Induce Hypersensitivity Reactions Research Articles

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) after administration of corticosteroids: Case series and review of literature.

Cutaneous manifestations of drug-induced type IV reactions vary widely, with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) being a less common presentation. Corticosteroids (CS), primarily known for their anti-inflammatory effects, rarely induce hypersensitivity reactions. The aim of this case series is to report four cases of SDRIFE following systemic prednisolone therapy and to review existing CS classification proposals to better understand cross-reactivity of CS. Patients recruited at a German dermatology centre underwent allergologic evaluation including prick and patch testing with various CS. Positive cases underwent oral challenge testing with alternative agents. The classification systems of Coopman et al. and Baeck et al. were taken into account. Despite a paucity of literature, CS-induced type IV reactions do occur, including SDRIFE. Classification systems based on chemical structure provide insight into cross-reactivity patterns. Provocation tests with alternative CS highlight the complexity of managing CS hypersensitivity. SDRIFE may develop following systemic prednisolone therapy. Classification systems are helpful in understanding cross-reactivity and help in the selection of alternative preparations but are not always reliable. Individualised assessment is crucial for managing CS hypersensitivity, with consideration of alternative agents and emergency use of CS when necessary.

Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Managing Severe Adverse Reactions to Biologicals in Severe Asthma.

The use of biological agents in the treatment of various inflammatory and malignancy conditions has expanded rapidly. However, these agents can induce hypersensitivity reactions, posing significant clinical challenges. We conducted a retrospective study that included nine patients with severe asthma who experienced hypersensitivity reactions to biological agents (omalizumab, benralizumab and dupilumab). Hypersensitivity reactions to biologicals in severe asthma were observed in 9 of 68 patients treated. In five cases, treatment was stopped or changed to another available biological, and for four patients administered under close surveillance, titrated provocation or desensitization was applied. Successful desensitization was achieved in three of the patients, allowing them to continue therapy without adverse reactions. Improvements in asthma control were observed post-desensitization, leading to the reduced need for systemic steroid treatments and an increase in quality of life. This study highlights the importance of recognizing hypersensitivity reactions to biologicals to have an appropriate approach for patients with severe asthma. As an effective approach for patients experiencing hypersensitivity reactions to biological agents, desensitization allows treatment continuation.

Soybean Antigen Protein-Induced Intestinal Barrier Damage by Trigging Endoplasmic Reticulum Stress and Disordering Gut Microbiota in Weaned Piglets.

Endoplasmic reticulum (ER) stress is a crucial factor in the pathogenesis of intestinal diseases. Soybean antigenic proteins (β-conglycinin and soy glycinin) induce hypersensitivity reactions and intestinal barrier damage. However, whether this damage is associated with ER stress, autophagy, and the gut microbiome is largely unclear. Therefore, in this study, we aimed to investigate the effect of dietary supplementation with soy glycinin (11S glycinin) and β-conglycinin (7S glycinin) on intestinal ER stress, autophagy, and flora in weaned piglets. Thirty healthy 21-day-old weaned "Duroc × Long White × Yorkshire" piglets were randomly divided into three groups and fed a basic, 7S-supplemented, or 11S-supplemented diet for one week. The results indicated that 7S/11S glycinin disrupted growth performance, damaged intestinal barrier integrity, and impaired goblet cell function in piglets (p < 0.05). Moreover, 7S/11S glycinin induced ER stress and blocked autophagic flux in the jejunum (p < 0.05) and increased the relative abundance of pathogenic flora (p < 0.01) and decreased that of beneficial flora (p < 0.05). In conclusion, 7S/11S glycinin induces intestinal ER stress, autophagic flux blockage, microbiota imbalance, and intestinal barrier damage in piglets.

