Management of Penicillin Allergy in the Perioperative Setting.

The selection of perioperative antibiotic prophylaxis is challenging in patients with a history of penicillin allergy; as such, we present a literature review exploring current best practices and the associated supporting evidence, as well as areas for future research. Guidelines recommend the use of alternative agents in patients with an IgE-mediated hypersensitivity reaction, but those alternative agents are associated with worse outcomes, including an increased risk of surgical site infection, and higher cost. More recent data suggest that the risk of cross-reactivity between penicillins and cephalosporins, particularly cefazolin, is extremely low, and that cefazolin can be used safely in most penicillin-allergic patients. Studies have therefore explored how best to implement first-line cefazolin use in patients with a penicillin allergy label. A variety of interventions, including preoperative allergy de-labeling with incorporation of penicillin skin testing, use of patient risk-stratification questionnaires, and utilization of clinician algorithms to guide antibiotic selection intraoperatively, have all been shown to significantly increase cefazolin utilization without a corresponding increase in adverse events. Further studies are needed to clarify the most effective interventions and implementation strategies, as well as to evaluate whether patients with severe delayed hypersensitivity reactions to penicillin should continue to be excluded from receipt of other beta-lactams.

Disease burden and predictors associated with non-response to antihistamine-based therapy in chronic spontaneous urticaria.

Background: H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses. Objective: To assess the comorbidity burden and healthcare resource utilization (HRU) associated with non-response to H1AH-based treatments; to identify predictors of non-response. Methods: Optum® de-identified Electronic Health Record dataset (2007-2020) was used to identify adult patients with CSU who initiated a H1AH, alone or in combination with other oral non-biologics (index treatment). Based on twelve-month treatment patterns observed after index treatment initiation, patients were categorized as responders (continued index treatment or had only 1 next H1AH treatment without corticosteroids) or non-responders (continued corticosteroids or had 2 or more treatment switches). Patient characteristics and HRU were assessed in the 12 months before (baseline) and ≥12 months after (follow-up) index treatment initiation. Baseline predictors associated with non-response were identified using machine learning. Results: There were 17 062 patients who met inclusion criteria, and 14824 (86.9%) were classified as non-responders. A higher proportion of non-responders had records of CSU-related symptoms, comorbidities, polypharmacy, and certain laboratory tests than responders at baseline. A higher proportion of non-responders than responders visited an allergist or dermatologist during follow-up (59.5% vs 53.0%). Non-responders had a larger increase in hospitalizations (15.7% vs -2.4%) than responders during follow-up vs baseline. Predictors of non-response included index and baseline treatment classes, types of specialists seen, chronic pulmonary disease, depression, and female sex. Conclusion: A large proportion of CSU patients treated with H1AH-based therapies had uncontrolled disease, contributing to increased HRU and patient burden. Non-responders had more comorbidities and HRU at baseline and follow-up, with steep increases in follow-up hospitalizations relative to baseline, highlighting an urgent need for early disease control.

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.

Allergy Electronic Health Record Documentation: A 2022 Work Group Report of the AAAAI Adverse Reactions to Drugs, Biologicals, and Latex Committee.

The allergy section of the electronic health record (EHR) is ideally reviewed and updated by health care workers during routine outpatient visits, emergency room visits, inpatient hospitalizations, and surgical procedures. This EHR section has the potential to help proactively and comprehensively avoid exposures to drugs, contact irritants, foods, and other agents for which, based on an individual's medical history and/or genetics, there is increased risk for adverse outcomes with future exposures. Because clinical decisions are made and clinical decision support is triggered based on allergy details from the EHR, the allergy module needs to provide meaningful, accurate, timely, and comprehensive allergy information. Although the allergy section of the EHR must meet these requirements to guide appropriate clinical decisions and treatment plans, current EHR allergy modules have not achieved this standard. We urge EHR vendors to collaborate with allergists to optimize and modernize allergy documentation. A work group within the Adverse Reactions to Drugs, Biologicals, and Latex Committee of the American Academy of Allergy, Asthma & Immunology was formed to create recommendations for allergy documentation in the EHR. Whereas it is recognized that the term "allergy" is often used incorrectly because most adverse drug reactions (ADRs) are not true immune-mediated hypersensitivity reactions, "allergy" in this article includes allergies and hypersensitivities as well as side effects and intolerances. Our primary objective is to provide guidance for the current state of allergy documentation in the EHR. This guidance includes clarification of the definition of specific ADR types, reconciliation of confirmed ADRs, and removal of disproved or erroneous ADRs. This document includes a proposal for the creation, education, and implementation of a drug allergy labeling system that may allow for more accurate EHR documentation for improved patient safety.

Neuropathic pain and itch: mechanisms in allergic conjunctivitis.

PURPOSE OF REVIEW: Allergic conjunctivitis is highly prevalent and affects up to one third of the general population. The current understanding of the pathophysiology and therapeutic strategies center around the type 2 inflammatory pathway. However, there is an increasing body of evidence that suggests neurogenic mechanisms also play a role in allergic inflammation, with a substantial proportion of allergic conjunctivitis patients experiencing both ocular itch and pain. RECENT FINDINGS: Unmyelinated C fibres on the ocular surface transmit histaminergic itch and can be directly activated by mast cell mediators. The conjunctival mucosa also contains TRPV1+ (histamine-dependent) and TRPA1+ (histamine-independent) neurons that enhance ocular pain and itch in allergic conjunctivitis. Allergen-complexed IgE also binds directly to FcεRI expressed on peripheral neurons. Environmental aeroallergens can also directly stimulate neuronal nociceptors to release inflammatory substances. Allergic inflammation thus stimulates nerve terminals to release vasoactive and inflammatory neuropeptides, leading to a cyclical neuronal dysregulation that augments mast cell activity. These repetitive cycles lead to both peripheral and central sensitization and neuronal plasticity, resulting in decreased itch/pain thresholds and a heightened itch/pain response. SUMMARY: Neurogenic mechanisms including peripheral and central sensitization may drive chronic ocular itch and pain secondary to allergic inflammation. Research into these pathways may help to identify therapeutic targets in allergic conjunctivitis patients with refractory symptoms.

