Animal Models in the Study of Food Allergens: Long-Term Maintenance of Allergic Reactivity in Mouse Models of Food Allergy.

Multiple mouse models have been used to characterize mechanisms of allergic sensitization and anaphylaxis and are widely used for preclinical development of novel therapeutics. However, the majority of published works with mouse models of food allergy have very short intervals between the time of sensitization and the end of the study, and the duration of maintenance of reactivity has not been widely reported. This chapter focuses on two of the most commonly used mouse models with sensitization to peanut or ovalbumin, with the focus on the long-term durability of sensitization to allow for longer therapeutic protocols and assessment of sustained unresponsiveness.

A Mouse Model of Shrimp Allergy with Cross-Reactivity to Crab and Lobster.

Food allergies are a growing public health problem with recent estimates of 10% of the US population affected by this immunologic disease. The quality of life is greatly impaired in food allergic individuals and their caregivers due to constant vigilance and fear of accidental exposure. Shellfish allergies are of particular concern because their prevalence has increased over the past 15 years, now affecting an estimated 3% of the adult population and 1.3% of children in the USA. Additionally, they are rarely outgrown, can result in fatal reactions, and there are no FDA-approved therapies for shellfish allergies. Reactions to one type of shellfish, crustaceans (shrimp, lobster, and crab), can be especially severe. The major crustacean allergens are highly conserved across species, resulting in high cross-reactivity of IgE between shrimp, lobster, and crab in allergic individuals. To develop novel therapies for shellfish allergies, preclinical mouse models are required. In this chapter, we present detailed methodology to induce shrimp allergy in CC027 mice. Once sensitized, mice produce shrimp-specific IgE, that is cross-reactive with lobster and crab, and experience anaphylaxis upon shrimp challenge. This model can be used to further investigate mechanisms of sensitization and preclinical testing of therapies.

Case of Polyethylene Glycol Allergy Confirmed with Basophil Activation Test and Oral Challenge Successfully Immunized with SARS-CoV-2 Vaccine.

Polyethylene glycols (PEG) or macrogols are polymers of ethylene oxide widely used in drugs either as active substances or, more commonly, as excipients. We report a Caucasian 32-year-old woman with referred anaphylaxis almost instantly after oral intake of a macrogol-containing laxative. Despite an anaphylactic reaction, the patient showed negative results for both the skin test and specific IgE to monomer, while the basophil activation test and oral challenge were positive. The patient was later successfully vaccinated with a polysorbate 80-containing SARS-CoV-2 vaccine following an additional work-up. As a result, the inactive form of PEG cannot be fully diagnosed, and it is considered a "hidden" allergen. Allergens like polysorbates need special consideration due to their possible cross-reactivity by their specific derivatives.

Murine model identifies tropomyosin as IgE cross-reactive protein between house dust mite and coho salmon that possibly contributes to the development of salmon allergy.

Background: Recently, we have developed a method to identify IgE cross-reactive allergens. However, the mechanism by which IgE cross-reactive allergens cause food allergy is not yet fully understood how. In this study, we aimed to understand the underlying pathogenesis by identifying food allergens that cross-react with house dust mite allergens in a murine model. Material and methods: Allergenic protein microarray analysis was conducted using serum from mice intraperitoneally injected with Dermatophagoides pteronyssinus (Der p) extract plus alum or alum alone as controls. Der p, Dermatophagoides farinae (Der f), coho salmon extract-sensitized and control mice were analyzed. Serum levels of IgE against Der p, Der f, coho salmon extract, protein fractions of coho salmon extract separated by ammonium sulfate precipitation and anion exchange chromatography, and recombinant coho salmon tropomyosin or actin were measured by an enzyme-linked immunosorbent assay. A murine model of cutaneous anaphylaxis or oral allergy syndrome (OAS) was established in Der p extract-sensitized mice stimulated with coho salmon extract, tropomyosin, or actin. Results: Protein microarray analysis showed that coho salmon-derived proteins were highly bound to serum IgE in Der p extract-sensitized mice. Serum IgE from Der p or Der f extract-sensitized mice was bound to coho salmon extract, whereas serum IgE from coho salmon extract-sensitized mice was bound to Der p or Der f extract. Analysis of the murine model showed that cutaneous anaphylaxis and oral allergic reaction were evident in Der p extract-sensitized mice stimulated by coho salmon extract. Serum IgE from Der p or Der f extract-sensitized mice was bound strongly to protein fractions separated by anion exchange chromatography of coho salmon proteins precipitated with 50% ammonium sulfate, which massively contained the approximately 38 kDa protein. We found that serum IgE from Der p extract-sensitized mice was bound to recombinant coho salmon tropomyosin. Der p extract-sensitized mice exhibited cutaneous anaphylaxis in response to coho salmon tropomyosin. Conclusion: Our results showed IgE cross-reactivity of tropomyosin between Dermatophagoides and coho salmon which illustrates salmon allergy following sensitization with the house dust mite Dermatophagoides. Our method for identifying IgE cross-reactive allergens will help understand the underlying mechanisms of food allergies.

