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Purpose of Review: A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy., Recent Findings: A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation., Summary: Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To highlight the most recent insights on cow's milk allergy (CMA), its treatment, and management., Recent Findings: CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction, CMA may imply also a severe impairment of health-related quality of life at individual and family level as well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against Cow's Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-of-the-art specifically on CMA, including international evidence-based recommendations. The current results from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high degree of cross-reactivity with cow's milk proteins and risk for allergic reactions, goats' milk or other mammals' milk should not be used., Summary: The adoption and implementation of evidence-based recommendations may guide a proper diagnostics and management and awaited advances in knowledge will allow the development of a personalized treatment tailored on the specific CMA patient's profile., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Several novel immunotherapies have recently been reported for the treatment of cow's milk allergy (CMA). However, systematic methods for the selection of immunotherapy in clinical practice have not been investigated. In this review, we have provided suggestions for safe and effective immunotherapy for patients with CMA., Recent Findings: Recent studies on cow's milk immunotherapy, using lower target doses, heated or baked cow's milk, combination treatment with adjuvants, or various routes of immunotherapy, included school-aged children with severe allergies, infants, and patients with mild CMA. These patients were administered various maintenance doses for various time periods. In the selection of immunotherapy, it would be useful to consider the patient's age and CMA severity at baseline: threshold dose, history of cow's milk anaphylaxis, and cow's milk-specific IgE levels., Summary: Considering the risks and benefits for patients with CMA, appropriate treatment should be selected based on the current evidence. Low-dose oral immunotherapy may be useful in clinical practice for school-aged children with severe CMA. Additional studies are needed to assess the indications for immunotherapy to select appropriate treatments in real-life settings., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy., Recent Findings: The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions., Summary: The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.

Purpose of Review: Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice., Recent Findings: DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable., Summary: DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.

Purpose of Review: It is well known that many aspects of food allergy are lacking sufficient research and publication. Practising evidence-based medicine in this field is, therefore, a particular challenge. Internationally, there is considerable variation in practices and no agreed treatment pathways. The time was right to review the evidence and seek the views of experts in the field, industry and food allergic individuals to develop guidance for clinical practice and to plan future research. The purpose of this review was to summarize points of agreement and discrepancy in the recently published Diagnosis and Rationale for Action against Cow's Milk Allergy, US NIAID and UK NICE guidelines., Recent Findings: The publication of the three guideline documents on food allergies gives clinicians, scientists, industry, governments and patients the opportunity to review the information in a concise format and appreciate the role of clinical expertise in decision making. The guidelines covered all aspects of food allergy: prevalence and natural history, diagnosis, management and treatment and other aspects such as vaccinations., Summary: The guidelines summarized not only our current evidence base but also gaps in our knowledge. Use of these guidelines would facilitate high quality standardized care and indicate the direction of future research.

Purpose of Review: To describe the impact of the diagnosis and rationale for action against cow's milk allergy (DRACMA) guidelines on the decision process in the therapy of cow's milk allergy (CMA)., Recent Findings: We report here the experience of a 2-year application of DRACMA worldwide. Variations in the socioeconomic profile of CMA sufferers and their context can modify the application of DRACMA recommendations. As an example, we use the country-by-country modifications of the social structure and the modifications of the prices for special formula in Italy., Summary: The DRACMA guidelines were issued to inform formula choice for CMA treatment by integrating patients' underlying values, preferences and remarks into grading of recommendations assessment, development and evaluation (GRADE) recommendations, which serve to facilitate their interpretation. This method allows every pediatrician/allergist to follow the changing variables of formulas (cost, palatability, nutritional value) and tailor their prescription for individual patients accordingly. The art of CMA treatment has always relied on physicians' interpretation and the goal of the DRACMA guidelines is to provide a rationale-based and evidence-based indication for choosing an appropriate formula.

Purpose of Review: The introduction of extensively heated milk and egg protein into the diet has been explored in recent years., Recent Findings: Studies have suggested that a large subset of children who react to unheated milk or egg can tolerate extensively heated forms of these foods. Immunologic changes induced by a diet containing baked milk and egg are similar to changes that have been observed during oral immunotherapy trials. The baked milk and egg diet appears to accelerate the development of regular milk and egg tolerance when compared with strict avoidance., Summary: An oral challenge to extensively heated milk and egg into milk and egg allergic children's diets should be considered when appropriate. Oral food challenges are the most reliable means of establishing a diagnosis and should be undertaken under physician supervision.

