PURPOSE OF REVIEW:Anaphylaxis is a severe type 1 hypersensitivity reaction which is the result of mast cell degranulation causing multiorgan dysfunction. Currently, the most accepted biomarker measurement for mast cell mediated anaphylaxis is serum tryptase measurement. Serum tryptase measurement has limitations including an ideal window of collection during anaphylaxis and must be obtained by venipuncture collection. Urinary mast cell mediators are emerging mast cell biomarkers that can be used for evaluation of mast cell mediated anaphylaxis and mast cell activation. This review will highlight biomarker measurement with urinary mast cell mediators in anaphylaxis. RECENT FINDINGS:This review will highlight biomarker measurement of urinary mast cell mediators including N-methylhistamine, leukotriene E4, and 2,3-dinor-11beta-prostaglandin F2 alpha and their role in anaphylaxis. SUMMARY:Urine mast cell mediator collection obtained during acute anaphylaxis and compared to baseline measurements are emerging biomarkers for the detection of mast cell mediated anaphylaxis. Further research is needed to validate the utility of urinary mast cell mediators in anaphylaxis.
PURPOSE OF REVIEW:Precision allergy molecular diagnostic applications (PAMD@), previously referred to as component-resolved diagnosis (CRD), has progressively transformed the diagnostic approach to anaphylaxis. This review aims to provide an updated overview of its clinical utility, focusing on its role in improving etiologic identification, risk stratification, and patient management in anaphylaxis. RECENT FINDINGS:Advances in molecular allergology have expanded the range of available allergen components and improved the diagnostic accuracy of IgE-mediated testing. Specific molecular patterns are now clearly associated with clinically relevant sensitization and severity risk, particularly in food allergy (e.g. seed storage proteins, nsLTPs), hymenoptera venom allergy, cofactor-enhanced anaphylaxis (e.g. ω-5 gliadin or nsLTP), and delayed red meat allergy (α-gal). PAMD@ has demonstrated higher specificity compared with extract-based tests, allowing better discrimination between true allergy and cross-reactivity, reducing unnecessary dietary restrictions and diagnostic challenges. Emerging evidence also supports its role in guiding allergen immunotherapy and refining risk assessment in complex or idiopathic classified cases. SUMMARY:PAMD@ represents a major step toward precision medicine in anaphylaxis, shifting the paradigm from extract-based sensitization profiling to mechanism-based, clinically actionable diagnosis. Its integration into structured diagnostic algorithms enhances clinical decision-making, supports personalized management strategies, and improves patient safety. However, its optimal use requires careful interpretation within the context of clinical history and local sensitization patterns.
PURPOSE OF REVIEW:Allergen immunotherapy (AIT) remains the only disease-modifying treatment for respiratory allergic diseases and the only intervention capable of preventing systemic sting reactions in patients with venom allergy (VA). This review summarizes recent real-world evidence on the safety of AIT. RECENT FINDINGS:Randomized controlled trials (RCTs) have consistently established the safety of licensed AIT products; however, real-world data are needed to comprehensively evaluate the frequency and severity of adverse events (AEs) and identify risk factors in routine practice. Safety data collection through registries and prospective or retrospective cohorts has confirmed that AIT is generally well tolerated across larger and heterogeneous populations, healthcare settings, and AIT practices. However, rare systemic reactions (SRs) and exceptionally fatal reactions (FRs) continue to occur. Careful pretreatment evaluation and close monitoring remain crucial, particularly during subcutaneous immunotherapy due to the higher risk of systemic reactions. Data on sublingual immunotherapy support a more favourable safety profile, with infrequent systemic reactions and no fatal reactions reported to date. In venom allergy, new evidence on clonal mast cell disorders, hereditary α-tryptasemia and detection of KIT p. D816V in peripheral blood is refining risk stratification. SUMMARY:Systemic and severe adverse events associated with AIT are infrequent. Careful risk stratification and evaluation before initiating immunotherapy can help identify high-risk patients and optimize the benefit-risk balance.
