Allergen immunotherapy (AIT) is a well recognized and extensively studied therapeutic intervention for some allergic diseases. Every year new systematic reviews and meta-analysis provide the most powerful source of evidence to orient decision making on prevention or efficacy of AIT. We here discuss systematic reviews and meta-analyses on AIT (published January 2017 to February 2018).

We identified 4 systematic reviews and 10 meta-analyses. Subcutaneous and sublingual AIT (SCIT/SLIT) significantly reduced the development of asthma in children-adolescents with moderate/severe allergic rhinitis, but evidence for a short-term, preventive effect for new allergic sensitizations was non conclusive. SCIT/SLIT proved to significantly improve symptom and medication scores versus placebo or active comparators in respiratory allergy, with various effect sizes. Oral immunotherapy for IgE-mediated food allergy resulted in substantial benefit in desensitization rates. Data on venom AIT and latex AIT, although limited in quantity and quality, respectively, suggest a large and discrete beneficial effect.

Although current evidence extracted from meta-analyses and systematic reviews support AIT as an effective, relatively safe, and well tolerated alternative for some allergic diseases, heterogeneity and some methodological inconsistencies represent matters of concern as they may affect the validity and applicability of their results, especially in the context of individual, real-life settings.

A significant proportion of rhinitis patients without systemic IgE-sensitisation tested by skin prick test and serum allergen-specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate-to-severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR. Allergic rhinitis and LAR share many clinical features including a positive NAPT response, markers of type 2 nasal inflammation including sIgE in nasal secretions and a significant rate of asthma development. LAR should be considered as a differential diagnosis in those subjects of any age with symptoms suggestive of AR but no evidence of systemic atopy. Although LAR pathophysiology is partially unknown, in some patients sIgE can be demonstrated directly in the nasal secretions and/or indirectly via positive responses in basophil activation test (BAT). LAR can coexist with other rhinitis phenotypes, especially AR. The diagnosis currently relies on the positivity of NAPT to a single or multiple allergens. NAPT has high sensitivity, specificity and reproducibility, and it is considered the gold standard. BAT and the measurement of nasal sIgE can also contribute to LAR diagnosis. LAR patients benefit from the same therapeutic strategies than AR individuals, including the avoidance of allergen exposure and the pharmacotherapy. Moreover, several recent studies support the effectiveness and safety of allergen immunotherapy for LAR, which opens a window of treatment opportunity in these patients

Observations suggesting that aeroallergens trigger eosinophilic esophagitis (EoE) in a subset of patients raise questions about the implications this finding has on the evaluation and management of patients with EoE, including a potential role for allergen immunotherapy.

The majority of studies evaluating the potential role of aeroallergens as provocateurs of EoE have addressed this issue by assessing the seasonal variation in EoE diagnosis and/or symptom onset or worsening, with mixed results. For various reasons, reaching accurate conclusions based on this methodology is potentially fraught with error. In addition, studies examining the even harder to assess role of perennial aeroallergens in triggering EoE are lacking. Although clearly not the majority, there may be a subset of patients with EoE and allergic rhinitis in whom exposure to aeroallergens to which they are sensitized contributes to esophageal eosinophilia either through direct chronic esophageal mucosal contact with pollen allergens or from repetitive exposure of the esophageal mucosa to pollen allergens, mediators, and eosinophils in swallowed nasal secretions. Therefore, evaluation for and optimal treatment of comorbid allergic rhinitis in EoE patients are clearly indicated. Recognition of the potential role of aeroallergens as triggers of EoE also raises the question of whether allergen immunotherapy might be an effective form of EoE treatment. Reports of sublingual immunotherapy (SLIT) inducing EoE support the notion that aeroallergens can trigger EoE, but negate this approach as a potential form of EoE therapy. In fact, the use of SLIT is contraindicated in patients with EoE. The literature regarding the role of subcutaneous immunotherapy (SCIT) in patients with EoE is limited. Current evidence indicates that it should not be typically recommended; however, SCIT might benefit a subset of patients with EoE and uncontrolled allergic rhinitis on conventional therapies in whom SCIT would otherwise be indicated for allergic rhinoconjunctivitis, particularly in those with sensitizations to pollens containing allergens that cross react with food allergens. The purpose of this review is to discuss the current literature examining the role of aeroallergens in triggering EoE with a focus on the potential clinical implications of this finding on managing patients with EoE.

