Editorial

We open this new issue with an article that addresses a problem that so afflicts pediatric allergists and dermatologists: the therapy of atopic dermatitis (AD), often so frustrating because it is effective in the short term but with continuous relapses in long term. Atopic dermatitis is the most frequent chronic recurrent inflammatory skin disease in children; the pathogenesis of AD is complex and involves both systemic immune mechanisms and primitive skin alterations due to barrier defect, as well as a defective response to oxidative stress, in a multifactorial mixture of which it is difficult to understand the weight of each component and this has represented the most critical obstacle to the full and lasting effectiveness of any treatment. The entry of Tapinarof into the panorama of drugs available for the therapy of atopic dermatitis therefore appears particularly interesting also because in many aspects it reproduces effects similar to those obtained from corticosteroids without showing their side effects, having a completely different structure and mechanisms of action.  In fact, Tapinarof reduces inflammation and normalizes skin barrier function by ligand-dependent activation of AhR, resulting in downregulation of inflammatory Th2 cytokines implicated in AD, in modulation of keratinocyte differentiation, and increased expression of skin-barrier components, including many proteins such as filaggrin and ceramides. Additionally, Tapinarof promotes the antioxidant response to oxidative stress in many ways. Elena Galli et al discuss these aspects in their review article (p. 4) “Tapinarof as a new topical treatment in atopic dermatitis”. The authors explain the role of the AhR (Aryl hydrocarbon Receptor) that performs numerous functions being a protein with many binding sites: it is an important environmental sensor and a regulator of enzymes such as cytochrome P450s, as well as a transcription factor with a key role in regulating the synthesis of many cytokines implicated in the inflammatory cascade and in the immunological response. AhR is highly expressed in the skin and Tapinarof, used topically, works as a non-steroidal AhR agonist, leading to those clinical benefits that have been reported and that appear to be rapid in onset and long-lasting, while ensuring maximum long-term tolerability, as systemic absorption has been shown to be minimal or non-existent in adults and also in children. Tapinarof 1% cream was approved in the United States for the topical treatment of plaque psoriasis and subsequently the Food and Drug Administration (FDA) has significantly expanded the therapeutic options available for the management of AD in adults and children from 2 years of age. It is currently under evaluation by the EMA Committee. We all hope that Tapinarof will really mark a significant improvement in the approach to AD, but ongoing and future clinical trials and real-life studies will be essential to confirm its long-term safety and efficacy in patient populations. 

We also point out another truly curious and interesting article, especially considering the alarms raised by the changes in living styles in recent decades: people spend more and more time indoors and homes are small thermal power plants perfectly insulated from the outside for energy saving reasons. This has led to greater attention to indoor pollutants: the indoor environment can in fact present unfavorable conditions for health, with the accumulation of pollutants and allergens, both internally produced (such as formaldehyde or combustion gases from kitchens) and coming from outside and sealed in the home. In 2024, researchers from the National Aeronautics and Space Administration (NASA) ¹ announced that common indoor plants could provide a natural way to help fight sick building syndrome. In particular, some houseplants known for their air purifying capabilities can cause a significant improvement in indoor air quality as has been widely demonstrated. But the topic is very little widespread and has been substantially ignored by scientific communication. Then comes the article: “The role of plants in improving indoor air quality” by Alessandro Travaglini et al. (p. 17) which is an interesting and original analysis of how we can improve indoor air quality. Pioneering studies such as the NASA work mentioned above have shown that some plants can absorb volatile organic compounds (VOCs) such as benzene, formaldehyde and xylene. VOCs are organic compounds that have a high vapor pressure at room temperature. They are common and exist in a variety of contexts and products, not limited to household mold, upholstered furniture, art and craft supplies, dry-cleaned clothing. Unfortunately, although on paper and in experimental studies houseplants (and some species in particular) demonstrate an effective role in removing these pollutants, the possible benefits linked to their action are very limited and the data are not very encouraging: plants can remove small quantities of pollutants per hour and per unit of surface area, which is therefore far less than the needs of a healthy environment with “clean” air. It is therefore necessary to resort to air purifiers that instead perform their action sufficiently and effectively. We can only agree with the authors who conclude: “the best solution lies in the use of tools aimed at purifying the air while plants are more important in creating a pleasant environment”. Let’s not underestimate the fact that plants, by creating a pleasant environment, can have a very positive effect on the mood and psyche of children and adults inhabitant who spend a lot of time and even grow in closed environments and that houseplants ultimately have a synergistic effect with respect to technological air purifiers.

