Severe Systemic Allergic Reactions Research Articles

The Prevalence of Self-Reported Systemic Allergic Reaction to Hymenoptera Venom in Beekeepers Worldwide: A Systematic Literature Review and Meta-Analysis.

Beekeepers represent a high-allergic risk population group due to their unavoidable seasonal or persistent exposure to the elicitors of Hymenoptera venom allergy, bees in particular. A systematic literature review and meta-analysis aimed to estimate the prevalence of self-reported systemic allergic reaction to Hymenoptera venom among beekeepers worldwide. We rigorously reviewed and conducted meta-analysis on observational studies retrieved from seven electronic databases (MEDLINE via PubMed, Web of Science Core Collection, Scopus, Academic Search Complete, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature, Zoological Record), spanning data from inception to August 1, 2023. The Joanna Briggs Institute Prevalence Critical Appraisal Tool was employed to assess the risk of bias. A meta-analysis was conducted to synthesize evidence. Out of 468 studies, eight original articles met the inclusion criteria. The estimated overall lifetime and one-year prevalence of self-reported systemic allergic reaction to bee venom were 23.7% (95% CI: 7.7-53.4) and 7.3% (95% CI: 5.8-9.2), respectively. The estimated lifetime prevalence of self-reported systemic allergic reaction to bee venom for grades III-IV (severe systemic allergic reaction) was 6.0% (95% CI: 3.0-11.7). In general, substantial heterogeneity and a high risk of bias were observed across the majority of studies. The impact of geographical location and climate differences on the estimated lifetime prevalence is suggestive for severe systemic allergic reaction. Future observational cross-sectional studies should employ rigorous study designs, using validated questionnaires, and thoroughly report the observed health outcomes, verified by physicians.

Risk Factors Associated with Severe Systemic Allergic Reaction after Wasp Sting in Subjects with a History of European Hornet Sting Allergy.

To make the treatment approach in patients suffering a European hornet sting allergy reaction more personalized, preparing them also for possible future risks. In Slovenia an extended retrospective observational cohort epidemiological study about the natural history of Hymenoptera venom sensitivity is in progress. The study is based on data from the healthcare records of the University Clinic Golnik (UCG) and data collected by a questionnaire sent to patients from May 2019 to April 2021. For a pilot study, we selected patients who were referred to UCG because of an allergic reaction to European hornet sting and had been re-stung later by a wasp (n=68). The association between severe systemic allergic reactions (SSAR) after wasp sting and potential risk factors in subjects with a history of hornet sting allergy was assessed univariately using the likelihood ratio test. Among 68 European hornet allergic patients 27 reacted with an SSAR and 41 reacted with a mild SAR. Among 27 patients with SSAR, 4 reacted with an SSAR also to a subsequent wasp sting. Among 41 patients with a mild European hornet sting SAR nobody reacted with an SSAR to a subsequent wasp sting. The association between the severity of the wasp SAR reaction in European hornet allergic patients was statistically significant (p=0.022). Our results suggest that patients with severe European hornet SAR should be considered for wasp venom immunotherapy or prophylactic prescription of epinephrine auto-injector as they are at risk for an SSAR also after wasp string.

PHARMACOKINETICS AND PHARMACODYNAMICS OF ARS-1 AND MANUAL INTRAMUSCULAR INJECTION IN SUBJECTS WITH/WITHOUT ALLERGIC RHINITIS

<h3>Introduction</h3> The intranasal (IN) epinephrine spray (ARS-1) is an investigational, needleless alternative to epinephrine injection for patients with severe systemic allergic reactions. <h3>Methods</h3> This single-dose, partially randomized crossover phase 1 study investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of ARS-1 2 mg IN (under normal conditions and with induced rhinitis) and manual intramuscular (IM) injection (0.3 mg and 0.5 mg) in subjects with seasonal allergies. IRB approval was obtained for this study. <h3>Results</h3> Thirty-six subjects were included in the study. Mean C_max values (pg/mL) with ARS-1 (491) and ARS-1 with rhinitis (309) were higher than or similar to those for 0.3 mg (283) or 0.5 mg (452) IM injection. Median t_max values (minutes) were lowest with ARS-1 (20.0) and ARS-1 with rhinitis (6.00) compared with either IM dose (both 45.00). Mean E_max for systolic blood pressure (SBP; mmHg), diastolic blood pressure (DBP; mmHg), and heart rate (HR; bpm) with ARS-1 (20.8, 10.0, 18.5 respectively) and ARS-1 with rhinitis (15.0, 7.15, and 10.8) was higher than or comparable to that of 0.3 mg IM (13.4, 5.26, and 11.1) and 0.5 mg IM (15.2, 5.69, 13.6). Similarly, the mean AUEC_last in SBP, DBP, and HR for both ARS-1 groups was higher than or similar to either IM group. <h3>Conclusion</h3> PK and PD parameters with ARS-1 2 mg with and without allergic rhinitis were higher/better or comparable with those of 0.3 or 0.5 mg IM injection.