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health-care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health-care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long-term control medication, and improved forced expiratory volume in 1 second (FEV1 ) (moderate SOE). SLIT may decrease quick-relief medication use, and improve disease-specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from -0.03 to +0.765) and systemic allergic reactions (risk differences ranged from -0.03 to +0.06) were a common occurrence in SLIT and control groups. Life-threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported.

There is moderate-to-high strength evidence that SLIT improves allergic asthma symptoms, reduces long-term control medication use, and improves FEV1 based on studies of HDM, birch, and grass. SLIT rarely is associated with life-threatening adverse events.

Successful AIT induces establishment of long-term clinical tolerance against allergens resulting in reduction of symptoms and decrease in the need for pharmacotherapy, ultimately improving quality of life for patients suffering from IgE-mediated diseases. In recent years, improved insight into the mechanisms of AIT has allowed a better understanding of the complexity of allergen-specific immune responses. Immune tolerance induced in successful AIT implies several cellular and molecular events responsible for inhibition of both early- and late-phase responses to allergen challenge. Although the diseasemodifying effect of AIT and its high efficacy have revolutionized the treatment of allergic diseases, some patients do not respond to the treatment. Therefore, there is a need for development of laboratory tests and biomarkers to assess the effects of AIT on development of immune tolerance to allergens, to allow early identification of responder patients. Many efforts have been undertaken in order to identify biomarkers with a potential to predict and monitor the clinical outcome for more effective AIT. In this review, we explore and discuss the most recent findings on the diverse mechanisms of immunotherapy and potential biomarkers for monitoring clinical and immunological response to AIT, focusing on various forms of AIT together.

The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy.

AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life. Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.

The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up.

Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature.

A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.

The development and widespread use of vaccines, which are defined by the World Health Organization as "biological preparations that improve immunity to a particular disease," represents one of the most significant strides in medicine. Vaccination was first applied to reduce mortality and morbidity from infectious diseases. The World Health Organization estimates that vaccines prevent 2 to 3 million human deaths annually, and these numbers would increase by at least 6 million if all children received the recommended vaccination schedule. However, the origins of allergen immunotherapy share the same intellectual paradigm, and subsequent innovations in vaccine technology have been applied beyond the prevention of infection, including in the treatment of cancer and allergic diseases. This review will focus on how new and more rational approaches to vaccine development use novel biotechnology, target new mechanisms, and shape the immune system response, with an emphasis on discoveries that have direct translational relevance to the treatment of allergic diseases.

Anaphylaxis is a severe and potentially life-threatening allergic reaction. There are numerous potential causes, with food allergy being the leading cause in children and the focus of this review. Most reactions involve an IgE-mediated mechanism, although non-IgE-mediated and nonimmunologic reactions can occur. Various cofactors to be discussed can place certain individuals at an increased risk of severe or fatal anaphylaxis. The clinical manifestations of anaphylaxis are broad and may involve multiple body systems. Diagnosis of food-related anaphylaxis is primarily based on signs and symptoms and supported, wherever possible, by identification and confirmation of a culprit food allergen. First-line treatment of anaphylaxis is intramuscular administration of epinephrine. Long-term management is generally focused on strict allergen avoidance and more recently on food desensitization using immunotherapy. This review provides an overview of anaphylaxis with a specific focus on food allergy.

Tree nut allergy is a potentially life-threatening disease that is increasing in prevalence, now affecting 1% of the general population in the United States. While other food allergies often resolve spontaneously, tree nut allergies are outgrown in less than 10% of cases. Due to the likelihood of cross-sensitization to multiple tree nut allergens, the current treatment guideline is strict avoidance of all nuts once one tree nut allergy has been diagnosed. For example, walnut and pecan are highly cross-reactive, along with cashew and pistachio, but the extent of clinical, IgE-mediated cross-reactivity among other tree nuts remains unclear, therefore making avoidance of all tree nuts a safe approach. There have been recent advances in immunotherapy for food allergies. For instance, there are investigational immunotherapies for milk, egg and peanut allergies, specifically oral immunotherapy, sublingual immunotherapy and epicutaneous immunotherapy. However, there are no large randomized controlled clinical trials for tree nut allergies. Even though there has been less research into tree nut allergy immunotherapies, the evidence of T-cell cross-reactivity among tree nuts exists in animal models and in T cells from allergic patients indicates that immunotherapeutic interventions may be possible. Here, we review the literature regarding epidemiology, allergen homology and cross-reactivity among tree nuts, and explore how current findings can be employed for effective therapy.