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FOOD HYPERSENSITIVITY AND ECZEMA 

Atopic dermatitis is one form of eczema, which begins in early infancy and is characterized by extreme pruritus, chronically relapsing course, and distinctive distribution. Atopic dermatitis is typically the first manifestation of a child prone to develop atopic disease, with 50% of all atopic dermatitis developing in the first year of life and 80% by 5 years of age. Approximately 80% of children with atopic dermatitis develop asthma or allergic rhinitis, with many losing their atopic dermatitis (AD) with the onset of respiratory allergy. The acute rash of AD is typically an erythematous, papulovesicular eruption, frequently with 

FOOD HYPERSENSITIVITY AND ATOPIC DERMATITIS

Food hypersensitivity has a pathologic role in many children with atopic dermatitis. To establish the causative association between food hypersensitivity and AD, clinical studies have been performed to address t demonstrate that removal of the causative agent leads to resolution of the disorder; introduction of the causative agent provokes the disorder; and avoidance of the causative agent prevents the disorder. As with other chronic, atopic disorders (e.g., asthma), a variety of factors

The therapeutic effect of removing foods to which children with AD are allergic has been addressed in a number of studies. Atherton et al reported that two thirds of children with AD between the ages of 2 and 8 years showed marked improvement during a double-blind cross-over trial of egg and milk exclusion. The trial was conducted over a 12-week period in the patients' homes. Unfortunately, 45% of the patients enrolled in this study dropped out or were excluded from analysis,

Allergic reactions to foods were very specific. Although patients frequently had positive skin tests [and RASTs] to several members of a botanical family or animal species, indicating immunologic cross-reactivity, the frequency of patients experiencing symptomatic intra-botanical or intra-species cross-reactivity is variable. Legume cross-reactivity was evaluated in 69 children with AD utilizing prick skin tests, in vitro measurements of specific IgE antibodies (immunodot blot) and Western blot analysis. Extensive immunologic cross-reactivity was demonstrated in skin prick tests, RASTs, and immunoblots in most patients; however, only 2 patients were symptomatic to more than one legume when challenged orally. Both patients had a history of severe allergic reactions to peanut and experienced mild reactions to a soy challenge, and both outgrew their reactivity to soy within 2 years. Similar studies with cereal grains showed significant IgE antibody cross-reactivity between grains (wheat, barley, rye, oat) and grass pollens but clinical cross-reactivity among the grains in only about 20% of patients. Although intra-species immunologic cross-reactivity is common, approximately 5% of egg-allergic children reacted to chicken, and about 10% of milk-allergic children reacted to beef. Consequently, the practice of avoiding all foods within a botanical family when one member is suspected of provoking allergic symptoms appears to be unwarranted. Interestingly, 90% of children allergic to cow's milk react to goat's milk, and approximately 40% of children reacting to beef also react to lamb.


TABLE 3 -- FOODS RESPONSIBLE FOR 80% OF POSITIVE CHALLENGES IN 470 PATIENTS WITH ATOPIC DERMATITIS
Food Positive Challenge Positive History Total %
Egg 178 35 213 57
Milk 96 47 143 38
Peanut 28 82 110 29
Soy 55 4 59 16
Wheat 43 0 43 11

Children with AD and newly diagnosed food hypersensitivity were found to have high spontaneous basophil histamine release (SBHR) from peripheral blood

A number of investigators have evaluated the effect of excluding dietary allergens on the development of AD in young infants. In the 1930s Grulee and Sanford were first to report a decrease in the incidence of AD in breastfed infants.  Since that time there have been numerous conflicting reports about the relative benefit of breast feeding infants to prevent or delay the onset of atopic disease. The potential benefit of breastfeeding is complicated by transmission of food antigens in maternal breast milk. We evaluated six exclusively breastfed infants (age 2.5 to 6 months) who developed classic infantile AD. Each infant had a positive prick skin test to egg and experienced complete clearing of eczematous lesions when their mothers totally eliminated egg-containing foods from their diet. Four of the six infants were challenged on a clinical research unit by first feeding their mothers eggs and then having their mothers breastfeed. All infants developed an eczematous rash 4 to 36 hours after their mothers ingested eggs. This evidence and findings from other studies support the practice of placing selected mothers on

In a prospective, randomized allergy prevention trial, Zeiger et al compared the benefits of maternal and infant food allergen avoidance on the prevention of allergic disease in infants at high risk for allergic disease. Breastfeeding was encouraged in both prophylaxis and control groups. In the prophylaxis group, mothers eliminated egg, milk, and peanut from their diets, a casein hydrolysate formula was utilized for supplementation or weaning, and solid foods were delayed until 6 months. In the control group, mothers' diets were unrestricted, infants received cow milk formula for supplementation or weaning, and the American Academy of Pediatrics

In families at high risk for atopic disorders, however, it would seem prudent to avoid exposing young infants to food allergens that provoke lifelong sensitization (e.g., peanuts, nuts, fish, or shellfish) for the first 2 to 3 years of life. In highly motivated "high-risk" families, avoidance of cow's milk for the first year and egg for the first 2 years may prevent some AD and food allergy. Mothers of high-risk infants might also be prudent to avoid peanuts, nuts, fish, and shellfish while breastfeeding and perhaps even during the third trimester of pregnancy because these foods do not generally comprise a major part of the diet. Whether it is beneficial for all lactating mothers in high-risk families to avoid milk and eggs remains

