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Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30 September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE‐mediated food allergy. Methods: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1 October 2012 to 30 June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS‐2 tool. All evaluations will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta‐analysis will be performed if there are three or more studies of the same index test and food. Results: A protocol for the systematic review and meta‐analyses is presented and was registered using Prospero prior to commencing the literature search. Discussion: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings. [ABSTRACT FROM AUTHOR]

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0–18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for pediatric urticaria are implemented. Methods: The EAACI Task Force for pediatric CU disseminated an online clinical survey among EAACI pediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centers. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly pediatric allergists (80%) and pediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (eg, autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd‐generation antihistamine as first‐line treatment of whom 64.8% updosed as a second line. Omalizumab was used as a second‐line treatment by 1.7% and third line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Pediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re‐evaluate, update, and standardize guidelines on the diagnosis and management of CU in children. [ABSTRACT FROM AUTHOR]

IgE‐mediated food allergy (FA) is a potentially life‐threatening condition with a negative impact on quality of life and an increasing prevalence in westernized countries in the recent two decades. A strict avoidance of the triggering food(s) represents the current standard approach. However, an elimination diet may be difficult and frustrating, in particular for common foods, (eg, milk, egg, and peanut). Food allergy immunotherapy (FA‐AIT) may provide an active treatment that enables to increase the amount of food that the patient can intake without reaction during treatment (ie, desensitization), and reduces the risk of potential life‐threatening allergic reaction in the event of accidental ingestion. However, several gaps need still to be filled. A memorable Latin orator stated: "Est modus in rebus" (Horace, Sermones I, 1, 106‐07). This sentence remembers that there is a measure in everything to a proper proportion of therapy. The common sense of measure should find application in each stage of treatment. A personalized approaching should consider the specific willing and features of each patient. Efforts are devoted to improve the efficacy, the safety but also the quality of life of patients suffering from FA. In the near future, it will be important to clarify immunologic pathways of FA‐AIT, and to identify reliable biomarkers in order to recognize the most suitable candidates to FA‐AIT and algorithms for treatments tailored on well‐characterized subpopulations of patients. [ABSTRACT FROM AUTHOR]

In the era of precision medicine, allergen immunotherapy (AIT) represents a landmark for the management of IgE‐mediated allergic diseases. AIT is recognized as a potentially curative therapy and is currently accepted and routinely prescribed worldwide. However, there are still unmet needs. The efforts of researchers are aimed at implementing current immunotherapeutic strategies to improve the standard care of patients suffering from IgE‐mediated respiratory allergic diseases. In addition, over the horizon, the most realistic option is the active treatment of IgE‐mediated food allergy with oral immunotherapy. Preclinical studies and clinical trials are increasingly conducted to identify innovative forms of AIT administration, potential biomarkers, alternative immunotherapeutic allergen candidates, and new adjuvants. Telemedicine could represent a further emerging field capable of supporting health service delivery and improving clinical outcomes of AIT. [ABSTRACT FROM AUTHOR]

IgE‐mediated food allergy (FA) has been emerging as a public health priority, mainly in children. It represents a heavy burden for the entire society and not only for the patients and their families. There is evidence that in children with persistent FA, at least to cow's milk, hen's egg, and peanut, oral immunotherapy (OIT) may increase the reaction threshold to food allergen(s), while receiving active therapy (the so‐called "desensitization"). Furthermore, OIT protects patients from the occurrence of severe reactions in the event of accidental ingestion of the culprit food during treatment. However, many gaps are still unsolved, including safety issues, identification of predictive biomarkers, and post‐desensitization efficacy. This article briefly summarizes the current evidence and the main needs in OIT to stimulate the development of longitudinal, prospective, well‐designed studies able to fill the current gaps soon. [ABSTRACT FROM AUTHOR]

Abstract: The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology—later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist. [ABSTRACT FROM AUTHOR]

Allergic diseases are common and frequently coexist. Allergen immunotherapy ( AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology ( EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation ( AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis ( AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post- AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post- AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials. [ABSTRACT FROM AUTHOR]

Background There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy ( AIT) for the prevention of allergic disease. Methods Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses. Results A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term ( RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma ( RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile. Conclusions AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT. [ABSTRACT FROM AUTHOR]

The so-called local allergic rhinitis ( LAR) has been proposed as a phenotype of rhinitis with Th2-driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of 'systemic' atopy (negative skin prick test and serum allergen-specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this 'Rostrum' was to critically discuss data and implications of the ' LAR concept' in paediatrics. In the natural history of rhinitis due to IgE-mediated reactions triggered by exposure to allergens, a ' LAR' can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to 'systemic' IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term 'local allergic rhinitis' may be inappropriate, as rhinitis is always 'local', while IgE sensitization can be either 'local' or 'systemic'. [ABSTRACT FROM AUTHOR]

Background The European Academy of Allergy and Clinical Immunology ( EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy ( AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease. Methods We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized. Discussion The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT. [ABSTRACT FROM AUTHOR]

