Methods We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test — one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. Results Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P = 0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. Conclusions The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.)

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Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since our last comprehensive review. Although firm prevalence data are lacking, there is a strong impression that food allergy has increased, and rates as high as approximately 10% have been documented. Genetic, epigenetic, and environmental risk factors are being elucidated increasingly, creating potential for improved prevention and treatment strategies targeted to those at risk. Insights on pathophysiology reveal a complex interplay of the epithelial barrier, mucosal and systemic immune response, route of exposure, and microbiome among other influences resulting in allergy or tolerance. The diagnosis of food allergy is largely reliant on medical history, tests for sensitization, and oral food challenges, but emerging use of component-resolved diagnostics is improving diagnostic accuracy. Additional novel diagnostics, such as basophil activation tests, determination of epitope binding, DNA methylation signatures, and bioinformatics approaches, will further change the landscape. A number of prevention strategies are under investigation, but early introduction of peanut has been advised as a public health measure based on existing data. Management remains largely based on allergen avoidance, but a panoply of promising treatment strategies are in phase 2 and 3 studies, providing immense hope that better treatment will be imminently and widely available, whereas numerous additional promising treatments are in the preclinical and clinical pipeline.

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Food Allergy: A practice parameter update—2014." This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion.

/pdf/food-allergy-a-practice-parameter-update-2014-1rcvmuxqro.pdf

Food allergy: a practice parameter update-2014.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)60690-0.pdf

Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial

Hugh A. Sampson, MD, Roy Gerth van Wijk, MD, Carsten Bindslev-Jensen, MD, PhD, Scott Sicherer, MD, Suzanne S. Teuber, MD, A. Wesley Burks, MD, Anthony E. J. Dubois, MD, Kirsten Beyer, MD, Philippe A. Eigenmann, MD, Jonathan M. Spergel, MD, PhD, Thomas Werfel, MD, and Vernon M. Chinchilli, PhD New York, NY, Rotterdam and Groningen, The Netherlands, Odense, Denmark, Davis, Calif, Chapel Hill, NC, Berlin and Hannover, Germany, Geneva, Switzerland, and Philadelphia and Hershey, Pa

/pdf/standardizing-double-blind-placebo-controlled-oral-food-1nl1skf4io.pdf

Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report

Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial

Background: Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention.



Aims of the study:  The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein.



Methods:  Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment.



Results:  Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5–50 mg (1/40–1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects.



Conclusions:  We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion.

Successful oral tolerance induction in severe peanut allergy

Background Most children with detectable peanut-specific IgE (P-sIgE) are not allergic to peanut. We addressed 2 non–mutually exclusive hypotheses for the discrepancy between allergy and sensitization: (1) differences in P-sIgE levels between children with peanut allergy (PA) and peanut-sensitized but tolerant (PS) children and (2) the presence of an IgE inhibitor, such as peanut-specific IgG 4 (P-sIgG 4 ), in PS patients. Methods Two hundred twenty-eight children (108 patients with PA, 77 PS patients, and 43 nonsensitized nonallergic subjects) were studied. Levels of specific IgE and IgG 4 to peanut and its components were determined. IgE-stripped basophils or a mast cell line were used in passive sensitization activation and inhibition assays. Plasma of PS subjects and patients submitted to peanut oral immunotherapy (POIT) were depleted of IgG 4 and retested in inhibition assays. Results Basophils and mast cells sensitized with plasma from patients with PA but not PS patients showed dose-dependent activation in response to peanut. Levels of sIgE to peanut and its components could only partially explain differences in clinical reactivity between patients with PA and PS patients. P-sIgG 4 levels ( P  = .023) and P-sIgG 4 /P-sIgE ( P 4 /Ara h 1–sIgE ( P  = .050), Ara h 2–sIgG 4 /Ara h 2–sIgE ( P  = .004), and Ara h 3–sIgG 4 /Ara h 3–sIgE ( P  = .016) ratios were greater in PS children compared with those in children with PA. Peanut-induced activation was inhibited in the presence of plasma from PS children with detectable P-sIgG 4 levels and POIT but not from nonsensitized nonallergic children. Depletion of IgG 4 from plasma of children with PS (and POIT) sensitized to Ara h 1 to Ara h 3 partially restored peanut-induced mast cell activation ( P  = .007). Conclusions Differences in sIgE levels and allergen specificity could not justify the clinical phenotype in all children with PA and PS children. Blocking IgG 4 antibodies provide an additional explanation for the absence of clinical reactivity in PS patients sensitized to major peanut allergens.

https://www.jacionline.org/article/S0091-6749(15)00102-5/pdf

IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens.

Summary
Background Peanut allergy is severe and rarely resolves.

Objective To test the efficacy and safety of a new oral immunotherapy (OIT) protocol for peanut allergy.

Method Twenty-two peanut-allergic children underwent oral challenge. OIT was administered by gradual updosing with 2-weekly increments (8–38 weeks) to 800 mg of protein (5 peanuts/day) followed by 30-week maintenance. Oral challenge was repeated after 6 and 30 weeks maintenance.

Results Twenty-two children (median 11 years) had positive challenges (threshold 1–110 mg). Nineteen of 22 (86%) tolerated updosing and maintenance at 800 mg protein/day. One of 22 dropped out; 2/22 tolerated updosing and maintenance at 200–400 mg protein. Reactions, mostly mild, occurred in 86% during immunotherapy, adrenaline was not required. Eight of 8 with pre-immunotherapy peanut IgE<27.3 kU/L required no dose adjustment compared with 5/13 with pre-immunotherapy peanut IgE27.3 kU/L. Twelve of 22 (54%) required a transient dose reduction because of reactions possibly related to extrinsic factors: tiredness, infection and exercise. After 6 weeks, 12/22 (54%) had no reaction to a 2.6 g protein challenge. After 30 weeks, 14/22 (64%) tolerated 6.6 g protein. The median tolerated peanut dose increased 1000-fold following immunotherapy, from 6 to 6459 mg of protein.

Conclusions and Clinical Relevance We used a novel protocol using gradual updosing, and higher maintenance dose resulting in a better outcome compared with rush protocols. There was a 1000-fold increase in the amount of peanut tolerated with a good safety profile. No serious adverse events occurred. Most subjects tolerated five peanuts and all were protected against amounts likely during accidental ingestion. New information is provided on ‘extrinsic factors’, updosing method and factors associated with success (trial registration http://ClinicalTrials.gov– ID number NCT01259804).

Cite this as: K. Anagnostou, A. Clark, Y. King, S. Islam, J. Deighton and P. Ewan, Clinical & Experimental Allergy, 2011 (41) 1273–1281.

Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cea.13874

Sabita Islam

Papers

Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial

Successful oral tolerance induction in severe peanut allergy

IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens.

Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome.

Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine.