Lessons from atopy patch testing in Atopic Dermatitis

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.     

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.     

High frequency of atopic asthma in a pulmonary clinic population

Seventy-two consecutive adult asthmatic patients seen in the Pulmonary Clinic at Rhode Island Hospital were tested for atopy by prick test with 14 standard aeroallergens and by in vitro total and specific IgE determinations (FAST). A total of 58.3 percent of patients were found to be atopic by these tests. There was a significant difference between the mean total serum IgE in atopic and nonatopic asthma and in atopic asthma and control subjects. The age onset was lower in atopic asthmatic patients, and they were more likely to have a history of chronic rhinitis than nonatopic subjects. Family history of rhinitis or asthma and severity of asthma was not different between the two groups. Since our outpatient facility has a large allergy clinic in proximity to the pulmonary clinic, which was the source of our patient population, this investigation has a negative bias toward allergy. Nevertheless, this study reveals that atopy is common in adult asthmatic patients, and a battery of allergy tests (skin tests or in vitro tests) together with total serum IgE is able to differentiate between atopic and nonatopic asthma.     

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.     

Atopic eczema and allergy

Although the pathomechanisms of respiratory atopy are well established, the role of IgE-mediated hypersensitivity in the elicitation and maintenance of eczematous skin lesions in atopic eczema (AE) is still controversial. There is, however, evidence for exogenous elicitation of AE by contact with aero- or food allergens (house dust mite, cat, and so forth). Recent investigations show that epidermal Langerhans’ cells bind IgE via different receptors, especially the high-affinity receptor (FcεRI), which is significantly more strongly expressed in lesional skin of AE compared with other inflammatory skin diseases including allergic contact dermatitis. The clinical relevance of IgE-mediated sensitization in AE has been evaluated by the so-called atopy patch test (APT). The APT shows a much higher specificity compared with the skin prick test and radioallergosorbent test. However, allergic reactions do not play a decisive role in every case of AE. Other factors, such as nonspecific skin irritability or psychosomatic interactions, have to be considered. The concept of “extrinsic” versus “intrinsic” types of AE seems attractive. The concept of AE starting with T_H2 inflammation, becoming T_H1 inflammation in chronicity, and finally progressing to an autoimmune disease with IgE antibodies against autologous epidermal proteins is very attractive. Based on new knowledge, new methods in diagnosis, treatment, and prevention will develop, including more effective avoidance strategies, more potent anti-inflammatory treatment (eg, immunomodulation or topical immunophyllins), and new ultraviolet modalities. The new findings have given rise to a possible new classification of eczema/dermatitis. The concept of “patient management,” including all aspects from avoidance to therapy, has gained acceptance.     

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.     

Specific IgE to Common Food Allergens in Children with Atopic Dermatitis

Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. Objectives: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. Methods: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Results: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk (31%), hen's egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Conclusion: Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.     

Définitions des termes utilisés en allergologie alimentaire chez l’enfant

In so far as there are no recent medical references that specify terms used in allergy, and particularly terms dealing with food allergy, it seemed to us that it would be of use to compile a glossary that would be helpful in daily practice. The defined terms (plus comments) have been retained according to sequences that correspond to steps in a food allergy work-up. The following terms are entered successively in this review: atopic dermatitis; SCORAD; asthma; pulmonary function tests; medications for children; symptoms and severity of food allergies; immediate skin tests; intradermal tests or “atopy patch-tests”; allergen-specific and total serum IgE levels; oral provocation test; labial provocation test; other tests used in allergy work-ups; allergy, hypersensitivity, atopy; allergens, allergies, sensitizations, allergic cross-reactions; treatment of an allergic reaction.     

Percutaneous sensitization to almond oil in infancy and study of ointments in 27 children with food allergy

A five month old child with atopic dermatitis developed contact dermatitis to almond with positive patch test, positive prick test, and class 4 anti-almond IgE. Focal lesions of persistent eczema were correlated with application of almond oil for 2 month on cheeks and buttocks. The child had not ingested almond and her mother did not report almond intake during her breast-feeding. This observation points to the problems of possible percutaneous sensitisation to food proteins. The study of skin ointments containing components of food origin in 27 food sensitized atopic patients confirm that the choice of an ointment for lesional skin is of importance.     