Synthetic imperatorin derivatives alleviate allergic reactions via mast cells.

Anaphylaxis is a severe systemic allergic reaction that exhibits multiple clinical symptoms. The Mas-related G protein-coupled receptor X2 (MRGPRX2) is recognized as a key cell receptor mediating allergic diseases and drug-induced anaphylactoid reactions. Thus, it has been a promising target for preventing and treating these reactions. Based on the potential activity of imperatorin and active structural feature of MRGPRX2, we first demonstrated that the synthetic imperatorin derivatives (IDs) could significantly inhibit MRGPRX2 agonist-induced degranulation and cytokine release in LAD2 cells, as well as alleviate local and systemic anaphylaxis in mice. The IC50 value of the most promising compound is an order of magnitude lower than that of imperatorin. IDs were further identified to display anti-pseudo-allergic activity by binding MRGPRX2 with the tertiary nitrogen substructures, just liking the reported MRGPRX2-ligand. These results would propose evidence for discovery of agents for treating MCs-dependent allergic disorders.

Real-life experience with hazelnut oral immunotherapy

Introduction ( contexte de la recherche ) Hazelnut oral immunotherapy (H-OIT), a promising alternative to hazelnut-free diet for patients with hazelnut allergy, has not been extensively studied. The primary objective was to investigate the effectiveness of H-OIT for hazelnut allergic children. Retrospective medical record review of children treated by H-OIT in the University Hospital of Lyon (France) was reported. Clinical and laboratory data were collected, and the satisfaction of the children treated by H-OIT was evaluated using a questionnaire. A total of 70 patients treated by H-OIT for an IgE-mediated hazelnut allergy (94.3%) or an IgE sensitization to hazelnut (5.7%) were included. Among these, 22.9% entered the maintenance phase at one-year consultation and 60.0% entered the maintenance phase during the study period. At home, 57.1% of the patients experienced at least one side effect and 2.9% experienced severe systemic allergic reactions. Among the 212 OFCs conducted at hospital, 3.3% led to severe systemic reactions and epinephrine was used four times. A total of 21.4% of children discontinued treatment; aversion to hazelnut was main reason. Forty-two children aged 8 or more and their parents answered the questionnaire. H-OIT was considered a strain for children but effective, and they would recommend H-OIT to other allergic children. H-OIT appeared effective and well accepted by children. This is counterbalanced by a high rate of H-OIT discontinuation, mainly due to aversion to hazelnut, and an important rate of adverse reactions, which are however mostly mild.

Atopy and Idiopathic Anaphylaxis

Idiopathic anaphylaxis (IA) is a severe systemic allergic reaction where no cause is found. Prior studies have shown that IA patients may have higher rates of atopy. We investigated the association between specific atopic conditions, including asthma, allergic rhinitis, and eczema, and IA.