Positive Predictive Values of Anaphylaxis Diagnosis in Claims Data: A Multi-Institutional Study in Taiwan.

Real-world data sources can facilitate essential understanding of the epidemiological features of anaphylaxis. However, the accuracy of case-identifying definitions based on diagnosis codes for anaphylaxis in healthcare databases remains understudied. We conducted a cross-sectional study analyzing claims data from the largest multi-institutional healthcare system in Taiwan during 2017-2021. We included patients with incident anaphylaxis identified by either ICD-10-CM codes for anaphylaxis (Group 1) or ICD-10-CM codes for severe allergic or drug adverse events and additional modifier codes for acute allergy events (Group 2). We randomly selected 20% of the cases to determine the positive predictive value (PPV) of anaphylaxis case-identifying definitions in Groups 1 and 2 after review of electronic medical records by two physicians. From the original cohort (n = 2,176), we randomly selected 433 patients with either a diagnosis of anaphylaxis (Group 1), or a diagnosis of severe allergic and drug adverse events with additional modifier codes for acute allergy events (Group 2). In Group 1, we judged 135 / 170 patients as true anaphylaxis cases, giving a PPV of 79.4% (95% CI: 73.3-85.5). In Group 2, we judged 47 / 263 patients as true anaphylaxis cases, giving a PPV of 17.9% (95% CI: 13.3-22.5). In conclusion, acceptable PPVs were observed when anaphylaxis cases were identified by ICD-10-CM codes for anaphylaxis, but not by ICD-10-CM codes for severe allergic or drug adverse event with additional modifier codes for acute allergy events. Our multi-institutional findings could serve as a fundamental reference for further studies of anaphylaxis based on real-world healthcare databases.

Anaphylaxis following a pleural puncture bringing back a rock water-like liquid.

INTRODUCTION: Anaphylaxis is a life-threatening medical emergency. Its occurrence in the hospital environment should lead to the first evocation of a drug allergy or a latex allergy. However, many other etiologies need to be investigated early. We publish this case report to highlight a rare differential diagnosis of drug allergy, namely hypersensitivity caused by Ecchinoccocus granulosis. CLINICAL CASE: An 18-year-old female patient with no previous pathological history, from a rural environment, consulted for a 4-month history of right basi-thoracic pain without any other associated clinical sign. Her physical examination revealed a right pleuritic syndrome. Chest radiograph showed a right pleural opacity. The patient had a pleural puncture bringing back a rocky water-like fluid. Five minutes later, the patient had an injection of paracetamol to relieve the pain. Thirty minutes later, plaques of urticaria on the extremities and trunk and arterial hypotension occurred. The diagnosis of grade III anaphylaxis was retained. Following vascular filling and administration of antihistamines, the evolution was rapidly favorable. The thoraco-abdominal ultrasound showing the presence of a ruptured liver hydatid cyst in the pleura. A surgical treatment was thus proposed. Despite contact with latex gloves and the administration of paracetamol after surgery, the patient did not present any allergic reaction. Thus the retained cause of the anaphylaxis was ecchinoccocus granulosis. CONCLUSION: Anaphylaxis following a pleural puncture bringing back a rock water-like liquid must suggest the diagnosis of complicated hydatic cyst.

Influencing Children Through the Art of Storytelling Using a Medically-Informed Children's Book.

