Is immunotherapy with fungal vaccines effective? Purpose of review Although allergen immunotherapy (AIT) for fungi has been performed for many years, evidence clearly demonstrating its clinical benefit are still lacking. Here, we reviewed the available studies assessing efficacy and safety of AIT for molds. Recent findings Studies on AIT for fungi were performed only for the two predominating mold species in the external environment, namely Cladosporium and Alternaria. There is no evidence for other mold species. Recent finding in the literature are lacking; the 2 most recent studies on AIT for molds were published in 2011. Overall, 13 studies were identified (the first was published in 1986), but only nine of these compared AIT to placebo. The studies are small (median study sample size, 27 patients) and of low quality, owing to several defects leading to moderate-to-high risk of bias. Symptoms improvement and medication use reduction, which are the main outcome measures of the studies, were inconsistently demonstrated. There are some concerns about safety with Cladosporium extracts, whereas vaccines with Alternaria extracts seem to be safe and well tolerated. Summary Low strength evidence suggests that mold AIT is efficacious for the treatment of respiratory allergies. High-quality studies with an adequate sample size are needed. Correspondence to Danilo Di Bona, MD, PhD, School and Chair of Allergology and Clinical Immunology, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, Bari 70124, Italy. Tel/. Fax: +0039 080 5478167; e-mail: danilo.dibona@uniba.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

B-cell responses in allergen immunotherapy Purpose of review The establishment of long-term clinical tolerance in AIT requires the involvement of basophils, mast cells, allergen-specific regulatory T and B cells, downregulation of effector type 2 responses, and increase in production of specific IgG, particularly immunglobulin G4 (IgG4) antibodies. This review aims to provide an overview of the role of B cells in AIT, their mechanism of action, and their potential for improving AIT. Recent findings In-depth research of B cells has paved the way for improved diagnosis and research on allergic diseases. B cells play a central role in allergy and allergen tolerance through the production of immunglobulin E (IgE)-blocking antibodies. However, an increasing body of evidence has emerged supporting a role for B cells in regulating immune responses that extends beyond the production of antibodies. Regulatory B cells play an important role in immunosuppression, mediated by secretion of anti-inflammatory cytokines. Summary Successful AIT establishes the reinstatement of immune tolerance toward allergens, reduces allergic symptoms, and improves clinical treatments in patients. B cells play a central role in this process through antibody-independent immune regulatory processes in addition to the production of IgE-blocking antibodies. Correspondence to Mübeccel Akdis, MD, Ph.D., Swiss Institute of Allergy and Asthma Research (SIAF) Herman-Burchard-Strasse 9, CH- 7265 Davos, Switzerland. Tel: +41 81 4100848; fax: +41 81 4100840; e-mail: akdism@siaf.uzh.ch Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Immunoglobulin A and microbiota in primary immunodeficiency diseases Purpose of review With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients. Recent findings The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown. Summary Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency. Correspondence to Helen Louisa Leavis, MD, PhD, Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. Tel:+31 88 75 555 55; e-mail: h.leavis@umcutrecht.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

‘Googling’ anaphylaxis Purpose of review Anaphylaxis is a systemic allergic reaction and without the appropriate treatment can progress fast and may be fatal. Information about allergy and immunology topics including anaphylaxis can be easily found online and are widely searched by patients as well as medical personnel. Social media and search engines not only bring a number of benefits to users but also carry risks for breaches of confidentiality and privacy, unprofessional behaviour, malpractice and litigation. Social media use by medical healthcare workers has liability risks and can result in malpractice. Recent findings We used PubMed with the terms anaphylaxis; social network; mobile apps that revealed a very small number of publications addressing the use of these platforms and anaphylaxis. Google Trends and KWFinder were used to analyse the relative search interest and absolute search volumes on ‘anaphylaxis’. Summary Multiple sources exist on the Internet for health-related searches for both healthcare providers and patients. We analysed different websites, mobile apps, Facebook, YouTube and Twitter. To avoid any posting of patient identifiers, it is imperative to be aware of the 18 HIPAA identifiers. We list websites with accurate information about anaphylaxis for the use of both patients and healthcare professionals for purposes of patient education. Further research on health information-seeking behaviour is clearly needed. Correspondence to Ves Dimov, Department of Allergy and Immunology, Cleveland Clinic Florida, Weston, FL 33331, USA. E-mail: allergygoaway@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Anaphylaxis: advances and challenges besides allergy No abstract available