Real-life experience with hazelnut oral immunotherapy

BackgroundHazelnut oral immunotherapy (H-OIT), a promising alternative to hazelnut-free diet for patients with hazelnut allergy, has not been extensively studied. ObjectiveTo investigate the effectiveness of H-OIT for children with hazelnut allergy. MethodsRetrospective medical record review of children treated by H-OIT in the University Hospital of Lyon (France) was reported. Clinical and laboratory data were collected, and the satisfaction of the children treated by H-OIT was evaluated using a questionnaire. ResultsA total of 70 patients treated by H-OIT for an immunoglobulin E-mediated hazelnut allergy (94.3%) or an immunoglobulin E sensitization to hazelnut (5.7%) were included. Among these, 22.9% entered the maintenance phase at 1-year consultation and 60.0% entered the maintenance phase during the study period. At home, 57.1% of the patients experienced at least 1 adverse effect and 2.9% experienced severe systemic allergic reactions. Among the 212 oral food challenges conducted at hospital, 3.3% led to severe systemic reactions and epinephrine was used 4 times. A total of 21.4% of children discontinued treatment; aversion to hazelnut was the main reason. There were 42 children aged 8 years or more and their parents who answered the questionnaire. H-OIT was considered a strain for children but effective and was recommended to other children with allergy. ConclusionH-OIT seemed to be effective and well accepted by children. This is counterbalanced by a high rate of H-OIT discontinuation, mainly owing to aversion to hazelnut, and an important rate of adverse reactions, which are however mostly mild. Trial RegistrationClinicalTrials.gov Identifier: NCT04841850.

Анафилаксия среди детей, госпитализированных с острыми аллергическими реакциями: пятилетний ретроспективный анализ

Objective. To determine the frequency, range of triggers, features of clinical symptoms and treatment of anaphylaxis in children hospitalized with severe systemic allergic reactions in the pediatric department in Moscow. Patients and methods. We conducted a retrospective analysis of 1197 medical records of children admitted to the Z.A.Bashlyaeva Children's City Clinical Hospital with severe allergic reactions over the period from 2016 to 2020 to determine the clinical criteria for anaphylaxis. The diagnosis of anaphylaxis was made retrospectively in 86 patients based on corresponding reports of 2 independent allergy specialists. Results. The incidence of anaphylaxis among children hospitalized with severe allergic reactions was 7.18%. The use of the new WAOAG (2020) anaphylaxis criteria, compared with the previously adopted NIAID/FAAN (2006), slightly increased the coverage of patients diagnosed with anaphylaxis (7.18% vs 7.01%, respectively). Food allergens were the predominant cause of anaphylaxis in children (78%); the second most important trigger were medications (5%), and 7% of patients had idiopathic anaphylaxis. The main causes of food anaphylaxis were tree nuts (31%), cow's milk (19%), fish/seafood (16%), and chicken egg (9%); the frequency of anaphylactic reactions to peanuts did not exceed 4%. The incidence of anaphylaxis to cow's milk and chicken egg was higher in the group of children younger than 3 years (p = 0.003, p = 0.01, respectively), and the incidence of anaphylaxis to fruits was lower (p = 0.05) compared with patients aged 3-18 years. The proportion of anaphylaxis to tree nuts in children was highest and irrespective of patient age. In the development of anaphylaxis, skin/mucosal (98%) and respiratory (71%) symptoms were the most frequent, followed by gastrointestinal symptoms (29%) and laryngeal symptoms (26%). In hospital, anaphylaxis was diagnosed in 10 (12%) patients, and only 21% of children received epinephrine for the treatment of anaphylaxis. At discharge, epinephrine was recommended for 13% of patients. Conclusion. The diagnosis of anaphylaxis is to be excluded in patients with severe allergic reactions, since its incidence in this group of patients reaches 7.18%. Food allergens are the main trigger of anaphylaxis in children in the Russian Federation. The age-dependent spectrum of food anaphylaxis triggers in Russia suggests the use of diagnostic allergy panels in infants that include not only cow's milk, chicken egg, fish, but also tree nuts. Less than 1/4 of children receive epinephrine in the treatment of anaphylactic reactions; the rate of verification of the diagnosis of anaphylaxis and prescription of epinephrine is extremely low and does not exceed 13%. Key words: anaphylaxis, anaphylactic reaction, trigger, allergen, children, food allergy, infants

