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.     

Relationship between atopic dermatitis and wheeze in the first year of life: analysis of a prospective cohort of Thai children.

BACKGROUND: Patients with atopic dermatitis show increased risk of concomitant respiratory symptoms such as wheeze and cough. However, limited data is available on respiratory symptoms in atopic dermatitis patients when the disease is in remission. OBJECTIVE: The aim of this study was to investigate the relationship between atopic dermatitis and wheeze during periods of active disease and remission of atopic dermatitis. METHODS: The study formed part of the Prospective Cohort Study of Thai Children (PCTC) involving children born during the period October 2000 to September 2002. The principal caregiver in each family was identified and interviewed about socioeconomic factors, paternal health, and exposure to tobacco smoke. Data on wheeze and atopic dermatitis were collected from questionnaires administered at 6 and 12 months after birth. RESULTS: Of the 4245 live births included in the PCTC cohort, 4021 (94.7%) participated in the follow-up survey at age 6 months and 12 months. The prevalence of wheeze and eczema were 13.8% and 7.4%, respectively. There was also a significant association between current atopic dermatitis and wheeze in the same period (P < .01). However, no significant association was observed between previous atopic dermatitis and wheeze when atopic dermatitis was in remission. CONCLUSION: There is a significant increase in the risk of wheeze in infants with current atopic dermatitis but not in those in whom the disease is in remission.     

Dermatite atopique de l'enfant et allergie au blé

Wheat allergy amounts to 14–18% during atopic dermatitis, is often manifested by delayed reactions, either on the skin or in the digestive tract. Negative skin prick tests and specific IgE do not rule out the diagnosis. Patch testing seems to be more adapted to this food, but its specificity is low in the young infant. Diagnosis requires an elimination-provocation test, the latter being carried out on several days due to the frequency of delayed reactions.     

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.     

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 multifood allergy syndrome

Multiple food intolerance in infants and young children is increasingly diagnosed. More than 40% of infants less than 1 y.o. could be affected. The syndrome is characterized by the seriousness of atopic dermatitis (SCORAD > 50), by enterocolitis or failure to thrive or various associations of symptoms that may change over time. The evolution is long-lasting. Common food allergens are milk, egg, soy, wheat, but other ones can be implicated. The diagnosis is established by standardized oral challenges. Multiple etiopathogenic factors are involved: atopy, gastro-enteritis induced intestinal hyperpermeability, precocity of food diversification, breast-feeding continued after the onset of symptoms. Amino-acid based formulas have changed the evolution.     

Food allergy and the respiratory tract

Previous studies have confirmed that IgE-mediated, food allergy-induced respiratory tract symptoms occur, typically accompanied by cutaneous or gastrointestinal symptoms. The possibility that respiratory tract symptoms are food allergy induced should be considered in patients who have a current or past history of one or more of the following: atopic dermatitis, wheezing (or experiencing anaphylactic symptoms) after ingesting a particular food or foods, and confirmed food allergy. Moreover, the work-up of food allergy in asthma should be considered in patients in whom asthma is poorly controlled despite persistent use of appropriate asthma medications. A definitive diagnosis of food allergy should be based on clinical history, appropriate laboratory testing, and, when indicated, well-controlled oral food challenges. Treatment is based on establishing a safe elimination diet and an emergency plan for managing reactions caused by accidental ingestion.     

Eosinophils are neither migrated nor activated in the skin lesions of atopic dermatitis in infants.

Eosinophils and eosinophil cationic protein (ECP) were examined in the skin lesions of 10 infants with atopic dermatitis (aged 4 months to 7 years). In all 10 patients, neutrophils and eosinophils were rarely seen in these lesions. Moreover, in the immunohistochemical study, ECP was scarcely detected in any of them. Our results suggest that eosinophils are neither migrated nor activated in the skin in atopic dermatitis in infants.     

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.     

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.     

Gianotti-Crosti syndrome: case report of a pruritic acral exanthema in a child

Gianotti-Crosti syndrome (GCS) is a sporadic dermatosis affecting mainly children. It is characterized by multiple, confluent, monomorphic and pruritic pink to red-brown papules or papulovesicles, distributed symmetrically on the face, extensor surfaces of the extremities and buttocks, commonly sparing the trunk, palms and soles. This can be preceded by a viral infection, and may be accompanied by fever, hepatosplenomegaly, or lymphadenopathy. Personal and family history of atopy appears to be a risk factor in the subsequent development of GCS, thus frequently diagnosed as atopic dermatitis. We report a case of a 4-year-old boy from our institution with generalized, pruritic, papulovesicular rashes on the face and extremities for one month. He was diagnosed to have atopic dermatitis and treated as such, before presentation to our institution. As the signs and symptoms in GCS are similar to atopic dermatitis, we suggest that this diagnosis be considered when presented with a similar case.     

Dermatite atopique et allergie alimentaire chez l'enfant

Food allergy is known to provoke flares of atopic dermatitis (AD). The prevalence of food allergy in infants with atopic dermatis has been estimated to be 40%. Atopy patch testing is a novel approach to diagnose food-induced AD, but standardization of atopy patch test extracts needs addional studies. Oral food challenge is the gold standard for diagnose of food allergy. Nevertheless, the method used for oral food challenges in cases of late eczematous reactions remains to be defined. Food appears to aggrevate eczematous lesions in young children, and it is recognized that allergy testing needs to be standardized in order to prove that relationship.     

