The Molecular Signature Related to Local Inflammatory and Immune Response in Canine Cutaneous Hypersensitivity Reactions: A Preliminary Study.

Cutaneous hypersensitivity reactions (CHRs) are complex inflammatory skin disorders that affect humans and dogs. This study examined the inflammatory and immune responses leading to skin damage, inflammation, and irritation by investigating gene expression through quantitative PCR (qPCR) and protein localization through the immunohistochemistry (IHC) of specific receptors and molecules involved in CHRs. Formalin-fixed paraffin-embedded (FFPE) samples from canine CHR skin (n = 20) and healthy dog skin (n = 3) were analyzed for expression levels of eight genes, including members of the pattern recognition receptor (PRR) family, CD209 and CLEC4G, the Regakine-1-like chemokine, and acute phase proteins (APPs), LBP-like and Hp-like genes. Additionally, we examined the local involvement of IL-6, Janus Kinase 1 (JAK1), and the signal transducer activator of transcription 3 (STAT3) in the CHR cases. The study demonstrated statistically significant increases in the expression levels of CD209, Hp-like (p < 0.01), LBP-like, Regakine-1-like, and CLEC4G (p < 0.05) genes in CHRs compared to healthy controls. Conversely, IL-6, JAK1, and STAT3 showed no significant difference between the two groups (p > 0.05). Protein analysis revealed JAK1 and STAT3 expression in CHR hyperplastic epithelial cells, dermal fibroblasts, and endothelial cells of small capillaries, indicating a possible involvement in the JAK/STAT pathway in local inflammatory response regulation. Our findings suggest that the skin plays a role in the development of CHRs.

Cutaneous adverse reactions associated with COVID-19 vaccines: Current evidence and potential immune mechanisms.

As the number of vaccinated individuals has increased, there have been increasing reports of cutaneous hypersensitivity reactions. The main COVID-19 vaccines administered include messenger ribonucleic acid vaccines, non-replicating viral vector vaccines, inactivated whole-virus vaccines, and protein-based vaccines. These vaccines contain active components such as polyethylene glycol, polysorbate 80, aluminum, tromethamine, and disodium edetate dihydrate. Recent advances in understanding the coordination of inflammatory responses by specific subsets of lymphocytes have led to a new classification based on immune response patterns. We categorize these responses into four patterns: T helper (Th)1-, Th2-, Th17/22-, and Treg-polarized cutaneous inflammation after stimulation of COVID-19 vaccines. Although the association between COVID-19 vaccination and these cutaneous adverse reactions remains controversial, the occurrence of rare dermatoses and their short intervals suggest a possible relationship. Despite the potential adverse reactions, the administration of COVID-19 vaccines is crucial in the ongoing battle against severe acute respiratory syndrome coronavirus 2.

Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams.

BACKGROUND: Amoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs). METHODS: mDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3+, CD4+, CD8+, CD4+Th1, and CD4+Th2, by flow cytometry. RESULTS: Higher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV. CONCLUSIONS: mDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction.

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS.

BACKGROUND: Hypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs. METHODS: The safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0. RESULTS: This study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR025 for angioedema. The ROR025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR025. An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs. CONCLUSIONS: The risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

Abbreviation of Desensitization Protocol for Pediatric Patients with Lysosomal Storage Diseases Receiving Enzyme Replacement Therapy.

INTRODUCTION: Lysosomal storage diseases (LSDs) constitute a group of metabolic disorders characterized by the accumulation of substrates within lysosomes. For their treatment, disease-specific enzyme replacement therapy (ERT) is employed. In cases of hypersensitivity reactions that may occur during these treatments, desensitization of enzyme therapy becomes necessary. Repeated desensitization procedures may result some degree of tolerance. This study presents cases of patients received abbreviated desensitization protocols following repeated desensitization procedures. METHOD: During the period between September 2019 and January 2024, pediatric patients who experienced anaphylactic reactions to ERT and whose desensitization protocols were abbreviated after receiving uneventful treatment with desensitization for at least a year were included in the study. RESULT: Six patients, four with Pompe disease, one with mucopolysaccharidosis type 2, and one with mucopolysaccharidosis type 4, had been receiving uninterrupted ERT by desensitization for at least 1 year. The mean age of the patients was 117.6 months (median: 104.5, IQR: 85.2-144). All patients experienced anaphylaxis as the initial reaction. Skin and intradermal tests were repeated on patients prior to protocol abbreviation. Premedication previously given to all patients was discontinued, and desensitization protocols were subsequently shortened by increasing the infusion rate and/or reducing the number of steps. CONCLUSION: The study investigated patients whose desensitization protocols were abbreviated. It demonstrated that some level of tolerance could be attained through repeated applications. This approach aims to identify concise, safe, and efficient protocols, thereby reducing hospitalizations, nosocomial infections, and treatment expenses.

