Systemic Anaphylactic Reactions Research Articles

#1491 Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange

Abstract Background and Aims Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. The anti-VWF nanobody Caplacizumab is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. This study evaluates the treatment of acute iTTP with caplacizumab and immunosuppression, but without TPE, in comparison to the conventional management with TPE, caplacizumab and immunosuppression. Method All patients in this study were identified from the Austrian Thrombotic Microangiopathy Registry (ATMAR) and the German REACT-2020 TTP registry (ClinicalTrials.gov identifier: NCT04985318). A total of 42 acute iTTP episodes in 41 patients were managed with a treatment regimen aimed at avoiding first-line TPE if the platelet count increased after the first dose of 10 mg caplacizumab, and the patient's condition and organ function remained stable (TPE-free cohort). This treatment modification was implemented based on shared decision making. An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 iTTP patients, receiving frontline caplacizumab treatment with TPE and immunosuppression (TPE cohort). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractoriness, and iTTP-related deaths. Results The primary outcome parameter, time to platelet count normalization, was not significantly different between TPE-free and TPE-based management (Kaplan-Meier estimator and log-rank test, Table 1 and Fig. 1). The median time to platelet count normalization was 3 days in the TPE-free cohort and 4 days in the TPE cohort. There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths. For evaluation of the short-term treatment response, both cohorts were assessed for the time to platelet count doubling. The median time to platelet count doubling was 1 day in both cohorts. Four patients in the TPE-free cohort did not immediately respond to the first caplacizumab injection and subsequently underwent TPE, after a maximum monitoring period of 40 hours. In these patients, TPE was initiated at a median of 1.5 days after the first caplacizumab dose, and TPE was performed for a median of 4.5 days. This delayed platelet response could be attributed to concomitant diseases and factors, e.g. active HIV and hepatitis B virus coinfection, active CMV infection, concomitant antiplatelet antibodies in association with an ovarian teratoma, and multiple platelet transfusions before the correct diagnosis. During overall follow-up, complications were observed in 11 patients (26.2%) in the TPE-free group and 16 patients (27.1%) in the TPE group, excluding complications of iTTP that were evaluated as outcome parameters. Serious complications occurred in 4 patients (6.8%) from the TPE cohort while on TPE, including severe systemic anaphylactic reactions with severe hypotension, generalized seizure and supraventricular tachycardia. Bleeding complications were reported without a significant difference between groups. Conclusion For the first time since the introduction of TPE in the early 1990s, the results of our study systematically challenge the absolute need for TPE and suggest a paradigm shift in acute iTTP management. In detail, our treatment approach was successfully implemented in 38 of 42 acute iTTP episodes (90.5%). We observed no significant difference in the time to platelet count normalization between patients with iTTP treated with and without TPE. The analysis of key secondary outcomes did not reveal significant differences in the proportion of patients who achieved a clinical response or experienced exacerbations, refractoriness, or TTP-related deaths. In conclusion, Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP.

Immediate Hypersensitivity Reactions Induced by COVID-19 Vaccines: Current Trends, Potential Mechanisms and Prevention Strategies.

As the world deals with the COVID-19 pandemic, vaccination remains vital to successfully end this crisis. However, COVID-19-vaccine-induced immediate hypersensitivity reactions presenting with potentially life-threatening systemic anaphylactic reactions are one of the reasons for vaccine hesitancy. Recent studies have suggested that different mechanisms, including IgE-mediated and non-IgE-mediated mast cell activation, may be involved in immediate hypersensitivity. The main culprits triggering hypersensitivity reactions have been suggested to be the excipients of vaccines, including polyethylene glycol and polysorbate 80. Patients with a history of allergic reactions to drugs, foods, or other vaccines may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination, administering different vaccines for the primary and following boosters, changing the fractionated doses, or pretreating the anti-IgE antibody. This review discusses the current trends, potential mechanisms, and prevention strategies for COVID-19-vaccine-induced immediate hypersensitivity reactions.

Anaphylactic Reactions in People Taking Amophophallus Paeoniifolius (Suweg)

Systemic anaphylactic reactions are a rare condition with a prevalence of around 1.6-5.1%. Based on the latest epidemiological data the ratio of fatal anaphylactic reactions is approximately 1%. To diagnose anaphylaxis, sampson criteria are used. Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergycausing substance. Anaphylaxis, it was acknowledged that no criteria will provide 100% sensitivity and specificity, but it was believed that the criteria proposed are likely to capture more than 95% of cases of anaphylaxis. Anaphylaxis itself occurs in 15 of 10,000 patients and is characterized by acute reactions, with diffuse erythema, pruritus, urticaria, angioedema, bronchospasm, laryngeal edema, hyperperistalsis, hypertension, cardiac arrhythmias, hemolytic anemia. Most symptoms develop quickly (five to 30) minutes after exposure. A 44-year-old with an anaphylactic reaction has been reported. The administration of epinephrine 0.3-0.5 cc deltoid IM and general management of anaphylaxis in the initial acute condition of anaphylactic reaction is given to the patient.

Food Allergen Nitration Enhances Safety and Efficacy of Oral Immunotherapy in Food Allergy.

(1) Background: Posttranslational protein modifications have been demonstrated to change protein allergenicity. Previously, it was reported that pretreatment with highly nitrated food proteins induced a tolerogenic immune response in an experimental mouse model and in human immune cells. Here, we investigated a possible therapeutic effect of modified proteins and evaluated the safety of oral exposure to highly nitrated proteins in an experimental food allergy model. (2) Methods: BALB/c mice were orally sensitized towards ovalbumin (OVA) under gastric acid suppression. Thereafter, treatment via intragastric gavage with maximally nitrated OVA (nOVAmax) and OVA as a control was performed six times every 2 weeks. On the last day of experiments, all the treated mice were orally challenged with OVA. Systemic anaphylactic reaction was determined by measuring the core body temperature. Moreover, antibody levels, regulatory T cell numbers, cytokine levels and histology of antrum tissues were analyzed. (3) Results: After oral immunotherapy, OVA-specific IgE titers were decreased while IgG1 titers were significantly elevated in the mice receiving OVA. After oral challenge with OVA, nOVAmax-treated allergic animals showed no drop of the core body temperature, which was observed for OVA-allergic and OVA-treated allergic animals. Significantly fewer eosinophils and mast cells were found in the gastric mucosa of the allergic mice after nOVAmax treatment. (4) Conclusions: Oral immunotherapy with nOVAmax reduced allergic reactions upon allergen exposure and the number of allergen effector cells in the gastric mucosa. Thus, maximally nitrated allergens enabled an efficient and safe treatment for food allergy in our experimental model.

Immunotherapy with insect venoms: Entomologist's expertise secures choice of treatment

Hymenoptera venom allergy may lead to severe allergic reactions to the point of life-threatening anaphylaxis. Between 0.3% to 7.5% of adults1 and 0.15% to 3.4% of children2 develop systemic anaphylactic reactions, varying from mere cutaneous to severe organ symptoms.3 The only causal therapy is Hymenoptera venom immunotherapy (IT).4 In affected patients, it is important to distinguish between honeybee and Vespula (yellow jacket) stings. This requires a detailed medical history that frequently requires photographic evidence.

Manifestations cliniques de l’allergie aux venins d’hyménoptères

The collection of anamnesis data is fundamental in allergology, especially in cases of suspected allergy to hymenoptera venom. The various clinical symptoms and their chronology must be systematically collected in the medical files. Whether there is a locoregional reaction, a systemic anaphylactic reaction or organ damage, the subsequent therapeutic attitude will be different. These semiological elements make it possible to decide whether or not an immunotherapy is indicated and whether emergency medications should be prescribed.

Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation.

Dimerized translationally controlled tumor protein (dTCTP) amplifies allergic responses through activation of several types of immune cells and release of inflammatory mediators. In particular, dTCTP plays an important role in histamine release by triggering mast cells and has been proposed as a target in the treatment of allergic diseases. dTCTP-binding peptide 2 (dTBP2) is known to attenuate severe allergic rhinitis and asthma through inhibition of dTCTP activity on airway epithelial cells and T cells; however, it is unclear whether dTBP2 affects mast cell function and mast cell disease. In this study, we explored the effects of dTBP2 on mast cell degranulation and allergen-induced anaphylactic reactions. We found that bacterial product lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased calcium mobilization in mast cells, which is essential for degranulation. Furthermore, dTBP2 directly and dose-dependently inhibited in vitro mast cell degranulation enhanced by compound 48/80, suggesting a direct and potent anti-anaphylactic activity of dTBP2. dTBP2 also significantly suppressed the dTCTP-induced degranulation and histamine release through inhibition of the p38 MAPK signaling pathway and suppression of lysosomal expansion and calcium mobilization in mast cells. More importantly, in vivo administration of dTBP2 decreased mortality and significantly attenuated histamine release and inflammatory cytokine production in compound 48/80-induced systemic anaphylactic reactions. These results suggest that dTBP2 is beneficial for the control of anaphylaxis with increased dTCTP.

Ефективність алергенспецифічної імунотерапії пилковими алергенами в дітей із позиції молекулярної алергології

Мета роботи — встановити можливі причини неефективності алергенспецифічної імунотерапії (АСІТ) пилковими алергенами (бур’янів) у дітей із сезонним алергічним ринітом і/або бронхіальною астмою на підставі вивчення гіперчутливості до алергенів, аналізу анамнестичних даних. Матеріали та методи. Проведено алерготестування 192 дітей. 52 пацієнтам проведене анамнестичне опитування з акцентом на перехресну алергію та супутню патологію верхніх дихальних шляхів, а також на ефективність АСІТ. Статистична обробка результатів проведена в програмі Statistica for Windows 6.0. Результати. Серед хворих на поліноз переважала гіперчутливість до амброзії (56 %), циклахени (46 %) та соняшника (58 %). До злакових рослин (райграс, грястиця, вівсяниця) чутливі 10—20 % пацієнтів. 23 % дітей мають сенсибілізацію до 5 та більше алергенів (в середньому до 3,3 ± 0,4). 52 % дітей мають супутню харчову алергію, 15 % — синдром оральної алергії, третина дітей — аденоїдні вегетації, гіпертрофію глоткових мигдалин, у 13 % алергічний риніт ускладнювався синуситом. Незадовільний клінічний ефект АСІТ пилковими алергенами асоціювався з наявністю поєднаної пилково-грибкової сенсибілізації, перехресної харчової та пилкової алергії, із сенсибілізацією до 4 та більше пилкових алергенів, з полівалентною алергією, а також спостерігався при поєднанні алергічного риніту із синуситом (р < 0,05). Висновки. Перед початком АСІТ дітям із полінозами необхідно визначити групу ризику стосовно можливої неефективності цього методу терапії та рекомендувати їм визначення специфічних імуноглобулінів класу Е до мажорних та мінорних алергенів для прогнозування ефективності АСІТ.

The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods

Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP.We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HVallergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.

Global View on Ant Venom Allergy: from Allergenic Components to Clinical Management

Hymenoptera venom allergy is characterised by systemic anaphylactic reactions that occur in response to stings from members of the Hymenoptera order. Stinging by social Hymenoptera such as ants, honeybees, and vespids is one of the 3 major causes of anaphylaxis; along with food and drug exposure, it accounts for up to 43% of anaphylaxis cases and 20% of anaphylaxis-related fatalities. Despite their recognition as being of considerable public health significance, stinging ant venoms are relatively unexplored in comparison to other animal venoms and may be overlooked as a cause of venom allergy. Indeed, the venoms of stinging ants may be the most common cause of anaphylaxis in ant endemic areas. A better understanding of the natural history of venom allergy caused by stinging ants, their venom components, and the management of ant venom allergy is therefore required. This article provides a global view on allergic reactions to the venoms of stinging ants and the contemporary approach to diagnose and manage ant venom allergy.

Postmortem diagnostics of assumed suicidal food anaphylaxis in prison: a unique case of anaphylactic death due to peach ingestion

Suicidal ingestion of food which the victim is aware they are allergic to is an exceptional occurrence in the forensic field. To the best of our knowledge, no cases of suicidal food anaphylaxis have been reported to date. Therefore we present the first case described in the literature. A 30-year-old prisoner was found dead inside his cell with the remains of a peach remains next to his body, and a handwritten farewell note in his pocket. The autopsy revealed only non-specific findings, while laboratory investigations (serological, toxicological, histological, and immunohistochemical) played a pivotal role in determing the cause and manner of death. In particular, a high titer of both total and specific IgE antibodies was detected, as well as an increase of the tryptase level in cadaveric blood. Moreover, a massive concentration of salicylates was measured in the gastric contents. Microscopically, cellular residues characterized by a vegetal structure were observed in the gastric contents and elements suggestive of mast cells were detected in the glottis, lungs, and myocardium. The immunohistochemical investigation with anti-CD117 and anti-tryptase antibodies showed positivity for mast cells, some of which appeared degranulated. Such findings were entirely consistent with an acute systemic anaphylactic reaction triggered by allergy. Therefore, the prisoner’s death was attributed to self-induced food anaphylaxis caused by the ingestion of peaches. This conclusion was achieved based only on circumstantial data, anamnestic information, autopsy findings, and multiple laboratory results. This integrated approach should be used to pursue a post-mortem diagnosis of anaphylaxis.

ORMDL2 Deficiency Potentiates the ORMDL3-Dependent Changes in Mast Cell Signaling.

The systemic anaphylactic reaction is a life-threatening allergic response initiated by activated mast cells. Sphingolipids are an essential player in the development and attenuation of this response. De novo synthesis of sphingolipids in mammalian cells is inhibited by the family of three ORMDL proteins (ORMDL1, 2, and 3). However, the cell and tissue-specific functions of ORMDL proteins in mast cell signaling are poorly understood. This study aimed to determine cross-talk of ORMDL2 and ORMDL3 proteins in IgE-mediated responses. To this end, we prepared mice with whole-body knockout (KO) of Ormdl2 and/or Ormdl3 genes and studied their role in mast cell-dependent activation events in vitro and in vivo. We found that the absence of ORMDL3 in bone marrow-derived mast cells (BMMCs) increased the levels of cellular sphingolipids. Such an increase was further raised by simultaneous ORMDL2 deficiency, which alone had no effect on sphingolipid levels. Cells with double ORMDL2 and ORMDL3 KO exhibited increased intracellular levels of sphingosine-1-phosphate (S1P). Furthermore, we found that concurrent ORMDL2 and ORMDL3 deficiency increased IκB-α phosphorylation, degranulation, and production of IL-4, IL-6, and TNF-α cytokines in antigen-activated mast cells. Interestingly, the chemotaxis towards antigen was increased in all mutant cell types analyzed. Experiments in vivo showed that passive cutaneous anaphylaxis (PCA), which is initiated by mast cell activation, was increased only in ORMDL2,3 double KO mice, supporting our in vitro observations with mast cells. On the other hand, ORMDL3 KO and ORMDL2,3 double KO mice showed faster recovery from passive systemic anaphylaxis, which could be mediated by increased levels of blood S1P presented in such mice. Our findings demonstrate that Ormdl2 deficiency potentiates the ORMDL3-dependent changes in mast cell signaling.

A rare case report on pediatric shellfish allergy

Shellfish are extensively consumed worldwide because of their nutritional value. In general they are good sources of low-fat protein rich in several essential vitamins and minerals as well as in the essential nutrients omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) [1]. Shellfish belongs to “The Big 8” food groups causing allergy, which often does not outgrow during childhood. However, increase in IgE – mediated sea food allergy has been linked to shellfish. Seafood- associated shellfish include crustaceans & molluskans [2]. These may cause mild local symptoms & lead to severe systemic anaphylactic reactions by ingestion, inhalation, or contact. Globally, the prevalence of shellfish allergy estimated to be 0.5% to 2.5% of the general population [3]. There are limited data showing the prevalence of shellfish allergy in children.

Comparison of the Safety Profiles of 3 Different Hymenoptera Venom Immunotherapy Protocols: A Retrospective 2-Center Study of 143 Patients

Introduction: Venom immunotherapy (VIT) is highly effective and the treatment of choice for patients with a history of systemic anaphylactic reactions to a Hymenoptera sting. It has been assumed that VIT protocols with a rapid dose increase during the induction phase are associated with a higher frequency of systemic reactions (SR); however, study data addressing this issue are conflicting. Objective: The aim of this study was to compare the safety of 3 different Hymenoptera VIT protocols (half-day ultra-rush, 3-day rush, 3-week cluster). Methods: This retrospective 2-center study included 143 Hymenoptera venom-allergic patients, who underwent 147 VIT procedures during the years 2015–2018. Twenty cluster, 75 rush, and 52 ultra-rush VIT protocols were performed with honeybee (54 protocols) and wasp (93 protocols) venom. All documented side effects were classified into large local and SR (Ring and Messmer classification). Results: SR were observed during 11 (7.5%) VIT procedures and did not exceed severity grade II. SR occurred more frequently in cluster compared to accelerated protocols. This result was observed for both honeybee (cluster: 25%, rush: 8.7%, and ultra-rush: 15.8%) and wasp VIT (cluster: 12.5%, rush: 0%, and ultra-rush: 6.1%), though the differences were statistically significant only in the wasp VIT subgroup. Honeybee venom elicited more SR than wasp venom (14.8 and 3.2%, respectively, p = 0.01). The risk for SR did not depend on age, sex, concomitant antihypertensive medication, hypertryptasemia, or severity of the index sting reaction. Conclusion: Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster VIT protocols in our study.

Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NAC study)

BackgroundPrevious studies of paracetamol overdose treatment show that a 2-bag, 20-h intravenous (IV) acetylcysteine regimen decreased the incidence of non-allergic anaphylactic reactions compared to the 3-bag, 21 h IV regimen, but have not examined efficacy of the 20-h 2 bag regimen. MethodsThis was a multi-centre observational study of paracetamol overdose presentations treated with a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) compared to a 3-bag regimen, performed from 2009 to 2019. Patients were referred from the emergency department to the inpatient toxicology units for continued management. For the primary non-inferiority analysis: subjects had single, acute ingestions, a serum paracetamol-concentration performed 4 to 8-h post-ingestion. The primary outcome was development of acute liver injury (ALI), defined as peak ALT>150 U/L; and > double admission baseline ALT (for presentations within 24 h post-overdose). Secondary outcomes included adverse reactions to acetylcysteine (cutaneous and systemic). FindingOut of 6419 paracetamol overdoses, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 the 3-bag acetylcysteine regimen. When presentation bloods were performed 4 to 8-h post-overdose, 21 (3.1%) developed ALI with the 2-bag regimen vs 16 (2.9%) with the 3-bag regimen (Difference: 0.2%, 95%CI:-1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference -0.4%, 95%CI -1.75, 0.91). When presentation bloods were performed 8 to 24-h post-overdose, 70 (21%) developed ALI with the 2-bag regimen vs 46 (23%) with the 3-bag regimen (Difference: -2%, 95%CI -9.12 to 5.36). There were significantly less cutaneous and systemic non-allergic anaphylactic reactions recorded after treatment with the two-bag than the three-bag regimen (1.3% [n = 17] and 7.1% [n = 65], Difference: -5.8%, 95%CI -7.6 to -4.0, p < 0.0001), respectively. InterpretationA two-bag intravenous acetylcysteine regimen was found to be non-inferior to the three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose. No important differences were seen for any other presentations. The two-bag regimen also decreased the incidence of both non-allergic anaphylactic reactions and gastrointestinal adverse events from acetylcysteine treatment. FundingAW is funded by a National Health and Medical Research Council (NHMRC) Early Career Fellowship ID 1159907. GI is funded by a NHMRC Senior Research Fellowship ID 1061041. The NHMRC had no role in the design, writing of this manuscript. The corresponding author (AW) had full access to all the data in the study and final responsibility for the decision to submit the manuscript for publication.

Mast Cell-Mediated Reactions In Vivo.

Mast cells are involved in many physiological reactions in which their functions can be very diverse. Models of allergic skin inflammation and systemic anaphylactic reactions in mice are validated methods in which the role of mast cells is well established. In this chapter, we will therefore present protocols for passive cutaneous anaphylaxis and contact hypersensitivity, i.e., models which can be used to identify and characterize the role of mast cells as well as mast cell mediators and receptors in allergic IgE-dependent and IgE-independent skin inflammation, and for passive systemic anaphylaxis, a model ideally suited to characterize the systemic effects of mast cell-derived mediators and mast cell receptors.

How fast does wasp venom immunotherapy affect a regulatory T cell subpopulation (CD4+ CD25+ Foxp3+) and the synthesis of interleukins 10, 21 and transforming growth factor β1?

IntroductionThe literature describes the influence of venom immunotherapy (VIT) on the subpopulation of T regulatory cells (CD4+ CD25+ Foxp3+) and the synthesis of IL-10, TGF-β1 as well as many other cytokines at various times after immunotherapy.AimTo assess changes in the percentage of cells of CD4+ and CD25+ in peripheral blood and serum concentrations of IL-10, IL-21 and TGF-β1 in the early stages of VIT.Material and methodsThe study included 18 patients who were allergic to wasp venom and who in the past underwent systemic anaphylactic reaction after stinging, meeting the criteria to qualify for VIT. The immunoenzymatic method (ELISA) was used to assess concentrations of cytokines IL-10, IL-21 and TGF-β1 and the surface antigens CD4 and CD25 on the cells. The concentrations were determined by flow cytometry method at baseline (before VIT) and after 2.5 and 24 h from the VIT starting point.ResultsThe mean values of the activity of T lymphocytes CD4+ CD25+ FoxP3+ and concentrations of the cytokines IL-10, IL-21 and TGF-β1 are shown in table.ConclusionsA 24-hour activation assessment of serum concentrations of cytokines IL-10, IL-21 and TGF-β1 during the first day of the Hymenoptera venom immunotherapy by ultra-rush protocol does not show the significant dynamics of change of the examined parameters.

A case report on unusual cause of young ischemic Cerebrovascular Accident: a rare complication of honey bee stings

Honey bee stings usually won’t require hospitalization. The clinical features of Bee stings can be from local reactions such as pain, wheal, flare, edema, swelling to systemic anaphylactic reactions and infrequent major complications reported from different studies include rhabdomyolysis, acute renal failure, acute pulmonary edema, disseminated intravascular coagulation, stroke, encephalopathy and very rarely cerebral hemorrhage. (1,2) Stroke following bee sting can be due to toxins itself, following anaphylactic shock or pain induced catecholamines surge. Here we report a case on ischemic Cerebrovascular accident following multiple Bee stings complicated with anaphylactic shock.

REGULATORY AND METHODOLOGICAL ASPECTS OF STUDYING ALLERGENIC PROPERTIES OF NEW MEDICINES AT THE PRECLINICAL STAGE

The assessment of allergic risk at the preclinical stage of drug development has been a debatable issue due to the integration of national requirements for medicines authorisation with those of the Eurasian Economic Union (EAEU). The article summarises mechanisms and factors involved in the development of drug hypersensitivity, as well as the main national and foreign regulatory requirements. It also cites the results of allergic risk assessment studies involving standard guinea pig tests, such as systemic anaphylactic reactions and active cutaneous anaphylaxis, for a number of medicines with the molecular weight of the active substance of more than 1000 Da and less than 1000 Da. Data analysis confirms that the number of positive reactions for high molecular weight compounds (&gt;1000 Da) is significantly higher than the number of positive reactions for low molecular weight compounds (&lt;1000 Da). There were some false-positive results detected. The results of foreign studies confirm the lack of correlation between the experimental data obtained in similar tests in guinea pigs and the clinical data. Thus, standard tests in guinea pigs cannot adequately predict the risk of immediate hypersensitivity reactions to new medicines in clinical practice. Negative or positive results should not be regarded as confirmation of potential absence or presence of anaphylactic reactions in clinical practice.

Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial

BackgroundAllergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo.MethodsFifty-eight AR elderly patients who were monosensitized to house dust mites were individually randomized in comparable numbers to one of two parallel groups with the following interventions: 2 years of perennial AIT using PURETHAL Mites or placebo. The symptoms and medication scores were presented as the AAdSS and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen-specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were monitored. The intent-to-treat population was analysed.ResultsAfter 24 months of AIT, AAdSS significantly decreased from 4.27 ± 1.58 to 1.82 ± 0.71 (p < 0.05). The TCRS was significantly decreased after 2 years of AIT. Serum-specific IgG4 against D. pteronyssinus, D. farinae, Der p1, and Der p2 increased during the AIT trial in the study group. The RQLQ score was significantly improved in patients who received AIT, from 1.86 (95% CI 1.51–1.78) to 1.26 (95% CI 1.09–1.55). Two mild systemic anaphylactic reactions (degree I) were reported after injections in the active group during the AIT therapy.ConclusionThe DBPC trial showed AIT for house dust mite allergens was effective and safe in elderly patients with allergic rhinitis.Trial registrationThis randomized, double-blinded placebo-controlled (DBPC) trial was conducted at one centre (ClinicalTrials.gov no. NCT03209245)