PURPOSE OF REVIEW:The understanding of anaphylaxis has evolved over time beyond the classical IgE-mediated paradigm. This review examines the role of Mas-related G protein-coupled receptor X2 (MRGPRX2) in non-IgE-mediated mast cell activation, a mechanism increasingly recognized in mast cell activation, anaphylaxis, and other mast cell-driven conditions. RECENT FINDINGS:Recent studies have identified MRGPRX2 as a key receptor in rapid mast cell degranulation in response to a broad range of cationic ligands such as drugs, neuropeptides, and host defence-related peptides. Structural and signalling insights have clarified its dual coupling to Gi and Gq pathways. Clinically, MRGPRX2 has been implicated in immediate reactions to antibiotics, neuromuscular blocking agents and other compounds, often occurring upon first exposure. Additionally, emerging evidence suggests roles in chronic urticaria, neurogenic inflammation, and host defence, as well as growing interest in MRGPRX2 as a therapeutic target. SUMMARY:MRGPRX2 represents a paradigm shift in mast cell biology, providing a solid base for non-IgE-mediated hypersensitivity. Improved understanding of this pathway may enhance diagnostic accuracy and enable the development of targeted therapies, although significant challenges remain in distinguishing activation mechanisms in clinical practice.
PURPOSE OF REVIEW:Anaphylaxis is a life-threatening systemic hypersensitivity reaction with highly variable clinical expression and unpredictable severity. Increasing evidence suggests that host-microbiota interactions may contribute to interindividual variability in allergic sensitization and effector responses. This review summarizes current mechanistic, preclinical, and emerging human data supporting a role for the microbiota in modulating anaphylaxis risk and severity. RECENT FINDINGS:Recent experimental studies demonstrate that gut microbial composition and function influence susceptibility to systemic allergic reactions through effects on immune maturation, epithelial barrier integrity, and mast cell biology. Microbiota-derived metabolites, particularly short-chain fatty acids, can directly suppress mast cell activation and degranulation via epigenetic mechanisms. In parallel, preclinical models indicate that dysbiosis exacerbates anaphylactic responses, whereas microbial restoration attenuates disease severity. Emerging translational evidence further suggests that commensal bacteria may directly metabolize food allergens, reducing IgE-binding capacity and effector cell activation. Human studies, although limited, report associations between microbial signatures, allergen-specific IgE levels, and clinical phenotypes, as well as links between microbiota composition and oral immunotherapy outcomes. SUMMARY:Current evidence supports a biologically plausible role for the microbiota in shaping anaphylaxis susceptibility and severity; however, findings remain largely associative. Future longitudinal and mechanistic studies are needed to establish causality and evaluate the translational potential of microbiota-targeted strategies for the prevention and management of anaphylaxis.
PURPOSE OF REVIEW:Anaphylaxis attributable to non-immunoglobulin E (IgE)-mediated mechanisms represents an increasingly recognized and clinically challenging subset of severe hypersensitivity reactions. This review synthesizes recent advances in the understanding of IgE-independent pathways, with emphasis on literature published in the last 18 months, and highlights their implications for precision diagnostics and therapeutic targeting. RECENT FINDINGS:Major IgE-independent mechanisms have attracted substantial recent attention. First, the Mas-related G protein-coupled receptor X2 (MRGPRX2) has been consolidated as a central mediator of IgE-independent drug reactions, with new humanized knock-in mouse models revealing its capacity to amplify both IgE-dependent and IgE-independent systemic anaphylaxis. Second, clonal mast cell disorders-including systemic mastocytosis and monoclonal mast cell activation syndrome-are now recognized as major risk amplifiers for severe and fatal anaphylaxis, particularly following Hymenoptera venom exposure, reinforcing the role of the KIT D816V mutation in lowering the mast cell activation threshold. Third, a comprehensive biomarker meta-analysis confirms that tryptase, platelet-activating factor (PAF), and urinary prostaglandin D2 each contribute differentially to non-IgE reactions, with PAF and PAF-acetylhydrolase emerging as particularly relevant in IgE-independent severity pathways. SUMMARY:Non-IgE-mediated anaphylaxis encompasses mechanistically distinct entities that demand tailored diagnostic algorithms. Recognizing MRGPRX2 activation, complement and IgG-dependent pathways, and clonal mast cell disease in the clinical work-up of unexplained or recurrent anaphylaxis is relevant. Emerging biomarkers and therapeutic targets - including MRGPRX2 antagonists - hold promise for transforming the management of this underdiagnosed condition.