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.     

"In vivo" and "in vitro": tests in the diagnosis of trichophyton allergy

A group of 100 patients with Trichophyton allergy and a control of group of 100 without fungal allergy have been compared in order to evaluate the diagnostic value of skin prick and intradermal tests and assay of Trichophyton specific IgE. The evaluation of sensitivity, specificity efficacy, positive and negative predictive values suggests that skin tests in two steps, prick and intradermal and research of specific IgE must be used to a better diagnostic approach. In cases were allergy is not cleared by antifungal therapy specific immunotherapy is worthwhile to be tried with a great percentage of success.     

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.     

Faut-il contre-indiquer l’utilisation des émollients à base d’avoine chez l’enfant atopique ?

Atopic dermatitis is the first atopic symptom. Local treatment makes use of emollient cream. Oat cream extracts were suspected of causing sensitization. This study was performed in 202 children with atopic dermatitis. Two subgroups were analysed: group 1, 105 children who had applied oat cream (Exomega®, Laboratoires Ducray, France) and group 2, 97 children who had never applied oat cream. Patch tests were positive for Rhealba® oat extract (total extract or protein fractions) in five cases (2.4%): three in group 1 and two in group 2. This result is clinically relevant in group 1, with increased eczema after use of Exomega®. Oat oral food challenge was negative in three children with an oat-positive skin prick test. There was no statistical difference between the two groups concerning age or positivity of oat tests and the results of other allergologic tests. Relevant oat cream allergy in children with atopic dermatitis concerned 1.4% of cases. These data suggest that emollient patch tests should be performed in children with atopic dermatitis, in order to use or exclude emollient cream. Further studies are required to evaluate changes in oat sensitization in older children.     

Predictive value of the sulfidoleukotriene release assay in oral allergy syndrome to celery, hazelnut, and carrot.

BACKGROUND: Patients sensitized to birch pollen frequently suffer from a food allergy to plant foods such as celery, carrots, or hazelnut. One of the main manifestations of birch pollen-related food allergy is the oral allergy syndrome. Skin tests and allergen-specific immunoglobulin (Ig) E determinations are poor predictors of such reactions when assessed by double-blind placebo-controlled food challenge (DBPCFC). OBJECTIVE: To investigate whether a cellular test based on leukotriene release from basophils, the cellular antigen stimulation test in combination with enzyme-linked immunosorbent assay (CAST-ELISA), is predictive of pollen-related food allergy. METHODS: Birch pollen-sensitized patients with positive DBPCFC to celery (n=21), hazelnut (n=15), and carrot (n=7) underwent skin tests along with determination of specific IgE and CAST-ELISA for the respective allergens. The results were compared with those of 24 birch pollen-sensitized patients with negative open food challenge to celery, hazelnut, and carrot. RESULTS: While skin prick tests had a sensitivity of 85%, 80%, and 29% for commercial extracts of celery, hazelnut, and carrot, respectively, prick testing with self-prepared extracts yielded sensitivities of 100%, 80%, and 100%, respectively. For specific IgE determinations, sensitivities were 71%, 73%, and 57%, respectively, and the respective specificities were 67%, 73%, and 60%. For CAST-ELISA with various sources and doses of allergens, the sensitivity varied from 71% to 95% for celery, 73% to 80% for hazelnut, and 43% to 86% for carrot. The respective specificities were 67% to 92%, 75% to 88%, and 77% to 91%. Analysis of the predictive value of CAST-ELISA with receiver operating characteristic curves showed that the results of the tests were more predictive of pollen-related food allergy than quantitative allergen-specific IgE determinations. CONCLUSIONS: CAST-ELISA is more specific than routine diagnostic tests for the diagnosis of pollen-related food allergy to celery, hazelnut, and carrot.     

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.     

