Asthma Symptoms and Bronchial Reactivity in School Children Sensitized to Food Allergens in Infancy

Food allergy in infancy usually disappears but is followed primarily by respiratory allergy. We hypothesized that children allergic to common food allergens in infancy are at increased risk of wheezing illness and bronchial hyperresponsiveness during school age. In a case-control study 69 children 7.2 to 13.3 years of age allergic to egg (N = 60) and/or fish (N = 29) in early life (first 3 years) who attended our allergy outpatient clinic were recruited. They received follow-up for 1 year and were evaluated by parental questionnaire, skin prick testing, spirometry, and metacholine bronchial challenge. Another 154 children (70 sensitized to inhaled allergens) recruited selectively from a general population sample with no history of food allergy during their first 3 years served as control subjects. Twenty-three children (38.3%) maintained their sensitization to egg and 19 (65.5%) to fish; the prevalence of sensitization to ≥ 1 inhaled allergen(s) increased from 59.4% to 71% during childhood. Current asthma symptoms were reported more frequently in the study group than in either control groups, sensitized to inhaled allergens and non-sensitized. Children of the study group showed a significantly increased frequency of positive response to metacholine bronchial challenge compared to the control group as a whole; the difference was statistically indicative when study groups separately were compared to the sensitized control subjects. Multivariate logistic regression analysis showed that bronchial hyperresponsiveness, as well as reported current asthma symptoms were associated with early wheezing and early sensitization to inhaled allergens but not with atopic dermatitis in infancy or persistence of egg or fish allergy. Children allergic to egg or fish in infancy are at increased risk for wheezing illness and hyperactive airways in school age; asthma and bronchial hyperresponsiveness development is mostly determined by wheezing and senzitization to inhaled allergens in early life regardless of atopic dermatitis in infancy or retention of food allergy.     

Eczema phenotypes and IgE component sensitization in adolescents: A population-based birth cohort

BackgroundEczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns.MethodsThis birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC.ResultsPersistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome.ConclusionsEarly-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.     

Epicutaneous Immunity and Onset of Allergic Diseases - Per-“Eczema”tous Sensitization Drives the Allergy March

Resultsfrom recent epidemiological studies strongly suggest that ingestion of food promotes immune tolerance to food antigens, whereas exposure to food antigens through skin leads to allergic sensitization. A “dual-allergen-exposure hypothesis” has been proposed to explain those findings. However, several other recent studies have demonstrated that some allergic diseases can be successfully treated by recurrent epicutaneous exposure to allergens. At a glance, these two sets of findings seem to be contradictory, but we think they provide important clues for understanding the mechanisms behind the allergy march.Here, we propose that per-“eczema”tous sensitization drives the allergy march, and we introduce results from several published studies in support of this hypothesis. We hope that this review may help in establishment of new strategies for preventing the allergy march in the near future.     

变态反应疾病的自然进程及干预

变态反应疾病的发生和发展一直备受关注，其变态反应症状可表现在胃肠道、皮肤、鼻腔、支气管等不同部位，流行病学研究发现婴儿或儿童早期出现的某种变态反应症状常常预示着未来其他变态反应疾病的发生，这种现象被称为变态反应疾病的自然进程。本文就变态反应疾病的自然进程的相关研究进行综述，以为变态反应疾病的预防和治疗提供线索。     

Recent developments and advances in atopic dermatitis and food allergy

This review highlights recent advances in atopic dermatitis (AD) and food allergy (FA), particularly on molecular mechanisms and disease endotypes, recent developments in global strategies for the management of patients, pipeline for future treatments, primary and secondary prevention and psychosocial aspects. During the recent years, there has been major advances in personalized/precision medicine linked to better understanding of disease pathophysiology and precision treatment options of AD. A greater understanding of the molecular and cellular mechanisms of AD through substantial progress in epidemiology, genetics, skin immunology and psychological aspects resulted in advancements in the precision management of AD. However, the implementation of precision medicine in the management of AD still requires the validation of reliable biomarkers, which will provide more tailored management, starting from prevention strategies towards targeted therapies for more severe diseases. Cutaneous exposure to food via defective barriers is an important route of sensitization to food allergens. Studies on the role of the skin barrier genes demonstrated their association with the development of IgE-mediated FA, and suggest novel prevention and treatment strategies for type 2 diseases in general because of their link to barrier defects not only in AD and FA, but also in asthma, chronic rhinosinusitis, allergic rhinitis and inflammatory bowel disease. The development of more accurate diagnostic tools, biomarkers for early prediction, and innovative solutions require a better understanding of molecular mechanisms and the pathophysiology of FA. Based on these developments, this review provides an overview of novel developments and advances in AD and FA, which are reported particularly during the last two years.     