Background Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective. Methods Children who were successfully desensitized with oral immunotherapy were randomized to two maintenance regimens for 1 year: group A had to eat 150-200 ml milk daily, group B had to eat 150-200 ml milk twice weekly. Both regimens were associated to a totally free diet. Maintenance of tolerance and adverse events were recorded during 1 year. Specific IgE, IgG4 and prick-by-prick test to milk were carried out before immunotherapy (T0), before maintenance (T1), and after 1 year (T2). Results Recorded episodes included asthma, oral itching, urticaria, rhinitis, abdominal pain variously combined, usually associated with concomitant illness or exercise. The episodes were 8 in group A and 9 in group B, with no difference. None of the children discontinued the feeding maintenance. Specific IgG4 increased at T1 and remained high at T2. Specific IgE and skin reactivity significantly decreased at T2. There was no difference in those parameters between the groups. Conclusion After achieving desensitization to cow milk with oral immunotherapy, a maintenance regimen with milk given twice weekly is as effective as the daily maintenance. [ABSTRACT FROM AUTHOR]

To cite this article: Calderon MA, Gerth van Wijk R, Eichler I, Matricardi PM, Varga EM, Kopp MV, Eng P, Niggemann B, Nieto A, Valovirta E, Eigenmann PA, Pajno G, Bufe A, Halken S, Beyer K, Wahn U. Perspectives on allergen-specific immunotherapy in childhood: An EAACI position statement. Pediatr Allergy Immunol 2012: 23: 300-306. Abstract This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen-specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential. The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation. [ABSTRACT FROM AUTHOR]

To cite this article: Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, Passalacqua G. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: A randomized controlled study. Pediatr Allergy Immunol 2011: 22: 803-807. Abstract Background: Pre-seasonal, pre-coseasonal and continuous regimens of immunotherapy have been proposed, but their efficacy was never compared. This phase IV open study was designed to compare the clinical efficacy of a continuous and a coseasonal sublingual immunotherapy (SLIT) for grass allergy over 3 years. Methods: Children with rhinitis/asthma because of grass were randomized to SLIT given continuously (all year long) or coseasonally. The treatment started in October 2005 in the continuous SLIT group and in March 2006 in the coseasonal group Diary cards for clinical symptoms (from 0 = none to 3 = severe), and drug intake were recorded form March to June in 2005 (baseline), 2006 2007, and 2008. Specific IgE and IgG4 were evaluated every year. Results: Eighty children (age range 8-16) were randomized and 72 completed the study. In the first year, the symptom + medication score improved by 44% in the continuous group and by 20% in the coseasonal group (p = 0.04). Symptoms, chest symptoms, and drug intake separately showed a greater decrease vs. baseline in the continuous group. In the second year, the global score decreased in both groups with no significant difference, whereas symptom score decreased more in the continuous group. In the 3rd year, there was no difference in clinical parameters between the two groups. Specific IgG4 were significantly higher vs. baseline since the 1st year in the continuous group and since the 2nd in the coseasonal group. Conclusion: In grass pollen allergy, the continuous regimen performs better than the coseasonal in the first season, whereas in the subsequent years, the two regimens are nearly equivalent. [ABSTRACT FROM AUTHOR]

In Italy, according to the International Study on Asthma and Allergies in Childhood study, the prevalence of current asthma, allergic rhinoconjunctivitis, and atopic eczema in 2006 was 7.9%, 6.5%, and 10.1% among children aged 6-7 and 8.4%, 15.5%, and 7.75% among children aged 13-14 yr. University education in this field is provided by the Postgraduate Schools of Pediatrics and those of Allergology and Clinical Immunology, as well as several annual Master courses. The Italian Society of Pediatric Allergology and Immunology (SIAIP) was founded in 1996 and counts about 1000 members. SIAIP promotes evidence-based management of allergic children and disseminates information to patients and their families through a quite innovative website and the National Journal 'Rivista Italiana di Allergologia Pediatrica'. In the last decade, four major regional, inter-regional, and national web-based networks have been created to link pediatric allergy centers and to share their clinical protocols and epidemiologic data. In addition, National Registers of Primary Immune-deficiencies and on Pediatric HIV link all clinical excellence centers. Research projects in the field of pediatric allergy and immunology are founded by the Italian Ministry of Education, University and Research (MIUR) and by the National Research Council (CNR), but the overall investments in this research area are quite low. Only a handful Italian excellence centers participate in European Projects on Pediatric Allergy and Immunology within the 7th Framework Program. The European Academy of Allergy and Clinical Immunology currently hosts two Italians in its Executive Committee (EC) and one in the EC of the Pediatric Section; moreover, major European Academy of Allergy and Clinical Immunology meetings and courses in the area of pediatrics (e.g., PAAM, Venice, 2009) have been held in Italy in the last 3 yr. Italian hallmarks in the management of allergic diseases in childhood are a quite alive and spread interest in Molecular Allergology and a remarkable predominance of sublingual (SLIT) compared to the subcutaneous (SCIT) immunotherapy. [ABSTRACT FROM AUTHOR]

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM. [ABSTRACT FROM AUTHOR]

Caminiti L, Passalacqua G, Magazzù G, Comisi F, Vita D, Barberio G, Sferlazzas C, Pajno GB. Chronic urticaria and associated coeliac disease in children: A case–control study. Pediatr Allergy Immunol 2005: 16: 428–432. © 2005 Blackwell Munksgaard Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case–control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5–10 wk, whereas the disappearance of serological markers occurred in longer times (5–9 months). Conclusions. The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU. [ABSTRACT FROM AUTHOR]

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy-one AD children (age range 14–158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD– group), while in 33 AD persisted (AD+ group). At enrollment, AD+ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD+ children developed more respiratory symptoms in comparison to AD– children (p < 0.001). None of the AD– children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of omalizumab for treatment of refractory solar urticaria (SU) in a 16-year-old Caucasian girl.

A letter to the editor is presented concerning the adherence of preschool children to sublingual immunotherapy.