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.     

Pearls and Pitfalls in Diagnosing IgE-Mediated Food Allergy

The term “food allergy” is used by many patients and clinicians to describe a range of symptoms that occur after ingestion of specific foods. However, not all symptoms occurring after food exposure are due to an allergic, or immunologic, response. It is important to properly evaluate and diagnose immunoglobulin E (IgE)-mediated food allergy as this results in reproducible, immediate onset, allergic reactions that can progress toward life-threatening anaphylaxis. Proper diagnosis requires understanding of the common foods that cause these reactions in addition to key historical elements such as symptoms, timing and duration of reaction, and risk factors that may predispose to development of IgE-mediated food allergy. Diagnostic testing for food-specific IgE can greatly aid the diagnosis. However, false-positive test results are very common and can lead to overinterpretation, misdiagnosis, and unnecessary dietary elimination. This review discusses important aspects to consider during evaluation of a patient for suspected IgE-mediated food allergy.     

Food allergy: a challenge for the clinician

Adverse reactions to food resulting in gastrointestinal symptoms and due to immunologic reactions (allergy) are discussed: their pathogenesis, the prevalence of food allergens and the clinical digestive expressions of food allergy in children and adults are reviewed. In IgE-mediated food allergy, the usefulness of the biological available tests is considered, mainly CAP tests, for proceeding to the diagnosis and the monitoring of the allergic disease. Finally, the best actual diagnostic tools in food allergy are considered (clinical history, skin tests, biological tests and food oral challenges), with their limitations and indications.     

Gastrointestinal food allergies: do they exist?

Gastrointestinal (GI) symptoms are often attributed to adverse reactions to foods (ARF), but it is not always clear whether such reactions are caused by food allergy. A reaction to food proteins that is mediated by immunologic events is referred to as food allergy or food hypersensitivity. One of the most common types of food allergy is the IgE-mediated immediate hypersensitivity reaction to foods, which can give rise to dermatologic and respiratory tract symptoms in addition to GI complaints. Other GI forms of food allergy include food protein-induced enterocolitis or gastroenteropathy, celiac disease, and some cases of eosinophilic gastroenteritis. Because most patients complaining of adverse reactions to food have non-immune mechanisms for their complaints, it is important to distinguish the various types of ARF, as their management may differ substantially. Recent advances in the field of food allergy provide opportunities to improve diagnostic methods and develop new modalities for management that will complement the current practice of allergen avoidance.     

4 Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut

Despite the progress made in understanding the mechanisms of allergic disease, the pathophysiology and clinical significance of intestinal allergic reactions is largely unclean The intestinal mucosa is pre-destined for allergic reactions against food proteins and other antigens, and a number of studies indicate that allergic reactions occur in the GI tract. However, only a few epidemiological data are available, and the mechanisms are poorly understood. Intestinal allergic reactions may be different to classical IgEmediated reactions because patients with intestinal allergy often have negative skin tests and low levels of serum IgE. There is increasing evidence that, as with the findings in the skin and lung, mast cells and eosinophils play a central role in mediating intestinal allergic reactions. Furthermore, both types of cell are found to be activated in a number of other GI inflammatory diseases such as inflammatory bowel disease, celiac disease and eosinophilic gastroenteritis. However, the relationship between these pathologies and intestinal allergy is largely unclear. A major clinical problem is the lack of appropriate means for confirming the diagnosis of intestinal allergy. However, new test systems have been developed—such as the measurement of eosinophil mediators in stool samples or endoscopic provocation tests performed locally at the intestinal mucosa, which may improve the possibility of identifying afflicted patients on an objective basis. Since symptoms of intestinal allergic reactions are variable and nonspecific, the diagnosis requires the use of multiple tests and the exclusion of other pathologies such as infectious disease or non-immunological intolerance reactions. The preferred therapeutic option is avoidance of the allergens of relevance; however, this approach can be realized only in some patients, whereas others require additional treatment, for example, with oral cromoglycate or corticosteroids. Although we do not yet know to what extent intestinal allergic reactions may be an aetiological factor in GI diseases, such reactions should be considered in the differential diagnosis of unclear intestinal inflammation and irritable bowel syndrome.     

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.     

