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Background: Shellfish allergy is a major cause of food allergy and anaphylaxis worldwide. Several allergenic proteins have been described in the last few years, but the only diagnostic tool that still enables discrimination between allergic and nonallergic sensitized persons is the oral food challenge (OFC). Objective: The aim of this study was to evaluate the usefulness of the nasal allergen provocation test (NAPT) as a diagnostic tool in shellfish allergy. Methods: Forty-five patients with confirmed sensitization to shrimp by a positive skin prick test (SPT) result with a commercial shrimp extract were recruited and classified as sensitized-allergic or sensitized-nonallergic based on current tolerance to shrimp intake, the result of an OFC with a freeze-dried cooked shrimp mixture extract, or a recent history of anaphylaxis induced by shrimp ingestion. These patients and 10 controls not sensitized to shrimp underwent NAPT with a freeze-dried cooked shrimp mixture extract. The response was evaluated using acoustic rhinometry and a visual analog scale. Results: Significant differences (P=.001) were found between the sensitized-allergic group (18/20 positive NAPT, 90%) and both the sensitized-nonallergic group (2/18 positive NAPT, 11.1%) and controls (0/10 positive NAPT). NAPT enables differentiation between allergic and nonallergic persons with a sensitivity of 90%, specificity of 89%, positive predictive value of 90%, and negative predictive value of 89%. Conclusions: Our results indicate that NAPT makes it possible to differentiate between sensitized symptomatic patients and sensitized tolerant patients and could be a valuable diagnostic tool when assessing shrimp allergy.

Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P

In India, bee stings are very common, seen mainly in farmers and honey collectors. Usually, it presents with local reactions and anaphylaxis. It rarely requires urgent hospitalisation. Other major complications seen are acute renal failure, intravascular coagulation, rhabdomyolysis and acute pulmonary oedema. Stroke as a presentation is uncommon. We report a case of a 45-year-old man presenting with right-sided hemiplegia and aphasia due to multiple bee stings. Diffusion MRI showed left middle cerebral artery territory hyperacute infarct.

A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.

Background Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about allergens implicated in hypersensitivity reactions to these seeds. The present work aimed to identify the allergens involved in IgE-mediated reactions in five patients with a clinical history of severe systemic symptoms after flaxseed consumption. Methods Proteins susceptible to be allergens with IgE-binding capacity were purified from flaxseed extract by chromatographic techniques. Their identification was achieved via MALDI-TOF mass spectrometry. Immunoassays were performed using the five allergic patient's era either by testing them individually or as a pool. Results Proteins susceptible to be allergens with IgE-binding capacity were purified from flaxseed extract by chromatographic techniques. Their identification was achieved via MALDI-TOF mass spectrometry. Immunoassays were performed using the five allergic patient's era either by testing them individually or as a pool. Results: Four out of five patients recognized a low-molecular-mass protein (around 13kDa) by immunoblotting of the flaxseed extract, while two patients recognized a protein of approximately 55 kDa. They were identified by mass spectrometry as flaxseed 2S albumin, included into WHO/IUIS allergen nomenclature as Lin u 1,and 11S globulin, respectively. Inhibition assays revealed in vitro IgE-cross-reactivity of Lin u 1 with peanut and cashew nut proteins, while IgE recognition of 11S globulin by patients' sera was partially inhibited by several plant-derived sources. Conclusions Seed storage proteins from flaxseed were involved in the development of severe symptoms in five individuals and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, it is the first time that the 11S globulin is identified as a potential allergen. We consider that these data should be taken into account for a more accurate diagnosis of patients.

Objective Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. Methods In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after approval by Oral Food Challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. Results All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. Conclusion This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab obviously reduced the severity of reactions.

Introduction Alpha-gal syndrome is a potentially severe food allergy caused by the presence of alpha-gal-specific IgE. The aim of this study is to describe our series of 13 patients. Material and methods This work is a retrospective study of patients diagnosed in 2016 and 2017. Skin tests were performed with commercial extract and gelaspan as well as specific IgE determination for alpha-gal and different types of meat. Results Thirteen patients diagnosed with alpha-gal syndrome were analyzed; 9 of them had anaphylaxis, 6 of whom had been diagnosed with idiopathic anaphylaxis. All had a positive skin test with gelaspan, though this was not true with the commercial extracts, whose results were less conclusive. Conclusions We believe that a diagnosis of idiopathic anaphylaxis may prevent the identification of patients with alpha-gal syndrome. The gelaspan skin test is more useful than commercial extracts.

Background: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. Objective: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. Methods: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term “anaphylaxis” with “death”, “study design”, and “main outcomes” (incidence). Results: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. Conclusion: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

This case study is a rare example of cardiac hydatidosis in a high-income country, where a middle-aged man presented with a ruptured right ventricular cyst causing anaphylaxis, pulmonary emboli and dissemination ofEchinococcusthroughout the lung. He survived the cyst rupture and underwent cardiac surgery but had incomplete resection and experienced progressive cardiopulmonary hydatidosis despite antihelminthic therapy. As a result, he experienced an array of cardiopulmonary sequelae over his lifespan. This case report highlights rare clinical manifestations of hydatid disease and potential complications of its treatment.

Introduction Mast cells are regarded as a kind of classical anaphylaxis cells. However autoimmune diseases and allergic reactions have many similarities or overlaps. A large number of papers have proved that mast cells play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). It is speculated that IgE, anti‐IgE antibodies, FcεRI, and anti‐FcεRI antibodies activate mast cells through autoimmune pathways and participate in the disease process of SLE. Naturally occurring protein molecules not only exist in monomer form, but also in polymer of protein molecules. Therefore, whether IgE, FcεRIα, anti‐IgE antibodies, and anti‐FcεRI antibodies also exist in polymeric forms in the natural state is worthy of further investigation. Methods The serum samples and clinical data of 131 patients with SLE were collected from Qilu Hospital (Qingdao). Sixty healthy individuals were collected as the control group. Serum FcεRIα, anti‐IgE, and anti‐FcεRI were detected by enzyme‐linked immunosorbent assay. Serum IgE was detected by rate scatter nephelometry. A Chinese hamster ovarian cancer cell line CHO3D10 transfected with human FcεRIα was cultured and the cell protein extract was prepared. The existence forms of FcεRIα in the cell protein extract were detected by the native‐page method. Results The serum FcεRIα in SLE patients was significantly higher than that in control group (3.52 [2.18, 4.71] µg/ml and 1.87 [1.52, 2.33] µg/ml, respectively; p, First, as autoimmune diseases and allergic reactions have many similarities or overlaps, we compared the differences in serum IgE, FcεRIα, anti‐IgE, and anti‐FcεRI levels of systemic lupus erythematosus group and healthy control group for the first time. The serum FcεRIα in SLE patients is significantly higher than that in the control group and anti‐IgE is significantly lower than that in the control group, which provides a new reference basis for the understanding and further discussion of the inflammatory mechanism of the disease. Second, this study has revealed that the FcεRIα has one kind of monomer and two kinds of polymers in the degeneration conditions, which is worthy of further investigation.

Anaphylaxis-related emergency department (ED) visits and hospitalizations are increasing. Triggers for anaphylaxis include food, medications, and stinging insects. Idiopathic anaphylaxis accounts for 30% to 60% of cases of anaphylaxis in adults and up to 10% of cases in children with novel allergens such as galactose-α-1,3 galactose reclassifying these cases. Recent practice guidelines have recommended against the routine use of systemic corticosteroids and antihistamines for the prevention of biphasic reactions and recommend an extended observation, up to 6 hours, for those with risk factors for biphasic anaphylaxis and those with lack of access to epinephrine and to emergency medical services.

Epinephrine is a lifesaving medication to treat systemic allergic reactions including anaphylaxis. Epinephrine autoinjectors (EAIs) are expensive, not available everywhere in the world, and shortages can limit their access. Epinephrine prefilled syringes and epinephrine kits are lower-cost alternatives to EAIs. Advantages, disadvantages, and costs of available products are discussed and the socioeconomic factors impacting access to EAIs described. EAIs designed for infants also are discussed.

There is a myriad of immunologic and nonimmunologic pathways by which the clinical phenotype of anaphylaxis can be produced. An understanding of these pathways is essential for the prevention as well as the treatment of anaphylactic episodes.

There is strong evidence of an association between severe anaphylaxis, especially hymenoptera venom induced, and mast cell (MC) disorders. It has been thought that intrinsic abnormalities in MCs, including the presence of the activating KIT D816V mutation in mastocytosis or of genetic trait, hereditary alpha-tryptasemia, may influence susceptibility to severe anaphylaxis. This article evaluates the potential mechanisms leading to severe MC activation, as well as the differential diagnosis of and range of symptoms attributable to MC mediator release. Also, we offer a global classification for disorders related to MC activation.

Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods.

Delayed administration of epinephrine (adrenaline), the first-line and only effective treatment of a systemic allergic reaction (SAR) and anaphylaxis, is associated with increased mortality. However, epinephrine is underused because of a lack of consensus as to when it should be administered and an inappropriate fear of using epinephrine and potential adverse effects from the medication. The authors emphasize that SARs and anaphylaxis should be considered as a spectrum, and that affected individuals be educated on its safety and repeatedly given instructions as to when and how epinephrine should be used at the first symptoms or signs of SAR and anaphylaxis.

There are significant anaphylaxis data and knowledge gaps that result in suboptimal patient care and outcomes. To address these gaps there is need for collaborative, multidisciplinary research networks to strategically design practice changing research specific to the following anaphylaxis themes: Population Science, Basic and Translational Sciences, Acute Management, and Long-Term Management. Top priorities are to refine anaphylaxis diagnostic criteria, identify accurate diagnostic and predictive anaphylaxis biomarkers, standardize postanaphylaxis care (observation periods, hospitalization criteria), and determine immunotherapy best practices. Addressing these gaps will result in improved, optimal care and clinical outcomes for patients with or at risk of anaphylaxis.

Background The mechanism of coronavirus disease 2019 (COVID-19) vaccine hypersensitivity reactions is unknown. COVID-19 vaccine excipient skin testing has been used in evaluation of these reactions, but its utility in predicting subsequent COVID-19 vaccine tolerance is also unknown. Objective To evaluate the utility of COVID-19 vaccine and vaccine excipient skin testing in both patients with an allergic reaction to their first messenger RNA COVID-19 vaccine dose and patients with a history of polyethylene glycol allergy who have not yet received a COVID-19 vaccine dose. Methods In this multicenter, retrospective review, COVID-19 vaccine and vaccine excipient skin testing was performed in patients referred to 1 of 3 large tertiary academic institutions. Patient medical records were reviewed after skin testing to determine subsequent COVID-19 vaccine tolerance. Results A total of 129 patients underwent skin testing, in whom 12 patients (9.3%) had positive results. There were 101 patients who received a COVID-19 vaccine after the skin testing, which was tolerated in 90 patients (89.1%) with no allergic symptoms, including 5 of 6 patients with positive skin testing results who received a COVID-19 vaccine after the skin testing. The remaining 11 patients experienced minor allergic symptoms after COVID-19 vaccination, none of whom required treatment beyond antihistamines. Conclusion The low positivity rate of COVID-19 vaccine excipient skin testing and high rate of subsequent COVID-19 vaccine tolerance suggest a low utility of this method in evaluation of COVID-19 vaccine hypersensitivity reactions. Focus should shift to the use of existing vaccine allergy practice parameters, with consideration of graded dosing when necessary. On the basis of these results, strict avoidance of subsequent COVID-19 vaccination should be discouraged.

There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization's Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.

After treating the acute anaphylactic reaction, the clinician's next task is to prevent a recurrence. The patient should be observed in the ED. How long this observation period should last depends on their clinical course, risk factors, and social support. All patients should be discharged with a prescription for 2 epinephrine autoinjectors and counseled on appropriate use. The patient should also receive education on the signs and symptoms of anaphylaxis and avoiding triggers. The patient should follow-up with an allergy specialist who can confirm triggers and provide immunotherapy as indicated.

Anaphylaxis is a systemic allergic reaction that can be caused by food, drugs, insect bites, or unknown triggers in infants and toddlers. Anaphylaxis rates are increasing. Infants and toddlers may have increased exposure to known and unknown allergens, decreased ability to describe their symptoms, and an expanded differential diagnosis for consideration on presentation. The most common symptoms in these age groups are cutaneous and gastrointestinal. Age-specific language may be helpful for caregivers to identify and describe the symptoms of anaphylaxis in infants and toddlers. Long-term management of anaphylaxis includes allergy evaluation to guide avoidance and assess prognosis and education on allergic reaction management; this incorporates the prescription of epinephrine autoinjector and provision of an allergy emergency plan.

Background The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain’s susceptibility is not known. Objective We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. Methods We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. Results In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Conclusions Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.

Perioperative anaphylaxis is relatively rare but can be life-threatening. The incidence in China is unknown and may differ from other global geographic regions. This study was therefore designed to understand the incidence of perioperative anaphylaxis in China.We enrolled 112 tertiary care hospitals from seven distinct geographic areas in mainland China. We collected information about Ring and Messmer III and IV reactions from September 2018 to August 2019. A collaborative educational learning network was used to reduce diagnostic errors. Information about patient characteristics, clinical features, treatment, and clinical outcomes were recorded and analysed.A total of 447 cases of 5 078 118 surgical procedures met inclusion criteria. The incidence of suspected perioperative anaphylaxis throughout China was one in 11 360 anaesthetics (95% confidence interval [CI], with a range of 1:12 521 to 1:10 397). The incidence in South China was higher (one in 6050; 95% CI, from 1:8013 to 1:4859) than in Northeast China (one in 19 262; 95% CI, from 1:33 088 to 1:13 585) (P0.01) with an increasing trend from the north to the south. The most common clinical manifestations were hypotension (91.1%) and tachycardia (65.3%). The majority of patients (83.4%) were given epinephrine. A total of 27 patients (6.0%) required cardiopulmonary resuscitation. Ultimately, nine patients died (2.0%).This nationwide survey showed an incidence of perioperative anaphylaxis of one in 11 360, but this varied significantly by region. The underlying reason for this pattern remains unknown and could be attributable to environmental or genetic influences, which requires further investigation.ChiCTR1900025956.

