Eosinophilic granulomatosis with polyangiitis (EGPA) is a multiorganic syndrome that affects the cardiovascular, neurologic, renal, and gastrointestinal systems with an incidence ranging from 0 case to 67 cases per one million person-years, and its pathophysiology remains unknown. It is believed that genetic factors, the environment, and changes in immune system function contribute to the development of EGPA, overlapping the immune mechanisms of vasculitides and the pathologic mechanisms in eosinophilic syndromes. This disease is commonly divided into two phenotypes depending on the presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA-positive patients usually have more vasculitic manifestations like peripheral neuropathy, purpura, renal involvement, and biopsy-proven vasculitis. The keystone of EGPA therapy is systemic corticosteroids (CS) as monotherapy or in combination with other immunosuppressive treatments, and recently the efficacy of eosinophil-targeted biotherapy, anti-interleukin-5 (IL-5), has been shown to be efficacious in EGPA. Although this phenotype/phase distinction has not yet had an impact on the current treatment strategies, emerging targeted biotherapies under evaluation could lead to a phenotype-based approach and personalised treatment regimens for EGPA patients. The present review describes the new therapeutical approaches with biological drugs for EGPA.

A case report of fish allergy is exposed. The responsible allergen was fish collagen, and there was no sensitization to parvalbumin (main fish allergen). The patient acquired collagen sensitization by occupational exposition, not by ingestion.

The advent of biological drugs has opened up new therapeutic possibilities in the field of eosinophilic gastro-intestinal diseases (EGIDs). EGIDs are chronic inflammatory diseases of the gastrointestinal tract unrelated to drugs or infections, and eosinophilic esophagitis (EoE) is the most frequent form. EGIDs are complex disorders, which pathogenesis is still partially unknown. The diagnosis of EGIDs relies on the combination of different data, such as clinical manifestations, laboratory tests, endoscopic, and histological data. The gold standard at present is the histological examination obtained from biopsies under endoscopic guidance, but the diagnostic criteria for each disorder are still not fully defined, and few clinical scores are validated, for all these reasons, conducting clinical trials on EGIDs is challenging. The dietary approach remains currently a first-line treatment, despite its efficacy being influenced by patients’ compliance. Exclusion diets, nevertheless, involve potential nutritional deficiencies. Two of the pivotal pharmacological therapies for the treatment of EGIDs are proton pump inhibitors (PPIs), especially for EoE, and systemic or topical steroids. Long-term corticosteroid therapies are, however, associated with even severe side effects, so steroid-sparing therapies are needed to achieve the same results, in the last years monoclonal antibodies have been studied. To date, dupilumab is the only approved biological drug for EoE therapy, but many others are currently being tested in clinical trials also for the other forms of EGIDs. This work presents a complete review of the role of biological drugs in EGIDs to date, systematically structured by pathology.

Asthma is a chronic condition characterized by inflammation throughout the entire bronchial airways. Recent findings suggest that ventilation inhomogeneity and small airway dysfunction (SAD) play a particularly significant role in asthma development and clinical manifestations. Obesity is a considerable risk factor for asthma development and morbidity in children and adults. A growing body of evidence suggests that SAD is linked to more severe asthma and poor asthma control in obese patients. However, the knowledge about the relationship between peripheral airway compromise and obesity in asthma is limited, mainly because of the historical lack of access to non-invasive assessment methods for studying SAD. Conventional lung function measurements, like spirometry, cannot accurately assess small airway function. However, in recent years, new specialized tests available in outpatient settings have been found to distinguish SAD from large airway obstruction more accurately compared to spirometry. Therefore, understanding the degree of peripheral airway implication in the underlying pathology is critical for effective asthma control and therapeutic decisions. This review highlights recent findings on the impact of SAD on asthma patients who are obese. Additionally, it explores how new diagnostic methods, such as impulse oscillometry (IOS), may be used in outpatient settings to detect small airway impairment in obese asthma at an early stage, potentially leading to improved asthma treatment.

