Mast cell activation syndrome (MCAS) is a challenging specialized condition that allergists-immunologists treat in the outpatient setting. Despite the wide prevalence of the disease, clinicians may feel overwhelmed to provide consistent compassionate care for these patients for a multitude of reasons. Patients uniformly describe feeling unheard during a clinical encounter and thereby often end up seeing multiple physicians and specialists which further complicates their medical care. As such, it is important to characterize patients with MCAS accurately, which includes the assessment of coexistent mimicking or confounding conditions to achieve best medical care outcomes.
Hereditary alpha-tryptasemia (HαT) is a common autosomal dominant genetic trait that results from increased copy numbers of the TPSAB1 gene encoding α-tryptase. Studies have shown that increased relative α-tryptase expression can modify mast-cell-mediated reactions and contribute to increased severity of anaphylaxis. HαT is an independent risk modifier for reaction severity in patients with Hymenoptera venom allergy and systemic mastocytosis. Additionally, there is emerging evidence that HαT and α-tryptase expression more generally are also associated with increased risk of severe reactions to other allergens. Tryptase genotyping may be a promising biomarker for risk stratification of IgE-mediated allergic reaction severity in the future.
Allergy to venoms of stinging insects (bees, yellow jackets, hornets, wasps, and stinging ants) causes large local reactions or systemic reactions, including anaphylaxis. Diagnostic evaluation includes skin testing and/or serum venom-specific IgE and basal serum tryptase (to identify underlying mast cell disorders). Patients with sting anaphylaxis should be prescribed epinephrine and venom immunotherapy which prevents allergic reactions in up to 98% of patients. Most patients may safely discontinue venom immunotherapy after 5 years, although high-risk patients need to continue indefinitely. Further research is needed to improve the predictive value of diagnostic testing and the safety and efficacy of treatment.
Anaphylaxis can be caused by several different mechanisms. Novel therapies on the horizon target these numerous pathways, including tyrosine kinase inhibitors, recombinant allergen-specific blocking antibodies, and monoclonals targeting KIT or inhibitory receptors. This article discusses potential new therapies for both the prevention and treatment of anaphylaxis that are currently in clinical development.
Anaphylaxis is a potentially life-threatening allergic reaction that is increasing worldwide. While it is often straightforward to diagnose, at times the diagnosis remains uncertain, especially if there is no clear trigger, symptoms overlap with other conditions, or patients mainly report subjective symptoms without confirmatory physical findings. Unfortunately, there is no gold-standard test for diagnosing anaphylaxis, so clinicians must rely on clinical criteria to assess its likelihood. The first widely accepted clinical criteria were published in 2006 by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network, and in 2020, the World Allergy Organization proposed updates to these criteria. The new 2024 Anaphylaxis Clinical Support Tool addresses discrepanices between previous criteria.
Anaphylaxis is a life-threatening allergic condition that affects all ages, and research suggests that prevalence is increasing worldwide. The changing epidemiology of anaphylaxis is attributable to factors such as improved diagnosis, new drug therapies, climate change, and changes in national and international guidelines. Risk factors for severe and fatal anaphylaxis include older age, lung disease, beta-blockers, angiotensin-converting enzyme inhibitors, cardiovascular disease, and mast cell disorders. Furthermore, epidemiology of anaphylaxis is variable depending on the trigger. Understanding anaphylaxis epidemiology is important to support identification of patients at higher risk and candidates for therapies that can reduce future anaphylaxis risk.
Immediate hypersensitivity reactions (IHRs) to iodinated contrast media generally occur due to non-immunoglobulin E (IgE)-mediated release of histamine and other inflammatory mediators from mast cells and basophils. IgE-mediated reactions have also been described. Although premedication was previously recommended routinely for prior reactors, based on the substantially lower rate of IHR with low osmolar contrast media, premedication has become controversial as to whether the potential for benefit exceeds the potential for harm. Switching contrast agents, skin testing to contrast agents, drug provocation testing, and rapid drug desensitization are additional risk-reduction strategies that can be considered in properly selected patients.
Health equity is achieved when all individuals can reach their full health potential. In food-induced anaphylaxis, this goal remains unmet. Disparities in prevalence, diagnosis, and care are influenced by race, income, and environmental determinants. This article reviews emerging evidence on inequities in food allergy, emphasizing the need to understand who is most affected and why, and outlining strategies to promote equitable prevention and treatment.
