Double-blind Placebo-controlled Oral Food Challenge Research Articles

Frequency of Food Allergy in School-Aged Children in Eight European Countries—The EuroPrevall-iFAAM Birth Cohort

The prevalence of food allergy was estimated in children aged 6 to 10 years in 8 European countries.Children from the EuroPrevall birth cohort managed from birth to 2.5 years to prospectively track food allergy onset were reassessed at the ages of 6 to 10 years (N = 6105) in 8 countries (Iceland, United Kingdom, Netherlands, Germany, Poland, Lithuania, Spain, and Greece).School-aged children from the 2005 multicenter European birth cohort were managed by using an online parental questionnaire (n = 6069), clinical visits including a structured interview (n = 2322) regarding previous and current food reactions and food consumption, a physical examination, and skin-prick testing (SPT) (n = 2188). Double-blind placebo-controlled oral food challenges (DBPCFCs) were performed for children (n = 46 of 238 eligible) whose history and SPT (≥3 mm) suggested possible allergies to cow’s milk, hen’s egg, wheat, soy, peanut, hazelnut, white fish, oily fish, or crustaceans. Whole cohort frequency results were extrapolated from fully assessed children.The prevalence of a food allergy to at least 1 confirmed allergen was 0.8%, adjusted to 1.4% to 3.8% by extrapolating to include children without a DBPCFC. Adverse reactions to foods were reported in 16.2% of online questionnaires, similar to face-to-face interviews. Most children consumed cow’s milk, hen’s egg, and wheat products; fewer consumed soy and crustaceans. A total of 10.2% were sensitized to at least 1 food (positive SPT); sensitization was most common to peanut (5.6%) and hazelnut (5.2%). A total of 10.4% were offered DBPCFC, but only 46 children participated. A total of 20 DBPCFCs were positive in 17 children; positive challenges occurred for hazelnut (n = 7), peanut (n = 3), and hen’s egg (n = 1).The estimated prevalence of food allergy in European children was 1.4% to 3.8%. The most common allergies were to peanut and hazelnut.In this study, researchers estimated the true prevalence of sensitization and food allergy in school-aged children in 8 European countries by using a previously established systematic approach to verify food sensitization and allergies in a large number of children from the participating countries. Although a substantial number of participants declined to a DBPCFC, this study reveals the feasibility, utility, and importance of including testing and DBPCFC evaluation in longitudinal food allergy studies.

Dog Ownership at 3 Months of Age is Associated With Protection Against Food Allergy

T Marrs, K Logan, J Craven. Allergy. 2019;74(11):2212–2219 A secondary, ad hoc analysis evaluating the association between dog ownership and food allergy development was performed in The Inquiring About Tolerance (EAT) cohort. The EAT study enrolled 1303 healthy and exclusively breastfed 3-month-old infants from the general population across England and Wales into a randomized trial investigating whether the early dietary introduction of six allergenic solids (egg, peanut, milk, wheat, cod and sesame) reduced the prevalence of food allergy diagnosed from 12–36 months …

Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort.

The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. A follow-up assessment at age 6-10years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.

Conjunctival provocation test in diagnosis of peanut allergy in children.

Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

Atopic Dermatitis and Food Allergy: An Associated Genetic Burden

Background: The association with food allergy (FA) in children with atopic dermati tis (AD) confronts the allergists with one of their most genetic challenges. The fluctuating clinical course of the diseases and the large variety of the environmental triggering factors make the identification of the offending food(s) rather difficult. Since foods are common triggering factors of AD in infancy and in childhood, it would seem obvious that elimination diets should be useful in the identification of the offending food(s) in these patients. Objective: Historical information re ferred by parents and elimination diets are rarely helpful for the identifica tion of the offending foods and only double-blind placebo-controlled oral food challenges (DBPCOFC) are useful for the di agnosis. The diagnosis of FA in infancy and in childhood is a chal lenge both for the pediatrician and allergist because it can be easily ac com plished only when there is a relation between the ingestion of the of fending food(s) and the onset of the symptoms, and when it can be demonst rated that these symp toms are the consequence of an immunological reac tion. How ever, the underlying immunologic mechanisms may be difficult to doc ument, and the only immunologic mechanism easily to prove in current practice is the IgEmediated one. Conclusion: In this article we analyze the first steps in achieving the diag nosis of FA. The manifestations due to FA, including cow’s milk (CM) allergy (CMA), are common also to other diseases, and in addition no reliable labo ratory tests are available, therefore the diagnosis should be done on a prov en demonstration that the symptoms are correlated to the ingestion of the specific food, and that the diagnostic tests indicate an immunologic pathoge nesis.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy

Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.