INTRODUCTION: The purpose of this study is to demonstrate how children learn about a health topic from an interactive reading session. Due to the large number of children with allergies, the specific topic chosen for this research study was peanut allergies. The goal of the project was to educate children on a leading, medically-relevant health topic through a story about a child with a peanut allergy. METHODS: For the purposes of the research project, author Mykayla Vollmer wrote, illustrated, and published the children's book "A Party Without Peanuts: How Food Allergies Affect Friends." The children's book was then read in a group setting at local third grade classrooms and students were provided adequate time to ask questions following the reading session. The students were assessed through both pre- and post-read surveys to evaluate knowledge gained during the session. Specific topics discussed in the reading include allergies, anaphylaxis, preventative measures, and treatments. RESULTS: There was a total of 65 pre- and post- read surveys matched in data analysis. There was a significant increase from a pre-read score of 5.38 (76.92%) to a post-read score of 6.38 (91.21%) for the overall survey with a mean difference of 1.0. In addition to comparing the overall results of the study, each question in the survey was assessed on an individual basis. 4 of the 7 questions demonstrated a significant change in percent of students who answered correctly following the reading session. CONCLUSIONS: The overall findings of the study demonstrated that through interactive readings sessions students significantly increased their scores between pre- and post-read questionnaires. This study serves to encourage the use of children's books as an educational tool for young learners.

Contrast Agent Administration as a Source of Liability: A Legal Database Analysis.

Background Radiology ranks high in terms of specialties implicated in medical malpractice claims. While most radiologists understand the risks of liability for missed findings or lapses of communication, liability for the use of contrast agents in imaging procedures may be underappreciated. Purpose To review the clinical context and outcomes of lawsuits alleging medical malpractice for contrast-related imaging procedures. Materials and Methods Two large U.S. legal databases were queried using the terms "Contrast" and "Radiology OR Radiologist" from database inception to October 31, 2022, to identify cases with published decisions or settlements related to medical malpractice in patients who underwent contrast-related imaging procedures. The search results were screened to include only those cases involving the practice area of health care law where there was at least one claim of medical negligence against a health care institution or provider. Data on the medical complications alleged by patients after contrast agent administration and on the trial were extracted and reported using descriptive statistics. Results A total of 151 published case summaries were included in the analysis. Anaphylactic reaction following contrast agent administration was the most common medical complication observed (30% [45 of 151 cases]), of which failure to diagnose developing anaphylaxis or failure to treat the anaphylactic reaction made up the majority of allegations (93% [42 of 45]). Inappropriate management of contrast media extravasation (27% [41 of 151]) and alleged contrast agent-induced acute kidney injury (13% [19 of 151]) were the next most frequent causes of lawsuits. Of the 11 cases of alleged kidney injury that went to trial, all resulted in a judgment in favor of the defense. Conclusion This study highlights the key reasons for medical malpractice lawsuits associated with use of contrast media and outcomes from these lawsuits. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Trop in this issue.

[Precise diagnosis and management of anaphylaxis based on phenotypes and endotypes].

Anaphylaxis is the most severe allergic reaction, demanding immediate management by health care providers, which is currently underdiagnosed and undertreated in China. In addition to the classic IgE-mediated pathway, non-IgE dependent pathway has also been extensively studied in the pathogenesis of anaphylaxis. Recently, the atypical symptoms induced by widespread used monoclonal antibodies and biologics have been reported. The goal of this article is to recognize the phenotypes (triggers and presentation) and understand its characteristics through endotypes (mechanisms) of anaphylaxis. Ultimately, the aim is to help allergists and health care providers guide a precision approach to diagnose and manage of anaphylaxis.

Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.

Educating Children Through the Art of Storytelling Using a Medically-Informed Children's Book.

INTRODUCTION: The purpose of this study is to demonstrate how children learn about a health topic from an interactive reading session. Due to the large number of children with allergies, the specific topic chosen for this research study was peanut allergies. The goal of the project was to assess how students learn from a children's book. METHODS: For the purposes of the research project, Vollmer wrote, illustrated, and published the children's book "A Party Without Peanuts: How Food Allergies Affect Friends". The children's book was then read in a group setting in third-grade classrooms and a question-and-answer session was held. The students were assessed through both pre- and post-read surveys to evaluate knowledge gained during the session. Specific topics discussed include allergies, anaphylaxis, preventative measures, and treatments. RESULTS: There was a total of 65 pre- and post- read surveys matched in data analysis. There was a significant increase from a pre-read score of 5.38 (76.92%) to a post-read score of 6.38 (91.21%) for the overall survey with a mean difference of 1.0. In addition, each individual question was assessed and it was found that 4 of the 7 questions demonstrated a significant change in percent of students who answered correctly following the reading. CONCLUSION: The overall findings of the study demonstrated that through interactive reading sessions students significantly increased their scores between pre- and post-read questionnaires. This study serves to encourage the use of children's books as an educational tool for young learners.