"Antibiotic hypersensitivity reactions in Cystic Fibrosis: A thorough inspection on a stumbling block in patient care".

One hurdle in the management of CF, a disease characterized by progressive endobronchial infection, is the presence of hypersensitivity reactions to antimicrobials due to prolonged and repetitive treatment courses. The aim of this review is to compile existing data and provide insight to medical professionals on a long-debated topic for optimum patient care. Clinical studies were inducted from the last 15 years and filtered based on their relativity to drug hypersensitivity reactions (DHRs), antibiotics and CF. After completing the selection process, 10 clinical studies were thoroughly examined. The most frequent antibiotic group related to DHRs were beta-lactams. Frequency of the most common overall type of reaction (immediate or nonimmediate) differed among clinical studies. Although severe reactions seem rare comparatively, they do occur during and even after completion of treatment regimens. The prevalence of true drug allergies should be confirmed using a variety of tests available, however, should not be confused with overall DHR rates. Genetic mutations, gender and lifetime antibiotic dose were not related with an increased risk for DHR development. On the contrary, the most important factor according to most studies was the cumulative antimicrobial dose in a given period of time, especially when delivered parenterally. DHRs are an indisputable problem in the management of CF patients. Understanding possible risk factors and increased awareness is vital in both hospital and outpatient settings as early detection can decrease the severity of the reactions.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Three new discovery effector proteins from Candidatus Liberibacter asiaticus psy62 inhibit plant defense through interaction with AtCAT3 and AtGAPA.

KEY MESSAGE: We identify three SDEs that inhibiting host defence from Candidatus Liberibacter asiaticus psy62, which is an important supplement to the pathogenesis of HLB. Candidatus Liberibacter asiaticus (CLas) is the main pathogen of citrus Huanglongbing (HLB). 38 new possible sec-dependent effectors (SDEs) of CLas psy62 were predicted by updated predictor SignalP 5.0, which 12 new SDEs were found using alkaline phosphate assay. Among them, SDE4310, SDE4435 and SDE4955 inhibited hypersensitivity reactions (HR) in Arabidopsis thaliana (Arabidopsis, At) and Nicotiana benthamiana leaves induced by pathogens, which lead to a decrease in cell death and reactive oxygen species (ROS) accumulation. And the expression levels of SDE4310, SDE4435, and SDE4955 genes elevated significantly in mild symptom citrus leaves. When SDE4310, SDE4435 and SDE4955 were overexpressed in Arabidopsis, HR pathway key genes pathogenesis-related 2 (PR2), PR5, nonexpressor of pathogenesis-related 1 (NPR1) and isochorismate synthase 1 (ICS1) expression significantly decreased and the growth of pathogen was greatly increased relative to control with Pst DC3000/AvrRps4 treatment. Our findings also indicated that SDE4310, SDE4435 and SDE4955 interacted with AtCAT3 (catalase 3) and AtGAPA (glyceraldehyde-3-phosphate dehydrogenase A). In conclusion, our results suggest that SDE4310, SDE4435 and SDE4955 are CLas psy62 effector proteins that may have redundant functions. They inhibit ROS burst and cell death by interacting with AtCAT3 and AtGAPA to negatively regulate host defense.

Safety and oncological effectiveness after desensitization in patients with previous hypersensitivity reactions to chemotherapy.

