Allergies, Volume 5, Issue 4 (December 2025) – 13 articles

Shellfish allergy is among the most common food allergies (FAs) worldwide and represents a severe immunoglobulin E (IgE)-mediated FA with tropomyosin functioning as the predominant pan-allergen. Current management of shellfish allergies is strictly palliative with allergen avoidance, underscoring the critical need for disease-modifying therapies. While conventional allergen-specific immunotherapy (AIT) approaches, namely oral and sublingual immunotherapies, demonstrate capacity for desensitization, more clinical applications are needed in the potential safety concerns and prolonged treatment durations. Innovative treatments, such as the design of modified shellfish allergens, DNA vaccine technologies, and nanoparticle-based delivery platforms such as virus-like particles (VLP), show efficacy and potential in inducing protective antibodies while promoting antigen-specific immune tolerance with reduced allergenic risks. These innovative approaches hint at a promising pathway in achieving safe, effective, and long-lasting clinical tolerance for shellfish allergy. This review describes the current perspectives on allergen immunotherapy regarding shellfish allergy and analyzes emerging therapeutic strategies poised to overcome these limitations. Full article

Pediatric food allergies are an escalating public health concern, with nut allergies representing a primary cause of persistent hypersensitivity and anaphylaxis. New data suggests that pediatric populations with multiple nut allergies (MNA) may be at higher anaphylaxis risk than their counterparts with single nut allergies. Despite this, there is an absence of literature posing multiple nut allergies against singular nut allergy cases. The majority of the research in this topic is directed towards singular nut allergy, without any differentiation between children with one versus multiple sensitivities. Epidemiological evidence indicates that multiple nut allergies are associated with lifelong sensitization, high cross-reactivity potential and increased risk and severity of reactions. Compounding clinical risk factors reinforce the already high risk associated with MNA and indicate that these children require careful monitoring and individual management. Diagnostic tools, including component-resolved diagnostics and oral food challenges, enable differentiation between true multi-nut sensitization and cross-reactivity, guiding targeted interventions. Management strategies must therefore be multifaceted, encompassing selective allergen avoidance, emergency preparedness with epinephrine auto-injectors, asthma control, nutritional support, and psychosocial care. Recognizing MNA as a distinct, high-risk phenotype highlights the necessity of precision-based, biomarker-driven clinical approaches to optimize safety, reduce morbidity, and improve quality of life for affected pediatric populations. Full article

Alpha-gal syndrome (AGS) is an emerging, relatively newly recognized allergic disorder with clinical manifestations that occur as a result of hypersensitivity reactions to oligosaccharide galactose-α-1,3-galactose (α-gal), a carbohydrate present in lower-mammalian meat, dairy products, and some biopharmaceutical products. These reactions are delayed with oral ingestion of the antigen but can be immediate with intravascular or other parenteral antigenic exposure. Over the past 15 years, many revelations have occurred in the realm of AGS. However, there is still a huge unmet need related to its pathophysiology, diagnostics, timely recognition, and management. This article is geared towards providing a review of AGS for healthcare providers (HCPs) from all realms of medicine. It is a universal challenge, with cases being recognized from various parts of the world. Hence, it is critically important for HCPs planet-wide to pay heed to the prompt recognition of AGS and educate their patients. This can prevent morbidity as well as potentially fatal complications like severe anaphylaxis. It is a narrative clinical review. The PubMed database was searched from 2009 to 2025. Alpha-gal syndrome and related topics were included in the search engine. Full article

Background: Pruritus is burdensome across dermatoses. Beyond Staphylococcus, broader components of the cutaneous microbiome—bacteria, fungi, and viruses—and their products shape itch via barrier disruption, immune polarization, and direct neurosensory activation. Methods: We conducted a narrative review of human and translational studies. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 27 August 2025 using terms for itch, skin microbiome, bacteriotherapy, proteases, PAR, TRP channels, IL-31, Malassezia, and AHR ligands. English and Italian records were screened; randomized trials, systematic reviews, and mechanistic studies were prioritized; and unsupported single case reports were excluded. Results: Beyond Staphylococcus aureus, microbial drivers include secreted proteases activating PAR-2/4; pore-forming peptides and toxins engaging MRGPRs and sensitizing TRPV1/TRPA1; and metabolites, especially tryptophan-derived AHR ligands, that recalibrate barrier and neuro-immune circuits. Commensal taxa can restore epidermal lipids, tight junctions, and antimicrobial peptides. Early studies of topical live biotherapeutics—Roseomonas mucosa and Staphylococcus hominis A9—report reductions in disease severity and itch. Fungal communities, particularly Malassezia, contribute via lipases and bioactive metabolites with context-dependent effects. Across studies, heterogeneous itch metrics, small samples, and short follow-up limit certainty. Conclusions: The cutaneous microbiome actively contributes to itch and is targetable. Future studies should prioritize standardized itch endpoints, responder stratification, and robust safety for live biotherapeutics. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by pruritus and eczematous lesions that significantly impacts patient quality of life. This review covers the intricate interplay of barrier dysfunction, immune dysregulation, and microbial dysbiosis in the complex pathophysiology of AD. The roles of epigenetic factors and environmental exposures are also examined. The evolving understanding of these factors has revolutionized AD treatment. Beyond foundational topical agents, the landscape for moderate-to-severe AD treatment is now dominated by highly targeted immunotherapies, such as biologics and Janus Kinase (JAK) inhibitors, that precisely block specific inflammatory pathways. Emerging strategies explore microbiome modulation and vitamin D supplementation. This paradigm shift from broad immunosuppression to precision medicine offers improved disease control and reduced systemic toxicities and enables more personalized AD management, significantly benefiting patients. Full article

Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are common comorbid sinonasal conditions. CRS is classically divided into two distinct phenotypes: CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP). The purpose of this retrospective observational study is to determine whether aeroallergen sensitization profiles in patients with comorbid CRS and AR can distinguish between CRSwNP and CRSsNP. A total of 241 patients diagnosed with comorbid CRS and AR who underwent skin prick testing or in vitro allergy testing in a single tertiary rhinology practice were included for evaluation. The rates of allergen-specific sensitizations in CRSwNP patients were compared with those in CRSsNP patients. Of the allergens tested in the routine panels, Dermatophagoides pteronyssinus (OR = 1.82, p = 0.03), Alternaria (OR = 2.55, p < 0.01), and animal dander (OR = 1.48 for cat and OR = 3.01 for dog, p < 0.01) were predictive of CRSwNP. Sensitization to any grass allergen was also predictive of CRSwNP (OR = 2.09, p < 0.01). Multiple perennial aeroallergens showed strong associations with CRSwNP; however, broad sensitization to perennial allergens as a whole group was not significantly predictive of CRSwNP (OR = 1.83, p = 0.22). Full article

Severe asthma is a heterogeneous condition often resistant to conventional corticosteroid therapy, necessitating the identification of novel biomarkers and therapeutic targets. This study investigates immunological, transcriptional, and proteomic biomarkers in severe asthma patients from the Brazilian ProAR cohort. Cytokines were measured using a multiplex technology and the differential sputum cell count was performed by cytospin preparations. Sputum transcriptomics was performed by RNA-seq using Ion S5 next-generation sequencing platform. The proteomic study of sputum was performed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) using Q Exactive Orbitrap technology. Compared to mild-to-moderate asthma (MMA) and treatment-controlled severe asthma (SAC), the treatment-resistant severe asthma (SAR) group exhibited increased sputum neutrophilia, eosinophilia, and elevated IL-6 and TNF levels, correlating with impaired lung function. Transcriptomic and proteomic analyses revealed a Th2-independent molecular signature characterized by downregulation of the Hippo signaling pathway and upregulation of JAK–STAT inflammatory cascades. Distinctive microRNA profiles suggest regulatory involvement in inflammatory and proliferative processes. These findings align with prior studies, reinforcing the presence of an IL-6- and TNF-high severe asthma phenotype across diverse populations. Our results highlight key inflammatory pathways that may underlie corticosteroid resistance, offering potential targets for personalized therapeutic interventions in severe asthma. Full article

Atopic eczema is the most prevalent chronic dermatitis in childhood, characterised by relapsing pruritic lesions and significant heterogeneity in clinical expression and immunological profile. The disease impacts quality of life and healthcare systems, especially when persistent into adulthood. Epidemiological data from the International Study of Asthma and Allergies in Childhood (ISAAC) demonstrate significant geographic and temporal variability in the prevalence of atopic eczema, with an overall upward trend observed in paediatric populations across most regions. A systematic literature search was conducted in PubMed, ScienceDirect, and the Cochrane Library to identify relevant studies published between 1990 and 2025. Seven studies met the inclusion criteria—six cross-sectional and one prospective—conducted in the urban centres of Athens, Thessaloniki, and Patras. Sample sizes ranged from 517 to 3076 participants, encompassing children and adolescents aged 6 to 17. Prevalence rates ranged from 4.5% to 16.1% in children and 8.9% in adolescents, with notable geographic and temporal variability. Male sex, younger age, environmental exposures, and a family history of atopic diseases were identified as key risk factors. Comparative data from European studies reflect similar trends, with increasing atopic eczema prevalence and plateauing asthma rates suggesting distinct etiological pathways. The psychosocial and economic burden of atopic eczema remains substantial, highlighting the need for early recognition and effective management. Despite methodological variability and limitations in study design, findings indicate an underestimation of atopic eczema prevalence in Greece and underscore the importance of standardised epidemiologic surveillance. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder increasingly recognized for its association with psychiatric comorbidities. However, the extent of this association compared to dermatologic controls in Asian populations remains underexplored. We sought to evaluate the prevalence and risk of psychiatric comorbidities in adult patients with AD compared to those with melanocytic naevi using a nationwide population-based cohort. Methods: We conducted a retrospective cohort study utilizing the Korean National Health Insurance Service (NHIS) database, including individuals diagnosed with AD (ICD-10 code L20.0) or melanocytic naevi (ICD-10 code D22, excluding melanoma) between 1 January 2010 and 31 December 2023. Patients were required to have at least five years of diagnostic history and be 25 years or older at the end of the study. Psychiatric comorbidities were identified based on ICD-10 codes. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to compare psychiatric morbidity between groups. Results: Among 1,902,114 individuals (1,813,320 with AD and 88,794 with naevi), psychiatric comorbidities were more prevalent in the AD group (28.2%) compared to the naevi group (27.1%) (adjusted OR 1.04, 95% CI 1.02–1.05). While differences for major depression, bipolar disorder, and personality disorders were not statistically significant, other psychiatric categories suggested significantly higher prevalence in the AD group. Sex-stratified analysis revealed a higher overall psychiatric morbidity in women compared to men; however, the relative risk increase associated with AD was slightly greater in men than in women. Comparison with previous international studies suggests that Korea’s healthcare accessibility and nationwide mental health programs may contribute to the smaller observed difference. Conclusions: This large-scale cohort study highlights a modest but significant association between AD and psychiatric comorbidities in adults. Our findings underscore the importance of integrating mental health assessment into routine dermatologic care for AD patients to improve comprehensive disease management. Full article

