Exploring the spectrum of allergic disorders that continue to challenge the Allergist-Immunologist: From hereditary angioedema to metal implant allergy

In the intricate tapestry of allergic/immunologic disorders, we find ourselves continuously navigating through a diverse array of conditions that characterize our specialty, each presenting its own unique challenges and intricacies. From the hereditary complexities of angioedema to the delicate balance of allergen reactivity patterns in individuals with asthma, our field encapsulates a breadth of knowledge essential for the care of our patients. This editorial aims to illuminate the multifaceted nature of allergy and immunology by delving into topics that range from the complexities of hereditary angioedema (HAE) to the delicate balance of allergen reactivity patterns seen in patients with asthma to the nuances of venom immunotherapy and metal implant reactions. As stewards of patient well-being, it is imperative that we continue to grasp the depth and scope of our specialty, for it is through this understanding that we can better serve those who entrust us with their care.

HAE continues to be a popular topic for the Proceedings, and this issue is no exception.^1–13 Within the pages of this issue, Radojicic and Anderson¹⁴ address the challenging topic of HAE with normal C1 esterase (HAE-nl-C1INH). Because this condition is fraught with diagnostic challenges and poorly evidenced pharmacologic management, the authors conducted a narrative review of practical considerations in the clinical management of HAE-nl-C1INH by using illustrative clinical vignettes to highlight and/or address select challenges. What the readership will find particularly useful from this article is a stepwise approach for diagnosing and managing suspected HAE-nl-C1INH.

Although asthma and allergic rhinitis are closely interrelated, our understanding of allergen skin test reactivity patterns in subjects with asthma remains limited. In addressing this gap, Katial et al.¹⁵ embarked on a comprehensive investigation to elucidate the relationship between skin test responses, asthma severity, disease onset, and immunoglobulin E (IgE) levels. By drawing from a cohort of 500 patients with asthma randomly selected from the National Jewish Health electronic medical record system, their study reveals compelling insights.¹⁵ Remarkably, 86% of the participants presented with rhinitis, whereas 75% tested positive to at least one allergen, with a notable gender disparity that favored higher sensitization rates in men.¹⁵ Furthermore, the study uncovers that positivity for perennial allergens was notably higher in cases of childhood-onset asthma compared with adult-onset asthma. Noteworthy correlations emerged, which demonstrated that elevated serum IgE levels were closely linked with skin test reactivity. These findings underscore the critical role of allergen sensitization in asthma, irrespective of its severity, the presence of concurrent rhinitis symptoms, or the timing of asthma onset.

In continuing with another set of challenges of interlinked respiratory conditions, our understanding of the relationship among upper-airway diseases and asthma and chronic obstructive pulmonary disease (COPD) remains deficient. In addressing this gap, Aydın et al.¹⁶ embarked on a comparative study to assess sinonasal symptoms in patients with asthma and COPD, shedding light on the extent of upper-airway involvement in these conditions. Their study cohort comprised 55 patients with asthma, 33 individuals with COPD, and 24 healthy controls, which yielded intriguing findings.¹⁶ Notably, the prevalence of nasal symptoms soared among the patients with asthma, with an overwhelming 98% reporting such symptoms, a stark contrast to the 52% observed in patients with COPD and a mere 38% in healthy controls.¹⁶ Furthermore, analysis of median 22-item Sino-Nasal Outcome Test scores and rhinosinusitis rates revealed significantly higher values among patients with asthma compared with both patients with COPD and controls. The authors' conclusions underscore a significant association between chronic rhinosinusitis, as diagnosed by guideline criteria, and asthma. This study provides valuable insights into the intricate interplay between upper-airway diseases and respiratory conditions, emphasizing the heightened susceptibility of patients with asthma to sinonasal symptoms and chronic rhinosinusitis.

In advancing our comprehension of upper-airway diseases, Wang et al.¹⁷ embarked on a comparative study aimed at delineating the clinical nuances between seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). Questionnaires with regard to medical history, severity of symptoms, diagnosis, and treatment status were collected from 296 patients with SAR and 448 with PAR.¹⁷ In their analysis of clinical characteristics, the authors found that patients with SAR exhibited more severe overall clinical symptoms than did those with PAR, especially rhinorrhea and ocular symptoms. Their meticulous analysis revealed that the patients with SAR manifested notably more severe overall clinical symptoms compared with their PAR counterparts, with particularly heightened presentations of rhinorrhea and ocular symptoms. This discernment further illuminates the intricate differences between SAR and PAR, offering clinicians a nuanced understanding crucial for tailored management strategies and improved patient care.

