Oral Milk Challenge Research Articles

A comprehensive approach integrating epinephrine use into symptom-based scoring systems to improve severity grading of reactions at milk oral challenge

A comprehensive approach integrating epinephrine use into symptom-based scoring systems to improve severity grading of reactions at milk oral challenge

Molecular allergy diagnostics in predicting oral cow's milk challenge outcome in Finnish children.

Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy. A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergyunderwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4),beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes. Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alphalactalbumin, and BSA than did children with mild reactions. Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.

Pharyngeal biorhythms during oral milk challenge in high-risk infants: Do they predict chronic tube feeding?

Eating difficulties are common in high-risk neonatal intensive care unit (NICU) infants; mechanisms remain unclear. Crib-side pharyngo-esophageal motility testing is utilized to assess contiguous swallowing physiology, and cross-system interplay with cardio-respiratory rhythms. Aims were to: (1) identify whether distinct pharyngeal rhythms exist during oral milk challenge (OMC), and (2) develop a chronic tube feeding risk prediction model in high-risk infants. Symptomatic NICU infants (N=56, 29.7 ± 3.7 weeks birth gestation) underwent pharyngo-esophageal manometry with OMC at 40.9 ± 2.5 weeks postmenstrual age (PMA). Exploratory cluster data analysis (partitioning around k-medoids) was performed to identify patient groups using pharyngeal contractile rhythm data (solitary swallows and swallows within bursts). Subsequently, (a) pharyngeal-esophageal, cardio-respiratory, and eating method characteristics were compared among patient groups using linear mixed models, and (b) chronic tube feeding prediction model was created using linear regression. Three distinct patient groups were identified with validity score of 0.6, and termed sparse (high frequency of solitary swallows), intermediate, or robust (high swallow rate within bursts). Robust group infants had: lesser pharyngeal and esophageal variability, greater deglutition apnea, pharyngeal activity, and esophageal activity (all p < 0.05), but less frequent heart rate decreases (p < 0.05) with improved clinical outcomes (milk transfer rate, p < 0.001, and independent oral feeding at discharge, p < 0.03). Chronic tube feeding risk=-11.37 + (0.22 × PMA) + (-0.73 × bronchopulmonary dysplasia) + (1.46 × intermediate group) + (2.57 × sparse group). Robust pharyngeal rhythm may be an ideal neurosensorimotor biomarker of independent oral feeding. Differential maturation of cranial nerve-mediated excitatory and inhibitory components involving foregut, airway, and cardiac rhythms distinguishes the physiologic and pathophysiologic basis of swallowing and cardio-respiratory adaptation.

Shorter Dosing Interval Is Associated With Multiple Doses Of Epinephrine Required To Resolve Allergic Reaction At Milk Oral Challenge

Shorter Dosing Interval Is Associated With Multiple Doses Of Epinephrine Required To Resolve Allergic Reaction At Milk Oral Challenge

Differences in Egg and Milk Food Challenge Outcomes Based on Tolerance to the Baked Form

To determine if a history of tolerance versus avoidance of baked egg or cow’s milk influenced the outcomes of an oral food challenge to egg or whole cow’s milk.The study included 569 pediatric patients who underwent egg or cow’s milk oral challenges at the Children’s Hospital of Philadelphia from 2012 to 2015.This was a retrospective chart review of pediatric patients who underwent whole egg and cow’s milk oral food challenges.More patients passed the whole egg food challenge if they previously tolerated baked egg (75%) versus avoidance (58%, P = .01) or never ingested (45%, P < .0001). Among the positive reactions, those patients who tolerated baked egg reacted at higher doses (3.0 g) and required epinephrine less often (10%) than those patients with egg avoidance (0.69 g, P = .03; 22%, P = .02) or who never ingested (0.88 g, P = .01; 32%, P = .0001). No difference was found among patients with cow’s milk allergy. Those who never ingested egg or cow’s milk had the poorest oral food challenge outcomes and the highest rates of atopic dermatitis (66% for patients with egg allergy and 86% for patients with milk allergy).This study shows that children who were known to be able to tolerate baked egg had higher food challenge pass rates (tolerance). Additionally, in those patients who did react, they were able to tolerate higher doses and had less-severe reactions if they previously tolerated baked egg. This association was not observed with patients with cow’s milk allergy.Known tolerance of baked egg may be a helpful marker for identifying children who will have more favorable food challenge outcomes. Although the effects of including baked egg in the diet on altering the natural history of egg allergy remains inconclusive, the results of this study support that tolerance of baked egg may help to promote tolerance of concentrated egg. Patients should be evaluated by an allergist early to possibly allow for introduction of baked egg into the diet. If baked egg tolerance has been established, the pediatrician can encourage parents to continue it in the diet. Further studies are needed to determine if the same benefit may be seen with cow’s milk and identify markers for favorable food challenge outcome.

Testing the Cow's Milk-Related Symptom Score (CoMiSSTM) for the Response to a Cow's Milk-Free Diet in Infants: A Prospective Study.

The diagnosis of cow’s milk allergy (CMA) is particularly challenging in infants, especially with non-Immunoglobulin E (IgE)-mediated manifestations, and inaccurate diagnosis may lead to unnecessary dietary restrictions. The aim of this study was to assess the accuracy of the cow’s milk-related symptom score (CoMiSSTM) in response to a cow’s milk-free diet (CMFD). We prospectively recruited 47 infants (median age three months) who had been placed on a CMFD due to persisting unexplained gastrointestinal symptoms. We compared data with 94 healthy controls (median age three months). The CoMiSSTM score was completed at recruitment and while on the exclusion diet. In 19/47 (40%) cases a response to the diet occurred. At recruitment CoMiSSTM was significantly higher in cases compared to controls (median score 8 vs. 3; p-value: <0.05), 9 cases had a score ≥12 and 8/9 normalized on CMFD. An oral milk challenge was performed in all 19 responders and six of these had a positive reaction to cow’s milk (CM). In eight infants IgE allergy tests were positive. The receiver operation characteristic (ROC) curve identified a CoMISSTM score of 9 to be the best cut-off value (84% sensitivity, 85% specificity, 80% positive (PPV) and 88% negative predictive value (NPV)) for the response to CMFD. We found CoMiSSTM to be a useful tool to help identify infants with persisting gastrointestinal symptoms and suspected CMA that would benefit from CMFD.

Food allergy in children with refractory gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) and food allergy are frequent disorders of childhood. The purpose of this study was to determine the frequency of food allergy in children with refractory GERD. A total of 151 children resistant to pharmacologic GERD treatment underwent skin prick test, specific immunoglobulin E, eosinophil count, atopy patch test (APT), and oral food challenge, and were then divided into three groups according to the results of oral milk challenge and allergy work-up: group A1, positive oral milk challenge and positive IgE-mediated allergy test; group A2, positive milk challenge and negative IgE-mediated allergy test; and group B, negative oral milk challenge and negative allergy tests. There were 35, 30 and 86 patients in group A1, group A2 and group B, respectively. A total of 28 of 35 patients in group A1 had cow's milk allergy and the other seven patients had egg allergy. APT positivity was more common in group A2. Endoscopic esophagitis was observed in six group A1 patients and in four group A2 patients. Bloody stools, atopic dermatitis and recurrent wheezing episodes were significantly more common in group A1 than in group A2 and group B (P < 0.001, for both). Cow's milk allergy was observed frequently in children resistant to pharmacologic GERD treatment. Combined skin prick and specific IgE tests, APT and oral food challenge is essential for avoidance of unnecessary elimination diet.

What makes children outgrow food allergy?

What makes children outgrow food allergy?

Heating does not decrease immunogenicity of goat's and ewe's milk

URE 1. A, SDS-PAGE (A-1) and Western blot analysis (A-2) with u , and EM allergies and milk-tolerant negative control showed high an d (A-3). ALA, a-Lactalbumin; BLG, b-lactoglobulin; CC, cow’s che ecular weight; SA, serum albumin. extensive amino acid sequence identity of milk proteins (85%100%; see Tables E1 and E2 in this article’s Online Repository at www.jaci-inpractice.org) and similar proteome profiles that imply similarity of protein functions. However, selective GM and ewe’s milk (EM) allergy without CMA (GEMA) have been reported, including anaphylaxis to cheeses from GM and EM in CM-tolerant children. GEMA implies existence of unique GM and EM-allergenic epitopes that are different from CMallergenic epitopes. Among children with CMA, >70% can tolerate extensively heated CM in baked products. We sought to determine the effects of heating on the immunogenicity of GM and EM proteins in children with GEMA. We recruited 17 subjects with milk allergy from Spain, Greece, and the United States; 13 were males; median age was 7.2 years, and 25% to 75% interquartile range (IQR) was 4.0 to 9.9 years. The study was approved by the Institutional Review Boards at The Mount Sinai School of Medicine, Pediatric Hospital “P & A Kiriakou,” and Hospital Infantil Universitario Nino Jesus; informed consent was obtained from the subjects. Eight subjects with CM allergy tolerated extensively heated oral milk challenge but reacted to unheated milk challenge. Nine subjects had history of convincing, immediate allergic symptoms on ingestion of GM or EM or both (Table I). The 8

Milk-induced wheezing in children with asthma

BackgroundFood allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. ObjectivesThis study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma. Methods32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge. ResultsReactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. ConclusionThis study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.

