Type I Kounis syndrome in a young woman without chest pain: a case report.

BACKGROUND: Kounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40-70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain. CASE PRESENTATION: A 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome. CONCLUSION: Kounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

A case of anaphylactic shock to human fibrinogen infusion during cardiac surgery.

Human fibrinogen (FIB) has been clinically proven to be considerably effective for the treatment of postoperative bleeding, with reported cases of allergic reactions to human FIB being rare. Here, we report a case of an anaphylactic shock in 27-year-old patients with rheumatic heart valve disease who received a human FIB infusion during mitral valve replacement, aortic valve replacement, and tricuspid valve-shaping surgery. The patients showed generalised profuse sweating, a barely noticeable skin rash, faint pulse, systolic pressure < 50 mmHg, and a heart rate of 71 beats/min. We share insights from a case of severe allergy to human FIB infusion during cardiac surgery, through which we have gained experience in the processes of diagnosing and treating. This report aims to provide a preliminary summary of the characteristics of this case to serve as a reference for fellow clinicians.

Pediatric idiopathic anaphylaxis: practical management from infants to adolescents.

Idiopathic anaphylaxis (IA) remains a frustrating challenge for both patients and physicians. The aim of this paper is to focus on IA in pediatric ages and suggest possible diagnostic algorithms according to specific age ranges (infants, children, and adolescents). In fact, in a variable percentage of patients, despite extensive diagnostic tests, the cause of anaphylactic episodes cannot be identified. Moreover, the lack of a unanimous IA definition requires a careful and detailed diagnostic workup. Prompt recognition of signs and symptoms, especially in younger children, and an accurate clinical history often allow a choice of the most appropriate diagnostic tests and a correct differential diagnosis.

Allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of IgE F(ab')2 epitopes.

Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab')2. Consequently, HMK-12 Fab-mediated targeting of Cε2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of two epitope sites on the Cε2 homodimer domain of IgE F(ab')2 may have implications for the development of novel therapies for allergic disease.

Hymenoptera venom allergy in children and adolescents.

PURPOSE OF REVIEW: This review will identify and summarize the published existing data pertaining specifically to Hymenoptera venom allergy in children and adolescents, highlighting the major studies currently available on venom immunotherapy (VIT) and its prognosis in children. RECENT FINDINGS: The current review covers the incidence and prevalence of Hymenoptera venom allergy (HVA) in children, factors influencing occurrence and severity of reactions (age, sex, comorbidities, etc.), indications to perform diagnostic tests and start VIT in children, different existing VIT protocols and their safety and efficacy. SUMMARY: Hymenoptera venom allergy is the second most common cause of anaphylaxis in children and it considerably affects quality of life. Cutaneous reactions are the most prevalent clinical presentation in children who usually have a more favourable prognosis than adult patients. However, studies on HVA in children and adolescents are still limited. Currently VIT is the only treatment able to modify the natural history of HVA in adults as well as in children, and to protect patients from systemic reactions after subsequent stings.

The risk of anaphylaxis on holidays.

PURPOSE OF REVIEW: The goal of this review is to summarize the potential causes of anaphylaxis in the different holiday contexts, providing practical suggestions aimed to mitigate the stress challenged by allergic patients because of unfamiliar situations. RECENT FINDINGS: A regard was reserved to potential food triggers, particularly uncommon ones and typical of certain destinations, and to arthropods responsible for anaphylaxis. SUMMARY: This review highlights the potential risk of anaphylaxis due to the unusual contexts more experienced during holidays (i.e., travels, outdoor activities and eating out). Moreover, it underlines the need for a further allergological education in these cases, in order to prepare allergic patients to avoid and manage undesired situations.

[Allergy and anaphylaxis]. / Allergie en anafylaxie.

Allergy is a medical condition of frequent occurrence. In the Netherlands approximately 20% of the population has some kind of respiratory allergy, due to pollen and dust mites. The occurrence of allergy on foods, antibiotics, other medications, contrast fluid and insect poison is estimated to be 2% in the adult population. Because of this large and diverse group of allergy triggers it is very likely that physicians, regardless of background or medical specialty, will come across questions regarding allergy at some point in their career. The severity of an allergic reaction can vary, with anaphylaxis as one of the most severe and potentially life-threatening reactions (among DRESS, SJS, TEN and acute FPIES). This article describes the backgrounds of IgE-mediated allergy and anaphylaxis, like pathophysiology, diagnostics and treatment.