Study of food allergy in the Spanish population

BackgroundThe aim of the study was to investigate the prevalence of food allergy in patients referred to our Allergy Unit and to evaluate the diagnostic methods used.MethodsWe selected 674 patients referred to the Allergy Unit of our hospital from May 2002 to October 2004. The prevalence of symptoms was determined by a standardized questionnaire, prick-prick test, and serum specific IgE. In a second phase, double- blind oral challenge tests were administered.ResultsFood allergy was found in 106 patients (15.7%): 71 adults (67 %) and 35 children (33 %). The prevalence of food allergen sensitization was 14 % in adults and 20.8 % in children. A total of 89.6 % of the patients experienced symptoms immediately. Only 29.2% the patients of sought medical attention and adrenaline was administered to five (16.1 %). The foods most frequently involved in allergic reactions were fruits (56.6%) and tree nuts (22.6%).The most common symptoms were oral allergy syndrome (46.2 %), urticaria (32.1 %), and anaphylaxis (14.2 %).Combining the results of the questionnaire with those of prick-prick tests in patients whose allergy was confirmed by double-blind, placebo-controlled food challenge (9.1 %) showed a sensitivity of 95.5 %, a negative predictive value of 96 %, a specificity of 75 % and a positive predictive value of 73%.Conclusions1. The prevalence of food allergy in our sample was 9.1 %. 2. The foods most frequently involved in allergic reactions were fruits and tree nuts. 3. The most common symptoms were oral allergy syndrome, urticaria, and anaphylaxis. 4. Combining our questionnaire with in vivo tests allowed us to diagnose 75-96% of patients with no food allergy and 95 % of food allergy patients.     

Meeting the nutritional needs of the low-birth-weight infant

Approximately 5% of young children and 3-4% of adults exhibit adverse immune responses to foods in westernized countries, with a tendency to increase. The pathophysiology of food allergy (FA) relies on immune reactions triggered by epitopes, i.e. small amino-acid sequences able to bind to antibodies or cells. Some food allergens share specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. These allergens encounter specialized dendritic cell populations in the gut, which leads to T-cell priming. In case of IgE-mediated allergy, this process triggers the production of allergen-specific IgE by B cells. Tissue-resident reactive cells, including mast cells, then bind IgE, and allergic reactions are elicited when these cells, with adjacent IgE molecules bound to their surface, are re-exposed to allergen. Allergic reactions occurring in the absence of detectable IgE are labeled non-IgE mediated. The abrogation of oral tolerance which leads to FA is likely favored by genetic disposition and environmental factors (e.g. increased hygiene or enhanced allergenicity of some foods). For an accurate diagnosis, complete medical history, laboratory tests and, in most cases, an oral food challenge are needed. Noticeably, the detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Novel diagnostic methods currently under study focus on the immune responses to specific food proteins or epitopes of specific proteins. Food-induced allergic reactions represent a large array of symptoms involving the skin and gastrointestinal and respiratory systems. They can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms and thus differ in their nature, severity and outcome. Outcome also differs according to allergens.     

Food-dependent exercise-induced anaphylaxis--update and current data

Exercise-induced anaphylaxis (EIA) is defined as the onset of allergic symptoms during, or immediately after, exercise, the clinical signs being various degrees of urticaria, angioedema, respiratory and gastrointestinal signs and even anaphylactic shock. Food-dependent exercise-induced anaphylaxis (FDEIA) introduces food in the syndrome and is revealed by a chronological sequence in which food intake, followed by exercise, induces symptoms after a varying period. When the food intake and the exercise are independent of each other, there are no symptoms. FDEIA is not very frequent. Identifying the culprit food allergen depends on the patient's eating habits. Crustaceans and wheat flour are the two commonest but others foods can be implicated. The patho-physiology of FDEIA has not been clearly established but it appears to result from degranulation of mast cells. As with food allergy, FDEIA diagnosis is based on interview, skin and biological tests and challenge. For the clinical signs of allergy, antihistamines, corticosteroids and epinephrine may be administered. Prophylaxis aims to prevent a recurrence; the patient should be given an emergency kit to deal with any recurrent episode. After the food allergen has been identified, it should be avoided for at least 4 to 5 hours before any exercise.     