In shifting focus to lower respiratory tract diseases in conjunction with immunodeficiency, Onalan et al.¹⁸ delved into the intricate interplay between bronchiectasis and the duration required to attain target trough IgG levels in individuals diagnosed with common variable immunodeficiency (CVID). The authors compared trough IgG levels in 61 patients with CVID, including 21 with bronchiectasis and 40 without bronchiectasis, all of whom had received the same dose of IGRT for 2 years.¹⁸ Their study objectives also extended to elucidating the correlation between IgG levels and infection frequency. Patients with bronchiectasis exhibited significantly lower trough IgG levels and efficacy coupled with a prolonged duration necessary to achieve the target IgG level compared with those without bronchiectasis.¹⁸ This extended duration was markedly associated with heightened infection rates. In light of these findings, the authors stress the profound clinical implications of bronchiectasis, emphasizing its substantial impact on attaining target trough IgG levels and subsequent management strategies in patients with CVID.

The utility of metal patch testing as a preoperative screening tool in patients with orthopedic prosthetic implants is a growing concern that underscores the need for more effective preoperative screening tools. To fill this gap, Taliercio et al.¹⁹ assessed the utility of patch testing in surgical candidates based on a previous reported metal allergy history. In a retrospective review, the authors identified 67 patients who underwent metal patch testing in conjunction with metal implant surgery.¹⁹ Ten patients were surgical candidates without a history of metal sensitivity, 31 were surgical candidates with a history of metal sensitivity, and 26 were postsurgical patients.¹⁹ Twenty-nine of the patients (43%) had positive patch testing results; this included only one (10%) in the presurgical group without a history of metal sensitivity, 17 (55%) in the presurgical group with a history of metal sensitivity, and 11 (42%) in the postsurgical group.¹⁹ The authors conclude that ambiguity persists in the utility of patch testing for surgical decision-making.¹⁹ They suggest that American Contact Dermatitis Society guidelines and coordination of care among the surgeon, allergist, and patient remain the criterion standard of care. In recognizing the significance of these findings for patients who need orthopedic prosthetic implants, this paper was selected for this issue’s “For the Patient” section entitled Metal implant allergy: the diagnostic utility of skin patch testing. This segment, found in the final pages of the print version of this issue and also available online, comprises a one-page article synopsis presented in an easily understandable format designed to assist patients in comprehending the content of the full article.

In transitioning to the realm of Hymenoptera venom immunotherapy Brunetto et al.²⁰ confront the pressing necessity for swift desensitization among patients allergic to Hymenoptera venom, aiming to mitigate the risk of potentially life-threatening anaphylactic reactions. To address this need, the authors explore the safety and efficacy of an accelerated induction protocol by using aluminum hydroxide depot preparations derived from Vespula species or Apis mellifera by using high initial doses. After an induction protocol that started with the highest concentration of depot venom extract of 100,000 standard quality units, they report that this protocol was well tolerated by 19 of 20 patients.²⁰ The authors cautiously conclude that, pending further validation of their work, an accelerated induction protocol by using depot aluminum adsorbed extracts starting with the highest venom concentration could offer an alternative treatment modality for patients needing rapid desensitization to bee and wasp venoms.

In moving next to drug allergy, Genis et al.²¹ address the insufficiency of information and consensus with regard to amphotericin B desensitization protocols within the pediatric population. The authors share their firsthand experience, detailing five successful cases of desensitization by using liposomal amphotericin B. Their meticulous documentation not only adds valuable data to the existing literature but also offers a potential blueprint for the allergist/immunologist who grapples with similar challenges, particularly in the context of fungal infections resistant to alternative antifungal agents. By shedding light on effective desensitization strategies, this work expands our understanding and provides guidance for clinicians navigating the complexities of pediatric drug allergies.

This issue’s Patient-Oriented Problem Solving (POPS) case presentation explores the evaluation and treatment of a 16-year-old boy who presented with septic bursitis, who, due to concern of a penicillin allergy label, was started on a cefepime infusion but developed an immediate cutaneous adverse reaction and periorbital edema. The POPS case presentation is a recurring feature of the Proceedings written by an allergy/immunology fellow-in-training from one of the U.S. allergy/immunology training programs.^22–32 The POPS series aims to provide an innovative and practical learning experience for the allergist/immunologist in training by using a didactic format of clinical presentation and deductive reasoning. In this issue’s POPS, Mari and Banks,³³ from the San Antonio Uniformed Services Health Education Consortium (San Antonio, TX), lead the reader through this learning process, illustrating how removing a penicillin allergy label in a hospitalized adolescent with a remote penicillin and recent cephalosporin allergy can reduce potential harms.

In summary, the collection of articles found within the pages of this issue probes an array of topics surrounding allergic diseases, ranging from the complexities of HAE to the delicate balance of allergen reactivity patterns in patients with asthma to the nuances of venom immunotherapy and metal implant reactions that afflict patients. The diversity of these articles exemplifies how the complexities of allergic disease pathogenesis and development continue to challenge the allergist/immunologist. In keeping with the overall mission of the Proceedings, which is to distribute timely information with regard to advancements in the knowledge and practice of allergy, asthma, and immunology to clinicians entrusted with the care of patients, we hope that the articles found within this issue will continue to foster enhanced patient management and outcomes. On behalf of the Editorial Board, we hope you can make practical use of the diverse literature offered in this issue of the Proceedings.