Systemic Allergic Reactions Research Articles

The case report of AQP4 and MOG IgG double positive NMOSD treated with subcutaneous Ofatumumab

Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease with IgG against aquaporin 4 (AQP4) in more than two thirds of patients. Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody is found in some AQP4-negative NMOSD patients and MOG antibody-associated disease (MOGAD) is thought to be distinct from NMOSD. Due to the high disabling nature of NMOSD, treatment strategy on first attack is crucial for good prognosis. Rituximab (RTX), an anti-CD20 monoclonal antibody (mAb), is the first-line treatment for NMOSD. However, RTX can be limited by the relatively high rate of systemic allergic reaction. Herein, we reported a rare case of AQP4 and MOG-IgG double positive NMOSD patient effectively and safely treated with ofatumumab (OFA), a novel fully humanized anti-CD20 mAb.

The first successful desensitization protocol in exenatide allergy: a case report

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists are important treatment options in obese patients with type 2 diabetes. To date, few immediate allergic reactions due to GLP-1 receptor agonists were reported. One report revealed that a patient with a level 1 anaphylaxis according to Brighton Criteria due to an exendin based GLP-1 receptor agonist was able to tolerate liraglutide (Human GLP-1 analogue), the alternative GLP-1 receptor agonist. Since exenatide is the only available GLP-1 receptor agonist covered by insurance in Turkey, a drug desensitization protocol, the only therapeutic method in hypersensitivity reactions used in case of absence of an alternative drug, was considered. Here, we report a successful desensitization protocol for the first time in two obese diabetic patients with an immediate hypersensitivity to exenatide.Case presentationThe first patient was a 47 year-old female. She was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes after the last dose, following a week of an exenatide BID 5 mcg/20 mcl treatment. Although the reaction was sudden onset, it did not meet the Brighton Criteria of anaphylaxis. The second patient was a 46 year-old female. She had a large local immediate injection site reaction that appeared 15 min following an exenatide BID 5 mcg/20 mcl injection. The injection site reaction was not accompanied by a systemic allergic reaction. We performed desensitization with exenatide to two patients who need GLP-1 receptor agonist treatment. Protocol was completed in 7 steps in approximately 3 h, with the aim of reaching the daily dosage of exenatide. Throughout this process, we observed that both cases tolerated the protocol without any complaints or complications. Following the protocol, the patients safely tolerated the treatment for 3 months.ConclusionsWe present the first successful desensitization protocol to exenatide in both local and/or systemic immediate hypersensitivity reactions and indicate the importance of desensitization in patients who do not have alternative therapies.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Imunoterapija kod pacijenata sa prvim tipom preosetljivosti na Hymenoptera venome

Hymenoptera venom allergy (HVA) is an anaphylactic reaction that occurs after the sting of Hymenoptera insects: honeybee (Apis mellifera), wasp (Vespula vulgaris) or hornet (Vespa crabo). Hymenoptera insects can cause IgE-mediated hypersensitivity reactions in insect-sensitized patients, ranging from local to severe systemic reactions and even fatal anaphylaxis. Systemic allergic reactions (SAR) after Hymenoptera insect stings have been reported in up to 7.5% of adults and up to 3.4% of children. They can be limited to the skin or cause severe reactions such as dizziness, dyspnea, nausea, and loss of consciousness, shock, cardiac or respiratory arrest. Patients with HVA are advised to carry an emergency kit consisting of an epinephrine auto-injector (AAI), H1-antihistamines and corticosteroids depending on the severity of the previous SAR. The only treatment that can potentially prevent SAR is immunotherapy with the appropriate venom (VIT). Venom immunotherapy (VIT) has been reported to be effective in 77%-84% of patients treated with bee venom and in 91%-96% of patients treated with wasp venom. The latest European Academy of Allergy and Clinical Immunology (EAACI) guidelines provide evidence-based recommendations for the use of VIT. It is recommended in children and adults who are hypersensitive to the venom because it leads to a significant improvement in quality of life-compared to wearing an adrenaline auto-injector. By receiving increasing doses of venom over 3 to 5 years, VIT leads to a change in the immune response and tolerance to the respective venom. Molecular diagnostics, which uses recombinant allergens, enables detection of true sensitization and thus improves the selection of appropriate venom for long-term VIT. This review aims to provide information on immunotherapy recommendations, as well as risk factors for SAR during and after VIT.