PURPOSE OF REVIEW:Anaphylaxis during pregnancy is uncommon but remains one of the most critical emergencies in obstetric medicine because maternal deterioration and fetal hypoxia evolve simultaneously. Despite established treatment recommendations, diagnostic uncertainty and persistent concerns regarding epinephrine use continue to contribute to jeopardize preventable morbidity/mortality. This review examines recent advances in the recognition, management, and prevention of pregnancy-associated anaphylaxis, with emphasis on emerging concepts that may improve maternal-fetal safety. RECENT FINDINGS:Physiological pregnancy-related cardiovascular and respiratory adaptations can obscure classic manifestations of anaphylaxis, creating important diagnostic blind spots and increasing the risk of delayed recognition. Growing evidence indicates that maternal hypotension and hypoxemia represent the main threats to fetal wellbeing. Epinephrine hesitancy remains common in clinical practice. New insights into mast cell disorders, hereditary alpha-tryptasemia, and MRGPRX2-mediated reactions are refining risk stratification and expanding understanding of severe and perioperative anaphylaxis. Recent epidemiological studies also highlight the predominance of drug-related and cesarean-associated triggers and support the implementation of multidisciplinary care pathways, allergy evaluation, and targeted prevention strategies. SUMMARY:Maternal anaphylaxis should be viewed as a time-critical obstetric emergency in which prompt recognition and immediate epinephrine administration are essential to optimize maternal and fetal outcomes. Future progress will depend on pregnancy-adapted diagnostic approaches, improved risk identification, systematic prevention efforts, and coordinated multidisciplinary management across obstetric, anesthetic, emergency, and allergy services.
PURPOSE OF REVIEW:Biosimilars are increasingly shaping the management of pediatric allergic diseases and offering cost-effective alternatives to originator biology. This review summarizes the scientific and regulatory principles of biosimilars and examines the role of biosimilars in pediatric allergology, focusing on their clinical applications, opportunities, and challenges. RECENT FINDINGS:Biosimilars were developed through a stepwise comparability process, including analytical, pharmacokinetic, pharmacodynamic, and clinical evaluations, to ensure equivalence with reference products. Among pediatric allergies, biologics targeting type 2 inflammation have significantly improved outcomes in several diseases, including asthma, atopic dermatitis, chronic spontaneous urticaria, and food allergies. Omalizumab is currently the only biologic drug with an approved biosimilar that has demonstrated comparable efficacy, safety, and immunogenicity, even after switching. However, concerns remain regarding limited availability of long-term pediatric data. SUMMARY:Biosimilars represent a promising and sustainable opportunity to broaden access to advanced pediatric allergology therapies. Their integration into clinical practice, supported by growing evidence and appropriate clinical governance, has the potential to optimize treatment outcomes and improve long-term disease management. Further evidence on their risk-benefit profiles will help support their effective and informed use in the pediatric population.
PURPOSE OF REVIEW:Antimicrobial resistance (AMR) is increasingly recognised as a global public health emergency that threatens the foundations of modern medicine. While much attention has focused on antimicrobial overuse, under-emphasised drivers such as inaccurate drug allergy labels continue to undermine antibiotic stewardship efforts. Beta-lactam allergy (BLA) labels, particularly penicillin allergy labels, are among the most prevalent and most consequential of these inaccuracies. Mounting evidence demonstrates that the vast majority of individuals labelled as beta-lactam allergic are not truly allergic, yet these labels persist across healthcare systems and generations, driving the use of broader-spectrum, less effective, more toxic and resistance-promoting antibiotics. In this timely review, we argue that beta-lactam de-labelling should no longer be viewed as a niche allergy intervention but as a core antimicrobial stewardship strategy and an ethical obligation in the era of the AMR pandemic. RECENT FINDINGS:Drawing on emerging inpatient and outpatient evidence, including recent paediatric inpatient de-labelling studies, we examine clinical, behavioural, system-level and ethical barriers to de-labelling and propose a reframing of beta-lactam de-labelling as a public health intervention essential for preserving antibiotic effectiveness. SUMMARY:We conclude by outlining policy-relevant recommendations for embedding de-labelling into routine care pathways, particularly in low and middle-income countries (LMICs), where the consequences of AMR are likely to be most severe.
