Management of atopic dermatitis: practical guidelines suggested by the conclusion of systematic assessment in 500 children

Allergic management of AD may be worthwhile since allergy may trigger the disease. A systematic evaluation of sensitizations overtime and study of their clinical involvement in 500 children with AD was carried out, including minor, moderate, and severe patients (defined by clinical scores). Standardized methods assessed the possibility of contact dermatitis as well as IgE dependant allergies. Contact dermatitis concerned fragrances and nickel. Contact dermatitis was observed in minor and moderate AD with a progressive increase: 11% of children under 2 years and 58% in those over 15 years of age. Later in older children, sensitization to cosmetics and occupational allergens occurred in close connection with the specific environment. As for IgE sensitization, investigation should be electived advised in moderate and severe AD. Inhalant allergen sensitization was observed in 66% in moderate AD and 93% in severe AD in the group of 7 or 15 years. Clinical confrontation was a better indicator of cutaneous involvement than atopen patch-test. It mainly concerned respiratory symptoms. In severe AD, food allergy was constantly observed and presented as a marker for severe atopic dermatitis. The main trophallergen differ according to the age and cultural habits: in children under 2 years of age, eggs, peanuts, milk, fish were the main offending agents. Later, main trophallergens were wheat flour, shellfish. Although spontaneous decrease of food allergy is sometimes observed, it must be pointed out that food allergy may still persist as a triggering factor in teenagers as well as in adult-hood. The allergologic diagnosis of atopic dermatitis should not focus on IgE dependent sensitization without patch testing.     

Aliments et dermatite atopique

Food allergy plays a pathogenetic role in subset of patient with atopic dermatitis, as proven over the past decade by laboratory and clinical investigations. Likely 40% of infants and young children may present with food allergy, whatever the severity of atopic dermatitis. The identification of the subset of patient with relevant food allergy requires a thorough a clinical history, the appropriate laboratory tests, food allergy being proven in all cases by elimination diets followed by provocation tests. Atopic dermatitis may be cured or largely improved by elimination diets, but the latter need a peculiar education of patient and physicians because the common causal foods involved (egg, milk, wheat, soil, peanut) are ubiquitous in industrial foods and since elimination diets are at risk of nutritional imbalances. Most food allergies resolve following early childhood and atopic dermatitis in older children and adults is largely less related to food allergy.     

Quoi de neuf en allergologie pédiatrique en 2005 ? Partie 4. Allergie cutanée,alimentaire, médicamenteuse et aux insectes (Une revue de la littérature internationale d'octobre 2004 à octobre 2005)

Allergological work-up and treatment of french children with atopic dermatitis have been the subject of a recent consensus. Food avoidance is useless for prevention of atopic dermatitis, and should be indicated in children with severe atopic dermatitis associated with food allergy only. Exposure, sensitization and allergy rates to nuts increase with age, and avoidance of nuts (even tolerated) is recommended in young children allergic to one or several nuts to prevent the risk of sensitization and allergy to an increasing number of nuts. Threshold values of skin prick-tests and specific IgE determinations with a 90-100% predictive value for food allergy are highly variable from one study to another one, and depend on numerous factors such as age of the children, the allergens used, etc. The diagnostic value of patch-tests and skin application food tests remains controversial. Treatment of food allergy is based on the eviction of the allergenic foods. However, probiotics and « desensitization » to foods may be efficacious in some patients. In children that have outgrown their food allergy, tolerance should be maintened by regular consumption of the foods. However, the parents should be informed that relapses requiring an emergency treatment may occur. Finallly, in children as in adults, repeated mosquito bites induce a desensitization, and most children outgrow their allergy between five to fourteen years.     

Etiologic implication of foods in atopic dermatitis: evidence against

Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.     

Aspects cliniques des allergies cutanées graves (toxidermies exclues)

Some skin diseases require emergency medical intervention when they are life-threatening or when the eruption is spectacular and brutal and the patient has an elevated temperature. We will discuss the clinical presentations of these conditions, excluding cutaneous drugs eruptions. Patients with severe atopic dermatitis may require brief hospitalisation if their eczema is generalized, refractory to classical therapy, or there are infectious complications, as in the Kaposi-Juliusberg syndrome when the condition is associated with a secondary herpetic infection. Acute urticaria and angioedema are frequent causes of emergency room-visits. They can be the result of drug allergy, food allergy, allergy to stinging insects or contact urticaria. However, the cause is not always identified, even after a complete allergy work-up. Some cases of contact eczema are spectacular, in particular when the face is severely oedematous. Paraphenylenediamine, topical corticosteroids and topical non-steroidal anti-inflammatory drugs are often the cause of severe delayed-type hypersensitivity reactions.     

Intérêt des tests épicutanés dans la dermatite atopique du nourrisson

The diagnostic workup of allergy is adapted to the age of the child, the clinical features and the suspected allergen. Patch tests investigate delayed hypersensitivity and so theoretically they are indicated in atopic dermatitis of the infant. Nevertheless, not all cases of atopic dermatitis are allergic in origin. Patch tests are recommended in the infant with moderate to severe atopic dermatitis which recurs with topical corticosteroids and in particular circumstances revealed by the history. Elimination procedures in accordance with the results of the allergological investigation always result in improvement in the infant with atopic dermatitis and may modify the natural history of the condition. In the absence of a reference test such as challenge tests in food allergy, the positivity of patch tests is always correlated with their clinical relevance. Patch tests are carried out for contact allergens, inhalant allergens and foods. The food extracts used for these tests should be standardized to allow routine use. Studies are currently being carried out to validate the use of a simplified patch test series in the infant.     

Patch tests in the diagnosis of food allergies in the nursing infant

The atopy patch-test has been shown to be useful in diagnosis of delayed reactions in infants with atopic dermatitis or digestive symptoms. The combination of skin prick testing and patch testing can significantly enhance the accuracy in diagnosis of specific food allergy in infants with atopic dermatitis or digestive symptoms.     

What are the links between food allergy and atopy ?

Food allergy and atopy are closely linked. In children, food allergy is often the first clinical manifestation of atopy and involved in flares of atopic dermatitis. It is usually disappearing with ageing except for some particular allergens. Asthma and/or allergic rhinitis might develop later particularly if there are some risk factors as familial history of atopy or sensitization to aeroallergens. However some food allergies as allergy to peanut or tree nuts may persist in adulthood sometimes inducing severe clinical manifestations especially in asthmatic patients. In adult, food allergy is mostly associated with oral syndrome linked to cross reactivity between pollen and raw food (fruits or vegetables). Systemic manifestations are more frequent in patients living in the Mediterranean area in relation to direct sensitization (without pollen allergy) to lipid transfer proteins that are particularly resistant.     

Specific IgE to Common Food Allergens in Children with Atopic Dermatitis

Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. Objectives: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. Methods: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Results: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk (31%), hen's egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Conclusion: Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.     

"Atopy patch tests" in the diagnosis of delayed food hypersensitivity

The prevalence of atopic diseases is increasing worldwide. Food allergies are the earliest manifestation of atopy. Atopic eczema affects about 18% of infants in the first 2 years of life and the main cause is allergy to multiple foods. A strong association has been shown between atopic eczema and IgE mediated allergy to milk, egg or peanut, but more than two-thirds of patients intolerant to food proteins have no evidence of IgE sensitization to the relevant food protein. Recently, patch testing with proteins has been found to be helpful in diagnosing food allergy in cases where skin prick tests and estimation of specific antibodies have failed. The methodology of atopy patch test (APT) is unstandardized, and contradictory results have been reported. In contrast to the more standardized APT methodology with aeroallergens, the sensitivities and specificities of food allergens can easily be estimated with food challenge tests. With multiallergic children adding of APTs to the skin prick tests and specific antibody estimation tests give more information for planning a wide enough elimination diet to get the skin and gastrointestinal tract symptomless in order to perform the challenge test which remains the only reliable test for food allergy. Standardization of the APT materials and reading procedure will add to the reliability of this new test method.     

Contact reactions to food

Cutaneous adverse reactions to foods, spices, and food additives can occur both in occupational and nonoccupational settings in those who grow, handle, prepare, or cook food. Because spices are also utilized in cosmetics and perfumes, other exposures are encountered that can result in adverse cutaneous reactions. This article describes the reaction patterns that can occur upon contact with foods, including irritant contact dermatitis and allergic contact dermatitis. The ingestion of culprit foods by sensitized individuals can provoke a generalized eczematous rash, referred to as systemic contact dermatitis. Other contact reactions to food include contact urticaria and protein contact dermatitis provoked by high-molecular-weight food proteins often encountered in patients with atopic dermatitis. Phototoxic and photoallergic contact dermatitis are also considered.     

