Severe Milk Allergy Research Articles

Efficacy and Safety of Baked Milk Oral Immunotherapy in Children With Severe Milk Allergy: A Randomized, Double-blind, Placebo-controlled Phase 2 Trial

Efficacy and Safety of Baked Milk Oral Immunotherapy in Children With Severe Milk Allergy: A Randomized, Double-blind, Placebo-controlled Phase 2 Trial

Informing Risk Management for Patients With Cow’s Milk Allergy Based on Threshold Dose Distributions Using Low-Dose Food Challenges

The safe consumption of foods depends on their allergen content in relation to patients' lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL), as well as other factors. In the case of milk, data on LOAEL and NOAEL are limited and conflicting. To determine the threshold dose distribution and the lowest individual eliciting dose (ED) for milk in a large group of milk-allergic patients METHODS: Individuals with confirmed cow's milk allergy who underwent a diagnostic or pre-oral immunotherapy open milk oral food challenge at the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between 2010 and 2015 were included. A subgroup of patients with severe milk allergy underwent a modified challenge with a 90- to 120-minute interval after a starting dose of 0.3 mg cow's milk protein. A total of 866 participants (193 with diagnostic challenges and 673 with pre-oral immunotherapy challenges) were included in the study. The discrete ED01 and ED05, or values derived in which 1% or 5% of the respective allergic population would be predicted to experience an allergic reaction, were 1.1 to 1.9 and 4.7 to 5.6 mg milk protein, respectively, and values for cumulative doses for ED01 and ED05 were 0.9 to 1.8 and 5.2 to 6.2 mg milk protein, respectively. No patients, including the most severely milk-allergic individuals who underwent the modified challenge, reacted to the first 0.3 mg protein dose. This report provides valuable information about milk NOAELs, LOAELs, and EDs that might assist regulators in decisions about food labeling in general, and milk in particular.

Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial

Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P= .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P= .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Omalizumab effectiveness in patients with a previously failed oral immunotherapy for severe milk allergy.

BackgroundSome studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt.MethodsSingle‐center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8–24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8‐week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re‐evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL).ResultsDuring OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all.ConclusionIn this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy

Introduction: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. Objectives: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. Methods: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. Results: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). Conclusions: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

Immunogenicity of Milk Protein-Containing Hydrophilic Gel Patch for Epicutaneous Immunotherapy for Milk Allergy.

Epicutaneous immunotherapy (EPIT) involving the skin's immune system is easy to use, painless and has a low risk of systemic side effects; it can be applied to food allergies that have a high morbidity rate in children. In this study, we evaluated the safety and efficacy of hydrophilic gel patch (HG) for EPIT. Milk protein concentrate (MPC)-containing HG was applied to the skin that maintained a barrier function or formed puncture holes with microneedle, and MPC-specific antibodies were measured. The clinical study was conducted involving patients with severe milk allergy. No specific immune response was induced when immunizing to intact skin, and antibody production was observed by forming puncture holes. It was suggested that MPC contained in HG has immunogenicity and a very small amount of MPC was delivered to intact skin. In the clinical study, the symptom induction threshold increased in four of eight subjects, allowing them to consume milk and switch to oral immunotherapy. Although local skin reactions and temporary elevation of specific IgE antibodies were observed, no systemic side effects appeared throughout the study. EPIT using HG is a safe method to enable oral administration even in patients with severe milk allergies.

Occupational asthma, rhinitis, contact dermatitis, and severe milk allergy caused by primary occupational exposure to casein

Occupational asthma, rhinitis, contact dermatitis, and severe milk allergy caused by primary occupational exposure to casein

The Impact of Baked Egg and Baked Milk Diets on IgE- and Non-IgE-Mediated Allergy.

Baked milk (BM) and baked egg (BE) diets are increasingly used in the management of milk and egg allergy, rather than avoidance. Children with tolerance versus reactivity to BM and BE may have smaller skin prick test and lower specific IgE, and BM-tolerant children have less basophil reactivity and more peripheral T regulatory cells. However, most milk- and egg-allergic children tolerate BM and BE and an individual's reactivity is unpredictable. Non-reactivity is due to conformational changes in the allergens. Significant differences in the published advice about methods of introduction exist from graded introduction at home to a medically supervised full dose. These approaches carry different risks and may have different immunological effects. Reactivity to BM is a predictor of a severe milk allergy. Therefore, medical supervision for BM and BE introduction is prudent. The baked diet allows dietary liberation. Most, but not all, BM- and BE-tolerant children continue eating the baked foods. The prognosis of children who can eat BM and BE is favorable with likely resolution of their allergy over the next few years. Murine models of BE diets demonstrate that heated egg can impart clinical protection against anaphylaxis and cause immune changes. Most observational human studies of BM and BE diets demonstrate clinical resolution of allergy and favorable immune changes versus regular care controls. However, the one randomized controlled trial for the BE diet in BE-tolerant children did not support an immune-modifying effect of the BE diet. Another study of BE immunotherapy is expected to be completed in 2018. There is currently no evidence for prevention of allergy with the baked diets. There may be a future role for BM and BE in liberating the diets of individuals with non-IgE-mediated allergy given recent studies that a subset of these patients can consume BM without a clinical reaction.

Exercise Should Be Added to Food Challenge Tests to Predict Anaphylaxis During Oral Tolerance Induction for Severe Milk Allergy Patients

Exercise Should Be Added to Food Challenge Tests to Predict Anaphylaxis During Oral Tolerance Induction for Severe Milk Allergy Patients

Milk and wheat allergy, and celiac disease

Cow's milk, egg, wheat, soy, peanut, and fish account for about 90% of the food allergies but there are considerable differences from one country to another. Milk allergy is among the best characterized food allergies, particularly in infants and small children. Only part of the children with early allergy to cow's milk grow into shool-age with milk allergy but those that do often have severe symptoms and high specific IgE level to milk. In accordance, attaining tolerance to cow's milk is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4. Recent data point that analysis of IgE response to milk components may help in determining those with higher risk for persistent or more severe milk allergy. Among wheat allergic patients, co-sensitization to cow's milk and hen's egg is common. Wheat ingestion may trigger immunoglobulin E (IgE)-mediated immediate symptoms, including urticaria, angioedema, bronchial obstruction, nausea and abdominal pain, or in severe cases, even systemic anaphylaxis. Delayed reactions include gastrointestinal symptoms and worsen-ing of atopic dermatitis. In addition to food allergy, wheat ingestion may cause exercise-induced anaphylaxis, or celiac disease (CD), and inhalation and handling of wheat flour aller-gens may lead to respiratory allergy, or contact urticaria on the skin. Wheat IgE is commonly found in all ages of atopic children when whole grains are used as an antigen either in skin prick tests or serum IgE measurements. The specificity of this IgE re-sponse in identifying clinical disease, however, is poor. It is of importance to recognize dis-ease-determining components in the IgE response. Several studies have shown that sensiti-zation particularly to omega-5 gliadin is associated with challenge-proven wheat-allergy. Moreover, recent data imply that gliadin-positive patients have more likely severe reactions after wheat ingestion. A well-characterized severe clinical entity is also wheat-dependent, ex-ercise-induced anaphylaxis in which sensitization to omega-5 gliadin is a prerequisite. We have analyzed especially the gliadin-sepcific responses in wheat allergy. Sensitization to gliadin with a SPT wheal of ≥5 mm at the time of the diagnostic challenge was associated with a slower course of recovery from wheat hypersensitivity (p = 0.019), and a SPT wheal of ≥ 3 mm to gliadin at any time was associated with the development of asthma. Recently, we examined IgE response to 22 wheat components in children with challenge positive wheat allergy and their controls. The results show that wheat-allergy diagnosis can be improved considerably by component-based ap-proach. In the future, wheat IgE diagnosis should include at least measurement of IgE to gli-adins. Gluten and its major component, gliadin, is essential also in the pathogenesis of celiac dis-ease. Gliadin can be a target of both cellular and humoral immune responses. Approximately 90 percent of patients with celiac disease have the HLA-DQ2 haplotype, explaining the family-association of the disease but still leaving open the wide variability in prevalence between dif-ferent Caucasian populations. Both IgA and IgG antibodies can be seen in CD patients but the most sensitive diagnostic work-up is to define tissue transglutaminase (tTG) transglutami-nase IgA antibodies.

An Anaphylactic Reaction After Primary Exposure to an Aprotinin Test Dose in a Child With a Severe Milk Allergy

ANAPHYLACTIC REACTION to aprotinin is usually seen after previous exposure to the drug and is rarely seen on primary exposure. 1 Beierlein W. Scheule A.M. Dietrich W. et al. Forty years of clinical aprotinin use: A review of 124 hypersensitivity reactions. Ann Thorac Surg. 2005; 79: 741-748 Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar , 2 Dietrich W. Spath P. Ebell A. et al. Prevalence of anaphylactic reactions to aprotinin: Analysis of two hundred forty-eight reexposures to aprotinin in heart operations. J Thorac Cardiovasc Surg. 1997; 113: 194-201 Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar , 3 Milano C.A. Patel V.S. Smith P.K. et al. Risk of anaphylaxis from aprotinin re-exposure during LVAD removal and heart transplantation. J Heart Lung Transplant. 2002; 21: 1127-1130 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar , 4 Scheule A.M. Beierlein W. Lorenz H. et al. Repeated anaphylactic reactions to aprotinin in fibrin sealant. Gastrointest Endosc. 1998; 48: 83-85 Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar There is only one previous case report describing a severe anaphylactic reaction after primary exposure to aprotinin with a positive aprotinin-specific immunoglobulin (Ig) E. 5 Cohen D.M. Norberto J. Cartabuke R. et al. Severe anaphylactic reaction after primary exposure to aprotinin. Ann Thorac Surg. 1999; 67: 837-838 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar However, Beierlein et al, 6 Beierlein W. Scheule A.M. Ziemer G. Anaphylactic aprotinin reaction. Ann Thorac Surg. 2000; 69: 1298 Abstract Full Text Full Text PDF PubMed Google Scholar in a letter to the editor, raised doubts concerning the interpretation of this case report by stressing that the presence of aprotinin-specific IgE means presensitization, and, hence, such a reaction cannot be considered a primary exposure.

A CASE OF SEVERE MILK ALLERGY : Relationship with Type I and Type III Allergic Reactions

A CASE OF SEVERE MILK ALLERGY : Relationship with Type I and Type III Allergic Reactions