Diagnosis Of Cow's Milk Allergy Research Articles

Serum eosinophil-derived neurotoxin: a new promising biomarker for cow's milk allergy diagnosis.

Cow's Milk Allergy (CMA) diagnosis is often a challenge due to the non-specific nature of symptoms and lack of a confirmatory diagnostic test. To our knowledge no previous studies investigated serum Eosinophil-Derived Neurotoxin (sEDN) in CMA. So, we aimed to assess the role of sEDN in CMA diagnosis. Forty-five infants with CMA were compared to 45 infants with functional gastrointestinal disorders (FGIDs) and 45 healthy controls. For all participants, Cow's Milk-related Symptom Score (CoMiSS) was documented, and sEDN level with hematological parameters were measured before starting elimination diet. Receiver operation characteristic (ROC) curve identified sEDN > 14 ng/mL and CoMiSS > 9 as the optimal cut-off points to discriminate CMA from other groups with sensitivity 86.67%, 97.78% and specificity 60.00%, 78.89% respectively. Additionally, absolute neutrophil count (ANC) showed the highest sensitivity and specificity (80.0% and 78.89%) among hematological parameters. Although CoMiSS and ANC showed a significant positive correlation with sEDN in CMA group, CoMiSS was the only significant predictor for sEDN in multivariate linear regression. sEDN showed high sensitivity in discriminating infants with and without CMA. Therefore, it is suggested as a potential biomarker for CMA diagnosis. Also, ANC should be closely monitored in these infants. CMA presents with high heterogeneity, which complicates the diagnosis especially non-IgE-mediated and mixed types. So, oral food challenge continues to be the gold standard for its diagnosis. ROC curve identified CoMiSS > 9 as the best cut-off point to identify CMA. However, CoMiSS is a good awareness tool for CMA but not a diagnostic tool. sEDN level was significantly higher in infants with CMA with a good diagnostic performance in differentiating them than those without CMA. So, it is suggested as a potential biomarker for CMA diagnosis. ANC could have a role in CMA diagnosis and differentiating it from FGIDs.

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 status and feeding difficulties in children up to 2 years of age with cow's milk allergy.

To assess the nutritional status and incidence of feeding difficulties in Polish children up to 2 years of age with cow's milk allergy (CMA) on cow's milk proteins-free diet. A cross-sectional, multi-center study included children aged 6 months to 2 years with confirmed or suspected (without oral food challenge) diagnosis of CMA on the elimination diet for at least 1 month. The primary outcomes were an assessment of proportion of children with impaired nutritional status (with the weight for length and body mass index (BMI) z-score > 1 and <-1), and feeding difficulties according to the Montreal Children's Hospital Feeding Scale. Children with confirmed and suspected CMA were assessed separately. A 144 children with confirmed CMA and 88 with suspected CMA were included (57 and 78% with multiple food allergies, respectively). Among children with confirmed CMA, one-third (35.5%) of participants had any nutritional status impairment regardless of definition. Among those, most of children had mild malnutrition (10.4 vs. 9%) and possible risk of overweight (11.1 vs. 9.7%; following respectively BMI for age and weight for length z-scores). Only 16.0% of children had feeding difficulties. Feeding difficulties was identified to be a risk factor for moderate malnutrition compared to children without feeding difficulties (odds ratio 10, 95% confidence interval: 4-27). Mild malnutrition and possible risk of overweight are concern in children up to 2 years of age on cow's milk proteins-free diet. Feeding difficulties are less common, however, may affect the nutritional status.

The role of online symptom questionnaires to support the diagnosis of cow's milk allergy in children for healthcare professionals - A Delphi consensus study.

Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Further Insights into the Gut Microbiota of Cow's Milk Allergic Infants: Analysis of Microbial Functionality and Its Correlation with Three Fecal Biomarkers.

Cow's milk allergy (CMA) is one of the most prevalent food allergies in children. Several studies have demonstrated that gut microbiota influences the acquisition of oral tolerance to food antigens at initial stages of life. Changes in the gut microbiota composition and/or functionality (i.e., dysbiosis) have been linked to inadequate immune system regulation and the emergence of pathologies. Moreover, omic sciences have become an essential tool for the analysis of the gut microbiota. On the other hand, the use of fecal biomarkers for the diagnosis of CMA has recently been reviewed, with fecal calprotectin, α-1 antitrypsin, and lactoferrin being the most relevant. This study aimed at evaluating functional changes in the gut microbiota in the feces of cow's milk allergic infants (AI) compared to control infants (CI) by metagenomic shotgun sequencing and at correlating these findings with the levels of fecal biomarkers (α-1 antitrypsin, lactoferrin, and calprotectin) by an integrative approach. We have observed differences between AI and CI groups in terms of fecal protein levels and metagenomic analysis. Our findings suggest that AI have altered glycerophospholipid metabolism as well as higher levels of lactoferrin and calprotectin that could be explained by their allergic status.