Barrier Dysfunction Caused by Environmental Proteases in the Pathogenesis of Allergic Diseases

Skin barrier dysfunction has emerged as a critical driving force in the initiation and exacerbation of atopic dermatitis and the "atopic march" in allergic diseases. The genetically determined barrier deficiency and barrier disruption by environmental and endogenous proteases in skin and epithelium are considered to increase the risk of sensitization to allergens and contribute to the exacerbation of allergic diseases. Sources of allergens such as mites, cockroaches, fungi, and pollen, produce or contain proteases, which are frequently themselves allergens. Staphylococcus aureus, which heavily colonizes the lesions of atopic dermatitis patients and is known to trigger a worsening of the disease, also produces extracellular proteases. Environmental proteases can cause barrier breakdown in the skin, not only in the epithelium, and stimulate various types of cells through IgE-independent mechanisms. Endogenous protease inhibitors control the functions of environmental and endogenous proteases. In this review, we focus on the barrier dysfunction caused by environmental proteases and roles of endogenous protease inhibitors in the pathogenesis of allergic diseases. Additionally, we examine the subsequent innate response to Th2-skewed adaptive immune reactions.     

Food Allergy and Atopic Dermatitis: How Are They Connected?

Food allergy predominantly affects children rather than adults with atopic dermatitis (AD). Early food sensitization has been found to be significantly associated with AD. Three different patterns of clinical reactions to food allergens in AD patients have been identified: 1) immediate-type symptoms, 2) isolated eczematous late-type reactions, and 3) combined reactions. Whereas in children, allergens from cow’s milk, hen’s egg, soy, wheat, fish, peanut, or tree nuts are primarily responsible for allergic reactions, birch pollen–related food allergens seem to play a major role in adolescent and adults with AD in Central and Northern Europe. Defects in the epidermal barrier function seem to facilitate the development of sensitization to allergens following epicutaneous exposure. The relevance of defects in the gut barrier as well as genetic characteristics associated with an increased risk of food allergy remain to be further investigated. Many studies focus on sufficient strategies of prevention, which actually include breastfeeding or feeding with hydrolyzed formula during the first 4 months of life.     

Prevention of allergic diseases

The prevalence of asthma and allergic diseases has increased in recent years, particularly in the industrialized world. Allergic disease begins to manifest in the first years of life. The disorder usually manifests initially in the form of food allergy and atopic dermatitis, followed in later stages by respiratory allergy with rhinitis and/or asthma. This has led to the adoption of preventive measures in those children with a high risk of atopy, based on the following considerations: 1) A family history of allergic diseases (asthma, eczema, and/or allergic rhinitis); 2) A personal history of atopy such as atopic dermatitis, particularly when associated to food allergy; and 3) The existence of allergic sensitization, particularly to pneumoallergens, of early or late onset, but persistent during childhood. Prevention is established at three different levels: primary prevention, avoiding sensitization; secondary prevention, avoiding appearance of the disease; and tertiary prevention, avoiding the symptoms. The present study discusses current knowledge of prevention and its efficacy, with mention of the importance of breastfeeding and the use of pre- and probiotics for securing adequate prevention.     

Skin Barrier-Related Molecules and Pathophysiology of Asthma

The concept of “atopic march” has been well appreciated both by physicians and by dermatologists; eczema (atopic dermatitis) often precedes the development of airway diseases such as asthma and allergic rhinitis in atopic subjects. However, the underlying mechanisms for atopic march are less elucidated. It has been conceived that genetic susceptibility to atopy determines the phenotype of allergic diseases progressive from the skin to the airways, but recent discovery of filaggrin gene mutations that disturb the barrier function of the skin in patients with asthma and eczema now suggests the crucial role of epicutaneous sensitization as a precursory event for the development of asthma. In the present review, we describe updated genetic and immunological evidences that suggest the relationship between skin barrier-related molecules and the pathology of asthma.     

