to the nasal mucosa) allergic reactions. They also decrease microvascular permeability, edema and mucus secretion.

Corticosteroids are available in oral and nasal dosage forms (Table 4). Nasal corticosteroids are effective in reducing congestion, sneezing, rhinorrhea, thick postnasal discharge and nasal pruritus (Table 1) and should be reserved for moderate to severe allergic rhinitis. Their onset of action is not seen until 12 hours after the first dose, with maximal efficacy achieved between three to 14 days of therapy. Side effects with nasal corticosteroid usage are minimal and include nasal irritation, nasal burning and drying. Instructing patients to direct the spray away from the nasal septum can prevent these side effects; however, if a patient develops nasal irritation or bleeding, the nasal steroid should be discontinued. Pharmacists should instruct patients that nasal dryness can be minimized with the use of nasal saline prior to administring the nasal spray. The aqueous nasal corticosteroid preparations (fluticasone propionate, beclomethasone dipropionate, and triamcinolone) are most effective for patients with “drier” noses and predominant nasal congestion. The nonaqueous preparations (beclomethasone, budesonide, triamcinolone acetonide) are most efficacious in patients with rhinorrhea or “wet” noses. At recommended doses, nasal steroids are associated with low systemic absorption, with the exception of dexamethasone sodium phosphate. To maximize effectiveness, treatment with intranasal corti-costeroids should be started prior to allergen exposure and be administered on a regular rather than on an as needed basis. Nasal steroids can be given to patients who should not receive antihistamines or decongestants (e.g., patients with glaucoma, hypertension, prostatic hypertrophy) and the lowest dose that provides relief of symptoms should be used.

A meta-analysis of randomized clinical trials comparing the efficacy of regular-use intranasal corticosteroids to oral antihistamines, supports the superiority of intranasal corticosteroids in relieving nasal congestion, sneezing, postnasal drip and pruritus.A clinical trial comparing the efficacy of as-needed use of loratadine (oral H1 receptor antagonist) with fluticasone propionate (intranasal corticosteroid), showed superiority with the intranasal corticosteroid in the treatment of seasonal allergic rhinitis.

Oral steroids primarily affect the late-phase reaction and because of the risk of systemic effects (adrenal axis suppression, slowed bone growth in children, osteoporosis), should be reserved for patients with severe symptoms that are refractory to intranasal steroids. The corticosteroids of choice are prednisone or methylprednisolone for five to seven days of treatment. Oral steroids should be avoided in patients with hypertension, diabetes, glaucoma and peptic ulcer disease.

Table 4: Steroid Nasal Sprays for the Treatment of Allergic Rhinitis
Generic Name	Brand Name	Daily Dose/Nostril
Beclometasone dipropionate	Vancenase AQ Beconase AQ Beconase	1­2 puffs bid 1­2 puffs bid 1 puff tid
Budesonide	Rhinocort Rhinocort AQ	2 puffs bid 1­2 puffs qd
Flunisolide	Nasalide Nasarel	2 puffs bid 2 puffs bid
Fluticasone proprionate	Flonase	1­2 puffs qd
Triamcinolone acetonide	Nasocort Nasocort AQ	2 puffs 1­2 puffs qd
Mometasone furoate	Nasonex	2 puffs qd
Dexamethasone Na phosphate	Dexacort Tubinaire	1­2 puffs bid

Children

Oral antihistamines or nasal cromolyn remain first-line agents in the treatment of childhood allergic rhinitis. In 1998, the FDA reported that a few nasal corticosteroids might have a temporary adverse effect on growth in children; however, the long-term effects on growth remain unclear. For this reason, intranasal corticosteroids should be used in children at the lowest effective dose and height should be monitored routinely.

Pregnant Women

Oral antihistamines or nasal cromolyn remain first-line agents for allergic rhinitis during pregnancy. Oral decongestants should be avoided during the first trimester due to reports of abdominal wall defects to the fetus. Chlorpheniramine and tripelennamine are the preferred antihistamines and pseudoephedrine is the preferred decongestant. Intranasal corticosteroids may be used only if nasal cromolyn cannot adequately control allergic symptoms.

