Food allergy, biologic therapies, and diagnostic precision: Expanding frontiers in allergy and immunology

This issue of Allergy & Asthma Proceedings highlights the evolving breadth and complexity of allergic and immunologic disease, spanning food allergy and anaphylaxis, chronic spontaneous urticaria (CSU), hereditary angioedema (HAE), asthma prevention, biologic therapy during pregnancy, drug hypersensitivity, and medical education. Collectively, the articles underscore the increasingly nuanced interplay among immune dysregulation, environmental exposures, patient-centered outcomes, and health-care disparities. They also reinforce the growing importance of diagnostic precision and individualized management strategies in contemporary allergy/immunology practice.

Previous publications in the pages of the Proceedings have identified food allergy and anaphylaxis as recurrent themes,^1–16 underscoring the continuing clinical importance of these topics to the practicing allergist/immunologist, and this issue is no exception. Among the most intriguing and rapidly evolving food allergy syndromes is galactose-α-1,3-galactose (α-gal) syndrome, a disorder that continues to reshape our understanding of food allergy pathogenesis. In this issue, Platts-Mills et al.¹⁷ review the role of tick bites in the development of immunoglobulin E (IgE) antibodies directed against α-gal, emphasizing the distinctive delayed allergic reactions associated with mammalian meat ingestion. The authors discuss how tick-induced pruritus and basophil infiltration may promote IgE class switching, while also examining the broader epidemiologic implications of expanding deer and lone star tick populations. Their review further revisits the historical association between cetuximab hypersensitivity and α-gal sensitization as well as the biologic importance of α-gal as a major xenotransplantation barrier between primates and pigs.

Additional insights into food allergy diagnostics are provided by Hismiogullari et al.,¹⁸ who evaluated key factors in diagnosing sesame allergy in children. In this retrospective diagnostic accuracy study of 49 children undergoing oral food challenge, tahini-based skin-prick testing (SPT) demonstrated superior predictive performance compared with sesame-specific IgE testing. A tahini SPT cutoff of 7.5 mm provided both high sensitivity and specificity, whereas sesame-specific IgE showed lower diagnostic accuracy. Interestingly, younger children and children with atopic dermatitis were more likely to demonstrate clinical nonreactivity during oral food challenge. The authors conclude that tahini-based SPT may represent a more clinically useful diagnostic tool in pediatric sesame allergy assessment.

In addressing a less common seed allergen, Acikalin et al.¹⁹ present one of the largest pediatric series to date that examined IgE-mediated pumpkin seed allergy. Among the 25 children evaluated, immediate reactions were universal, with anaphylaxis occurring in nearly two-thirds of patients. Atopic comorbidities and co-allergies, particularly to tree nuts and other seeds, were highly prevalent. Notably, pumpkin pulp was tolerated in all the patients, which suggests important distinctions between seed and pulp allergenicity. Their accompanying structured literature review identified only 14 previously reported cases worldwide, which underscores both the rarity and potential severity of pumpkin seed allergy and the need for greater clinician awareness in regions with high seed consumption.

Despite advances in food allergy diagnosis, disparities in food allergy outcomes remain a major public health concern. Esteban et al.²⁰ examine the influence of social contextual factors on food allergy-related emergency department (ED) utilization in children. Their study of 1512 pediatric patients demonstrated higher rates of ED use among Black and Latino children compared with non-Latino White children. However, much of this disparity seemed attributable to social and neighborhood-level determinants, including public insurance status, Supplemental Nutrition Assistance Program participation, and community resource availability. Importantly, disparities were negligible among the children already connected to routine allergy care, which suggests that access to specialty allergy services may represent an important protective factor against food allergy–related emergency utilization.

Liu et al.²¹ also examine important gaps in anaphylaxis management by evaluating national patterns of epinephrine prescribing at discharge among adults treated for anaphylaxis in U.S. EDs. Despite guideline recommendations, only 14% of the patients discharged after anaphylaxis received an epinephrine prescription. Older adults and Hispanic patients were significantly less likely to receive prescriptions, whereas most patients experienced relatively short ED observation periods. The authors conclude that substantial opportunities remain to improve adherence to anaphylaxis discharge guidelines and reduce disparities in emergency allergy care.

For patients with CSU, predicting long-term disease control and understanding the factors that influence remission remain major clinical challenges, particularly in those who require biologic therapy. This issue features two important contributions that address CSU and biologic management. In the first, Savas et al.²² investigated predictors of delayed treatment-free remission in patients with antihistamine-refractory CSU who were receiving omalizumab. Among 163 adults, a longer symptom duration before biologic initiation and the presence of coexisting autoimmune disease independently predicted delayed remission. These findings support the concept that earlier initiation of biologic therapy as well as underlying autoimmune comorbidity may substantially influence long-term disease trajectories in CSU.

