Mast cells (MCs) are fascinating cells of the innate immune system involved not only in allergic reaction but also in tissue homeostasis, response to infection, wound healing, protection against kidney injury, the effects of pollution and, in some circumstances, cancer. Indeed, exploring their role in respiratory allergic diseases would give us, perhaps, novel therapy targets. Based on this, there is currently a great demand for therapeutic regimens to enfeeble the damaging impact of MCs in these pathological conditions. Several strategies can accomplish this at different levels in response to MC activation, including targeting individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth, or inducing mast cell apoptosis. The current work focuses on and summarizes the mast cells’ role in pathogenesis and as a personalized treatment target in allergic rhinitis and asthma; even these supposed treatments are still at the preclinical stage.

Mast cells are immune system cells with the most disparate functions, but are also among the least understood. Mast cells are implicated in several known pathological processes, tissue homeostasis, and wound repair. However, they owe their notoriety to allergic diseases, of which they represent the effector cell par excellence. In both allergic and not upper airway pathologies, mast cells play a key role. Exploring the mechanisms through which these cells carry out their physiological and pathological function may help us give a new perspective on existing therapies and identify new ones. A focus will be placed on non-allergic rhinitis, a poorly recognized and often neglected condition with complex management, where the role of the mast cell is crucial in the pathogenetic, clinical, and prognostic aspects.

Concern has arisen about hypersensitivity reactions in patients with allergic reactions to drugs containing polyethylene glycol (PEG) or polysorbate 80 (PS80), excipients of currently available anti-SARS-CoV-2 mRNA vaccines. However, the actual utility of PEG and PS80 skin allergy testing is currently still debated. We retrospectively analyzed all cases of patients on whom we performed allergometric skin tests for PEG and PS80 in the context of a pre-vaccination screening (for patients with multiple hypersensitivity reactions to drugs for which these excipients were among the suspected agents) or following suspected hypersensitivity reactions to anti-SARS-CoV-2 vaccines. A total of 134 tests were performed for PEG and PS80, eight of which produced uninterpretable results (due to dermographism or non-specific reactions). Of the remaining 126 cases (85 pre-vaccinal and 41 post-vaccine reactions), 16 (12.7%) were positive for PEG and/or PS80. Stratifying by clinical indication, there were no statistically significant differences in the proportion of positive tests between patients evaluated in the context of the pre-vaccination screening and those evaluated after a vaccine reaction (10.6% vs. 17.1%, respectively, p = 0.306). Allergometric skin tests for PEG and PS80 in our case series resulted positive in an unexpectedly high proportion of patients, suggesting that testing for allergy to these two excipients should not be ignored in case of reasonable clinical suspicion.

Purpose of review: To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the combination of them in managing patients with IgE-mediated food allergies. Recent findings: Recent studies suggest that OIT and biologics, alone or together, can have a role as disease-modifying treatments for food allergies. The FDA has recently approved omalizumab as a treatment for food allergy. Other biologics are currently under evaluation and further studies are needed to assess the efficacy and safety of these therapies. Summary: The allergology scenario is rapidly evolving, the recent introduction and approval of new therapeutic strategies such as biotechnological drugs and allergen immunotherapy is changing the therapeutic paradigm: we are witnessing a shift from a strategy based on avoiding the trigger and reversing an allergic reaction already in progress, to one that aims to modify the natural history of the disease by acting on the immunological mechanisms that determine it. This approach is consistent with the modern perspective of a personalized patient-tailored medicine. In this opinion review, we will provide a brief analysis of current and future therapeutic options for IgE-mediated food allergy, focusing on OIT, biologics and their combination.

Purpose of review: To provide an accessible, comprehensive overview of past, present, imminent, and future therapies for systemic mastocytosis. Recent findings: Based on recent trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved two drugs for treating advanced systemic mastocytosis: avapritinib and midostaurin. The FDA also approved imatinib for selected cases of aggressive systemic mastocytosis without the D816V c-Kit mutation. Moreover, for the first time, a cytoreductive molecule, avapritinib, has been approved for patients with indolent systemic mastocytosis. Summary: Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.

Randomized controlled trials have demonstrated responses to clinical parameters, but a significant proportion of allergy patients in real-life settings would have been excluded from such studies. Therefore, real-world research is needed, and there is a growing body of information on allergen immunotherapy’s long-term effectiveness and safety. Real-world evidence can be a valuable instrument to better understand the patient’s journey and the effectiveness and safety of therapies. For this purpose, a registry will be used for the first time in Italy to evaluate the impact of allergen immunotherapy on several outcomes, including quality of life and disease-related effects in the pediatric and adult allergic population with a socio-economic assessment and respect to real-world health.