Serious Drug Induced Hypersensitivity Reactions among Hospitalized Infants and Children

Background There are very limited data concerning the epidemiology of drug hypersensitivity in Egypt. Aim We sought to investigate the magnitude of serious drug hypersensitivity reactions among hospitalized infants and children in a tertiary hospital over a period of one year. Patients and Methods This study is a cross sectional one that was conducted over a period of one year from the middle of October 2020 to the middle of October 2021. The study was carried out in Children’s Hospital, Ain Shams University. We screened for patients with serious drug hypersensitivity reactions among a total of 10440 hospital admissions over a period of 12 months. Positive cases were further assessed with complete clinical and laboratory assessment. Results Out of total admissions of 10440 patients over the study period, 35 (0.335%) patients had clinical manifestations of serious drug hypersensitivity reactions. Concerning those 35 patients, they were 21 (60%) males and 14 (40%) females with age ranging between 3 to 193 months with median (IQR) = 50 (24-96) months. Four patients (11.4%) were known to be allergic; with 1(2.9%) having allergic rhinitis, 1 (2.9%) having urticaria, and 2 (5.7%) having cow milk protein allergy. Ten patients (28.6%) had family history of allergic disorders. Eleven patients (31.4%) had manifestations of anaphylaxis, 18 (51.4%) severe urticaria/angioedema, while the remaining 6 (17.1%) had manifestations of Stevens-Johnson syndrome. Concerning results of laboratory investigations, anemia was found in 29 (82.9%) patients, leukocytosis in 9 (25.7%) patients, leukopenia in 8 (22.9%) patients and thrombocytosis in 4 (11.4%) patients, while none of them had eosinophilia. CRP and ESR were elevated in 24 (68.6%) and 15 (42.9%) patients respectively. All of the 35 patients could overcome the drug hypersensitivity reaction with proper management Conclusions Although rare, drug hypersensitivity reactions represent an important health issue that should be clearly well reported, registered, and properly managed. Further wider scale and multicenter studies are warranted to gather more data and investigate the prevalence of each type of drug hypersensitivity reactions among children including those which are not reported in our study.

Gyógyszerallergiák tesztelése az SZTE Bőrgyógyászati és Allergológiai Klinika allergológiai osztályán

The authors present protocols of the options, available panels in drug allergy testing applied at the Department of Dermatology and Allergy, University of Szeged. In suspicion of drug induced hypersensitivity reaction we recommend performing lymphocyte transformation test (LTT), prick testing, intradermal testing and patch testing according to the assumed immune -mechanism. If these examinations are negative, the next step is the drug provocation test, which is the gold standard in the diagnosis of drug allergy. We summarize methods, indications, and the evaluation of each tests. There are increasing patients presenting hypersensitivity reactions who require proper identification of the culprit drug.

Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.

Nanomedicines and macromolecular drugs can induce hypersensitivity reactions (HSRs) with symptoms ranging from flushing and breathing difficulties to hypothermia, hypotension, and death in the most severe cases. Because many normal individuals have pre-existing antibodies that bind to poly(ethylene glycol) (PEG), which is often present on the surface of nanomedicines and macromolecular drugs, we examined if and how anti-PEG antibodies induce HSRs to PEGylated liposomal doxorubicin (PLD). Anti-PEG IgG but not anti-PEG IgM induced symptoms of HSRs including hypothermia, altered lung function, and hypotension after PLD administration in C57BL/6 and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Hypothermia was significantly reduced by blocking FcγRII/III, by depleting basophils, monocytes, neutrophils, or mast cells, and by inhibiting secretion of histamine and platelet-activating factor. Anti-PEG IgG also induced hypothermia in mice after administration of other PEGylated liposomes, nanoparticles, or proteins. Humanized anti-PEG IgG promoted binding of PEGylated nanoparticles to human immune cells and induced secretion of histamine from human basophils in the presence of PLD. Anti-PEG IgE could also induce hypersensitivity reactions in mice after administration of PLD. Our results demonstrate an important role for IgG antibodies in induction of HSRs to PEGylated nanomedicines through interaction with Fcγ receptors on innate immune cells and provide a deeper understanding of HSRs to PEGylated nanoparticles and macromolecular drugs that may facilitate development of safer nanomedicines.

