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Background Although most of cow's milk ( CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk-specific IgE and IgG4 plays a major role. Objective We aimed to investigate differences in IgE and IgG4 antibody binding to CM epitopes between patients with persistent CM allergy ( CMA) and those that naturally became tolerant. Methods Sera from 35 children with proven CMA (median age at inclusion of 10 months) were analyzed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from five major CM proteins were measured with a peptide microarray-based immunoassay. Results At baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and β-casein ( P<.01, false discovery rate [ FDR]<.1). Interestingly, differences between IgE and IgG4 binding intensity to CM peptides decreased when the patients became tolerant. Conclusions Our results suggest that the overlap between IgE and IgG4 might be important in natural tolerance acquisition. Further studies are needed to confirm our data and can eventually lead to development of more targeted treatment of food allergy. [ABSTRACT FROM AUTHOR]

Introduction Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. Methods In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the Immuno CAP- FEIA and a standardized diagnostic procedure including oral challenges where indicated. Results A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Conclusion Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology ( EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis. [ABSTRACT FROM AUTHOR]

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's ( EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention. [ABSTRACT FROM AUTHOR]

Background The measurement of specific serum immunoglobulin E ( sIgE) and the skin prick test (SPT) are accepted tools in the diagnostic work-up of suspected food allergy. Often only one of the methods is used to determine sensitization; however, it is still under debate whether these two methods can be used interchangeably. Objectives To investigate the concordance of SPT and sIgE serum assays with regard to suspected food allergy. Methods In 395 children referred to our clinic with suspected cow's milk allergy and in 268 children with suspected hen's egg allergy specific immunoglobulin E (IgE) was measured, a SPT and an oral food challenge performed. A weal size ≥ 3 mm and sIgE ≥ 0.35 kU/L were considered positive. The weal size of the SPT and the level of food-specific IgE were tested for correlation for each allergen. Results Of the 395 (23%) children orally challenged with cow's milk, 92 showed no corresponding results for SPT and sIgE as either positive or negative. For hen's egg, in 27 of 268 (10%) children differing test results for SPT and sIgE in serum were obtained. Moreover, regarding the quantitative values for sIgE and SPT in children with or without clinically relevant food allergy, sIgE and SPT correlated badly. Conclusions The concordance between SPT and sIgE is surprisingly low for cow's milk and hen's egg on an individual basis. Therefore, the tests should not be used interchangeably. Especially in children who receive a negative test result the alternative test should also be used. Furthermore, our data indicate again that oral food challenges are still the method of choice to diagnose food allergies. [ABSTRACT FROM AUTHOR]

To cite this article: Calderon MA, Gerth van Wijk R, Eichler I, Matricardi PM, Varga EM, Kopp MV, Eng P, Niggemann B, Nieto A, Valovirta E, Eigenmann PA, Pajno G, Bufe A, Halken S, Beyer K, Wahn U. Perspectives on allergen-specific immunotherapy in childhood: An EAACI position statement. Pediatr Allergy Immunol 2012: 23: 300-306. Abstract This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen-specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential. The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation. [ABSTRACT FROM AUTHOR]

To cite this article: Muraro A, Clark A, Beyer K, Borrego LM, Borres M, Lødrup Carlsen KC, Carrer P, Mazon A, Rancè F, Valovirta E, Wickman M, Zanchetti M. The management of the allergic child at school: EAACI/GA2LEN Task Force on the allergic child at school. Allergy 2010; 65: 681–689. Allergy affects at least one-quarter of European schoolchildren, it reduces quality of life and may impair school performance; there is a risk of severe reactions and, in rare cases, death. Allergy is a multi-system disorder, and children often have several co-existing diseases, i.e. allergic rhinitis, asthma, eczema and food allergy. Severe food allergy reactions may occur for the first time at school, and overall 20% of food allergy reactions occur in schools. Up to two-thirds of schools have at least one child at risk of anaphylaxis but many are poorly prepared. A cooperative partnership between doctors, community and school nurses, school staff, parents and the child is necessary to ensure allergic children are protected. Schools and doctors should adopt a comprehensive approach to allergy training, ensuring that all staff can prevent, recognize and initiate treatment of allergic reactions. [ABSTRACT FROM AUTHOR]

