A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

United States Drug Allergy Registry (USDAR) grading scale for immediate drug reactions.

BACKGROUND: There is no accepted grading system classifying the severity of immediate reactions to drugs. OBJECTIVE: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium. METHODS: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research. RESULTS: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis. CONCLUSION: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice.

Direct challenges are the gold standard for most antibiotic allergy evaluations.

Antibiotic allergies are frequently encountered in clinical practice, and delabeling of these allergies has individual and public health benefits. This review focuses on the evidence supporting graded challenges without preceding skin testing in adult and pediatric patients to the major groups of antibiotics including penicillins, cephalosporins, sulfamethoxazole, fluoroquinolones, tetracyclines, macrolides, metronidazole, carbapenems, and aztreonam. The cost savings, time savings, and evidence for performing graded challenges outside of an allergy/immunology office are also reviewed for graded challenges to penicillins.

Outcomes of oral food challenges in a real-world setting, with predictors of outcomes.

BACKGROUND: Oral food challenge (OFC) remains the reference standard for food allergy (FA) diagnosis. OBJECTIVE: This study reports a single-center observational experience with all OFCs conducted over 3 years. METHODS: All OFCs performed at an outpatient office were tracked. The OFCs were conducted without strict prespecified inclusion or exclusion criteria. Demographic information along with results of diagnostic testing and results of the OFCs were recorded. RESULTS: A total of 1132 OFCs were performed, with a median age of 4 years (interquartile range = 2.0-10.0). Of the 1132 OFCs, 862 (76.1%) tolerated the food, whereas 232 (20.5%) experienced a reaction, and 38 (3.4%) did not complete the OFC because of food refusal. The highest percentage of tolerated food was shellfish (91.1%), with the lowest percentage of tolerated food being baked egg (66.1%). There were 66 (5.8%) OFCs that were deemed to be high risk, of which 35 (53.0%) tolerated the food. More than 50% of reactions occurred on the first or second dose, with the most common clinical symptom being urticaria or angioedema, with 29.2% of reactions treated with epinephrine. There were several factors that predicted tolerating an OFC, including the food challenge, the reason for food avoidance, older age at the time of OFC and less reactive skin prick testing, and lower food-specific immunoglobulin E levels. CONCLUSION: Certain factors can predict tolerating an OFC, and even those considered to be high risk can be safely completed in an outpatient setting, with most tolerating the food, and most reactions not requiring treatment with epinephrine.

Drug allergy in older adults: A study from the United States Drug Allergy Registry.

BACKGROUND: Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown. OBJECTIVE: To assess the characteristics and outcomes of drug allergy evaluations in older adults. METHODS: We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics. RESULTS: Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved. CONCLUSION: Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels.

The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies.

The primary factor that limits long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD continues to evolve. Consensus definitions of CLAD and the major CLAD phenotypes were recently updated and clarified, but it remains to be seen whether the current definitions will lead to advances in management or impact care. Understanding the potential differences in pathogenesis for each CLAD phenotype may lead to novel therapeutic strategies, including precision medicine. Recognition of CLAD risk factors may lead to earlier interventions to mitigate risk, or to avoid risk factors all together, to prevent the development of CLAD. Unfortunately, currently available therapies for CLAD are usually not effective. However, novel therapeutics aimed at both prevention and treatment are currently under investigation. We provide an overview of the updates to CLAD-related terminology, clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential strategies to treat and prevent CLAD.

Real-world tree nut consumption in peanut-allergic individuals.

BACKGROUND: Individuals with peanut allergy often avoid tree nuts, yet true rates of tree nut allergy in peanut-allergic individuals are as low as 7%. OBJECTIVE: To examine tree nut sensitization patterns in peanut-allergic individuals, patient and family choice regarding tree nut consumption, and factors that influence consumption of tree nuts. METHODS: All patients presenting for peanut allergy evaluation to an outpatient allergy office were included during a 4-month period. In addition to demographic information, sensitization to tree nuts and tree nut consumption were collected. Logistic regression was performed to generate odds ratios with 95% CIs in univariate and multivariate analyses for variables that predict tree nut consumption. RESULTS: A total of 258 individuals with peanut allergy were enrolled. Ninety-five (36.8%) consumed all tree nuts ad libitum, 63 (24.4%) consumed some but not all tree nuts, and 100 (38.8%) consumed no tree nuts. Of the 100 electively avoiding all tree nuts, the most commonly reported reason was fear of cross-contact (50%). Although there was no difference between rates of sensitization between individual tree nuts (P = .056), cashew and pistachio had higher serum specific IgE levels compared with other tree nuts (P < .001). The tree nut most commonly consumed by peanut-allergic individuals was almond (P < .001). Consumption of foods with precautionary labeling was the strongest predictor of tree nut consumption in peanut allergic individuals (P < .001) CONCLUSION: Our data highlight the potential for safe introduction of tree nuts in peanut-allergic individuals and indicate that peanut-allergic individuals who consume foods with precautionary labeling are most likely to consume tree nuts.

Efficacy of epinephrine and diphenhydramine rinses in decreasing local reactions to subcutaneous aeroallergen immunotherapy.

