Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell-Mediated Reactions.

PURPOSE OF REVIEW: To provide an overview on the current understanding of genetic variability in human tryptases and summarize the literature demonstrating the differential impact of mature tryptases on mast cell-mediated reactions and associated clinical phenotypes. RECENT FINDINGS: It is becoming increasingly recognized that tryptase gene composition, and in particular the common genetic trait hereditary alpha-tryptasemia (HαT), impacts clinical allergy. HαT has consistently been associated with clonal mast cell disorders (MCD) and has also been associated with more frequent anaphylaxis among these patients, and patients in whom no allergic trigger can be found, specifically idiopathic anaphylaxis. Additionally, more severe anaphylaxis among Hymenoptera venom allergy patients has been linked to HαT in both retrospective and prospective studies. An increased relative number of α-tryptase-encoding gene copies, even in the absence of HαT, has also been associated with systemic mastocytosis and has been shown to positively correlate with the severity of mast cell-mediated reactions to vibration and food. These findings may be due to increased generation of α/ß-tryptase heterotetramers and differences in their enzymatic activity relative to ß-tryptase homotetramers. HαT is a naturally occurring overexpression model of α-tryptase in humans. Increased relative α-tryptase expression modifies immediate hypersensitivity symptoms and is associated with more frequent and severe mast cell-mediated reactions, ostensibly due to increased α/ß-tryptase heterotetramer production.

Level of Awareness of Certified Non-critical Care Physicians in Diagnosing, Managing, and Disposing Anaphylactic Cases.

Background: Anaphylaxis is known as an acute, severe hypersensitivity reaction that rapidly initiates after exposure to a triggering agent. It is a life-threatening condition, and early recognition and swift intervention are crucial to saving patients' lives. Objective: The objective of this study is to assess the ability of certified non-critical care physicians to recognize, manage, and dispose cases of anaphylaxis. Methods: A survey consisting of 19 questions was developed by expert emergency consultants to evaluate physicians' knowledge regarding the recognition, management, and disposition of anaphylactic episodes. Responses were collected through in-person surveys conducted with physicians from various specialties and varying clinical experience levels at a tertiary care center in the Eastern Province of Saudi Arabia. Results: In this cross-sectional study, a total of 173 physicians completed the survey, with 81.5% being consultants and 18.5% specialists. Only 5.2% correctly identified all three proposed anaphylaxis clinical scenarios, 16.8% identified two scenarios correctly, and 51.4% identified only one scenario. While 42.8% recognized the first-line management of anaphylaxis, only 24.3% and 24.9% knew the correct epinephrine dose and route, respectively. Regarding the disposition of patients experiencing an anaphylactic episode, 61.9% of responders opted to dispose the case to the emergency department. Conclusion: Our study reveals a knowledge gap among non-critical care physicians practicing in a tertiary care center concerning the identification and management of anaphylaxis. Raising awareness of this life-threatening condition is imperative to address this serious issue.

El pediatra de Atención Primaria y la anafilaxia / The primary care pediatrician and anaphylaxis

La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. El diagnóstico de anafilaxia es clínico y debe realizarse de manera precoz. Aparece en las 2 primeras horas tras exposición al alérgeno, en los primeros 30 minutos en alergia alimentaria y más precozmente con medicamentos intravenosos o picaduras de himenópteros. Los síntomas cutáneos suelen ser los primeros en manifestarse y están presentes en la mayoría de los casos, más de un 80%. Pueden ser leves o transitorios e incluso no estar presentes en un 18% de los casos. Si se afecta el sistema cardiocirculatorio estaríamos ante un shock anafiláctico. La causa más frecuente en Pediatría son los alimentos. Existen cofactores cuya presencia aumenta la probabilidad de anafilaxia; los más importantes son: el ejercicio, los fármacos, la fiebre y el estrés. El tratamiento de elección es la adrenalina intramuscular. Tanto los padres como los niños deben saber identificar los signos y/o síntomas del inicio de la anafilaxia para instaurar el tratamiento pautado en el plan de acción escrito.

Anaphylaxis is a severe, rapid and potentially fatal allergic reaction. The diagnosis of anaphylaxis is clinical and must be early. It appears in the first 2 hours after exposure to the allergen, in the first 30 minutes in food allergy and earlier with intravenous drugs or hymenoptera stings. Cutaneous symptoms are generally the first to appear and are present in most cases, more than 80%. They may be mild or transitory, or absent in 18% of cases. If the cardio-circulatory system is affected, an anaphylactic shock occurs. The most frequent cause in pediatrics is nutrition. There are several cofactors whose presence increases the likelihood of anaphylaxis; the most important are: exercise, medication, fever and stress. The treatment of choice is intramuscular adrenaline. Parents and children should be able to identify the signs and/or symptoms of anaphylaxis in order to implement the treatment prescribed in the written action plan. (AU)

Cold-induced anaphylaxis triggered by drinking cold water.

