Sublingual-oral rush desensitization to mixed cow and sheep milk: a case report.

We attempted an oral rush desensitization with mixed cow and sheep milk in a 6-year-old boy who had had adverse reactions to cow and goat milks. Skin prick tests and specific immunoglobulin (Ig) E to cow, sheep and goat milks were positive. The double-blind, placebo-controlled food challenge with cow milk was positive too. He underwent a 12-day sublingual-oral desensitization treatment with mixed cow and sheep milk. Specific IgE and IgG4 were measured. Open oral challenges with cow milk, sheep milk and sheep cheeses were also performed after the desensitization. At the end of the desensitizing treatment our patient could tolerate 120 mL of mixed milk. Specific IgE levels did not vary, whereas an increase of specific IgG4 concentrations was observed. Open oral challenges with cow and sheep milks and sheep cheeses were negative. Oral rush desensitization may represent an alternative approach to the treatment of food allergy in children.     

Oral Specific Desensitization in Food-Allergic Children

The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG₄ showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.     

Skin testing and food challenges for the evaluation of food allergy

Skin testing by prick technique has an excellent safety record in the evaluation of food hypersensitivity. Skin prick tests for the common food allergens are excellent tools for identifying those at very low risk of reaction on eating the food but are of variable value in identifying patients who will be positive on challenge. Intradermal skin tests to foods are less safe and appear to add no predictive information. Skin tests to less common food allergens, especially fruits, are less well characterized and may require use of the food item itself as the source of allergen rather than a commercial extract. For a few foods, the CAP system fluorescent enzyme immunoassay (Pharmacia, Peapack, NJ) recently has been shown to have good ability to identify patients at very high probability of reaction on oral challenge. Oral challenge remains the definitive method of demonstrating sensitivity or tolerance to a food. The double-blind, placebo-controlled food challenge is the gold standard of diagnosis, but in many situations, simpler open or single-blind challenge procedures may be substituted. With careful, incremental dosing and a low starting dose, oral challenges for food hypersensitivity have an excellent safety record. Skin prick tests are of little value in the evaluation of adverse food reactions not mediated by IgE. Oral challenge is relied upon in this situation for definitive diagnosis, but challenges may be cumbersome if the time course of the presumed reaction is not rapid.     

Egg and milk allergy in asthmatic children: assessment by immulite allergy food panel, skin prick tests and double-blind placebo-controlled food challenges

There is a perception that asthmatic symptoms may be worsoned by ingestion of certain foods. This study aimed to investigate whether ingestion of cow's milk or egg might induce respiratory symptoms in asthmatic children. Fifty asthmatic children aged 1.5 to 6 years old, with positive Immulite Food Panel FP5 test results were included in the study. Fifty healthy children within the same age group were accepted as control group. Total serum IgE levels were measured and skin prick tests for food allergens including milk and egg were performed. All of the subjects underwent oral, double-blind, placebo-controlled challenge with fresh egg and cow's milk powder. Two medical histories were confirmed by double-blind, placebo-controlled challenge in 9 patients (22.2%). Skin prick tests were positive in 9 patients (18%) with milk and 18 patients (36%) with egg antigen. Two children experienced wheezing, one after ingesting milk and the other after egg challenge (4%). In the control group no positive reactions were seen with egg or milk challenges. Our findings confirm that food allergy can elicit asthma in children, but its incidence is low, even with major allergens such as egg and milk. History, specific IgE determinations and skin prick tests are not reliable in diagnosing food reactions. Since any diet can cause rapid deficiencies in infancy, diet restrictions must not be applied, without performing double-blind, placebo-controlled challenge.     

Work up of patients with history of beta-lactam hypersensitivity

IntroductionBeta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction.Materials and methodsSixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed.ResultsSixty-seven patients (54 ♀), with a mean age±SD of 36.6±19.3 years (4–78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results.ConclusionsOf the 67 studied cases with history of beta-lactam hypersensitivity reactions, 18 (27%) were confirmed after testing. A combination of skin testing, specific IgE determination and drug challenge is necessary since none has sufficient sensitivity to be used alone.     

Angioedema induced by inhalation of vapours from cooked white bean in a child

BackgroundThere are few references of allergic reaction to beans in childhood. We report the case of a seven years old boy who suffered from angioedema associated to inhalation of vapours from cooked white bean.Methodsskin prick tests (SPT) were performed by prick-by-prick with cooked white bean and legumes. It was also determined total IgE and specific IgE antibodies to bean and legumes with the use of the CAP enzymo-immunoassay. Subsequently, a oral challenge test was carried out with white bean.ResultsThe prick-by-prick with white bean was positive in our case, and negative in ten controls patients. Specific IgE in patient serum, assayed by CAP was positive for white bean and green bean. The patient developed angioedema after ingestion cooked white bean.Conclusionwe demonstrated a type I hypersensitivity to white bean in a seven years old child by SPT, specific IgE antibodies and challenge test.     

