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Food allergy (FA) is a potentially life‐threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE‐mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized‐controlled trials or quasi‐controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022. Population: Human adults, children, and adolescents with IgE‐mediated FA. Intervention: IT and/or biologics. Comparator: Placebo or standard‐of‐care (allergen avoidance). Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life‐threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long‐term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long‐term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions. [ABSTRACT FROM AUTHOR]

This article discusses the topic of food allergies, which are adverse reactions to certain foods that involve the immune system. Food allergies can be classified into IgE-mediated forms and non-IgE-mediated forms, and they have a significant impact on patients' quality of life and healthcare systems. The article addresses various unmet needs in the field of pediatric food allergies, including the dietary management of food allergies, psychological support for children and parents, disease prevention strategies, environmental factors, and diagnostic biomarkers. The authors emphasize the importance of further research to improve our understanding of food allergies and address the gaps in knowledge. [Extracted from the article]

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta‐analyses to assess the accuracy of diagnostic tests for IgE‐mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta‐analyses were undertaken for food‐test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double‐blind placebo‐controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2‐sIgE had 92%, Cor a 14‐sIgE 95%, Ana o 3‐sIgE 94%, casein‐sIgE 93%, ovomucoid‐sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies. [ABSTRACT FROM AUTHOR]

The article provides an executive summary of the EAACI guidelines on the diagnosis of IgE-mediated food allergy. The guidelines were developed by a multinational and multidisciplinary group of experts and aim to provide recommendations for best clinical practice in diagnosing food allergies. The article highlights the importance of accurate diagnosis, as misdiagnosis can lead to unnecessary food exclusions or potentially severe reactions. The guidelines include recommendations for the use of various diagnostic tests, such as skin prick testing, specific IgE testing, molecular IgE testing, and the basophil activation test. The article also identifies research priorities and challenges in implementing the guidelines in clinical practice. [Extracted from the article]

Multisystem inflammatory syndrome in children (MIS‐C) is a rare, but severe complication of coronavirus disease 2019 (COVID‐19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS‐C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS‐C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS‐C, diagnosis, treatment, follow‐up, and the role of COVID‐19 vaccinations. MIS‐C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS‐C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS‐C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short‐term outcome, MIS‐C patients should be followed‐up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID‐19 vaccination is a safe and effective measure to prevent MIS‐C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS‐C developed by the Immunology Section of the EAACI. [ABSTRACT FROM AUTHOR]

Background: Food allergen immunotherapy (FA‐AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA‐AIT. Methods: An EAACI task force conducted an online survey to gather relevant information regarding FA‐AIT practice and setting‐specific resources after reviewing the published literature and congress abstracts throughout Europe. Results: We identified 102 FA‐AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital‐based (77.5%), publicly funded (80.4%) and delivered FA‐AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA‐AIT for a median of 9 years [1–24] to a median of 105 [5–2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4–6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%‐63%), eosinophilic esophagitis (56%‐48%) and age below 5 years (47%‐41%). Conclusions: In Europe, FA‐AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer‐reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first‐line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis. [ABSTRACT FROM AUTHOR]

The absence of acute graft-versus-host disease and the low acute toxicity displayed by our patient after alpha/beta/CD19-depleted haplo-HSCT may suggest this approach as a valid therapeutic strategy. SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression. Keywords: interferon; leukoencephalopathy; primary immunodeficiency; SAMD9L; transplantation EN interferon leukoencephalopathy primary immunodeficiency SAMD9L transplantation 1 4 4 01/05/22 20220101 NES 220101 I To the Editor, i Interferonopathies are a growing group of rare monogenic autoinflammatory diseases characterized by overexpression of type I interferon-stimulated genes (ISG).1 Sterile alpha motif domain-containing protein 9 (SAMD9) and SAMD9-like protein (SAMD9L) are well-known ISG and cell proliferation antagonists whose mutations have been associated with various disorders (Table 1). Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy. [Extracted from the article]

Keywords: COVID-19; juvenile idiopathic arthritis; tocilizumab EN COVID-19 juvenile idiopathic arthritis tocilizumab 1 4 4 01/05/22 20220101 NES 220101 To the Editor, The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still raging and continues to have a serious impact on global health care and the economy across nations. Opoka-Winiarska et al.8 reported that eight JIA patients on immunosuppressive therapy with no history of infection had anti-SARS-CoV-2 antibodies, although 62 JIA patients did not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than 32 healthy children. This variant B.1.1.7 has shown an increased mortality rate of COVID-19 among elderly populations, but not younger individuals.10 The risk of B.1.1.7 in COVID-19 has not yet been identified among patients with RMDs. [Extracted from the article]

Keywords: allergy; BNT162b2; children; COVID-19; hypersensitivity; pediatric; vaccine EN allergy BNT162b2 children COVID-19 hypersensitivity pediatric vaccine 1 5 5 01/05/22 20220101 NES 220101 Abbreviations BAT basophil activation test COVID-19 coronavirus disease 2019 mRNA messenger ribonucleic acid ACKNOWLEDGEMENTS This work was supported by the research grant COVID19F02 from the Food and Health Bureau of the Government of Hong Kong. Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patients with PEG allergy. Allergy, BNT162b2, children, COVID-19, hypersensitivity, pediatric, vaccine. [Extracted from the article]

Keywords: C1 inhibitor deficiency; hereditary angioedema; intronic mutation; SERPING1 gene EN C1 inhibitor deficiency hereditary angioedema intronic mutation SERPING1 gene 1 4 4 01/05/22 20220101 NES 220101 Abbreviations ARMS PCR allele-specific polymerase chain reaction BK bradykinin C1 INH C1 inhibitor protein GAPDH glyceraldehyde-3-phosphate dehydrogenase HAE hereditary angioedema To the Editor, Hereditary angioedema (HAE) is a rare life-threatening disease that manifests clinically with episodes of swelling of the deeper layers of the skin or mucosa in different anatomical locations.1 HAE is mainly caused by mutations in the I SERPING1 i gene, which codes for the inhibitor of the first component of complement (C1 INH), leading to a quantitative decrease in C1 INH plasma levels (type I HAE, 85% of cases) or functional impairment of C1 INH with normal plasma levels (type II HAE, 15% of cases).2 C1 inhibitor is the main regulator of activated enzymes of the contact phase, controlling the production of bradykinin (BK). C1 inhibitor deficiency, hereditary angioedema, intronic mutation, SERPING1 gene A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations. Haploinsufficiency due to deletion within the 3'-UTR of C1-INH-gene associated with hereditary angioedema. [Extracted from the article]

Multicentric Castleman disease in a DOCK8-deficient patient with Orf virus infection Keywords: DOCK8 deficiency; epidermodysplasia verruciformis; idiopathic multicentric Castleman disease; lobular capillary hemangioma; orf virus infection EN DOCK8 deficiency epidermodysplasia verruciformis idiopathic multicentric Castleman disease lobular capillary hemangioma orf virus infection 1 5 5 01/05/22 20220101 NES 220101 To the Editor, Castleman disease (CD) is a rare lymphoproliferative disorder, which is mostly seen in adult HIV patients. Epidermodysplasia verruciformis, idiopathic multicentric Castleman disease, lobular capillary hemangioma, orf virus infection, DOCK8 deficiency We present a case of a DOCK8-deficient patient who had iMCD-NOS and orf virus-infected giant lobular capillary hemangiomas. [Extracted from the article]