Editorial

This second issue of the IJPAI for 2026 offers a broad and highly practical overview on various topics, through a series of case reports: they shed light either by recalling rare and often overlooked conditions or by formulating suggestive hypotheses.

First, we would like to highlight some original studies of great practical and speculative interest.

The first, “Potential Role of Nickel Allergy in Gut-Brain Interaction Disorders” (p. 3), is by the pediatric gastroenterology group led by Roberto Berni Canani. The authors address the topic of nickel allergy from an original perspective and offer us the opportunity to rethink the role that nickel allergy may play in the genesis of many gastrointestinal disorders for which we cannot identify a precise trigger.

We know well that nickel allergy is predominantly a contact allergy and rarely presents with systemic or gastrointestinal symptoms; it follows that the need to start a nickel-free diet arises in sporadic, if not exceptional, cases.

In this prospective observational study, the authors assessed the presence of nickel sensitization in a cohort of pediatric and adult patients with difficult-to-classify functional gastrointestinal disorders, such as irritable bowel syndrome, demonstrating that the prevalence of nickel allergy was 45%. This value is significantly higher than that found in the general population.

This data is certainly highly suggestive and suggests that nickel hypersensitivity may represent a key factor causing or contributing to the development of functional gastrointestinal symptoms, a factor that has been overlooked or underestimated until now.

However, the authors emphasize that the issue needs further study and confirmation, and therefore further studies will be needed to support the decision to modify the diet by reducing nickel intake (elimination is virtually impossible because nickel is present in a large quantity of foods) in sensitized subjects with functional disorders.

The second paper we present concerns atopic dermatitis, a disease in which the immunological and non-immunological mechanisms underlying its pathogenesis have become increasingly clear in recent decades. However, during this same period, we have also witnessed the development of our knowledge of the microbiome and its close interactions with the immune system. In particular, studies on the skin and gut microbiome have opened new perspectives on the potential impact of these connections on immunological balance. The article, “Atopic Dermatitis and the Holobiome: A Review of Molecular Mechanisms and Host-Microbiota Interactions,” is the work of the Atopic Dermatitis Committee coordinated by Elena Galli (p. 7). In this review, the authors summarize the salient and critical points of research in the field and of the most recently published studies. They critically comment on current knowledge of the holobiome, focusing on its complex interaction with various pathogenetic factors, such as epidermal barrier dysfunction, Th2-mediated inflammation, microbial dysbiosis, and Staphylococcus aureus colonization. Given the extreme heterogeneity of the studies and the numerous variables that make unambiguous interpretation difficult, the authors limit themselves to presenting the future implications of these findings, if confirmed, and some hypotheses/suggestions for potential therapeutic strategies to modify the skin microbiome and, consequently, host-microbe interactions.

Daria Calanchini et al. present a case of sunflower seed-induced anaphylaxis in a child (p. 24). The authors describe the case of a 6-year-old boy with seasonal allergic rhinitis who presented with an episode of anaphylaxis during exercise. He had ingested food containing sunflower seeds approximately 1 hour earlier. A skin prick test confirmed polysensitization not only to inhalant allergens but also to sunflower seeds. Sunflower (Helianthus annuus) belongs to the Asteraceae family; the sunflower molecular allergens identified to date are: Hel a 3, a lipid transfer protein, certain 2S albumins (Hel a 2S, Hel a 15, Hel a 16, Hel a 17), and oleosins. In particular, the latter two groups of allergens are highly stable and closely related to anaphylaxis. Although the physician does not have all the identified molecular allergens available and must rely on skin prick tests, it is good practice to confirm the diagnosis with a targeted molecular investigation.

An interesting case report, “Fixed drug eruption induced by clarithromycin in a pediatric patient,” is presented by Federica Tonello et al. (p. 19). Fixed drug eruption is a delayed adverse skin reaction characterized by recurrent lesions at the same anatomical site following re-exposure to the causative agent. The authors report the case of an 8-year-old girl with a history of recurrent rashes, initially diagnosed as urticaria multiforme in the context of suspected beta-lactam hypersensitivity. However, collaboration with the pediatric dermatologist led to a more thorough assessment of the clinical picture and a revision of the diagnostic workup. This enabled an accurate differential diagnosis in the context of allergic drug reactions underlying different pathogenic mechanisms, but with often nearly overlapping clinical expressions. This case highlights the importance of interdisciplinary collaboration which, together with a detailed history and targeted allergy assessment, leads to appropriate management while avoiding unnecessary pharmacological restrictions.

Cascone et al. authored the paper “Persistent Elevation of FeNO Despite Clinical Control in Pediatric Allergic Asthma: A Case Report Highlighting the Impact of Allergic Rhinitis” (p. 15). They describe the case of a 12-year-old boy with allergic rhinitis and asthma who, despite good asthma control, continued to exhibit elevated FeNO levels in his exhaled breath. This experience therefore fits into the debate on the usefulness of FeNO in the management of asthmatic children, a still open and hotly debated issue. The reported experience suggests using and correctly interpreting this test, not for asthma management, but for monitoring inflammation of all airways from the nose to the lungs. FeNO is therefore confirmed as a non-invasive biomarker of eosinophilic inflammation, and is very useful for monitoring the inflammatory condition of the airways in the follow-up of pediatric asthma but which cannot be considered a criterion for diagnosis. FeNO is therefore confirmed as a non-invasive biomarker of eosinophilic inflammation, very useful for monitoring airway inflammation in pediatric asthma follow-up, but cannot be considered a criterion for evaluating asthma control.