Evaluation of Cow's Milk Related Symptom Score [CoMiSS] accuracy in cow's milk allergy diagnosis.

Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool to recognize cow's milk allergy (CMA) symptoms in infants. We aimed to assess the best cut-off point of CoMiSS in our country and investigate other parameters suggested to raise the strength of CoMiSS in CMA diagnosis. We enrolled 100 infants with CMA-suggestive symptoms with documentation of CoMiSS initially and 4 weeks after cow milk-free diet (CMFD) followed by an open food challenge (OFC) test. Infants with symptom recurrence upon challenge were diagnosed with confirmed CMA. Initial mean CoMiSS was 15.76 ± 5.29, being higher in the confirmed CMA group (84% of infants). Following CMFD, median CoMiSS significantly reduced to 1.5 in the confirmed CMA group compared to 6.5 in the negative group. Receiver operation characteristic (ROC) curve identified a CoMiSS score of ≥12 as the best cut-off value with 76.19% sensitivity, 62.50% specificity and overall accuracy of 74.00%. Mucoid stool, bloody stool and faltering growth were reported in 80, 41 and 52% of confirmed CMA infants, respectively, with considerable improvement following CMFD. Our study revealed a CoMiSS score of ≥12 to be the best cut-off point. However, CoMiSS cannot be used alone for accurate diagnosis of CMA. CoMiSS ≥12 can predict a positive response to CMFD; nevertheless, CoMiSS is a good awareness tool and cannot be regarded as a stand-alone CMA diagnostic test. CoMiSS reduction following CMFD was predictive of a reaction to OFC to diagnose CMA as well as for monitoring symptom improvement. Symptoms commonly associated with CMA as mucoid stool, bloody stool, marked abdominal distention not responding to medical treatment and faltering growth, in addition to their improvements in response to CMA are suggested parameters to be added to CoMiSS to improve its accuracy.

Characteristics of cow's milk allergy and sensitization in Chinese patients.

Characteristics of cow's milk allergy and sensitization in Chinese patients.

The health economic impact of cow's milk allergy in childhood: A retrospective cohort study.

BackgroundCow's milk allergy (CMA) is one of the most common food allergies among children. Whilst avoidance of cow's milk protein is the cornerstone of management, further treatment of symptoms including those affecting the gastrointestinal, skin and respiratory systems plus other allergic comorbidities, maybe required. This study aimed to quantify the wider economic impact of CMA and its management in the United Kingdom (UK).MethodsWe conducted a retrospective matched cohort study on children with CMA (diagnosis read code and/or hypoallergenic formula prescription for ≥3 months) examining healthcare data (medication prescriptions and healthcare professional contacts) from case records within The Health Improvement Network (A Cegedim Proprietary Database) in the UK. A comparative cost analysis was calculated based on healthcare tariff and unit costs in the UK.Results6998 children (54% male; mean observation period 4.2 years) were included (n = 3499 with CMA, mean age at diagnosis 4.04 months; n = 3499 matched controls without CMA). Compared to those without CMA, medications were prescribed to significantly more children with CMA (p < 0.001) at a higher rate (p < 0.001). Children with CMA also required significantly more healthcare contacts (p < 0.001) at higher rate (p < 0.001) compared to those without CMA. CMA was associated with additional potential healthcare costs of £1381.53 per person per year.ConclusionThe findings of this large cohort study suggest that CMA and its associated co‐morbidities presents a significant additional healthcare burden with economic impact due to higher prescribing of additional medications. Further research into management approaches that may impact these clinical and economic outcomes of CMA is warranted.

Modern diagnostics in IgE-mediated cow’s milk allergy

Cow's milk allergy (CMA) is the most common food allergy in infants and young children. Allergic reactions can vary from mild to severe, like an anaphylactic shock. In case of CMA diagnosis suspicion skin prick tests (SPT), immunoassays of specific IgE (sIgE) in blood serum (in vitro tests) and oral food challenge (OFC) tests can be performed. SPT wheal diameter and the level of serum specific IgE to milk do not correlate with severity of clinical symptoms, while procedure of OFC is often difficult or even imposible in practice. Therefore component resolved-diagnostics (CRD) tests are a new diagnostic tool, which allows for a better correlation of laboratory test results with the observed clinical symptoms and indicate the triggering allergens.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - IV - A quality appraisal with the AGREE II instrument.