Management of the Patient with Multiple Food Allergies

Food allergies affect 6% of children and 3% to 4% of adults in the United States. Although several studies have examined the prevalence of food allergy, little information is available regarding the prevalence of multiple food allergies. Estimates of prevalence of people allergic to multiple foods is difficult to ascertain because those with allergy to one food may avoid additional foods for concerns related to cross-reactivity, positive tests, or prior reactions, or they may be reluctant to introduce foods known to be common allergens. Diagnosis relies on an accurate history and selective IgE testing. It is important to understand the limitations of the available tests and the role of cross-reactivity between allergens. Allergen avoidance and readily accessible emergency medications are the cornerstones of management. In addition, a multidisciplinary approach to management of individuals with multiple food allergies may be needed, as avoidance of several food groups can have nutritional, developmental, and psychosocial consequences.     

IgE-mediated food allergy--extensive review of the literature

Adverse reactions to food, i.e. food allergy and intolerance have gained considerable attention. This overview focuses on the diagnosis and management of IgE-mediated food allergy that is believed to be responsible for most immediate-type food-induced hypersensitivity reactions. Clinically, these reactions are characterised by a variety of signs and symptoms that occur within minutes or hours after consumption of the offending food. Reactions may be limited or more generalised with involvement of the skin, nose, eyes, and/or lungs. In more severe cases, cardiovascular symptoms including hypotension, shock, cardiac dysrhythmias and death can occur. In food-allergic individuals, IgE is produced against naturally occurring food components, primarily glycoproteins that usually retain their allergenicity after heating and/or proteolysis. While adults tend to be allergic to fish, crustaceans, peanuts and tree nuts, children tend to be allergic to cow's milk, egg white, wheat and soy more frequently. "Emerging" food allergens include tropical fruits, sesame seeds, psyllium, spices and condiments. These allergies frequently represent a cross-allergy to an allergen derived from another source, e.g. pollens or natural rubber latex. The evaluation of IgE-mediated food allergy relies on a careful history, physical examination, appropriate skin testing or in vitro testing with food extracts, and/or double blind, placebo-controlled food challenges. Avoidance remains the mainstay of therapy. However, allergens may be "hidden" and labelling can be non-precise or misleading, thereby severely hampering prevention. Patients with severe allergies should keep at hand an emergency kit with adrenaline, an antihistamine and an injectable rapid onset-of-action corticosteroid. At present there is no evidence to support the use of immunotherapy, except for research purposes. Production of "hypoallergenic" food is hampered by incomplete methods for assessing the allergenic potential of such novel foods.     

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.     

Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives

Adverse reactions to food that result in gastrointestinal symptoms are common in the general population; while only a minority of such individuals will have symptoms due to immunologic reactions to foods, gastrointestinal food allergies do exist in both children and adults. These immune reactions are mediated by immunoglobulin E-dependent and -independent mechanisms involving mast cells, eosinophils, and other immune cells, but the complexity of the underlying mechanisms of pathogenesis have yet to be fully defined. Knowledge of the spectrum of adverse reactions to foods that affect the digestive system, including gastrointestinal food allergy, is essential to correctly diagnose and manage the subset of patients with immunologically mediated adverse reactions to foods. Potentially fatal reactions to food necessitate careful instruction and monitoring on the part of health care workers involved in the care of individuals at risk of anaphylaxis. New methods of diagnosis and novel strategies for treatment, including immunologic modulation and the development of hypoallergenic foods, are exciting developments in the field of food allergy.     

Diagnostic tests for patients with suspected allergic disease. Utility and limitations

STUDY OBJECTIVE: To evaluate the clinical efficacy of diagnostic tests used for persons with suspected allergic disease. DESIGN: Information synthesis based on historical review of developments in the understanding of the pathophysiology of allergic diseases and on selected recent literature on efficacy of specific diagnostic tests. MAIN RESULTS: Skin testing is most effective when based on clues from the patient's history. The sensitivity and specificity of skin testing methods are compared: skin prick testing alone is often sufficient to identify or exclude immunoglobulin E (IgE)-mediated hypersensitivity, including food allergy. Except for penicillin and certain macromolecules, skin testing is not useful for evaluating drug allergy. Skin test titration may be useful for determining the starting dose for immunotherapy; otherwise it is rarely necessary. The patch skin test helps identify the cause of allergic contact dermatitis. Bronchial provocation testing is useful in special cases. Oral provocation testing may be used to identify allergy or other intolerance to suspected foods, food additives, and certain drugs. Provocation testing is time-consuming and requires special precautions. In-vitro methods for identifying allergen-specific IgE are especially useful when skin testing is unreliable, equivocal, or cannot be done. In-vitro tests should be used as adjuncts to the clinical interview and examination. CONCLUSIONS: Tests that are effective for identifying allergenic substances usually can be determined from a careful patient interview. Clinicians should be aware of nonspecific test results and allergy tests of unproven effectiveness.     

