Severity Of Anaphylaxis Research Articles

Anaphylaxis: Definition and criteria.

Anaphylaxis is a systemic allergic reaction that may be severe and life-threatening. With more than a dozen anaphylaxis definitions proposed over the past several decades and several diagnostic criteria in circulation, there is a need for a multinational consensus definition to simplify management across specialties. Anaphylaxis diagnostic criteria are more alike than they are different, and approaches of the National Institute of Allergy and Infectious Disease, World Allergy Organization, and Brighton Collaborative help to add granularity and perspective to patient management. Anaphylaxis occurs across a spectrum of severity within populations, although, among individual patients, there is some evidence to suggest more consistency for an individual allergen. Still, severity is influenced by a number of factors that demonstrate variability: factors that relate to allergen triggers, patient characteristics, and treatments received. Severity of anaphylaxis impacts management, and recent guidelines provide approaches that consider individual factors to inform both strong and conditional recommendations. Conditional recommendations serve as navigational signals for shared decision-making when patient expertise is leveraged to inform individual preferences and values together with clinician expertise in anaphylaxis management to provide patient care bespoke to each patient. As novel approaches to both prevention and treatment of anaphylaxis emerge, an understanding of the significance of strong and conditional recommendations becomes critical to providing individualized and appropriate care for patients at risk for anaphylaxis.

A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice

The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. Atotal of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.

Asparaginase-specific basophil recognition and activation predict Asparaginase hypersensitivity in mice.

Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment.

Prehospital and In-Hospital Treatment with Adrenaline and Related Prognosis in Anaphylaxis Patients

Introduction: Although intramuscular adrenaline is the recommended first-line treatment for anaphylaxis, not all patients receive this treatment. The consequences in daily clinical practice are sparsely described. This study aimed to investigate the treatment administered to anaphylactic patients and the related prognosis. Methods: A retrospective register-based study of patients with anaphylaxis referred to the allergy centre, Odense University Hospital (2019–2021). Each patient’s medical records were reviewed for contacts with the emergency departments and the prehospital emergency medical service in the Region of Southern Denmark. The World Allergy Organization (WAO) grading system was used to assess the severity of prehospital and in-hospital anaphylaxis. Furthermore, the treatment administered to the patients was registered. Results: In total, 315 patients were included. The prehospital system had contact with 256 of these patients (two were released prehospitally following treatment and 12 patients had insufficient data to assess anaphylaxis). Of the remaining 242 patients, 115 had anaphylaxis prehospitally (WAO grades 3–5); 59% (67/115) received adrenaline. Among the 67 patients who received prehospital adrenaline, 9 patients (13.4%; 95% CI: 6.3–24.0%) still had anaphylaxis at arrival at the emergency department. Of the 48 patients that were not treated with prehospital adrenaline, 17 patients (35.5%; 95% CI: 22.1–50.5) had anaphylaxis at the arrival to the emergency department. Among the 127 patients without prehospital anaphylaxis (WAO grades 0–2), 22 patients (18.2%; 95% CI: 11.8–26.2%) who did not receive prehospital adrenaline had anaphylaxis at arrival to the emergency department, while none of the 6 patients treated prehospitally with adrenaline had anaphylaxis. Conclusion: Omission of prehospital adrenaline in anaphylactic patients is associated with more severe anaphylactic symptoms at arrival to the hospital. Adrenaline treatment remains suboptimal since only half of the patients received prehospital adrenaline and only 1 out of 4 patients, with clinical signs of anaphylaxis, received adrenaline inside the hospital.

Risk Factors for Refractory Anaphylaxis in the Emergency Department

Background: Anaphylaxis is a serious allergic reaction that has a rapid onset and can result in death. Identifying the factors that trigger anaphylaxis and increase its severity is important for preventing refractory anaphylaxis (RA). In this study, we aimed to determine the factors associated with an increased risk of developing RA. Preventive measures to reduce the frequency and intensity of anaphylactic events are essential to provide the best care for allergic patients. Aggravating factors can trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided.Methods: We retrospectively analyzed the data of 1378 patients over the age of 18 who were diagnosed with anaphylaxis in our clinic between January 1, 2020, and December 31, 2024. We divided the patients into two groups: anaphylaxis and RA. We evaluated the patients’ clinical characteristics in the ED, demographic information, and elicitors that caused anaphylaxis.Results: Of the 1384 anaphylaxis patients included in the study, 46 (3.3%) were diagnosed as RA. We determined that having a history of anaphylaxis is the most important determinant of the increased risk of RA. Having a history of anaphylaxis (OR: 2.87, 95% CI: 1.71–5.72), beta‐blockers/ACEI use (OR: 2.47, 95% CI: 1.71–5.42), IV contrast agent (OR: 2.33, 95% CI: 1.64–5.39), and low blood pressure or related symptoms (OR: 2.34, 95% CI: 1.67–5.43) were more frequently associated with severe reactions.Conclusion: We found that having low blood pressure or related symptoms, a known history of anaphylaxis, beta‐blockers/ACEI, and IV contrast agent are risk factors for RA. To prevent mortality and morbidity in patients with this risk factor, early interventions such as rapidly repeating epinephrine doses and rapid fluid resuscitation should not be avoided.

Impact of Reaction Setting on the Management, Severity, and Outcome of Pediatric Food-Induced Anaphylaxis: A Cross-Sectional Study.

Impact of Reaction Setting on the Management, Severity, and Outcome of Pediatric Food-Induced Anaphylaxis: A Cross-Sectional Study.

Effect of 5-hydroxypyrimidine derivatives and reference drug Aerius on systemic anaphylaxis, concentration of immunoglobulin E and cytokines tested in Balb/c mice

Imbalance of Th1/Th2 lymphocytes and cytokines is responsible for increasing rate of pathology, such as allergy, autoimmune processes and cancer. Pyrimidines have a wide spectrum of pharmacological activity, for example antiallergic properties. The aim of this study is to investigate effects of 5-hydroxypyrimidine derivatives on systemic anaphylaxis, concentrations of immunoglobulin E (IgE) and cytokines in comparison with Aerius in experiments on ovalbumin-induced systemic anaphylaxis model. Effects of 7-day course of intraperitoneal (i/p) administration of SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg, Aerius (i/p, 1.3 mg/kg) were studied in 140 male Balb/c ovalbumin-sensitized mice. 120 mice were immunized by two injections (two-week interval) of ovalbumin (100 mg per mouse) mixed with aluminum hydroxide (5 mg per mouse). 20 mice were used as intact control. Administration of SNK-411, SNK-578, or Aerius began after second immunization and lasted for 7 days. Within one hour after last injection of the compounds, 70 mice received injection of ovalbumin (100 mg dissolved in 0.1 mL saline) in retroorbital sinus. 70 mice from control and experimental groups were euthanized by decapitation. IgE, Interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-11, IL-17A, IL-17F, Interferon gamma (IFNγ), IL-13 concentrations were measured in blood sera. Administration of SNK-411, SNK-578 at the dose of 50 mg/kg decreased systemic anaphylaxis, lowered IgE concentration by 1.5-1.6 times compared to ovalbumin control group whereas Aerius did not reduce concentration of IgE. Administration of SNK-411, SNK-578 at 25 mg/kg, and 50 mg/kg, and Aerius decreased concentration of Th-2 cytokines (IL-4, IL-5, IL-13) compared to ovalbumin-treated control group. SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg increased level of IL-2. SNK-578 at 50 mg/kg increased concentration of IFNγ up to intact control level and decreased concentration of IL-6. 7-day administration of 5-hydroxypyrimidine derivatives at the dose of 50 mg/kg decreased severity of systemic anaphylaxis. SNK-411, SNK-578, Aerius lowered levels of proallergic cytokines in serum of sensitized mice. In contrast to Aerius, the 5-hydroxypyrimidine derivatives decreased serum IgE concentrations.

Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals.

A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected. HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.

Antiallergic Effects of Technologically Processed Antibodies to MHC II.

The risk of developing anaphylactic reactions to medications introduces additional difficulties for effective pharmacotherapy. Using a model of systemic anaphylaxis in mice, we showed that preventive administration of a preparation containing technologically processed antibodies (TPA) to MHC II induces an anti-anaphylactic effect comparable to that of dexamethasone (when assessing the severity of systemic anaphylaxis 30 and 60 min after challenge injection of the model antigen ovalbumin). The revealed activity may be related to the ability of TPA to MHC II to regulate the antigen presentation system and shift the immune response towards the production of IgG instead of IgE typical of anaphylactic reaction.

Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

IntroductionIn 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. MethodsThe medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients’ demographic and clinical characteristics were further analyzed depending on the severity of the reaction. ResultsOne thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25–75] age: 42 [33–52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1–7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1–6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5–17.0); p = 0.011, OR (CI) = 10.3 (1.6–63.3)]. ConclusionThis multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.

Extrinsic and Intrinsic Modulators of Anaphylaxis.

The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.

Food-Induced Anaphylaxis: Data From the European Anaphylaxis Registry.

Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years. To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA). We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA. We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V= 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V= 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V= 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V= 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR= 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR= 1.78; CI, 1.09-2.95). Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA.

Relationship between Tryptase and Hypotension in Anaphylaxis during Anesthesia.

Hypotension is a cardiovascular symptom that appears at the onset of anaphylaxis. It is considered an important factor as it affects the severity of anaphylaxis; however, its details remain to be elucidated. In this study, we investigated the characteristics of hypotension at the onset of anaphylaxis during anesthesia, along with the relationship between hypotension, tryptase and histamine. The minimum systolic blood pressures of patients diagnosed with anaphylaxis using the clinical diagnostic criteria of the World Allergy Organization guidelines were extracted from electronic anesthesia records. We analyzed changes in tryptase and histamine that were measured after the onset of anaphylaxis. We analyzed the relationship of tryptase and histamine with the minimum systolic blood pressure and the severity of anaphylaxis. Of 55,996 patients, 25 were diagnosed with anaphylaxis during anesthesia (0.045%). Among these patients, the minimum systolic blood pressure was less than 90 mmHg. Furthermore, the minimum systolic blood pressure was inversely correlated with tryptase levels immediately to 1 hour, and 2 to 4 hours after the onset of anaphylaxis. The minimum systolic blood pressure was inversely correlated with the severity of anaphylaxis. The severity of anaphylaxis was positively correlated with tryptase levels immediately to 1 hour, and 2 to 4 hours after the onset of anaphylaxis. Hypotension tended to reflect the severity of anaphylaxis. Tryptase is an adjunct in the diagnosis of hypotension and may be a useful indicator of the severity of anaphylaxis. A larger-scale study is needed to validate these results.

Anaphylaxis in infancy and factors associated with severity

AimIt is difficult to determine the diagnosis and clinical severity of anaphylaxis in the infant age group. The aims of this study were to evaluate demographic and clinical characteristics of infants diagnosed with anaphylaxis and identify predictive factors for severe anaphylaxis. MethodsChildren aged 1 month to 2 years who were diagnosed with anaphylaxis in the pediatric emergency department between 2015 and 2021 were retrospectively analyzed. According to the Sampson Rating Scale, severity of anaphylaxis were determined as mild, moderate and severe. ResultsThe study included 78 infants; 44 (56%) of them were male, the median age was 8 months. Nine (12%) of the patients diagnosed with mild anaphylaxis, 49 (63%) were moderate, and 20 (25%) were severe. Patients diagnosed as mild and moderate anaphylaxis were defined as group I, and patients diagnosed as severe anaphylaxis were defined as group II. The most common triggering factor for anaphylaxis was food (68/78), the most common foods were cow's milk (n=33) and eggs (n=19). Drug-induced anaphylaxis was associated with more severe outcomes compared with other anaphylaxis triggers (P=0.020). Gastrointestinal system signs were significantly more frequent in group I patients compared to group II (P=0.038). In our population of infants, respiratory and neurogical related symptoms were found to be independent factors associated with a more severe anaphylaxis (odds ratios 7 [95% confidence interval, 1.56–39.09] and 5 [95% confidence interval, 1.10–31.90, respectively). ConclusionFoods are the most common triggers for anaphylaxis in infants. Drug-related anaphylaxis cases were more severe compared to food-related cases. Respiratory and neurological system related symptoms were found to be independent factors associated with a severe anaphylaxis.