Background: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases. [ABSTRACT FROM AUTHOR]

Background: Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction. Methods: Children with challenge proven immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy or hen’s egg (HE) allergy were randomly assigned to SOTI or elimination diet as a control group. Specific oral tolerance induction treatment was performed at home on a daily basis according to a study protocol with fresh CM or lyophilized HE protein. Re-evaluation of clinically relevant food allergy was performed by food challenge after a median of 21 months. Children in the SOTI group received a secondary elimination diet for 2 months prior to follow-up challenge to evaluate persistence of induced oral tolerance. Results: At follow-up challenge, nine of 25 children (36%) showed permanent tolerance in the SOTI group, three of 25 (12%) were tolerant with regular intake and four of 25 (16%) were partial responders. In the control group, seven of 20 children (35%) were tolerant. Allergen-specific immunoglobulin E decreased significantly both in children who developed natural tolerance during the elimination diet ( P < 0.05) and in those with SOTI ( P < 0.001). Conclusions: Specific oral tolerance induction seems a valid treatment option for patients with persistent food allergy. Indications may be given if avoidance cannot be guaranteed or for those who are eager to eat the food in question. Advantages of SOTI are the increased threshold dose for allergic reactions and the substantially reduced risk of severe allergic reactions after inadvertent ingestion of the allergen. However, careful monitoring during SOTI is mandatory. [ABSTRACT FROM AUTHOR]

Background: Approximately two-thirds of egg-allergic infants become tolerant within the first 5 years of life. Objective: We sought (1) to compare the recognition of sequential (linear) and conformational binding sites of ovomucoid, ovalbumin and ovotransferrin, by IgE antibodies of children with persistent and transient egg allergy, (2) to identify immunodominant IgE-and IgG-binding epitopes of ovomucoid, and (3) to compare epitope-specificity of IgE antibodies between patients with differing natural histories of egg allergy. Methods: Using immunodot-blots or ImmunoCAPs, IgE-antibodies against conformational (native) and sequential (reduced and alkylated) egg proteins were determined at the time of clinical reactivity in patients who retained their allergy and in those who developed clinical tolerance. IgE- and IgG-binding epitopes were mapped for ovomucoid using overlapping decapeptides on SPOTs membranes. Recognition of the major IgE-binding epitopes were compared between patients with differing natural histories of egg allergy. Results: The patients with long-lasting egg allergy had a higher concentrations of IgE antibodies against sequential and native ovomucoid and ovalbumin than the children who subsequently gained tolerance ( P < 0.01). Four major IgE-binding epitopes were identified in ovomucoid at amino acid 1–10, 9–20, 47–56, and 113–124. IgE antibodies of all seven patients with persistent egg allergy recognized these epitopes whereas none of the 11 children who outgrew their egg allergy did so. Conclusions: Patients with persistent egg allergy develop IgE antibodies against more sequential and conformational epitopes of ovomucoid and ovalbumin. The presence of serum IgE antibodies to specific sequential epitopes of ovomucoid may be used as a screening instrument for persistent egg allergy. [ABSTRACT FROM AUTHOR]

Background For immunotherapeutic approaches, ‘critical’ amino acids (AAs) within allergenic epitopes are replaced with alternate AAs to eliminate IgE antibody binding. Objective To determine the critical AAs for IgE binding in β-casein and β-lactoglobulin (BLG). Methods Peptides of 10–14 AAs in length were synthesized on a derivatized cellulose membrane with single AA substitutions (alanine or glycine) at each position. Membranes were incubated with a pool of sera from 15 cow's milk-allergic patients and individual sera from six of the 15 patients. In cases where no decrease in binding occurred with a single AA substitution, peptides with two AA substitutions were generated and labelled. Results Using pooled patient sera, single AA substitutions led to complete elimination of binding to six of 11 peptides for β-casein and to all six peptides for BLG. Substituting two AAs led to an elimination of binding to four of the remaining five β-casein epitopes. However, in three of the 11 modified β-casein peptides and five of the six BLG peptides, no decrease in IgE binding occurred in at least one individual patient. For these patients, critical AAs other than those defined by the patient serum pool were identified, indicating a heterogeneous pattern of IgE recognition. Conclusion These results indicate that AAs critical for IgE binding are more heterogeneous than initially defined by pooled milk-allergic patient sera. For future immunotherapeutic interventions with mutated peptides, critical AAs should also be identified with individual patient sera to account for heterogeneity of IgE binding between patients. [ABSTRACT FROM AUTHOR]