Treatment strategies for postviral olfactory dysfunction: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.

Asthma diagnosis using patient-reported outcome measures and objective diagnostic tests: now and into the future.

PURPOSE OF REVIEW: The global prevalence of asthma continues to increase; however, asthma remains under-diagnosed and under-treated. This results in a significant burden on the healthcare system and preventable patient morbidity and mortality. Over-diagnosis of asthma based on clinical history alone also complicates patient management. This heightens the importance of a prompt and accurate asthma diagnosis. Therefore, a review of the literature was performed regarding both objective diagnostic testing for asthma and using patient-reported outcome measures. RECENT FINDINGS: The cornerstone of asthma diagnosis remains spirometry with testing for bronchodilator reversibility testing for pediatric and adult populations. This test may need to be repeated at multiple time points due to its low sensitivity. Peak flow measurement, fractional exhaled nitric oxide testing, and allergy testing are useful adjuncts to the diagnosis and phenotyping of asthma. Bronchoprovocation testing is reserved for people with high clinical suspicion for asthma, but negative spirometry. Novel noninvasive testing modalities may play a diagnostic role in the future. The advent of remote digital health monitoring technology has resulted in revisiting patient-reported outcome measures for the diagnosis and monitoring of asthma. SUMMARY: Overall, improved diagnostic tools for asthma are crucial for earlier recognition and treatment of the disease and improved patient care outcomes worldwide.

Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.

Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Samples of serum and a novel matrix from circulating plasmablasts called "medium-enriched for newly synthesized antibodies" (MENSA) were collected during weeks 1, 2, and 4. Antibodies specific for 10 C. difficile antigens were measured in each sample. Among the 46 C. difficile-infected patients, 9 (19.5%) experienced recurrence within 8 weeks of primary infection. Among the 37 nonrecurrent patients, 23 (62%; 23/37) had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. MENSA and serum levels of immunoglobulin A (IgA) and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer a recurrence. Early identification of patients at risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost, and morbidity due to recurrent CDI.

Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma.

Asthma is a chronic respiratory disease characterized by chronic airway inflammation and airflow obstruction. Up to ten percent of asthmatics have severe asthma, and many remain uncontrolled despite optimal medical management. With our increased understanding of the heterogeneity of asthma and its complex pathophysiology, several biomarkers have been developed and in the recent past, several biologic therapies for severe asthma have been developed and are now in widespread use. Although these biological agents have shown great benefit in treating severe asthma, not all patients respond equally well, and some do not derive any benefit. As much of the current literature of these medications have not assessed biomarkers or have used different cutoffs, it is often challenging to decide the best medication for an individual patient. Here, we review common asthma subtypes, current available biologic therapies for asthma, the clinical application of currently available type 2 biomarkers, as well as summarizing the evidence on how patient characteristics and biomarkers can help with choosing the optimal biologic for a patient that has the highest likelihood of success.

Anatomy of a successful stewardship intervention: Improving perioperative prescribing in penicillin-allergic patients.

OBJECTIVE: To evaluate whether a series of quality improvement interventions to promote safe perioperative use of cephalosporins in penicillin-allergic patients improved use of first-line antibiotics and decreased costs. DESIGN: Before-and-after trial following several educational interventions. SETTING: Academic medical center. PATIENTS: This study included patients undergoing a surgical procedure involving receipt of a perioperative antibiotic other than a penicillin or carbapenem between January 1, 2017, and August 31, 2019. Patients with and without a penicillin allergy label in their electronic medical record were compared with respect to the percentage who received a cephalosporin and average antibiotic cost per patient. METHODS: A multidisciplinary team from infectious diseases, allergy, anesthesiology, surgery, and pharmacy surveyed anesthesiology providers about their use of perioperative cephalosporins in penicillin-allergic patients. Using findings from that survey, the team designed a decision-support algorithm for safe utilization and provided 2 educational forums to introduce this algorithm, emphasizing the safety of cefazolin or cefuroxime in penicillin-allergic patients without history of a severe delayed hypersensitivity reaction. RESULTS: The percentage of penicillin-allergic patients receiving a perioperative cephalosporin improved from ∼34% to >80% following algorithm implementation and the associated educational interventions. This increase in cephalosporin use was associated with a ∼50% reduction in antibiotic cost per penicillin-allergic patient. No significant adverse reactions were reported. CONCLUSIONS: An educational antibiotic stewardship intervention produced a significant change in clinician behavior. A simple intervention can have a significant impact, although further study is needed regarding whether this response is sustained and whether an educational intervention is similarly effective in other healthcare systems.

Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.

BACKGROUND: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes. METHODS: We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients. RESULTS: We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative. CONCLUSION: Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections.

Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa.

Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using VH next generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class switch.

Immediate Reactions After the First Dose of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Messenger RNA Vaccines Do Not Preclude Second-Dose Administration.

Addressing coronavirus disease 2019 (COVID-19) vaccine hesitancy and minimizing potential vaccine contraindications are critical to combatting the pandemic. We describe a practical approach to immediate adverse events after the first dose of messenger RNA vaccines for severe acute respiratory syndrome coronavirus 2, focusing on diagnosis and management of allergic reactions.

One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1-receptor binding domain (RBD) and S1-N-terminal domain. For diagnosis, the combined [IgA + IgG + IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values ≥0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients-a possible source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19-vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2-specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines.