Treatment Of Cow's Milk Allergy Research Articles

Cow's milk allergy treatment. An expert consensus

The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology.

The future of cow's milk allergy - milk ladders in IgE-mediated food allergy.

Cow's milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow's milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child's age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child's dietary intake.

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Nutritional Strategies for the Prevention and Management of Cow's Milk Allergy in the Pediatric Age.

Cow's milk allergy (CMA) is one of the most common pediatric food allergies. The prevalence and severity of CMA have increased dramatically in the last decades, under the pressure of environmental factors in genetically predisposed individuals. Among the environmental influences, nutritional factors play a crucial role. Diet is the most modifiable factor, representing a potential target for the prevention and treatment of CMA. In this review, we report the most scientific-based nutritional strategies for preventing and managing pediatric CMA. In addition, we propose the most complete supplement of compounds able to prevent nutrient deficiencies in CMA pediatric patients and to positively influence the disease course.

Oral immunotherapy for Immunoglobulin E-mediated cow's milk allergy in children: A systematic review and meta analysis.

BackgoundCow's milk allergy (CMA) is the most common allergy in infants that decreases the quality of life of patients and their families. Standard treatment for CMA is the strict avoidance of milk; new treatment strategies such as oral immunotherapy (OIT) have been sought for patients with CMA. We aimed to assess the clinical efficacy and safety of OIT in the treatment of children with immunoglobulin E‐mediated CMA (IMCMA).MethodsWe searched all randomized controlled trials in which OIT is used to treat children with IMCMA from five international electronic databases. We estimated a pooled risk ratio (RR) for each outcome using a Mantel–Haenzel fixed‐effects model if statistical heterogeneity was low.ResultsEleven studies were chosen for meta‐analysis, including a total of 469 children (242 OITs, 227 controls). One hundred and seventy‐six patients (72.7%) in the OIT were desensitized compared with 49 patients (21.6%) in the control group (RR: 7.35, 95% confidence interval (CI): 2.82–19.13, p < .0001). The desensitization effect of OIT was particularly significant in children over 3 years old (RR: 18.05, 95% CI: 6.48–50.26, p < .00001). Although adverse effects were common, they usually involved mild reactions, but epinephrine use was more common in the OIT group (RR: 7.69, 95% CI: 2.16–27.33, p < .002).ConclusionOIT can lead to desensitization in the majority of individuals with IMCMA, especially in patients over 3 years old. A major problem of OIT is the frequency of adverse events, although most are mild. OIT may be an alternative treatment in the future.

Hypoallergenicity assessment of an extensively hydrolyzed whey-protein formula in cow's milk allergic infants.

Background Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA).ObjectivesHypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey‐protein formula (eHWF) in CMA children were assessed.MethodsIn this prospective, randomized, international, multi‐center study (Trial NL3889), 34 children with confirmed CMA (74% IgE‐mediated) underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) with an eHWF developed with non‐porcine enzymes, supplemented with prebiotic short‐chain galacto‐ and long‐chain fructo‐oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7‐day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16‐weeks follow‐up.ResultsOf the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE‐mediated CMA) completed the DBPCFC and 7‐day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow‐up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient.ConclusionsThe newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability.Trial registrationTrial NL3889, https://www.trialregister.nl/trial/3889.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update – XIV – Recommendations on CMA immunotherapy

BackgroundThe prevalence of cow's milk allergy (CMA) is approximately 2–4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. ObjectiveThese evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. MethodsWAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. ResultsAfter a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled “conditional” due to the low certainty about the health effects based on the available evidence. ConclusionsClinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Lactobacillus acidophilus KLDS 1.0738 inhibits TLR4/NF-κB inflammatory pathway in β-lactoglobulin-induced macrophages via modulating miR-146a.