Screening of food allergens in cereals using real-time PCR

Allergen is a substance that induces hypersensitivity reactions. Most of the food allergens are protein in nature and cause life-threatening allergies as well as influencing the quality of life. The present study was designed to evaluate the screening of major allergens in commercially available processed food commodities of wheat, soybean species and the cross reactivity of peanut in tree nuts using real-time PCR. Analysis of the results demonstrates that the SYBER Green qPCR assay is a quick and reliable method for screening of allergens. A total of 42 food samples were collected for these studies and analyzed results. Peanut allergen was detected in tree nuts of walnut, coconut, almond, and hazelnut, wheat allergen was detected in rice, oat, barely and buckwheat, while soybean allergen was detected in the species of pea, broad bean, bean seed, and kidney bean. This study will provide information for affected consumers and to do meaningful risk assessment.

Allergy in Cancer Care: Antineoplastic Therapy-Induced Hypersensitivity Reactions

As the backbone of oncological treatments, systemic chemotherapy is still one of the main pawns in cancer care, alone or in combination with newer targeted agents. All chemotherapy agents can be associated with a type of adverse event called an infusion reaction, which can be characterized as unpredictable, non-dose related, and unexplained by the cytotoxic profile of the drug. For some of these events, a certain immunological mechanism can be identified by blood or skin testing. In this case, we can speak of true hypersensitivity reactions that occur as a response to an antigen/allergen. The current work summarizes the main antineoplastic therapy agents and their susceptibility to induce hypersensitivity reactions and also includes a review of clinical presentation, diagnostic methods in hypersensitivity reactions, and perspectives to overcome these negative events in the treatment of patients suffering from various types of cancer.

First Report of Pseudomonas cichorii Causing Bacterial vein necrosis on Perilla plants [Perilla frutescens (L.) Britton.] in South Korea.

Perilla (Perilla frutescens L.) is the second most important upland crop and the third largest edible oil crop in Korea (Shin and Kim 1994). During a disease survey in Busan, Korea in September 2021, symptoms of vein necrosis were observed in perilla plants, with incidences of approximately 30% and 50% in two fields. Symptoms of spots on the perilla appeared as leaf dryness and spots with water-soaked blotches largely concentrated on the mid-veins of leaves. The lesions were initiated with water-soaked spots on the leaf or stem and gradually turned black or brown. Necrosis was also observed in the stems. A bacterium was isolated on Luria-Bertani (LB) agar from diseased leaf tissues that were surface-disinfected with 70% ethyl alcohol for 3-5 min and then washed with sterile water three times. Three pieces of sterilized leaf tissue (size: 0.5 × 0.5 cm) were mixed with 500 µL sterile water for 30 min, and then the suspension was serially diluted and spread on LB agar. Subsequently, isolates were cultivated on LB agar and King's Medium B agar (KMB) (Schaad et al. 2001), and they were predominantly cream-colored and circular bacterial colonies with undulated margins. The bacterial colonies on KMB displayed fluorescence under 365 nm UV light. The isolates were analyzed with the GEN III MicroPlate (Biolog, Hayward, CA, USA), and all isolates were identified as Pseudomonas cichorii, a devastating plant bacterium that damages a wide range of host plants worldwide, including in South Korea (Hikichi et al. 2013; Ramkumar et al. 2015). To identify the species of the bacterial pathogen, genomic DNA of four isolates (BS4922, BS4167, BS4345, and BS4560) was extracted, and the 16S rRNA gene and hrcRST gene were amplified with universal primers, 27F/1492R and Hcr1/Hcr2, and sequencing was then done (Patel et al. 2019). In the BLAST analysis, the 16S rRNA sequences (GenBank OM060656, OM275434, OM275435, OM275436) showed a 100% and 99% similarity to P. cichorii strains MAFF 302698 (AB724286) and P. cichorii strain Pc-Gd-4 (KU923373), respectively. Further, hrcRST gene sequences (GenBank OM143596, OM268864, OM268865, and OM268866) showed high similarity (>99%) with P. cichorii strain P16-51 (MG518230). A pathogenicity test of the four isolates was performed on 3 - 4 weeks old perilla plants by creating wounds with a needle on the lower leaves and stems, and then the plants were inoculated by spraying inoculum (108 CFU/ml). The plants that served as the negative control were wounded and sprayed with unsterilized water. The inoculated perilla plants were placed in a greenhouse at 28 ± 2oC , 80-85% relative humidity, and a natural photoperiod. The inoculation site began to show symptoms of water-soaked brown lesions. Disease symptoms such as leaf dryness, water-soaked blotches on the mid-vein of leaves, and necrosis on plant stems were observed in the inoculated plants 7-10 days after inoculation, whereas the plants of the negative control group did not show any symptoms. The bacteria were re-isolated from the diseased tissues of the plants, and DNA sequence analysis identified them as P. cichorii. Additionally, all isolates induced hypersensitivity reactions in tobacco and tomato leaves within 24 h after inoculation. To our knowledge, this is the first report of P. cichorii infecting perilla in South Korea. The findings in this study will provide the basic information for the development of diagnostic tools and management measures against P. cichorii in perilla.