Prawns, barnacles, and nonsteroidal anti-inflammatory drugs: effect modifiers or diagnostic confounders [corrected]

A 42-year-old woman with no history of atopy reported several episodes of generalized urticaria and shortness of breath after eating shellfish (prawns and barnacles) but with good tolerance of the same foods between episodes. Skin prick tests (SPTs), serum enzyme allergosorbent tests (EAST) for specific immunoglobulin (Ig) E, Western blot and inhibition assays, and oral challenge tests with prawns, barnacles, nonsteroidal anti-inflammatory drugs (NSAIDs), and alcohol as potential effect modifiers were performed. Specific IgE to both barnacle and prawn were detected by SPTs and EAST. Results from a Western blot of raw prawn revealed an IgE binding band of 37 kDa and IgE binding bands of 143, 83, 38, 32, and 20 kDa appeared in the raw barnacle assay. Oral challenge tests were positive with prawns and prawn extract only if preceded by NSAIDs. Oral challenges with NSAIDs alone, prawns alone, barnacles with or without NSAIDs and alcohol led to no reaction. A synergistic effect of NSAIDs in inducing anaphylaxis after prawn intake was confirmed. No similar effect was achieved with barnacles despite the presence of specific IgE. Additional factors needed to elicit a clinical reaction in food allergy may not be obvious and several oral challenge protocols are mandatory in such cases.     

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.     

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.     

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.     

Anaphylaxis to proton pump inhibitors

Proton pump inhibitors (PPI) are widely used for the treatment of peptic ulcer, but cases of anaphylactic reactions have rarely been described. We present a patient who experienced an episode of urticaria 30 minutes after oral intake of an omeprazole capsule. Skin prick tests to omeprazole, pantoprazole and lansoprazole were positive. Challenge test with lansoprazole was carried out and within 45 minutes the patient developed urticaria, facial edema, vomiting, and hypotension. Oral challenge with other imidazole derivatives (ketoconazole, cimetidine, metronidazole) were carried out with good tolerance. Serum tryptase levels determined 3 hours after the adverse reaction to lansoprazole were elevated. Specific IgE to PPI were not detected by an enzyme-linked immunosorbent assay technique. The clinical findings, positive skin prick test to PPI and elevated serum tryptase levels suggest that an IgE-mediated mechanism was implicated in the reactions to both omeprazole and lansoprazole. Skin prick tests may be a useful tool for detecting patients sensitized to PPI. An experimental protocol was used to detect specific IgE antibodies against PPI, which may explain RAST negativity. The previous findings suggest that cross-reactivity between PPI exists, but not with other imidazoles.     

Molecular diagnosis of allergy to Anisakis simplex and Gymnorhynchus gigas fish parasites

BackgroundThere has been an increase in the prevalence of hypersensitivity to Anisakis simplex. There are fish parasites other than Anisakis simplex whose allergenicity has not yet been studied.ObjectiveTo assess IgE hypersensitivity caused by fish parasite allergens in patients with gastro-allergic symptoms after consumption of fish, shellfish or cephalopods, compared with healthy subjects, pollen allergic individuals and children with digestive symptoms after eating marine food.MethodsWe carried out in vivo tests (skin prick) and in vitro tests (specific IgE determination, Western blot) and component resolved diagnostics (CRD) using microarray analysis in all patients.ResultsCRD better detected sensitisation to allergens from marine parasites than skin prick tests and determination of specific IgE by CAP. Sensitisation to Gymnorhynchus gigas was detected in 26% of patients measured by skin prick tests and 36% measured by IgE.ConclusionsThe prevalence of hypersensitivity to marine parasite allergens other than Anisakis simplex should be studied, and the most appropriate technique for this is CRD.     

Eosinophilic esophagitis

BackgroundEsophagitis is an increasingly diagnosed disease. Patients with gastroesophagic reflux, dysphagia, vomiting or abdominal pain, with a torpid response to the treatment, could be suffering from it.Material and methodsA 37 year-old male patient with background of gastroesophagic reflux and dysphagia for solids since 2002, self-limited diarrhea episodes and intolerance to alcoholic drinks due to epigastric pain. Skin prick tests, specific IgE, histamine release test and basophil activation test were carried out.ResultsSkin prick test to the usual allergens with negative result; prick-prick tests to egg white and yolk, milk and apple with positive result to egg white; total serum IgE within normal levels, specific IgE to egg white with positive result; histamine release test (HRT) and basophil activation test (BAT) with positive result to egg white and yolk.ConclusionThe patient was diagnosed eosinophilic esophagitis. The commercial food extracts have a great variability in their allergenic composition, which could result in false negative results in the prick test. Prick-prick with the natural food is a more sensitive technique than prick in the diagnosis of food allergy. There are other useful in vitro techniques, apart from specific IgE, in the diagnosis of food allergy. In our case, an exclusion diet of the involved food was more effective than other treatments for remission of the symptoms.     