Pharmacologic Comparison of Agents and Stepwise Approach to Treatment

According to the guidelines developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, antihistamines should be used as first-line agents in mild to moderate rhinitis, whereas intranasal steroids should be used as first-line treatment in more severe disease. These guidelines have been challenged by a meta-analysis of randomized clinical trials that has demonstrated the superior efficacy and rapid relief of nasal symptoms with intranasal corticosteroids in mild to moderate rhinitis compared with oral antihistamines.In fact, a recently published clinical trial showed superiority of as-needed treatment with an intranasal corticosteroid when compared with an oral antihistamine. This suggests that intranasal corticosteroids should be considered first-line agents in treating mild, moderate and severe allergic rhinitis; therefore, a change in the stepwise pharmacologic treatment approach of allergic rhinitis would be beneficial. If symptoms remain uncontrolled with either an oral antihistamine or intranasal corticosteroid alone, combination therapy with these agents may provide additional relief. An oral decongestant, intranasal cromolyn or intranasal ipratropium should be added to therapy for symptoms unresponsive to combination oral antihistamine and intranasal corticosteroid.

All the intranasal corticosteroids are equally effective in controlling all of the allergic rhinitis symptoms.A review of the intranasal steroids currently available showed mometasone furoate and fluticasone propionate to have lower systemic bioavailabilities than the older steroids, which may reduce the potential for adverse systemic effects with prolonged use. A combination of antihistamine with a decongestant has been found to be superior in controlling allergic symptoms than either agent alone. Ipratropium is generally not recommended unless rhinorrhea is the only allergic symptom. Ipratropium and oral antihistamines are ineffective for nasal congestion, which can be treated with a decongestant or a nasal steroid. Cromolyn nasal spray is less effective than nasal steroids in relieving allergic rhinitis and patients may initially need antihistamines and/or decongestants due to the delayed onset of action of cromolyn. Finally, cromolyn is slower in controlling eye symptoms when compared with ocular antihistamines.

Immunotherapy is indicated for patients with symptoms for more than six months each year and who are unable to achieve symptomatic relief with environmental modification or pharmacotherapy. Immunotherapy is a slow and gradual process of injecting antigens responsible for eliciting allergic symptoms in a patient with the hope of increasing tolerance to the antigen. Immunotherapy works by activating specific suppressor T lymphocytes. This decreases IgE production, blunting the usual seasonal increase in IgE levels and reducing mast cell and basophil degranulation in response to allergen challenge, and producing IgG blocking antibodies. Skin testing to identify the offending allergen is a pre- requisite to immunotherapy.

Immunotherapy is initiated with weekly injections of small amounts of antigen. The amount of antigen and the length of time between injections are slowly increased. Maintenance injections are given once every three to four weeks. The most common side effect is a local swelling reaction at the injection site. Other, more serious reactions, such as generalized urticaria, bronchospasm and anaphylaxis, occur rarely. Immunotherapy is usually continued for at least 3 years provided there is symptomatic improvement after 6 months. About 80% to 85% of patients obtain long-lasting symptomatic relief during immunotherapy and 60% continue to derive symptom relief after immunotherapy is discontinued.

Mast Cell Stabilizers

Mast cell stabilizers inhibit both early- and late-phase allergic reactions by inhibiting allergen-induced degranulation and release of mediators from sensitized mast cells. They reduce nasal itching, sneezing, rhinorrhea and nasal congestion (Table 1); however, they do not relieve the effects of existing histamine. Therefore, treatment with intranasal cromolyn should be started prior to allergen exposure (1-2 weeks). Patients may need oral antihistamines and/or decongestants during the initial phase of cromolyn therapy as the agent can take three to seven days for relief of allergic symptoms. Cromolyn is well tolerated, with only mild nasal irritation and unpleasant taste; however, its major disadvantage is its frequent (four to six times per day) dosing requirements (Table 5). Pharmacists should instruct patients to blow their noses prior to taking the drug, as cromolyn must come into contact with the entire nasal membrane for optimal absorption.

Table 5: Other Nasal Sprays
Generic Name	Brand Name	Daily Dose/Nostril
Cromolyn	Nasalcrom	1 puff QID
Ipratropium Br	Atrovent	2 puffs TID
Azelastine HCL	Astelin	2 puffs BID

Anticholinergics

Cholinergic receptors are important in the production of nasal secretions. Ipratropium bromide, a topical anticholinergic agent, is effective in controlling watery rhinorrhea, and is particularly useful in the treatment of non-allergic or vasomotor rhinitis (Table 5).However, it has no effect on sneezing, nasal itching and nasal congestion. The most common side effects are headaches, nose bleeds, and nasal dryness which can be reduced with the use of a saline nasal spray.

Mucolytics

Mucolytics, such as guaifenesin, are used in allergic rhinitis to thin tenacious secretions. Prospective, blinded studies to demonstrate their efficacy in allergic rhinitis are lacking.