Food-induced anaphylaxis incidence rates in 0 to 19 year-olds and 0 to 4 year-olds are reported as 0.2 and 7.0 per 100 person years respectively, with increased hospitalizations reported in the United States. Avoidance has been our traditional approach to prevent food-induced anaphylaxis and it involves reading nutrition labels, understanding forms of allergen exposure, food allergy policies outside the home, and communicating effectively about personal risk. Active approaches have also emerged including oral immunotherapy and omalizumab, which are both Food and Drug Administaration-approved. Many other options are currently in development, for example, epicutaneous immunotherapy, sublingual immunotherapy, and a variety of biologic drugs.
This article examines the evolving understanding of β-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs) in the context of anaphylaxis. While once considered relative or absolute contraindications, current evidence shows minimal absolute risk of severe reactions and supports continuation in most patients, particularly when cardiovascular disease is present. For venom and allergen immunotherapies, large studies and guidelines endorse individualized risk-benefit assessment and shared decision-making. Caution remains for patients with unpredictable anaphylaxis, and glucagon may aid adrenaline-resistant cases in BB users. Discontinuation is rarely necessary, with cardiovascular protection usually outweighing theoretic allergic risk.
Anaphylaxis is a systemic clinical syndrome that rapidly evolves after an exposure to an inciting agent activates effector cells such as mast cells and basophils. Anaphylaxis can be triggered by a wide variety of agents, including drugs. Over the past decade, our understanding of drug-induced anaphylaxis (DIA) has become dramatically more nuanced, with a growing appreciation of multiple endotypes resulting in the phenotype of anaphylaxis. This review will discuss epidemiology, clinical features, mechanisms, clinical evaluation, and management of DIA.
There has been a large amount of research into novel, noninjectable routes of epinephrine recently. These routes, such as intranasal and sublingual, can deliver epinephrine in a needle-free way to achieve similar pharmacokinetics as seen with autoinjectors. In fact, there is now an intranasal epinephrine device available to prescribe patients at-risk for anaphylaxis. Thus, clinicians should be familiar with studies of these new routes of epinephrine delivery and use a shared decision-making approach with patients/families to decide if noninjectable epinephrine is appropriate for them.
This article compares 12 national and international anaphylaxis guidelines published between 2006 and 2025, highlighting evolving methodological frameworks, diagnostic criteria, and treatment approaches. While consensus supports prompt epinephrine use, differences remain in definitions, risk stratification, and post-acute care. Gaps in education, early childhood care protocols, and global harmonization continue to exist. The analysis emphasizes the shift from crisis-based to proactive anaphylaxis management and underscores the need for equity-focused, evidence-based interventions.
This article provides a comparative overview of anaphylaxis management in the community, with a focus on the home, restaurants, school, flight, and workplace settings in Canada, The United State of America, and Europe. While early recognition and prompt epinephrine use are critical, barriers such as underuse of epinephrine auto-injectors, inadequate training, and inconsistent legislation contribute to morbidity and mortality. We conducted a comparative narrative review of anaphylaxis management across community settings, synthesizing evidence from international guidelines, epidemiologic studies, and legislative frameworks. Adapting effective models from school programs to high-risk settings, alongside improved public education, can reduce disparities and improve outcomes.
Allergen immunotherapy is the only treatment modality that can modify severity of allergic rhinitis. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both effective treatment options. SLIT has a better safety profile with rare reports of systemic reaction events. In this article, we will review evidence pertaining to efficacy of individual treatment allergens and assess relative efficacy and safety of SLIT versus SCIT.
Pharmacologic treatment of rhinitis includes intranasal and oral therapies targeting inflammation and histamine activity. Intranasal corticosteroids and non-sedating antihistamines are first-line due to high efficacy and safety. Intranasal ipratropium, cromolyn, and decongestants offer symptom-specific relief. Oral medications such as antihistamines, leukotriene receptor antagonists, decongestants, and corticosteroids, vary in efficacy and side effects. Emerging therapies like biologics and CRTH2/DPP-4 inhibitors show promise in clinical and preclinical studies.
Chronic rhinitis and chronic rhinosinusitis can negatively impact quality of life and lead to the development of asthma, myocardial infarction, stroke, sleep disturbance, learning impairment, anxiety, and depression. This article provides an overview of the differential diagnoses of these 2 conditions, including: antibody deficiencies, defects of mucociliary clearance, obstructive sleep apnea, odontogenic conditions, neoplasms, otologic conditions, eating-related disorders, medication-related conditions, disease mimickers, and headache and facial pain conditions.