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by adult-onset asthma, chronic rhinosinusitis with nasal polyps (CRSwNPs), and aspirin/NSAID hypersensitivity, presenting recurrent asthma exacerbation and poor clinical outcomes. Patients with NERD have heterogeneous clinical phenotypes/endotypes, and the management of NERD remains challenging. Dysregulation of arachidonic acid (AA) metabolism and persistent eosinophilic airway inflammation are the major pathogenic mechanisms in the upper and lower airways of NERD. To date, increased levels of urinary leukotriene E4 (uLTE4) [a terminal metabolite of the lipoxygenase (LOX) pathway] have been the most relevant biomarker for NERD. It is demonstrated that mast cells, platelets, and epithelial cells can amplify upper and lower airway inflammation in NERD, and several potential biomarkers based on these complicated and heterogeneous mechanisms have been suggested. This review summarizes potential biomarkers for application in the management of NERD.

In Europe, allergen products from different manufacturers can be labeled using the same unit with yet different definitions of that unit, which may cause confusion, as is the case for the index of reactivity (IR). In this context, house dust mite (HDM) Staloral 300 IR/mL, from Stallergenes Greer, and HDM Osiris 300 IR/mL, from ALK-Abelló, were characterized in vitro. Qualitatively, namely in terms of protein and allergen profiles, the two products were similar. Quantitatively, and despite the same 300 IR/mL labeling, the two products were shown to have different biological potencies, with HDM Staloral 300 IR/mL displaying a 2.4 times higher total allergenic activity (TAA) than HDM Osiris 300 IR/mL. This higher biological potency of HDM Staloral 300 IR/mL was paralleled by higher allergen and protein contents, namely 1.5 times more Der p 1 and Der f 1, 3.0 times more group 2 allergens, 2.7 times more Der p 23, and 1.8 times more protein. In contrast, HDM Staloral 300 IR/mL was shown to contain far fewer culture medium-derived proteins than HDM Osiris 300 IR/mL.

The incidence of asthma, a heterogeneous inflammatory disease affecting over 300 million people worldwide, continues to increase in developed countries. Human epithelial cells (ECs) express the alarmin-type cytokine thymic stromal lymphopoietin (TSLP) following tissue injury triggered by several environmental insults, which include allergens, smoke, pollutants, or other irritants. Furthermore, TSLP has an emerging but well-documented pathogenic role in asthma. TSLP has been called a “master switch” of allergic inflammation at the epithelial-dendritic cell (DC) interface, where it supports T helper 2 (Th2) inflammatory polarization and promotes the maintenance of Th2 memory responses. Therefore, targeting TSLP/TSLP-mediated signaling may represent an attractive therapeutic strategy for asthma. Several studies of anti-TSLP drugs are ongoing; the first-in-class anti-TSLP monoclonal antibody (mAb) tezepelumab, the immunoglobulin G1 antibody fragment CSJ117, or TSLP-traps [a combination of anti-interleukin-13 (anti-IL-13) and anti-TSLP mAbs] all represent promising new treatment approaches. This article reviews the characteristics of TSLP and discusses the treatment of severe asthma through TSLP-associated mechanisms.

Lettuce allergy is uncommon and usually attributed to lipid transfer protein (LTP) sensitization. Most LTP-sensitized patients present with heterogeneous symptoms not only to lettuce, but to a large number of other foods and pollen allergens, including peaches, apples, Platanus, and mugwort, with peach LTP being considered as the primary sensitizer. The case of a medical student with a history of lettuce allergy investigated by skin prick tests (SPTs) and oral food challenge (OFC) is presented in this report. SPTs showed sensitization exclusively to lettuce and not to any other known cross-reacting allergens, which contrasts with previous literature and highlights the uniqueness of this case. During OFC, the patient developed generalized symptoms including abdominal discomfort, bilateral tinnitus, facial flushing, generalized itching, and urticaria. No cardiopulmonary compromise was observed at the time, and the reaction was managed with oral antihistamines. More sophisticated molecular analysis is required to identify the patient’s sensitization profile; however, SPTs and OFCs remain the most practical clinical approach. Lettuce allergy deserves further attention and investigation.

