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Background: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA., Methods: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk., Results: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group., Conclusion: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting., Methods: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab., Results: Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kU A /L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to ≥6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to ≥6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% ≥6000 mg)., Conclusion: Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise-induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow's milk and wheat allergies., Methods: This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow's milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients' clinical characteristics and symptoms were analyzed., Results: The EPT results were positive for cow's milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD-positive and EIARD-negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD-positive patients, 13 patients (cow's milk, n = 7; wheat, n = 6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow's milk, n = 4; wheat, n = 4)., Conclusion: EIARDs were observed after slow OIT for cow's milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The efficacy and safety of cow's milk (CM) low-dose oral immunotherapy (LOIT) at one-year follow-up have been previously reported. We investigated the outcome of fixed long-term LOIT in children with severe CM allergy., Methods: Children with positive reactions to oral food challenge (OFC) with 3 mL CM were included. The LOIT group (n = 33) ingested up to 3 mL CM for 1 year. After a two-week CM avoidance, 3 and 25 mL OFCs were performed. Children with positive reactions continued with 3 mL ingestion, with OFCs repeated yearly. Regular home consumption of 25 mL CM after passing the OFCs was defined as 25 mL short-term unresponsiveness (25 mL STU). The historical control group (n = 16) with reactions to 3 mL OFC eliminated daily CM ingestion., Results: The proportion of 25 mL STU in the LOIT group was 27%, 52%, and 61% after 1, 2, and 3 years, respectively, and the 3-year percentage was significantly higher than that in the historical control group (13%, P = .002). In the LOIT group, only one child developed severe symptoms. Furthermore, in this group, CM- and casein-specific immunoglobulin E (sIgE) levels decreased significantly and casein-specific IgG and IgG 4 levels increased significantly after 3 years, whereas the historical control group presented no significant change in these parameters. Baseline sIgE levels were significantly low in children achieving 25 mL STU., Conclusion: Continued fixed LOIT yields immunologic improvement and may be effective and safe for severe CM allergy., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Severe reactions may develop during cow's milk (CM) oral immunotherapy (OIT). We investigated the safety and efficacy of low-dose OIT with heated milk (HM) or unheated milk (UM) in children with anaphylaxis., Methods: Children with symptom onset after ingestion of 3-mL HM on a double-blind, placebo-controlled food challenge were randomly assigned to the HM (n = 17) or UM (n = 16) group. HM group ingested milk powder heated at 125°C for 30 seconds, whereas the UM group used UM. Patients were hospitalized for 5 days; the HM or UM was gradually increased to 3 mL/day; 3-mL/day ingestion was continued at home. One year later, the patients underwent 2-day consecutive 3- and 25-mL HM-oral food challenges (OFCs) after 2-week avoidance., Results: At baseline, milk- and casein-specific immunoglobulin E (IgE) levels were 56.0 and 51.4 kUA/L in the HM group, and 55.2 and 65.6 kUA/L in the UM group, respectively. One year later, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively. Rates of moderate or severe symptoms and respiratory symptoms per home dose were significantly lower in the HM than in the UM group (0.7% and 1.2% vs 1.4% and 2.6%, respectively, P < .001). β-lactoglobulin-specific IgG 4 levels significantly increased from baseline only in the UM group, whereas casein-specific IgG 4 levels significantly increased from baseline in both groups., Conclusions: HM-OIT induced immunological changes more safely than the UM-OIT. The possibility of lower treatment efficacy with HM-OIT needs to be evaluated in larger studies., (© 2020 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.)