Specific oral tolerance in food allergy can be induced by oral administration of the offending food, starting with very low dosages, gradually increasing the daily dosage up to an amount equivalent to a usually relevant dose for daily intake, followed up by a daily maintenance dose. Unfortunately, the body of scientific evidence concerning specific oral tolerance induction (SOTI) is still rather poor. Following a couple of case reports, only a few studies on a limited number of patients including different allergens are available. So far, no placebo-controlled, long-term study has been published. Concerning the underlying immunological mechanism, a limited number of studies have reported on changes in antibody production, and more recently on the role of different T-cell populations. The individual pattern of clinical reaction during SOTI seems to vary considerably between patients and from allergen to allergen. Arguments in favour of SOTI are the safety for an inadvertent intake of the offending food and the increased quality of life. Arguments against SOTI are the necessity for a regular intake and possible long-term compliance problems. Indications to consider SOTI in the future might be (i) importance of the incriminated food for the individual nutritional regimen, (ii) avoidance of the corresponding food cannot be assured and (iii) persistent severe food allergy. However, before SOTI can be recommended for the daily praxis, more studies are warranted to clarify whether certain patients may profit from SOTI and to understand the underlying mechanism. [ABSTRACT FROM AUTHOR]

Background The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of food allergy. Objective To evaluate the diagnostic capacity of the SPT in predicting the outcome of oral food challenges, and to determine decision points for the weal size and the skin index (SI) that could render double-blind, placebo-controlled food challenges unnecessary. Methods In 385 children (median age 22 months), 735 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. Three hundred and thirty-six of 385 (87%) children suffered from atopic dermatitis. SPT was performed in all children. Diagnostic capacity, receiver–operator characteristics (ROC) curves and predictive decision points were calculated for the mean weal size and the calculated SI. Results Three hundred and twelve of 735 (43%) oral food challenges were assessed to be positive. Calculation of 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 13.0 and 17.8 mm for HE, and 12.5 and 17.3 mm for CM, respectively. However, using the SI, the corresponding cut-off levels were 2.6 and 3.7, respectively, for HE, and 2.7 and 3.7 for CM. For wheat, 95% and 99% decision points of 2.2 and 3.0 were found in children below 1 year of age. Conclusion Predictive decision points for a positive outcome of food challenges can be calculated for HE and CM using weal size and SI. They may help to avoid oral food challenges. [ABSTRACT FROM AUTHOR]

Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value. To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy. We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated. A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat. In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice. [ABSTRACT FROM AUTHOR]

Cow milk allergy (CMA) is one of the most common food allergies in childhood. Patients with CMA present with a wide range of immunoglobulin (Ig)E- and non-IgE-mediated clinical syndromes. Limited information is known about the specific humoral and cellular responses to cow milk proteins in these various forms of CMA.The aim of the study was to determine IgE, IgA, IgG1 and IgG4 antibody levels and lymphocyte proliferative responses to the major cow milk allergens in patients with IgE- and non-IgE-mediated CMA.One hundred and forty cow milk allergic patients, 6 months to 22 years of age, were included in the study. One hundred and thirteen patients had IgE-mediated CMA, 11 had milk protein-induced enterocolitis syndrome and 16 had allergic eosinophilic gastroenteritis. Twenty-one patients without food allergy, 8 months to 18 years of age, served as controls. Serum IgE, IgA, IgG1 and IgG4 antibodies toα-,β-, andκ-casein,α-lactalbumin andβ-lactoglobulin were measured using enzyme-linked immunosorbent assays. For a subset of these patients, we performed lymphocyte proliferation assays to the various milk allergens.Patients with IgE-mediated CMA had higher specific IgE concentrations to casein compared with whey proteins (P < 0.001). In this group of patients, there was a positive correlation between IgE levels and levels of the other isotypes for all four milk proteins (P < 0.001). In general, the caseins were the more allergenic and antigenic proteins in all groups of patients. Patients with enterocolitis syndrome produced less milk protein-specific IgG4 (P < 0.05) and had a trend for higher IgA antibody levels when compared to the control group. Lymphocyte proliferative responses in all groups with CMA were significantly higher than controls (P < 0.05), although this response was similar in patients with IgE- and non-IgE-mediated CMA.There is a distinct pattern of humoral antibody response in the different forms of CMA. Patients with IgE-mediated CMA have an elevated polyisotypic response to cow milk protein. The relative lack of specific IgG4 production in patients with enterocolitis syndrome may be involved in the pathogenesis of the disease. In general, caseins appear to be the predominant allergen in patients with CMA. [ABSTRACT FROM AUTHOR]