Contact sensitization in children with atopic dermatitis

Background

Atopic dermatitis is a common illness in childhood. Children with atopic dermatitis are prone to develop cutaneous sensitization due to skin barrier dysfunction.

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.     

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.     

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.     

The Relationship Between Advances in Understanding the Microbiome and the Maturing Hygiene Hypothesis

Expanding knowledge about an interaction of the bacterial colonization with pathogenic and non-pathogenic bacteria and the human immune system leads to speculation on potential effects on health and disease. Recent advances in sequencing technologies and new bioinformatic possibilities now allow investigating the microbes that colonize the human gut, skin and airways in more detail. In light of the hygiene hypothesis, the impact of the microbial composition of individuals with allergic sensitization and/or atopic diseases, i.e., allergic asthma or atopic eczema, were investigated in several clinical trials. Altered diversity of gut microbiota during infancy as well as colonization with specific pathogenic and apathogenic bacteria has been linked with an elevated risk for allergy. There are ongoing attempts to establish intervention strategies aimed at modifying initial colonization patterns in early life. While results from animal models, in-vitro data and epidemiological studies encourage the concept of a relationship between the microbiome and the development of allergic diseases, the transfer of these findings to intervention strategies still seems to be a major challenge.     

Role of aeroallergens in the etiopathogenesis of atopic dermatitis

Atopic dermatitis is a chronic relapsing inflammatory skin disease. It is most frequent in childhood and its clinical manifestations vary with age. The etiopathogenic mechanisms that explain this process are still poorly understood; several studies performed in adults speculate on the possible role of aeroallergens through direct contact with the skin but, because the etiology of this disease varies with age, studies in children of different ages are required.Aims: (i) To determine whether children with atopic dermatitis are sensitized to inhalant allergens. (ii) To determine whether these inhalant allergens cause dermatitis or whether they provoke allergic respiratory disease (asthma, rhinitis) concomitant with atopic dermatitis. (iii) To evaluate whether sensitization to a particular allergen takes place at any age or whether there are differences according to age.Material and methods: This study was performed in the following groups: (i) 64 children with atopic dermatitis, divided into two subgroups, one consisting of 37 children who also presented allergic respiratory disease (asthma, rhinitis) (AR) and another subgroup of 27 patients who presented atopic dermatitis only. (ii) Control group: eight children who presented AR only, to determine whether this group reacted to patch testing with inhalant allergens. (iii) Control group: seven healthy children to rule out non-specific positive tests in the non-atopic population. All groups were divided by age according to the phases of atopic dermatitis: early childhood phase (< 2 years): 21, childhood phase (2-10 years): 37, adolescent phase (> 10 years): 21. In all children total serum IgE determination (RIA), allergen-specific IgE determination (RAST), prick- and patch test were performed. In the three tests the same allergens were used, consisting of the usual components of standardized inhalant and food allergens. When the results of patch testing were positive, biopsy and histopathological analysis were performed and monoclonal antibodies were used to determine reproducibility of the eczematous lesion.Results: Sensitization was found to differ among patients with atopic dermatitis according to whether they presented respiratory symptoms and according to age with a clear predominance of food sensitization in the group aged less than 2 years. In the group aged 2-10 years, mixed sensitization predominated, mainly because of simultaneous respiratory involvement, but it is highly probably that inhalant allergens participate in the etiopathogenesis of atopic dermatitis. In children aged more than 10 years sensitization to inhalant allergens predominated as most presented respiratory symptoms. Patch testing was positive in 34.3 % of patients with atopic dermatitis and approximately half were positive to dust mites. The patch test is of great diagnostic value in atopic dermatitis and none of the tests were positive in the control group. All the biopsies of patch tests with inhalant allergens reproduced the lesions typical of eczema, demonstrating their involvement in the etiopathogenesis of dermatitis.     

