Fatal Hypersensitivity Reaction Research Articles

Current update on anaphylaxis: anaphylaxis management in recent guidelines.

Anaphylaxis is a potentially fatal hypersensitivity reaction but frequently underrecognized. Although its incidence rates vary according to geographical location, it seems clear that there has been a general increase in recent years, either because of greater recognition of this entity or because it is progressing proportionally to the presence of allergic diseases in the world. The development of anaphylaxis management guidelines adapted to local or regional needs seems of utmost importance. Furthermore, it is necessary to assess their implementation and their positive effect regarding diagnosing and treating anaphylaxis. In this review we explore the currently existing definitions of anaphylaxis and its epidemiology, the potential triggers of anaphylaxis and guideline recommendations in terms of diagnosis and management, proposing a novel anaphylaxis calculator and reviewing the current scoring methods for anaphylactic episodes.

HLA-B*57:01 typing in a Malaysian cohort: implications of abacavir hypersensitivity in people living with HIV.

Background: Abacavir (ABC)in combination with other antiretroviral drugs, is used to treat people living with HIV (PLWH). However, it is linked to a fatal hypersensitivity reaction in susceptible individuals, and is strongly associated with the HLA-B*57:01 allele. Materials & methods: A total of 152 patients, 50 PLWH and 102 HIV-1negative patients, were assessed for the HLA-B*57:01 allele through a sequence-specific primer PCR. Results: All PLWH tested negative for the HLA-B*57:01 allele, but two HIV-negative patients were found to have HLA-B*57, with one of them expressing the HLA-B*57:01 allele. Conclusion: Given the low prevalence of this risk allele in the population, testing for the presence of HLA-B*57:01 in PLWH may not provide significant benefit for the reported population.

Mast Cells and Basophils in IgE-Independent Anaphylaxis.

Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management.

A Stevens-Johnson syndrome due to rifampicin in a patient with acquired immune deficiency syndrome (AIDS) and pulmonary tuberculosis

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially fatal hypersensitivity reactions that can be drug-induced, especially in patients with AIDS. This report aims to highlight the diagnosis and management of a patient with acquired immunodeficiency syndrome (AIDS) that consumed multiple drugs including anti-tuberculosis drugs that develop SJS. Case presentation: A 30-year-old male patient with AIDS administered with chief complaints of burning sensation all over the bodies and erythematous macules scattered across the stomach and back, followed by blisters distributed across the chest, back, face, lips, hands and feet, as well as genitals for 3 days. Patient was diagnosed with AIDS and under ARV medication since about 5 years ago and dan cotrimoxazole for 9 months. Couple months before admission, patient was diagnosed with tuberculosis and under anti-tuberculosis treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE)) but stopped due to drug-induced hepatitis (DIH) which then changed to another regiment (streptomycin, levofloxacin, and ethambutol (SLE)) followed by another regiment (rifampicin, isoniazid and ethambutol (RHE)). The patient diagnosed with drug-induced SJS, however, in order to find out the SJS drugs inducer, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis (ALDEN) score as causality assessments tool was applied and rifampicin decided to be the precursor. The patient was managed for 13 days prior to discharge with improved condition. Conclusion: Diagnosing process for drug-induced in patient with AIDS, in addition to multiple drugs consumption, is a challenge. A multidisciplinary approach and appropriate causality assessments tool should be considered before administering further management and medications.

Silibinin attenuated pseudo-allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway.

Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cells. Many endogenous or exogenous factors could cause this reaction. Silibinin is the main chemical component of silymarin and has been reported to have pharmacological activities. However, the anti-allergic reaction effect of silibinin has not yet been investigated. This study aimed to evaluate the effect of silibinin to attenuate pseudo-allergic reactions in vivo and to investigate the underlying mechanism in vitro. In this study, calcium imaging was used to assess Ca2+ mobilization. The levels of cytokines and chemokines, released by stimulated mast cells, were measured using enzyme immunoassay kits. The activity of silibinin was evaluated in a mouse model of passive cutaneous anaphylaxis (PCA). Western blotting was used to explore the related molecular signaling pathways. In results, silibinin markedly inhibited mast cell degranulation, calcium mobilization, and preventing the release of cytokines and chemokines in a dose-dependent manner via the PLCγ and PI3K/Akt signaling pathway. Silibinin also attenuated PCA in a dose-dependent manner. In summary, silibinin has an anti-pseudo-allergic pharmacological activity, which makes it a potential candidate for the development of a novel agent to arrest pseudo-allergic reactions.