Peanut oral immunotherapy in adolescents: study protocol for a randomized controlled trial.

BackgroundPeanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk.Methods/DesignWe have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18–year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC).During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol.The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks.Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications.DiscussionThis double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life.Trial registrationClinicalTrial.gov: NCT02046083 (23 January 2014).

Positive reactions to placebo in children undergoing double‐blind, placebo‐controlled food challenge

The gold standard in the diagnosis of food allergy is the double-blind, placebo-controlled oral food challenge (DBPCFC). During this challenge, patients receive the allergenic food and placebo on separate randomized days, while being monitored for clinical reactions. Interestingly, some reactions are assessed as positive although the patients had received placebo. The aim of our study was to analyze incidence and characteristics of positive placebo reactions during DBPCFCs. In food-allergic children, we retrospectively analyzed positive placebo reactions in DBPCFCs in 740 placebo challenges in our department. Individual characteristics were compared, such as age or IgE levels, as well as clinical symptoms. Of all placebo challenges, 2.8% (21 of 740) were assessed as positive. Young children (age ≤ 1.5 years) had more (P = 0.047) positive placebo challenges (4.0%) compared to older children (age > 1.5 years; 1.5%). Children with positive placebo challenges had higher levels of total IgE (median 201 kU/L) compared to negatively classified children (median 110 kU/L). In children with positive placebo reactions, skin symptoms were observed significantly more often, with a worsening of atopic eczema (AE) as the most reported symptom. Placebo reactions in DBPCFC are not common. Worsening of AE is the most frequent clinical reaction associated with positive placebo challenges, and young children (age ≤ 1.5 years) seem to be affected more often. Therefore - contrary to current recommendations - DBPCFC tests should be considered in infants and young children, especially those with a history of AE.

Formula Selection for Management of Children With Cow Milk Allergy Influences the Rate of Acquisition of Tolerance: A Prospective Multicenter Study

Canani R Berni, R Nocerino, G Terrin. J Pediatr. 2013 Apr. [pii: S0022-3476(13)00284-9. doi: 10.1016/j.jpeds.2013.03.008 [Epub ahead of print]] To examine whether formula selection in children with cow’s milk allergy (CMA) will affect development of tolerance to cow’s milk protein. A total of 260 CMA infants, ages 1 to 12 months. CMA was confirmed at the initial visit through clinical evaluation, skin prick testing (SPT) (immunoglobulin E [IgE]-mediated CMA), atopy patch testing (APT) (non–IgE-mediated CMA), and double-blind, placebo-controlled oral food challenges (DBPCFC). This open-label, nonrandomized study evaluated the acquisition of tolerance in infants with CMA fed …

Long-term follow-up of oral immunotherapy for cow's milk allergy

Long-term follow-up of oral immunotherapy for cow's milk allergy

Recent advances in the diagnosis and therapy of peanut allergy

Peanut allergy is a life-threatening, IgE-mediated allergic disease. In developed countries, the prevalence rate of peanut allergy in school-aged children is reported to be in excess of 1% and continues to rise, representing a major public health concern. Peanut allergy is diagnosed on the basis of a relevant clinical history combined with results of skin-prick testing and/or peanut-specific IgE levels. A double-blind placebo-controlled oral food challenge is the gold standard for diagnosis. Currently, there is no approved treatment or disease-modifying therapy for peanut allergy. This review discusses recent advances in molecular diagnostic techniques for peanut allergy and highlights advances in peanut allergy therapeutics, discussing allergen-specific and allergen-nonspecific treatments that are currently in Phase I/II clinical trials.