Although there is a general perception that the prevalence of food allergy is increasing, data supporting this are limited. Food is the least common cause of fatal anaphylaxis, and fortunately, it is a very rare event; however, it is also unpredictable. There is widespread consensus that severe reactions cannot be predicted in a clinically meaningful way. Certain food triggers are more frequently associated with fatal anaphylaxis than others. In observational studies, peanut and tree nuts account for at least 30% to 50% of fatalities, with seafood and cow's milk also associated with fatal reactions. Fatal food-induced anaphylaxis is most likely to occur during adolescence and young adulthood, although the reasons for this are unclear. International guidelines agree that intramuscular (IM) epinephrine is the treatment of choice for managing food-triggered anaphylaxis and has a good safety profile when given by the IM route. However, fatalities still occur despite the timely administration of epinephrine. Food-allergic individuals must navigate a world that requires daily vigilance for allergens and preparedness for allergic reactions. Although the actual risk of fatal reactions is minimal, it is not zero, and severe reactions are unpredictable. Clinicians need to help patients better understand the very low but real risk of fatal reaction and enable them to lead as normal a life as possible through appropriate education, safety netting, and risk reduction.

Although relatively rare, immediate perioperative hypersensitivity reactions (POH) are important complications of drug administration prior to, during and after surgical and other interventional procedures. Both the incidence of immediate POH as well as their major culprits are difficult to establish and vary considerably between reports; the incidence may be as high as 1:1250 or almost a tenfold lower.(1) Most studies have a yield of positive allergy test results of 50 to 60%, suggestive of an immunoglobulin E (IgE)-mediated reaction. Neuromuscular blocking agents (NMBA) were shown to be the most common cause of immediate POH in various countries including France and Australia,(2) while other countries (U.S.A., U.K., Spain, Denmark) identify antibiotics to be the primary culprit.(1, 3, 4).

Background Natto (fermented soybeans)-induced hypersensitivity is characterized by delayed symptom onset that hampers diagnosis. We aimed to clarify the clinical utility of the basophil activation test (BAT) in the diagnosis of natto-induced hypersensitivity. Methods Five patients with a history of anaphylaxis and chronic urticaria suspected of natto-induced hypersensitivity and seven with chronic spontaneous urticaria clinically unrelated to natto were enrolled in the patient and control groups, respectively. The BAT was performed with two incubation times, 15 min and 1 h, in combination with various concentrations of natto-mucilage extract. Results In controls, CD203c levels in basophils remained low in the 15-min incubation but were significantly increased in the 1-h incubation. In the patient group, in the 15-min condition, basophil CD203c was significantly upregulated by natto mucilage but not by soybean vs controls (P = 0.001). Low concentrations of natto mucilage were sufficient to upregulate basophil CD203c in the anaphylaxis cases, but high concentrations were required to induce the same effect in the urticaria cases. Finally, the dose-dependent pattern of the BAT results differed significantly between the anaphylaxis and urticaria cases (P = 0.006). Thus, a strong background reaction was observed in the BAT with 1 h incubation; 15 min of incubation was sufficient to identify patients with natto-induced hypersensitivity and may distinguish the clinical phenotype of natto-induced hypersensitivity, i.e., anaphylaxis or urticaria. Conclusions The BAT with a 15-min incubation period is useful in diagnosing natto-induced hypersensitivity.

The challenge of delabeling amoxicillin allergy is an important issue for patients and clinicians, especially when anaphylaxis is reported. A recent study has proposed a clinical decision rule, PEN-FAST, to identify low-risk penicillin allergies.To validate the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy and to identify clinical predictive factors of amoxicillin immediate hypersensitivity.We retrospectively analyzed medical records of patients with a suspected immediate amoxicillin allergy who carried out an allergologic evaluation by a specialist in the Allergy Unit of Strasbourg University Hospital from 2015 to 2020.A total of 142 adult patients (88 women [62.0%]; median age, 52 [interquartile range, 40.3-62.0] years) were analyzed. Most of them reported anaphylaxis (68.8%). Internal validation of PEN-FAST score revealed a good discrimination with area under the curve of 0.86 (95% confidence interval, 0.79-0.92). A cutoff of less than 3 points for PEN-FAST was used to classify 29 from 142 patients at low risk of allergy, of whom only 2 (6.9%) received positive results of allergy testing. The negative predictive value for successful delabeling was 0.93 (95% confidence interval, 0.77-0.99). Predictive clinical features for immediate amoxicillin hypersensitivity were time since reaction (P.001), time elapsed between drug intake and first symptom (P.001), severity grade reaction (P.001), and treatment or hospitalization required (P.001).PEN-FAST has been validated to identify low-risk penicillin allergies in our European cohort of patients mainly reporting anaphylaxis. This is the first reported external validation of a penicillin allergy clinical decision rule internationally.