BackgroundSince the publication of The World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines in 2010, a number of other guidelines, expert opinions, and position papers relating to the management of cow's milk allergy (CMA) have been published. We aimed to systematically review the quality of the guidelines on CMA diagnosis and management in children and/or adults published between 2010 and 2020.MethodsThe MEDLINE, EMBASE, ISI Web of Science, World Health Organization Global Index Medicus, and Turning Research into Practice databases as well as website guideline repositories were searched from January 2010 until May 2020. Any clinical practice recommendations and/or guidelines focusing on the diagnosis and management of CMA in children and/or adults developed or endorsed by professional scientific societies or organizations were included. The guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool, a 23-item tool organized within 6 domains and 2 global rating items.ResultsWe included 12 guidelines; 8 were developed by national and 4 by international organizations. The quality scores for each domain varied: of all domains, the clarity of presentation domain had the highest median score (92%; Q1-Q3 81–100%), whereas rigor of development had the lowest median score (30%; Q1-Q3 15–67%). The median scores (Q1-Q3) for individual domains were as follows: scope and purpose 82% (70–99%), stakeholder involvement 63% (21–79%), rigor of development 30% (15–67%), clarity of presentation 92% (81–100%), applicability 68% (57–75%), and editorial independence 75% (69–100%). The median overall score was 70% (58–89%). Only 1 guideline (from the National Institute for Health and Care Excellence [NICE]) achieved top ratings (100%) in five domains and the overall score. Three guidelines (from the NICE, the British Society for Allergy & Clinical Immunology [BSACI] and WAO) achieved the highest ratings (100%) in at least 3 domains and the overall score.ConclusionThe majority of identified guidelines were of good or very good quality. However, the weakest point was the rigor of development domain, mostly due to unclear description of strengths and limitations of the body of evidence and the procedure for updating the guidelines.

Complementary bottles during the first month and risk of cow's milk allergy in breastfed infants.

To assess the impact of complementary feeding bottles given at maternity hospital and/or over the first month after discharge from the maternity ward on cow's milk allergy (CMA) risk in breastfed infants. Case-control study involving infants aged 6-9months and who were breastfed for at least 1month. In 554 cases with a diagnosis of CMA and 211 controls, feeding bottles at maternity hospital, feeding bottles during the first month of life, avoidance of dairy products during pregnancy or breastfeeding, family history of allergy, intake of antibiotics and consumption of proton-pump inhibitors or antacids by the infant during the first month of life were associated with increased risk of CMA in a univariate model. In a multivariate model, only feeding bottle at maternity hospital (OR=1.81 [1.27; 2.59]), family history of allergy (OR=2.83 [2.01; 3.99]) and avoidance of dairy products during pregnancy or breastfeeding (OR=5.62 [1.99; 15.87]) were independent risk factors of CMA. Complementary bottles given at maternity hospital to newborns who will be exclusively breastfed increases the later risk of CMA. Similarly, avoidance of dairy products during pregnancy or breastfeeding should be discouraged.

Screening for Cow Milk Allergy in Infants and Preschool Children

Abstract Background Cow milk allergy (CMA) is the third most common food allergy that triggers anaphylactic reactions. Lactose intolerence, infantile colic and gastroesophageal reflux are the most common conditions which overlap with CMA causing both over and underdiagnosis. There are no wide population based epidemiological studies for the prevalence of CMA among Egyptian children. We sought to evaluate the prevalence of CMA among infants and preschool children and to correlate the parental reporting of CMA to the available diagnostic tools. Methods We conducted a cross sectional study that included 800 Egyptian children aged 3 months -5 years, who were enrolled consecutively from the primary care units and outpatient clinics of Children’s Hospital, Ain Shams University. Detailed history taking and clinical examination were done and those with suggestive history of CMA were subjected to further evaluation including skin prick test (SPT) and oral challenge test (OCT). Results The study comprised 390 girls (48.8%) and 410 boys (51.2%). Their weight centiles ranged between 5th and 97th percentiles, with median (IQR)=25(5-50) percentiles and mean(SD)=36.1(31.9). CM was introduced at age of 1-12 months, mean (SD): 9 (6) months with median (IQR): 12 (9-12) months. Forty (5%) subjects had suggestive history of CMA, 32 of whom completed their evaluation. The diagnosis of cow milk allergy was confirmed in 8/40 children (20%), comprising 1 % of the whole study sample. CMA was probably excluded at the time of the study in 21 subjects (52.5%), while diagnosis remained undetermined in 11/40 cases (27.5%) (8 refused to undergo SPT &amp; OCT while 3 were lost to follow up). Conclusion The prevalence of CMA in Egyptian infants and preschool children is estimated to be around 1 % with possible overestimation of cow milk allergy diagnosis according to parental reports.