Rhinitis induced to mace

Results Skin prick test to mace and ginger (10%) were positive and specific IgE to Pru p3 and mace were detected. Double-blind, placebocontrolled, oral food challenge (DBPCFC) with this spice showed rhinitis in few minutes and was negative to ginger. Through electrophoresis of peach, Pru p3, mace and ginger extracts were identified and the corresponding proteins purified and characterized as allergens. Mace extract was recognized by both anti-Pru p3 and antiTLPs antibodies, however immunoblotting study with patient sample demostrated proteins bands immunodetection in this extract with similar molecular weight to peach thaumatins. Finally skin prick tests with these purified allergens (Pru p 2.1 y 2.2) were positive. Conclusion Thaumatin-like proteins are a new family of pollen and fruit allergens. Because of the sequence homologies between PR-5 proteins and thaumatin, an intensely sweet tasting protein isolated from the fruits of the West African rain forest shrub Thaumatococcus daniellii, these molecules are referred to as thaumatin-like proteins (TLP’s). To our knowledge, this is the first report on the implication of TLPÂ s in spice allergy. Unfortunately, information on fundamental aspects of the TLP family remains quite limited, this means that challenging fundamental and applied studies need to be conducted to characterize TLP’s significance and clinical involvement.

Food allergy in gastroenterologic diseases: Review of literature

Food allergy is a common and increasing problem worldwide. The newly-found knowledge might provide novel experimental strategies, especially for laboratory diagnosis. Approximately 20% of the population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the "gold standard" for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be classified on the basis of immunologic or nonimmunologic mechanisms and the organ system or systems affected. Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges. The primary therapy for food allergy is to avoid the responsible food. Antihistamines might partially relieve oral allergy syndrome and IgE-mediated skin symptoms, but they do not block systemic reactions. Systemic corticosteroids are generally effective in treating chronic IgE-mediated disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental therapies for IgE-mediated food allergy have been evaluated, such as humanized IgG anti-IgE antibodies and allergen specific immunotherapy.

Gastrointestinal manifestations of cow's milk allergy

To review and discuss the relationship between cow's milk allergy (CMA) and some gastrointestinal manifestations, such as gastroesophageal reflux, constipation, food protein-induced enterocolitis, and food-induced eosinophilic proctocolitis, with respect to diagnostic strategies that might eliminate the need for a double-blind, placebo-controlled oral food challenge (DBPCFC). A review of pertinent PubMed articles, published during the past 10 years, was performed. To obtain positive and negative predictive values known as posterior probabilities and to calculate the likelihood ratio, only those studies including both patients and control subjects were selected for analysis. With respect to gastroesophageal reflux, a typical 24-hour esophageal pH monitoring pattern might obviate the performance of a DBPCFC in patients with symptoms of reflux suspected of having CMA, provided this pH pattern is confirmed in other studies. A relationship between CMA and constipation has been reported in only one prospective controlled study; the clinical and laboratory variables of perianal lesions, histologic abnormalities, and signs of hypersensitivity had likelihood ratios of 2.2, 2.4, and 3.7, respectively, and posttest probabilities of 83, 84, and 88%, respectively. Therefore, a DBPCFC is warranted. In reference to food protein-induced enterocolitis, clinical and laboratory criteria suggested in the literature for defining a food challenge as positive have not been prospectively evaluated in the untreated state. Some simple stool tests, such as fecal tumor necrosis factor-alpha and alpha1-antitrypsin determination, might be candidates for diagnostic studies in patients with food protein-induced enterocolitis, if prospectively evaluated. In infants with food-induced eosinophilic proctocolitis, rectal biopsy invariably shows eosinophilic infiltration and thus makes performance of a DBPCFC unnecessary. Although the current diagnosis of gastrointestinal manifestations of CMA usually depends on a DBPCFC, investigators continue to study other options for confirming the diagnosis.

Occupational rhinoconjunctivitis and food allergy because of aniseed sensitization

Aniseed is a spice frequently used in Mediterranean cooking and, as with other Umbelliferae, it has been involved in clinical allergy. This investigation was undertaken to study the allergens implicated in a case of occupational allergy to aniseed associated with rhinoconjunctivitis and gastrointestinal symptoms. Skin prick tests were performed to inhalant allergens, spices used in the patient's workplace (aniseed and cinnamon), and 12 other Umbelliferae spices, birch, and mugwort. A nasal challenge test to aniseed and cinnamon and a double-blind placebo-controlled oral food challenge test to aniseed were also performed. The molecular weights of the allergens were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting and cross-reactivity among Umbelliferae species by enzyme immunoassay inhibition. Skin prick tests showed a positive immediate response to aniseed, asparagus, caraway, coriander, cumin, dill, and fennel extracts, and an intense late response to aniseed. Skin prick tests to celery, carrot, birch pollen, and mugwort pollen extracts were negative. Results of a nasal challenge test were positive to aniseed and negative to cinnamon; an aniseed oral food challenge test yielded a positive response. The molecular weights of the main immunoglobulin (Ig)E-binding proteins in aniseed extracts were approximately 48, 42, 39, 37, 34, 33, and 20 kD. Caraway, fennel, cumin, and coriander extracts showed similar IgE-binding patterns. Enzyme immunoassay inhibition studies with the patient's serum revealed cross-reactivity among the IgE components from aniseed, caraway, coriander, fennel, and dill extracts. We demonstrate the presence of aniseed allergens in a case of occupational rhinoconjunctivitis and food allergy, with molecular weights for this spice that differed from those previously reported.