Quoi de neuf en allergologie pédiatrique en 2004 ? Partie 3 : allergie cutanée,alimentaire, médicamenteuse et aux venins d'insectes (Une revue de la littérature internationale d'octobre 2003 à septembre 2004)

Severity and risk of persistence/relapse of atopic dermatitis are correlated with total IgE levels and food sensitization. Weaning to hypoallergenic formula improves SCORAD and gut barrier function in breastfed infants with persistent atopic dermatitis. Risk of anaphylaxis is high in children with cold-induced urticaria, and these children should be provided with an epinephrine autoinjector. Occult sensitizations are important risk factors for food allergy. The predictive values of serum egg-specific IgE levels are debated. The diagnostic value of atopy patch-tests with foods is confirmed in children with non-immediate food hypersensitivity reactions. Risk of persistence of food allergy is high in children with high specific IgE levels and/or with a low rate of decrease in food-specific IgE levels. Oral desensitization induces tolerance in children with persistent cow's milk allergy, except for children with very high levels of specific IgE. However, tolerance to anaphylactogenic food may be temporary, with the occurence of severe relapses after a few months. Ten per cent of children treated with penicillins are sensitized to these antibiotics. However, only a few of these children are at risk of developing allergy to penicillins. Non allergic hypersensitivity to non steroidal anti-inflammatory drugs is frequent in children. Sublingual immunotherapy may be efficient in children with latex hypersensitivity. A clinically important number of non-hyposensitized children do not outgrow hymenoptera venom allergy. In contrast, venom immunotherapy leads to a significantly lower risk of systemic reaction to stings. Thus, children with moderate to severe allergic reactions to hymenoptera stings should receive specific immunotherapy.     

Phenotypes of IgE-mediated food allergy in Turkish children

Data on food allergy-related comorbid diseases and the knowledge on factors associating specific food types with specific allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test. Egg (57.8%), cow's milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef (5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization were more frequent in children with isolated tree nuts-peanut allergy compared with those with egg or milk allergy (p < 0.001); whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow's milk and tree nuts-peanut allergy (p < 0.001). Children with food allergy were 3.1 (p = 0.003) and 2.3 (p = 0.003) times more likely to have asthma in the presence of allergic rhinitis and tree nuts-peanut allergy, respectively. Interestingly, children with atopic dermatitis were 0.5 (p = 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p = 0.002) and having multiple food allergies (OR, 5.4; p < 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number of food allergies.     

Effect of extensively hydrolyzed milk formula on growth and resistance to bronchitis and atopic dermatitis in infants and toddlers.

OBJECTIVE: This study aimed to evaluate the adverse effects of extensively hydrolyzed milk formula on growth in infants and toddlers. METHODS: Prospectively, 45 infants and toddlers with a positive history of cow's milk allergy confirmed by positive skin prick test and high IgE levels for either alpha-lactalbumin, beta-lactoglobulin, or casein and positive single-blind food challenge received extensively hydrolyzed milk formulas for 1 year. Sex-normalized percentiles of heights and weights of infants and toddlers before their enrollment in the study were compared to those at the end of the study. The contribution of breastfeeding, early use of bottle feeding and intake of adapted or special milk formulas, and history of bronchitis and atopic dermatitis on toddlers' growth were also evaluated by multivariate analysis. RESULTS: Similar percentiles of the children's weight and height were observed at the beginning of the study and 1 year later. According to the multivariate analysis, sex, breastfeeding, early bottle feeding, ingestion of adapted or special milk formulas, atopic dermatitis, and bronchitis were not correlated with either the children's weight or height at diagnosis of the allergy or at 1 year of follow-up (P > .10). Weights and heights were not different between toddlers who had atopic dermatitis or bronchitis during the study period and those who did not. CONCLUSIONS: Growth of infants and toddlers with cow's milk allergy was not affected by the intake of extensively hydrolyzed milk for 1 year. Atopic dermatitis and bronchitis did not appear to have any deleterious effect on these children's growth.     

