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.     

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.     

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.     

La marche de l'allergie : que reste-t-il de l'histoire dite naturelle de l'allergie ?

Until recently, it was generally agreed that the natural history of allergy overlapped with that of asthma. The dominant concept was that allergy, in particular, allergy to perennial aeroallergens, was the most important cause of asthma. The classical curves of the age-related incidence of the main allergic syndromes, i.e. those closely associated with asthma, made it appear that the first step in the natural history of atopy was atopic dermatitis, followed by asthma and rhinitis. Allergy to one or more foods, especially cow milk and egg, began early in life, very often disappeared, leaving place for the development of sensitivity to aeroallergens. This classic schema allowed one to suppose that primary prevention was possible and that by avoiding the main allergens very early in life one could reduce the subsequent risk of allergic sensitization and, therefore, of asthma as well. The interest in prevention was explained by the growing prevalence of allergic diseases, which had become an important public health problem. In fact, the natural history of asthma and allergy is much more complex, being a real puzzle in which one must take into account the allergens, life style (rural or urban), contact with animals, endotoxins, parasites, atmospheric pollution (e.g. the association between diesel particles and pollen), hygiene, infections and immunizations, breast feeding, pasteurized or non-pasteurized cow milk, the diet and many other factors. The aim of this critical review is to try to untangle this maze.     

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.

Histamine reactivity of affected and unaffected skin in endogenous eczema and in chronic allergic contact dermatitis

In 30 patients with atopic dermatitis and 40 with allergic contact dermatitis in the chronic stage intracutaneous tests were performed with 0.1 ml histamine 1:10,000 in affected and non-affected skin. The erythematous and wheal reactions were compared with 40 age- and sex-matched controls. The diameters of the erythema and wheals were significantly reduced in affected and non-affected skin of the atopic dermatitis (p less than 0.01). In allergic contact dermatitis only the erythema of the affected and non-affected skin was reduced (p less than 0.05), but not the wheal reaction. The erythematous reaction was, however, less reduced in non-affected skin than in the affected one of the allergic contact dermatitis (p less than 0.05). The reduced histamine reactivity seems to be a typical basic mechanism in atopic dermatitis. It is suggested to be due to the histamine mediated immune modulation and the increased release from mast cells, leading to a refractory behaviour of histamine receptors of the blood vessels like in tachyphylaxis. It is interpreted as a secondary phenomenon in allergic contact dermatitis. Although the histamine reaction shows differences for the groups of patients, it is not suitable to discriminate single cases.     

Allergic and nonallergic reactions to nitroglycerin.

Allergic and nonallergic reactions to nitroglycerin occur. The aims of this study were to review the different manifestations of nitroglycerin allergy, to explain how to evaluate for it, and to discuss its treatment. We reviewed relevant literature in peer-reviewed journals, computerized databases, and references identified from relevant bibliographics. Nitroglycerin's most common side effects are headache, facial flushing, head throbbing, fainting, hypotension, tachycardia, and syncope. The majority of reported skin reactions to topical and transdermal nitroglycerin products are irritant contact dermatitis, allergic contact dermatitis, and urticaria. Five cases of presumed allergic reactions to oral, sublingual, intravenous, or perianal nitroglycerin products have been described. Patch testing may be helpful in subjects with skin reactions to topical or transdermal nitroglycerin. In subjects with positive patch tests to nitroglycerin (allergic contact dermatitis), transdermal nitroglycerin patches and other topical nitroglycerin products should be avoided. Most patients with contact dermatitis to nitroglycerin have tolerated oral nitroglycerin, sublingual nitroglycerin, or oral isosorbide challenges.     

Invited Commentary: Recommendation for a North American Pediatric Patch Test Series

Given the increased recognition of pediatric allergic contact dermatitis and lack of patch testing consensus in children, we present a minimum basic 20-allergen North American pediatric series, for screening children ages 6–12 with suspected contact allergy.     

Current Strategies in Treating Severe Contact Dermatitis in Pediatric Patients

Allergic contact dermatitis in children is underdiagnosed and undertreated, and its incidence is increasing. Appropriate history taking and the suspicion for allergic contact dermatitis is essential, and patch testing remains the gold standard in diagnosis. Avoidance of the offending allergen, once identified, is the first goal of treatment. Medical therapies include topical corticosteroid and topical immunomodulators. In severe cases, oral corticosteroids or immunomodulators are utilized, although prospective randomized trials for the treatment of this disease in children are lacking. A PubMed literature search was performed to identify publications on allergic contact dermatitis in the pediatric population with the keywords: dermatitis, children, allergic contact dermatitis, pediatrics, contact hypersensitivity, contact allergy, treatment, and management. This review will address the major principles behind the diagnosis and management of this disease in the pediatric population, and highlight useful strategies that may result in improved treatment of this condition.     

Nickel Sensitivity in Asthma Patients

Nickel sulphate frequently causes allergic contact dermatitis; less known effects are nasal inflammation (rhinitis) and bronchial asthma. In this study, we aimed to find if there is a relationship between asthma and nickel sensitivity. Asthmatic patient, non-asthmatic atopic, and healthy control groups were patch tested with nickel sulphate. Nickel sensitivity was more prevalent in the asthmatic patient group compared to the non-asthmatic atopic and healthy control groups.     

Nickel Sensitivity in Asthma Patients

Nickel sulphate frequently causes allergic contact dermatitis; less known effects are nasal inflammation (rhinitis) and bronchial asthma. In this study, we aimed to find if there is a relationship between asthma and nickel sensitivity. Asthmatic patient, non-asthmatic atopic, and healthy control groups were patch tested with nickel sulphate. Nickel sensitivity was more prevalent in the asthmatic patient group compared to the non-asthmatic atopic and healthy control groups.     

