Tryptase values in anaphylaxis and insect allergy,                            Purpose of review To recognize the relevance of serum tryptase measurement as a useful tool for the diagnosis of allergic diseases and mast cell disorders. Recent findings Recent data on the role of mast cells and tryptase in allergic and other diseases provide new understanding into the mechanisms and causes of anaphylaxis. Summary Measurement of transiently elevated tryptase levels shortly after a severe reaction can help elucidate mechanism behind the reaction in identifying mast cell activation. Hymenoptera venom allergy represents an important cause of morbidity and mortality worldwide. Venom allergy is a typical IgE-mediated reaction because of sensitization to one or more allergens of the venom, and accounts for 1.5–34% of all cases of anaphylaxis. There is a preferential association between insect venom allergy and mastocytosis. The diagnosis of a clonal mast cell disease leads to therapeutic consequences concerning the treatment of venom allergy. In conclusion, baseline tryptase levels support the clinical diagnosis of anaphylaxis and mast cell disorders, determine venom immunotherapy treatment and is relevant in deciding on lifelong treatment. Correspondence to Patrizia Bonadonna, Allergy Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, Verona 37126, Italy. Tel: +39 458126166; fax: +39 458126178; e-mail: patrizia.bonadonna@aovr.veneto.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Gender differences in anaphylaxis Purpose of review Is sexual dimorphism also true in anaphylaxis as described in other allergic diseases? Possible gender differences in the epidemiology, triggers, severity, outcomes of anaphylaxis as well as in the pathogenesis of the disease are discussed. Recent findings Hormonal status and the X-chromosome-coded factors deeply involved in the regulation of T-cell and B-cell responses may influence the gender difference noticed in allergic diseases, such as asthma and rhinitis. Little is known if sex is also relevant for anaphylaxis, although the description of catamenial anaphylaxis is intriguing. However, epidemiologic bias, lack of reliable animal models for the human disease, differences into diagnostic codes and not harmonized clinical grading unfortunately represent hurdles to obtain meaningful information on this topic. Summary The female sex predisposes to a dysregulation of the immune response as suggested by the increased prevalence of autoimmunity and atopy. In anaphylaxis, pathomechanisms are not fully disclosed, triggers are numerous and IgE-dependent mast cell degranulation only represents a part of the story. Improvement into the definition of the disease including a more careful coding system and better investigations about triggers seem the only way to allow a more precise assessment of the possible different risk for women to develop anaphylaxis. Correspondence to Paola Parronchi, MD, Department of Experimental and Clinical Medicine, University of Firenze, Largo Brambilla 3, 50134 Firenze, Italy. Tel: +39 557947421; e-mail: paola.parronchi@unifi.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ocular allergy: update on clinical trials Purpose of review The purpose of this article is to provide an update on the advances made through recent clinical trials regarding the treatment of the signs and symptoms of allergic conjunctivitis and its associated conditions. Recent findings Recent studies have demonstrated significant advancement in the various forms of immunotherapy treatments. Nutritional interventions such as probiotics have surfaced as a viable complementary treatment option. Novel delivery methods such as contact lenses have been further studied along with a new tacrolimus formulation to improve ocular levels of the drug. Summary Currently, the primary advances in treatment for allergic conjunctivitis has shifted from new ophthalmic agents to immunotherapy and improvement of drug delivery. This includes the classic subcutaneous and sublingual and the novel epicutaneous and intralymphatic immunotherapy delivery systems as well as an edible rice vaccine. New targets for treatment have spurred research into new antagonist drugs such as (OC000459), a prostaglandin D2 antagonist. The Marinosolv formulation using tacrolimus shows promise and may be considered for other ophthalmic agents in the future. Other nonpharmacological treatments such as stenting and mechanical barrier gel have demonstrated their usefulness in treating ocular symptoms. Correspondence to Leonard Bielory, MD, University Ophthalmology and Allergy Associates, 400 Mountain Avenue, Springfield, NJ 07081, USA. Tel: +1 973 912 9817; e-mail: drbielory@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Asthma and anaphylaxis Purpose of review Both asthma and anaphylaxis are recognized noncommunicable hypersensitivity conditions, which should be correctly diagnosed and treated/controlled in order to