Next-generation sequencing-based HLA typing reveals the association of HLA-B*46:01:01 and HLA-DRB1*09:01:02 alleles with carbamazepine-induced hypersensitivity reactions in Vietnamese patients with epilepsy

Several studies have reported an association between certain human leukocyte antigen (HLA) alleles and carbamazepine (CBZ)-induced hypersensitivity reactions in patients with epilepsy. Here, the relationship between the clinical spectrum and the HLA allele profiles in patients with CBZ-induced hypersensitivity reactions was investigated using next-generation sequence (NGS) data obtained from 65 Vietnamese patients with epilepsy, including 33 with CBZ-tolerance and 32 patients with CBZ-hypersensitivity, in which only 8 with severe cutaneous adverse drug reactions and 24 were mild-hypersensitive patients. Three loci of HLA class I (HLA-A, -B, and -C) and two loci of HLA class II (HLA-DQA1 and -DRB1) were included in our analysis. We observed a higher prevalence of three alleles, HLA-B*46:01:01, HLA-DQA1*03:02:01, and HLA-DRB1*09:01:02, in the CBZ hypersensitivity group compared to that in the CBZ tolerant group. Notably, all hypersensitive patients with HLA-DQA1*03:02:01 also harbored HLA-DRB1*09:01:02. We also used molecular modeling to gain mechanistic insight into the interactions of HLA-B*46:01 and HLA-DRB1*09:01 with CBZ. Our findings proposed the direct interaction of CBZ with peptide-binding pockets of these HLA proteins. The sensitivity and specificity of HLA-B*46:01:01 in considering with the appearance of HLA-DRB1*09:01:02 were 46.88% and 84.85%, respectively. Our data suggest that the presence of HLA-B*46:01:01/HLA-DRB1*09:01:02 is a potential marker of CBZ-induced hypersensitivity reactions in Vietnamese patients.

Taxanes induced hypersensitivity reactions in cancer chemotherapy patients reported at adverse drug reaction monitoring centre at a tertiary care hospital