Синдром Стивенса — Джонсона как острая тяжелая аллергическая реакция у ребенка

Stevens — Johnson syndrome is a rare severe acute systemic allergic reaction. Most often, this reaction is induced in children by an exposure to pathogenic microorganisms and intake of medications, mainly occurring with damage to the skin and mucous membranes of at least two organs. Despite the fact that the disease is rare in pediatric practice, its relevance is due not only to the fact that children with Stevens-Johnson syndrome have a sharply increased risk of complications and death, but also to the fact that today there are no universal regulatory algorithms and standards for the management of such patients. The diagnosis verification is based on the clinical symptoms of the disease and a competently collected anamnesis. Unfortunately, the current polypragmasia, as well as the difficulties of differentiating between the symptoms manifested in Stevens-Johnson syndrome, which are often regarded by doctors as the debut of an acute respiratory disease, complicates the interpretation of the disease inducer and leads to a late diagnosis, which in turn delays the elimination of allergen and therapy, eventually affecting the course and outcome of pathology. The article describes a clinical case in a patient with first-time Stevens — Johnson syndrome in response to the combined effects of such etiological factors as primary cytomegalovirus infection and drug administration. The patient was managed in a hospital setting with differential diagnosis and the appointment of intensive and rational therapy, which led to a favorable outcome of the disease.

Food allergies and acute allergic reactions: diagnostic options

Introduction. Anaphylaxis is a systemic potentially life-threatening hypersensitivity reaction featuring the rapid onset, manifestations of the respiratory tract and/or hemodynamics and usually, but not always, accompanied by changes in the skin and mucous membranes [1]. The cause of developing an acute generalized reaction in food anaphylaxis may be the minimum culprit product amount that has entered the patient's body through the mouth or through the skin/mucous membranes. Patients like these are, as a rule, first seen by a paediatrician, a related specialist, or a paramedic. Since the doctors often consider the symptoms of foodborne anaphylaxis separately, the latter does not cause proper suspicion: angioedema and/or acute urticaria accompanying rhinorrhea, acute bronchospasm or laryngitis developed extremely quickly or immediately after contact with an allergen.The aim of the work was to acquaint paediatricians and doctors of related specialties with the food anaphylaxis symptoms, to justify the need for an allergologist-immunologist to consult these patients in order to resolve the issue of required component-resolved diagnosis of allergy and development of an individual elimination diet, taking into account the patient's sensitization profile.Materials and methods. Clinical observation of a child (boy, age — 12 months) with symptoms of atopic dermatitis and episodes of food anaphylaxis in the anamnesis; general clinical examination and allergological examination of the patient by component allergodiagnostics were performed.Results. Sensitization to ovalbumin (Gald 2 -16.60 kU/l) and ovomucoid (Gald 1-9.01 kU/l) was established. The detected sensitization is a predictor of severe systemic allergic reactions to eggs.Discussion. Component diagnostics performed as prescribed by an allergologist not only confirms the causative allergen, but also evaluates the risks of developing acute reactions if the allergen is accidentally introduced to the child and the timing of the patient's tolerance formation. This sensitization will cause sudden systemic allergic reactions for years to come.Conclusion. It is important for a specialist to timely suspect food anaphylaxis, differentiate it from other emergency and urgent conditions, and give the patient the correct recommendations on the need for consultation with an allergologist-immunologist. Only a thoughtful, comprehensive medical approach to each acute condition in a child will significantly reduce the risk of repeated episodes of food anaphylaxis.

Randomized controlled trial of ragweed sublingual immunotherapy tablet in the subpopulation of Canadian children and adolescents with allergic rhinoconjunctivitis