Ophthalmic Agents

Ocular symptoms of allergic rhinitis, including conjunctivitis and itchy, watery eyes, can be treated with ophthalmic antihistamine, decongestant, corticosteroid, mast cell stabilizer and nonsteroidal anti-inflammatory preparations. Some of the over-the-counter (OTC) products in Table 6 contain an antihistamine (i.e., pheniramine or antazoline) and a decongestant (i.e., naphazoline). These OTC antihistamines have limited efficacy compared with the prescription ophthalmic antihistamines, such as levocabastine, emedastine, ketotifen and olopatadine, which are more potent. Oxymetazoline has a faster onset of action and better decongestant effects than naphazoline or tetrahydrozoline. The main side effects are localized burning and stinging, followed by dry eyes and headache.

Table 6: Ocular Preparations
Drug	Dosage
Antihistamine
Levocabastine 0.05% (Livostin)	1 eye drop BID
Mast Cell Stabilizers
Lodoxamide trimethamine 0.1% (Alomide)	1 ­ 2 drops QID
Cromolyn 4% (Crolom)	1 ­ 2 drops 4 to 6 times a day
Nonsteroidal Anti-inflammatory
Ketoralac 0.5% (Acular)	1 drop QID
Decongestant/Antihistimine Combinations
Naphazoline 0.025%, Pheniramine 0.3% (Opcon-A), (Naphcon A)	1 ­ 2 drops every 4 hours up to 4 times a day
Naphazoline 0.05%, antazoline phosphate 0.5% (Vascon-A)	1 ­ 2 drops every 4 hours up to 4 times a day

Decongestants stimulate the alpha-adrenergic receptors in the vascular smooth muscle of the turbinates, leading to nasal mucosal capillary vasoconstriction and relief of nasal congestion. They have no effect on itching, sneezing, or rhinorrhea. Decongestants are available in oral and topical dosage forms (Table 3) The nasal preparations are more effective than the oral in relieving nasal congestion. However, when used for more than five consecutive days, rebound congestion (referred to as rhinitis medicamentosa) may occur, which is not seen with the oral agents.

With rebound congestion, the nasal mucosa becomes unresponsive to decongestants and the recommended substitute is an intranasal corticosteroid. Patients should be advised to use intranasal decongestants acutely for a few days and oral decongestants when therapy is required for more than five consecutive days.

Decongestants most commonly cause CNS stimulation (insomnia, dizziness, nervousness, agitation), increased blood pressure, tachycardia and urinary retention. These side effects are common with oral agents and can also be observed with the topical dosage forms at higher doses. Caution is advised when decongestants are used in patients with hypertension, glaucoma, prostatic hypertrophy, arrhythmias, diabetes, hepatic or renal impairment or hyperthyroidism. Hypertensive crisis can result from combining decongestants with monoamine oxidase inhibitors or tricyclic antidepressants.

Table 3: Topical and Oral Decongestants for the Treatment of Allergic Rhinitis
	Duration	Dose
Topical
Phenylephrine HCl	4 h	2 sprays q 4 h
Naphazoline HCl	4 – 6 h	2 sprays q 6 h
Tetrahydrozoline	4 ­ 6 h	2 sprays q 4 h
Oxymetazoline	12 h	2 sprays q 12 h
Xylometazoline	10 h	2 sprays q 8 h
Oral
Ephedrine Sulfate	4 h	25 ­ 50 mg q 4 h
Pseudoephedrine	4 ­ 6 h	60 mg q 4- 6 h
-SR	12h	120 mg q 12h

Greater understanding of both the etiology and pathophysiology of allergic rhinitis has made it possible to target patient-specific symptoms with therapy. Pharmacologic agents, including antihistamines, decongestants, corticosteroids, mast cell stabilizers, anticholinergics and mucolytics, differ in their effectiveness for controlling allergic symptoms (Table 1). If it is possible to anticipate the onset of allergic symptoms, such as in seasonal rhinitis, medications should be initiated prophylactically.

Antihistamines

Antihistamines have been used in the treatment of allergic rhinitis due to their efficacy in blocking H₁ histamine receptors. Oral H₁ antagonists block the early- but not the late-phase allergic reaction; therefore, they are effective in controlling sneezing, pruritus, rhinorrhea, and ocular symptoms, but ineffective in alleviating congestion. Antihistamines are appropriate for patients with sporadic symptoms due to their rapid onset of action (within 30 minutes). Since antihistamines do not relieve the effects of existing histamine, they should be administered prior to allergen exposure for best results.