Background: Although local reactions (LR) to subcutaneous immunotherapy (SCIT) occur in 26-86% of patients, there are no well-studied strategies to manage LRs. Objective: To complete a prospective, randomized, single-blind, controlled trial that compared pre-rinsing SCIT syringes with diphenhydramine, epinephrine, or placebo in patients who were receiving aeroallergen SCIT and experiencing LRs despite pretreatment with an antihistamine. Methods: Patients ages ≥5 years who were receiving aeroallergen SCIT per a conventional dosing schedule and who were experiencing LRs despite premedicating with an oral antihistamine were randomized to diphenhydramine, epinephrine, or placebo rinse, and were followed up for three subsequent visits. At each visit, the patients were asked (yes or no) if LRs improved. Results: A total of 490 patients were enrolled in the study. Seventy-four of the 490 patients (15.1%) experienced an LR despite pretreatment with an oral antihistamine and were randomized into an intervention group. At visit 1, an epinephrine rinse was strongly associated with decreasing LR compared with both diphenhydramine rinse and placebo (p < 0.001). There was no difference among the intervention groups at visits 2 and 3. In patients who reported a consistent outcome at all three visits, the epinephrine rinse was significantly associated with a decrease in LR compared with both diphenhydramine rinse and placebo rinse (p = 0.05). Conclusion: In patients who received aeroallergen SCIT per a conventional dosing schedule, an epinephrine rinse significantly decreased LR at the first visit, and also within a population that reported a consistent outcome at all three study visits. In patients already premedicating with an oral antihistamine, adding an epinephrine rinse is a safe and effective strategy to decrease LRs to aeroallergen SCIT.

Systemic reactions to subcutaneous immunotherapy: Effects of dosing and aeroallergen content.

BACKGROUND: Systemic reactions are a known risk of subcutaneous immunotherapy (SCIT) for aeroallergens. OBJECTIVE: To identify the dose of SCIT that results in the most systemic reactions to SCIT (SCITSRs) and other risk factors for SCITSRs. METHODS: We performed a retrospective review of all SCIT encounters from 2013 to 2017 at a multisite allergy/immunology practice. SCITSRs were identified from the electronic health record through immunotherapy encounters in which epinephrine was administered. Collected data included patient demographics, the dose of immunotherapy at the time of the SCITSR, the presence or absence of asthma, and aeroallergen content. The control group was generated randomly from the same cohort during the same period. RESULTS: There were 86,949 SCIT visits, with 81 SCITSRs (0.9 per 1000 injections). A total of 77.8% of reactions occurred at a dose of 1:1 0.1 mL and above. The presence of cat (81.5% vs 63.0%, P = .01), dog (67.9% vs 37.0%, P < .001), and grass extracts (85.2% vs 67.5%, P = .01) were associated with SCITSRs. Asthma was not significantly associated with SCITSRs. The presence of dust mites, trees, weeds, and molds was not associated with SCITSRs. There were no months or seasons where SCITSRs were more likely to occur. Individuals who experienced SCITSRs had a mean (SD) higher number of included aeroallergenic groups compared with controls (5.86 [1.88] vs 5.00 [1.92], P < .001). CONCLUSION: Risk factors for SCITSRs in a multisite allergy/immunology practice included administration of the highest immunotherapy doses; inclusion of cat, dog, and grass extracts; and the number of aeroallergenic groups included in the extract. This information helps further characterize risk for patients receiving SCIT.

Allergy topics for dental practitioners.

Penicillin allergy, local anesthetic hypersensitivity, latex allergy, contact hypersensitivity, and anaphylaxis are among the allergic reactions encountered in dental practice. This article reviews the literature pertaining to these important areas of overlap between dentistry and allergy/immunology. The epidemiology, diagnosis, and management of penicillin allergy as it relates to dentistry are reviewed. The relevant literature regarding local anesthetic and latex hypersensitivity is discussed. In addition, the presentation, evaluation, and management of contact hypersensitivity, including that to metals, are addressed. Recognition and appropriate treatment of anaphylaxis also are reviewed. This article will help dentists understand potential areas of comanagement with allergists/immunologists to optimize patient care.

A survey of inpatient practitioner knowledge of penicillin allergy at 2 community teaching hospitals.

BACKGROUND: The negative effect of the penicillin allergy label on antibiotic use and patient outcomes has brought to light the need for thorough penicillin allergy assessments and heightened practitioner education. OBJECTIVE: To evaluate practitioner knowledge of penicillin allergy and the clinical approach to the patients with penicillin allergy. METHODS: An electronic survey was distributed to attending physicians, residents, pharmacists, nurse practitioners, and physician assistants practicing adult inpatient medicine at 2 community-based teaching hospitals from February to April 2016. RESULTS: A total of 276 (39%) of 716 practitioners completed surveys were analyzed. Most respondents were attending physicians (45%) with more than 10 years of experience (53%). Approximately half of the respondents indicated that they were unfamiliar with the rate of cross-reactivity between penicillin and cephalosporin (46%), carbapenem (42%), and monobactam (48%) antibiotics. When evaluating the role of penicillin skin testing and temporary induction of drug tolerance in the case vignettes, only 41% and 19% of respondents appropriately considered these options as the leading antibiotic management plan, respectively. Despite acknowledging the need for allergy/immunology consultation in clinical scenarios, 86% of respondents indicated that they never consult an allergist or immunologist or do so only once per year. Overall, pharmacists had a better understanding of the natural history of penicillin allergy and antibiotic cross-reactivity (P < .05). CONCLUSION: There is an overall limited understanding of the management of patients with a history of penicillin allergy in the hospital setting, where collaborative efforts between allergy and nonallergy health care practitioners are sparse. The expansion of a multidisciplinary approach may optimize antimicrobial prescribing in this subset of patients.