BackgroundPost hoc analyses of randomized placebo-controlled trials have demonstrated efficacy and tolerability of the ragweed sublingual immunotherapy (SLIT)-tablet in Canadian adults with ragweed pollen-induced allergic rhinitis/conjunctivitis (AR/C). This post hoc analysis evaluated the efficacy and tolerability of the ragweed SLIT-tablet in the subpopulation of Canadian children and adolescents with AR/C in a previously described randomized, double-blind, placebo-controlled trial.MethodsThe trial (NCT02478398) was conducted in North American and European children/adolescents ages 5–17 years with ragweed pollen-induced AR/C with or without asthma (FEV1 ≥ 80% predicted). Participants were randomized to daily ragweed SLIT-tablet (12 Amb a 1-U) or placebo for up to 28 weeks. The primary endpoint was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary endpoints were TCS during the entire RPS, and DSS and DMS during peak RPS. Post hoc analyses of the primary and key secondary endpoints were conducted in the subpopulation of Canadian participants.ResultsOf the 1025 randomized participants, 246 (SLIT-tablet, n = 116; placebo, n = 130) were in the Canadian subpopulation. In the total study population, relative TCS (95% CI) improvement with ragweed SLIT-tablet versus placebo was − 38.3% (− 46.0%, − 29.7%; least square [LS] mean difference, − 2.73; P < 0.001) during peak RPS. In the Canadian subpopulation, relative TCS improvements with ragweed SLIT-tablet versus placebo were − 40.8% (− 54.5%, − 20.2%; LS mean difference, − 1.59; P = 0.001) during peak RPS and − 36.6% (− 50.2%, − 16.5%; LS mean difference, − 1.36; P = 0.002) during the entire RPS. DSS and DMS during peak RPS in the Canadian subpopulation improved with SLIT-tablet versus placebo by − 30.6% (− 45.2%, − 7.7%; LS mean difference, − 0.94; P = 0.010) and − 77.2% (− 97.5%, − 44.2%; LS mean difference, − 0.66; P = 0.003), respectively. No events of anaphylaxis, airway compromise, intramuscular epinephrine administration, eosinophilic esophagitis, or severe treatment-related systemic allergic reactions were reported in the overall population or Canadian subpopulation.ConclusionEfficacy and safety of the ragweed SLIT-tablet in Canadian children/adolescents with ragweed pollen-induced AR/C was consistent with the total study population. The ragweed SLIT-tablet resulted in clinically meaningful improvement in symptoms, decreased symptom-relieving medication use, and was well tolerated in Canadian children/adolescents.Trial registration: clinicaltrials.gov, NCT02478398. Registered June 23, 2015, https://clinicaltrials.gov/ct2/show/NCT02478398?term=NCT02478398&draw=2&rank=1

Severe Systemic Allergic Reaction after Topical Application of Mupirocin

Mupirocin (MUP) is a natural derivative of crotonic acid extracted from Pseudomonas fluorescens. This antibiotic has a unique chemical structure and mechanism of action.It is often used topically for the treatment of cutaneous infections to prevent skin and soft tissue infections caused by S. aureus isolates and where the MRSA isolates are epidemic. Furthermore, MUP may be used as a choice drug for nasal decolonization.Despite some side effects, mupiro¬cin has been reported to be safe and to cause allergic reactions in only extremely rare cases. This paper is a report on a rare case of severe systemic allergic reaction resulting from treatment with mupirocin ointment in a 39 year old male patient who had a history of burn injury.

Severe homocysteinemia in two givosiran-treated porphyria patients: is free heme deficiency the culprit?

Givosiran is a novel approach to treat patients with acute intermittent porphyrias (AIP) by silencing of ∂-ALA-synthase 1, the first enzyme of heme biosynthesis in the liver. We included two patients in the Envision study who responded clinically well to this treatment. However, in both patients, therapy had to be discontinued because of severe adverse effects: One patient (A) developed local injection reactions which continued to spread all over her body with increasing number of injections and eventually caused a severe systemic allergic reaction. Patient B was hospitalized because of a fulminant pancreatitis. Searching for possible causes, we also measured the patients plasma homocysteine (Hcy) levels in fluoride-containing collection tubes: by LC–MS/MS unexpectedly, plasma Hcy levels were 100 and 200 in patient A and between 100 and 400 μmol/l in patient B. Searching for germline mutations in 10 genes that are relevant for homocysteine metabolism only revealed hetero- and homozygous polymorphisms in the MTHFR gene. Alternatively, an acquired inhibition of cystathionine-beta-synthase which is important for homocysteine metabolism could explain the plasma homocysteine increase. This enzyme is heme-dependent: when we gave heme arginate to our patients, Hcy levels rapidly dropped. Hence, we conclude that inhibition of ∂-ALA-synthase 1 by givosiran causes a drop of free heme in the hepatocyte and therefore the excessive increase of plasma homocysteine. Hyperhomocysteinemia may contribute to the adverse effects seen in givosiran-treated patients which may be due to protein-N-homocysteinylation.