Background/Aim Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen are the 3 COVID-19 vaccines authorized for emergency use in the United States. This study aims to analyze and compare adverse events following immunization associated with these COVID-19 vaccines based on Vaccine Adverse Effect Reporting System data. Methods We utilized Vaccine Adverse Effect Reporting System data from January 1, 2021 to April 30, 2021 to analyze and characterize adverse effects postvaccination with these authorized COVID-19 vaccines in the US population. Results A total of 141,208 individuals suffered at least one adverse events following immunization following 239.97 million doses of COVID-19 vaccination. The frequency of side effects was 0.04%, 0.06%, and 0.35% following administration of Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen vaccines, respectively. Most of the patients had mild systemic side effects, the most common being headache (0.01%) and fever (0.01%). The frequency of serious side effects including anaphylaxis (0.0003%) and death (0.002%) was extremely low. Conclusions The three COVID 19 vaccines have a wide safety profile with only minor and self-limiting adverse effects. However, continued monitoring and surveillance is required to review any unexpected serious adverse effects.

Summary Gonzalez-Estrada and colleagues report an estimated risk of severe or fatal perioperative anaphylaxis of one in 6,825 procedures during the period 2005–2014. This is slightly higher than that reported previously in France and England. Several predictors of near-fatal and fatal reactions are identified, such as increased age, cancer, and congestive cardiac failure.

We retrieved data on 8,940 anaphylaxis cases post-COVID-19 vaccination from the US Vaccine Adverse Event Reporting System and the European EudraVigilance from week 52/2020 through week 31/2021 and compared them with those of other vaccines. Overall, 837,830,000 COVID-19 vaccine doses were delivered in the US and Europe during the study period, for which the vaccine name was known. The mean anaphylaxis rate was estimated at 10.67 cases per 106 doses of COVID-19 vaccines (range: 7.99-19.39 cases per 106 doses depending on the vaccine). COVID-19 vaccines ranked fifth in reported anaphylaxis rates, behind rabies, tick-borne encephalitis, measles-mumps-rubella-varicella, and human papillomavirus vaccines (70.77, 20, 19.8, and 13.65 cases per 106 vaccine doses, respectively). COVID-19 vaccines are within the range of anaphylaxis rates reported across several common vaccines in these two passive reporting systems. These data should be communicated to reassure the general population about the safety profile of COVID-19 vaccines.

The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS. Key words: Anaphylaxis. Antimediator therapy. Mast cell activation syndrome. Mast cell mediator release–related symptoms. Tryptase.

BACKGROUND Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.

Objective To describe our current understanding of hereditary α-tryptasemia (HαT), how HαT fits into the evolutionary context of tryptases and contemporary framework of mast cell–associated disorders, and to discuss the future clinical and therapeutic landscape for symptomatic individuals with HαT. Data Sources Primary peer-reviewed literature. Study Selections Basic, clinical, and translational studies describing tryptase gene composition, generation, secretion, and elevation and the associated clinical impacts of HαT and treatment of such individuals were reviewed. Results HαT is a common autosomal dominant genetic trait caused by increased TPSAB1 copy number encoding α-tryptase. Approximately 1 in 20 White individuals have HαT, making it by far the most common cause for elevated basal serum tryptase levels. Although many individuals with HαT may not manifest associated symptoms, the prevalence of HαT is increased in patients with clonal and nonclonal mast cell–associated disorders wherein it is linked to more prevalent and/or severe anaphylaxis and increased mast cell mediator-associated symptoms. Increased generation of mature α/β-tryptase heterotetramers, and their unique physiochemical properties, may be responsible for some of these clinical findings. Conclusion HαT is a common modifier of mast cell–associated disorders and reactions. Nevertheless, whether HαT may be an independent cause of clinical phenotypes with which it has been associated remains unproven. Correct identification of HαT is critical to accurate interpretation of serum tryptase levels in the clinical evaluation of patients. Beyond HαT, we foresee tryptase genotyping as an important parameter in the standard workup of patients with mast cell–associated disorders and development of therapeutic modalities targeting these patients and associated clinical phenotypes.

Hypersensitivity (HS) reactions to antituberculosis drugs are difficult to manage, notably since the advent of multiresistant tuberculosis. In patients with immediate HS to antituberculosis drugs, a rapid desensitization(DS) procedure may represent an interesting alternative. Study objectives Describe the procedure for rapid oral DS with rifampicin syrup/suspension and demonstrate its contribution to the management of tuberculosis (TB). Methods A cross sectional study including patients followed-up for tuberculosis in pulmonology C department of Abderrahman Mami Ariana hospital between 2003–2020. Patients with confirmed immediate HS were desensitized with a suspension of Rifampicin (100 mg/5 ml). Informed consent of patients or guardian was required. Results Ultrarapid DS with rifampicin syrup/suspensionwas performed in 14 patients (8 men, 6 women, mean age 32 ± 12.5 years). The mean times between initiation of the treatment, the last administration of the drug and onset ofthe reactions were 16.5 days (range:3–47 days) and 204 minutes (20–420 min)respectively. Most reactions were urticaria, pruritus and erythema. Severe anaphylaxis was reported in 2 cases and Quincke edema in 1 case. Nine patients (64.3%) were successfully desensitized. In 5 patients (35.7%), ultrarapid desensitization failed. Conclusion Reactions to rifampicin are diverse and unpredictable. The severity of the allergic reaction and the absence of other effective therapeutic alternatives are arguments in favor of drug desensitization. Despite the diversity of protocols reported in the literature, the results of desensitization are generally favorable, with a significant success rate.