Management of Sideline Medical Emergencies.

Sideline medical care is typically provided by musculoskeletal specialists and orthopaedic surgeons with varying levels of training and experience. While the most common sports injuries are often benign, the potential for catastrophic injury is omnipresent. Prompt recognition of sideline emergencies and expeditious medical management are necessary to minimize the risk of calamitous events. Paramount to successful sideline coverage are both preseason and game-day preparations. Because the skillset needed for the sideline physician may involve management of injuries not commonly seen in everyday clinical practice, sideline providers should review basic life support protocols, spine boarding, and equipment removal related to their sport(s) before the season begins. Before every game, the medical bag should be adequately stocked, location of the automatic external defibrillator/emergency medical services identified, and introductions to the trainers, coaches, and referees made. In addition to musculoskeletal injuries, the sideline orthopaedic surgeon must also be acquainted with the full spectrum of nonmusculoskeletal emergencies spanning the cardiopulmonary, central nervous, and integumentary systems. Familiarity with anaphylaxis as well as abdominal and neck trauma is also critical. Prompt identification of potential life-threatening conditions, carefully orchestrated treatment, and the athlete's subsequent disposition are essential for the team physician to provide quality care.

Time trends in the epidemiology of food allergy in England: an observational analysis of Clinical Practice Research Datalink data.

BACKGROUND: Estimates for the prevalence of food allergy vary widely, with a paucity of data for adults. The aim of this analysis was to report trends in the incidence and prevalence of food allergy in England, using a national primary care dataset. METHODS: We analysed data from Clinical Practice Research Datalink between 1998 and 2018, with linked data to relevant hospital encounters in England. The main outcomes were incidence and prevalence of food allergy, according to three definitions of food allergy: possible food allergy, probable food allergy, and probable food allergy with adrenaline autoinjectors prescription. We also evaluated the difference in proportion of patients prescribed adrenaline autoinjectors by English Index of Multiple Deprivation (IMD), age, and by previous food anaphylaxis, and explored differences in patient encounters (general practice vs emergency department setting). FINDINGS: 7 627 607 individuals in the dataset were eligible for inclusion, of whom 150 018 (median age 19 years [IQR 4-34]; 82 614 [55·1%] female and 67 404 [44·9%] male) had a possible food allergy. 121 706 met diagnostic criteria for probable food allergy, of whom 38 288 were prescribed adrenaline autoinjectors. Estimated incidence of probable food allergy doubled between 2008 and 2018, from 75·8 individuals per 100 000 person-years (95% CI 73·7-77·9) in 2008 to 159·5 (156·6-162·3) individuals per 100 000 person-years in 2018. Prevalence increased from 0·4% (23 399 of 6 432 383) to 1·1% (82 262 of 7 627 607) over the same period and was highest in children under 5 years (11 951 [4·0%] of 296 406 in 2018) with lower prevalence in school-aged children (from 11 353 [2·4%] of 473 597 in 2018 for children aged 5-9 years to 6896 [1·7%] of 404 525 for those aged 15-19 years) and adults (42 848 [0·7%] of 5 992 454 in 2018). In those with previous food anaphylaxis, only 2321 (58·3%) of 3980 (975 [64·0%] of 1524 children and young people and 1346 [54·8%] of 2456 adults) had a prescription for adrenaline autoinjector. Adrenaline autoinjectors prescription was less common in those resident in more deprived areas (according to IMD). In the analysis of health-care encounters, 488 604 (97·1%) of 503 198 visits recorded for food allergy occurred in primary care, with 115 655 (88·4%) of 130 832 patients managed exclusively in primary care. INTERPRETATION: These estimates indicate an important and increasing burden of food allergy in England. Our findings that most patients with food allergy are managed outside the hospital system, with low rates of adrenaline autoinjector prescription in those with previous anaphylaxis, highlight a need to better support those working in primary care to ensure optimal management of patients with food allergy. FUNDING: UK Food Standards Agency and UK Medical Research Council.

A retrospective comparison of IgE-mediated cow's milk protein allergy management strategies in pediatric cohorts.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA. METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk. RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group. CONCLUSION: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

Uneventful vaginal delivery using epidural anesthesia in patient with exercise induced anaphylaxis: a case report and literature review.