Skin Tests versus Serology: Specific IgE May Suffice for Diagnosis of Vespid Venom Allergy and Follow-Up of Allergen Immunotherapy

Introduction: In adults, allergic reactions to insect stings are among the most frequent causes of anaphylaxis, a potentially life-threatening condition. Recurrent anaphylaxis following vespid stings may be prevented by allergen immunotherapy (AIT). The aim of this study was to evaluate the benefit of measuring venom-induced wheal area in intracutaneous skin tests (ICT), in comparison to various serological and clinical parameters, for the diagnosis of severe vespid venom allergy and during follow-up of AIT. Methods: We conducted a monocentric, retrospective evaluation of 170 patients undergoing AIT against vespid venoms. We scanned ICT wheals at baseline and at three time points after AIT initiation and measured wheal area using objective data analysis software. Results: We found that ICT histamine-induced and venom-induced wheal areas did not correlate. In addition, the venom-induced wheal area was independent from the minimal venom concentration required to elicit a wheal in an ICT and all other parameters. No correlation was found between wheal area and the severity of anaphylaxis. Wheal area standardized to the application of 0.1 μg/mL venom inversely correlated with anaphylaxis severity and positively correlated with venom-specific IgE levels. During AIT, mean areas of venom-induced wheals did not change. In contrast, venom-specific IgG and IgG4 levels, and the minimal venom concentration required to induce a positive ICT result increased, while the venom wheal area standardized to 0.1 μg/mL venom application and specific IgE levels decreased over time. Conclusion: Wheal area evaluation did not provide additional information over specific IgE analysis. We therefore recommend that ICTs are used only as a secondary measure for confirming serological test results.

Comparison of two diagnostic criteria in the diagnosis of anaphylaxis in a tertiary adult allergy clinic

BackgroundAnaphylaxis is a very dynamic issue with its incidence and trigger profile changing over the years. We aimed to compile the characteristics of anaphylaxis cases diagnosed in our clinic prospectively and to make a comparison between diagnostic criteria proposed by National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) and World Allergy Organization (WAO). MethodThree-item diagnostic criteria recommended by NIAID/FAAN (2006) were used in the diagnosis of anaphylaxis. The clinical features of the cases, risk factors, etiologies, severity of anaphylaxis, and treatment approach were determined. The same patients were also classified by current WAO diagnostic criteria. ResultsA total of 204 patients (158F/46 M, median age 45.3 years) were included. Drugs (65.2%), venom (9.8%) and food allergies (9.3%) were the top 3 etiologies. Among drug triggers, chemotherapeutics were the most common (17.7%), followed by antibiotics (15.3%) and non-steroidal anti-inflammatory drugs (14.2%). The patients were mostly diagnosed with the second criterion (84.8%), followed by the first criterion (11.8%) and the third criterion (3.4%) of the NIAID/FAAN criteria. In terms of WAO criteria, 82.8% of the patients were diagnosed with the first criterion, and 14.3% with the second criterion while 2.9% of the patients did not meet the WAO criteria. The severity of anaphylaxis was evaluated as grade-2, 3 and 4 in 30.9%, 64.2%, and 4.9% of the patients, respectively. Adrenaline was administered to 31.9% of the patients especially who had angioedema and bronchospasm (p = 0.04). ConclusionOur data suggest that covering more details in patient's history may prevent possible underdiagnosis and WAO diagnostic criteria seem to be insufficient in some patients. We believe that our results will contribute to the literature on anaphylaxis and would be groundwork for future studies.