Our previous study has confirmed that Lactobacillus acidophilus KLDS 1.0738 (La KLDS 1.0738) could alleviate β-lactoglobulin (β-Lg)-induced allergic inflammation. This study further explored its molecular regulation mechanism through an in vitro macrophage model. β-Lg-induced macrophages were treated with strains of viable or non-viable L. acidophilus and Toll-like receptor 4 (TLR4) inhibitor or miR-146a inhibitor. Our results revealed that β-Lg stimulation led to the increased expression of TLR4/NF-κB signal pathway in macrophages. Similar to TLR4 inhibitor treatment, La KLDS 1.0738 interventions significantly reduced the allergic inflammation by inhibition of TLR4 pathway, which was superior to the commercialL. acidophilus GMNL-185 strains (La GMNL-185) or the control, especially in living L. acidophilus-treated group. Furthermore, La KLDS 1.0738 strains could remarkably reduce transduction of TLR4 and inflammatory cytokine production, which was closely associated with up-regulation of miR-146a levels. MiR-146a inhibitor attenuated the alleviative effect of La KLDS 1.0738, indicating miR-146a might be a crucial mediator of L. acidophilus strains to reduce β-Lg-induced inflammation in macrophages through TLR4 pathway. In conclusion, these observations highlighted that probiotics might regulate host miRNA levels to down-regulate TLR4/NF-κB-dependent inflammation. PRACTICAL APPLICATIONS: Cow's milk allergy (CMA) is one of the most common diseases of food allergy, which has a high prevalence in infants and young children. La KLDS 1.0738 has been shown to be effective in alleviating β-Lg-induced allergic inflammation. Our study further found that treatment with La KLDS 1.0738 could suppress the TLR4/NF-κB signaling pathway via modulating miR-146a expression, thereby reducing the overexpression of downstream inflammatory factors. This study not only elucidates the specific pathway of La KLDS 1.0738 to relieve allergic inflammation, but also provides a new insight into the molecular mechanism for the remission and treatment of CMA by probiotics.

The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF+LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF+LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF+LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P<.001) for rice hydrolyzed formula vs EHCF+LGG; 2.62 (1.63-4.22, P<.001) for soy formula vs EHCF+LGG; 2.31 (1.42-3.77, P<.001) for EHWF vs EHCF+LGG; and 3.50 (2.23-5.49, P<.001) for amino acid-based formula vs EHCF+LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF+LGG cohort. The use of EHCF+LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

As soon as possible in IgE-cow's milk allergy immunotherapy.

Oral immunotherapy is a common treatment in cow's milk protein allergy. The Department of Pediatric Allergology at the Children's Hospital of Zaragozaperformed a retrospective analysis of 335 infants under 1year of age diagnosed with IgE-mediated cow's milk and early treated. Clinical evaluation, skin prick test, and serum-specific IgE level control were performed before starting and after finishing treatment. Upon completion of treatment, more than 98% of patients became tolerant to milk and no one presented serious adverse reactions. Nowadays, the remaining non-tolerant patients (1.8%) can take milk or derivatives daily-as prophylaxis-to a certain maximum dose and still remain asymptomatic. After immunotherapy, both positive skin prick tests and a progressive decrease in specific IgE levels were found, as desensitization to milk increased.Conclusion: Oral immunotherapy is a safe and effective treatment against allergy to cow's milk proteins in infants. Such treatment should be offered to the children's families from the first moment of diagnosis. What is known: • Cow's milk proteins are responsible for the earliest IgE-mediated allergic reactions in children. • Oral immunotherapy (OIT) is commonly used as cow's milk allergy treatment and it is proposed at different ages. What is new: • OIT it is an effective and safe method with no severe reactions at early ages. • The number of reaching successful treatments is awesome so we believe that immunity response can be molded at the first months of life, so the probability of success with infants is greater than in older children.

Prevention and Management of Cow's Milk Allergy in Non-Exclusively Breastfed Infants.

Introduction: The prevention and management of cow milk allergy (CMA) is still debated. Since CMA is much less frequent in breastfed infants, breastfeeding should be stimulated. Method: Literature was searched using databases to find original papers and reviews on this topic. Results: Hydrolysates with a clinical proof of efficacy are recommended in the prevention and treatment of CMA. However, not all meta-analyses conclude that hydrolysates do prevent CMA or other atopic manifestations such as atopic dermatitis. There are pros and cons to consider partially hydrolysed protein as an option for starter infant formula for each non-exclusively breastfed infant. A challenge test is still recommended as the most specific and sensitive diagnostic test, although a positive challenge test does not proof that the immune system is involved. The Cow Milk Symptom Score (CoMiSS™) is an awareness tool that enables healthcare professionals to better recognize symptoms related to the ingestion of cow milk, but it still needs validation as diagnostic tool. The current recommended elimination diet is a cow milk based extensive hydrolysate, although rice hydrolysates or soy infant formula can be considered in some cases. About 10 to 15% of infants allergic to cow milk will also react to soy. Mainly because of the higher cost, amino acid based formula is reserved for severe cases. There is no place for infant formula with intact protein from other animals as cross-over allergenicity is high. During recent years, attention focused also on the bifidogenic effect of prebiotics and more recently also on human milk oligosaccharides. A bifidogenic gastrointestinal microbiome may decrease the risk to develop allergic disease. The addition of probiotics and prebiotics to the elimination diet in treatment may enhance the development of tolerance development. Conclusion: Breastfeeding is the best way to feed infants. Cow milk based extensive hydrolysates remain the first option for the treatment of CMA for the majority of patients, while amino acid formulas are reserved for the most severe cases. Rice hydrolysates and soy infant formula are second choice options. Partial hydrolysates with clinical proof of efficacy are recommended in some guidelines in the prevention of CMA and allergic disease in at risk infants, and may be considered as an option as protein source in starter infant formula.

Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces β-lactoglobulin sensitization in mice.

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. 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. 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. 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.

Cow's Milk Allergy Prescribing Is Influenced by Regional and National Guidance.

Cow's milk allergy (CMA) is the most common food allergy in children with many clinical manifestations, leading to misdiagnoses such as gastro-oesophageal reflux, infantile colic, and lactose intolerance with inappropriate prescribing. We aimed to determine the impact of infant feeding guidelines on CMA prescribing in UK primary care using a simple and inexpensive training package. Prospectively collected data of infant feeding prescriptions in Northern Ireland from June 2012 to March 2014 were analysed with the intervention period between November 2012 and March 2013. A comparison was made between hypoallergenic formulae, appropriate for CMA, versus alternative prescriptions including antiregurgitation and colic products, lactose-free and partially hydrolysed milks, or infant Gaviscon. Comparing pre- and postintervention period, the total quantity of hypoallergenic formulae increased by 63.2% and alternative prescriptions decreased by 44.6% (P < 0.001). The total amount of all prescribed products decreased by 41.0% (P < 0.001). During the study period, the proportion of recommended CMA treatment increased from 3.4% before training to 9.8% in the short- and long-term follow-up (P < 0.001). The overall increase was £33,508 per year or £95.5 per general practitioner's surgery. We present the first study evaluating the impact of infant feeding guidelines on CMA prescribing in UK primary care. Practical advice and teaching of health professionals allowed for effective implementation of regional and national guidelines, with a significant impact on prescription patterns. This study shows promising results for prospective research on a national scale, including socioeconomical impact and cost-effectiveness.

Cow's Milk Allergy: A New Approach Needed?

Cow's Milk Allergy: A New Approach Needed?

Response to: Cost‐effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first‐line treatment for cow milk allergy in the UK

Response to: Cost‐effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first‐line treatment for cow milk allergy in the UK

How DRACMA changes clinical decision for the individual patient in CMA therapy

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). 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. 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.

Allergy to goat’s and sheep’s milk in a population of cow’s milk–allergic children treated with oral immunotherapy*

Cow's milk oral immunotherapy (CMOIT) is a recognized treatment for persistent cow's milk (CM) allergy. However, further data are necessary on tolerance to milk from other mammals. To describe the clinical and immunologic features of goat's and sheep's milk (GSM) allergy in patients who tolerated CM after CMOIT. Fifty-eight CM-allergic patients who successfully underwent CMOIT in our department were evaluated using skin prick test (SPT), specific immunoglobulin (Ig) E determination, enzyme-linked immunoassay (ELISA), and controlled oral challenge to assess allergy to GSM. Statistical analysis was carried out to identify markers of allergy to GSM. Fifteen of 58 (25.9%) patients were allergic to either goat's or sheep's milk or to both, as confirmed by a controlled positive oral challenge. Forty-seven percent of all positive oral challenges were classified as anaphylactic reactions. Specific IgE to CM casein, goat's whole milk, and sheep's whole milk was 13.2, 18.0, and 21.4 kU(A)/l in the group of GSM-allergic patients and 6.6, 6.5, and 6.5 kU(A) /l in the GSM-non-allergic patients (p < 0.05). Decision-making cut-off points based on sIgE for diagnosing symptomatic GSM allergy could not be determined. ELISA inhibition assays showed limited cross-reactivity (up to 77.2%) between CM casein and GSM casein in the group of GSM-allergic patients in contrast with almost 100% in GSM-not-allergic patients. We found a high prevalence (26%) of allergy to GSM in our population of CM-allergic children treated with oral immunotherapy. Therefore, tolerance to GSM should be assessed in order to provide accurate nutritional advice and minimize life-threatening accidental intake. Specific IgE to CM casein, goat's and sheep's whole milk is a good marker of this allergy. Although CM oral immunotherapy is a specific treatment for CM allergy, it may not be effective against allergy to the milk of other mammals.