The multiple roles of mite allergens in allergic diseases Purpose of review Mites are the most worldwide spread allergens and relevant causative of respiratory allergies. Life cycle, component allergens, biological activity and immunogenicity are discussed in depth. Recent findings It is now known that mite allergens are able to stimulate the innate immune system through different receptors, for example, TLRs and PARs. The activation of the cells in the airway mucosa is followed by type 2 polarizing cytokine production in predisposed individuals. This complex network plays a pivotal role into the promotion of Th2 differentiation. Summary This is a comprehensive review regarding all the mite allergens known so far, including their location within dust mites, composition, biological activities and binding receptors relevant to the fate of the immunological response. Correspondence to Professor Paola Parronchi, Department of Experimental and Clinical Medicine, University of Firenze, Largo Brambilla 3, 50134 Firenze, Italy. Tel: +39 0557947421; e-mail: paola.parronchi@unifi.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Pathogenesis and complications of chronic eye rubbing in ocular allergy Purpose of review To review the updated literature regarding eye rubbing complications and its association with ocular allergy disorders. Recent findings Atopy and ocular allergy disorders, mainly vernal keratoconjunctivitis (VKC), are strongly associated with rubbing-related complications, most probably via itching and watery eye sensations that trigger the habit of chronic eye rubbing. Vigorous and prolonged rubbing may lead to establishment of corneal remodeling and ectatic disorders, such as keratoconus. Keratoconus development in rubbed eyes can be caused by mechanical mechanisms of corneal thinning and its loss of rigidity, by elevated temperature of the epithelium during rubbing, by increased intraocular pressure (IOP) because of distending forces, and by inflammatory molecules that may serve as a causal mediator between eye rubbing and keratoconus. Other eye rubbing complications include acute hydrops and perforation, IOP spikes, iris prolapse and iridoschisis rupture of lens capsule and IOL dislocation, and even posterior segment disorders, such as glaucomatous optic neuropathy, retinal detachment and extrusion of implanted silicone oil in the eye. Summary Chronic eye rubbing in allergic eye diseases can lead to progression of keratoconus, and to other rare anterior and posterior segment complications. Strategies eliminating eye rubbing and its consequences are vital, mainly among at-risk populations, such as young children and individuals with allergic ocular disorders or corneal transplants. Correspondence to Abraham Solomon, MD, Department of Ophthalmology, Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel. Tel: +972 50 7874664; e-mail: dr.avi.solomon@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The role of component-resolved diagnosis in Hymenoptera venom allergy Purpose of review Component-resolved diagnostics (CRD) is a new tool aiming at detecting IgE-mediated sensitizations against individual, relevant allergens. Here, we discuss recent literature on molecular diagnosis in the field of Hymenoptera venom allergy (HVA) as well as CRD strengths and weaknesses. Recent findings CRD, using single molecules or panels of allergens, may discriminate between primary sensitization and cross-reactivity in patients with double/multiple positivity in diagnostic tests with whole extracts, allowing the specialist to choose the most suitable venom for specific immunotherapy (VIT), avoiding unnecessary VIT and reducing the risk of side effects. Future availability of the cross-reactive recombinant pairs of allergens of different species may further increase the diagnostic performance. CRD may be useful in patients with negative allergy tests and a proven history of a previous systemic reaction, including those with mast cell disorders, who could benefit from VIT. In honeybee venom allergy, different sensitization profiles have been identified, which could be associated with a greater risk of VIT failure or treatment side effects. Summary CRD is undoubtedly an innovative diagnostic method that leads to a more precise definition of the sensitization profile of the HVA patient. Together with a better knowledge of the molecular composition of different venom extracts, CRD may contribute to optimize patient-tailored therapy. Correspondence to Maria B. Bilò, MD, Allergy Unit, Department of Internal Medicine, University Hospital Ospedali Riuniti di Ancona, - Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60026, Italy. Tel +39 071 5963804;. fax: +39 071 5963253; e-mail: m.b.bilo@univpm.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Insect sting allergy: new guidelines from the European and USA consensus groups: algorithms and recommendations Purpose of review Guidelines on insect sting allergy and venom immunotherapy (VIT) have been updated. This review describes the evolution of these guidelines and their similarities and differences. Recent findings The US and European guidelines show the evolution of guideline development in the grading of recommendations and the transparency of the evaluation of evidence. The US and European guidelines on VIT are similar in most areas and complimentary in others. The European guidelines are limited to VIT and are based on a published systematic review; the US practice parameters cover all areas of the diagnosis and management of insect sting allergy and do not use the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. There is general agreement that both children and adults with cutaneous systemic reactions do not require VIT, and that there is minimal risk associated with β-blockers and angiotensin-converting enzyme inhibitors during VIT. There are minor differences in the details of VIT dose, regimen, and choice of venom, but agreement on the duration and risk factors for relapse after VIT. The US and European guidelines are complementary in their discussion of the relation of mastocystosis and insect sting anaphylaxis and the value of measuring basal serum tryptase. Summary The updated guidelines on insect sting allergy from the US and European groups differ in scope, with a somewhat different focus in specific areas but are complementary overall. Where they overlap, there are relatively few differences in recommendations, and these are subtle. The US practice parameter offers an annotated algorithm for the evaluation and treatment of patients with reactions to insect stings. Correspondence to David B.K. Golden, MD, Johns Hopkins University, 20 Crossroads Drive #16, Owings Mills, Baltimore, MD 21117, USA. Tel: +1 410 363 6144; e-mail: dgolden1@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Anaphylaxis in adolescents Purpose of review The frequency of hospitalization for anaphylaxis has increased over the last 20 years across Europe, Australia, and North America, particularly, for food and medication triggers. Adolescents show the highest risk for morbidity and fatality from food-induced anaphylaxis, yet there is little high-quality evidence addressing the reasons for this disproportionate vulnerability. Recent findings Recent data seem to suggest a possible increasing burden of food-induced anaphylaxis among adolescents. Trends in anaphylaxis mortality are stable in North America and the United Kingdom, but not in Australia where the incidence of fatal anaphylaxis has recently doubled. The age distribution of fatal anaphylaxis varies according to the nature of the culprit trigger, with data suggesting an age-related predisposition to fatal food anaphylaxis in adolescents and young adults. Adolescence represents a critical phase of transition when rapid and substantial physical, emotional, and social changes occur. Therefore, adolescents show challenges in self-management that are different from other age groups, contributing to a higher risk of poor anaphylaxis outcomes. Summary The purpose of this review is to summarize recent data on epidemiology and elicitors of anaphylaxis in adolescents and to address currently known barriers and potential facilitators to self-management of anaphylaxis in this vulnerable age group. Correspondence to Diego G. Peroni, MD, Full Professor of Paediatrics, Section of Paediatrics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. Tel: +39 50992635; e-mail: diego.peroni@unipi.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.