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.     

"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.     

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.     

Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge

Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.     

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.     

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.     

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.     

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.     

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.     

Diagnostic accuracy of atopy patch tests for food allergy in children with atopic dermatitis aged less than two years

BackgroundAtopy patch tests (APT) have been introduced as a valuable tool for the diagnosis of food allergy. However, interpretation of the readout of APT requires further clarification.ObjectiveTo investigate the accuracy of APT in identifying atopic sensitisation to hen's eggs (HE), cow's milk (CM), soybean and wheat in Chinese children with atopic dermatitis (AD) aged less than two years and to evaluate skin signs of APT for accurate diagnosis of food allergy.MethodsAPT was performed and food allergy confirmed by open oral food challenges with HE, CM, soybean and wheat in 150 Chinese AD children aged less than two years. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative likelihood ratio (LR−) of APT were calculated.ResultsErythema and infiltration were not sufficiently indicative of a positive APT. The PPV increased with the appearance of indurations and the number of papules. The true positive APT rate increased from scores of + to +++. The PPV and specificity were 100% while APT scores of +++ were obtained with HE, CM and wheat. The sensitivity of APT with HE, CM, soybean and wheat allergy ranged from 59.6% to 90.5%, while the specificity ranged from 82.1% to 92.4%.ConclusionThe APT is a suitable method for the diagnosis of AD in Chinese children aged less than two years with food allergies. Erythema and infiltration are not sufficient indicators of APT positivity. The PPV increases with indurations and the number of papules.     

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.     

Food allergy to wheat flour in adults

Wheat flour is a basic foodstuff. Food allergy has been especially described in children, in the form of atopic dermatitis. Food allergy in adults is rare and especially described in the form of anaphylactic shock sometimes induced by effort. Four observations of adult food allergy are presented. The IgE dependent mechanism is documented. The positive oral provocation tests needed doses of 17 to 30 grams. One crossed sensitivity between rye and barley was seen. The major allergen was probably gluten, particularly gliadines. Sensitization was probably due to prolonged inhalation of wheat flour. The authors stress the possibility of food allergy to wheat flour by other mechanisms, the difficulty of diagnosis, needed for a diet without cereal and gluten that is now non reimbursable.     

Food allergies and food intolerances

Adverse reactions to foods, aside from those considered toxic, are caused by a particular individual intolerance towards commonly tolerated foods. Intolerance derived from an immunological mechanism is referred to as Food Allergy, the non-immunological form is called Food Intolerance. IgE-mediated food allergy is the most common and dangerous type of adverse food reaction. It is initiated by an impairment of normal Oral Tolerance to food in predisposed individuals (atopic). Food allergy produces respiratory, gastrointestinal, cutaneous and cardiovascular symptoms but often generalized, life-threatening symptoms manifest at a rapid rate-anaphylactic shock. Diagnosis is made using medical history and cutaneous and serological tests but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed. Food intolerances are principally caused by enzymatic defects in the digestive system, as is the case with lactose intolerance, but may also result from pharmacological effects of vasoactive amines present in foods (e.g. Histamine). Prevention and treatment are based on the avoidance of the culprit food.     

Japanese Guideline for Food Allergy

Food allergy is defined as “a phenomenon in which adverse reactions (symptoms in skin, mucosal, digestive, respiratory systems, and anaphylactic reactions) are caused in living body through immunological mechanisms after intake of causative food.”Various symptoms of food allergy occur in many organs. Food allergy falls into four general clinical types; 1) neonatal and infantile gastrointestinal allergy, 2) infantile atopic dermatitis associated with food allergy, 3) immediate symptoms (urticaria, anaphylaxis, etc.), and 4) food-dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate-type food allergy).Therapy for food allergy includes treatments of and prophylactic measures against hypersensitivity like anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be conducted only if they are inevitable because they places a burden on patients. For this purpose, it is highly important that causative foods are accurately identified. Many means to determine the causative foods are available, including history taking, skin prick test, antigen specific IgE antibodies in blood, basophil histamine release test, elimination diet test, oral food challenge test, etc. Of these, the oral food challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions such as anaphylaxis.     

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.     

Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

Introduction and objectivesSince early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods.We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms.Materials and methodsIn patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT + APT were calculated.ResultsIn total 133 patients with suspected CMA (80) and HEA (53) were included in the study.In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%.In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD.ConclusionOur study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.     

Immunoglobulins in tears and sera in patients with atopic dermatitis.

The aim of the study was to investigate the role of circulating (i.e., present in the serum) and locally produced (i.e., in the lamina propria of mucous membranes) immunoglobulins including IgE. The IgG, IgA, IgM immunoglobulins, and IgE (total and specific) were measured in patients' sera with atopic dermatitis (AD) (n = 93). As control subjects 83 healthy volunteers, matched for sex and age, were included. The IgG and IgM levels were within the normal range. Mean value of the total IgA (2.55 +/- 0.26 g/L, in controls 1.49 +/- 0.32 g/L) and IgE (609 IU/mL, in controls below 40 IU/mL) levels were significantly elevated (p < 0.05) in sera of AD patients. Based on the serum total IgE levels (above or below 40 IU/mL) the patients were divided into RAST-positive and RAST-negative types of allergy, respectively. RAST-positive AD (n = 79) showed hypersensitivity to inhalant and food allergens determined by the specific IgE test. The majority of RAST-positive AD cases (n = 68) presented only skin manifestations, while the rest of the patients (n = 11) had rhinoconjunctivitis as well. RAST-positive AD patients with rhinoconjunctivitis showed an increased IgE level in tears (above 10 IU/mL). The specific IgE test positivity in tears correlated with elevated serum total IgE levels and specific IgE positivity (r = 0.925). Total and allergen-specific IgE in the tears can be used to diagnose allergy in vitro. It is believed that the mucosal permeability is enhanced in the atopic inflammatory process, and this may facilitate the transmission of environmental allergens.     

Japanese guidelines for food allergy 2020

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.     

Japanese guidelines for food allergy 2017

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.     

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.