PURPOSE OF REVIEW:Data on pediatric drug-induced anaphylaxis (DIA) are scarce, as drugs are less common triggers of anaphylaxis in children; however, drugs are associated with more severe reactions and unusual presentations. This review summarizes evidence on pediatric DIA, covering epidemiology, clinical manifestations, triggers, and management focusing on pediatric specificities. RECENT FINDINGS:Available data shows that drugs are responsible for up to one-third of childhood anaphylaxis. Approximately half of DIA cases occur in healthcare facilities and triggers vary according to settings. In addition to beta-lactams and NSAIDs, other medications raise concerns in specific populations. Age-dependent and trigger-dependent differences regarding symptoms have been reported. Undertreatment remains a major problem. SUMMARY:The importance of DIA in children increases with age. Boys appear more frequently affected. Diagnosis is clinical but challenging especially in younger age groups and in perioperative settings. Elevated tryptase supports diagnosis but lacks sensitivity. Antibiotics and NSAIDs are major culprits, but in hospitalized patients, anesthetics and chemotherapeutic drugs are also relevant. Vaccines, biologicals, and immunotherapy extracts may be important in pediatric allergy practice. Immediate treatment is adrenaline, largely underused in children, even in hospital settings. All patients with DIA should undergo allergy evaluation to prevent recurrences and overlabeling of drug allergy.
PURPOSE OF REVIEW:Allergic diseases continue to increase globally, and accumulating evidence implicates early-life microbial exposures as central determinants of immune tolerance. This review synthesizes advances from 2024 to 2026 regarding probiotic-mediated immune modulation and their translational implications in allergy prevention and therapy. RECENT FINDINGS:Recent studies confirm strain-specific expansion of Foxp3+ regulatory T cells, suppression of Th2 polarization, reinforcement of epithelial barrier integrity, and durable epigenetic stabilization mediated by short-chain fatty acids such as butyrate. Clinical trials demonstrate benefit in perinatal prevention of atopic dermatitis, modulation of allergic rhinitis symptoms, early-life asthma risk reduction, and probiotic-adjuvanted oral immunotherapy. SUMMARY:Probiotics are evolving from adjunctive supplements to biologically active immune modulators with disease-modifying potential. Integration with allergen immunotherapy and precision microbiome profiling may redefine preventive and therapeutic strategies in allergic disease.
PURPOSE OF REVIEW:Circadian clocks are increasingly recognized as fundamental regulators of innate immune function, yet their relevance to allergy and clinical immunology has only recently been clarified. This review summarizes emerging evidence linking circadian regulation of innate immune cells to allergic inflammation and highlights the translational potential of circadian-informed therapeutic strategies. RECENT FINDINGS:Core clock components are rhythmically expressed in macrophages, mast cells, neutrophils and innate lymphoid cells, where they regulate inflammatory signalling, immunometabolism and activation thresholds. Disruption of these rhythms exaggerates cytokine production, inflammasome activation and mast cell mediator release, contributing to diurnal patterns of allergic disease such as nocturnal asthma. Human and experimental studies demonstrate that circadian misalignment driven by shift work, irregular sleep and mistimed feeding amplifies innate inflammation and worsens allergic outcomes. SUMMARY:Circadian regulation represents an underappreciated dimension of innate immunity in allergic disease. Aligning immunomodulatory therapies, vaccination, and lifestyle interventions with endogenous immune rhythms offers a rational approach to improving efficacy and reducing inflammatory burden. Future studies should prioritize time-stratified clinical trials and direct circadian phenotyping in allergic populations.
PURPOSE OF REVIEW:Drug-induced anaphylaxis during pregnancy, although uncommon, represent potentially serious clinical situation with significant maternal-fetal impact and relevant therapeutic implications. This topic is particularly timely given the need for guidance of health professionals dealing with this challenge and correct labelling patients with drug allergy/hypersensitivity. RECENT FINDINGS:Recent studies report a high prevalence of self-reported β-lactam allergy during pregnancy, with poor correlation with true allergy, underscoring the value of structured, safe, and effective diagnostic evaluation for appropriate delabeling. SUMMARY:These findings highlight the need for a systematic approach to drug-induced anaphylaxis in pregnancy, including accurate diagnosis and protocol-based management. Incorporating allergological evaluation into prenatal care can reduce unnecessary risks, optimize maternal and fetal outcomes, and promote rational medication use. Important knowledge gaps remain, emphasizing the need for prospective studies with standardized methodologies and expanded immunological assessment.