Prospective Follow-up Oral Food Challenge in Food Protein-Induced Enterocolitis Syndrome

Hwang JB, Sohn SM, Kim AS. Arch Dis Child. 2009;94(6):425–428PURPOSE OF THE STUDY. To determine tolerance rates to cow's milk and soy for infants affected by food protein-induced enterocolitis syndrome (FPIES).STUDY POPULATION. Twenty-three patients (7 female and 16 male) with infantile FPIES were prospectively followed.METHODS. Infants with a diagnosis of FPIES were diagnosed by positive oral food challenges for milk or soy formula at 36 days of age (SD: 14 days; range: 13–58 days). These infants were prospectively followed until >2 years of age. They underwent ≥2 follow-up oral challenges. The first follow-up oral challenges were performed at 6 months of age, and patients were randomly allocated to either milk (N = 11) or soy (N = 12). Second and third follow-up oral challenges were performed at 2-month intervals, in a crossed and switched-over manner. The challenge consisted of a single open oral feeding of 0.03 to 0.05 mg of cow's milk protein or soy protein per kg of body weight.RESULTS. Seventy-two oral food challenges with cow's milk or soy were performed in 23 patients with FPIES. There were 27 positive challenges (37.5%). For all positive challenges, projectile vomiting and lethargy were noted at ∼1 to 4.5 hours. Symptoms less commonly seen were cyanosis in 6 challenges (22.2%) and hypotension in 3 challenges (11.1%). No false-negative challenges were seen among the 45 negative challenges. Tolerance rates for milk at 6, 8, and 10 months of age were 27.3%, 41.7%, and 63.6%, respectively. Tolerance rates for soy at 6, 8, and 10 months of age were 75.0%, 90.9%, and 91.7%, respectively. Mean ages for outgrowing reactivity to cow's milk and soy among the 23 patients were 12.0 months (SD: 4.4 months; range: 6–20 months) and 7.8 months (SD: 2.1 months; range: 6–14 months), respectively. Solid-food FPIES was observed in 2 of the patients (rice, beef, and egg in 1 child >11 months of age and fish and shellfish in 1 child >12 months of age). These 2 children became tolerant to these foods after 2 years of age.CONCLUSIONS. The study reveals that infants with FPIES lose intolerance to soy protein at an earlier age, compared with cow's milk. The authors suggest that soy oral challenge should be performed at 6 to 8 months of age and that milk oral challenge should be conducted when the child is >1 year of age. Challenge should be conducted under close medical supervision. The authors also found that a smaller than previously published challenge dose (0.03 to 0.05 mg of cow's milk or soy protein per kg of body weight) was adequate in inducing symptoms.REVIEWER COMMENTS. Performing oral challenges in infants affected by FPIES is not a light undertaking, as evidenced by the number of children who had a positive oral challenge, cyanosis, and hypotension. This article gives insight to clinicians regarding when and how to perform oral challenges for infants affected by milk and/or soy protein-induced enterocolitis syndrome.

Mapping of the IgE and IgG4 sequential epitopes of milk allergens with a peptide microarray–based immunoassay

Peptide microarray analysis is a novel method that can provide useful information on the nature of specific allergies. We sought to determine the specificity and diversity of IgE and IgG4 antibodies binding to sequential epitopes of alpha(s1)-, alpha(s2)-, beta-, and kappa-caseins and beta-lactoglobulin by using a peptide microarray-based immunoassay. A microarray immunoassay was performed with sera from 31 children with IgE-mediated milk allergy (16 with positive oral milk challenge results [ie, the reactive group] and 15 with negative oral milk challenge results [ie, the tolerant group]). A library of peptides, consisting of 20 amino acids (AAs) overlapping by 17 (3-offset), corresponding to the primary sequences of alpha(s1)-, alpha(s2)-, beta-, and kappa-caseins and beta-lactoglobulin was printed on epoxy-coated slides. A region was defined as an epitope if it was statistically associated with reactive groups and recognized by at least 75% of reactive patients. By using this method, a total of 10 epitopes were identified: alpha(s1), AAs 28 to 50, 75% reactive and 26.7% tolerant; alpha(s2), AAs 1 to 20, 75% reactive and 13.3% tolerant; AAs 13 to 32, 75% reactive and 26.7% tolerant; AAs 67 to 86, 75% reactive and 33.3% tolerant; and AAs 181 to 207, 75% reactive and 20% tolerant; beta-casein, AAs 25 to 50, 75% reactive and 33.3% tolerant, AAs 52 to 74, 81.3% reactive and 26.7% tolerant; and AAs 154 to 173, 75% reactive and 33.3% tolerant; beta-lactoglobulin, AAs 58 to 77, 81.3% reactive and 40% tolerant; and kappa-casein, AAs 34 to 53, 87.5% reactive and 40% tolerant. Several regions have been defined as epitopes, which showed differential recognition patterns between reactive and tolerant patients. Further studies are needed to validate the utility of this assay in clinical practice.