Biological diagnosis of hereditary alpha-tryptasemia

Hereditary alpha-Tryptasemia (HαT) is the most frequent of TPSAB1/TPSB2 copy number variations. It is present in up to 6% of the general population and is associated with higher basal serum tryptase (bST) levels. HαT is considered a modifier of the frequency and severity of anaphylaxis in patients with clonal Mast Cell Disorders (MCD) or IgE-mediated allergy, particularly in venom-triggered or idiopathic anaphylaxis. Tryptase genotyping is adequately performed using droplet digital PCR (ddPCR), by comparing apparent copy numbers of α-tryptase, β-tryptase alleles and a housekeeping gene in digested and non-digested conditions. This method allows genotype resolution in most individuals. Tryptase genotyping is indicated in all symptomatic individuals with anaphylaxis history and/or Mast Cell Activation Syndrome (MCAS) suspicion and bST ≥8μg/L, in order to confirm or exclude HαT as an explanation of tryptase levels. In addition, tryptase genotyping is recommended for classification and risk-stratification of MCAS. Finally, in systemic mastocytosis, HαT status modifies the bST thresholds used for diagnostic, classification and risk-stratification purposes. Asymptomatic subjects or individuals with bST<6μg/L should not undergo tryptase genotyping, unless required for genotype resolution of related symptomatic individuals.

Different age groups present different clinics in anaphylaxis with children: one size does not fit all children.

Childhood anaphylaxis presents with a heterogeneous clinic. Elicitors and epidemiologic factors associated with anaphylaxis differ with age, geographic location and lifestyle. This study aimed to determine the clinical features and age-specific patterns of childhood anaphylaxis in a single referral center in Turkey. We conducted a retrospective study of anaphylaxis in children aged between 0 and 18 years of age, attending an allergy department in a children's hospital. A total of 95 children diagnosed with anaphylaxis were analyzed. Among all, 35.8% of the first anaphylaxis episodes occurred ininfancy and 57.9% in preschool age. Foods were the most common culprits (57.9%) and followed by drugs (15.8%). Patients with foodinduced anaphylaxis were younger in age (p < 0.001). Food-related anaphylaxis was most common with cow's milk (36.4%) and followed by tree nuts (20%). Cow's milk played a significant role as a trigger in infancy, and tree nuts as a trigger in preschoolers and school-age children. Mucocutaneous manifestations were almost universally present (94.7%), followed by respiratory compromise (56.8%), with gastrointestinal (55.8%), cardiovascular (9.5%), and neurologic (4.2%) symptoms being less common. Respiratory and cardiovascular system-related symptoms were found more frequently in school-age children (p = 0.02 and p = 0.014, respectively). The severity of anaphylaxis was higher in school-age children (p = 0.015). Findings reveal that children diagnosed with anaphylaxis differ in terms of etiological and clinical findings according to age groups. This difference shows the dynamically changing clinic of anaphylaxis over time and the importance of evaluating childhood anaphylaxis according to age groups.

Type 2 helper T cells convert into Interleukin-13-expressing follicular helper T cells after antigen repriming

Anaphylaxis caused by allergen sensitization and vaccination is a serious health concern. The severity of anaphylaxis is associated with the presence of immunoglobulin E (IgE) antibodies that bind to allergens with a high affinity. Here, we report the development of a unique Interleukin-13 (IL-13)-producing follicular helper T (TFH) cell subset, designated TFH2 cells, which is tightly associated with the production of high-affinity IgE antibodies. TFH2 cells had a transcriptionally hybrid phenotype between TH2 and TFH cells, which express GATA-binding protein 3 (Gata3) and B-cell/CLL lymphoma 6 (BCL-6), respectively. Adaptive transfer experiments demonstrated that type 2 helper T (TH2) cells were capable of differentiating into TFH2 cells upon secondary antigen stimulation. The type 2 TFH (TFH2) conversion process was entirely attenuated in T cell-specific deficient mice of Bcl6 (Bcl6f/f cd4-cre; Bcl6ΔT). Moreover, the transfer of IL-13 defective TH2 cells partially inhibited IgE responses and significantly decreased the high-affinity IgE, even though TFH development was intact. Therefore, IL-13 from TFH2 cells controlled the selective enrichment of IgE+ B-cells with a high affinity for allergens. A previously undefined unique TFH subset, TFH2, likely contributes to IgE responses. This suggests that the accumulation of antigen-specific TH2 cells in human patients with allergies is a high-risk factor for IgE-dependent allergic diseases.

Tumor-associated neutrophils and macrophages exacerbate antidrug IgG-mediated anaphylactic reaction against an immune checkpoint inhibitor

BackgroundWith the increased use of immune checkpoint inhibitors (ICIs), side effects and toxicity are a great concern. Anaphylaxis has been identified as a potential adverse event induced by ICIs. Anaphylaxis...