Background: Introduction and gradual incremental escalation of a low dose of baked milk may accelerate the resolution of severe cow's milk (CM) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked milk oral immunotherapy (OIT) in children with CM allergy after a low-dose baked milk oral food challenge (OFC)., Methods: In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 64 children with CM allergy and high milk and casein-specific IgE levels, who underwent a total of 171 milk OFC. Mean age at 1st OFC was 4.8 years. Mean CM-specific IgE was 47.9 kUA/L, and mean casein-specific IgE was 42.3 kUA/L., Results: Most children were treated with baked milk OIT. Our study shows that 67.2% of the children did not react to 1st low-dose baked milk OFC (168.6 mg of CM protein). Eighteen percent of children stopped the OIT at home. Finally, desensitization to fresh milk was achieved in 27 children (42.2% of children allergic to CM). Children with lower CM-specific IgE levels have a significantly higher probability of becoming desensitized to unbaked CM., Conclusion: Most children with CM allergy and high milk and casein-specific IgE levels tolerate the introduction of baked milk. However, the occurrence of anaphylactic reactions during OIT remains possible., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study., Methods: During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1 year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed ≥2 dL of milk daily, while the failure group consumed <2 dL of milk or were on a milk-avoidance diet., Results: Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥2 dL of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P < 0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = 0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = 0.01)., Conclusion: More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Cows 'milk protein allergy (CMPA) is the most common food allergy in infants in the United Kingdom. Infants with CMPA who are not exclusively breastfed require a substitute hypoallergenic formula, which are perceived as having a poor palatability. This study compares the palatability of different extensively hydrolysed formulas (EHFs) and explores healthcare professional (HCP) expectations of how palatability impacts infants and their families., Methods: Healthcare professional with experience of CMPA were recruited to take part in a home palatability test of four EHFs [Aptamil Pepti 1, Nutricia Ltd. (EHF W1); Althera, Nestle Health Science (EHF W2); Similac Alimentum, Abbott (EHF C1); Nutramigen LGG 1, Mead Johnson (EHF C2)] using a blind taste procedure. A randomised, complete block design was used to minimise order and carry-over biases. Participants completed a questionnaire about the impact of formula palatability on infants and their families., Results: A total of 100 HCPs took part (51 dietitians and 49 general practitioners). Overall, whey-based lactose-containing EHFs were ranked the most palatable: EHF W1 by 77% of participants and EHF W2 by 20%. EHF W1 was liked significantly more (P < 0.0001) than the other formulas. The vast majority of participants agreed that better palatability would result in an increased chance of non-rejection (96%), more content families (92%) and decreased healthcare costs (90%)., Conclusion: Amongst HCPs who manage infants with CMPA, whey-based lactose-containing EHFs were ranked the most palatable. HCPs expected that good palatability would result in better acceptance, more content infants and families, alongside decreased wastage and healthcare costs., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Extensively hydrolyzed casein formula (EHCF) has been proposed for the prevention and is commonly used for the treatment of cow's milk allergy (CMA). The addition of the probiotic Lactobacillus rhamnosus GG (LGG) to EHCF may induce faster acquisition of tolerance to cow's milk. The mechanisms underlying this effect are largely unexplored. We investigated the effects of EHCF alone or in combination with LGG on β-lactoglobulin (BLG) sensitization in mice., Methods: Three-week-old C3H/HeOuJ mice were sensitized by oral administration of BLG using cholera toxin as adjuvant at weekly intervals for 5 weeks (sensitization period). Two experimental phases were conducted: (i) EHCF or EHCF+LGG given daily, starting 2 weeks before the sensitization period and then given daily for 5 weeks and (ii) EHCF or EHCF+LGG given daily for 4 weeks, starting 1 week after the sensitization period. Diet free of cow's milk protein was used as control. Acute allergic skin response, anaphylactic symptom score, body temperature, intestinal permeability, anti-BLG serum IgE, and interleukin (IL)-4, IL-5, IL-10, IL-13, IFN-γ mRNA expression were analyzed. Peptide fractions of EHCF were characterized by reversed-phase (RP)-HPLC, MALDI-TOF mass spectrometry, and nano-HPLC/ESI-MS/MS., Results: Extensively hydrolyzed casein formula administration before or after BLG-induced sensitization significantly reduced acute allergic skin reaction, anaphylactic symptom score, body temperature decrease, intestinal permeability increase, IL-4, IL-5, IL-13, and anti-BLG IgE production. EHCF increased expression of IFN-γ and IL-10. Many of these effects were significantly enhanced by LGG supplementation. The peptide panels were similar between the two study formulas and contained sequences that could have immunoregulatory activities., Conclusions: The data support dietary intervention with EHCF for CMA prevention and treatment through a favorable immunomodulatory action. The observed effects are significantly enhanced by LGG supplementation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Optimally hydrolyzed β-Lactoglobulin (βLg) is a promising milk oral immunotherapy (OIT) candidate with respect to showing reduced B-cell reactivity but retaining the T-cell epitope. To demonstrate that an edible hypoallergenic βLg hydrolysate containing the T-cell epitope is suitable for OIT. We tested how chymotrypsin affected the retention of the T-cell epitope of βLg when preparing βLg hydrolysates using food-grade trypsin., Methods: We investigated the effect of chymotrypsin activity on the formation of the T-cell epitope-containing peptide of βLg (βLg 102-124 ) and prepared an edible βLg hydrolysate containing βLg 102-124 using screened food-grade trypsins. B-cell reactivity was determined using immunoassays in which ELISA was performed with anti-βLg rabbit IgG and Western blotting was performed with a milk-specific IgE antiserum., Results: In βLg hydrolysis performed by varying the activity of trypsin and chymotrypsin, chymotrypsin activity inhibited the formation of βLg 102-124 with an increase in hydrolysis time in a dose-dependent manner. βLg 102-124 was generated by two of five food-grade trypsins used at a ratio of 1:50 (w/w, enzyme/substrate) for 20 h at 40°C. The edible βLg hydrolysate retained βLg 102-124 and showed a reduction in molecular weight distribution and antigenicity against IgG and IgE., Conclusions: Chymotrypsin activity inhibited the formation of βLg 102-124 in the trypsin hydrolysate of βLg. This βLg trypsin hydrolysate is a novel candidate for peptide-based OIT in cow's milk allergy for safely inducing desensitization., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Many children with cow's milk allergy (CMA) develop tolerance, but, challenges in daily life may remain. Using the Food hypersensitivity famiLy ImPact questionnaire (FLIP), we sought to monitor changes in the impact of CMA over time., Methods: Families of children with CMA, who participated in the validation of the FLIP, were re-approached 6 months later for follow-up. Change in reported difficulties was assessed by paired sample t-test and mixed models, stratifying by outgrown vs. persistent CMA., Results: Impact on families with children who had outgrown CMA (n = 20) decreased in the FLIP's total score (p = 0.0001) and in two subscales; Health and Emotions (p = 0.0001) and Everyday Life (p = 0.0001). In contrast, no significant improvements were registered in nutritional concerns. Impact on the group with persistent CMA (n = 57) was unchanged at follow-up except for more impact on Everyday Life (p = 0.001). In the final analysis comparing longitudinal changes in the groups, the strongest differences were observed for the subscales Health & Emotions and Everyday Life; for the Nutrition subscale, the between-group changes also differed, but to lesser extent., Conclusions: We have documented the varying impact of CMA on parents and children over time. Families who were still affected continued to experience impact in daily life. Despite development of tolerance, families who were no longer affected revealed continuing nutritional concerns. Follow-ups should be offered even after outgrown CMA to encourage progression