Food-protein-induced enterocolitis syndrome caused by fish

IntroductionFood protein-induced enterocolitis syndrome (FPIES) occurs in infants. Typical symptoms include profuse vomiting and/or diarrhea several hours after ingestion of a given food. The disorder is a non-IgE mediated food hypersensitivity. The most frequently involved foods are milk and soy, but some cases of FPIES induced by solid foods have been described. We report 14 patients with FPIES due to fish protein.Material and methodsHistory and physical examination, skin prick test (SPT) with fish allergens and Anisakis simplex, prick-by-prick test with implicated fish and determination of specific IgE antibodies against fish were performed. In eight children atopy patch test (APT) were also performed. In nine patients an open oral food challenge with the implicated fish was carried out.ResultsThere were six boys and eight girls, aged from 9 to 12 months at diagnosis, with between two and six reactions to the offending fish proteins before the diagnosis was established. Four patients had a previous history of atopy. Presenting symptoms included diarrhea in two patients, profuse vomiting in six patients, and recurrent vomiting and subsequent diarrhea in three patients. In addition to these symptoms, associated septic appearance, apathy and lethargy were present in the remaining three patients. Onset of symptoms occurred a few minutes after fish ingestion in two patients and from 60 minutes to 6 hours in the 12 remaining patients. SPT to fish were negative in all patients. Serum food-specific IgE antibodies were negative in all patients except one. APT was positive in three patients. Open oral challenge (OC) was performed in nine infants and was positive in all. The patients were followed-up for between 1 and 7 years after diagnosis, and follow-up OC tests were performed after fish had been eliminated from the patients’ diet for 3-4 years. Four patients became clinically tolerant to the causal food. Three patients currently tolerate only one type of fish (swordfish).ConclusionsWe report 14 patients with FPIES caused by fish protein. The symptoms suggest a form of cell-mediated, non-IgE mediated food hypersensitivity. The gold standard for diagnosis is OC, although caution should be exercised in infants with several reactions or a recent diagnosis. After a period of elimination of the causal food from the diet, tolerance can develop.     

Robustness into advanced age of atopy-specific mechanisms in atopy-prone families

We evaluated atopy-associated parameters in 1,099 people (aged 6-84 years) from families with history for atopy. All were tested for serum total immunoglobulin E (IgE) and allergen sensitivity by skin prick test. Specific IgE tests were done in randomly selected families. There was a decline with age in serum total IgE values, and relative atopy "incidence rates" were slightly lower among those older than 60 years. However, there was no change with age in sensitivity or severity of atopy. Among those sensitized to ragweed (Ambrosia artemisilfolia), there was no age-associated change in IgE levels specific to Amb a 1, a major allergen extracted from ragweed, and no change in the binding affinity of IgE for the Amb a 1 allergen. Among families with atopic histories, the underlying atopic mechanisms are particularly robust, and the atopic propensity remains into advanced age. In addition, established atopic responses may be focused in an immune system compartment either independent of or minimally influenced by T-cell activity.     

Oral rush desensitization with tomato: a case report.

Adverse food reaction in which no immunological mechanism is demonstrated should be termed nonallergic food hypersensitivity or food intolerance. We present the case of a 12-year-old girl with a clinical history of abdominal pain, nausea, and general malaise after tomato intake which completely remitted with antihistamines. The patient underwent a complete allergy evaluation: skin prick tests, serum specific IgE and IgG4 tests to tomato, and double-blind placebo-controlled food challenge. Skin prick tests and specific IgE to tomato were negative while the food challenge was positive. At the end of the workup, the patient underwent an oral rush desensitizing treatment. At the end of the treatment the patient could eat a maintenance dose of 100 g of tomato daily with no side effects at all. This successful result suggests that the oral desensitizing treatment can be used in patients with nonallergic food hypersensitivity.     

Lait et atopie

Cow's milk allergy occurs frequently in infants and children. Its clinical manifestations are heterogeneous, making diagnosis sometimes difficult. The diagnosis is based on elimination-reintroduction of cow's milk proteins. Measurement of specific IgE and skin prick and patch tests may contribute to the diagnosis. Substitution of an extensively hydrolysed protein formula for cow’s milk represents the mainstay of treatment. In case of allergy to such a formula, an amino acid-based formula should be used. The course of cow's milk allergy is more prolonged than previously thought and seems even more protracted in children with multiple food allergies.     

Japanese Guideline for Food Allergy 2014

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food."Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy).The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral 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.