Die allergische Entzündung des Gastrointestinaltrakts

Allergic inflammation of the gastrointestinal tract is possibly underestimated regarding its frequency in untreated status recurrent disease of the stomach or intestine, that has to be considered in patients with unclear abdominal complaints. The illness is defined as immunologically mediated hypersensitivity reaction against exogenous antigens such as food antigens. In addition, other antigens such as pollen etc. should be considered as etiologic factors. Food intolerances without immunological background (e.g. malfermentation, enzyme deficiencies) and other gastro-enterologic diseases (e. g. Crohn's disease, ulcerative colitis, celiac disease, microscopic colitis, eosinophilic gastroenteritis) have to be ruled out. There are no laboratory parameters, which permit such a discrimination between gastrointestinal allergy and intolerance. Therefore, on the one hand the patients' history, on the other hand a global exclusion diagnostics is essential for the confirmation of the diagnosis. Classical allergologic tests (Prick, RAST/CAP etc.) have high false negative as well as false positive rates. The ,,golden standard for the verification of food allergies is the double-blind, placebo-controlled oral food challenge (DBPCFC). However, the significance of this approach is limited in case of gastrointestinal complaints, because validated methods to assess the induced symptoms are lacking. New test procedures such as local endoscopic provocation in the intestinal mucosa are tested at present. First line therapy is the elimination diet. Medical therapy is only necessary if the elimination diet fails to relief from symptoms. Other new therapeutic approaches (oral desensitization, probiotics etc.) are currently under investigation. A better understanding of the pathophysiology and an improvement of the diagnostic means should allow a more accurate assessment of the clinical significance of gastrointestinal allergies, which is of particular importance for the management of irritable bowel syndrome (IBS) and other GI diseases of unclear etiology that may be related to allergy.

Allergenicity of mare’s milk in children with cow’s milk allergy

Background: Cow’s milk allergy is a common disease of infancy and early childhood. If the baby is not breast-fed, a substitute for cow’s milk formula is necessary. Objective: The aim of this study was to investigate, in vitro and in vivo, the allergenicity of mare’s milk in a population of selected children with severe IgE-mediated cow’s milk allergy. Methods: Twenty-five children (17 male and 8 female) aged 19 to 72 months (median age 34 months) with IgE-mediated cow’s milk allergy were selected for this study. All the children underwent skin prick tests with cow’s milk and mare’s milk and double-blind placebo-controlled oral food challenge (DBPCOFC) with fresh cow’s milk, fresh mare’s milk, and, as placebo, a soy formula (Isomil, Abbott, Campoverde, Italy). We performed immunoblotting of cow’s and mare’s milk developed with IgE from allergic children. Results: All the children showed strong positive skin test responses to cow’s milk (4+); 2 children had positive skin test responses to mare’s milk (2+). All children had positive DBPCOFCs to cow’s milk; one child had a positive DBPCOFC to mare’s milk. No children reacted to the placebo (Isomil). In the cow’s milk, some proteins are able to strongly react with human IgE; when the sera are tested with mare’s milk, the bands corresponding to the same proteins are recognized by a lower percentage of sera. Conclusion: These data suggest that mare’s milk can be regarded as a good substitute of cow’s milk in most children with severe IgE-mediated cow’s milk allergy. It would be prudent, however, to confirm its tolerability by a supervised titrated oral challenge test. (J Allergy Clin Immunol 2000;105:1031-4.)

