Risk Of Systemic Reactions Research Articles

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Clinical significance of a basophil activation test for Japanese beekeepers naturally sensitized to honey bee venom.

The basophil activation test (BAT) has high sensitivity and specificity for diagnosing Hymenoptera venom allergy and is useful for predicting the clinical sensitivity of bee venom-allergic patients after venom immunotherapy. Patients sensitized to Hymenoptera venom are at risk for systemic reactions (SRs) to subsequent stings. Therefore, a tool that can predict the occurrence of SRs and the severity of Hymenoptera stings is needed. We performed BATs on Japanese beekeepers naturally sensitized to honey bee venom (HBV) and analyzed the positive threshold concentration for the occurrence of SRs following honey bee stings (HBS). Sixty-one beekeepers were interviewed and blood samples were taken. Data including history of HBS and the occurrence and severity of SRs to HBS were recorded. Blood samples were exposed to HBV-specific IgE antibodies (sIgE) and BAT was performed. Participants with HBV-sIgE ≥ class 1 were considered sensitized to HBV. The positive threshold for BAT scored as 0.0001, 0.001, 0.01, 0.1, and 1 μg/ml was classified as classes 5, 4, 3, 2, and 1, respectively. Samples negative at 1 μg/ml were classified as class 0. About 40% of beekeepers with a positive BAT threshold ≤ 0.1 μg/ml had SRs after HBS. The mean score of the BAT positivity threshold for beekeepers who developed SRs was significantly lower than that for beekeepers with no history of SRs (2.6 ± 0.8 vs 1.4 ± 1.1, P < 0.01). Analysis of the positive threshold of BAT in Japanese beekeepers naturally sensitized to HBV may be a useful tool for predicting the occurrence of SRs.

Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

Safety of allergen immunotherapy in children.

The current review discusses allergen immunotherapy (AIT) safety in children. AIT is a well tolerated and effective treatment for pediatric allergic conditions. While mostly well tolerated, severe reactions and near fatal reactions may occur with subcutaneous immunotherapy (SCIT) once in every 160 000 visits. Sublingual immunotherapy (SLIT) is associated more with local side effects, but severe systemic reactions, including anaphylaxis, have been rarely reported. Providing informed consent, recognizing risk factors for severe systemic reactions, such as severe or uncontrolled asthma, and mitigating the risk of severe reactions are important components to improving the safety of AIT. Overall, AIT is well tolerated in children, and data suggest that the incidence of systemic reactions in children receiving SCIT is no less than mixed populations of adult and pediatric patients. SLIT carries less risk for systemic reactions, and local oral site-application reactions are usually mild and resolve within 15 days of treatment.

A comparison of cluster versus standard subcutaneous multi-allergen immunotherapy systemic reaction risk

Cluster schedules for subcutaneous allergen immunotherapy require significantly fewer injections, but there have been conflicting reports regarding the risk of systemic reaction. We aim to compare the incidence of systemic reactions during the build-up stages of multi-allergen standard versus cluster immunotherapy.

Risk of anaphylaxis in cluster vs standard subcutaneous multiallergen immunotherapy

BackgroundCluster schedules for subcutaneous allergen immunotherapy (AIT) require significantly fewer injections, but there have been conflicting reports regarding the risk of systemic reactions (SR). ObjectiveTo compare the incidence of SRs during the build-up stages of multiallergen standard vs cluster immunotherapy. MethodsData on SRs were collected prospectively from 91 urban adult patients who underwent either standard or cluster AIT at the Johns Hopkins Allergy and Asthma Center from 2014 to 2022. The SRs were recorded during the build-up phase and compared for both protocols using Pearson's χ2, Fisher exact test, and multivariate logistic regression models. ResultsOverall, SR rates were 21% for patients in the standard schedule and 37% for patients in the cluster immunotherapy schedule, which was not statistically different (P = .08). However, the SR rate for each injection was 0.69% per injection in the standard protocol and 2.29% per injection in the cluster schedule (incident rate ratio = 3.3). All SRs (100%) in both groups occurred in the second half of the build-up phase. Multivariate regression revealed that the target prescription protein nitrogen units and the number of allergens in the treatment vial did not influence SR rates (odds ratio = 1.00 and 1.06, respectively). ConclusionThe overall incidence of SR was not statistically different for cluster and standard AIT protocols. However, because cluster patients received approximately half the number of injections, the risk for SR per individual injection is more than 3-fold higher than that of standard immunotherapy.

Venom allergen immunotherapy.

Venom immunotherapy (VIT) with Hymenoptera venom extracts is highly effective in preventing large local, systemic allergic, and anaphylactic reactions to insect stings. VIT is not required for patients with cutaneous systemic or large local allergic reactions to stings because it is uncommon for reactions to become more severe. The clinical history, with confirmatory skin or serum tests for venom IgE, can clarify the risk for future anaphylaxis and the need for VIT. For initial treatment, rush regimens are recommended because they have the same or less risk of systemic reactions than slower traditional regimens. VIT is relatively safe with a low incidence of systemic reactions. Injection-site reactions can be bothersome but do not predict systemic reactions to venom injections. Patients who need VIT should be screened for baseline serum tryptase and possible underlying mast cell disorders. VIT can be discontinued after five years in most patients, but those with known high-risk factors should continue VIT indefinitely.

Homologous COVID-19 BNT162b2 mRNA Vaccination at a German Tertiary Care University Hospital: A Survey-Based Analysis of Reactogenicity, Safety, and Inability to Work among Healthcare Workers.

At the start of the SARS-CoV-2 pandemic, healthcare workers had an increased risk of acquiring coronavirus disease (COVID)-19. As tertiary care hospitals are critical for the treatment of severely ill patients, the University Hospital Erlangen offered BNT162b2 mRNA vaccination against COVID-19 to all employees when the vaccine became available in Germany. Here, we performed a survey to assess the age- and sex-dependent reactogenicity and safety of BNT162b2 in a real-life setting with a special emphasis on the rate of vaccine-related incapacity to work amongst the employees. All vaccinated employees were invited to participate in the survey and received access to an electronic questionnaire between 31 March and 14 June 2021, which allowed them to report local and systemic adverse effects after the first or second vaccine dose. A total of 2372 employees completed the survey. After both the first and second dose, women had a higher risk than men for vaccine-related systemic side effects (odds ratio (OR) 1.48 (1.24–1.77) and 1.49 (1.23–1.81), respectively) and for inability to work (OR 1.63 (1.14–2.34) and 1.85 (1.52–2.25), respectively). Compared to employees ≥ 56 years of age, younger vaccinated participants had a higher risk of systemic reactions after the first (OR 1.35 (1.07–1.70)) and second vaccination (OR 2.08 (1.64–2.63)) and were more often unable to work after dose 2 (OR 2.20 (1.67–2.88)). We also recorded four anaphylactic reactions and received two reports of severe adverse effects indicative of vaccine complications. After the first and second vaccination, 7.9% and 34.7% of the survey participants, respectively, were temporarily unable to work, which added up to 1700 days of sick leave in this cohort. These real-life data extend previous results on the reactogenicity and safety of BNT162b2. Loss of working time due to vaccine-related adverse effects was substantial, but was outweighed by the potential benefit of prevented cases of COVID-19.

Successful use of a subcutaneous injection port for modified cluster venom immunotherapy

Hymenoptera venom allergy is a life-threatening allergic reaction that develops after a honeybee, vespids (wasps), or ant sting. Severe reactions can be life-threatening or fatal. Beekeeping families are at a higher risk of honeybee stings, the risk of systemic reaction in this group being 14% to 38%.1

Preference for Immunotherapy with Tablets by People with Allergic Rhinitis.

BackgroundPeople with allergic rhinitis (AR) who are not controlled on conventional therapy can be treated using allergy immunotherapy (AIT) administered as tablets, injections or drops. In the US, the use of sublingual immunotherapy as tablets (SLIT-tablets) is limited in comparison to subcutaneous immunotherapy (SCIT).ObjectiveThis study investigated patients’ preference for SLIT-tablets vs monthly or weekly SCIT from a US patient perspective.MethodsWe carried out a discrete choice experiment (DCE) consisting of two blocks with eight choice sets. Adults and caregivers of children with moderate-to-severe AR were included if they had not previously or were not currently receiving AIT. Three attributes were included in the design: the mode and frequency of administration, the risk of systemic reactions and the co-payment.ResultsA total of 724 adults with AR and 665 caregivers of children with AR were included in the study. Both adults and caregivers had a significant preference for SLIT-tablets compared with both weekly and monthly injections and for less risk of anaphylactic shock. Caregivers were more risk-averse than adults when choosing their treatment, and the younger the child, the more risk-averse the caregiver. The preference for SLIT-tablets was found for both monoallergic and polyallergic adults and caregivers of monoallergic and polyallergic children. Respondents not wanting AIT for free were more risk-averse than those indicating that they wanted AIT for free.ConclusionOur findings suggest that SLIT-tablets is the preferred route of administration for AIT among adults and caregivers of children with AR.

A single centre retrospective study of systemic reactions to subcutaneous immunotherapy

BackgroundSubcutaneous immunotherapy (SCIT) is the standard approach for treating patients with sensitizations to aeroallergens. However, immunotherapy can trigger severe systemic reactions if delivered inappropriately or to high risk patients. We sought to characterize and quantify SCIT systemic reactions requiring epinephrine administration during a 6-year period in a Canadian setting following the recommendations for components and dosages published in the 2010 Canadian Society of Allergy and Clinical Immunology (CSACI) Immunotherapy Manual.MethodsA single centre retrospective chart review was performed for all patients with systemic reactions to subcutaneous immunotherapy requiring intramuscular epinephrine injection between January 2011 and October 2017. Each systemic reaction requiring epinephrine was reviewed for baseline patient characteristics, details of the reaction, and reaction severity. Research ethics approval was obtained through McMaster University.Results28 of 380 patients experienced a systemic reaction requiring epinephrine administration, with an incidence rate of 1 per 1,047 injection visits (0.095%). 26 of the 28 reactions occurred within the mandatory 30-minute observation period post allergen immunotherapy. Of the 28 patients that experienced a systemic reaction to SCIT, 11 patients had asthma and 5 patients had a history of possible food allergy. All of the systemic reactions occurred during injections from vial number 4, and five patients reacted to their first shot of a re-ordered extract. 10 of the 28 patients required more than one intramuscular injection of epinephrine, and 20 of 28 patients were transferred to the hospital by ambulance.ConclusionsThis is the first Canadian study to review patients with systemic reactions to subcutaneous immunotherapy. Several best practice methods were employed throughout the study to optimize subcutaneous delivery of immunotherapy extract, and our recorded per injection incidence rate for systemic reactions was comparable or below the rate published in similar studies. The recommendations in the CSACI Immunotherapy Manual provide an approach to standardizing prescriptions for SCIT to maximize immunotherapy efficacy and reduce the risk of systemic reactions, though similar studies in larger multicenter settings are needed to confirm these observations. These observations provide important objective information to clinicians about the potential risks for systemic reactions in patients considering SCIT.

A Rare Case of Multiple Severe Anaphylaxis Caused by Thyme, Black Pepper, Wasp and Honey

Dried thyme, black pepper and honey are widely used worldwide. However, systemic allergic reactions to these substances are rarely reported. Here we report a 45-year-old case with multiple severe anaphylaxis to thyme, black pepper, honey and wasp, that occurred at different times. Her reactions to thyme, black pepper and wasp were IgE-mediated as confirmed with skin prick tests and/or serology. It was not possible to determine the underlying etiology of her honey allergy. Still, with her history and the risk of systemic reactions with bee secretions and/or pollen protein content of honey, she was advised not to consume any traces of the causative foods and informed about bee avoidance.

SYSTEMIC REACTIONS TO SUBCUTANEOUS IMMUNOTHERAPY TREATED WITH EPINEPHRINE: A CANADIAN EXPERIENCE

Introduction Subcutaneous immunotherapy (SCIT) is associated with a risk of systemic reactions. While previous studies have attempted to quantify this risk, Canadian data is lacking. We aimed to quantify and characterize SCIT systemic reactions requiring epinephrine administration in a Canadian setting. Methods We performed a retrospective chart review of patients with reactions to SCIT requiring intramuscular epinephrine from January 2011 to October 2017 at a single allergy practice in Canada. The 2010 WAO grading system was used to grade the reactions. Results 380 patients were on SCIT and there were a total of 29,334 injection visits. 28 (7.37%) patients required epinephrine administration (incidence rate of 1 in 1,047 injection visits or 0.095%). The age range was from 8 to 60 years (median 34 years). There were 19 (68.9%) males and 4 patients were younger than 18. 11 patients had asthma. No patients were on beta-blockers. All the injections were from vial #4 (most concentrated). Five (17.9%) patients reacted to the first shot of a new serum. Two reactions occurred more than 30 minutes after the injection. Three (10.7%) patients experienced grade 4 reactions. Of these, 2 had asthma and 1 had food allergies. Two patients with grade 4 reactions reacted to the first injection from a new vial. All 3 reactions occurred within 30 minutes of the injection. There were no fatalities. Conclusions To our knowledge, this is the first retrospective chart review of patients with SCIT reactions in Canada. Our findings provide a Canadian perspective and complement the available data on SCIT related reactions.

Predicting reactivity threshold in children with anaphylaxis to peanut.

Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63+ basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction. In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity.

Allergen immunotherapy: an updated review of safety.

Allergen immunotherapy is the only modality that can modify the immune response upon exposure to aeroallergens and venom allergens. This review will update the allergist on recent studies evaluating safety of sublingual and subcutaneous allergen immunotherapy. Multiple clinical trials and retrospective studies have been published evaluating overall safety of these therapies. The risk of systemic reactions with subcutaneous immunotherapy remains quite low, but near-fatal and fatal anaphylaxis does occur, requiring physicians to be aware of potential risks for such events. Sublingual immunotherapy has a high incidence of local site application reactions, but severe anaphylactic events are very uncommon. Subcutaneous immunotherapy and sublingual immunotherapy are beneficial in treating allergic rhinitis and venom hypersensitivity but should be administered only by physicians familiar with potential risk factors and able to manage treatment-related local and systemic allergic reactions.

Debates in allergy medicine: Molecular allergy diagnosis with ISAC will replace screenings by skin prick test in the future

In today’s clinical practice patients’ skin is used as screening organ for diagnosing type 1 allergy. According to European guidelines skin prick testing with a panel of 18 allergen extracts is recommended, in the US between 10 to 50 allergens are used. The specificity and sensitivity of skin testing is individually highly variable depending on age, body mass, and skin barrier status. In atopic inflammation skin testing gives more false positive results. Smaller skin area and strain limits prick testing in small children. Although the risk for systemic reactions in skin prick testing is very small, emergency medications must be available. Considering the fact that IgE is the only reliable biomarker for type I allergy, upfront IgE screening with ISAC, followed by fewer skin tests to approve positive sensitizations, is proposed. It is time to arrive in the age of molecular allergy diagnosis in daily patient care.

Allergic Reactions to Hymenoptera

Allergic reactions to insect venom can occur in individuals of all ages and may be preceded by a number of uneventful stings. These allergic reactions can be fatal. In the United States, at least 40 deaths due to insect stings occur each year; this number may be higher as some unexplained deaths may be caused by insect stings. This review details the epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, and acute and preventive treatment for allergic reactions to Hymenoptera. Figures show the honeybee, the European hornet, the Eastern yellow jacket, the red imported fire ant, the paper wasp, and the appearance of a pustule resulting from the sting of a fire ant. Tables list the risk of systemic reactions and clinical recommendations based on reaction to previous stings and venom skin test or serum immunoglobulin E test results, stinging insects of the order Hymenoptera, risk factors for severe reactions to stings, and risk factors for relapse after discontinuing venom immunotherapy. This review contains 6 highly rendered figures, 4 tables, and 62 references.

Anafilaxia secundaria a pruebas cutáneas Prick-to-Prick para alimentos y sus factores de riesgo

The diagnosis of food allergy requires a proper anamnesis and diagnostic testing with skin prick tests with fresh foods and/or standardized allergen, or specific IgE tests. The risk of systemic reactions is of 15-23 per 100,000 skin tests performed by prick method, specifically anaphylaxis at 0.02%. This paper reports the case of four patients, who while performing prick to prick test with fresh food presented anaphylactic reaction. Implicated foods were fruits of the Rosaceae, Anacardiaceae and Caricaceae families. The severity of anaphylaxis was: two patients with grade 4, one patient grade 2 and one grade 3, all with appropriate response to drug treatment. The risk factors identified were: female sex, personal history of atopy, previous systemic reaction to Hymenoptera venom, prior anaphylaxis to prick tests to aeroallergens. We found that a history of positive skin test for Betulla v, can be a risk factor for anaphylaxis in patients with oral syndrome. During testing prick to prick with food anaphylaxis can occur, so it should be made with aerial red team on hand. The history of positivity Betulla v is an additional risk factor in these patients.

Component-resolved diagnosis of peach allergy and its relationship with prevalent allergenic pollens in China

Component-resolved diagnosis of peach allergy and its relationship with prevalent allergenic pollens in China

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial

Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults. Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B. burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 μg, 60 μg, or 90 μg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347. 300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 μg, 51 to 60 μg, and 50 to 90 μg doses), and 149 to non-adjuvanted vaccines (50 to 30 μg, 49 to 60 μg, and 50 to 90 μg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41-0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13-0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 μg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4-20] of 50), injection-site pain (16 [32%, 21-45]), and tenderness (17 [34%, 23-47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17,321) and booster (19,056-32,824) immunisations. The 30 μg adjuvanted formulation induced the highest antibody titres after the booster: range 26,143 (95% CI 18,906-36,151) to 42,381 (31,288-57,407). The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin. Baxter.