to unrestricted diet, to prevent eating disorders and to promote healthy growth., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral immunotherapy (OIT) with cow's milk (CM) has been reported to induce a number of specific antibody responses, but these remain to be fully characterized. Our objective was to explore whether IgE and IgG4 epitope binding profiles could predict the risk of side effects during CM OIT., Methods: The study population consisted of 32 children (6-17 yr of age) with CM allergy: 26 children who successfully completed OIT and six children who discontinued therapy due to adverse reactions. We investigated sera drawn before and after OIT. We analyzed specific IgE and IgG4 binding to CM protein-derived peptides with a microarray-based immunoassay. Antibody binding affinity was analyzed with a competition assay where CM proteins in solution competed with peptides printed on the microarray., Results: IgE binding to CM peptides decreased and IgG4 binding increased following the OIT in children who attained desensitization. Compared with children who successfully completed OIT, those who discontinued OIT due to adverse reactions developed increased quantities and affinity of epitope-specific IgE antibodies and a broader diversity of IgE and IgG4 binding, but less overlap in IgE and IgG4 binding to CM peptides., Conclusions: Detailed analysis of IgE and IgG4 binding to CM peptides may help in predicting whether CM OIT will be tolerated successfully. It may thus improve the safety of the therapy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Prior exposure to partial whey hydrolysates has been shown to reduce the allergic response to whey in mice. This effect was more pronounced in combination with a diet containing non-digestible oligosaccharides (scGOS/lcFOS/pAOS). It is unknown which fractions/epitopes are responsible for this effect. Therefore, the prophylactic ability of synthetic peptides of β-lactoglobulin with/without a scGOS/lcFOS/pAOS-containing diet to reduce the allergic response in a mouse model for cow's milk allergy was investigated., Methods: Of 31 peptides, nine peptides were selected based on human T cell data. Mice were pre-treated orally with three peptide mixtures or single peptides for six consecutive days. During this period, they received a control or scGOS/lcFOS/pAOS-containing diet. Subsequently, mice were orally sensitized to whey and received an intradermal and oral challenge. After sacrifice, serum and mesenteric lymph nodes (MLN) were collected for further analysis., Results: Prior exposure to peptide mixtures 1 and 3 significantly reduced the acute allergic skin response to whey. Mixture 2 showed no effect. An additive effect of the scGOS/lcFOS/pAOS-containing diet was only observed for mixture 1. Of the peptides in mixture 1, one peptide (LLDAQSAPLRVYVEELKP) showed the strongest effect on the acute allergic skin response. This peptide also tended to decrease whey-specific antibody levels and to increase the percentages of CD11b+CD103+ dendritic cells and CD25+Foxp3+ T cells in the MLN., Conclusions: Prior exposure to specific peptides of β-lactoglobulin reduces the allergic response to whey, which may involve regulatory dendritic and T cells. Combining peptides with a sGOS/lcFOS/pAOS-containing diet enhances this effect., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cow's milk allergy (CMA) affects 2-3% of infants. It resolves in the great majority spontaneously during childhood. CMA encompasses a spectrum of clinical and immunologic characteristics. Non-IgE-mediated allergy typically resolves earlier than IgE-mediated allergy. The most documented prognostic characteristic is that intense-specific IgE response predicts persistence of CMA. Low serum levels of cow's milk (CM)-specific IgG4 are also associated with persistent CMA. Natural development of tolerance involves an immunologic shift where Th2 responses diminish, and Th1 as well as T regulatory cell responses strengthen. Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA, levels increase in serum. Specific oral immunotherapy (OIT) with CM induces desensitization in most cases where spontaneous recovery has not yet occurred. Data on long-term tolerance induction are still scarce. According to current research data, the immunologic changes induced by OIT resemble those seen during natural development of tolerance., (© 2012 John Wiley & Sons A/S.)