Table 1: Comparison of Pharmacologic Agents in Relief of Allergic Symptoms
Medication	Sneezing	Rhinorrhea	Nasal Congestion	Nasal Itching	Ocular Symptoms	Post-nasal Drip
Antihistamines
First Generation	++	++	O	++	++	O
Second Generation	++	O	O	++	++	O
Decongestants	O	O	++	O	O	O
Cromolyn Sodium	+	+	+	+	O	O
Steroids
Nasal	++	++	++	++	+	+
Oral	++	++	++	++	++	++
Ipratropium	O	+	O	O	O	O
Mucolytics	O	O	O	O	O	++
O – no effect on symptoms + – moderate effect on symptoms ++ – major effect on symptoms

First-generation Antihistamines

Although there is little difference among the first-generation agents in terms of clinical efficacy, some clinical studies have found chlorpheniramine and hydroxyzine more effective than other first-generation antihistamines.The first-generation antihistamines cross the blood-brain barrier, resulting in sedation, drowsiness, dizziness, confusion, and slowed reaction time. They also have anticholinergic side effects such as dry mouth, urine retention, constipation, and blurred vision. The severity of these adverse effects varies (Table 2), and sedation is not experienced by all users and may diminish as tolerance develops. Because of their anticholinergic and sedative side effects, first-generation antihistamines should be avoided in the elderly and in patients with narrow angle glaucoma or prostatic hypertrophy.Pharmacists should warn patients that the sedative effects are enhanced with the use of other central nervous system depressants, such as alcohol and sedatives. Patients should be encouraged to check with their pharmacist before taking nonprescription medications, as a number of cough and cold products contain alcohol. In an effort to minimize the adverse effects of the first-generation antihistamines, the second-generation agents were developed.

Table 2: Relative Sedative and Anticholinergic Side Effects of Antihistamines
	Daily Dose	Sedative	Anticholinergic
First Generation
Diphenhydramine	25-50 mg q 8 h	+++	+++
Clemastine Fumerate	1.34 mg q 12 h	++	+++
Chlorpheniramine Maleate		+	++
Immediate Release	4 mg q 6 h
Sustained Release	12 mg q 12 h
Second Generation
Fexofenadine	60 mg q 12 h	O	O
Loratadine	10 mg qd	O	O
Cetirizine	10 mg qd	O	O
O – None + – Low ++ – Moderate +++ – High

Second-generation Antihistamines

Second-generation antihistamines are cetirizine, fexofenadine and loratadine. In contrast to the first-generation agents, the second-generation antihistamines are highly selective peripheral histamine H₁-receptor antagonists. They do not readily cross the blood-brain barrier and do not bind to muscarinic cholinergic receptors. Thus, they are not associated with anticholinergic side effects or sedation (Table 2) at recommended doses (except for cetirizine, with 12% incidence of sedation).

Although the second-generation antihistamines are not more effective than the first-generation, they should be used preferentially due to a more favorable side effect profile and increased safety. The first-generation antihistamines have been associated with decreased work and academic performance, as well as higher risk of occupational and automobile accidents. In an attempt to minimize sedation, second-generation agents were given in the morning followed by the first-generation agents in the evening. However, studies showed that there was significant daytime sedation even when the first-generation antihistamines were dosed in the evening.

Intranasal Antihistamine

In contrast to oral antihistamines, azelastine may reduce nasal congestion. This agent is generally less effective than nasal corticosteroids in relieving nasal symptoms (rhinorrhea, sneezing, nasal pruritus). In clinical practice it is used either as first-line treatment for the symptoms of allergic rhinitis, or in conjunction with oral antihistamine or nasal corticosteroid therapy. Intranasal azelastine may cause sedation due to significant systemic absorption, and patients should be warned of the potential for drowsiness (11%) and bitter taste (20%).

The most effective method for controlling allergic rhinitis is to avoid allergen exposure; therefore, environmental control measures aimed at reducing concentrations of pollen, dust mites, mold and animal dander should be first-line therapy. Reducing pollen exposure by closing windows and doors, and utilizing air conditioners and limiting outdoor activities during high pollen season are important. Dust mites and their feces can be kept low with thorough cleaning and use of dehumidifiers to maintain humidity below 50%. The following measures will also minimize exposure to allergens:

• Carpets must be vacuumed frequently, and should be removed from the bedroom. Comforters and bedspreads should be vacuumed with a machine that has a high efficiency particulate air (HEPA) filter.
• The mattress, pillows and boxspring should be encased with plastic backings, frequently cleansed to prevent the accumulation of dust and dust mites.
• Bedding should be washed in hot water (>130º F) at least every two weeks to kill the ova and remove mites and pollen.Periodic airing for 10 minutes and sun exposure will kill dust mites in bedding, drapes and rugs.Foam instead of feather pillows should be used.
• Windows should be covered with washable curtains or shades instead of Venetian blinds, as these are excellent dust catchers. All blinds should be frequently washed.
• A HEPA filter in the bedroom can help keep the air clean, and the use of a dehumidifier can help reduce humidity during humid months, to reduce the growth of dust mites and indoor molds.
• Basements and cold outside walls promote mold growth and should be avoided by mold-sensitive individuals. Cooling systems should also be checked periodically for mold growth.
• Household plants should be eliminated from the bedrooms as their soil may be a rich source of mold, and storage of firewood inside the house should be avoided, as mold is present in the bark of wood.
• A face mask should be used during indoor and outdoor activities to avoid increased exposure to dust, mold and pollen (vacuuming, mowing, threshing).
• If a pet at home is the cause of the allergic symptoms, the pet should be kept out of the bedroom, and, if possible, away from carpeted areas. (Removing carpets altogether is best.) Applying special sprays can help control antigens from pets.Immunotherapy also has proven helpful in patients with allergies to pet dander.

Allergic rhinitis refers to inflammation of the nasal membrane caused by exposure to inhaled antigens. The sixth most prevalent condition in the United States, it affects 20% or 40 million Americans (10%-30% of adults and up to 40% of children) each year. Patients 18 to 44 years of age are most commonly affected, as the prevalence of allergic rhinitis increases throughout childhood and peaks in the late second and third decades of life. The estimated annual direct costs are 4.5 billion dollars and the indirect costs related to absenteeism and productivity loss from work and school are 3.8 million dollars. If severe allergic rhinitis is not properly treated, it can lead to asthma, rhinosinusitis and otitis media.

Allergic rhinitis is an immunologic response characterized by symptoms of sneezing, rhinorrhea, nasal congestion, post-nasal drip due to posterior drainage of mucus hypersecretion, and pruritic eyes. A combination of strategies involving environmental modification and pharmacologic management should be used to provide symptomatic relief. The guidelines developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology have been challenged by recently published clinical trials suggesting a change in the stepwise approach to pharmacologic treatment. With less than 15% of symptomatic patients seeking treatment from a physician, pharmacists are in a key position to identify patients with allergic rhinitis, address environmental factors, target pharmacologic therapy to patient-specific symptoms and prevent complications from allergic rhinitis.

Allergic rhinitis can be divided into seasonal and perennial forms, based on the time of symptom onset and duration. In seasonal allergic rhinitis, the nasal and ocular symptoms, such as tearing and conjunctivitis, occur during well-defined seasons. Perennial allergic rhinitis refers to allergy symptoms that persist most of the year because of allergy to antigens present year-round. Other conditions that mimic signs and symptoms of allergic rhinitis include benign and malignant tumors, nasal septal deviation, nasal polyps and pregnancy.

Pathophysiology

The induction and elicitation of the allergic response can be divided into an immediate- and a late-phase reaction. The immediate reaction occurs within minutes as allergens enter the body through inhalation and interact with T-cell and B-cell lymphocytes to produce IgE antibodies. These antibodies will then attach to mast cells and basophils. Upon re-exposure to the same allergen, the mast cell- and basophil-bound IgE cross-link, leading to degranulation of mast cells and release of preformed mediators (histamine, leukotrienes, prostaglandin and bradykinin). The clinical responses to these inflammatory mediators are rhinorrhea, sneezing, itching and vascular engorgement resulting in nasal congestion.Four to 24 hours later, a late-phase inflammatory reaction follows via migration and activation of inflammatory cells, including eosinophils, neutrophils, macrophages, basophils and monocytes in the nasal mucosa. The patient experiences renewed allergic symptoms (worsening nasal secretions and congestion) without additional allergen exposure.

Allergens

Seasonal: Pollens and outdoor mold spores most frequently cause seasonal allergic rhinitis; the most troublesome allergen in North America is ragweed pollen. Tree pollen occurs predominately in April to May, grass pollen in May to June, and ragweed pollen in August to October. Outdoor mold spores occur in soil, water and rotting matter, and are released into the air when lawns are disturbed by mowing of grass and by raking of leaves. The spores are ubiquitous, stay airborne over long periods, and are most prominent from July through November.

Perennial: Perennial allergic rhinitis is caused by indoor allergens, such as house dust mites, animal dander, cockroaches and indoor mold spores. Dust mites thrive in humidity >50% and damp conditions within the home encourage the growth of indoor molds, particularly Cladosporium and Penicillium.