Pathogenic variant in SERPING1 gene causing autosomal dominant hereditary angioedema in early childhood.

A female in early childhood presented with 6 months of transient swelling of multiple areas of her body, often, but not always, associated with minor trauma. Labs drawn were significant for low C4, low CH50, low C1 esterase inhibitor (C1-INH) antigen and low C1-INH function, which is concerning for hereditary angioedema (HAE) with abnormal C1-INH. Genetic testing through the Invitae Hereditary Angioedema Panel revealed a variant in the SERPING1 gene, c.686-7C>G (Intronic), which was classified as a variant of unknown significance, but is likely pathogenic given patient's clinical presentation and recent functional proof of pathogenicity. HAE should be recognised in paediatric patients even without family history. Recognising the symptoms of HAE and confirming diagnosis in early childhood has become more important recently as the first prophylactic therapy, lanadelumab, was approved in February 2023 for long-term prophylaxis in early childhood, which can significantly improve morbidity and quality of life.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Current and future management of chronic spontaneous urticaria and chronic inducible urticaria.

Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.

Management paradigms for chronic rhinosinusitis in individuals with asthma: An evidence-based review with recommendations.

BACKGROUND: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence-based management strategies for CRS in this population. METHODS: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit-harm assessments, as well as value judgment and recommendations, were provided RESULTS: Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes. CONCLUSION: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status.

Delabeling penicillin and other antibiotic allergies in solid organ transplantation patients.

BACKGROUND: Immunocompromised populations including solid organ transplant (SOT) recipients have a high likelihood of need for antibiotic therapy for treatment of infection as well as for prophylaxis. Antibiotic allergy is commonly reported and often leads to the use of alternative, second-line antibiotics, which have been associated with poor outcomes, increased adverse effects, and higher cost. Formal allergy assessment and allergy testing can serve as an important antimicrobial stewardship tool in optimizing antibiotic regimens for this patient population. METHODS: A PubMed search with relevant keywords was performed. Review of relevant professional society guidelines was also performed. RESULTS: Documented penicillin and sulfonamide allergies are common impediments to the treatment and prophylaxis of immunocompromised populations, but are rarely formally evaluated in practice; however, there is evidence that most patients with documented allergy to these antibiotics can, in fact, tolerate penicillins and sulfonamide antibiotics. Implementation of an antibiotic allergy evaluation and testing program has been shown to increase the use of first-line antibiotics and can be cost saving. CONCLUSION: Antibiotic allergies have significant clinical consequences, especially in immunocompromised populations. Evaluation of these allergies to prevent the avoidance of first-line antibiotics should be a standard part of the workflow for these patients, prior to transplant. Programs can be tailored to the available personnel and resources of the organization.

Efficacy and safety of an e-consult program for COVID-19 vaccine allergy concerns.

Background: Although severe allergic reactions to coronavirus disease 2019 (COVID-19) vaccines are rare, fear of allergic reactions remains a major source of vaccine hesitancy. For concerned patients and providers alike, allergist consultation is recommended for further guidance on the risk of vaccination. The electronic consultation (e-consult) medium has the potential to make this guidance more widely accessible, thereby supporting vaccination efforts. Objective: To determine the safety and efficacy of an e-consult program for COVID-19 vaccine allergy concerns. Methods: We performed a retrospective analysis of a single-center COVID-19 vaccine allergy e-consult program. Data on demographics, allergy history, and outcomes after recommendations were gathered via review of the electronic medical record (EMR). Patients without EMR data available following the e-consult were called to inquire about vaccination status. Results: Our study included 64 patients, most of whom (51.6% [33/64]) had e-consults placed for second-dose concerns. E-consults were completed within 2 days for all patients. The most common recommendation was that patients receive any COVID-19 vaccination available (62.5%, [40/64]). Forty-one patients (64.1%) were vaccinated after receiving recommendations from an allergist, 11 of whom (26.8%) reported a vaccine reaction. Most of these reactions were nonallergic (9/11 [81.2%]). No anaphylactic events were reported. Conclusion: Results of our study suggest that e-consults were a safe and effective method of providing guidance with regard to COVID-19 vaccine risk in patients with concerns about allergic reactions. The efficiency of this medium, highlighted by the 2-day turnaround time in our study, has the potential to expand access to vaccine risk evaluations by board-certified allergist/immunologists.

A Review of Adverse Reactions to Biologics Used in Allergy-Immunology Practice.

Biologic agents have become an integral therapeutic option for practicing allergists-immunologists for the management of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and various immunologic conditions. As these agents vary considerably from traditional small-molecule drugs, various adverse reactions have been noted. A different approach must be used to classify these reactions beyond the classic Gell-Coombs classification system as it does not capture many of the adverse events seen with biologic therapy. This article addresses the available literature on proposed classification systems and diagnostic modalities for adverse events associated with biologics and reviews each approved agent used frequently in allergy-immunology practice.

At-home compounding preparation of slow desensitization of elexacaftor/tezacaftor/ivacaftor for delayed hypersensitivity rash.

As elexacaftor/tezacaftor/ivacaftor has proven to have robust clinical efficacy for eligible persons with cystic fibrosis, desensitization should be offered to those with maculopapular eruption hypersensitivity reactions to achieve tolerance. As presented in this case, if provided with tools for crushing and mixing the medication, a successful escalation protocol can be completed at home without coordinating the help of a compound pharmacy.

Non-IgE-Mediated Drug Hypersensitivity Reactions.

PURPOSE OF REVIEW: Non-IgE-mediated drug reactions have traditionally been poorly defined and studied, though they are the most common form of hypersensitivity. Their presentations are highly variable and can range in severity from mild, cutaneous-only reactions to severe systemic disease. RECENT FINDINGS: The most notable advance in non-IgE-mediated hypersensitivity reactions is in diagnostics. HLA alleles have traditionally been used for identifying certain patients at risk for abacavir hypersensitivity syndrome, but more recent studies have shown several other HLA alleles associated with severe cutaneous adverse reactions with various medications. This article also highlights the use of delayed intradermal testing for radiocontrast media and patch testing for delayed antibiotic reactions. Drug reactions remain a major cause of morbidity and reason for treatment changes. Non-IgE-mediated reactions have had an increase in research interest over the past decade with an increased emphasis on better understanding the clinical presentation and underlying pathophysiology.