The objective of this study is to develop an evidence-based nursing practice protocol to cope with anaphylaxis by identifying the effect of early administration of epinephrine on the recovery of patients when anaphylaxis occurs due to computed tomography (CT) contrast agents, and to evaluate its feasibility. Anaphylaxis caused by CT contrast agents is a life-threatening systemic hypersensitivity reaction compared to normal allergic reactions, requiring immediate administration of epinephrine and other emergency drugs; however, no practical guidelines have been established for such emergency management, requiring the development of evidence-based nursing practice protocols. The study design is a methodological and cross-sectional study that aims to develop an evidence-based nursing practice protocol. An evidence-based nursing practice protocol for anaphylaxis management generated by contrast agents was developed in accordance with the 3-step (12 more specific steps) development of clinical practice guideline based on the literature of the final 12 selected (including 2 guidelines). It was applied to practice after implementing the training of the medical staff on the final protocol developed, and evaluated the effectiveness of anaphylaxis management for 6 months before and after the application of the protocol. Based on the analysis of the evidence, we make six recommendations for managing anaphylaxis caused by contrast agents based on early administration of epinephrine and apply the protocol to clinical practice. After protocol application, awareness of anaphylaxis and onset time of epinephrine administration was accelerated, but significant differences were not confirmed. In the case of anaphylaxis due to CT contrast agents, evidence-based coping protocols were created. The developed protocol should be continued for use in practice, with continued assessment of its effectiveness.

Hymenoptera venom anaphylaxis is the most frequent cause of anaphylaxis and responsible for about 20% of all fatal anaphylaxis cases in adults. We report two cases of fatal hymenoptera venom anaphylaxis with undiagnosed underlying mastocytosis and review the risk factors for severe or fatal hymenoptera venom anaphylaxis, as well as the specificities of its association with mastocytosis. As hymenoptera venom allergic patients with underlying clonal mast cell disorder generally lack typical skin lesions of mastocytosis, its diagnosis can easily be missed, underscoring the importance and need for diagnostic strategies in order to correctly identify these patients. Predominant cardiovascular symptoms in the absence of urticaria or angioedema following an insect sting are suggestive of underlying clonal mast cell disorder, and should be distinguished from panic attack or vasovagal syncope. Similarly, an unexplained syncope or an "idiopathic" anaphylaxis might reveal mastocytosis or hereditary alpha-tryptasemia. Acute and basal serum tryptase measurements should always be integrated in the diagnostic work-up of an insect sting reaction or unexplained syncope or shock of any origin.

Background The incidence of fatal and near-fatal outcomes after perioperative anaphylaxis is unknown in the USA. Previously identified risk factors of neuromuscular-blocker-induced fatal perioperative anaphylaxis include male sex, obesity, and use of beta blockers. We examined the incidence of fatal and near-fatal outcomes after perioperative anaphylaxis in the USA and the underlying risk factors using a large national database. Methods Using the Nationwide Inpatient Sample from 2005 to 2014, we identified cases of fatal and near-fatal perioperative anaphylaxis, defined as perioperative anaphylaxis cases complicated by respiratory or cardiac arrest, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results Amongst 5223 perioperative anaphylaxis cases, the proportion of near-fatal or fatal cases attributable to perioperative anaphylaxis was 7.0% (95% confidence interval [CI]: 6.2–7.7), with near-fatal perioperative anaphylaxis cases accounting for 5.0% (95% CI: 4.4–5.6%) and fatal cases accounting for 2.0% (95% CI: 1.5–2.5%) of cases overall. Thus, the incidence of fatal or near-fatal perioperative anaphylaxis is 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal perioperative anaphylaxis include age (≥65 yr); undergoing a cardiac procedure; and comorbid conditions of weight loss, non-metastatic solid tumours, metastatic cancer, paralysis, coagulopathy, renal failure, congestive heart failure, fluid and electrolyte disorder, and neurological disorders. Individuals with near-fatal or fatal perioperative anaphylaxis reactions had increased lengths of stay and hospital costs compared with controls. Conclusions The incidence of fatal or near-fatal perioperative anaphylaxis in the USA was 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal outcomes include older age, cardiac procedures, and specific comorbidities.

Macrolides are antibiotics that can be used to treat various infections. Allergic reactions to macrolides are rare, but may include minor to severe skin reactions, as well as systemic life-threatening reactions such as anaphylaxis. Hypersensitivity reactions can occur in any mode of administration and to almost all antibiotics. The purpose of the study was to determine whether there are reactions to macrolides in the study population, and to determine statistically significant differences in the occurrence of allergic reactions to macrolides between boys and girls of the same age and whether there are differences in the occurrence of allergic reactions between respondents in urban and rural areas. The sample consists of 1605 respondents, the sample was randomly selected and stratified by sex, and all data were processed in the statistical program. The results of the research show that 9.1% of the total population of boys and girls aged 15 from the Tuzla Canton are allergic to some type of antibiotic. The percentage of allergic reactions in the total population of 15-year-olds from suburban settlements is slightly higher than among peers in urban areas, but the differences are not statistically significant. A higher rate of allergic reactions was recorded in the group of boys from urban and rural areas. Macrolide allergies were found only in a group of boys in rural areas. This study confirmed that allergies to macrolides are rare and revealed differences in the occurrence of allergic reactions between girls and boys.