Glucocorticoids (GCs) remain the cornerstone of asthma treatment due to their potent anti-inflammatory and eosinophil-suppressive effects in the airways, including the induction of peripheral eosinophil apoptosis and downregulation of type 2 cytokine signaling. However, emerging evidence reveals a paradoxical role for GCs in the bone marrow, where they enhance eosinophil production (eosinopoiesis), especially under allergic, infectious, or surgical stress conditions. This duality reflects a complex immunoendocrine interplay involving GC-induced modulation of eosinophil progenitor survival, proliferation, and responsiveness to eosinopoietic cytokines such as interleukin-5 and granulocyte-macrophage colony-stimulating factor. Furthermore, GCs synergize with lipid mediators like cysteinyl-leukotrienes and prostaglandins, modulating both transcriptional and adhesion molecule profiles that prime eosinophil precursors for migration and differentiation. This review examines the molecular and cellular mechanisms underlying GC-induced eosinopoiesis, its functional link to airway inflammation, and its clinical implications for asthma management. We also explore potential therapeutic strategies aimed at selectively modulating bone marrow eosinophil output without compromising the peripheral anti-inflammatory benefits of GCs. Understanding this paradoxical duality holds significant translational potential for improving disease control and preventing asthma exacerbations. Full article

Both allergic rhinitis and chronic rhinosinusitis with or without nasal polyps have important factors in common with asthma. They are often present simultaneously, they have similar pathogenesis processes, and they have synergistic effects on the clinical manifestations. There are also important considerations regarding the common treatment of these pathologies. Taking all these into account, it is possible to place these diseases under the “united airway disease” umbrella. However, matters such as embryologic origins, anatomy and function of the upper and lower airways, as well as cases where the aforementioned pathologies can be observed independently and have different treatment responses, make up reasonable counterarguments for the “united airway disease”. This narrative review attempts to put all these factors into perspective for a slightly better understanding of the complexity of this topic. We will take into consideration factors such as epidemiological data, pathogenesis and pathology, clinical considerations, and the benefits of a common treatment. Full article

This study aimed to evaluate the effects of different dosimetric parameters of photobiomodulation therapy (PBMT) in an experimental model of chronic obstructive pulmonary disease (COPD). C57BL/6 mice were assigned to the following groups: Baseline, COPD, and COPD treated with PBMT at doses of 1 J, 3 J, 5 J, and 7.5 J. Treatment was performed using a diode laser (660 nm, 100 mW) applied for 10 s, 30 s, 50 s, and 120 s, respectively, over 15 consecutive days. COPD was induced by orotracheal instillation of cigarette smoke extract twice weekly for 45 days. Analyses included total cell count, immune cell profiling by flow cytometry, pulmonary infiltration of inflammatory markers, necrosis, apoptosis, and reactive oxygen species (ROS) production. Data were analyzed using one-way ANOVA followed by the Newman–Keuls post hoc test, with statistical significance set at p < 0.05. PBMT significantly reduced inflammatory cell infiltration, with the most pronounced anti-inflammatory effects observed at doses of 1 J and 3 J, highlighting the importance of appropriate dosimetry in optimizing the therapeutic outcomes of PBMT for COPD. Full article

Pruritus (itching) is an underrecognized but often debilitating symptom in patients with central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). It is often considered a paroxysmal symptom. Although less studied than pain or spasticity, pruritus can significantly impair the quality of life. This review aims to provide a comprehensive overview of the pathophysiological mechanisms underlying pruritus in demyelinating CNS disorders, its clinical presentations, and the available treatment options. We explore the central origins of neuropathic itch, focusing on spinal cord, brainstem, and cerebral lesions, with particular emphasis on white matter involvement and spinothalamic tract dysfunction. In addition, we review pruritus triggered or exacerbated by disease-modifying therapies (DMTs) used in MS and NMOSD. Full article