Texas Allergy Experts
texasallergyexperts.com

The role of Allergy in Eczema and Atopic Dermatitis

(Note this work is written for experts in the field by one of the leaders in food allergy, Jonathan Spergel MD and extracted from Uptodate SUMMARY

●Although there has been some controversy with regard to the role of allergy in atopic dermatitis (eczema), the bulk of the data indicate that allergy plays a role in selected patients with AD.  

●Infants and young children with AD are more commonly sensitized to foods, whereas children over five years and adults are more commonly sensitized to aeroallergens. However, evidence of allergen sensitization is not proof of clinically relevant allergy.  

●In patients with AD, the rate of sensitization to foods (positive skin or in vitro test) ranges from 30 to 80 percent, depending upon the population. The rate of confirmed food allergy is much lower. Food allergies play a role in exacerbating AD in up to 33 percent of patients with severe AD, 10 to 20 percent with moderate AD, and 6 percent with mild AD. Elimination of food allergens in patients with AD and confirmed food allergy can lead to significant clinical improvement.  

●Foods should not be eliminated from the diet randomly without any clinical suspicion. Nor should foods be excluded from the diet long term (as opposed to short term for diagnostic purposes) based upon positive skin or in vitro tests or patient history alone. Test results should be correlated with the clinical history and clinical reactivity confirmed when necessary by double-blind, placebo-controlled food challenge (DBPCFC) or elimination/challenge test.  

●The data on the role of aeroallergens in exacerbating AD are less extensive. Dust mites are consistently the most common positive aeroallergen, and also appear to be the most clinically relevant. Immune reactions, both immunoglobulin E (IgE) and T cell mediated, to Malassezia species can also worsen AD.  

INTRODUCTION — There is some controversy with regard to the role of allergy in atopic dermatitis (eczema). Some clinicians believe that allergic responses to aeroallergens are a rare cause of exacerbations of atopic dermatitis (AD) and that food allergy is generally not a factor. Other clinicians believe that allergy plays a strong role in exacerbating AD in some patients   They believe that food allergies trigger symptoms primarily in young children and environmental allergens play a greater role in older children and adults.

Despite its name, AD itself is not   necessarily associated with allergic sensitization. However, overall, the data indicate that allergy plays a role in selected patients with AD.

 

ATOPIC ASSOCIATIONS — Patients with atopic dermatitis (AD) have higher rates of allergic diseases than the general population. Up to 80 percent of children with AD develop asthma and/or allergic rhinitis later in childhood  . The converse is true as well. A higher rate of AD is seen in teenagers with asthma than those without asthma (risk ratio [RR 4.5, 95% CI 3.1-6.5)  . Ten to 20 percent of patients with AD have food-induced urticaria/anaphylaxis  compared with 1 to 3 percent of the general population   In infants with eczema, the prevalence of the allergic antibody immunoglobulin E (IgE)-mediated food allergy confirmed by double-blind, placebo-controlled food challenge (DBPCFC), except in patients with a history of anaphylaxis and positive specific IgE, ranges from 33 to 63 percent  . Earlier onset (<3 months of age) and more severe AD is associated with high egg, milk, and/or peanut-specific IgE  Patients with AD and concomitant egg, peanut, or dust mite allergy are more likely to have AD that persists beyond five years of age .

AD is also associated with elevated serum IgE. A high total serum IgE level is a strong risk factor for AD in children from birth to six years of age  . Interleukin-13 (IL-13) variants are associated with slightly higher total IgE levels and sensitization to food allergens, most commonly hen's egg, in young children with AD . In adults, elevated total IgE is associated with persistent eczema with a wide distribution after 10 years of follow-up  .

ALLERGEN SENSITIZATION — Numerous studies have demonstrated an increased rate of sensitization to both food and aeroallergens in patients with atopic dermatitis (AD) . On average, 50 percent of children and 35 percent of adults with AD are sensitized to common allergens. However, these proportions vary widely (7 to 78 percent)  .

Evidence of allergen sensitization is not proof of clinically relevant allergy. Confirming clinical reactivity is especially important when food allergies are suspected in young children, since avoidance of food allergens can put growing children at nutritional risk

Infants and young children with AD are more commonly sensitized to foods (wheat and egg sensitization are most prevalent)  . Children over five years and adults are more commonly sensitized to aeroallergens (dust mite sensitization is most prevalent in both children and adults) . A higher rate of dust mite sensitization in patients with AD is also seen with atopy patch testing (APT)  

Several studies have compared allergic sensitization patterns in patients with AD from different countries. The findings demonstrate a wide variability in sensitization patterns between countries and confirm that allergic sensitization is associated with higher socioeconomic status:

●In the International Study of Asthma and Allergies in Childhood (ISAAC), 28,591 children aged 8 to 12 years from 20 countries were examined for flexural eczema and skin tested to at least six common aeroallergens  . The point prevalence of AD ranged from <1 to 14 percent. The percentage of children who had at least one positive skin prick test ranged from 0 to 74 percent. The association of AD and allergic sensitization was stronger in affluent versus nonaffluent countries (odds ratio [OR 2.69, 95% CI 2.31-3.12 versus 1.17, 0.81-1.70).