The role of patch testing for chemical and protein allergens in atopic dermatitis

Many patients who present for evaluation of allergic contact dermatitis have an atopic diathesis. Although the immunologic basis of atopic dermatitis differs from that of allergic contact dermatitis—and patients with atopic dermatitis are less easily sensitized under experimental conditions—atopic patients do develop allergic contact dermatitis, and patch testing is a valuable part of their medical care. Delayed (7-day) patch test readings are especially important in atopic patients to distinguish allergy from irritancy and to evaluate for steroid allergy. The utility of atopy patch tests to aeroallergens such as dust mite is increasingly recognized; aeroallergens may be the cause of a type of protein contact dermatitis.     

Percutaneous sensitization to almond oil in infancy and study of ointments in 27 children with food allergy

A five month old child with atopic dermatitis developed contact dermatitis to almond with positive patch test, positive prick test, and class 4 anti-almond IgE. Focal lesions of persistent eczema were correlated with application of almond oil for 2 month on cheeks and buttocks. The child had not ingested almond and her mother did not report almond intake during her breast-feeding. This observation points to the problems of possible percutaneous sensitisation to food proteins. The study of skin ointments containing components of food origin in 27 food sensitized atopic patients confirm that the choice of an ointment for lesional skin is of importance.     

Faut-il contre-indiquer l’utilisation des émollients à base d’avoine chez l’enfant atopique ?

Atopic dermatitis is the first atopic symptom. Local treatment makes use of emollient cream. Oat cream extracts were suspected of causing sensitization. This study was performed in 202 children with atopic dermatitis. Two subgroups were analysed: group 1, 105 children who had applied oat cream (Exomega®, Laboratoires Ducray, France) and group 2, 97 children who had never applied oat cream. Patch tests were positive for Rhealba® oat extract (total extract or protein fractions) in five cases (2.4%): three in group 1 and two in group 2. This result is clinically relevant in group 1, with increased eczema after use of Exomega®. Oat oral food challenge was negative in three children with an oat-positive skin prick test. There was no statistical difference between the two groups concerning age or positivity of oat tests and the results of other allergologic tests. Relevant oat cream allergy in children with atopic dermatitis concerned 1.4% of cases. These data suggest that emollient patch tests should be performed in children with atopic dermatitis, in order to use or exclude emollient cream. Further studies are required to evaluate changes in oat sensitization in older children.     

Sweat allergy

Sweat allergy is defined as a type I hypersensitivity against the contents of sweat, and is specifically observed in patients with atopic dermatitis (AD) and cholinergic urticaria (CholU). The allergic reaction is clinically revealed by positive reactions in the intradermal skin test and the basophil histamine release assay by sweat. A major histamine-releasing antigen in sweat, MGL_1304, has been identified. MGL_1304 is produced at a size of 29 kDa by Malassezia (M.) globosa and secreted into sweat after being processed and converted into the mature form of 17 kDa. It induces significant histamine release from basophils of patients with AD and/or CholU with MGL_1304-specific IgE, which is detected in their sera. Patients with AD also show cross-reactivity to MGL_1304-homologs in Malassezia restricta and Malassezia sympodialis, but MGL_1304 does not share cross antigenicity with human intrinsic proteins. Malassezia or its components may penetrate the damaged epidermis of AD lesions and interact with the skin immune system, resulting in the sensitization and reaction to the fungal antigen. As well as the improvement of impaired barrier functions by topical interventions, approaches such as anti-microbial treatment, the induction of tolerance and antibody/substance neutralizing the sweat antigen may be beneficial for the patients with intractable AD or CholU due to sweat allergy. The identification of antigens other than MGL_1304 in sweat should be the scope for future studies, which may lead to better understanding of sweat allergy and therapeutic innovations.     

Patterns of Allergic Sensitization in High IgE Syndromes

Dramatic elevations in the serum IgE level are seen both in polygenic allergic diseases such as atopic dermatitis and food allergy, and in a growing list of monogenic primary immune deficiencies (PIDs). Although the IgE produced in patients with PID has generally been considered to be driven by dysregulated IL-4 production and thus lack antigen specificity, in fact allergen-specific IgE can be detected by skin and serum testing in many of these patients. However, perhaps not surprisingly given the distinct immunologic pathways involved, the patterns of allergic disease and atopic sensitization vary widely between syndromes, leading to strikingly different clinical phenotypes.     

Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction

Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.