After initial reports of anaphylaxis to the messenger RNA (mRNA) COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC) put forth guidance stating that patients with a history of anaphylaxis to vaccine components like polyethylene glycol (PEG) should not receive the mRNA COVID-19 vaccines.1 To address this clinical challenge and decrease vaccine hesitancy, we published an approach to guide COVID-19 vaccination in high-risk allergy individuals.2-4 While the etiology of anaphylaxis to mRNA COVID-19 vaccines remains unclear, PEG continues to be an important focus.5,6 Paclitaxel contains polyoxyl-35 castor oil --a PEG derivative and structurally similar to the excipient in Pfizer-BioNTech and Moderna COVID-19 vaccines-- and docetaxel contains polysorbate 80 --the excipient in Janssen COVID-19 vaccine. Given this, we sought to assess the utility of pre-vaccine excipient skin testing (ST), risk stratification and COVID-19 vaccine tolerability in oncology patients with a history of paclitaxel or docetaxel hypersensitivity reaction (HSR).

Anaphylaxis has rapidly spread around the world in the last several decades. Environmental factors seem to play a major role, and epigenetic marks, especially DNA methylation, get more attention. We discussed several GEO opening data classifications with TOP 100 specific methylation region values (normalized M-values on line) by machine learning, which are remarkable to classify specific anaphylaxis after monoallergen exposure. Then, we sequenced the whole-genome DNA methylation of six people (3 wormwood monoallergen atopic rhinitis patients and 3 normal-immune people) during the pollen season and analyzed the difference of the single nucleotide and DNA region. The results’ divergences were obvious (the differential single nucleotides were mostly distributed in nongene regions but the differential DNA regions of GWAS, on the other hand), which may have caused most single nucleotides to be concealed in the regions’ sequences. Therefore, we suggest that we should conduct more “pragmatic” and directly find special single-nucleotide changes after exposure to atopic allergens instead of complex correlativity. It is possible to try to use DNA methylation marks to accurately diagnose anaphylaxis and form a machine learning classification based on the single methylated CpGs.

Introduction: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. Methods: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). Results: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). Conclusion: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.

BACKGROUND Patient-reported allergies to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) may preclude certain patients from receiving aspirin as venous thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA). The purpose of the study was to (1) determine whether the use of non-aspirin agents due to a self-reported aspirin or NSAID allergy was associated with a higher incidence of VTE and (2) determine the rate of true allergic reactions in patients who reported an allergy but still received aspirin. METHODS Prospectively collected data from 45,171 patients who underwent primary TJA between 2000 and 2019 were reviewed. Patients who reported an allergy to aspirin or NSAIDs were identified (n = 823). Using a validated VTE risk calculator, each patient was assigned a risk score based on 26 comorbidities. Bleeding complications, VTEs that occurred within 90 days postoperatively, and allergic reactions were collected as end points. Multivariable logistic regression was performed to determine the factors associated with VTE. RESULTS The overall incidence of aspirin or NSAID allergy was 1.8%. Only 80 of 267 patients (30%) reported an allergy to only aspirin and still received aspirin. Compared with patients who received aspirin without a history of allergy (n = 17,648), patients who received non-aspirin thromboprophylaxis due to allergy (n = 383) had a higher incidence of VTE (2.87% versus 0.24%, p < 0.001). On multivariable regression, these patients had an 8-fold increase in VTE risk (adjusted odds ratio, 7.94; 95% confidence interval, 2.86 to 22.07; p < 0.001). The incidence of true allergic reactions to aspirin among those with a reported allergy was 1.8% (number needed to harm = 55). No patients developed anaphylaxis or severe hypersensitivity reactions. CONCLUSIONS Patients with a self-reported allergy to aspirin or NSAIDs were at a significantly increased risk for VTE if they received non-aspirin thromboprophylaxis agents following TJA. Future research should evaluate the usefulness of preoperative allergy testing when selecting a VTE prophylactic agent in patients with self-reported allergies. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Anaphylaxis is a rapid, potentially fatal, immediate hypersensitivity reaction. Preformed and newly formed biochemical mediators, including histamine, tryptase, carboxypeptidase A, prostaglandin D2, leukotrienes, and platelet-activating factor (PAF) are released systematically during the degranulation of mast cells and basophils. PAF is a proinflammatory phospholipid, synthesized and secreted by mast cells, monocytes and fixed tissue macrophages whose binding to its receptor on target cell-platelet, monocytes, macrophages, and neutrophils results in many of the manifestation of acute allergic reaction and anaphylaxis.