Predictors of a positive oral food challenge to cow's milk in children sensitized to cow's milk

Introduction and objectivesThe diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA. Material and methodsWe retrospectively studied 72 patients [median age, four years; age range 0.75–15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables’ discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA. ResultsThe OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p<0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by β-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥0.95kU/L yielded 88.9% sensitivity and 90.9% specificity. ConclusionsIn our center, casein-specific IgE >0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history.

How guideline can shape clinical practice globally: the diagnosis and rationale for action against cow's milk allergy experience.

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. 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. 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.

Precision medicine in cow's milk allergy: proteomics perspectives from allergens to patients

Cow's milk allergy (CMA) is one of the most common food allergies, especially during childhood. CMA is an immunological mediated adverse reaction to one or more cow's milk proteins, which are normally harmless to a non-allergic individual, as the result of a failure of oral tolerance. To make a correct diagnosis of CMA and a proper treatment is critical in clinical practice. Application of proteomics along with new bio-informatics tools in the field of food allergy is one of the hot topics presented in recent years. In the present review, we focus on recent applications of proteomics to the field of cow's milk allergy, from allergens quantification to the diagnosis, treatment and prognosis. Furthermore, we also shed a light on potential future directions and developments, that are parts of personalized medicine but also of the One Health approach. SignificanceThe field of food allergies is becoming a milestone in public health. Food allergies, in fact, can cause life-threatening reactions and profoundly influence the quality of life. Precise, fast and reliable diagnosis of food allergies, and in particular milk allergies is essential to avoid severe allergic reactions and also to prevent dangerous and eventually unnecessary dietary restrictions; but this can be difficult also due to a complex interaction of genetic background, environment, and microbiota. In this sense, proteomics represents steps toward researching food and milk allergy integrated with the clinic to improve pathophysiology, diagnosis, therapy, and prognosis.

Cow's milk allergic children-Can component-resolved diagnostics predict duration and severity?

Cow's milk allergy (CMA) affects 2% of all children. This study investigatescomponent-resolved diagnostics(CRD) to cow's milk proteins in children suspected of CMA, by correlating the level of CRD with outcome of the oral challenge. Furthermore, we evaluate the ability of serial CRD measurements to distinguish children with persistent CMA from children developing tolerance. We included data from 78 children referred to the Allergy Centre during a 13-year period. Results from oral food challenges including threshold, severity, and sensitization data (IgE antibodies to whole milk protein, IgE components toward milk and skin prick test (SPT)) were collected. The milk allergic children were re-evaluated with sensitization data and rechallenges regularly. Thirty-nine children had negative first challenges, and 39 had positive first challenges. The positive group was rechallenged and separated into 3 groups depending on time to remission. At inclusion, children with persistent CMA had significantly larger size of SPT and higher levels of s-IgE to milk and CRD compared to the other groups. SPT wheal size was significantly larger in children with persistent CMA compared to children outgrowing CMA. Furthermore, a correlation between s-IgE level to cow's milk and casein and the severity of the allergic reaction elicited by food challenges was found. Oral food challenge cannot be replaced by s-IgE to whole milk protein or milk components nor SPT in the diagnosis of CMA; however, high levels of milk components and s-IgE to milk increase the risk of a long-lasting or persisting CMA.

Cow's Milk Allergy in Infancy and Later Development of Juvenile Idiopathic Arthritis: A Register-Based Case-Control Study.

We examined the association between cow's milk allergy (CMA) and juvenile idiopathic arthritis (JIA). The material for this case-control study was collected from national registers of all children born in Finland between 2000 and 2010 and diagnosed with JIA (n=1,298) and age-, sex-, and place-matched controls (n=5,179). We identified 235 children with CMA; 66 of these children also had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA and to test whether exposure to antibiotics would be a covariate for this association. In boys (but not in girls), a diagnosis of CMA and the use of hypoallergenic formula in infancy were associated with the later development of JIA (odds ratio=2.4, 95% confidence interval: 1.6, 3.6). The association was most evident in boys who were diagnosed with JIA before age 3 years or diagnosed with CMA with predominantly gastrointestinal symptoms. There was no statistically significant additive interaction between CMA and antibiotic exposure in the later development of JIA. These associations may reflect impaired maturation of intestinal immunity and integrity in boys with a risk of JIA. Predisposing factors related to JIA pathogenesis seem to display a sex-linked disparity.

