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Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.

Predicting reaction threshold and severity are important to improve the management of food allergy, however the determinants of, and relationship between, these parameters are significant knowledge gaps. Identifying robust predictors could enable the reliable risk-stratification of food-allergic individuals. In this series of young people with CM-allergy undergoing DBPCFC – the largest reported in the literature – we did identify any baseline marker which predicted the occurrence of anaphylaxis at challenge, consistent with existing data. 1 There is one report of IgE-sensitisation being predictive of severity in CM-allergy, 5 however the authors included non-reactive patients in their analysis which significantly skewed the analyses, resulting in misleading conclusions. 6 IgE-sensitisation in our cohort, particularly to casein, was predictive of LOAEL. Including an assessment of casein IgE may therefore be of clinical utility when evaluating patients with CM-allergy in the clinical setting.

Background: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. EDs can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow’s milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5mg to 13.9mg cow’s milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow’s milk of 0.5mg protein. Methods: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5mg cow’s milk protein (approximately 0.015ml of fresh cow’s milk). Children over 1 year underwent formal challenge to cow’s milk to confirm clinical reactivity. Results: 172 children (median age 6 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis which responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitisation which were associated with objective reactivity to the single-dose challenge using 0.5mg cow’s milk protein. Conclusions: These data support an estimated ED05 for cow’s milk of 0.5mg protein. Values for ED05 above 0.5mg for cow’s milk protein proposed for allergen risk management need to be reviewed.

Olfactory and gustatory dysfunctions (OGD) have been reported as relevant symptoms that may predict presence of coronavirus disease 2019 (COVID-19) in adults, associated with mild or moderate disease1, 2, 3. However, published data on OGD in children are scant, likely due to several factors specific to the pediatric population such as a lower incidence of infection, the tendency of COVID-19 to be asymptomatic4, 5, and the difficulty of studying childhood OGD with objective methods. Two case reports have been published to date: one with 3 adolescents6, and the other describing a 17-year-old girl with beta-thalassemia who presented total loss of smell and taste for 8 days7 . Current data on the prevalence of OGD are based on only 2 small cohorts of COVID-19–positive children8, 9. In a related study, Mannheim et al.10 describe that 19 (30%) of 64 infected children (0–17 years old) presented nasal congestion, rhinorrhea, and total loss of smell, though providing no data on the exact number of patients with olfactory dysfunction exclusively.

A document by Emilio Nuñez-Borque. Click on the document to view its contents.