The number of hospitalisations due to an anaphylactic reaction to food is continuously increasing. Therefore, there is an urgent need to seek effective therapy. Currently, the only way to treat food allergies is to avoid allergens and to administer intramuscular adrenaline if an accidental allergen intake occurs. The only causal therapeutic strategy is specific oral immunotherapy. An increasing amount of data confirms this therapy's effectiveness and safety, but the results remain inconclusive due to the lack of long-term follow-up. In this state-of-the-art review, we briefly summarise the latest placebo-controlled randomised controlled trials on oral immunotherapy (OIT) to treat food allergy. During the paper's review, we asked the following questions: does the therapy permanently increase the amount of allergen consumed without symptoms? Does it significantly increase or decrease the occurrence of severe systemic reactions - requiring the administration of adrenaline or hospitalisation? Many authors describe outcomes such as an increase in the amount of allergen that can be safely ingested; however, significant clinical benefits such as decreased hospitalisations or anaphylaxis incidence are rarely included in the results. To date, there is no unified protocol of therapy, which makes comparisons between studies difficult because of significant differences in types, doses, and routes of administration of the allergen, timeline for up-dosing and maintenance, duration of the therapy, and primary outcomes of OIT.

Dengue, with four viral serotypes, causes epidemics in tropical and sub-tropical regions. Allopathic antiviral therapies and a vaccine of general use are lacking. The homeopathic medicine Apis mellifica, advised in anaphylaxis from honeybee sting, is proposed to address the life-threatening dengue shock syndrome, which develops from dengue hemorrhagic fever and has features of anaphylaxis. In both dengue and anaphylaxis, immunoglobulin E activates, and released vasoactive mediators (importantly histamine, tryptase and platelet-activating factor) cause, a vascular permeability enabling shock. In dengue, another mechanism, namely antibody-dependent enhancement, due to secondary infection with a heterologous dengue serotype, is associated with release of vasoactive mediators. The homeopathic medicine Apis mellifica indicates plasma leak, shock, and the serous effusion that is noted in dengue patients, and is a suggested prophylactic and therapeutic medicine for dengue shock syndrome.

More than 50 years after Propranolol was introduced to the pharmaceutical market as a drug that can lower the heart rate, beta-blockers (BAB) are still widely used in the pharmacotherapy of cardiovascular diseases. However, the use of BAB has a number of limitations, first of all, due to adverse drug events (AE) that develop during their use. The purpose of our review was to study the features of the BAB AE manifested by injuries of the skin and its appendages. The clinical manifestations of them are the development or exacerbation of psoriasis, lichen planus, contact dermatitis, acrocyanosis, Raynaud's disease, alopecia, hyperhidrosis, vitiligo, anaphylaxis, and allergic skin reactions. True medicinal psoriasis occurs in patients taking BAB with no family or previous history and most often mimics erythrodermic psoriasis and palmar-plantar pustular psoriasis. Systemic use of BAB can also be accompanied by exacerbation of vitiligo. In patients with segmental vitiligo, the results of Doppler flowmetry and iontophoresis showed increased blood flow in vitiligo foci compared with normal skin. The development of anaphylactic reactions against the background of BAB therapy may be due to the modulation of adenylate cyclase, which can affect the release of anaphylactogenic mediators, as well as a decrease in the severity of cardiovascular compensatory changes. The peculiarities of the development of such reactions may be the resistance of patients to traditional treatment, which is due to the development of paradoxical reflex vagotonic effects when using adrenaline. Some of the mentioned AE may pose a potential threat to the life and health of the patient and therefore require additional discussion.

Histamine is one of the most important and extensively studied biological molecules in the human body. It plays a constitutive role within almost every bodily system, but most notably within the stomach, where it regulates acid secretion, the central nervous system, where it acts as a neurotransmitter, the cardiovascular system, where it affects cardiac output and vascular permeability, and it has a well-established role in allergy and anaphylaxis. Histamine exerts its effects through four distinct receptor subtypes: H1, H2, H3 and H4. Predominantly, though not exclusively, these take the form of G-protein-coupled receptors. Clinically used antihistamines demonstrate inverse agonism to the histamine receptor and drugs are available with activity at H1, H2 and H3 receptors. H1 antihistamines are used in the treatment of allergy, and are classified as either first or second generation. First-generation antihistamines have significant sedative side effects. H2 antihistamines are predominantly used for the treatment of gastroesophageal reflux and peptic ulcer disease; however, the most widely used of these, ranitidine, has been withdrawn from use due to (impurity related) safety concerns. H3 antihistamines have been explored for the treatment of neurological disease and to date the only licenced H3 antihistamine is used for the treatment of narcolepsy. Multiple uses have been suggested for H4 antihistamines, including immunomodulation, the treatment of asthma and even as an analgesic. However, no (commercially available) drug exists as of yet.