Gastrointestinal food hypersensitivity: Symptoms, diagnosis and provocation tests.

As many as 25% of the general population in Western countries believe that they suffer from adverse reactions to food. However, the actual prevalence of food allergy is much lower. Food-induced allergic reactions cause a variety of symptoms including cutaneous, gastrointestinal and respiratory tract. Food allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE-mediated (cellular) mechanisms. The clinical diagnosis is based on a careful history, laboratory findings (total and specific IgE), skin prick test, elimination diet and food challenges. New intestinal provocation tests have also been applied to pick up the allergic response of the duodenal mucosa by endosonography and external ultrasound. The management of food allergy continues to be a strict avoidance of the offending food item.     

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. There is conflicting evidence in the literature on the role for IgE mediated allergy in gastrointestinal reactions to staple foods. AIM: The aim was therefore to study the role of IgE mediated allergy in a group of patients with a history of gastrointestinal symptoms related to staple foods (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC, identified by screening of 96 consecutive patients referred to our allergy clinic for investigation of suspected gastrointestinal symptoms due to staple foods. METHODS: The screening included diaries as well as elimination diets and open and blinded food challenges. The frequency of atopy were compared between the double blind positive and double blind negative patients. RESULTS: The positive DBPCFC in the 15 patients included eight patients with milk intolerance, four with wheat flour, two with egg, and one with rye flour. There was no indications of an allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick test and radioallergosorbent test were negative for the relevant allergens. The frequency of atopy was four of 21 (19%) in the double blind negative group and three of 15 (20%) in the double blind positive group. CONCLUSION: In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods suggesting other mechanisms in adults than in children. Future studies may include measures of local events in the shock organs in relation to food intake, for instance utilising inflammatory markers in jejunal fluids.     

Differentiating Food Allergies from Food Intolerances

Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non–IgE mediated), including celiac disease and gluten sensitivity.

Poppy seed allergy: a case report and review of the literature.

Seeds of the poppy plant are traditionally used in bakeries, e.g., for garnishing bread or making cakes. Reports of allergic type I sensitivity to poppy seed are rare. According to the literature, severe reactions may occur, affecting mainly patients with allergy to pollens or nuts. We report on a 16-year-old boy who has developed erythema and angioedema, conjunctivitis, and dyspnea due to inhalation of poppy seed. Skin-prick tests were positive for poppy seed, hazelnut, and chickpea. The concentration of specific IgE for poppy seed, hazelnut, and peanut were 3.36 kU/L (class 2), 1.5 kU/L (class 2), and 6.17 kU/L (class 3), respectively. Allergic reactions associated with inhalation of food allergens have been reported for some foods but not for poppy seed. This is the first report on inhalative allergy to the poppy seed. Although poppy seeds are not commonly used, we underline the possible importance of such rare and often hidden sources of allergens, especially in patients with nut allergy.     

Management of allergic problems in primary care: time for a rethink?

Allergic diseases affect 20-30% of the UK population and when severe are associated with considerable morbidity and occasional mortality. Initiatives to improve allergy services in the UK have been led by consultant allergists and have focussed on increasing the number of hospital training posts to improve access to specialist services. A high profile campaign to raise awareness of the lack of allergy services has so far failed to generate further training numbers for allergy as a single specialty. Although the campaign to improve tertiary allergy services continues, most mild or moderate allergy symptoms (e.g. hayfever, allergic asthma, urticaria and some food allergy problems), can be managed successfully in primary care with appropriate interest and training. Despite the high and increasing numbers of patients with allergy and the ease with which the majority of symptoms can be controlled, many doctors in primary care are reluctant to take a more proactive approach to managing allergic conditions. This appears to be due to concerns about overburdening an already busy service, but may also be due to recommendations from allergy specialists which have implied that high quality allergy care is not possible without identification of specific allergic triggers using skin prick tests or blood tests. In reality, symptoms can usually be controlled using pharmacotherapy, although a working knowledge of the appropriate guidelines is helpful. In this paper, we propose minimum levels of knowledge for all practitioners in order to raise the standards of primary care allergy management, and provide recommendations for training for those wishing to manage successfully more difficult allergy cases and allergy diagnosis.