In extending these observations beyond disease remission to patient-centered outcomes, Dash et al.²³ prospectively evaluated the relationship between disease activity and quality of life in CSU by using the Urticaria Activity Score over 7 days and the Chronic Urticaria Quality of Life Questionnaire. Although both measures improved substantially over 6 months of therapy, the correlation between symptom activity and quality of life weakened as disease control improved. Analysis of their findings suggest that residual psychosocial burden may persist despite apparent clinical remission, which emphasizes the importance of incorporating both symptom-based assessments and patient-reported quality-of-life measures into comprehensive CSU management.

HAE remains another recurring focus of the Proceedings.^24–39 In this issue, Schmalzried et al.⁴⁰ present a systematic review that evaluated the use of icatibant for acute HAE attacks in pediatric patients. In reviewing three open-label phase III pediatric studies that involved 43 children and adolescents, the authors report rapid symptom relief, favorable tolerability, and the feasibility of self- or caregiver-administration in older pediatric patients.⁴⁰ Although comparative pediatric trials remain limited, analysis of these findings supports icatibant as a practical and targeted therapeutic option for the treatment of acute HAE attacks in children.

The expanding use of biologic therapies across allergic diseases has generated increasing interest in their safety during pregnancy. In this issue, Ventura and Clayton⁴¹ report a multicenter retrospective study that evaluated pregnancy outcomes among patients exposed to dupilumab during pregnancy. Compared with matched controls, patients exposed to dupilumab demonstrated no significant increase in overall pregnancy complications or in maternal-, fetal-, or labor-related adverse outcomes. These findings provide important preliminary reassurance with regard to dupilumab use during pregnancy in patients with asthma, eczema, and eosinophilic esophagitis, while also underscoring the need for larger prospective studies that evaluate long-term maternal and neonatal outcomes.

Drug hypersensitivity and the challenge of distinguishing true allergic reactions from nonimmunologic adverse events remain central concerns in allergy practice. Galata et al.⁴² examined 101 patients referred for suspected local anesthetic hypersensitivity. Despite a broad spectrum of reported reactions, including 18 patients with severe symptoms, they found that immunologically mediated allergy was exceedingly rare. Only one patient demonstrated a positive skin test result, and this patient subsequently tolerated an alternative anesthetic during provocation testing. Their findings reinforce the importance of guideline-based evaluation and a careful clinical history in avoiding unnecessary drug avoidance and procedural delays.

With shifting attention to asthma prevention and modifiable environmental risk factors, Liu et al.⁴³ evaluated dietary patterns and asthma risk among 7216 children by using data from the National Health and Nutrition Examination Survey. Children who consumed a dietary pattern characterized by refined foods, red meat, and high sugar intake demonstrated an increased risk of asthma, whereas a more balanced, fruit- and vegetable-enriched dietary pattern seemed protective, particularly among children 3 to 5 years of age. The authors suggest that early childhood may represent a critical window for dietary interventions to reduce the risk of asthma development.

This issue also addresses an increasingly important aspect of academic medicine and fellowship recruitment in the digital era. Hamid et al.⁴⁴ conducted a national analysis of U.S. allergy and immunology fellowship program web sites, which demonstrated substantial variability in their comprehensiveness. Although most programs provided curriculum and leadership information, fewer included wellness initiatives, alumni outcomes, or trainee demographic data. The authors conclude that improving web site content may enhance recruitment, applicant engagement, and program visibility within an increasingly competitive virtual recruitment environment.

Rounding out this issue is the latest installment in the “Patient-Oriented Problem Solving” series,^{12,16,45–50} which continues to provide a practical educational framework for allergy/immunology fellows-in-training. In this issue, Luu et al.⁵¹ present the case of a 34-year-old woman with cyclical abdominal pain and rash. Through careful clinical reasoning and multidisciplinary evaluation, the authors identify the underlying disorder responsible for the patient’s recurrent symptoms. This case underscores the importance of recognizing cyclical symptom patterns and maintaining a broad differential diagnosis when evaluating complex multisystem allergic presentations.

In summary, the articles featured in this issue collectively highlight the rapidly evolving landscape of allergy and immunology, encompassing food allergy and anaphylaxis, CSU, HAE, asthma prevention, biologic therapies, drug hypersensitivity, health-care disparities, and physician education. Several recurring themes emerge throughout the issue, including the importance of diagnostic precision, the expanding role of biologic therapies, the influence of environmental and social determinants on allergic disease outcomes, and the growing recognition of patient-centered quality-of-life measures in chronic allergic disorders. Together, these contributions reflect the mission of Allergy & Asthma Proceedings: to provide timely, clinically relevant information that advances the science and practice of allergy, asthma, and immunology while ultimately improving patient care.

On behalf of the Editors and Editorial Board, we thank our readers for their continued support and hope that the articles in this issue provide practical insight and value in daily clinical practice.