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.     

Japanese guidelines for atopic dermatitis 2020

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.     

Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner

Background: Epicutaneous sensitization to allergens is important in the pathogenesis of not only skin inflammation such as atopic dermatitis but also "atopic march" in allergic diseases such as asthma and food allergies. We here examined antibody production and skin barrier dysfunction in mice epicutaneously administered papain, a plant-derived occupational allergen belonging to the same family of cysteine proteases as mite major group 1 allergens.Methods: Papain and Staphylococcus aureus V8 protease were patched on the backs of hairless mice. Tran- sepidermal water loss was measured to evaluate the skin barrier dysfunction caused by the proteases. Papain or that treated with an irreversible inhibitor specific to cysteine proteases, E64, was painted onto the ear lobes of mice of an inbred strain C57BL/6. Serum total IgE levels and papain-specific IgE and IgG antibodies were measured by ELISA.Results: Papain and V8 protease patched on the backs of hairless mice caused skin barrier dysfunction and increased serum total IgE levels, and papain induced the production of papain-specific IgG1, IgG2a, and IgG2b. Papain painted onto the ear lobes of C57BL/6 mice induced papain-specific IgE, IgG1, IgG2c, and IgG2b, whereas papain treated with E64 did not. IgG1 was the most significantly induced papain-specific IgG subclass among those measured.Conclusions: We demonstrated that the epicutaneous administration of protease not only disrupted skin barrier function, but also induced IgE and IgG responses in a manner dependent on its protease activity. These results suggest that protease activity contained in environmental sources contributes to sensitization through an epicutaneous route.     

Are the most common food allergens in an Iranian atopic population compatible with worldwide reports? A systemic review and meta-analysis with molecular classification of frequent allergens

BackgroundUndesirable immunological responses to alimentary allergens are one of the hallmarks of atopic diseases. The prevalence of common food allergens is dissimilar among different communities with distinct nutritional habits and genetic characteristics.AimTo assess the prevalence of the most common food allergens in Iran, using different reliable studies.MethodsAll studies determining sensitization to common food allergens that were indexed in PubMed, Web of Science, Google Scholar, ProQuest, Scopus, Iran Medex, and Magiran were included in this review. To perform a meta-analysis, STATA 14 and metaprop command was applied. A logistic-normal random-effects model with Freeman–Tukey double arcsin transformation was applied to combine the findings of different studies and evaluate their heterogeneity. Random pooled estimate (ES) (pooled prevalence), 95% confidence interval (95% CI) and p-value were determined.ResultsA total of 23 studies with data from a total of 6126 children and adults met the inclusion criteria for entering this meta-analysis. The respective pooled prevalence of a positive family history of allergy and positive specific IgE to at least one food allergen was 72% (95% CI: 66–77%) and 41% (95% CI: 33–49%), respectively. Our results in the total population revealed that allergic sensitization to egg yolk, cow’s milk (CM), egg white, and wheat were 25% (95% CI: 16%–35%), 24% (95% CI: 19–29%), 23% (95% CI: 18%–28%), and 9% (95% CI: 6%–14%), respectively. Walnut, peanut, and soybean sensitization was detected in 23% (95% CI: 17%–31%), 23% (95% CI: 13%–33%), and 20% (95% CI: 12%–28%) of patients, respectively. Random pooled ES for sensitization to shrimp and fish was 32% (95% CI: 21–45%) and 12% (95% CI: 6–20%), respectively. The result of analysis in different age groups revealed that allergic sensitization to milk, egg white, and egg yolk declines in higher age groups; while shrimp sensitization increases in older patients. In patients with atopic dermatitis, egg white was the most frequent food allergen 29% (95% CI = 18–42%); while wheat was the least frequent 8% (95% CI = 4–14%).ConclusionsConsidering the prevalence of different food allergens, the results of the current meta-analysis revealed that egg yolk and cow’s milk had the second and third rate after shrimp, respectively. The high prevalence of sensitization to shrimp may be attributed to its high consumption in coastal areas and/or cross-reactivity of shrimp with some aeroallergens such as mites.     

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.