Coronavirus disease 2019 (COVID-19) pandemic was a great challenge for healthcare professionals globally and also for allergists/immunologists. The Pegaso low-care COVID center's experience in managing a low-care center for COVID-19 patients was reported, trying to bring out the relevance of this type of structure in reducing the length of stay of patients in high-care settings with the consequent effect of avoiding the collapse of major hospitals. The experience of managing a low-care setting with a day hospital service inside emphasizes, even more, the role of the allergists/immunologists during the COVID-19 pandemic contributing to keeping the medical staff's specialty in a strategic role in the battle against this common enemy. Sharing all the information on public health organizations is crucial to cope in the best possible way with the present and future challenges.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and paranasal sinuses. Eosinophilic inflammation is described as a common endotype. The anti-interleukin-5 (IL-5) antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe CRSwNP when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, therapy monitoring and follow-up documentation are required, and therapy discontinuation has not been adequately established yet. In this paper, recommendations for monitoring the course and efficacy of therapy as well as for reviewing the duration and possible termination of therapy are provided. For this purpose, a literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching MEDLINE, PubMed, and the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including October 2022 were considered. Based on the international literature and previous experience, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given by an expert panel on the basis of a documentation sheet.

Coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) in March 2020. Despite the availability of therapies and the adoption of security measures, the most effective method to fight COVID-19 remains the induction of immunity through vaccines. Scientific communities have developed several types of COVID-19 vaccines since the beginning of the pandemic, including those with innovative messenger RNA (mRNA) technology. Patients with a history of allergic reactions may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Therefore, it is important that these patients are evaluated by an allergist to help monitor immediate-type adverse reactions and identify what vaccine component may elicit an allergic reaction. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination in high-risk patients, administering a different vaccine for the second dose in subjects reporting adverse reactions to the first dose, fractional dosing, or pretreating with anti-immunoglobulin E (IgE) monoclonal antibody. The scope of this review is to evaluate, through current evidence available in the literature, the accuracy of skin testing to the excipients of COVID-19 vaccines, especially polyethylene glycol (PEG) and polysorbate, in predicting allergic reactions to vaccination, despite the existing discordance of data and approaches to the question from the various clinical experiences, as to permit the safe administration of COVID-19 vaccines to populations around the globe.

Food allergy is characterized by an abnormal immune reaction that occurs reproducibly upon exposure to a specific food. This immune response can lead to a variety of symptoms, the prevalence of food allergies has increased in recent decades, most likely due to environmental factors that likely play a role in the expression of genetic susceptibility. Recent understanding of the immunopathogenesis of allergic diseases has suggested that these atopic diseases may be due to monogenic mutations associated with inborn errors of immunity (IEI). Aspects to be assessed in suspected IEI involve the onset of atopic disease within the initial months of life, the progression of the condition, and the response to conventional therapy. A prospective study was conducted on 385 patients admitted to the clinic with suspected immunodeficiency. Most children were referred for recurrent respiratory infections, but almost half had concurrent atopy (44%), atopy and autoimmunity (3%), autoimmunity (6%) and malignancy (1%). The results of the study underline the importance of the allergic phenotype and suggest that children with more severe allergic diseases should be screened for possible underlying inborn defects of immunity. If a congenital disorder of immunity is suspected, comprehensive immunologic testing is required, and genetic testing is essential to identify the specific genetic abnormalities. Molecular diagnosis provides a comprehensive understanding of congenital immune disorders, allowing tailored interventions and personalized surveillance strategies.