[Acute Aortic Dissection Complicated by IgA Deficiency].

Immunoglobulin A (IgA) deficiency is the most common type of primary immunodeficiency. When a patient receives a blood product transfusion, anti-IgA antibodies are formed. Second transfusion may sometimes cause an anaphylactic reaction, thus caution is necessary. Reported here is a case of Stanford type A acute aortic dissection performed in the patient with IgA deficiency with a history of blood transfusion. Red blood cells and platelet were washed and prepared, and flesh frozen plasma from IgA deficient donors was obtained. Thereafter, the surgery was safely performed.

Medical Students as Simulation Educators.

INTRODUCTION: Physicians are expected to educate patients, students, colleagues, as well as members of the interdisciplinary team. However, unlike in the United Kingdom and Canada, US medical schools do not require teaching as a competency for graduation. High-quality teaching and communication skills are necessary to ensure patient safety and trust. As the field of medicine becomes increasingly expansive and complex, it can no longer rely on empiric forms of knowledge exchange. Physician training must include pedagogy to create competent educators. In this project, the educational efforts of senior medical students providing simulation-based education to junior students were compared with that provided by faculty-led education. METHODS: The "Medical Students as Simulation Educators" (MSASE) course consists of a didactic and a teaching application component. The didactic component delivers learning modules on topics such as simulation education history, learning theories, debriefing and feedback, curriculum development, teaching methods, assessment, evaluation, and essentials of running the Laerdal SimMan 3G simulation system. After completing didactic courses, student educators apply their pedagogic skills in facilitator-guided, high-fidelity clinical simulations in areas such as anaphylaxis, heart failure, and atrial fibrillation. The evaluation of MSASE compared the knowledge gain of learners led by clinical faculty to those led by student-educators. Learners completed the same multiple-choice quiz (MCQ) before and after the simulation training. In addition, student satisfaction surveys were used to assess their attitudes to being taught by their peers. RESULTS: Scores from the pre- and post-tests were nearly identical in the faculty and student-led groups. The faculty-led group's average pre- and post-activity scores were 41.67% and 72.81%, respectively. The average increase in scores was 31.14%. The student-led group's average pre- and post-activity scores were 44.43% and 75.71%, respectively. The average increase in scores was 31.28%. The results of the student satisfaction survey were supportive of peers as educators. The survey used a 5-point scale with 1 representing "strongly disagree" and 5 representing "strongly agree". Aspects surveyed include learning objective identification and achievement, educator preparedness, organization and structure, simulation realism, complexity appropriateness, engagement level, quality of debriefing, and more. The average student satisfaction score for each aspect of the survey was greater than 4.5. The average of all elements surveyed was 4.75/5. CONCLUSIONS: Data support the contention that medical students are equally effective in simulation-based teaching as clinical faculty. Participating student educators and student learners reported satisfaction with the MSASE experience.

Influencing Children Through the Art of Storytelling Using a Medically-Informed Children's Book.

INTRODUCTION: The purpose of this study is to demonstrate how children learn about a health topic from an interactive reading session. Due to the large number of children with allergies, the specific topic chosen for this research study was peanut allergies. The goal of the project was to educate children about a leading, medically relevant health topic through a story about a child with a peanut allergy. METHODS: For the purposes of the research project, author Mykayla Vollmer wrote, illustrated, and published the children's book, A Party Without Peanuts: How Food Allergies Affect Friends. The children's book was then read, in a group setting, at local third grade classrooms and students were provided adequate time to ask questions following the reading session. The students were assessed through both pre- and post-read surveys to evaluate knowledge gained during the session. Specific topics discussed in the reading include allergies, anaphylaxis, preventative measures, and treatments. RESULTS: There were 65 pre- and post-read surveys matched in data analysis. There was a significant increase from a pre-read score of 5.38 (76.92%) to a post-read score of 6.38 (91.21%) for the overall survey with a mean difference of 1.0. In addition to comparing the overall results of the study, each question in the survey was assessed on an individual basis. 4 of the 7 questions demonstrated a significant change in percentage of students who answered correctly following the reading session. CONCLUSION: The overall findings of the study demonstrated that through interactive reading sessions students significantly increased their scores between pre- and post-read questionnaires. This study serves to encourage the use of children's books as an educational tool for young learners.

Pregnancy Plus Anaphylaxis: A Nurse's Perspective-Changing Health Scare.

Finding a deeper space for empathy.