Purpose of Review: Cow's milk allergy (CMA) is common in children and may lead to severe systemic reactions. Avoidance of the ingestion of cow milk is the only effective approach, but this does not exclude the inadvertent or accidental ingestion, or the assumption of milk hidden in other foods. As no pharmacological treatment is available, specific desensitization has been considered an attractive strategy., Recent Findings: In the last years, several trials of oral desensitization to cow milk, with different protocols, were published. Overall the results were favourable and demonstrated the achievement of a full tolerance in a high percentage of children. Mild side effects that can be easily managed by slowing the desensitization were reported frequently. The discontinuation of the procedure was necessary in less than 20% of children, on average, due to severe side effects., Summary: Oral immunotherapy (oral desensitization) seems to be a promising treatment strategy for cow milk allergy in children that can be applied also to other foods such as eggs or peanuts.

Purpose of Review: To identify and discuss studies on the molecular diagnosis of cow's milk allergy (CMA) with a view to update allergists since a general review of the methodology in 2006., Recent Findings: Seven basic research studies reporting the use of component-resolved diagnostics in CMA were found. All studies were on children positively reacting to a formal challenge with cow's milk. Six studies used natural allergens and three used recombinant milk proteins. Microarray platforms were customized and, thus, differed across studies. Three studies assessed the association between molecular-scale patterns and different presentations of the condition, that is the association between anaphylaxis, gastrointestinal symptoms and other severe phenotypes and the pattern of protein sensitization. Two studies assessed the association between positive oral food challenge and the persistence of milk allergy over time. Protein profiling could be useful to indicate appropriate specific immunotherapy., Summary: Accurate diagnosis of CMA is challenging and essential. The determination of the immunoglobulin E (IgE)-mediated response to sequenced and characterized allergens may be more useful in predicting the presence and severity of clinical allergy than the currently used skin or blood tests performed with whole extracts. However, as component recognition pattern heterogeneity is observed in different areas, further clinical studies are essential to correlate useful molecular diagnostics and biological markers with disease and patient profiles. Until such markers are found and validated in different age groups, oral food challenge remains the reference standard for the diagnosis of CMA.

Purpose of Review: To address what is currently the most significant, fundamental question in the management of milk-allergic patients: is the best pathway to developing tolerance to milk via complete avoidance or by regular intentional exposure to the offending agent?, Recent Findings: The current standard of care for the management of milk-allergic patients, and food-allergic patients in general, remains avoidance of suspected allergens. However, there is growing evidence that regular oral exposure to gradually increasing amounts of an allergenic food can lead to a desensitized state in most food-allergic children. A limited number of studies have attempted to demonstrate permanent tolerance induction. In those cases, a minority of participants has achieved this. Mechanisms of action have not been extensively evaluated, but when serologic studies have been reported, changes have been similar to those seen with standard subcutaneous immunotherapy. That is, food-specific IgE is typically unchanged or slightly decreased, whereas food-specific IgG4 increases substantially., Summary: Consumption of extensively heated cow's milk and treatment with orally or sublingually administered milk immunotherapy are promising therapeutic approaches. It remains to be determined whether or not the majority of milk-allergic patients can be permanently tolerized through these methods and what the mechanisms of action are for both desensitization and tolerization.

Cow's milk allergy affects approximately 2% of infants under 2 years of age. This review summarizes the recent advances in understanding its pathophysiology and immunological mechanisms. Apart from IgE-mediated atopic manifestations, T cell-mediated reactions have been demonstrated in infants with cow's milk allergy. The clinical spectrum ranges from immediate-type reactions, presenting with urticaria and angioedema to intermediate and late-onset reactions, including atopic dermatitis, infantile colic, gastro-oesophageal reflux, oesophagitis, infantile proctocolitis, food-associated enterocolitis and constipation. The exact mechanisms of these disorders are still poorly understood. Double-blind, placebo controlled food challenge, the definitive diagnostic test for cow's milk allergy, is increasingly being replaced by the measurement of food-specific antibodies, in combination with skin-prick or atopy patch testing. The treatment of cow's milk allergy relies on allergen avoidance and hypoallergenic formulae, or maternal elimination diets in breast-fed infants.