Cold urticaria is an inducible urticaria in which hives and angioedema appear after exposure to cold. The symptoms of cold urticaria often are limited to hives/angioedema. However, in up to 20% of cases, cold exposure may trigger anaphylaxis. We report the case of an 11-year-old boy previously diagnosed with chronic spontaneous urticaria who developed facial swelling, itchy hives, difficulty in breathing, vomiting and abdominal pain within 5 minutes of drinking cold water. He received a standard dose of non-sedating second-generation antihistamines at home. He was observed in the emergency room for 2 hours and discharged with an epinephrin autoinjector. During the subsequent outpatient clinic visit, an ice cube test was performed which confirmed the new diagnosis of comorbid cold-induced chronic urticaria. On further questioning, the parents reported occurrence of hives following swimming in the swimming pool. Cold-induced urticaria should be suspected in cases of anaphylaxis associated with cold exposure. Patients with chronic forms of urticaria who present with new anaphylaxis should be assessed for a potential concomitant cold-induced form.

Allergy to Gibberellin-regulated proteins in an adolescent: A case of orange-induced anaphylaxis mediated by cofactors.

This report is a case of anaphylaxis in an adolescent due to allergy to gibberellin-regulated proteins mediated by cofactors, in probable relation to a pollen/food allergy syndrome. It should also emphasizes the importance of obtaining a faithful clinical history, especially when it comes to adolescent patients as they tend to initiate toxic habits.

Fatal food anaphylaxis in adults and children.

Anaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients' associations.

Novel use of dynamic MR hydrography to rule out esophageal perforation post atrial fibrillation ablation in a patient with anaphylaxis to gadolinium.

Esophageal thermal injury is one of the most devastating complications of atrial radiofrequency ablation, and its diagnosis can be challenging. In this report, we highlight the novel use of free water as a contrast material to better visualize the esophageal lumen in a patient with anaphylaxis to Iodinated contrast media and Gadolinium who recently underwent atrial fibrillation ablation. This becomes particularly handy in patients with contrast allergy, and further emphasizes the role of multimodality imaging.

A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

Reversible Elevation of Tryptase Over the Individual's Baseline: Why is It the Best Biomarker for Severe Systemic Mast Cell Activation and MCAS?

PURPOSE OF REVIEW: Mast cell (MC) activation syndromes (MCAS) are conditions defined by recurrent episodes of severe systemic anaphylaxis or similar systemic events triggered by MC-derived mediators that can be measured in biological fluids. Since some symptoms of MC activation may occur due to other, non-MC etiologies and lead to confusion over diagnosis, it is of crucial importance to document the involvement of MC and their products in the patients´ symptomatology. RECENT FINDINGS: The most specific and generally accepted marker of severe systemic MC activation is an event-related, transient increase in the serum tryptase level over the individual baseline of the affected individual. However, baseline concentrations of serum tryptase vary among donors, depending on the genetic background, age, kidney function, and underlying disease. As a result, it is of critical importance to provide a flexible equation that defines the diagnostic increase in tryptase qualifying as MCAS criterion in all patients, all situations, and all ranges of baseline serum tryptase. In 2012, the consensus group proposed the 120% + 2 ng/ml formula, which covers the great majority of groups, including cases with low, normal, or elevated basal serum tryptase level. This formula has been validated in subsequent studies and has proven to be a robust and consistent diagnostic criterion of MCAS. The present article is discussing the impact of this formula and possible limitations as well as alternative markers and mediators that may be indicative of MCAS.

Acute hepatic rupture causing hemoperitoneum in a dog with anaphylaxis.

A 2-year-old spayed female Siberian Husky was presented with a history of acute onset lethargy, collapse, haematochezia and vomiting. The patient was severely tachycardic and hypotensive. Point-of-care ultrasound revealed gallbladder wall thickening and peritoneal effusion consistent with haemorrhage on subsequent abdominocentesis. Despite attempted medical stabilization over the course of several hours, including blood products and multiple autotransfusions, the patient progressed to cardiopulmonary arrest. The dog was successfully resuscitated but was subsequently euthanized. Necropsy revealed a severe, acute hemoperitoneum secondary to rupture of the left lateral liver lobe. A tear in the hepatic capsule was identified along with a large hematoma. A single adult nematode, consistent with Dirofilaria immitis, was found in a pulmonary vessel in the right caudal lung lobe. The remaining necropsy findings were supportive of the clinical diagnosis of anaphylaxis. This report details a case, with necropsy findings, supporting a diagnosis of anaphylaxis and severe, refractory hemoperitoneum resulting from hepatic rupture. Acute hepatic rupture should be considered in cases of anaphylaxis-related hemoperitoneum.

Simulation training for medical emergencies: Evaluation of dentists' long-term learning skills and confidence.

