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Chronic spontaneous urticaria (CSU) is a condition defined by the presence of recurrent urticaria, angioedema, or both, which persist for more than six weeks in duration and occurs in the absence of an identifiable trigger. Both children and adults can develop CSU, although it is more common in adults and in women than in men, with a peak occurrence in the third to fifth decades of life. It imposes a significant burden on patients, families and healthcare systems. The goal of therapy in patients with CSU is to achieve a level of symptom control and improvement in quality of life that is acceptable to the patient, while minimizing therapy-related side effects. The recent introduction of biologic drugs has changed the management of the disease. This work aims to provide a narrative review of the current state of biological therapy and the promising drugs under development for CSU.

Hypersensitivity reactions to polyethylene glycol (PEG) is an emerging challenge and the interest about this disease is growing since PEG is considered one of the possible causes of coronavirus disease 2019 (COVID 19) vaccine-associated anaphylaxis. PEG is used in a wide variety of pharmaceutical, medical, in-dustrial, cosmetic, and food products and can be an active ingredient or used as an excipient. PEG is present in several medications, and it may or may not be present in different formulations and dosages of the same drug. Lack of standardization nomenclature, inadequate labelling of products and lack of knowledge about PEG involvement in hypersensitivity reactions expose patients at risk of presenting multiple reactions before a diagnosis could be made. In this review we describe the main cases published in literature and propose an allergy work-up and management. (www.actabiomedica.it).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy (FA) characterized by delayed and severe gastrointestinal symptoms that typically occurs within the first year of life. Many aspects of this pathology are currently unclear. FPIES is classified as a non-IgE immune-mediated FA in which the immune response is thought to act mainly through cell-mediated mechanisms. In patients with FPIES, the symptom pattern is determined by the frequency and dose of food allergen in the diet. Diagnosis of FPIES may be difficult, mainly due to the lack of specific biomarkers to confirm or exclude the diagnosis. FPIES is a clinical diagnosis, mainly based on clinical features which, although not specific, are reproducible every time the patient takes the food. Different diagnostic criteria of FPIES were published over time in the literature. The present narrative review aims to analyze the current clinical evidence in epidemiology, pathophysiology, diagnosis, and management of this condition.

The change in forced expiratory volume in 1 s (FEV1) in response to a bronchodilator (ΔFEV1) is a diagnostic tool. Moreover, bronchodilation testing may give clinically relevant outcomes beyond diagnostic purposes. The present study aimed, therefore, to investigate the nationwide role of bronchodilation testing in daily practice. The study included 280 subjects, 202 (72.1%) males and 78 (27.9%) females; the mean age was 11.6 years. Notably, 67 (24%) children had bronchial reversibility (BDR). Age, initial FEV1, FEV1/FVC, and FVC were significantly associated with BDR (OR 1.16, 1.66, 0.71, and 0.67, respectively). Interestingly, 39 (58.2%) children with BDR had no bronchial obstruction. In conclusion, the BDR is usually associated with low values of the lung function parameters, even if within the normal ranges.

BACKGROUND: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for pediatric urticaria are implemented. METHODS: The EAACI Task Force for pediatric CU disseminated an online clinical survey among EAACI pediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centers. RESULTS: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly pediatric allergists (80%) and pediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (eg, autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2(nd) -generation antihistamine as first-line treatment of whom 64.8% updosed as a second line. Omalizumab was used as a second-line treatment by 1.7% and third line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). CONCLUSIONS: Even though most members of the Pediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update, and standardize guidelines on the diagnosis and management of CU in children.

In the last few years much attention has been focused on research on severe asthma and the role of biologicals in its treatment, also in children. However, mild asthma is way more common in childhood and still causes as many as 30-40% of asthma exacerbations requiring emergency consultation. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Nevertheless, updates on the strategies to manage these patients are coming, since evidence emerged on the role of inflammation also in these asthma phenotypes as well as on the potential side effect and risks of short-acting beta 2 agonists overuse, which is common in patients for which they have been prescribed as the only as-needed treatment. Unsurprisingly, international guidelines, including GINA, are starting to recommend associating a corticosteroid when using a reliver. In this paper we overview the (r)evolution regarding the management of intermittent and mild persistent asthma. We also focus on the importance of knowing the chemical and physical characteristics of drugs and inhaler devices in order to optimize the treatment and reach the distal airways, as well as of trying to achieve a good compliance to treatments, especially in adolescents, for which it is currently possible to rely also on new digital health technologies.