Background: Cancer chemotherapy involves highly complex regimens using antineoplastic agents like taxanes (paclitaxel, docetaxel) etc. Taxanes cause hypersensitivity reactions (HSRs) like redness, rashes, dyspnoea, severe anaphylaxis and death. In this study, adverse drug reactions (ADRs) associated with taxanes are described &amp; analysed on their severity and preventability. The present study aims to analyse and determine the prevalence of ADRs, especially HSRs in patients treated with taxanes.Methods: After getting IEC approval, the present study is done retrospectively by assessing the HSRs in suspected ADR reporting forms from December 2019 to February 2022 in ADR monitoring centre (AMC) in the Department of Pharmacology at Kurnool Medical College, Kurnool. Descriptive statistics used to analyse patient demography, frequency, various carcinomas under treatment &amp; organ involved, causality assessment using WHO-UMC Scale and Naranjo's Algorithm, severity assessment using modified Hartwig &amp; Siegel’s scale and preventability by modified Schumock &amp; Thornton scale.Results: A total of 258 ADRs were recorded, of which 30 cases reported HSRs with taxanes-paclitaxel (22) and docetaxel (8). The most commonly occurred HSR is shortness of breath. Naranjo’s algorithm showed 52.5% possible (score 1-4) HSRs. WHO-UMC causality assessment scale showed 56.4% as probable HSRs. Modified Hartwig &amp; Siegel severity scale showed 46.6% moderate (level 3). Modified Schumock and Thornton scale showed 76.9% as not preventable.Conclusions: Chemotherapy-related ADRs among cancer patients urges the oncologists to be actively involved in ADR reporting, in the need of the hour in order to mitigate, avoid their occurrence and reducing morbidity and mortality, when practiced with diligence.

Prevalence of Piperacillin-Tazobactam induced Hypersensitivity Reaction in Workers of Stallion’s Pharmaceutical Factory at Lahore

BACKGROUND &amp; OBJECTIVE: Piperacillin is an antibiotic that belongs to the ureidopenicillin family. Piperacillin-tazobactam provides cover against gram-positive, gram-negative bacteria and some bacteria of anaerobic nature. It is an extended-spectrum antibiotic and is used along with tazobactam which is an inhibitor of beta-lactamase. The main objective of our research was to identify the hypersensitivity reactions of piperacillin-tazobactam in pharmaceuticals factory and office workers.&#x0D; METHODOLOGY: A Cross-sectional study was conducted at Stallion Pharmaceuticals (Pvt) Ltd located at Sundar Industrial Estate Lahore, Pakistan, from March to April 2018, after approval from the institutional research committee. All the workers, including factory workers and office workers at Stallion Pharmaceuticals (Pvt) Ltd were included in this study. Data was collected from each respondent by immediate-type skin testing. Data analysis was done by SPSS version 25, the demographic data was evaluated by descriptive statistics, Fisher Exact test was used for comparison and p≤0.05 was taken as significant.&#x0D; RESULTS: The results of the study presented that hypersensitivity reaction was present in (7.5%) of males and (3.8%) of females. It was also observed that (8.8%) of factory workers had hypersensitivity reactions when they are gone through skin tests, and only (2.5%) of office workers were skin test positive. From the above results (11.2%) of all the respondents developed hypersensitivity reactions and (88.8%) showed no reaction when they were gone through skin tests, which contain 0.1 ml of piperacillin and tazobactam. Fisher exact test was applied, and results showed no significant difference between hypersensitivity reactions among factory and office workers as the p-value was 01.&#x0D; CONCLUSION: Hypersensitivity reaction to piperacillin-tazobactam was minimal in the factory &amp; office workers, and this was not significant.

PSUN62 A Rare Case of Atorvastatin Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report.