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.     

Differences in gut microbiota between allergic rhinitis,atopic dermatitis,and skin urticaria: A pilot study

Introduction.Several forms of allergy have been clinically presented, including, among others, atopic dermatitis (eczema), urticaria (hives), and allergic rhinitis (rhinitis). As their detailed pathogenesis continues to be researched, we aimed in the current study to compare gut microbiota differences between eczema, hives, and rhinitis patients.Methods.We enrolled 19 eczemas, nine hives, and 11 allergic rhinitis patients in this study. Fecal samples were examined using 16S ribosomal ribonucleic acid amplicon sequencing, followed by bioinformatics and statistical analyses. We compared microbiota in dermatitis (eczema), chronic urticaria (hives), and allergic rhinitis (rhinitis).Results.All clinical data were similar between the subgroups. The microbiota results indicated that Bacteroidales species were found in skin allergies, both urticaria and eczema, when compared to rhinitis. The microbiota differs substantially between those patients with atopic dermatitis (eczema), chronic urticaria (hives), and allergic rhinitis (rhinitis), thus indicating that the gut-skin and gut-nose axes exist. Gut flora colonies differ significantly between skin allergy and nose allergy. Bacteroidales species could be a clinical link between gut flora and skin allergy; of those, Bacteroids Plebeius DSM 17135 is significantly associated with the urticaria (hives) subgroup.Conclusion. Our results demonstrated high intra-group homogeneous and high inter-group heterogeneous microbiota. The clinical symptoms of eczema, hives, and rhinitis can all be linked to specific microbiota in the current study. In this pilot study, the Ruminococcaceae and Bacteroidales species are associated with allergic disease, in line with several previous published articles, and the abundance of Firmicutes Phylum is representative of intestinal dysbiosis. In the future, a larger cohort and thorough biochemical studies are needed for confirmation.     

Constitutional differences in the risk of hypersensitivity to cats in children]

Several risk factors for allergy to cats were studied in children and teenagers who had respiratory symptoms possibly of allergic origin and were chronically exposed to a cat. It appears that: atopic dermatitis significantly increases the risk, independently of the other parameters examined; a family history of presumed allergic respiratory disease without atopic dermatitis significantly increases the risk in boys carrying the rhesus phenotype cc; passive smoking significantly increases the risk for allergy to cats in rhesus CC antigen-bearing subjects, independently of all other parameters (family history or atopic dermatitis). These factors aggravating risk, which can easily be determined by each physician, may prove useful, once personalized, in strengthening the general recommendations given to parents but routinely disregarded due to the lack of readily identifiable constitutional markers to establish the undeniable risk of hypersensitivity to cats.     

The relationship between HIV infection and atopic dermatitis

Patients with HIV infection exhibit a wide range of skin pathology, including bacterial, fungal, and viral infections, skin tumors, inflammatory and eczematous eruptions, and drug rashes. HIV-infected adults commonly develop a condition that strongly resembles atopic dermatitis and is sometimes called “atopic-like dermatitis”; moreover, atopic dermatitis and other atopic disorders have been described as common manifestations of pediatric HIV infection. Conditions such as sinusitis, asthma, and hyper-IgE syndrome, and laboratory abnormalities, eg, elevated IgE levels, eosinophilia, and possible Th1-Th2 imbalances, suggest a predilection for atopic disorders in these patients. It is of interest to examine the immune perturbations intrinsic to HIV infection, and their possible role in triggering atopic dermatitis, and to consider whether other abnormalities, such as xerosis, bacterial or viral superantigens, or epidermal barrier disruption with altered presentation of cutaneous aeroallergens, might play a significant role.     

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.     

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.     

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.     

Demographic,clinical and allergological characteristics of Eosinophilic Esophagitis in a Spanish central region

BackgroundEosinophilic esophagitis (EoE) is a chronic inflammatory emerging disease of the oesophagus with immunoallergic aetiology. The allergens involved have not been clearly defined and may depend on the exposure of the population to aeroallergens or food antigens.Materials and methodsPatients diagnosed with EoE between 2006 and 2011 were referred to our Allergy Section. Patch and skin prick tests (SPT) with aeroallergens and foods were performed, and total and specific IgE levels, eosinophil cationic protein levels and eosinophil count were determined.Results43 patients were included. 36 (83.7%) were atopic. 29 patients presented choking, 19 dysphagia, 9 food impaction with urgent endoscopy, 4 chest pain, 1 isolated vomiting and 1 epigastric pain. 22 had two or more symptoms. The mean duration of symptoms was 3.73 years. Concomitant allergic diseases included rhinoconjunctivitis and/or asthma (31 patients), IgE food allergy (21 patients) and atopic dermatitis (3 patients).32 (74%) were sensitized to aeroallergens, of which 90% were sensitized to pollens; 23 (54%) showed positive tests to foods and 12 of them (52%) to lipid transfer proteins (LTP).Of the 29 pollen-allergic patients, 15 (52%) were sensitized to plant foods and 10 (34.4%) to LTP.ConclusionsOur findings support those reported in the literature: the disease is more common in men aged 30–40 years with at least a three-year history of symptoms of esophageal dysfunction, sensitized to pollens, the predominant aeroallergen in our area, but also to plant foods or panallergens. These results increase the evidence for an immunoallergic aetiology and can help us in the early diagnosis of EoE.