Eosinophilic Pneumonitis Complicated by ARDS Following DRESS Syndrome: Case Report

Introduction: Drug reaction syndrome with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal hypersensitivity reaction, The reaction usually manifests as a febrile skin rash accompanied by lymphadenopathy and malaise between two and eight weeks after drug exposure. The pulmonary manifestations of DRESS are variable and may include interstitial pneumonia, pleural effusion, pneumonia, pulmonary nodules and (in the most severe cases) acute respiratory distress syndrome (ARDS). We report the observation of an acute eosinophilic pneumonitis which is unique in that it is part of a DRESS syndrome following the use of non-steroidal anti-inflammatory drugs and Ciprofloxacin. Observation: This was a 63-year-old patient admitted to the outpatient department of the Mohamed VI University Hospital in Marrakech for acute respiratory distress. Her history included a chronic depressive syndrome for 7 years under Taraxet and Deroxat; a megaloblastic anemia under Tardyferon; a non-dialyzed renal failure; a Gout having been under Zyloric for 7 months; a DRESS syndrome following the intake of non-steroidal anti-inflammatory drugs and Ciprofloxacin (Cystitis) having been hospitalized in the dermatology department 15 days before. The diagnosis of community-acquired pneumonia had been evoked and treated with Amoxicillin-clavulanic acid + Azithromycin (Suspicion of covid infection and appearance of Crazy Paving on thoracic Angioscanner), The evolution had been marked the following day by severe respiratory distress with hypoxia at 68% with MHC at 15, the respiratory frequency was at 51 cycles per minute with generalized cyanosis, signs of respiratory struggle. The blood gases on admission:Ph 7. 43 PaCo2 40.3 pAo2 45 HCo3- 25.8, PaO2/FiO2 at 98; The picture of hypoxaemia on a severe and very hypoxaemic pneumopathy required orotracheal intubation. Refractory hypoxemia (PaO2/FIO2 = 69 in the control gasometry despite a PEEP = 14 cmH2O, deep sedation completed with .....

Current situation of anaphylaxis in Japan: Data from the anaphylaxis registry of training and teaching facilities certified by the Japanese Society of Allergology – secondary publication

BackgroundAnaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. MethodsBetween February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. ResultsThis study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. ConclusionsThe present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.

Peanut (Arachis hypogaea) allergen powder-dnfp for the mitigation of allergic reactions to peanuts in children and adolescents

ABSTRACT Introduction Peanut allergy can result in severe, sometimes fatal hypersensitivity reactions that place a considerable burden on the lives of patients. This article reviews the first approved immunotherapy for the mitigation of allergic reactions following accidental peanut exposure, peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®, Aimmune Therapeutics). Areas covered This article highlights the unmet need for patients with peanut allergy, describes the therapeutic landscape, and reviews the development of and clinical data for PTAH. Expert opinion PTAH offers a standardized preparation of peanut allergen, with a tolerability and efficacy profile clearly defined through its robust clinical development and trial program. In children 4–17 years old, PTAH provides a standardized, approved product that many clinicians sought prior to initiating oral immunotherapy. PTAH reduced the likelihood of more severe reactions following exposure to peanut protein; although peanut avoidance remains essential, PTAH will enable more individuals with peanut allergy to participate in activities of daily life with less anxiety.

Prolonged Drug-Induced Hypersensitivity Syndrome/DRESS With Alopecia Areata and Autoimmune Thyroiditis.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B treatment and with development of extensive alopecia areata and autoimmune thyroiditis. DIHS/DRESS is a severe cutaneous adverse reaction that may require prolonged treatment until symptoms resolve. Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy. DIHS/DRESS patients also should be educated and followed for potential autoimmune sequelae.

The Etiology, Clinical Features, and Severity of Anaphylaxis in Childhood by Age Groups