PURPOSE OF REVIEW:Systemic lupus erythematosus (SLE) is typically considered an acquired disease; nevertheless, a growing body of evidence suggests that, particularly in patients with severe disease and early onset, SLE may be due to single-gene mutations. To identify Inborn Error of Immunity genes that can cause monogenic SLE, we conducted a literature review. For each gene, we evaluated the plausibility of the reported association and defined the prevalent pathological pathway implicated in disease pathogenesis. RECENT FINDINGS:In the latest International Union of Immunological Societies (IUIS) classification, SLE is mentioned as a phenotype in only a subset of the genes identified in this review as SLE-related. At least 25 additional genes included in the most recent IUIS classification have also been recently linked to SLE and should be analyzed in patients with suspected monogenic SLE. SUMMARY:Genes related to different immunological pathways (from innate to adaptive immunity) can influence SLE development. A detailed clinical history, including previous infections, and a complete immunological evaluation should be performed in all patients with SLE at diagnosis, especially when monogenic SLE is suspected. Given the large number of genes and pathways associated with SLE, next-generation sequencing should be preferred over Sanger sequencing.
PURPOSE OF REVIEW:Penicillins and other beta-lactam antibiotics are the most frequent drugs involved in allergic drug reactions. Our aim was to outline major questions regarding immediate hypersensitivity reactions with a special focus on amoxicillin, a drug that can induce selective responses, and on the common determinants shared by all penicillins, the structure formed by the beta-lactam ring bound to proteins. This review analyzes recent research and contextualizes the findings in relation to the previous literature, which we define as the classical model. This includes an analysis of antibiotic prescription patterns, clinical entities induced by specific immunoglobulin E antibodies, other proposed mechanisms involved in immediate reactions, and the value of diagnostic tests including drug provocation. RECENT FINDINGS:Amoxicillin, alone or in combination with the beta-lactamase inhibitor clavulanic acid, is the most frequent penicillin involved in hypersensitivity drug reactions in many countries. Early reports of this pattern from Spain have been and continue to be confirmed by other groups. Analysis of the recent literature shows the complexity of this area, notwithstanding the findings of earlier studies, which mainly focused on allergy to penicillin based on the classical concept of major and minor determinants of benzyl penicillin. SUMMARY:The amoxicillin model, together with other drugs in the penicillin group, provides relevant information about what is known and what questions must be addressed in future research on beta-lactam allergies.
PURPOSE OF REVIEW:Modern oncologic therapies, including immune checkpoint inhibitors (ICIs), targeted kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), bispecific antibodies, and adoptive cellular therapies, have transformed cancer care while introducing diverse cutaneous adverse events (cAEs). This review summarizes recent advances in the mechanistic understanding, clinical patterns, and management of dermatologic toxicities associated with contemporary cancer therapeutics. RECENT FINDINGS:Emerging evidence indicates that therapy-associated cAEs often reflect distinct biological mechanisms rather than nonspecific drug reactions. These toxicities can be conceptually organized into four major mechanistic paradigms: immune disinhibition, epithelial signaling inhibition, cytotoxic epithelial injury, and cytokine-driven immune activation. While immune checkpoint inhibitors remain the most extensively characterized model, newer therapeutic platforms, including ADCs and immune-engaging cellular therapies, have introduced additional toxicity patterns that are only beginning to be systematically characterized. Recent clinicopathologic studies have clarified cytotoxic epithelial injury patterns associated with ADCs, while early clinical series suggest cytokine-mediated inflammatory eruptions may occur during cellular immunotherapies. At the same time, advances in immunopathologic profiling have supported the development of mechanism-directed management strategies, including targeted cytokine blockade for steroid-refractory immune-mediated dermatoses. SUMMARY:Cutaneous adverse events associated with modern cancer therapies increasingly represent mechanism-based toxicities linked to therapy-specific biological pathways. Integrating clinical morphology with treatment class and immunologic mechanisms provides a practical framework for diagnosis and management. Mechanism-directed dermatologic care, including early recognition, targeted immunomodulation, and multidisciplinary collaboration, may improve toxicity control while preserving oncologic efficacy.