Abstract Clinical Case A 77 year-old female presented to emergency department with progressively worsening rash that started one week ago. On physical examination blanching erythema was noted in lower back, buttocks and extremities. There was no desquamation or involvement of oral mucosa. No lymphadenopathy or hepatosplenomegaly was noted. Laboratory investigations showed white blood cell count of 21.2×10^3/uL, with 33.1% eosinophils. Creatinine was elevated at 2.8mg/dL from baseline of 0.8mg/dL. Further lab work revealed alkaline phosphate 2314 IU/L, aspartate transaminase 587 IU/L, and alanine transaminase 620 U/L, total bilirubin 7.3mg/dL with direct bilirubin of 5.1mg/dL, Immunoglobulin E level of 2000 IU/ml and normal Tryptase levels. Serology for viral hepatitis, Epstein-Barr virus, Cytomegalovirus and Human immunodeficiency virus was negative. Autoimmune workup including antinuclear Antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), mitochondrial antibody, smooth muscle antibody, double stranded DNA, anti-histone antibody, rheumatoid factor, Sjogren's antibody and centromere antibody were negative. Urinalysis, urine protein electrophoresis and serum protein electrophoresis were also normal. Computed tomography (CT) scan of chest showed mild supraclavicular and mediastinal lymphadenopathy. Review of medical records revealed that patient was recently discharged from hospital with a prescription of Atorvastatin following admission for transient ischemic attack 6 weeks ago. Skin biopsy showed superficial perivascular dermatitis with extravasation of red blood cells with no diagnostic evidence of vasculitis, granuloma or malignancy. Based on biopsy findings, recent drug administration followed by appearance of rash, hematological abnormality, lymphadenopathy and multi-system involvement and after exclusion of other possible causes, diagnosis of DRESS syndrome was made. Atorvastatin was held and patient was given Methylprednisolone for three days followed by Prednisone 1mg/kg with taper. Rash as well as kidney and liver functions improved drastically within two days. Discussion Our patient presented with one week of rash associated with deteriorating kidney and liver functions. Atorvastatin was initiated five weeks prior to development of rash. All the possible infectious etiologies and malignancy was ruled out based on the laboratory work mentioned above. Work up for vasculitis was also negative. DRESS syndrome is a late onset drug induced hypersensitivity reaction which usually manifests 3 weeks to months after the offending drug is started. It is very rare with an incidence of 0.9-2 per 100,000 patients per year and accounts for 10-20% of all cutaneous adverse drug reactions. DRESS syndrome if untreated carries significant risk of mortality, between 10-20%. RegiSCAR (European Registry of Severe Cutaneous Adverse Reaction) scoring system can be used to help diagnose DRESS syndrome. It takes into account multiple factors including fever, lymphadenopathy, eosinophilia, rash, number of organs involved, disease duration, skin biopsy findings and negative results of investigations to rule out alternate causes of patient's symptoms. Patient responded well to systemic steroids followed by oral steroids with taper. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Development and initial validation of a modified lymphocyte transformation test (LTT) assay in patients with DRESS and AGEP

BackgroundThe lymphocyte transformation test (LTT) is an in vitro assay used to diagnose drug induced hypersensitivity reactions by detecting the activation and expansion of drug-specific memory T cells to the suspected implicated drug. Traditionally radiolabelled thymidine (3H-thymidine) has been used but requires the handling and disposal of radioactive materials.ObjectiveTo examine safe alternatives to 3H-thymidine, test assay modifications for improved assay sensitivity and evaluate the modified LTT in patients with DRESS and AGEP.MethodsFour proliferation detection assays (BRDU, CyQUANT™, MTT and XTT) were screened for LTT sensitivity. XTT the most sensitive and practical was selected for further evaluation Modifications like autologous serum (AS) and regulatory T cell depletion (T-REG) were tested for improved assay sensitivity. Finally, an initial evaluation of the XTT–LTT was performed in 8 patients with DRESS and 2 with AGEP including cytokine testing.ResultsOf the non-radioactive alternatives we tested, XTT a colorimetric assay was the most sensitive and practical to move to evaluation. The addition of AS increased background signal. Depletion of T-REGs improved sensitivity but cell sorting time and risk of contamination limited benefit.Of eight patients diagnosed with DRESS and 2 with AGEP tested with XTT–LTT assay results showed our assay matched clinical findings of implicated drugs in 8/10 patients when using a stimulation index (SI) ≥ 2 and 8/10 with analysis by ANOVA. All ten patients were correctly diagnosed by either analysis.ConclusionXTT appears to be a safe, viable alternative to 3H-thymidine, with high sensitivity and allowing direct cytokine quantification on specific patient cells.

Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel (PTX). However, no intravenous lipid emulsion of PTX has been approved for clinical treatment, and systemic safety profiles have not yet been reported. Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion (PTX Emul) and describe its characteristics, colloidal stability, and systemic safety profiles in terms of acute toxicity, long-term toxicity, and toxicokinetics. We also compare PTX Emul with conventional PTX injection. Results showed that PTX Emul exhibited an ideal average particle size (approximately 160 nm) with narrow size distribution and robust colloidal stability under different conditions. Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential. In addition, where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs, including the decreased AUC and increased plasma clearance and volume of distribution, PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose, moderate body weight change, decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose. A fundamental understanding of the systemic safety profiles, high tumor-targeting efficiency, and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Hypersensitivity and in-stent restenosis in coronary stent materials.

Coronary heart disease (CHD) is a type of cardiovascular disease with the highest mortality rate worldwide. Percutaneous transluminal coronary intervention (PCI) is the most effective method for treating CHD. However, in-stent restenosis (ISR), a long-term complication after PCI, affects the prognosis of patients with CHD. Previous studies have suggested that hypersensitivity reactions induced by metallic components may be one of the reasons of this complication. With the emergence of first- and second-generation drug-eluting stents (DES), the efficacy and prognosis of patients with CHD have greatly improved, and the incidence of ISR has gradually decreased to less than 10%. Nevertheless, DES components have been reported to induce hypersensitivity reactions, either individually or synergistically, and cause local inflammation and neointima formation, leading to long-term adverse cardiovascular events. In this article, we described the relationship between ISR and hypersensitivity from different perspectives, including its possible pathogenesis, and discussed their potential influencing factors and clinical significance.

Severe anaphylaxis following administration of radiocontrast in patient undergoing coronary intervention

Radiocontrast material is among the common drugs causing allergic reaction. Mostly it is well tolerated. The symptoms range from mild with urticaria to fatal anaphylaxis, developing rapidly. Anaphylaxis is the most severe form of radiocontrast media (RCM) induced hypersensitivity reaction. With more use of diagnostic and therapeutic procedure, the use of the radiocontrast media is increasing. We report here two cases of severe anaphylactic reaction that occurred during the coronary intervention for myocardial infarction.

Anaphylaxis and allergic reactions to COVID-19 vaccines: A narrative review of characteristics and potential obstacles on achieving herd immunity.

Background and AimsCoronavirus disease 2019 (COVID‐19) is a highly contagious infection, and new variants of its causative virus continue to emerge all around the world. Meanwhile, mass vaccination represents a highly effective measure to reduce the disease burden. Not only do vaccines immunize individuals, but they also protect the entire population through achieving herd immunity. They are composed of various ingredients, some of which may induce hypersensitivity reactions, namely anaphylaxis and cutaneous allergic reactions. This review aims to provide an explicit overview of the pathophysiology, suspected responsible components, and management of COVID‐19 vaccine‐induced allergic reactions, and their effect on acquiring herd immunity.MethodsTo perform this narrative review, a comprehensive literature search based on our selected terms was conducted in online databases of PubMed/Medline and Google Scholar for finding the relevant studies published from 2019 to 2022.ResultsCOVID‐19 vaccines introduce several advantages that outweigh their potential risks, such as allergic reactions. Allergic reactions are mainly attributed to polyethylene glycol and polysorbate excipients that can provoke IgE‐mediated reactions and hypersensitivity reactions. These reactions should be managed properly to avoid having serious sequelae.ConclusionIt is of great importance to immediately recognize and manage vaccine hypersensitivity reactions, especially anaphylaxis, to avoid allergic patients being excluded from the vaccination program, and more importantly, to stop the spreading of unfounded vaccine hesitancy leading to delayed herd immunity.

Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration.

PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.