Histaminergic urticaria-angiodema is a common complaint in children. According to clinical criteria, it is classified as acute and chronic urticaria. A further clinical classification relies on triggering factors. We focus on diagnosis and therapeutic strategies. We report the main progresses in the field and issues that remain to be understood. (www.actabiomedica.it)

It is widely reported in the literature that CD4, CD8 and total T cell count are significantly reduced in critically ill patients with COVID‐19. Few weeks ago, we suggested natural killer (NK) cell count as a marker of severity in 34 hospitalized COVID‐19 patients. On this topic, our research group firstly described a novel potential COVID19 severity marker, Krebs von den Lungen‐6. This study aimed to investigate how a combination of COVID19 severity markers could be helpful in the clinical management of these patients. The combination of these validated, reproducible and non‐expensive bioindicators showed a good accuracy in discriminating between severe and non‐severe patients, suggesting a promising value of this approach in the early prediction of a more aggressive disease phenotype. Despite its monocentric design, our study confirms the reliable dysregulation of innate immune responses, particularly involving NK cells, and suggests that surveillance of a peripheral biomarkers’ panel, including lymphocyte cell counts and KL‐6, may be useful in the clinical management of severe COVID‐19 patients. This article is protected by copyright. All rights reserved.

Introduction: Cow’s milk is a frequent trigger of allergic reactions in childhood. Cow’s milk proteins can be present in pharmaceutical excipients. Methods: We have analyzed paediatric literature on allergic reactions to cow’s milk proteins in medication, focusing on the different routes of administration (inhaled, parental and oral). Results: Dry-powder inhalers may contain lactose as excipient. Lactose can be rarely contaminated with milk proteins and it may induce allergic reactions in patients with cow’s milk allergy. Case reports have described immediate hypersensitivity reactions to methylprednisolone sodium succinate 40 mg injection, a formulation that contains lactose as excipient. Some cases of anaphylaxis after receiving diphteria-tetanus-pertussis vaccine injection in children allergic to milk have been reported. Cow’s milk proteins can be detected also in oral polio vaccine, certain probiotics and lactulose syrup. Conclusions: We suggest caution in administration of pharmaceuticals containing milk allergens in children allergic to milk. (www.actabiomedica.it).

The management of chronic diseases are paramount in health care in these days. Among them, there has been an expansion of allergic and immunologic diseases, especially in children. Thanks to the action of the Italian Society of Pediatric Allergy and Immunology (SIAIP), the quality level of care has progressively grown. SIAIP developed a task force with the purpose of proposing updated models for assessing, and prescribing treatment in the allergy and immunology field that have been issued in this supplement. In a very difficult time for everyone, current developments covering a broad range of topics in the field are presented. All Authors have to be thanked, since they have participated with passion and have taken valuable time away from their professional and private interests. We hope that the readership will enjoy these papers.

Primary immunodeficiencies (PIDs) are inherited disorders classically characterized by increased susceptibility to infections. Nevertheless, in the last two decades, genomic analysis (such as NGS) coupled with biochemical and cellular studies led to a more accurate definition for a growing number of novel genetic disorders associated with PIDs. This revealed new aspects of the immune system and its function and regulation within these diseases. In particular, it has been clarified that the clinical features of PIDs are much broader that originally thought and extend beyond an increased susceptibility to infections. More specifically, immune dysregulation is very often described in novel characterized PIDs and can lead to multiple autoimmune diseases, lymphoproliferation and malignancies. If not promptly diagnosed, these could negatively impact patient’s prognosis. The aim of this review is to increase the awareness of recently discovered PIDs, characterized predominantly by immune dysregulation phenotypes. Findings highlighted in this review suggest screening for immunodeficiency in patients with lymphoproliferation or early onset/multiple autoimmune diseases. Prompt diagnosis would potentially allow most successful treatment and clinical outcome for patients with PIDs. (www.actabiomedica.it)