Anaphylaxis caused by artisanal honey in a child: a case report

BackgroundHoney is a rare cause of food allergy, especially in children, but it can cause severe systemic allergic reactions. In the pediatric age group, only a few cases have been reported in the literature. Honey allergy may be caused by pollen content or bee-derived proteins. A role for Compositae has been suggested among pollen allergens. Allergology workup of a patient with suspected honey allergy is not well defined. Here we describe a rare case of anaphylaxis in a 5-year-old boy, sensitized to Compositae pollen (ragweed and mugwort), after the ingestion of artisanal honey.Case presentationThe Slavic patient was referred to our hospital emergency department for generalized urticaria and breathing impairment. All the symptoms occurred approximately 30 minutes after the ingestion of a meal containing salmon and artisanal honey. The allergology workup revealed that a skin prick-by-prick test with the implicated artisanal honey was positive, while a variety of different commercial honey and salmon products yielded negative results. Skin prick test and serum-specific immunoglobulin E (IgE) results were also positive for Compositae pollen (ragweed and mugwort). Patients sensitized to weed pollens who ingest bee products may experience an immediate allergic reaction because of the cross-reaction between weed pollens and Compositae bee product pollen. In this case, primary sensitization may be due to airborne Compositae pollen. Commercial honey is heavily processed due to pasteurization and filtration, which removes most of the pollen. These observations highlight the role of Compositae pollen in the observed allergic reaction and suggest that the different pollen content in the artisanal honey relative to commercial honey was responsible for the allergic reaction in our patient.ConclusionsThis is the first reported pediatric case of honey-induced anaphylaxis in a child under 6 years of age sensitized to Compositae pollen. Pediatricians should be aware of the potential risk of severe allergic reactions upon ingestion of honey and bee products, especially in patients sensitized to weed pollens. To diagnose honey allergy, obtaining a proper clinical history is essential. In addition, skin prick-by-prick tests are helpful, and may represent a simple method to screen for honey allergy in patients sensitized to Compositae pollen, in light of the potential risk.

Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial

Ragweed sublingual immunotherapy (SLIT) tablet reduces symptoms and symptom-relieving medication use in adults with allergic rhinitis with or without conjunctivitis (AR/C) but has not been evaluated in children. This international, multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of ragweed SLIT-tablet in children with AR/C. Children (N= 1025; 77.7% polysensitized) aged 5 to 17 years with ragweed pollen-induced AR/C with or without asthma (FEV1 ≥80% predicted) were randomized 1:1 to daily ragweed SLIT-tablet (12 Amb a 1-Unit) or placebo for up to 28 weeks (NCT02478398). The primary end point was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary end points were TCS during the entire RPS, and DSS and DMS during the peak RPS. Relative TCS (95% CI) improvements with ragweed SLIT-tablet versus placebo were-38.3% (-46.0% to-29.7%; least square [LS] mean difference,-2.73; P < .001) during peak RPS and-32.4% (-40.7% to-23.3%; LS mean difference,-1.86; P < .001) during the entire RPS. DSS and DMS during peak RPS improved with SLIT-tablet versus placebo by-35.4% (-43.2% to-26.1%; LS mean difference,-1.40; P < .001) and-47.7% (-59.8% to-32.5%; LS mean difference,-1.84; P < .001), respectively. Asthma DSS, short-acting β-agonist use, and nocturnal awakenings during peak RPS improved with SLIT-tablet versus placebo by-30.7%,-68.1%, and-75.1%, respectively (all nominal P ≤ .02). No events of anaphylaxis, airway compromise, or severe treatment-related systemic allergic reactions were reported. Ragweed SLIT-tablet significantly improved symptoms and decreased symptom-relieving medication use in children with ragweed pollen-induced AR/C and was well tolerated.

Toxic epidermal necrolysis in the practice of a family doctor

Toxic epidermal necrolysis is a severe delayed-type systemic allergic reaction, in which there is a combined lesion of the skin and mucous membranes. 2 cases of toxic epidermal necrolysis from the practice of a family doctor are described in the article. Timely diagnosis and rational treatment of the disease in the first case led to a favorable outcome, in the second case, the outcome of the disease was unfavorable.

Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations.

To describe inherited and acquired genetic variants and clinical entities associated with increased basal serum tryptase (BST), distinguish these levels from those which acutely rise due to mast cell activation, and finally to characterize the association between chronically elevated basal serum tryptase and episodic mast cell activation. Hereditary alpha-tryptasemia is a commonly inherited genetic cause for basally elevated serum tryptase and explains elevated BST in many individuals who do not have evidence of clonal myeloid or mast cell disease. When clonal myeloid disease is present, BST may be elevated and can be a biomarker of a number of disparate disorders of the myeloid compartment. Elevated BST is most commonly caused by hereditary alpha tryptasemia but may also be indicative of clonal myeloid disease. Clinical reports suggest that elevated BST is associated with increased risk for more severe systemic allergic reactions to a number of eliciting agents and exposures. Additional studies are needed to determine the role that inherited or acquired genetic variants associated with elevated BST and clonal or non-clonal myeloid diseases may play in these reactions.

Vedolizumab use after failure of TNF-\u03b1 antagonists in children and adolescents with inflammatory bowel disease

BackgroundVedolizumab is safe and effective in adult patients with Crohn’s disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD.MethodsTwelve patients (7 female; 7 CD; 5 UC), aged 8–17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits.ResultsIn the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p < 0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups.ConclusionThese results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.

The Anisakis Transcriptome Provides a Resource for Fundamental and Applied Studies on Allergy-Causing Parasites.

BackgroundFood-borne nematodes of the genus Anisakis are responsible for a wide range of illnesses (= anisakiasis), from self-limiting gastrointestinal forms to severe systemic allergic reactions, which are often misdiagnosed and under-reported. In order to enhance and refine current diagnostic tools for anisakiasis, knowledge of the whole spectrum of parasite molecules transcribed and expressed by this parasite, including those acting as potential allergens, is necessary.Methodology/Principal FindingsIn this study, we employ high-throughput (Illumina) sequencing and bioinformatics to characterise the transcriptomes of two Anisakis species, A. simplex and A. pegreffii, and utilize this resource to compile lists of potential allergens from these parasites. A total of ~65,000,000 reads were generated from cDNA libraries for each species, and assembled into ~34,000 transcripts (= Unigenes); ~18,000 peptides were predicted from each cDNA library and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping. Using comparative analyses with sequence data available in public databases, 36 (A. simplex) and 29 (A. pegreffii) putative allergens were identified, including sequences encoding ‘novel’ Anisakis allergenic proteins (i.e. cyclophilins and ABA-1 domain containing proteins).Conclusions/SignificanceThis study represents a first step towards providing the research community with a curated dataset to use as a molecular resource for future investigations of the biology of Anisakis, including molecules putatively acting as allergens, using functional genomics, proteomics and immunological tools. Ultimately, an improved knowledge of the biological functions of these molecules in the parasite, as well as of their immunogenic properties, will assist the development of comprehensive, reliable and robust diagnostic tools.

Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial.

The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period. Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis. Key exclusion criteria were FEV1 less than 70% of predicted value or hospitalization due to asthma within 3 months before randomization. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months. 1:1:1 randomization to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (dosage groups: 6 SQ-HDM [n = 275] or 12 SQ-HDM [n = 282]) in addition to ICS and the short-acting β2-agonist salbutamol. Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. Among 834 randomized patients (mean age, 33 years [range, 17-83]; women, 48%), 693 completed the study. The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo (hazard ratio [HR]: 0.72 [95% CI, 0.52-0.99] for the 6 SQ-HDM group, P = .045, and 0.69 [95% CI, 0.50-0.96] for the 12 SQ-HDM group, P = .03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo group were 0.09 (95% CI, 0.01-0.15) for the 6 SQ-HDM group and 0.10 (95% CI, 0.02-0.16) for the 12 SQ-HDM group. There was no significant difference between the 2 active groups. Compared with placebo, there was a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95% CI, 0.49-1.02] for the 6 SQ-HDM group, P = .11, and 0.64 [95% CI, 0.42-0.96] for the 12 SQ-HDM group, P = .03) and a significant increase in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13% for the 6 SQ-HDM group, 20% for the 12 SQ-HDM group, and 3% for the placebo group), mouth edema, and throat irritation. Among adults with HDM allergy-related asthma not well controlled by ICS, the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction, with an estimated absolute reduction at 6 months of 9 to 10 percentage points; the reduction was primarily due to an effect on moderate exacerbations. Treatment-related adverse events were common at both active doses. Further studies are needed to assess long-term efficacy and safety. clinicaltrialsregister.eu Identifier: 2010-018621-19.