●Similar findings were seen in a study of five- to six-year-old children with AD and allergic sensitization in East and West Germany  . Only 36 percent of children with AD in East Germany were skin prick test-positive to at least one food or inhalant allergen, compared with 50 percent of children with AD in West Germany.

●In a randomized early prevention trial for asthma, baseline evaluation of 2184 infants with AD from atopic families included total serum immunoglobulin E (IgE) and specific IgE to eight food and inhalant allergens  . A total of 53 percent of infants had IgE ≥30 kU/L, with the percentage ranging from 35 to 67 percent in 12 different countries. Ninety-six percent of the infants had complete specific IgE results. Over half of these infants were sensitized (specific IgE ≥ 0.70 kU/L); 19 percent, monosensitized; and 37 percent, polysensitized. Nearly one-half were sensitized to at least one food and one-third were sensitized to one or more inhalant allergens (egg white, 42 percent; cow's milk, 27 percent; peanut, 24 percent; house dust mite, 21 percent; cat dander, 13 percent; tree pollen, 8 percent; grass pollen, 8 percent; and Alternaria, 4 percent). Rates of specific allergen sensitization varied widely between countries. As an example, the rate of egg white sensitization was 54 percent in Australia and 23 percent in Belgium.

FOOD ALLERGIES — Two types of dermatologic manifestations are believed to be associated with food allergies: urticaria/anaphylaxis and food-exacerbated atopic dermatitis (AD). Only the second type of reaction is examined here.  

In food-exacerbated AD reactions, ingestion of the food acutely is thought to cause a flare of the patient's AD (increased erythema and pruritus of eczematous lesions)   The flare occurs within minutes to a few hours if the reaction is immunoglobulin E (IgE) mediated, but may take hours to days if the reaction is non IgE mediated. The patient has persistent lesions if the food is eaten chronically.  

The diagnosis of food allergy involves two steps: identification of the food sensitization and confirmation of clinical allergy  . Identification involves history taking and allergy testing. Patients are unlikely to have food allergies as a trigger of their severe AD if they have periods of clear skin on a regular diet without medication. Food allergy is a more likely trigger if the onset or worsening of AD correlates with exposure to the food. Infants with AD and food allergy may have additional findings that suggest the presence of food allergy, such as vomiting, diarrhea, and failure to thrive  

Food allergy can be evaluated by either prick skin testing or in vitro testing for food-specific IgE. Eosinophilia may be a predictor of food allergy in patients with AD  The diagnostic utility of patch testing for foods in patients with AD is under investigation and is discussed in detail separately.  

In patients with AD, the rate of sensitization to foods ranges from 30 to 80 percent, depending upon the population, but the actual rate of confirmed food allergy is much lower  . As an example, 52 percent of children in a birth cohort who developed AD during the first six years of life were sensitized to at least one food allergen, but only 15 percent had challenge-confirmed food allergy  . Wheat was the most common food to which patients were sensitized, but egg was the most common food to which patients were allergic, as confirmed by food challenge.

Most patients with food sensitization and AD fall into a gray area in which the test is neither negative nor above the 95 percent positive predictive value (PPV). Other patients may have suspected non IgE-mediated food allergy, for which no standardized diagnostic tests are available. Food challenges need to be performed in these cases to confirm clinical reactivity to the food(s) in question and prevent malnutrition from inappropriate food avoidance  

Clinical reactivity can be confirmed by double-blind, placebo-controlled food challenge (DBPCFC) for suspected IgE-mediated allergy or reproducible findings upon elimination and reintroduction of the food for suspected non IgE-mediated allergy. There is a risk of a more severe reaction, including anaphylaxis, when foods are reintroduced  . The rate of food-exacerbated AD varies with the severity of the eczema. Approximately 1 to 3 percent of children with mild AD, 5 to 10 percent with moderate AD, and 20 to 33 percent with severe AD have food-induced AD [35. Food-exacerbated AD is rare in adults. (

The following studies are illustrative:

●A subset of patients with AD (22 percent) was identified in a birth cohort of 512 children followed until two years of age  . The children with AD were evaluated for food allergy. Food allergy was diagnosed based upon a history of an immediate reaction to a food allergen and a positive skin prick test/specific serum IgE or a history of suspected food allergy with no immediate reaction and either an open elimination/challenge test (performed twice, considered allergic if positive both times) or a DBPCFC.

Thirty-two percent of children in the above study were sensitized to at least one allergen [31. However, clinical reactivity was confirmed in only 18 percent. Two children developed AD after they had developed tolerance to the food. The rest of the children (16 percent) developed AD and adverse reactions to food simultaneously and were considered to have food-exacerbated AD. Six children had non IgE-mediated cow's milk allergy only. Eight children had IgE-mediated food allergy. The mean SCORAD (SCORing Atopic Dermatitis) index, a measure of AD severity, was higher in children with non IgE or IgE-mediated food allergy than children without food allergy (28 and 30 versus 20, respectively).

