Effects of an Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety and Infection Risk in Infants with Cow's Milk Protein Allergy: A Randomized, Multi-Center Trial.

This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content (2.20 g/100 kcal) supports normal growth in infants with cow's milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.

Symptom scores in the diagnosis of pediatric cow's milk protein allergy: A systematic review.

BACKGROUND: Cow's milk protein allergy (CMPA) is an immune-mediated allergic response to proteins in milk that is common in infants. Broad CMPA symptoms make diagnosis a challenge, particularly in primary care. Symptom scores may improve a clinician's awareness of symptoms, indicating a need for further testing. This systematic review examined the development and evaluation of such symptom scores for use in infants. METHODS: CENTRAL, MEDLINE, EMBASE and CINAHL databases were searched from inception to 3 December 2019 (Updated 14 November 2020) for diagnostic accuracy studies, randomised controlled trials, observational studies, economic evaluations, qualitative studies and studies reporting development of the tools. Data were not suitable for meta-analysis due to clinical and methodological heterogeneity, so were narratively synthesised. RESULTS: We found two symptom scores evaluated in one and fourteen studies, respectively. Estimated sensitivity and specificity ranged from 37% to 98% and 38% to 93%. The evaluations of each tool were at high risk of bias or failed to address issues such as clinical and cost-effectiveness. CONCLUSIONS: Estimates of accuracy of symptom scores for CMPA offered so far should be interpreted cautiously. Rigorous, conflict-free research based on well-defined roles for the tools is urgently required.

Lip Dose Challenges in Food Allergy: Current Practice and Diagnostic Utility in the United Kingdom.

BACKGROUND: Lip dose challenges (LDCs) are often performed as an initial step before oral food challenges (OFCs). However, guidance on how to perform and interpret LDCs is unclear, and data are lacking regarding the diagnostic accuracy of LDCs. OBJECTIVE: To investigate current practice with respect to LDCs among UK allergy health care professionals, and to evaluate the diagnostic utility of LDCs in children undergoing OFCs for IgE-mediated food allergy. METHODS: We used an electronic survey to assess the use of LDCs by UK Allergy clinics. Separately, we prospectively recruited children undergoing "low-risk" OFCs for suspected IgE-mediated food allergy from 2 large specialist allergy units in London. LDC was performed 30 minutes before the OFC, by applying the food to the inner lip for 30 seconds. Objective symptoms were considered a positive outcome. All patients subsequently proceeded to OFC regardless of LDC outcome, and outcome assessed according to PRACTALL consensus. RESULTS: We received 147 responses to the online survey, representing 67% of registered pediatric allergy clinics in the United Kingdom. Eighty percent of respondents (representing 81% of responding centers) included LDC as the first step of OFC in routine clinical practice. There was a wide variation in both how LDCs were performed and interpreted, with one-third not proceeding to OFC if LDC resulted in subjective symptoms. In the prospective study, 198 children (mean age, 7 years) with conclusive OFCs were included. Foods tested were tree nuts (30%), peanut (16.6%), egg (16%), fish (10.5%), milk (6%), shrimp (4%), and other (16.9%). There were 12 positive LDCs (1 of which triggered systemic symptoms: generalized urticaria) and 31 positive OFCs. Two children with positive LDCs went on to have a negative diagnostic OFC. Sensitivity of LDC was 32%, specificity 98%, with a false-negative rate of 68%. CONCLUSIONS: Most UK allergy clinics included LDC as an initial step during OFC, despite a wide variation in how LDCs are performed and interpreted, which raises major concerns about the reproducibility and the validity of the test. We found that LDC had poor sensitivity as an alternative or initial step to formal OFC.

Pollen food syndrome amongst children with seasonal allergic rhinitis attending allergy clinic.

BACKGROUND: There is limited information regarding the onset and sensitization patterns of pollen food syndrome (PFS) in children. The aim was to explore this within children referred to a specialist allergy clinic at a London Tertiary Hospital. METHODS: A total of 54 patients with seasonal allergic rhinitis (SAR) were enrolled in equal numbers in three age groups; 0-5, 6-10, 11-15 years. Families completed a questionnaire on rhinitis, food symptoms and quality of life. Children underwent skin prick testing (SPT) to fresh fruits, nuts and a blood test for microarray analysis. RESULTS: Clinical diagnosis of PFS was made in 26/54 (48%), increasing with age (group 1 = 3 (17%), group 2 = 9 (50%), group 3 = 14 (78%) (p = 0.03)). Microarray demonstrates children aged 2.8 years sensitized to pan-allergens and 4.5 years symptomatic to pan-allergens. Peach, cherry, carrot and strawberry SPT had the highest sensitivity and NPV at 100%. The sensitivity of PR10 molecules on microarray was 92%, PPV 62% and NPV 87%. Microarray confirmed 69% of allergens on clinical history compared to 61% by SPT. Microarray and SPT had a 19% false-negative rate. The quality-of-life data showed moderate impact across all domains, and patients with PFS were significantly more likely to have increased anxiety over time spent preparing food (p = 0.029). CONCLUSIONS: We demonstrate that SAR occurs in children from 1.4 years and PFS from 4.5 years with a changing pattern of pan-allergen sensitization. Microarray and SPT have moderate concordance in confirming allergens. PFS impacts negatively on quality of life and should be assessed in all paediatric allergy patients.