INTRODUCTION: Taxanes and platinum are first-line treatments in gynecological tumors with high rates of hypersensitivity reactions (HSRs), leading to discontinuation of treatment. Desensitization involves induction of temporary tolerance to previously sensitized medications. The aims of this study are to describe HSRs to paclitaxel and carboplatin and evaluate the safety and effectiveness of desensitization protocols in gynecological cancer patients. METHODS: Original, retrospective, descriptive, analytical study, approved by Bioethics and Research Committee, included >18-year-old patients with gynecological tumors experiencing HSRs to first-line chemotherapy. Patients underwent 3-bag-12-step desensitization. RESULTS: 174 desensitization (95 paclitaxel, 79 carboplatin) in 33 female patients, mean age 45.5 years (18-71y). Cancer diagnosis: breast 8 (24.2%), ovarian 14 (42.2%), endometrial 2 (6.1%) and cervix 9 (27.2%). HSR occurred in paclitaxel during cycles 1-2 and in carboplatin after 6 cycles. The most frequently seen HSR symptom was cardiovascular with paclitaxel (94.7%), and cutaneous (93.3%) with carboplatin. Three-bags 12-steps desensitization protocol (initial dilution 1:100) in 5.67hrs. All patients reached total dose desensitization: 82% with no reaction, 12% mild, 6% moderate and 0% severe reaction. Mean disease-free interval and progression-free interval in months (m): breast cancer 29 m and 14 m, ovarian 22 m and 9 m, endometrial 40 m and cervical cancer: 67.5 m and 27 m. Twenty-five patients (73.5%) are still alive. CONCLUSION: HSRs to paclitaxel manifest in the first 1-2 cycles and to carboplatin after 6 cycles. Symptoms include cardiovascular, atypical neuromuscular and urticaria. Changing treatment lines impacts prognosis. Our study revealed that ovarian cancer patients undergoing desensitization protocols achieved longer progression-free intervals. All patients successfully reached total dose desensitization. This study provides evidence of the effectiveness and safety of desensitization and promising perspective for continuing first-line treatment with HSRs.

Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions.

PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.

Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor).

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Healthcare Providers' knowledge, attitudes and practice in relation to drug hypersensitivity reactions at King Abdulaziz Medical City in Riyadh.

Background: Drug hypersensitivity reactions (DHRs) are immune-mediated responses triggered by exposure to a drug. DHRs are responsible for serious adverse drug reactions (ADRs) and are considered the fifth leading cause of death. This study aims to assess and evaluate the knowledge, practice, and attitudes of healthcare providers (HCPs) towards DHRs. Methods: A cross-sectional survey was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Healthcare providers, including pharmacists, physicians, and nurses, were recruited using a convenience sampling method to complete the survey. The survey comprised three domains: knowledge (14 items), attitudes (5 items), and practices (6 items), utilizing a standardized self-administered questionnaire. Results: The survey was completed by 373 healthcare providers. The respondents were predominantly female (72.1 %) with a mean age of 33.8 ± 7.8 years. Of the respondents, 64 % were nurses, 25 % pharmacists, and 11.3 % physicians. Educational levels varied, with 53 % holding a bachelor's degree, 22 % an associate degree, and 25 % a master's degree or higher. The median knowledge score was 48. Female healthcare providers, those with advanced levels of education, and physicians had higher knowledge scores compared to male and nurse participants (p < 0.05). One-third of the respondents (33 %) were satisfied with their knowledge of DHRs, and 42 % believed HCPs should receive more advanced training in DHR management. Less than a quarter of HCPs reported inquiring about patients' histories of hypersensitivity reactions. Conclusions: The study revealed that healthcare workers had a relatively low level of knowledge about drug hypersensitivity reactions and lacked a consensus on DHR management. While displaying a positive attitude towards DHRs, they often did not translate this attitude into consistent clinical practice.

Evaluation of accompanying allergic disease in children with proven drug allergies.

Background/aim: Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with proven common drug allergies. Materials and methods: Children with drug hypersensitivity confirmed by diagnostic allergy tests at our center between January 2010 and December 2020 were screened retrospectively. Patients with the most common drug allergies (due to antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], and antiepileptic drugs) were selected for analysis. Age, sex, the culprit drug, initial reaction characteristics, diagnostic test results, and the study physician who diagnosed concomitant allergic diseases were noted. Results: A total of 168 patients (boys, 51.2%) with a median age of 12 years (IQR = 8-16.3) were included in the study. The culprit drug was an antibiotic in 63% (n = 106), NSAID in 25% (n = 42) and anticonvulsant in 11.9 % (n = 20) of the patients. Drug hypersensitivity reactions were immediate in 74.4 % (n = 125) and delayed in 25.6 % (n = 43) of the patients. Seventy-five patients (44.6 %) had at least one allergic disease, most commonly rhinitis (27.3 %, n = 46) or asthma (25 %, n = 42). Fifty-five patients underwent skin prick tests with aeroallergens, producing a positive result in 60% (n = 31). The prevalence of allergic disease was not differing according to the culprit drug. The frequency of developing at least one concomitant allergic disease was 47.2% (n = 50/106) for antibiotic hypersensitivity, 52.4% (n = 22/42) for NSAID hypersensitivity, and 15% (n = 3/20) for anticonvulsant hypersensitivity (p < 0.00).Immediate drug hypersensitivity reactions were more frequent in children who had allergic diseases (80 % vs. 64.5 %; p = 0.027). Conclusion: Nearly half (44.6%) of the children with proven drug hypersensitivity had concomitant allergic diseases and immediate reactions were more common in this group. Children evaluated for drug hypersensitivity should be assessed for other allergic diseases.

Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019.

Recent evidence has emerged concerning delayed cutaneous hypersensitivity reactions after infliximab or adalimumab applications in patients with coronavirus disease 2019 (COVID-19). A few real-world studies compared the events, clinical features, and prognosis of infliximab- or adalimumab-related delayed cutaneous hypersensitivity reactions in COVID-19 patients. Disproportionality analysis and Bayesian analysis were utilized to determine the suspected adverse events of delayed cutaneous hypersensitivity reactions after infliximab or adalimumab use based on the Food and Drug Administration's Adverse Event Reporting Systems (FAERS) from May 2020 to December 2021. Additionally, the times to onset and fatality rates of delayed cutaneous hypersensitivity reactions following infliximab or adalimumab were compared. In total, 475 reports of delayed cutaneous hypersensitivity reactions were associated with infliximab or adalimumab. Females were affected almost twice more than males. Among the two therapies, infliximab had the highest association with delayed cutaneous hypersensitivity reactions based on the highest reporting odds ratio (2.14, 95% two-sided confidence interval [CI] = 1.2-3.81), proportional reporting ratio (1.95, χ2 = 7.03), and empirical Bayesian geometric mean (1.94, 95% one-sided CI = 1.2). Infliximab-related delayed cutaneous hypersensitivity reactions had earlier onset (0 [interquartile range (IQR): 0-0] days vs. 166.5 (IQR: 18-889.5) days, p < 0.05), while adalimumab-related delayed cutaneous hypersensitivity reactions have higher fatality rate (0.44% vs. 0.00%). Based on the FAERS database, we profiled delayed cutaneous hypersensitivity reactions related to infliximab or adalimumab application in patients with COVID-19 with more points of occurrences, clinical characteristics, and prognosis.

A practical guide to address reactions to vaccines in children.

Currently available vaccines are safe, but, potentially, any vaccine can cause an allergic reaction and, albeit very rare, anaphylaxis can occur. Although its rarity, the precise diagnostic management of a suspected anaphylaxis postvaccination is of paramount importance due to the risk of a potentially serious reaction after re-exposure, while a misdiagnosis might lead to an increase in the number of children that interrupt vaccinations resulting in an unjustifiably individual and collective risk of loss of protection against immune preventable diseases. In the light that most cases of suspected allergy to a vaccine are not effectively confirmed in up to 85% of the cases referred for an allergy evaluation, patients can continue the vaccination schedule with the same formulation and tolerance of the booster doses. The patient assessment has to be done by an expert in the vaccine field, usually an allergist or an immunologist depending on the country, to select subjects at risk of allergic reactions and to perform the correct procedures for vaccine hypersensitivity diagnosis and management, in order to guarantee safe immunization practices. The aim of this review is to provide a practical guidance for the safe management of allergic children undergoing immunization procedures. The guide is referred both to the evaluation of children who have previously experienced a suspected allergic reaction to a specific vaccine and their management in case of further booster doses, and to children allergic to a component of the vaccine to be administered.

Outcomes of a Undiluted, One-Bag Desensitization Protocol for Chemotherapeutic Agents.