●Other studies have reported similar findings with regard to the frequency of food-induced AD reactions in relation to the severity of AD. Food allergies play a role in exacerbating AD in up to 33 percent of patients with severe AD, 10 to 20 percent with moderate AD, and 6 percent with mild AD  

●In another birth cohort study, 22 percent (122 of 562) of children had AD. Fifteen percent (18 of 122) were confirmed to have food allergy (by skin prick test, specific IgE, and food challenge). Most children were also sensitized to other foods that they tolerated. Self-reported food allergy was confirmed in less than one-third of cases.

●In a study of 3- to 15-year-old patients with AD and suspected food allergies, 75 percent (52 of 69) had positive challenges (average two foods, range one to three), based upon comparing pre- and post-challenge photographs of representative skin lesion sites . Most patients had negative-specific IgE to the challenge-positive foods. Exclusion of these foods from the diet for three months led to significant clinical improvement.

●A meta-analysis showing lack of benefit of exclusion diets in patients with AD is held up by some as evidence of lack of a role for food allergy in AD  . However, 9 out of 10 of the randomized trials in this meta-analysis enrolled patients with AD who were not selected for a suspicion of food allergy based upon clinical history and/or test results. The single trial that did select for patients with suspected food allergy (positive specific IgE to egg and suspected egg allergy) demonstrated that an egg elimination diet led to improvements in the extent and severity of AD in half of infants with AD.

Food elimination diets — The findings above highlight that foods should not be eliminated from the diet randomly without firm clinical suspicion. Nor should foods be excluded from the diet long term (as opposed to short term for diagnostic purposes) based upon positive skin or in vitro tests or patient history alone.

Test results should be correlated with the clinical history and clinical reactivity confirmed when necessary by DBPCFC or elimination/challenge test. Elimination of food allergens in patients with AD and confirmed food allergy can lead to significant clinical improvement. Patients should be evaluated at regular intervals to determine if the food allergy has resolved.  

ENVIRONMENTAL ALLERGIES — There are less data on the role of environmental allergies in atopic dermatitis (AD) compared with food allergies. The data available suggest that environmental allergens are a trigger of AD in a small subset of children and adults. Patients who have environmental allergies as a trigger of AD have persistent disease with chronic exposure to an allergen in the environment.

Aeroallergens — Exposure to aeroallergens may occur by inhalation or by direct skin contact.

There are several lines of evidence that support the concept that immune responses in AD skin can be elicited by aeroallergens in sensitized patients:

●In one study of schoolchildren, sensitization to aeroallergens, particularly cat and dust mite, correlated with disease severity   These children had persistent AD on areas of exposure (eg, on areas of their arms not covered by a shirt).

●A small study of adults with AD demonstrated that exposure to grass pollen in an environmental challenge chamber for two consecutive days resulted in a significant worsening of AD (increased SCORAD [SCORing Atopic Dermatitis scores and itch intensity) compared with exposure to clean air (placebo) [40.

●Atopy patch tests (APT) to aeroallergens elicit delayed-type eczematous reactions on uninvolved skin in 40 to 85 percent of patients with AD  Rates of positive APT are generally lower in young children with mild AD and higher in older children and adults with moderate to severe AD. Positive APT reactions are also more frequent in patients that have AD in an air-exposed distribution pattern. However, APT results do not always correlate with disease extent, severity, or localization [45. Dust mites are consistently the most common positive aeroallergen and also appear to be the most clinically relevant  

●Intranasal and bronchial challenges with aeroallergens cause pruritus and flare up of AD lesions in some patients with AD  .

●Effective measures to reduce house dust mite allergen lead to modest improvement in AD in patients with sensitization to one or more aeroallergens  

●T cells that selectively respond to Dermatophagoides pteronyssinus (Der p 1) and other aeroallergens have been isolated from AD skin lesions and allergen patch test sites  

An additional line of evidence in support of the role of environmental allergies in AD is that therapies used for other atopic diseases are also effective in AD. Dust mite subcutaneous immunotherapy in adults with chronic moderate AD improved eczema severity scores and reduced use of topical glucocorticoids  Anti-immunoglobulin E (IgE) (omalizumab) therapy improved AD in patients with concomitant asthma  .)

Malassezia — Malassezia yeast is part of the normal cutaneous microflora and is found predominantly in lipid-rich areas, such as the head and neck. Immune reactions, both IgE and T cell mediated, to Malassezia species can also worsen AD   IgE specific to Malassezia has been found in adolescent and adult patients with refractory head and neck AD. These patients may respond to antifungal therapy (eg, a one- to two-month course of daily itraconazole orketoconazole followed by long-term weekly treatment). In addition, topical calcineurin inhibitors may inhibit the growth of Malassezia.