A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children highly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability., (Copyright (c) 2009 John Wiley & Sons A/S)

There is little information on the regional distribution of food allergy in Australia. We examined the influence of latitude (a marker of sunlight/vitamin D status) on food allergy, as measured by 2007 infant hypoallergenic formula (IHF) prescription rates in children ages 0-2 yrs. Data were compiled from the 52 statistical divisions in mainland Australia plus the island of Tasmania (n=53 observations). Data from the Australian Department of Health and Aging and the Australian Bureau of Statistics were analysed by statistical division. There was significant regional variability in hypoallergenic formula prescription rates (per 100,000 population/yr), with the highest rates in southern Australia (14,406) and the lowest in the north (721), compared with a national average of 4099. Geographical factors (decreasing latitude and increasing longitude) were associated with a higher rate of IHF prescriptions, such that rates were higher in southern vs. northern regions, and in eastern compared with western regions. Controlling for longitude, physician density and markers of socioeconomic status, southern latitudes were associated with higher hypoallergenic formulae prescription rates [beta, -147.98; 95% confidence interval (CI)=-281.83 to -14.14; p=0.03]. Controlling for latitude, physician density and markers of socioeconomic status, eastern longitudes were also associated with higher hypoallergenic formulae prescription rates (beta, 89.69; 95% CI=2.90-176.49; p=0.04). Among young children, hypoallergenic formula prescription rates are more common in the southern and eastern regions of Australia. These data provide support for a possible role of sun exposure/vitamin D status (amongst other potential factors) in the pathogenesis of food allergy., (Copyright (c) 2009 John Wiley & Sons A/S)

Specific Oral Tolerance (SOTI) is a promising therapy of food allergy, specially for IgE-mediated cow milk allergy (CMA) in pediatric age. Randomized controlled trials have reported that about 35% of children, at least 5 years of age, became full tolerant to cow milk proteins after SOTI. Regard to the safety, literature describes about 200 children who underwent SOTI, with no fatal events. Nevertheless, a considerable percentage of those children (15%-20%) had to stop SOTI, because of important adverse effects. Numerous protocols have been described, some audacious and other prudent, however all demand an intense commitment either of the doctors and of the families. The information about the follow up of the children who underwent SOTI are still insufficient. For these reasons, we think that SOTI is still an experimental therapy., (Copyright (c) 2009 John Wiley & Sons A/S)

Cow's milk allergy (CMA) is the most common form of food allergy affecting 2.5% of children, but the diagnosis is often difficult. Both intestinal microbiota and barrier function seem to be disturbed in patients with food allergies, and administration of probiotics has been shown to normalize intestinal microbiota and alleviate symptoms. We hypothesized that the differences in intestinal metabolic activity and permeability could lead to detectable changes in the end-products of metabolism in patients with CMA. This could offer new diagnostic possibilities. The urinary concentrations of 37 organic acids were studied by a mass spectrometry-based method in 35 infants aged under 1 yr with atopic eczema, 16 of them having CMA diagnosed with a double-blind placebo-controlled food challenge test. The control group consisted of the remaining 19 infants with only atopic eczema. In a second study, Lactobacillus rhamnosus GG (LGG) or placebo was administered to the infants with CMA for 4 wk and the urinary organic acids were analysed again. CMA patients and patients with only atopic eczema had statistically significant differences in urinary concentrations of hydroxybutyrate (p<0.001); adipate and isocitrate (p<0.01 for both); homovanillate, suberate, tartarate, 3-indoleacetate and 5-hydroxyindoleacetate (p<0.05 for all). These concentrations did not change significantly following LGG administration to the CMA patients, but a trend towards the control group was seen. Thus, CMA is associated with changes in some urinary organic acid levels. These differences between atopic infants with and without CMA could be investigated as a novel approach for CMA diagnosis., (Copyright (c) 2009 John Wiley & Sons A/S)

Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4(1/2) yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP before and after a 6-wk treatment period and at 4(1/2) yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4(1/2) yr of age, had higher levels of Immunoglobulin G(4) antibodies to ovalbumin and beta-lactoglobulin and also higher IgG(4)/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4(1/2) yr of age. The highest IgG(4)/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG(4) and high ratios of IgG(4)/IgE antibodies to food allergens are more likely to consume these foods at 4(1/2) yr than infants with low levels and ratios.

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4-5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and alpha-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or alpha-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and alpha-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.