BACKGROUND: Hypersensitive reactions (HSRs) often require that the provoking medication be discontinued but chemotherapeutic drugs are often essential for the treatment of the disease. Rapid drug desensitization is a procedure that induces temporary tolerance to the drug allowing continuation of treatment in patients who have presented HSRs. Most of the desensitization protocols use 3 bags with sequential dilutions of the drug, which are infused in gradual steps. However, it has not been sufficiently investigated whether dilution is essential for successful desensitization. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of a new one-bag desensitization protocol which uses a single solution of 1 mg/mL throughout the procedure allowing to reduce time and simplifying the desensitization procedure. METHODS: Retrospective observational study was carried out in adult patients with HSRs to chemotherapy agents who received a new nondilution one-bag desensitization protocol between 2016 and 2021. RESULTS: A total of 130 desensitization procedures with an undiluted one-bag protocol were performed on 17 patients with HSRs to chemotherapy. One hundred and seven (82.3%) were for desensitization to CBDCA, 15 (11.5%) for oxaliplatin, 4 (3.1%) for paclitaxel and 4 (3.1%) for brentuximab. All of the 130 procedures were successfully accomplished, and all patients could receive their target dose. No breakthrough reactions (BTRs) occurred in 77% (100/130) of desensitizations, and only mild reactions (grade 1) with skin symptoms were observed in 23% (30/130) of desensitizations. CONCLUSION AND RELEVANCE: The undiluted one-bag desensitization protocol was safe and effective and has been adopted as the standard of care at our institution in treating patients with HSRs to chemotherapeutic drugs as it requires less time and simplifies the desensitization procedure, optimizing risk management.

Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies: Safety and efficacy of desensitization.

BACKGROUND: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations. OBJECTIVE: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization. METHODS: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients. RESULTS: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction. CONCLUSION: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment.

Interleukin-6 as a biomarker of hypersensitivity reactions in chemotherapeutics and monoclonal antibodies.

BACKGROUND: In recent years, a new type of immediate hypersensitivity reaction known as cytokine release began to emerge, and within this phenotype of reactions, interleukin-6 is the most frequently associated with the presence during drug administration. Chemotherapeutic agents (QT) and monoclonal antibodies. OBJECTIVE: Determine interleukin-6 levels in hypersensitivity reactions to QT and monoclonal antibodies. METHODS: Observational and prospective study that was carried out from March 1, 2021 to March 1, 2022 in a university hospital in northeastern Mexico. Symptoms, severity, interleukin-6 levels, and skin tests of hypersensitivity reaction were evaluated at QT and monoclonal antibodies. RESULTS: A total of 41 patients with oncological disease were included, the most frequent being ovarian cancer. Symptoms as initial hypersensitivity reaction were neuromuscular in taxanes and cutaneous in Platinums.41.5% presented elevation of interleukin-6, and it was found more frequently in presence of metastases. Positive skin tests were found more frequently in the carboplatin and doxorubicin groups. The most frequently presented phenotype was type I in paclitaxel, carboplatin, and doxorubicin, and mixed-reaction (type I and cytokine release) in oxaliplatin. CONCLUSION: With the increasing prevalence of hypersensitivity reactions to biologic and antineoplastic therapies, interleukin-6 should be recognized as a biomarker in immediate hypersensitivity reactions to QT and monoclonal antibodies.

Rapid drug desensitization to taxanes: a descriptive study from Turkey.

AIM: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD). METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards. RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male. CONCLUSION: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Contact allergy to corticosteroids: Is the European baseline series sufficient?

BACKGROUND: Patients are consecutively screened for contact allergy to corticosteroids with budesonide and tixocortol-21-pivalate in the European baseline series. Centres using TRUE Test also include hydrocortisone-17-butyrate. A supplementary corticosteroid patch test series is used in case of suspicion of corticosteroid contact allergy or when a marker of corticosteroid contact allergy is positive. OBJECTIVE: The aims were to evaluate (1) the efficacy of corticosteroids in the TRUE Test and (2) co-sensitization patterns. METHODS: This retrospective study analysed patients patch tested with TRUE Test corticosteroids plus supplementary corticosteroid series in the period 2006-2020 at the Department of Dermatology and Allergy Centre, Odense University Hospital. RESULTS: Of 1852 patients tested, 119 were sensitised to TRUE Test corticosteroids and supplementary testing found additional reactions to other corticosteroids in 19 of 119 patients. TRUE Test corticosteroids gave more positive and stronger reactions compared to allergens in petrolatum/ethanol. Fourteen percent of sensitised patients were co-sensitised to multiple corticosteroid groups. Baeck group 3 corticosteroids accounted for 9 of 16 patients not identified by TRUE Test. CONCLUSIONS: Budesonide, hydrocortisone-17-butyrate, and tixocortol-21-pivalate in combination are sensitive corticosteroid markers. In case of clinical suspicion of corticosteroid contact allergy, patch testing with supplementary corticosteroids is highly recommended.