PURPOSE OF REVIEW:Cutaneous drug hypersensitivity reactions (CDHRs) are immune-mediated adverse events with significant morbidity and mortality. Their diverse clinical presentations, complex pathophysiology, and growing list of causative agents pose considerable diagnostic and therapeutic challenges. This review summarizes recent advances aimed at improving the identification and management of CDHRs. RECENT FINDINGS:A multi-dimensional diagnostic approach is now recommended, integrating detailed clinical phenotyping, validated causality assessment scales, and objective testing - including skin tests, in-vitro assays (e.g. LTT, ELISpot), and pharmacogenomic screening for high-risk HLA alleles. Innovations in test methodology have enhanced diagnostic accuracy. Concurrently, insights into immune mechanisms have driven the development of targeted therapies, such as TNF-α inhibitors, JAK inhibitors, and interleukin antagonists, offering new options for severe or refractory cases. SUMMARY:The integration of optimized diagnostic tools enables more precise identification of culprit drugs. Furthermore, the advent of mechanism-based biologics and small-molecule agents, alongside proactive HLA screening, is shifting the management paradigm from reactive treatment toward precision medicine and primary prevention. These advances collectively aim to reduce the burden of CDHRs, improve patient outcomes, and guide safer prescribing practices.
PURPOSE OF REVIEW:The management of immunoglobulin E (IgE)-mediated allergic diseases and allergen immunotherapy (AIT) is complicated by high interindividual variability and the unavailability of reliable predictive biomarkers. Given the complexity of the immune response underlying these processes, integrating artificial intelligence (AI) could revolutionize the clinical management of these patients. RECENT FINDINGS:Recent literature highlights how machine learning (ML) can efficiently stratify patients by analyzing omics data and molecular sensitization profiles. Models such as long-term memory recurrent neural network and stochastic latent actor-critic enable the prediction of therapeutic adherence, while deep learning (DL) enables the integration of unstructured data from wearable sensors and environmental parameters for real-time monitoring. At the same time, federated learning (FL) is emerging as a crucial solution for multicenter research, ensuring data privacy in compliance with international standards and regulations. Conversely, although generative AI supports the synthesis of clinical records, recent studies highlight its limitations in terms of reliability for direct patient use. SUMMARY:Integrating AI into AIT management could lead to even more efficient precision medicine, improving diagnostic accuracy and predicting therapeutic outcomes. However, while AI serves as a fundamental decision-making aid, specialist supervision remains essential to ensure patient safety and to interpret complex data.
PURPOSE OF REVIEW:In recent years, the global consumption of herbal medicines has been increasing, accompanied by increasing reports of immediate hypersensitivity reactions (IHRs). Given the potential impact on patient safety, there is an increasing need to tighten regulations on herbal medicine use to reduce the incidence of herbal medicine-induced IHRs. Hence, this review consolidates current evidence on the pathophysiological mechanisms, clinical manifestations, and regulatory responses related to IHRs caused by herbal medicines, before providing perspectives for future research in diagnosis, pharmacovigilance, and policymaking. RECENT FINDINGS:Immunoglobulin E (IgE)-mediated and non-IgE-mediated mechanisms are implicated in IHRs. Bioactive constituents and impurities in herbal medicines have been identified as possible causes of IHRs. Clinically, herbal-induced IHRs present with cutaneous, respiratory, and systemic symptoms that may progress to anaphylaxis. Regulatory bodies worldwide have implemented regulatory frameworks and pharmacovigilance systems, however there is still room for improvement. SUMMARY:IHRs to herbal medicines represent a growing safety concern in integrative healthcare. Future research should emphasize mechanistic characterization, improved pharmacovigilance, and well-planned regulation on herbal medicines. Strengthening clinician awareness and adverse-event reporting will be critical to safeguarding patients and ensuring the evidence-based integration of herbal medicines into modern medical practice.