Hereditary Angioedema is a rare disease in pediatric rather than in adult age, and lies somewhere between inborn errors of immunity and monogenic allergic diseases. Symptoms begin to appear in adolescence or in any case after the first decade of life and tend to increase in frequency and severity. This is perhaps the reason why this topic is so little discussed in the field of pediatric immunology and allergy and, although treatment and global management of the disease is rightly the prerogative of highly specialized centers, it is necessary to review some key points of the disease, of the pathogenesis and above all of the dangers of a missed diagnosis (or diagnostic suspicion). The topic is widely illustrated by Rhea Bansal et al. (p. 25) who illustrates the experience of the English centers with the largest number of cases on this pathology in the paper “Demographic and Clinical Variation in Pediatric Hereditary Angioedema: A Single Centre Service Evaluation.” The authors report data from a cohort of 33 children, a very large number if one considers the rarity of onset in pediatric age. The onset is described, the often ignored or underestimated nonspecific and specific symptoms are highlighted, which mislead and cause dangerous delays in diagnosis, sometimes even in spite of indicative family history (which may however be lacking!). As Pediatricians we must anticipate as much as possible at least the diagnostic suspicion and proceed with basic tests that anticipate the patient’s referral to a specialized center. We must be alarmed by the frequency of deaths from asphyxia that occurs much more frequently among undiagnosed subjects than among recognized patients who can now benefit from effective life-saving therapies.

The advent of biological drugs has radically changed the  management and the quality of life in a large number of allergic diseases; among these, severe asthma has certainly had a decidedly different therapeutic approach. The first advantages in severe asthma control were observed with omalizumab, and benefits have progressively consolidated with the use of other more targeted biological drugs such as dupilumab and mepolizumab that have led to the clinical control of asthma even in the most difficult cases.

The paper by Carolina Grella et al. (p. 11) “Biologics and Severe Asthma: Focus on dupilumab and Its Time to Efficacy in the Treatment of Severe Uncontrolled Asthma in Children - A Single Center Experience“ illustrates the clinical results of dupilumab therapy observed in an important Italian reference center for severe asthma and compares them with data from the literature. With their critical analysis of past experiences the Authors try to find and give us indications on how to orient ourselves in the choice of biological drugs for the treatment of severe asthma.

Finally a look at allergic rhinitis, another extremely widespread disease that now involves a quarter of the pediatric and adolescent population. Apparently the diagnosis could always be easy, but in some situations it is not at all. Cristina Serio et al. (p. 34) offers us a starting point in her paper about the “Development and Clinical Applicability of a Survey for Screening Allergic Rhinitis in children: A Retrospective Study”. It is a retrospective study on a single-center case study that uses its own study methodology and offers us the opportunity to evaluate it and compare it to our usual method.

A note on AI (Artificial intelligence) applied to food allergy. It is a tool that even pediatric allergology can no longer do without it. End in this issue we have an original contribution on this topic from the school of Michele Miraglia del Giudice (p. 30): “An Intelligent Analysis of Food Allergens Through Computer Vision and Generative Models”. In this study, hypotheses are made and the reliability of predictions of important clinical reactions to certain foods in allergic children with particular sensitization profiles is evaluated.

This is a very interesting and instructive experience and at the end of the simulation the Authors conclude that AI shows promise but, today, “does not replace ingredient disclosure or clinical precautions”. It is true. We need to train AI better with a greater amount of data ... and currently our experiential data are still too contradictory and not univocal!

References

https://www.co2meter.com/blogs/news/nasa-compiles-list-of-best-plants-to-clean-indoor-air?srsltid=AfmBOoqLbzkDcPKmwflIYQD1amRbcKmswqBo8Q6dB0XRxUUddx9CKlf9.