Cost-effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first-line treatment for cow milk allergy in the UK.

To estimate the cost-effectiveness of using an extensively hydrolysed formula (eHF; Nutramigen) compared with an amino acid formula (AAF; Neocate) as first-line treatment for cow milk allergy (CMA) in the UK, from the perspective of the National Health Service (NHS). A decision model was constructed depicting the treatment paths and associated resource use attributable to first-line management of CMA with the two formulae. The model was based on the case records of 145 AAF-treated infants and 150 matched eHF-treated patients from The Health Improvement Network (THIN) database [a nationally representative database of patients registered with general practitioners (GPs) in the UK]. The model estimated the costs and consequences of patient management over 12 months following their initial GP visit for CMA. Patients presenting with a combination of gastrointestinal symptoms and eczema accounted for 44% of all patients in both groups. Those with gastrointestinal symptoms alone and eczema alone accounted for up to a further 39% and 13%, respectively. Those with urticaria and faltering growth accounted for <5% and ≤6% of all patients, respectively. Patients' age and weight at presentation was a mean 2.6-2.8 months and 4.4 kg, respectively. It took a mean 2.2 months to start a formula after initially seeing a GP. Time to symptom resolution following the start of treatment was 1.2 months in both groups; hence, the mean number of symptom-free months during the 12 months following the initial GP visit was estimated to be 8.6 months in both groups. Patients treated with an eHF had a mean 13.1 GP visits over the 12 months compared to 17.5 visits made by AAF-treated patients (p < 0.001). The NHS cost of managing a CMA infant over the first 12 months following initial presentation to a GP was estimated to be £1853 and £3161 for an eHF-treated and AAF-treated patient, respectively. Starting treatment for CMA with an eHF was the cost-effective option, as there were no significant differences in clinical outcomes between the two groups. A prospective, randomized controlled trial would allow a definitive confirmation of these findings.

Oral desensitization for milk allergy in children

The purpose of this review is to research current evidence on cow's milk oral immunotherapy for the treatment of cow's milk allergy (CMA). The specific, active treatment for IgE-mediated food allergy included CMA, which is currently being investigated in human trials. Allergen-specific approaches include oral, sublingual and epicutaneous immunotherapy. Reports on oral immunotherapy (OIT) for the treatment of milk allergy have been more extensive and carried out mostly with native proteins. The aim of OIT with cow's milk is the achievement of desensitization or tolerance by patients suffering from CMA. Desensitization state can be achieved by approximately 36-92% of the children treated with specific immunotherapy; the rate of permanent tolerance is unknown. Longer duration of desensitization may result in permanent tolerance. The possibility of adverse events or reactions during OIT is quite frequent. Side-effects have been reported by patients in all published studies. OIT as an active treatment for CMA represents an emerging reality. Before this treatment can be used in clinical practice, additional studies are needed. Currently, many issues remain unanswered: severity and type of food allergy responsive to specific immunotherapy, degree of protection, 'shared schedules' of desensitization(s) in research settings and well established risk-to-benefit ratio. However the field of specific, active treatment of food allergy is poised for clinically important advances.

Cow's milk allergy as a global challenge

Cow's milk is a leading cause of food allergy especially in infants and children. 'Diagnosis and Rationale for Action against Cow's Milk Allergy' published by the World Allergy Organization has underlined that there is not enough information concerning geographical trends in cow's milk allergy (CMA) in children or adults. Experts from Australia, Asia, North America, Latin America, the Middle East and Europe have gathered together in a 2-day meeting in order to present various regional approaches to CMA. This report is a summary of the information that was presented at this meeting. Even though there seems to be uniformity concerning the diagnosis and treatment of CMA, the diagnostic approach to CMA shows variations among different regions. Common concerns were inadequate applications of challenge tests for the diagnosis and inadequate supply of the cow's milk substitute formulas. CMA is a global challenge and collaboration of the national and international scientific communities is essential to produce and update practical guidelines for CMA.