Stefania Arasi

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE‐mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT in the management of food allergy.

EAACI Guidelines on Allergen Immunotherapy: Allergic Rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side‐effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease‐modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project “EAACI Guidelines on Allergen Immunotherapy.” It aims to provide evidence‐based clinical recommendations and has been informed by a formal systematic review and meta‐analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product‐specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short‐term benefit. The strongest evidence for long‐term benefit is documented for grass AIT (especially for the grass tablets) where long‐term benefit is seen. To achieve long‐term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long‐term benefit and use in children.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta‐analysis

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.

EAACI Guidelines on Allergen Immunotherapy: Hymenoptera venom allergy

Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Treatment with omalizumab in a 16‐year‐old Caucasian girl with refractory solar urticaria

Based on recent evidence, including our results, we believe that the usefulness of the sIgE/total IgE ratio to predict tolerance to food allergens needs to be revisited in larger studies which can control for factors potentially influencing the results. In conclusion, in this cohort, the diagnostic performance of the OVA-sIgE/total IgE ratio was superior to sIgE or SPT to EW, OVA or OVM alone in predicting raw egg tolerance development in school-aged children and teenagers with IgE-mediated egg allergy. Acknowledgments The authors would like to thank Dr Paul Turner, MRC Clinician Scientist at Imperial College London, for his valuable comments on this letter.

Is it possible to make a diagnosis of raw, heated, and baked egg allergy in children using cutoffs? A systematic review

The diagnosis of IgE‐mediated egg allergy lies both on a compatible clinical history and on the results of skin prick tests (SPTs) and IgEs levels. Both tests have good sensitivity but low specificity. For this reason, oral food challenge (OFC) is the ultimate gold standard for the diagnosis. The aim of this study was to systematically review the literature in order to identify, analyze, and synthesize the predictive value of SPT and specific IgEs both to egg white and to main egg allergens and to review the cutoffs suggested in the literature. A total of 37 articles were included in this systematic review. Studies were grouped according to the degree of cooking of the egg used for OFC, age, and type of allergen used to perform the allergy workup. In children <2 years, raw egg allergy seems very likely when SPTs with egg white extract are ≥4 mm or specific IgEs are ≥1.7 kUA/l. In children ≥2 years, OFC could be avoided when SPTs with egg white extract are ≥10 mm or prick by prick with egg white is ≥14 mm or specific IgE is ≥7.3 kUA/l. Likewise, heated egg allergy can be diagnosed if SPTs with egg white extract are >5 and >11 mm in children <2 and ≥2 years, respectively. Further and better‐designed studies are needed to determine the remaining diagnostic cutoff of specific IgE and SPT for heated and baked egg allergy.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cows milk, hens egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.

The evolution of allergen and non-specific immunotherapy: past achievements, current applications and future outlook

Recent epidemiological studies estimated that more than 30% of European suffer from allergic rhinitis or conjunctivitis, while up to 20% suffer from asthma and 15% from allergic skin conditions, while for many other regions the prevalence is increasing. Allergen immunotherapy represents the only available treatment that can modify the allergic disease process, and thus is worth considering as a treatment in affected individuals. A beneficial effect of allergen immunotherapy has been shown in both adults and children affected by allergic rhinitis, allergic conjunctivitis, allergic asthma and hymenoptera venom allergy. The present study represents an overview on allergen immunotherapy, focusing on the principal aspects of the use of immunotherapy in the past, its recent clinical applications and future outlook.

EAACI guidelines on allergen immunotherapy: Prevention of allergy

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.

Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report

Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3–5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers’ preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.