Evaluation of the safety of dose escalation period of subcutaneous specific allergic immunotherapy in patients with rhino-conjunctivitis or allergic asthma previously vaccinated against SARS-CoV-2

BACKGROUND: More than 90% of the Spanish population has been vaccinated against the SARS-CoV-2 virus in our setting. The administration of this vaccine is not contraindicated in allergic subjects; however, it is unknown whether any precaution should be taken when initiating subcutaneous allergen immunotherapy after this vaccination. The objective of the study was to analyze the safety of subcutaneous allergen immunotherapy during the dose escalation phase in subjects sensitized to pollens or mites previously vaccinated against SARS-CoV-2. METHODS: An observational study with retrospective data collection from protocolled patients' medical records was designed. Outpatients older than 12 years with diagnosis of pollen or house dust mite allergic rhinitis with or without bronchial allergic asthma were selected who had completed the subcutaneous immunotherapy dose escalation phase. A complete SARS-CoV-2 vaccination was required for the inclusion. RESULTS: Three hundred and seventy-nine patients were included by 53 investigators. The mean age was 31 years old and 55,9% female. Time from last SARS-Cov-2 vaccination dose to subcutaneous immunotherapy initiation was 4.1 months (95%CI 3.8-4.4). subcutaneous immunotherapy with a pollen allergoid was administered to 135 patients (35.6%) with a total of 739 injections, while subcutaneous immunotherapy using a house dust mite allergoid was administered to 244 patients (64.4%) with a total of 1311 doses. During the dose escalation phase with the pollen allergoid, 45 patients (33.3%) suffered 93 local adverse reactions (12.6% of injections), while 17 patients (12.6%) experienced 17 systemic allergic reactions (2.3% of injections) of them 14 were World Allergy Organization Grade 1 and 3 of Grade 2. During the dose escalation phase with the house dust mite allergoid, 55 patients (22.5%) reported 133 local adverse reactions (10.1% of injections), and 7 patients (2.9%) showed 7 World Allergy Organization Grade 1 systemic reactions (0.5% of injections). No systemic reactions Grade 3 or higher were reported. CONCLUSIONS: The well-known safety profile of the subcutaneous allergen immunotherapy using pollen or house dust mite allergoids has not been changed after the SARS-CoV-2 vaccine administration. No relevant differences in the incidence of local or systemic allergic reactions during the dose escalation phase were identified, so it is considered that the patient’s safety has not been compromised to initiate this treatment after the SARS-CoV-2 vaccine administration.

Epinephrine autoinjectors: individualizing device and dosage to optimize anaphylaxis management in the community setting

Background: Anaphylaxis is the most severe manifestation of a systemic allergic reaction, and, in the community setting, the immediate administration of an epinephrine autoinjector (EAI) can be life-saving. Physicians are tasked with selecting the most appropriate EAI for each individual and counseling patients and/or their caregivers to maximize the likelihood of successful deployment of the EAI. Objective: To offer an evidence-based expert clinical perspective on how physicians might best tailor EAI selection to their patients with anaphylaxis. Methods: A group of eight adult and pediatric allergists with expertise in anaphylaxis management reviewed and assessed the published data and guidelines on anaphylaxis management and EAI device selection. Results: Personalized EAI selection is influenced by intrinsic individual factors, extrinsic factors such as the properties of the individual EAI (e.g., dose, needle length, overall design) as well as cost and coverage. The number and the variety of EAIs available have expanded in most jurisdictions in recent years, which provide a greater diversity of options to meet the characteristics and needs of patients with anaphylaxis. Conclusion: There currently are no EAIs with customizable dose and needle length. Although precise personalization of each patient's EAI remains an optimistic future aspiration, careful consideration of all variables when prescribing EAIs can support optimal management of anaphylaxis.

ORAL IMMUNOTHERAPY IN CHILDREN WITH PEANUT ALLERGY ALONE OR WITH OTHER FOOD ALLERGY IN PALISADE

<h3>Introduction</h3> Being allergic to foods besides peanut, or not, might be considered of importance during the shared decision-making process for treatment options. We analyzed efficacy and safety of peanut (<i>Arachis hypogaea</i>) allergen powder-dnfp (PTAH) versus placebo in children with either peanut allergy alone (PAA) or with other food allergies (PA+FA) in PALISADE. <h3>Methods</h3> Data from participants with peanut allergy aged 4 to 17 years randomized 3:1 to PTAH or placebo in the phase 3 PALISADE trial were analyzed. <h3>Results</h3> Most children (n=325) had PA+FA (PTAH, n=245; placebo, n=80); 171 children had PAA (PTAH, n=127; placebo, n=44). Response rates for those tolerating ≥600 mg of peanut protein at trial exit were higher for PTAH vs placebo in both PA+FA and PAA groups: 65.3% vs 1.3% (<i>P</i><0.0001), respectively, for PA+FA, and 70.9% vs 9.1% (<i>P</i><0.0001) for PAA. In children with PA+FA, rates of participants reporting ≥1 serious adverse event (AE) were 0.4% for PTAH and 0% for placebo; rates were 2.9% and 1.3% for severe AE, respectively (<b>Table 1</b>)<b>.</b> In children with PAA, rates of participants reporting ≥1 serious AE were 5.5% for PTAH and 2.3% for placebo; rates were 7.1% and 0% for severe AE, respectively. Rates of participants reporting ≥1 systemic allergic reaction were 14.7% for PTAH vs 3.8% for placebo in the PA+FA group and 13.4% vs 2.3% in the PAA group. <h3>Conclusion</h3> Efficacy and safety of PTAH appeared similar within children exclusively allergic to peanut or not.

(42) Self-Reported Mental Health Symptoms Among Patients With a Systemic Allergic Reaction to the COVID-19 Vaccine

(42) Self-Reported Mental Health Symptoms Among Patients With a Systemic Allergic Reaction to the COVID-19 Vaccine

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.

Pocket reduction with High Concentrated oxygen oral gel: A Preliminary Case Report

Introduction: Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defense, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not fully ascertained many experimental investigations and clinical observations have shown wound healing to be impaired under hypoxia. Since the periodontal pocket harbours anaerobic microorganisms a high concentrated oxygen formulation could prove to be a lethal elimination tool. Objective: The main objective of this study was to evaluate efficacy of high concentrated oxygen oral gel on the reduction of periodontal pocket. Materials and methods: A female patient of age 28 years without any systemic complication or allergic reaction reporting to Outpatient department of Krishnadevaraya College of Dental Sciences was examined. After ascertaining the presence of periodontal pocket (≥ 5mm) without infrabony defects, she was enlisted for the study. Following scaling and root planing and oral hygiene reinforcement, daily application of (Blue®M) TM oral gel for 7 days into the pocket was carried out, re-evaluation of the pocket depth was done after 30 days. Conclusion: High concentrated oxygen (Blue®M)TM oral gel could be locally delivering drug in reduction of periodontal pocket.

The Lights and the Shadows of Controlled Sting Challenge With Hymenoptera.

Hymenoptera venom immunotherapy (VIT) is effective for protecting individuals with systemic allergic reactions caused by Hymenoptera stings. The need for a tool that shows the degree of protection afforded by VIT and the lack of useful biomarkers have made the sting challenge test (SCT) the gold standard for this disorder, although its use has both lights and shadows. SCT with Hymenoptera involves causing a real sting in a patient diagnosed with allergy to the venom of the stinging insect and who is undergoing treatment with specific immunotherapy. In Spain, SCT is included in the list of services offered by some hospitals and forms part of their daily clinical practice. This review aims to analyze the strengths and weaknesses of this test and to describe the standardized procedure and necessary resources, based on the experience of a group of Spanish experts and a review of the literature.

Allergies in Phlebology: A National Survey and Review of Literature

Abstract Background Type I and type IV hypersensitivity can play an important role in phlebology with potential severe consequences for patients and treatment results. Methods A review of literature was performed for allergic reactions in patients treated for venous insufficiency and venous leg ulcers (VLU), together with a study in the Dutch and European centre for adverse drug reactions. Besides, we performed a survey among 37 Dutch medical hospitals to investigate the incidence of treatment allergies. Results Hypersensitivity reaction is seen in 46–76% of patient with VLU; about 20% of these reactions are caused by wound dressings products. In 11 centres urticarial and respiratory complaints were seen and 3 systemic allergic reactions in phlebological treatments. In Europe 25 cases of systemic reactions were reported. Conclusion Patients with VLU with slow healing tendency should undergo allergy tests. Type I hypersensitivity with anaphylactic reaction, also to sclerosing fluid or tumescent, is very rare.

Effect of Roasting on the Conformational Structure and IgE Binding of Sesame Allergens.

Sesame can trigger a systemic allergic reaction. In the present study, we investigated the responses of the structure and IgE binding of sesame allergens to different roasting treatments (120, 150, and 180 °C for 5 to 30 min). We analyzed the tryptic digestion peptides using a label-free mass spectrometry method. The total amount of soluble proteins in sesame was significantly reduced by roasting at 180 °C, followed by 150 °C. Ses i 1 was the most stable protein during processing as it still possessed a higher protein abundance compared to other allergens after roasting under 180 °C. The most unstable allergens were Ses i 4 and Ses i 7, which suffered severe protein degradation at 180 °C. Roasting at 180 °C remarkably increased the secondary structure content of α-helices but decreased that of β-sheets, whereas roasting at 120 and 150 °C had a limited effect on the secondary structure of sesame proteins. Moreover, serum pool Western blot analysis showed that the main allergens were oleosin of Ses i 4 and Ses i 5. The IgE-binding ability of sesame allergens was significantly decreased under 180 °C roasting, as well as the solubility of sesame proteins, which showed remarkable congruence in changes. Relative quantification results indicate that individual sesame allergens respond differently to the roasting process. In general, sesame allergens are unstable under roasting treatment. Therefore, the allergenic potential of sesame allergens may be minimized by selecting appropriate parameters during processing.

In Vitro, Ex Vivo, and In Vivo Evaluation of Nanoparticle-Based Topical Formulation Against Candida albicans Infection.

Ketoconazole is commonly used in the treatment of topical fungal infections. The therapy requires frequent application for several weeks. Systemic side effects, allergic reactions, and prolonged treatment are often associated with non-compliance and therapy failure. Hence, we developed an optimized topical antifungal gel that can prolong the release of drug, reduce systemic absorption, enhance its therapeutic effect, and improve patient compliance. Ketoconazole-loaded PLGA nanoparticles were prepared by the emulsion/solvent evaporation method and were characterized with respect to colloidal properties, surface morphology, and drug entrapment efficiency. The optimized ketoconazole-loaded PLGA nanoparticles and commercially available silver nanoparticles were incorporated into a Carbopol 934P-NF gel base. This arrangement was characterized and compared with commercially available 2% ketoconazole cream to assess physical characteristics of the gel, in vitro drug release, ex vivo skin permeation and retention, and in vivo studies on Wister male albino rats. The results showed that polymeric PLGA nanoparticles were very effective in extending the release of ketoconazole in our optimized formulation. Nanoparticles were smooth, spherical in shape, and below 200 nm in size which is consistent with the data obtained from light scattering and SEM images. The ex vivo data showed that our gel formulation could strongly reduce drug permeation through the skin, and more than 60% of the drug was retained on the upper surface of the skin in contrast to 38.42% of the commercial cream. The in vivo studies showed that gel formulation could effectively treat the infection. This study demonstrates that our topical gel could be effective in sustaining the release of drug and suggests its potential use as a possible strategy to combat antifungal-resistant Candida albicans.

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.

Accelerated/rush allergen immunotherapy.

Accelerated allergy shot schedules for inhalant and venom allergens provide individuals with allergy symptom relief but in a shorter time frame than conventional therapy. Accelerated immunotherapy (IT) protocols allow patients to reach therapeutic doses in a shorter time frame while improving adherence and reducing direct costs (e.g., fewer office visits and medications) and indirect costs (e.g., less travel time, missed work or school). Rush IT and cluster IT are believed to work through mechanisms similar to conventional subcutaneous IT (SCIT). The risk for severe systemic reactions during accelerated IT is low when appropriately administered; however, life-threatening and fatal reactions do occur. To reduce the incidence of systemic allergic reactions during cluster and rush IT protocols, premedication is recommended. It is important to exclude individuals at high risk such as those with poorly controlled asthma or those who are on β-blockers to mitigate the risk for developing systemic allergic reactions. However, accelerated SCIT regimens offer increased convenience, faster improvement in allergy symptoms, and the potential to reduce health-care costs while providing equivalent safety outcomes compared with conventional IT protocols.

Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide: a protocol for a systematic review of observational studies

IntroductionSystemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for...

Delivery options for sublingual immunotherapy for allergic rhinoconjunctivitis: clinical considerations for North America

Background: Sublingual immunotherapy (SLIT) can be delivered via tablets (SLIT-T) or aqueous drops (SLIT-D). SLIT-D dosing recommendations using North American extracts were published in 2015. We review the 2015 recommendations in the context of recent research, and compare and contrast dosing, efficacy, safety, adherence, and cost of SLIT-T and SLIT-D for allergic rhinoconjunctivitis (ARC) in North America. Methods: Randomized controlled trials (RCT) of SLIT-D and SLIT-T trials were identified by a systematic PubMed search through March 1, 2022. Results: Dose-finding studies have been conducted for all approved SLIT-T; efficacy in North American populations was demonstrated in 11 RCTs. Approved SLIT-T are uniform internationally. Few dose-finding studies for SLIT-D have been conducted using North American extracts; efficacy was demonstrated in 2 RCTs. Extrapolation of dosing from SLIT-D studies conducted with extracts from other geographic regions is unreliable. Since the 2015 SLIT-D dosing recommendations, no new RCTs of SLIT-D have been conducted with North American extracts, whereas 6 SLIT-T RCTs have since been conducted in North America. Local allergic reactions are the most common adverse events with SLIT-T and SLIT-D, but both can induce systemic allergic reactions. Adherence to SLIT-D and SLIT-T remains a challenge. Patients must pay for SLIT-D directly, whereas SLIT-T is usually covered by insurance. Conclusion: As part of shared decision-making, patients should be informed about the scientific evidence supporting the use of SLIT-T and SLIT-D for ARC.

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.

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.