DIAGNOSIS OF FOOD HYPERSENSITIVITY IN PATIENTS WITH ATOPIC DERMATITIS

The double-blind placebo controlled oral food challenge remains the gold standard for diagnosing food hypersensitivity in chronic atopic disorders, such as AD. In the typical office practice, however, a careful history and evidence of food antigen-specific IgE antibodies (prick skin tests, RASTs) may indicate foods that can be eliminated for a 2- to 3-week dietary trial. Symptoms may be recorded in a diary during the trial period. If unequivocal improvement is documented, foods believed to be least likely to be responsible for reactions (e.g., foods other than egg, peanut, milk, soy, and wheat) are added back to the diet; however, any food suspected of causing a severe anaphylactic reaction should never be administered at home because of the potential for inducing anaphylactic shock. If a clear deterioration in the patient's AD occurs when a food is added back, it should be removed from the diet. If cause and effect can be established, the patient should remain on the avoidance diet unless it requires elimination of more than one major food (egg, milk, soy, or wheat) or two or more minor foods (all others). If severe symptoms persist on the

A recent study compared the results of DBPCFCs in 196 children and adolescents with AD to the concentrations of food-specific IgE antibodies determined with the Pharmacia CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) (reported in kU/L). Levels of food-specific IgE indicating the positive (PPV) and negative (NPV) predictive values for the test were calculated based on the outcome of the challenges. For egg, milk, peanut, and codfish allergies, diagnostic levels were

TABLE 5 -- POSITIVE PREDICTIVE VALUE AND NEGATIVE PREDICTIVE VALUE OF FOOD-SPECIFC IgE CONCENTRATIONS (kU/L) FOR PREDICTING REACTIONS UPON ORAL CHALLENGE

> 95% PPV > 90% PPV > 95% NPV > 90% NPV
Egg  6 2 -- 0.6
Milk 32 23 0.8 1
Peanut 15 9 Best NPV =85% at <0.35 kU/L
Fish 20 9.5 0.9 5
Soy Best PPV =50% at 65kU/L
2 5
Wheat Best PPV =75% at 100kU/L
5 79
PPV = positive predictive value; NPV = negative predictive value.
*There was no relationship between IgE level and severity.

or 95% PPV because many of these patients would still react to the food in question.

MANAGEMENT OF FOOD HYPERSENSITIVITY IN PATIENTS WITH ATOPIC DERMATITIS

Once food hypersensitivity is diagnosed, therapy consists of placing the patient on a diet completely eliminating all forms of the offending food allergen. Instructing the patient and family to read food labels to avoid hidden sources of the suspect food and to avoid potential sources of allergen contamination is 

MILK: Artificial butter flavor, butter, butter fat, buttermilk, casein, caseinates (sodium, calcium, etc.), cheese, cream, cottage cheese, curds, custard, Half & Half, hydrolysates (casein, milk, whey), lactalbumin, lactose, milk (derivatives, protein, solids, malted, condensed, evaporated, dry, whole, low-fat, non-fat, skim), nougat, pudding, rennet casein, sour cream, sour cream solids, sour milk solids, whey (delactosed, demineralized protein concentrate), yogurt. MAY be contained in brown sugar flavoring, natural flavoring, chocholate, caramel flavoring, high protein flour, margarine, Simplesse.
 
EGG: Egg (white, yolk, dried, powdered, solids), egg substitute, eggnog, globulin, livetin, lysozyme, mayonnaise, meringue, ovalbumin, ovomucin, ovomucoid, Simplesse.
 
WHEAT: Bread crumbs, bran, cereal extract, cracker meal, enriched flour, farina, gluten, graham flour, high gluten flour, high protein flour, malt, vital gluten, wheat bran, wheat germ, wheat gluten, wheat starch, whole wheat flour, spelt. MAY be contained in gelatinized starch, hydrolyzed vegetable protein, modified food starch, modified starch, natural flavoring, soy sauce, starch, vegetable gum, vegetable starch.
 
SOY: Hydrolyzed vegetable protein, miso, shoyu sauce, soy (flour, grits, nuts, milk, sprouts), soybean (granules, curd), soy protein (concentrate, isolate), soy sauce, textured vegetable protein (TVP), tofu. MAY be contained in hydrolyzed plant protein, hydrolyzed soy protein, hydrolyzed vegetable protein, natural flavoring, vegetable broth, vegetable gum, vegetable starch.
 
PEANUT: Cold pressed peanut oil, ground nuts, mixed nuts, Nu-Nuts artificial nuts, peanut, peanut butter, peanut flour. MAY be contained in African, Chinese, Thai, and other ethnic dishes, baked goods (pastries, cookies, and so forth), candy, chili, chocholate candy, egg rolls, hydrolyzed plant protein, hydrolyzed vegetable protein, marzipan, nougat.

A major reason that dietary management fails in food-allergic patients is because of inadequate patient instruction by the treating physician. Helpful information may be obtained from the 

NATURAL HISTORY OF FOOD HYPERSENSITIVITY IN ATOPIC DERMATITIS

Approximately one third of children with AD and food allergy will lose (or outgrow) their clinical reactivity to food over 1 to 3 years. Three factors appear to be important in determining the probability of patients losing their clinical reactivity: the food to which the patient is allergic (i.e., patients allergic to peanuts, nuts, fish, and shellfish are not likely to lose their clinical reactivity, whereas those allergic to soy, wheat, milk, and egg are much more likely to develop clinical tolerance); the level of specific IgE antibody to a particular food (i.e., the higher the level of food antigen-specific IgE, the less likely that clinical tolerance will develop in the subsequent few years), and the degree to which the patient adheres to the elimination diet (i.e., patients ingesting small amounts of allergen or having frequent accidental ingestions are less likely to develop clinical tolerance). Prick skin test results do not correlate with loss of clinical reactivity and may remain positive for many years after the food has been re-introduced into the diet. It is recommended that patients be re-challenged at set intervals (e.g., egg: every 2-3 years; milk, soy, and wheat: every 1-2 years; foods other than peanut, nuts, fish, and shellfish: every 1-2 years) to determine whether their food allergy persists. To