The diagnostic work-up of suspected food allergy includes the skin prick test (SPT), the measurement of food specific immunoglobulin E (IgE) antibodies using serologic assays, and more recently the atopy patch test (APT). For specific serum IgE and the SPT, decision points have been established for some foods allowing prediction of clinical relevance in selected cases. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. Controlled oral food challenges still remain the gold standard in the diagnostic work-up of children with suspected food allergy. Most food allergic children will lose their allergy over time. As there is no laboratory parameter, which can accurately predict when clinical tolerance has been developed, controlled oral food challenges are the measure of choice. In this article, the current knowledge of predictors for the outcome of oral food challenges is reviewed and proposals for the daily practical work-up in the case of suspected food related clinical symptoms are presented. [ABSTRACT FROM AUTHOR]

Specific serum IgE is considered as one of the important diagnostic measures in the diagnostic work-up of food allergy.To evaluate the role of specific serum IgE in predicting the outcome of oral food challenges, and to determine threshold concentrations of specific serum IgE that could render double-blind, placebo-controlled food challenges unnecessary.In 501 children (median age 13 months), 992 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. 440/501 (88%) children suffered from atopic dermatitis. For all children, specific IgE concentrations in serum were determined. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics-curves as well as predictive decision points were calculated.Four hundred and forty-five out of 992 oral food challenges with allergens were assessed as positive. Sensitivity of specific serum IgE was 97% for HE, 83% for CM, 69% for soy, and 79% for wheat. Specificity was 51% for HE, 53% for CM, 50% for soy, and 38% for wheat. Calculating 90%, 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 6.3, 12.6, and 59.2 kU/L for HE, respectively. Subdividing our children in those of below or above 1 year of age resulted in a markedly different predicted probability for HE. For CM, only the 90% predicted probability (88.8 kU/L) could be calculated. No decision points could be determined for CM, wheat and soy.In general, specific serum IgE levels showed a correlation with the outcome of positive oral food challenges for CM and HE. Meaningful predictive decision points can be calculated for HE, which may help to avoid oral food challenges in some cases. However, data need to be ascertained for each allergen separately. Furthermore, the age of the patient population under investigation must also be taken into account. [ABSTRACT FROM AUTHOR]

Currently, the diagnostic work-up of suspected food allergy includes skin prick tests, the measurement of food specific immunoglobulin E (IgE), and the atopy patch test, and double-blind, placebo-controlled food challenges. However, all of these methods, even double-blind, placebo-controlled food challenges (DBPCFC), may sometimes be misleading. This overview describes several pitfalls for standard diagnostic methods such as problems with irritative skin reactions mimicking IgE-mediated symptoms, the problem of non-IgE-mediated reactions, pitfalls arising from the way foods are prepared or processed, effects of the route of exposure, the role of augmentation factors lowering the threshold value for clinical reactions, the noncomparability of specific IgE decision points, the influence of the timing of diagnostic measures. In addition, the problem of alternative diagnostic measures is discussed. In conclusion, there are several pitfalls in the diagnostic work-up of food allergy, which may be misleading for the physician. Properly performed controlled oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals in order to avoid both unjustified diets, which may lead to severe impairments in growth and development, and to avoid unnecessary symptoms if an underlying food allergy is not correctly identified as a cause for the symptoms of the patient. [ABSTRACT FROM AUTHOR]

Background: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. Methods: The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Results: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. Conclusions: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Incidence and natural history of challenge proven cow's milk allergy in European children-Euro Prevall birth cohort" by A. A. Schoemaker in the previous issue along with a response from the authors to the same.