Allergen-specific immunotherapy for inhalant allergies, using allergen extracts of proven value, is highly effective in selected patients with allergic rhinoconjunctivitis and allergic asthma. Both subcutaneous and sublingual immunotherapy (SLIT) have been shown to modify the underlying cause of the disease, with long-term clinical benefits that persist for years after their discontinuation. Real-world studies have confirmed the long-term efficacy of allergen immunotherapy in allergic rhinitis (AR) and asthma and shown a reduction in the incidence of lower respiratory tract infections. Sublingual house dust mite (HDM) immunotherapy has been suggested to improve innate antiviral immunity—a likely explanation for this finding. Based on robust randomized controlled trials, the Global Initiative for Asthma (GINA) guideline has incorporated the use of SILT for the treatment of adults with HDM-driven asthma and concomitant AR, with sub-optimal control, regardless of the use of low-to-high doses of inhaled corticosteroids, as long as the patient’s forced expiratory volume in 1 second (FEV₁) is > 70%.

Respiratory changes are often associated with anxiety disorders, particularly panic disorder (PD). Individuals experiencing PD are subjected to unexpected panic attacks, marked by overwhelming anxiety and fear, leading to a variety of autonomic and respiratory symptoms. PD patients have increased sensitivity to carbon dioxide (CO₂). In response to respiratory stimulants like CO₂, patients with PD tend to hyperventilate and panic, triggering the activation of an excessively reactive fear network. While their respiratory physiology may appear normal, the presence of subtle breathing abnormalities and other functions related to bodily homeostasis. This fear network, comprising the hippocampus, medial prefrontal cortex, amygdala, and its connections to the brainstem, seems to be hypersensitive in PD’s patients. This review aims to present a comprehensive overview of the current landscape on the link between PD and respiratory disorders. In July 2023 a literature search was undertaken for articles examining the relationship between PD, respiratory disorders, and psychological implications. Multiple databases were searched: PubMed, PubMed Central, PsycINFO, Web of Science, Elsevier Journal, Health & Medical Collection, and Springer. The analysis of six studies focused on the correlation between PD and asthma revealed important links between these two disorders. Anxiety and panic can have significant impacts on the manifestation and aggravation of asthma. Furthermore, the review indicates that psychological therapeutic approaches, in particular cognitive-behavioral therapy, may represent a valid intervention to improve clinical outcomes in patients suffering from both disorders. Future investigations in this field may help highlight new intervention strategies in the psychological area to help individuals with PD decrease concomitant asthma, significantly improving their quality of life.

Nutritional therapy through exclusive enteral nutrition (EEN) is successful with Crohn’s disease (CD), but most patients relapse when returning to a normal diet. Personalized and sustainable diets over time have not been tried. This pioneering case report shows the successful response to the use of a skin prick test (SPT) with a 0.5 mm cutoff and a combination of parameters to guide the diet of a child with CD, ensuring continued remission and a regular diet over a follow-up period of 3 years. The 5-year-old patient had a history of chronic diarrhea. Laboratory showed anemia, hypoalbuminemia, high erythrocyte sedimentation rate (ESR), and fecal calprotectin (FCP) > 2,100 µg/g. Endoscopies revealed duodenal ulcer scar and ulcerative pancolitis. Simple endoscopic score for CD score (SES-CD) = 16 (severe). Pathology showed CD. EEN started with a polymeric formula, later moving to an elemental formula due to a suboptimal response. Medication included prednisolone, mesalazine, azathioprine, and methotrexate. Foods were introduced guided by the SPT and included 54 protein extracts from food tested every 3–4 months. The patient has clinical and histological remission despite having lamb, turkey, eggs, cereals (including wheat), and fish in his diet. FCP has been measured with every change in diet and maintained at < 100 µg/g with the reintroduction of food, with the exception of fish and eggs which, despite a negative SPT, gave mild symptoms and raised FCP to 223 µg/g. Both eggs and fish were successfully reintroduced (FCP < 100 µg/g) after 7 and 11 months respectively from failed reintroduction. This innovative approach based on SPT and strict clinical and follow-up inflammatory markers can potentially ensure remission, reintroducing foods with objective parameters, and improving the patient’s quality of life.