Exercise induced anaphylaxis (EIA) is a rare and potentially life-threatening syndrome characterized by anaphylaxis provoked by exercise. Although vaginal delivery with labor pain is a physical strain for women and a possible trigger for EIA, no consensus exists on the management strategy of delivery in patients with EIA. A 28-year-old primigravida was referred to our hospital because of history of EIA, associated with pruritus, urticaria, and respiratory distress, exacerbated during physical activity. To avoid physical stress, we chose scheduled labor induction with epidural anesthesia, and administered prophylactic intravenous hydrocortisone. She delivered vaginally with no symptoms suggestive of EIA during labor. Since it is quite possible for patients with EIA to develop anaphylaxis during vaginal delivery with labor pain, epidural anesthesia and prophylactic steroid administration may be the most rational approaches for delivery in pregnant women with EIA.

Prevalence and impact of the KIT M541L variant in patients with mastocytosis.

Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the KIT M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.

Prevalence of food allergy increased 1.7 times in the past 10 years among Japanese patients below 6 years of age.

BACKGROUND: While food allergy (FA) has been increasingly recognized as a growing public health burden worldwide, epidemiological studies on FA in Japan are limited. METHODS: This was a noninterventional, observational study using the administrative claims data from 2010 to 2019 (10 years). Patients with physician-diagnosed FA in Japan (prevalent cohort) were divided into high-risk or low-risk cohorts using adrenaline prescription. The high-risk cohort was further divided into anaphylaxis or nonanaphylaxis cohort based on the occurrence of anaphylaxis or a serious allergic reaction (SAR) during 1 year after adrenaline prescription. The primary objective was to examine yearly prevalence of FA. The secondary objectives were to describe demographics/clinical characteristics and healthcare resource utilization (HCRU), to evaluate the number of occurrences of anaphylaxis/SAR in the high-risk cohort, and the impact of anaphylaxis/SAR on HCRU. RESULTS: The overall standardized prevalence rate was 0.325% (95% confidence interval [CI], 0.311-0.339) in 2010 and 0.797% (95% CI, 0.790-0.804) in 2019 and predominant in patients age <6 years (preschool; 3.377% [95% CI, 3.229-3.525] in 2010 and 5.726% [95% CI, 5.663-5.789] in 2019). Majority of FA patients (>80%) were children/adolescent throughout the 10 years. While high-risk cohort was a relatively minor population (8.5% in the prevalent cohort in 2019), the occurrence of anaphylaxis/SAR in the high-risk cohort was 227,690/100,000 patient-years. Multivariate analysis showed a significant increase in HCRU variables in the anaphylaxis versus nonanaphylaxis cohort (e.g., 2.08 [95% CI, 2.05-2.11] times more FA-related outpatient visits). CONCLUSIONS: Prevalence of FA increased in a statistically significant way from 2010 to 2019; 1.7-fold increase was observed in patients <6 years old. Patients in the high-risk cohort appear to have suffered from frequent anaphylaxis/SAR, highlighting an unmet medical need for FA patients at "high-risk," considering the unavailability of approved medications to prevent anaphylaxis/SAR.

[A CASE OF FOOD-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS DUE TO POLISHED RICE].

A 14-year-old girl presented to our hospital with food-dependent exercise-induced anaphylaxis (FDEIA), possibly caused by rice. Despite experiencing four previous episodes of suspected FDEIA, she did not seek medical attention at her own discretion. On the fifth occurrence of symptoms, the general practitioner suspected FDEIA and referred the patient to our hospital. The only common factor in all five episodes was the consumption of rice, leading to the examination of the patient under suspicion of FDEIA caused by rice. Skin prick test results were positive for bran and polished rice, and exercise after consumption of polished rice resulted in anaphylaxis. Therefore, we diagnosed FDEIA caused by polished rice. Immunoblotting confirmed the presence of immunoglobulin E reacting with 14-16kDa rice bran protein in the patient's serum. The immunoblot inhibition test suggested that the rice bran protein to which the patient's serum reacted was also present in polished rice and no wash rice. As the patient may experience FDEIA after ingestion of no wash rice or rice flour, she was advised to eliminate these from her diet, treating them similarly to brown rice or polished rice.

Glutenin from the Ancient Wheat Progenitor Is Intrinsically Allergenic as It Can Clinically Sensitize Mice for Systemic Anaphylaxis by Activating Th2 Immune Pathway.

Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice.

Is Component-Specific Antibody Testing Sufficient to Replace the Oral Food Challenge in the Diagnostics of Peanut-Sensitized Children? A Proof-of-Concept Study.

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.