Introduction: Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction with an acute onset. Etiology, clinical presentation, risk factors, comorbidities of pediatric anaphylaxis may vary depending on the age of the child. Objective: The aim of this study was to investigate the etiology, clinical features, management of anaphylaxis in infants, preschoolers, school-age children, and adolescents. Methods: The patients presenting with anaphylaxis between January 2015 and December 2018 in a single pediatric tertiary hospital were evaluated retrospectively. Demographic data, the triggers, sign-symptoms, severity, and the management of anaphylaxis were recorded. Results: 239 patients were included in the study, 62.3% of whom were boys. The median age was 6.7 (IQR 2.33–12.83) years. 23.8% of the patients were infants, 15.5% were preschoolers, 33.5% were school-age children, and 27.2% were adolescents. Anaphylaxis mostly occurred at home. The most common causative agents were foods (39.3%), drugs (30.1%), and venoms (15.9%) of all cases. Main food allergens were cow’s milk and hen’s eggs in infants, cow’s milk and tree nuts in preschoolers, and tree nuts and legumes in school-age children. Cases of drug-induced anaphylaxis (DIA) were recorded mostly with antibiotics (40.3%), followed by NSAIDs (23.6%). The primary trigger of anaphylaxis was foods in infants and preschoolers and drugs in school-age children and adolescents. There was no difference between age groups in terms of the system involved and severity. Severe anaphylaxis was more common with DIA. Adrenaline was used in 69.8% of all cases with no significant difference between age groups. Conclusion: Etiology and symptoms of anaphylaxis may differ between age groups. Raising awareness, educating patients and their parents on anaphylaxis and its management is essential.

Genotyping for HLA Risk Alleles to Prevent Drug Hypersensitivity Reactions: Impact Analysis.

Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug–gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping HLA-B*5701 in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping HLA-B*5801 in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of HLA-B*5701 in abacavir initiators, as indicated in the drug label, and show genotyping of HLA-B*5801 in allopurinol initiators should be considered.

Drug Reaction with eosinophilia and systemic symptoms with alopecia universalis and vitiligo

Drug reactions with eosinophilia and systemic symptoms (DRESS) are rare and potentially fatal adverse hypersensitivity reaction to some drugs, especially anticonvulsants. The syndrome affects not only the skin but also other organs, especially the liver. The incidence can vary from 1 to 5 cases per 10.000 patients exposed to anticonvulsants.The recognition of the syndrome is of fundamental importance since the mortality rate is between 10 and 40%. Once the diagnosis is established, the triggering drug must be identified and discontinued. Corticosteroids are usually associated with therapy. Autoimmune sequelae have been reported, including vitiligo and rarely alopecia. Alopecia universalis is a variant of alopecia areata, characterized by hair loss throughout the body. We report a case of DRESS, associated with two autoimmune dermatological diseases: alopecia universalis and vitiligo.

A Relapsing Case of Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially fatal adverse hypersensitivity reaction often secondary to therapeutic medications. There is a wide variation in the incidence of the disease and is dependent on the genetic makeup of the individual. The most common presentation includes skin eruptions, fever, generalized lymphadenopathy, eosinophilia, and internal organ involvement (most commonly, liver, kidneys, and lungs). Some less common features are dysphagia, agranulocytosis, and chylous ascites. The most common drugs causing DRESS syndrome include carbamazepine, allopurinol, sulfasalazine, phenobarbital, and lamotrigine. Differential diagnosis has Steven-Johnson Syndrome/Toxic Epidermal Necrolysis, hypereosinophilic syndrome, and Sezary syndrome. Systemic corticosteroids are the first-line treatment for DRESS syndrome and the withdrawal of the offending agent and supportive therapy. We report a rare case of DRESS syndrome following the use of clarithromycin and moxifloxacin, where rapid steroid taper resulted in relapse.

Food-induced anaphylaxis in children – state of art

Food-induced anaphylaxis is the most frequent type of anaphylaxis and the most common cause of fatal acute hypersensitivity reactions in children. It typically occurs after accidental food exposure, after inhalation of food allergen, cutaneous contact and controlled oral food challenge. There is no consensus on a universal clinical definition of anaphylaxis or a uniform symptoms severity score. Recent advances in molecular allergology allow, in many cases, the detailed identification of the allergenic molecule responsible for anaphylaxis. Along with the development of precision medicine, new phenotypes and endotypes of anaphylaxis are being defined. The anaphylaxis course is entirely unpredictable, and even initially mild symptoms may herald a potentially fatal reaction. At the same time, a significant proportion of immediate food hypersensitivity episodes are mild and known as systemic allergic reactions. The occurrence and severity of clinical course of food-induced anaphylaxis are influenced by factors related directly to the child, coexisting diseases, the type and the nature of the allergen, or the presence of cofactors. The unpredictable course of anaphylaxis justifies immediate treatment based on rapid intramuscular administration of adrenaline, regardless of severity. Delayed adrenaline administration is associated with higher incidence of severe course and death. Appropriate and prompt treatment of anaphylaxis is even more critical during the COVID-19 pandemic due to difficult access to medical facilities, hence current treatment plans for food-induced anaphylaxis emphasise the need to administer adrenaline immediately after the onset of the first, even mild, but rapidly progressive symptoms and recommend that the patient have at least two adrenaline autoinjectors.

Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns.

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.

Refractory Anaphylaxis: Data From the European Anaphylaxis Registry.

Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances—requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases.

Pulmonary Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review

Background The syndrome of drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with anticonvulsants, sulfonamides, and allopurinol. The reaction commonly manifests as a febrile skin eruption with lymphadenopathy and malaise between two and eight weeks following drug exposure. Internal organ involvement occurs in close to 90 percent of patients, and multiple organs may be involved in approximately half of those affected (most commonly the liver, kidney, and lung). Its long latency period and its variable clinical pattern of presentation have earned it the moniker of “the great mimicker,” with delays in diagnosis leading to higher morbidity and mortality. Although less commonly affected in DRESS syndrome, lung involvement is associated with more severe clinical course and potentially worse outcome. Pulmonary symptoms may precede development of the other more common symptoms and signs of the syndrome, or they might develop later in the course of the disease. Lung involvement in DRESS presents with a plethora of manifestations from mild cough or dyspnea with nonspecific interstitial changes on chest imaging to acute respiratory distress syndrome (ARDS) with life-threatening hypoxic respiratory failure. Methods We performed a systematic review of literature from the PubMed database and selected cases of definite DRESS syndrome as defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) with a score of 6 or more who also had pulmonary involvement. Demographic data, pattern of lung involvement, culprit medication, latency period, laboratory findings, therapy, and outcome were described and compared with the literature. Results The most common pulmonary radiographic findings in DRESS were interstitial infiltrates in 50% of cases, followed by acute respiratory distress syndrome (ARDS) 31%. Symptoms of cough and shortness of breath (SOB) were present in 72% of patients at the time of presentation. SOB was the more common presenting symptom (81%) compared to cough (19%). In 95% of cases, another visceral organ was involved (most commonly liver or kidneys). 45% of cases were initially misdiagnosed as pneumonia and were treated with empiric antimicrobials. In a multivariate regression, a latency of 30 days or less and an age of 60 or less were associated with development of ARDS. Gender and eosinophil count were not associated with severity of pulmonary manifestations. All patients recovered, and in the vast majority of cases (95%), parenteral steroids were used for treatment in addition to supportive care and symptomatic management. Conclusion Albeit rare, DRESS is a potentially life-threatening syndrome which may present with a myriad of pulmonary signs and symptoms. Pulmonary manifestations are less common but are typically seen in more severe cases. Pulmonary manifestations may be a presenting sign of DRESS, and timely recognition is important in order to stop offending medication and decrease morbidity and mortality.

Epidemiology of Anaphylaxis in Critically Ill Children in the United States and Canada

BACKGROUND:Anaphylaxis is a rapid-onset, multisystem, and potentially fatal hypersensitivity reaction with varied reports of prevalence, incidence, and mortality. There are limited cases reported of severe and/or fatal pediatric anaphylaxis.OBJECTIVE:This study describes the largest cohort of intensive care unit pediatric anaphylaxis admissions with a comprehensive analysis of identified triggers, clinical and demographic information, and probability of death.METHODS:We describe the epidemiology of pediatric anaphylaxis admissions to North American pediatric intensive care units (PICUs) that were prospectively enrolled in the Virtual Pediatric Systems database from 2010 to 2015. One hundred thirty-one PICUs in North America (United States and Canada) were queried for anaphylaxis International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision codes from the Virtual Pediatric Systems database from 2010 to 2015 in the United States and Canada. One thousand nine hundred eighty-nine patients younger than 18 years were identified out of 604,279 total number of patients admitted to a PICU in the database during this time frame.RESULTS:The primary outcome was mortality, which was compared with patient and admission data using Fisher exact test. Secondary outcomes (intubation, length of stay, mortality risk scores, systolic blood pressure, and pupillary reflex) were analyzed using the Kruskal-Wallis test or Wilcoxon rank-sum test, as appropriate. One thousand nine hundred eighty-nine patients with an anaphylaxis International Classification of Diseases code were identified in the database. One percent of patients died because of critical anaphylaxis. Identified triggers for fatal cases were peanuts, milk, and blood products. Peanuts were the most common trigger. Children were mostly male when younger than 13 years, and mostly female when 13 years and older. Average length of stay was 2 days. There was a higher proportion of Asian patients younger than 2 years or when the trigger was food.CONCLUSIONS:This is the largest study to describe pediatric critical anaphylaxis cases in North America and identifies food as the most common trigger. Death occurs in 1% of cases, with intubation occurring most commonly in the first hour. The risk for intensive care unit admission in children underscores the serious nature of anaphylaxis in this population.