Stinging insect allergy: current perspectives on venom immunotherapy.

Systemic allergic reactions to insect stings affect up to 5% of the population during their lifetime, and up to 32% of beekeepers. Such reactions can be fatal, albeit very rarely, and fear of a further systemic reaction (SR) can lead to significant anxiety and quality of life impairment. A recent Cochrane systematic review confirmed that venom immunotherapy (VIT) is an effective treatment for people who have had a systemic allergic reaction to an insect sting. VIT reduces risk of a further SR (relative risk 0.10, 95% confidence interval 0.03-0.28), but VIT also reduces risk of a future large local reaction, and significantly improves disease-specific quality of life. However, health economic analysis showed that VIT is generally not cost effective for preventing future SRs; most people are stung infrequently, most SRs resolve without long-term consequences, and a fatal outcome is extremely rare. VIT only becomes cost effective if one is stung frequently (eg, beekeepers) or if quality of life improvement is considered. Thus, for most people with insect sting allergy, anxiety and quality of life impairment should be the overriding consideration when making treatment decisions, highlighting the importance of a patient-centered approach. Areas which need to be explored in future research include efforts to improve the safety and convenience of VIT such as the use of sublingual immunotherapy; quality of life effects of venom allergy in children and adolescents as well as their parents; and the optimal duration of treatment.

Clinical presentation and referral characteristics of food protein-induced enterocolitis syndrome in the United Kingdom.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a pediatric non-IgE-mediated allergic reaction to foods. The diagnosis of FPIES is clinical, with children presenting typically 2 to 4 hours after ingestion of a food protein. The most striking symptoms are vomiting, lethargy, and pallor. Misdiagnosis and delay in presentation to an allergist or gastroenterologist are common. OBJECTIVES: To investigate the pathway of patients with FPIES presenting to a specialist clinic in the United Kingdom to ascertain whether they experienced delays or misdiagnoses and to investigate their symptoms and triggers. METHODS: All patients with FPIES presenting over a 3-year period (2010-2013) in a tertiary pediatric allergy clinic in London were analyzed retrospectively. This was performed by searching electronically for all patients with a diagnosis of FPIES and manually reviewing paper notes. Presenting symptoms and management pathways were collated. RESULTS: Fifty-four patients were identified, with an average age of onset at 8 months. They initially presented to medical professionals other than an allergist or gastroenterologist. The most frequent presenting symptom was vomiting followed by signs suggesting shock or hypotension and diarrhea. Differential diagnoses included gastroenteritis, sepsis, and surgical abnormalities. The main eliciting foods were cow's milk, fish, egg, soy, and wheat. CONCLUSION: In the United Kingdom, FPIES typically has its onset at 8 months. Patients experience a delay of 12 months in the diagnosis of FPIES and frequently have multiple episodes and interim diagnoses. A great need remains for enhanced education of medical practitioners dealing with children about the varied presentations of FPIES.

Predicting positive food challenges in children sensitised to peanuts/tree nuts.

BACKGROUND: Children with atopic diseases in early life are frequently found with positive IgE tests to peanuts/tree nuts without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at first introduction. METHODS: A retrospective case-note and database analysis was performed. Recruitment criteria were: patients aged 3-16 yr who had a standardized food challenge to peanut and/or tree nuts due to sensitisation to the peanut/tree nut (positive spIgE or SPT) without previous consumption. A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis. RESULTS: There were 98 food challenges (47 peanut, 51 tree nut) with 29 positive, 67 negative and 2 inconclusive outcomes. A positive maternal history of allergy and a specific IgE >5 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.73; 95% CI 1.31-10.59; p = 0.013 and OR 3.35; 95% CI 1.23-9.11; p = 0.007, respectively). Adjusting for age, a three year-old with these criteria has a 67% probability of a positive challenge. There was no significant association between types of peanut/tree nut, other food allergies, atopic conditions or severity of previous food reactions and positive challenges. CONCLUSIONS: We have demonstrated an association between the presence of maternal atopic history and a specific IgE >5 kU/l, with a significant increase in the likelihood of a positive food challenge. Although requiring further prospective validation these easily identifiable components should be considered when deciding the need for a challenge.