Risk of allergy to food proteins in topical medicinal agents and cosmetics

The risk of allergy to food proteins in cosmetics and topical medicinal agents is poorly evaluated. IgE dependent contact urticaria and contact dermatitis are observed. Eleven cases (7 infants and 4 women) are reported. Wheat, egg, oats, milk, peanut proteins are incriminated by prick-tests or atopy patch-tests. Cases are related to a previous food allergy and other ones may indicate primary sensitization to topical creams mainly used for skin care of atopic dermatitis. A consecutive exercise induced anaphylaxis to wheat and a long lasting sensitization to wheat have been observed. A clear and accurate identification of food allergens in cosmetics and topical agents is necessary. Given the hyper-permeability of infant skin, topical products containing food proteins of known allergenicity are contra-indicated for neonates, and for infants with atopic dermatitis, which may be associated with skin hyper-permeability.     

Optimal management of atopic dermatitis in infancy

The necessity to optimise the management of atopic dermatitis of infants needs knowledge of three components: increase of prevalence, extreme frequency of food allergy and increase in the frequency of the syndrome of multiple allergies, that frequently develops into asthmatic disease. Management of DA in infancy (first year of life) is based on the global strategy of understanding the physiological Th2 polarisation at birth, that does not allow a re-equilibration of the Th1-Th2 balance that progresses in the first six months of life (in normal infants) making in this period a window of opportunity for sensitizations. Prevention in high-risk children (familial history of atopy) covers the non-exposure to in door pollutants (tobacco and volatile organic compounds), breast-feeding or a hypoallergenic formula for a hydrolysate of pork and soya proteins or better an extensive hydrolysate of casein. Four situations require moving to an amino acid substitute: failure to thrive, severe atopic dermatitis, a syndrome of multiple food allergies, allergy to hydrolysates. Reintroduction of foods should be considered with the least delay so as to induce digestive tolerance. It should take into account the clinical development, the intensity of the sensitisation and eventually depend on a realistic test of introduction. Management of DA searches for recovery of generalized eczema, failure to immediate improvement of quality of life prevention of immediate complications (local sepsis) acceleration of return to food tolerance. Prevention of ulterior development of asthma by immediately introducing measures to diminish respiratory exposure to allergens and tobacco is hoped for.     

Prevalence of and risk factors for the development of atopic dermatitis in schoolchildren aged 12–14 in northwest Croatia

BackgroundAtopic dermatitis is a common allergic disorder. A multifactorial background for atopic dermatitis has been suggested, with genetic as well as environmental factors influencing disease development. Our aim was to estimate the prevalence rate and associated factors for atopic dermatitis in northern Croatia using the methods of the internationally standardised ISAAC protocol.MethodsThe study was undertaken among 12–14-year-old schoolchildren. Data were collected using standardised ISAAC written questionnaire Phase One and some selected questions from the ISAAC supplementary questionnaire completed by parents.ResultsA total of 2887 children participated in the study. Estimated lifetime (ever) prevalence rate of atopic dermatitis symptoms was 7.55% and estimated 12-month prevalence rate was 5.75%. The factors found to be associated to the symptoms of atopic dermatitis ever were: positive family atopy, female gender, sleeping on feather pillow and contact with pets after age of seven, and to the symptoms in the past 12 months were: positive family atopy, female gender, sleeping on feather pillow, parasite infestation, and contact with pets in the first year of life.ConclusionsThe results of our study show that northern Croatia is a region with moderate prevalence rates of atopic dermatitis. Following risk factors were family atopy, female gender and sleeping on feather pillow. Because of controversial results of previous studies conducted on the same topic further investigations should be made.     

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.     

Allergic Contact Dermatitis in Children: Review of the Past Decade

Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. During the last decade, there has been a heightened awareness of this disease in the pediatric population. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred children with suspected ACD ranges from 27 to 95.6 %. The most common allergens in children in North America are nickel, neomycin, cobalt, fragrance, Myroxylon pereirae, gold, formaldehyde, lanolin/wool alcohols, thimerosal, and potassium dichromate. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up.     

Exacerbating factors and disease burden in patients with atopic dermatitis

The number of patients with atopic dermatitis is on the rise worldwide, and Japan is no exception. According to recent estimates of the percentage of patients with atopic dermatitis in Japan by age, the majority of patients are between 20 and 44 years old. Because the peak age of onset of atopic dermatitis is during infancy, many patients may experience prolonged symptoms from infancy to adulthood. A prolonged clinical course also increases the burden of atopic dermatitis on affected patients. Decreased productivity due to work disruptions, reduced daily activity, higher direct medical costs, fatigue, and daytime sleepiness due to sleep disturbances are typical burdens on patients with atopic dermatitis. In order to reduce these burdens, it is necessary to shorten its clinical course and achieve long-term control without relying on medications, possibly by using avoidance or coping measures of aggravating factors. Typical aggravating factors of atopic dermatitis include irritant dermatitis, food allergy in children, sweating, and psychological stress in adults. Food allergy places a heavy burden on the quality of life of affected patients and their families. The effectiveness of educational interventions for sweating and psychological stress is unclear. We must also evaluate the economic burden and cost-effectiveness of interventions on the patient as aggravating factors to be addressed.     

Japanese Guideline for Atopic Dermatitis 2014

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and coun- termeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2012 (ADGL2012)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2013" together with those for other allergic diseases.     

Japanese guidelines for atopic dermatitis 2017

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is an inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the “Guidelines for the Treatment of Atopic Dermatitis 2008” prepared by the Health and Labour Sciences Research and the “Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015)” prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the “Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016” together with those for other allergic diseases.