"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.     

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.     

Severe tomato allergy (Lycopersicon esculentum).

Although tomatoes are a commonly consumed food, severe allergic reactions to tomatoes are unusual or rarely reported. Previously reported allergic manifestations to tomato include urticaria/angioedema, dermatitis, oral allergy syndrome, rhinitis, and abdominal pain. The aim of this study was to report two patients with significant immediate hypersensitivity reactions to tomato and characterize the responsible allergen. We reviewed the history and documentation of tomato-specific immunoglobulin E (IgE) of two patients with adverse symptoms after ingesting tomato. Fresh tomato extracts prepared from the skin, seeds, and flesh of red, ripe tomatoes were evaluated for total protein content and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to characterize the tomato protein. IgE enzyme-linked immunosorbent assay (ELISA) using the patients' serum against the various tomato extracts was accomplished and IgE immunoblot was performed. Percutaneous skin tests or radioallergosorbent tests (RASTs) were positive to tomato in both patients. Both adults experienced laryngeal edema and one had anaphylaxis. Similar total protein contents were found in each of the tomato extracts and gel electrophoresis revealed similar protein profile for skin and seed extracts with protein bands discernible at molecular weights of 21, 33, and 43 kDa. One patient reacted specifically to a 43-kDa protein band on IgE immunoblot. The two cases show that severe allergic reactions to tomato occur in adults and one is associated with IgE binding to a 43-kDa protein.     

Measurement of levels of specific IgE by the Efficient New Enzymatic Allergy (ENEA) System II (CIS bio)

The diagnosis of IgE dependant food allergy relies on the demonstration of specific IgE by prick tests or in vitro tests. The ENEA System II (CIS bio international) is a new automatic assay analyser of specific IgE, that uses allergens coupled to a solid phase and a urease marked anti-IgE antibody. This study aims to compare the performance of the ENEA System II to that of Pharmacia CAP System for the assay of food specific IgE (milk, eggs, peanuts) by means of unit tests and multitests. Sixty three patients were included: 10 non atopic controls, 19 egg-allergic patients, 10 patients allergic to cow's milk, and 24 patients allergic to peanuts. The food allergy was proved by means of a double blind oral, labial or bronchial challenge and/or effective avoidance of the food. For both systems, the specificity of unit tests was 100%. Sensitivity was 60% and 100% with both systems, using milk and peanuts respectively. However, using eggs, it was only 74% with ENEA System II versus 95% with Pharmacia CAP System. The intra-trial variation coefficients were comparable. In contrast, inter-trial variation coefficient was very high for the ENEA System II (20.3% versus 7.3%). The multitest named "children's food" showed an important inter-set variability. In conclusion, the ENEA System II is a rapid automatic tester whose performance has to be improved. The actual thermostatically control of the system was shown to achieve quality assay. The conservation of the solid phase, recently perfected, is expected to suppress the inter-set variability.     

Food allergy in gastroenterologic diseases： Review of literature

INTRODUCTION Food allergy is recognized as a common worldwide prob- lem, and, like other atopic disorders, its incidence seems to increase. Moreover, food-related allergic disorders are the leading cause of anaphylactic reactions treated in the emer- genc…     

Food hypersensitivity reactions visualised by ultrasonography and magnetic resonance imaging in a patient lacking systemic food-specific IgE

BACKGROUND: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. METHODS: A 24-year-old female presented with self-reported food hypersensitivity, particularly related to the intake of egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo-controlled food challenge with raw egg was positive, but all other conventional tests of food hypersensitivity, including skin prick test, total and food-specific IgE in serum, were negative. A thorough investigation programme could not reveal any organic disease of the gastrointestinal tract. We extended the evaluation to include two new provocation tests, where intestinal wall thickening and the amount of luminal liquid were monitored by external abdominal ultrasound and MRI. RESULTS: Both ultrasound and MRI investigations indicated intestinal wall thickening and influx of large amounts of fluid into the proximal small intestines within 10 min of duodenal challenge with egg. The response was associated with abdominal pain and bloating. CONCLUSIONS: The response to provocation was typical of an immediate allergic reaction. Our results indicate that local food-induced hypersensitivity reactions can occur in the gut in the absence of systemic indications of IgE-mediated allergy. Abdominal ultrasonography and MRI might become valuable tools for documenting such responses.