decrease avoidable deaths. Nevertheless, their association is not completely clear. We here propose to review the current and new evidence-based data of asthma and anaphylaxis in the view of the new knowledge in the field that can support the quality practice and empower allergists and health professionals in treating symptoms and preventing death. Recent findings Hypersensitivity life-threatening conditions, such as anaphylaxis and asthma can coexist, mimic or worse each other. Asthma itself is not a strong predictor of more severe anaphylaxis. However, poor asthma control associated with more severe anaphylaxis reactions in all ages. In children, asthma is associated with the severity and recurrences of anaphylactic reactions. Summary Although recent data point for the association between asthma and anaphylaxis, we still do not have harmonized evidence to confirm if we are dealing with two independent comorbidities one worsening each other. However, as far as this review is covering two relevant public health problems in the field of allergy, it is mandatory put in place decisions supporting recommendations to better manage the affected patients and reduce the risk. General strategies should include regular notification of this association, optimization of the classification and coding for anaphylaxis and asthma (new ICD 11 anaphylaxis codes) in order to harmonize epidemiological stratified data, early diagnosis of asthma in childhood, regular investigation of asthma in cases of anaphylaxis and optimization of the asthma control and lung function for all patients with indication to provocation tests, desensitization or allergen immunotherapy regardless to the trigger. Implementation of these strategies will involve national and international support for ongoing efforts in relationship with networks of centres of excellence to provide personalized management for the most at-risk patients and prevent death. Correspondence to Luciana Kase Tanno, MD, PhD, Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, 371, av. du Doyen Gaston Giraud - 34295, Montpellier Cedex 5, France. Tel: +33 467336107; fax: +33 467633645; e-mail: luciana.tanno@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Impact of climate change on insect–human interactions Purpose of review To update the influence of the global climate change on Hymenoptera venom allergy. Recent findings Climate change facilitates biological invasions of hymenopteran species and plays a role in the impact of introduced species relevant for human health. It contributes to a rise in the incidence of sting injuries and allergy reactions across the world. Summary Global climate change has contributed to the expansion and the redistribution of allergenic insect species, increasing the number of allergy cases caused by stinging insects worldwide. Imported insects are trending species in systemic reactions for multiple stings or hymenopteran venom allergy. They represent a threat for humans and a challenge for the allergists. Correspondence to Arantza Vega, MD, PhD, Allergy Service, Hospital Universitario de Guadalajara, CL Donante de sangre s/n, 19002 Guadalajara, Spain. Tel: +34 949209200 (Ext 927) e-mail: avega@sescam.jccm.es Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Mastocytosis presenting as insect anaphylaxis: gender differences and natural history Purpose of the review Currently, there is strong evidence about an association between hymenoptera venom anaphylaxis (HVA) and mastocytosis. This review is focused on the most relevant clinical and biological features of systemic mastocytosis associated with HVA. Recent findings HVA is a relatively common complication that modifies the natural course of patients with mastocytosis, particularly men with indolent systemic mastocytosis without skin lesions (ISMs−) in whom HVA can be the presenting symptom in up to around one-half of the cases. Patients with ISMs− associated with HVA are typically males with cardiovascular symptoms in the absence of itching, urticaria, and angioedema during anaphylaxis. Noteworthy, ISMs− is characterized by a low bone marrow mast cell load and a low risk for disease progression. Early and more recent studies support that specific venom immunotherapy (VIT) is a well-tolerated and effective treatment in patients with mastocytosis. Summary VIT should be given life-long to all patients with mastocytosis and proven immunoglobulin E (IgE)-mediated HVA. In patients with negative venom skin test and undetectable IgE antibodies, additional studies such as component-based allergy testing might contribute to confirm an IgE-mediated mechanism of anaphylaxis in some cases, thus providing the indication of VIT. Correspondence to Iván Alvarez-Twose, MD, PhD, Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Complejo Hospitalario de Toledo, Ctra. Cobisa S/N, Toledo 45071, Spain. Tel.: +34925269336;. e-mail: ivana@sescam.jccm.es Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Current