Dose-response in double-blind, placebo-controlled oral food challenges in children with atopic dermatitis

Background: Double-blind, placebo-controlled oral food challenges (DBPCFCs) are considered the “gold standard” for diagnosing food hypersensitivity, but the dose that elicits positive challenges, or determinants that may predict dose-response relationships, have not been reported. Objective: Our purpose was to determine the quantity of food that elicits reactions during DBPCFCs and to evaluate parameters that may predict the provocative dose and severity of reaction. Methods: We reviewed challenge data for all positive challenges to 6 common allergenic foods in children with atopic dermatitis evaluated for food allergy over a 13-year period. Challenge food was generally administered in 6 doses at 10- to 15-minute intervals beginning with 400 to 500 mg and completing with a total of 8 to 10 g of food. An open feeding of a larger portion followed negative challenges. At the physician’s discretion, a lower starting dose was occasionally used (100 mg, 250 mg). Food-specific IgE antibody concentrations (radioallergosorbent test [RAST]) were determined on stored sera of 20% of the challenges selected randomly and 99.6% had prick skin tests (PSTs) performed to the challenged food. Results: A total of 196 children (45% male; median age 5 y 9 mo; atopic dermatitis 98%, asthma 62%) had 513 positive challenges distributed as follows: egg 267, milk 117, soy 53, wheat 40, peanut 24, fish 12. The percentage of children reacting at the first dose (500 mg or less) was as follows: egg 49%, milk 55%, soy 28%, wheat 25%, peanut 26%, and fish 17%. Twenty-six milk challenges and 22 egg challenges were positive at a first dose of 250 mg; 3 milk challenges and 7 egg challenges were positive at a first dose of 100 mg. Eleven percent of the reactions that occurred on the first dose were severe. The percentage reacting after the final dose of the DBPCFC (or during open challenge) were egg 11%, milk 12%, soy 19%, wheat 12.5%, peanut 8.7%, and fish 25%. There was not a strong correlation between PST absolute wheal size or score (adjusted for histamine controls) and dose at reaction or severity of reaction (Rs range –0.22 to 0.39 for particular foods). Serum concentration of food-specific IgE did not correlate well with the dose causing a reaction or with severity (Rs range –0.40 to 0.55 for particular foods). Conclusions: This food-allergic population may react to as little as 100 mg of food, possibly less, and the dose causing a reaction and the severity of reaction is not predicted by PST or RAST. Lower doses (100 mg or less) should be investigated for their appropriateness in initiating DBPCFCs. (J Allergy Clin Immunol 2000;105:582-6.)

Allergenicity of goat’s milk in children with cow’s milk allergy

Background: Cow’s milk allergy (CMA) is a common disease of infancy and childhood. An appropriate cow’s milk (CM) substitute is necessary for feeding babies with CMA. CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas. In several countries, including Italy, goat’s milk (GM) formulas are available, and some physicians recommend them for feeding babies with CMA. Objective: We sought to investigate, in vitro and in vivo, the allergenicity of GM in 26 children with proven IgE-mediated CMA. Methods: All the children underwent skin tests with CM and GM; detection of specific serum IgE to CM and GM; and double-blind, placebo-controlled, oral food challenges (DBPCOFCs) with fresh CM, GM, and, as placebo, a soy formula (Isomil, Abbott, Italy). CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM, respectively. Results: All the children had positive skin test responses and CAP results to both CM and GM, all had positive DBPCOFC results to CM, and 24 of 26 had positive DBPCOFCs to GM. In CAP inhibition tests, preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM. In immunoblotting inhibition assays, preincubation with CM completely extinguished reactivity to GM, whereas GM partially inhibited reactivity to CM. Conclusions: These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA. A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA. (J Allergy Clin Immunol 1999;103:1191-4.)

Predictive values of food-specific IgE in food allergy

Summary The double-blind placebo-controlled oral food challenge is the «gold-standard for the diagnosis of food hypersensitivity. This test can be time-consuming, expensive (hospitalisation, monitoring), and entails significant risks; it is therefore difficult to perform routinely. Alternatives to this procedure must therefore be found among the other complementary investigations. Laboratory assays of food-specific IgE, using a technique which gives a reliable quantitative response, can provide an almost certain diagnosis, at some levels, and therefore avoids the need for food challenges in a proportion of patients. We tested 6 foods and found diagnostic predictive cut-off values that can be used in everyday practice for 4 of the foods: egg, milk, peanut, fish.