Cow's Milk Allergy: the Relevance of IgE.

Cow's milk allergy (CMA) accounts for most diagnosed food allergies, mainly in the first year of life.1 CMA can cause severe anaphylaxis.2 CMA management is based on strict avoidance and the prescription of rescue medication. Cow's milk (CM) contains more than 40 proteins, including casein (Bos d 8), -lactalbumin (Bos d 4), and -lactoglobulin (Bos d 5), identified as major milk allergens.1 Serum specific IgE (sIgE) to casein characterized patients with persistent CMA,3 CM tolerance,4 and reactivity to baked milk.5 Oral immunotherapy (OIT) for CMA has been used with interesting outcomes as it may induce immunologic tolerance.1,2 However, a safety perspective represents a relevant concern, because reactions to OIT are frequent1,2 It has been demonstrated that sIgE to raw CM >50 kUA/L predicted not-tolerated OIT.6 Molecular-based allergy diagnostics have now become recently available in clinical practice. This method allows for defining and characterizing the sensitization profile that identifies potentially dangerous proteins and suggests a more precise prognosis. In this regard, Cingolani and colleagues reported that component resolved diagnosis had a good ability to define 2 phenotypes of CMA children: high-anaphylaxis and milder-risk.7 In particular, these phenotypes can be differentiated through measuring the level of sIgE to Bos d 8. We now report our experience concerning a retrospective cohort. This observational and retrospective experience evaluated the usefulness of ImmunoCAP and ISAC (please describe company, city, country) to detect anaphylaxis after CM ingestion. We evaluated children with CMA diagnosis who consecutively visited the Istituto Gaslini (a third tier children's hospital) in the last year. CMA diagnosis was performed on suggestive history consistent with CM sensitization (i.e. symptom occurrence after milk ingestion), documented milk sensitization, and a positive food challenge test. Anaphylaxis was defined according to validated criteria: briefly, suggestive history (sudden occurrence of symptoms, involving at least two systems, such as gastrointestinal and/or cutaneous and/or respiratory and/or cardiovascular after milk ingestion) consistent with documented CM sensitization.1 Serum sIgE to: raw CM allergen, Bos d 4, 5, and 8 were measured by the quantitative ImmunoCAP method and the semi-quantitative microarray-ISAC method (Thermo Fisher Italy). We Evaluated 53 patients (20 with anaphylaxis and 33 with CMA). Children with anaphylaxis presented: skin symptoms (89%), respiratory complaints (77%), gastrointestinal features (57%), and cardiovascular symptoms (11%). Children with CMA presented: skin symptoms (71%), gastrointestinal features (65%, mainly vomiting), and respiratory complaints (58%). The Table shows the clinical and immunologic characteristics of the 2 groups. The significant prevalence for male gender in anaphylaxis was consistent with that of Cingolani's study. The age was significantly lower in the anaphylaxis group, it conflicted with the findings of that study (surprisingly the age was particularly old in regards to CMA). Serum sIgE levels to raw CM allergen were significantly higher in the anaphylaxis group; however, there was no significant difference between the two groups for all molecular components as measured by both the ImmunoCAP and ISAC method. Table Clinical and imunological characteristics of patients Receiver operating characteristic (ROC) analysis showed that raw CM ImmunoCAP had a good specificity (86.7%), but weak sensitivity (52.9%), fair positive (69.2%), and negative (76.5%) predictive value, with Diagnostic Odds Ratio (ORDiagn) 7.3. The assessment of molecular components by ImmunoCAP was unsatisfactory in regards to area under the ROC curve (AUC), sensitivity, and specificity, despite the fair positive and negative values. The micro-assay ISAC method was also unreliable in our setting. We believe that the diagnostic work-up for CMA should consider a molecular-based allergy diagnostic as well as a raw allergen assessment to obtain more useful information for the management and possible identification of risk factors.

Evaluating the role of clinical history and laboratorial tests in IgE mediated cow's milk allergy diagnosis

Background IgE mediated cow’s milk allergy (CMA) is a frequent disease in pediatric population, and challenge tests are considered gold standard in its diagnosis, although its use is limited in clinical practice. An appropriated anamnesis and laboratorial analysis are the most frequent and feasible used tools. The aim of this study was to evaluate the role of these practices in IgE mediated CMA diagnosis.