Editorial

This new scientific year begins with highly relevant articles that open up new diagnostic and treatment perspectives for many chronic and acute conditions that are frequently encountered in our clinical practice. We first highlight the article by Minguzzi et al., “Small-molecule therapies in pediatric atopic dermatitis: current overview and future prospects” (p. 2), which illustrates these new molecules, describes their mechanism of action, and their therapeutic potential. Atopic dermatitis is one of the conditions that has benefited most from these new drugs, thanks to which it has seen significant improvements in clinical management and quality of life. As with many other allergic diseases, atopic dermatitis had seen significant therapeutic successes with biologics, as discussed in the previous issue; however, the development of these new molecules has further expanded the therapeutic portfolio, although for now, they primarily benefit adults. These “small molecules” work by modifying the mechanisms of allergic inflammation, interfering with signaling pathways within the cell. Indeed, they are capable of directly modulating the intracellular signaling cascades involved in the inflammatory response and substantially and selectively inhibiting the inflammatory pathway in which they are inserted. For adults, pharmacological formulations of some of these molecules are already available on the market, both orally and topically, while others are still in the experimental phase. Atopic dermatitis, however, is not the only indication: some of these molecules have other therapeutic indications. For example, apremilast, an oral PDE4 inhibitor, is approved for plaque psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease. Other topical PDE4 inhibitors such as crisaborole and difamilast have expanded the nonsteroidal options for mild to moderate atopic dermatitis, as they have been shown to have significant local anti-inflammatory effects while minimizing systemic exposure. Another topic worthy of special attention concerns drug allergies: to date, we still know too little about the potential factors that aggravate or trigger an adverse drug reaction. The Drug Commission, coordinated by Carlo Caffarelli, has published a review of nonsteroidal anti-inflammatory drugs as possible cofactors in hypersensitivity diseases (p. 25). Although most of the mechanisms of action are still not fully understood, we know that NSAIDs can be cofactors for many clinically relevant conditions, such as food-induced exercise-induced anaphylaxis, chronic urticaria, uncontrolled asthma, angioedema induced by angiotensin-converting enzyme inhibitors, and anaphylaxis caused by oral dust mites. For this reason, patients complaining of adverse reactions must be thoroughly evaluated, and any comorbidities must be analyzed. Consequent drug therapies must be chosen with great caution. The Allergy Diagnostics Commission, coordinated by Roberto Bernardini, has conducted two studies, both of considerable relevance to daily practice: “Basophil Activation Test: Clinical and Research Relevance in Allergy Diagnostics” (p. 36), which discusses the clinical significance of BAT, and another on the role of eosinophils in the diagnosis of allergic diseases (p. 44). These are niche topics, but they are highly relevant because the first is still a critical issue, while the second emphasizes the need to address differential diagnosis, which is not always easy. Furthermore, it highlights the peculiarity of eosinophils. While they play an important role in allergic diseases and represent a specific allergy marker, they also may reflect both severe immune system regulation disorders and serious hematological diseases. Regarding the basophil activation test, as we know, it is a flow cytometric test that indirectly measures histamine release by quantifying activation markers on the basophil membrane. The use of the this test in food allergies has been extensively studied, including its potential use in some specific scenarios, but it has not widespread and remains the prerogative of a few laboratories. The main reason for its limited application lies primarily in reproducibility issues as it requires trained and experienced personnel. Finally, a comprehensive overview of cold urticaria by Spinelli et al. in the form of a review on: cryoglobulins, cryofibrinogens, and cold agglutinins in pediatric cold urticaria: pathophysiological insights and clinical management (p. 31). This paper confirms the importance of understanding the pathophysiological mechanisms of each disease or clinical manifestation: only through a full understanding of the phenomenon and of all the key players can we develop effective, targeted, and curative therapies. Finally, a reminder to everyone: our 28th National Congress is coming soon, and we truly hope to see all of you in Naples for this unmissable event.