market trends in anterior ocular inflammatory disease landscape Purpose of review In the US anterior ocular inflammatory disease (AOID) composed of the spectrum of ocular allergies, different forms of infectious conjunctivitis, and dry eye diseases, affects over 40% of the population. This review evaluates the current economic costs for AOID associated pharmacotherapies. Recent findings In recent years, with improved understanding in pathophysiology of the AOID, providing novel targets for pharmacotherapy, have led to considerable improvements in outcomes for patients. Despite these advances, there continues to be a need for interventions that inhibit key inflammatory mediators or pathways in the ophthalmic space. In 2018, AOID drugs market represents ∼40% of the costs for the total ophthalmic drugs: dry eye (43%), antiinfectives (15%), antiallergics (13%), and antiinflammatory agents (29%). With increasing treatment costs, the need for improved, cost-effective modalities persists along with treatment algorithms to derive optimal benefits for patients. Summary There has been a dramatic increase in the economic burden of AOID with the annual expenditure for the prescription drugs approaching close to $11 billion in 2018. With increasing prevalence of ocular disease, further investment is required to provide more effective treatment options and deliver improved public health and economic outcomes. Correspondence to Leonard Bielory, MD, 400 Mountain Avenue, Springfield, New Jersey 07081. E-mail: drlbielory@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Office-based ocular procedures for the allergist Purpose The aim of this study is to suggest principles for ocular procedures to be performed by allergists in their offices in helping their diagnosis of ocular diseases and suggest better interactions between allergists and ophthalmologists. Recent findings Diagnosis of ocular allergy is based on clinical history and signs and symptoms, with the support of in-vivo and in-vitro tests for the identification of the specific allergen. Unfortunately, ocular manifestations are frequently misdiagnosed and not properly managed. Summary A multidisciplinary allergist–ophthalmologist approach may improve early differential diagnosis and the prognosis of patients with allergic disease and conjunctivitis through shared management and earlier etiological treatment. Correspondence to Andrea Leonardi, MD, Department of Neuroscience, Ophthalmology Unit, University of Padua, via Giustiniani 2, 35128 Padua, Italy. Fax: +39 049 875 5168; e-mail: andrea.leonardi@unipd.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The roles of omega-3 fatty acids and resolvins in allergic conjunctivitis Purpose of review Lipids are one of the most important constituents in our body. Advances of lipidomics are elucidating the new roles of various lipid molecules in allergic diseases. For example, some reports showed anti-inflammatory effects of omega-3 fatty acids (FAs), such as docosahexaenoic acid, eicosapentaenoic acid, and their metabolites, on allergic diseases. Here, we introduce the role of lipid mediators in allergic conjunctivitis mouse model. Recent findings Lipidomics using liquid chromatography–tandem mass spectrometry can profile numerous lipid molecules from small tissue samples such as conjunctival specimens. Lipidomics analysis showed that various inflammatory lipid mediators are produced in the conjunctival tissue of allergic conjunctivitis mouse model. Dietary omega-3 FAs reduced these inflammatory lipid mediators in the conjunctiva and alleviated allergic conjunctivitis symptoms in mouse models. In addition, the roles of specialized proresolving lipid mediators (SPMs) have been reported for allergic inflammation. Summary Lipid mediators have important roles for the pathophysiology of the allergic diseases including allergic conjunctivitis. Omega-3 FAs and SPMs are expected as new treatment tools for allergic conjunctivitis. Correspondence to Akira Matsuda, Laboratory of Ocular Atopic Diseases, Department of Ophthalmology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. Tel: +81 3 5802 1031; fax: +81 3 5802 5889; e-mail: akimatsu@juntendo.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Role of the ocular surface microbiome in allergic disease Purpose of review The purpose of this review is to provide an update regarding new and emerging data on the role of the ocular surface microbiome in allergic disease. Recent findings Recent findings support the role of the microbiome in the pathophysiology of allergic disease of the ocular surface. Summary Understanding the role of the ocular surface microbiome in allergic disease may provide a new target for the development of therapeutic interventions. Correspondence to Kara M. Cavuoto, MD, 900 NW 17th Street, Miami, FL 33136, USA. Tel.: +1 305 326 6324;. fax: +1 305 547 3675; e-mail: kcavuoto@med.miami.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.