Lessons from the clinical course of IgE‐mediated cow milk allergy in Israel

Cow milk and milk products are the most common food products consumed in Israel; rates of allergy to cow milk exceed those of peanuts in infants and children. The aim of the present study was to evaluate retrospectively the clinical features and natural course of immunoglobulin (Ig) E-mediated cow milk allergy (CMA) in Israel. Data of children diagnosed with CMA from 1995 to 2003, were collected regarding age at first and most recent reactions, symptoms and signs, family history of atopy, other allergic diseases, emergency department visits, hospitalizations, and treatment. Patients with transient CMA were compared to those with persistent CMA (> or =3 yr old). The study group consisted of 105 patients, 43 with transient CMA (age range: 0.48-11 yr). The remaining 62 patients (age range: 3-16.5 yr) did not achieve tolerance to cow milk during the follow-up period. No differences were found between the groups in mean age and symptoms and signs at the first allergic reaction and family history of atopy. Patients with persistent CMA had a higher rate of asthma than patients with transient CMA (61.2% vs. 18.6%, p < 0.001). Fifty patients with persistent CMA had 137 subsequent allergic reactions after diagnosis, 25% of the reactions were due to oral milk challenge at the clinic and 75% due to accidental exposure, of which 13% required an emergency department visit and 8%, hospitalization. Only 19% of the reactions were treated with epinephrine injection. In conclusion, in our experience, less than half of the children diagnosed with IgE-mediated CMA during 9 yr, outgrew it. The patients with persistent CMA have a higher prevalence of asthma compared with the general population or to children with transient CMA. The high number of recurrent allergic reactions due to accidental exposure and the low rate of epinephrine usage in these patients point to a need for better education of patients and their families.

Hyperreactivity to cow's milk in an infant with LE and tart cell phenomenon

LE and tart cells were demonstrated in a black male infant whose serum contained milk-percipitating antibodies and who had pulmonary infiltrates. Immunoblasts, plasmocytoid lymphocytes, and an LE cell were found in a milk-stimulated skin window. The presence of LE cells corresponded to the presence of ENA antibody. Tart cells varied with oral milk challenge. A large Arthus type of skin reaction to injected milk was demonstrated. An oral feeding of milk resulted in a decrease in plasma C3. Lymphocyte transformation resulted from in vitro milk stimulation. ENA (extractable nuclear antigen) antibody and resulting LE cell formation possibly represented the combination of nuclear protein with milk antigen. The pulmonary infiltrates may represent a hypersensitivity pneumonitis characterized by both Arthus and cell-mediated reaction to milk.

MILK ALLERGY

The diagnosis of milk allergy was confirmed in 89 children by oral challenge with milk and/or purified milk proteins. Most of these patients were diagnosed as allergic during the first 2 years of life. The symptoms of milk allergy usually began during the first few months of life. Eighteen of the total patients experienced spontaneous remission of milk hypersensitivity. Multiple symptoms were produced by oral milk challenge in 77% of the patients. Vomiting, diarrhea, abdominal pain, asthma, rhinitis, and atopic dermatitis were frequently presenting and challenge symptoms. Several patients had central nervous system symptoms, urticaria, or anaphylactic reactions following milk challenge. Seventy-eight per cent of the presenting symptoms were reproduced by oral milk challenges. Challenge feedings produced symptoms not found in the history in 18% of the patients. No consistent patterns of symptom combinations were found. The onset time of oral challenge reactions was usually within the first 12 to 24 hours. Some reactions occurred within a few minutes while others required 2 days or more before they were discernible. The duration of challenge reactions was usually between 12 to 24 hours. Allergic symptoms appeared much sooner after oral challenge in the patients who required less milk to elicit an allergic reaction. Forty-five patients were challenged with amounts of the purified milk proteins, casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin, present in the challenge doses of 100 ml skim milk. Every patient had an allergic reaction to one or more milk proteins. The frequencies of reactions were casein, 57%; BSA, 51%; beta-lactoglobulin, 66%; and alpha-lactalbumin, 54%. The reactions from oral challenge to skim milk or purified milk protein in a given patient were very similar. No correlation was found between the symptoms produced and the specific protein which produced these reactions. By oral challenge tests few patients (13%) were allergic solely to the heat labile protein, BSA. Only two of these patients could be actually managed on a processed milk in which BSA was inactive by laboratory tests.