INTRODUCTION: As the population ages and more patients experience medical emergencies during dental treatments, dentists must competently and confidently manage these situations. We developed a simulation training course for medical emergencies in the dental setting using an inexpensive vital sign simulation app for smartphones/tablets without the need for an expensive simulator. However, the duration for which this effect is maintained is unclear. This study was performed to evaluate the long-term educational effect at 3, 6, and 12 months after taking the course. MATERIALS AND METHODS: Thirty-nine dental residents participated in this course. Scenarios included vasovagal syncope, anaphylaxis, hyperventilation syndrome, and acute coronary syndrome, each of which the participants had to diagnose and treat. The participants were evaluated using a checklist for anaphylaxis diagnosis and treatment skills immediately after and 3, 6, and 12 months after the course. The participants were also surveyed about their confidence in diagnosing and treating these conditions by questionnaire before, immediately after, and 3, 6, and 12 months after the course. RESULTS: The checklist scores for anaphylaxis were significantly lower at 3, 6, and 12 months after the course than immediately after the course. The percentage of participants who provided a correct diagnosis and appropriate treatment for vasovagal syncope, hyperventilation syndrome, and acute coronary syndrome was lower at all reassessments than immediately after the course. CONCLUSION: Because medical emergency management skills and confidence declined within 3 months, it would be useful to introduce a refresher course approximately 3 months after the initial course to maintain skills and confidence.

Snail-induced anaphylaxis in patients with underlying Artemisia vulgaris pollinosis: the role of carbohydrates

Purpose: The importance of carbohydrates in anaphylaxis has been described with some foods. The current work intends to obtain clinical and immunological evidence of the importance of the O-glycans for IgE binding activity in anaphylactic reactions due to Helix aspersa (HA) ingestión and Artemisia vulgaris (AV) exposition. Methods: The studio focused on two cases of IgE-mediated anaphylaxis induced by snail ingestion in patients with underlying rhino-conjunctivitis and asthma due to AV. We performed on both patients: skin prick tests ( SPTs) with HA and AV and with a battery of aeroallergen, controlled nasal challenge and specific IgE to HA and AV, ImmunoCAP ISAC®, and a differential pattern of IgE recognition with SDS-PAGE Immunoblotting (SDSI) when these allergens have suffered an O-deglycosylation procedure. Results: The patients showed positive results in SPTs, nasal challenges, and serum-specific IgE against HA and AV. In patient 1, the SDSI detected several IgE-binding proteins in AV with a molecular mass of 22, 24, and 44 kDa, whereas a band of 12 kDa was detected in HA. On the other hand, patient 2’s serum revealed an IgE-binding zone between 75 and 20 kDa in the AV and a band of 24 kDa in the HA. When glycans were removed, patient 1’s serum only revealed the AV’s 22 and 24 kDa bands, whereas patient 2’s serum did not detect any IgE-reactive protein in the HA. Conclusions: Our data suggest that O-glycosylation can be relevant in patients with anaphylaxis due to snails and allergy to Artemisia vulgaris. This new entity representing cross-reactivity between AV and HA could be named Snail-Artemisia Syndrome (AU)

Fish Allergy and Related Conditions in Children: A Review.

Fish allergy is the important food allergies in childhood, often persisting into adulthood. It can cause severe hypersensitivity reactions, including fatal anaphylaxis; furthermore, avoiding-fish diet has negative nutritional and psychological effects. Recent research studies focus on epitope structures and aim to develop sensitive and specific diagnostic tools, which have a better correlation with clinical reactions. Protocols with hypoallergenic parvalbumin or other recombinant antigens are also under study and will likely lead to new immunotherapy protocols. IgE-mediated fish allergy differs substantially from other forms of immunological adverse reactions to fish, such as Food Protein-Induced Enterocolitis Syndrome and eosinophilic esophagitis. In addition, fish ingestion can cause non-immunological adverse reactions, such as in the case of scombroid poisoning, anisakiasis and toxic poisoning. This review aims to summarize the characteristics of the main immunological and non-immunological fish reactions, analyzing the epidemiology, clinical manifestations, diagnosis and therapy, with a particular focus on clinical management.

DNA methylation profiling reveals potential biomarkers of ß-lactams induced fatal anaphylactic shock.

Anaphylaxis is a serious reaction of systemic hypersensitivity with that rapid onset and sudden death. Drug hypersensitivity, particularly induced by ß-lactams, is one of the most frequent causes of anaphylaxis in adults. But identification of anaphylactic shock, in forensic sciences recently, is difficult, because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. Here, we detected DNA methylation signatures of ß-lactams-induced fatal anaphylactic shock with the Illumina Infinium Human Methylation EPIC BeadChip, to screen potential forensic biomarkers and reveal the molecular mechanisms of drug-induced anaphylaxis with fatal shock and sudden death. Our results indicated that DNA methylation was associated with ß-lactams-induced fatal anaphylactic shock, in which the hypomethylation played a vital role. We found that 1459 differentially methylated positions (DMPs) were mainly involved in ß-lactams-induced fatal anaphylactic shock by regulating MAPK and other signaling pathways. 18 DNA methylation signatures that could separate ß-lactams-induced anaphylactic shock from healthy individuals were identified. The altered methylation of DMPs can affect the transcription of corresponding genes and promote ß-lactams-induced fatal anaphylactic shock. The results suggest that DNA methylation can detect forensic identification markers of drug-induced anaphylaxis with fatal shock and sudden death, and it is an effective method for the forensic diagnosis.