Serum Baseline Tryptase Level as a Marker for the Severity of Anaphylaxis

Background: Anaphylaxis is a severe and potentially fatal allergic disease or hypersensitivity reaction with variable clinical presentation. Biomarkers in anaphylaxis could be useful to improve diagnosis, to allow endotyping of patients, and to predict risk. Objective: To investigate the role of serum basal tryptase (sBT) levels in the management of patients with anaphylaxis. Methods: Patients with at least 1 episode of anaphylaxis were selected among those who attended the Allergy Clinics of the Clinical Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, upon evaluation by allergy/immunology specialists of our medical staff. Demographic and clinical data were obtained using a structured questionnaire. sBT levels were determined using the ImmunoCAP Tryptase immunoassay. Results: 57 patients (56.1% female) with a median age of 35 years (range 7–87 years) participated in the study. sBT levels ranged from 2.57 to 21.19 ng/mL (mean 5.17 ng/mL), with no significant differences in patients with anaphylaxis due to different triggers. Mean levels were 4.93; 5.2; 5.41, and 5.24 ng/mL for patients who had anaphylaxis due to Hymenoptera venom (n = 17), foods (n = 13), drugs (n = 13), and idiopathic disease (n = 14), respectively. Significantly higher sBT levels were observed in patients with severe anaphylaxis (grade IV) than in patients with mild-moderate disease (grades II/III) (mean levels 6.61 vs. 4.71 ng/mL, respectively). Conclusion: High sBT levels may help to identify patients at increased risk of more severe anaphylaxis, prompting physicians to initiate immediate therapy to avoid further acute episodes.

An ounce of caution: Superparamagnetic iron oxide nanoparticle based magnetic resonance imaging contrast–associated anaphylaxis

Superparamagnetic iron oxide nanoparticles are increasingly used alternatives to gadolinium-based magnetic resonance imaging (MRI) contrast agents in the diagnosis of osteomyelitis in diabetic patients with renal failure. 1 Neuwelt A. Langsjoen J. Byrd T. et al. Ferumoxytol negatively enhances T2 -weighted MRI of pedal osteomyelitis in vivo. J Magn Reson Imaging. 2017; 45: 1241-1245 Crossref PubMed Scopus (6) Google Scholar Ferumoxytol is approved by the United States Food and Drug Administration and the European Medicines Agency for intravenous use for iron replacement therapy. 1 Neuwelt A. Langsjoen J. Byrd T. et al. Ferumoxytol negatively enhances T2 -weighted MRI of pedal osteomyelitis in vivo. J Magn Reson Imaging. 2017; 45: 1241-1245 Crossref PubMed Scopus (6) Google Scholar , 2 Nguyen K.L. Yoshida T. Han F. et al. MRI with ferumoxytol: a single center experience of safety across the age spectrum. J Magn Reson Imaging. 2017; 45: 804-812 Crossref PubMed Scopus (36) Google Scholar , 3 Muehe A.M. Feng D. von Eyben R. et al. Safety report of ferumoxytol for magnetic resonance imaging in children and young adults. Invest Radiol. 2016; 51: 221-227 Crossref PubMed Scopus (58) Google Scholar Ferumoxytol is composed of an iron–carbohydrate complex that minimizes dissociation and appearance of free iron into the serum. This stability allows the drug to be given in relatively large doses at rapid infusion rates while lowering the potential for immunogenic reactions as seen in low-molecular-weight iron dextran. 4 Pai A.B. Garba A.O. Ferumoxytol: a silver lining in the treatment of anemia of chronic kidney disease or another dark cloud?. J Blood Med. 2012; 3: 77-85 PubMed Google Scholar However, recent reports of severe hypersensitivity reactions have raised concern regarding its safety—these data led to a United States Food and Drug Administration–issued Black Box warning in 2015 for the risk of potentially fatal hypersensitivity reactions. 2 Nguyen K.L. Yoshida T. Han F. et al. MRI with ferumoxytol: a single center experience of safety across the age spectrum. J Magn Reson Imaging. 2017; 45: 804-812 Crossref PubMed Scopus (36) Google Scholar , 5 Varallyay C.G. Toth G.B. Fu R. et al. What does the boxed warning tell us? Safe practice of using ferumoxytol as an MRI contrast agent. AJNR. 2017; 38: 1297-1302 Crossref PubMed Scopus (36) Google Scholar We report a rare, life-threatening immediate hypersensitivity reaction potentially related to ferumoxytol MRI contrast agent.