Drug-induced Allergic Reactions Research Articles

Novel insights into the heterogeneity of FOXP3 + Treg cells in drug-induced allergic reactions through single-cell transcriptomics.

This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.

Drug-Induced Anaphylaxis: National Database Analysis.

(1) Background: National health system databases represent an important source of information about the epidemiology of adverse drug reactions including drug-induced allergy and anaphylaxis. Analysis of such databases may enhance the knowledge of healthcare professionals regarding the problem of drug-induced anaphylaxis. (2) Methods: A retrospective descriptive analysis was carried out of spontaneous reports (SRs) with data on drug-induced anaphylaxis (SRsAs) extracted from the Russian National Pharmacovigilance database (analyzed period 2 April 2019-21 June 2023). The percentage of SRsAs among SRs of drug-induced allergy (SRsDIAs) was calculated, as well as of pediatric, elderly, and fatal SrsAs. Drugs involved in anaphylaxis were assessed among total SRsAs, pediatric, and elderly SRsAs, and among fatal SRsAs. Demographic parameters of patients were assessed. (3) Results: SRsAs were reported in 8.3% of SRsDIAs (2304/27,727), the mean age of patients was 48.2 ± 15.8 years, and females accounted for 53.2% of cases. The main causative groups of drugs were antibacterials (ABs) for systemic use (44.6%), local anesthetics (20.0%), and cyclooxygenase (COX) inhibitors (10.1%). Fatal SRsAs were reported in 9.5% (218/2304) of cases, the mean age of patients was 48.0 ± 16.7 years, and females accounted for 56.4% of cases. Pediatric SRsAs accounted for 3.9% of pediatric SRsDIAs and 5.8% of all SRsAs, with a mean age of 11.8 ± 4.5 years, and females acccounted for 51.9% of cases. Elderly SRsAs accounted for 2% of elderly SRsDIAs and 2.8% of all SRsAs, and the mean age was 73.0 ± 5.3 years, and females accounted for 43.5% of cases. ABs caused 40% of SRsAs in the elderly, 42.9% in children, and 50% of fatal SRsAs. (4) Conclusions: Our study revealed a relatively high proportion of anaphylaxis among SRs of drug-induced allergy. ABs were the most prevalent causative agents, especially in fatal SRsAs.

Patient Adherence to Written Instructions following Complete Allergological Evaluation for Suspected Beta-Lactam Allergy: A Tertiary Hospital Study in Greece.

Beta-lactam (BL) antibiotics are among the most prescribed groups of drugs worldwide and have been implicated in a variety of allergic reactions. There is a paucity of literature regarding patient adherence to prescribed instructions following comprehensive allergy assessments. The objective was to follow up the clinical course of BL allergy in patients who underwent thorough allergological investigation for suspected BL allergy at a tertiary hospital and ascertain patients' compliance with the provided written instructions. An observational study in patients referred for suspected BL allergy who underwent a comprehensive allergy workup (in vivo ± in vitro tests, DPT in culprit and/or alternative BL) and who subsequently received written instructions was conducted. Data on the nature of the reported drug hypersensitivity reaction, the culprit BL drug, the allergological workup, and the detailed instructions provided in a written drug allergy report were collected retrospectively. Patients' compliance with the instructions was recorded by a telephone survey using a pre-defined questionnaire. Among the 212 patients meeting the inclusion criteria, 87 patients (72.4% women; mean age 50.1 years; age range 6-84 years) responded to the telephone survey and were included in this study. Surprisingly, 45 out of 87 (51.7%) patients did not adhere to the written instructions. The primary factor contributing to non-compliance was the fear of re-occurrence of a drug-induced allergic reaction (personal and/or triggered by their treating physician reluctance), accounting for 77.7% of cases. The analysis demonstrated that the initial reaction's severity and type, as well as the outcomes of skin testing, did not correlate with compliance to instructions (p > 0.05). Surprisingly enough, a drug provocation test (DPT), irrespectively of the result, emerged as a negative predictor for adherence, with only 40.6% of DPT patients complying compared to 77.8% of those who did not undergo DPT (p = 0.005; odds ratio = 0.195; 95% confidence interval: 0.058-0.655). Variables such as performing DPT with alternative or incriminated drugs or the result of the DPT (positive-negative) were not associated with patient compliance. Conversely, the type of instructions provided exhibited a noteworthy correlation with compliance. Patients who were explicitly instructed to entirely avoid all BL antibiotics demonstrated markedly higher adherence rates (83.3%) compared to those who were advised to have a partial or complete release of BLs (31.8% and 58.1%, respectively; p < 0.05). Notably, among compliant patients who received either the original culprit drug or the alternative (32 out of 87, 36.7%), no allergic reactions were reported. In contrast, among the 12 patients with written avoidance of all BLs, subsequent BL intake led to immediate reactions (Grade I and IV) in 2 patients (16.6%). A notable disparity in patient adherence to written instructions prohibiting or releasing beta-lactams was demonstrated. Less than half of the patients ultimately complied with the provided instructions, underscoring the need for tailored patients' education and strategies to improve adherence in the management of suspected BL allergy.

IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity

Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. The study recruited 393 patients. Apositive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and β-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

Knowledge, attitudes, and practices regarding drug allergy among healthcare providers in Eastern India

Background: Drug allergy (DA) or hypersensitivity is an immunologically mediated reaction producing stereotype symptoms which is challenging for health care providers (HCP). Objective of current study was to assess the knowledge, attitudes and practices of drug allergy among healthcare providers in eastern India. Methods: A 25-item self-administered DA questionnaire was developed and applied in our study. The questionnaire covered 3 domains: knowledge, attitudes, and practice patterns. From July 2020 to September 2020, HCPs participated in the cross-sectional study. Results: A total of 237 HCPs participated in the study, and all questionnaires were analysed. Among the respondents, 226 (95.4%) were nurses, 9 (3.8%) were doctors and 2 (0.8%) were pharmacists. The majority of HCPs agreed that drug-induced immediate allergic reactions were IgE mediated 225 (94.9%), occur within 6 hours of drug administration (89.9%), and epinephrine was the first choice for drug-induced anaphylaxis (76.8%). 97.9% HCPs agreed that penicillin skin test was valuable to predict the allergic reaction. More than 80% of the respondents would take patients’ allergic history before drug administration, while 75.5% agreed that they recognize and manage drug allergy timely when it occurs. Conclusions: Drug allergy was often diagnosed and managed inadequately, regardless of practice location, employment status and speciality in eastern India. The HCPs demonstrated a low level of knowledge regarding DA. Advanced education is urgently needed for better understanding and filling the gaps that exist in the knowledge and clinical practice of DA.

Acute Facial Edema in a Patient with Systemic Lupus Erythematosus

Allergies have been found to be associated with systemic lupus erythematosus (SLE). However, few reports have described angioedema occurring in elderly men with systemic lupus erythematosus. Herein, we report the case of an 85-year-old man who presented with angioedema with eosinophilia. The patient was initially thought to have a drug-induced allergy. The differentiation between allergic reactions caused by drugs and those caused by eosinophilia with SLE can be challenging. The effect of the withdrawal of the suspected culprit drug and allergic dermal findings can be key to differentiating the two conditions. SLE is prevalent among younger generations; hence, active immunity can induce various symptoms, including eosinophilia, which causes angioedema. Even older people with SLE can have a strong immune reaction, resulting in angioedema with eosinophilia. In cases of localized facial edema in elderly patients with SLE, it is critical to consider angioedema caused by eosinophilia as a differential diagnosis.

COMPARATIVE EFFECTS OF IV INJECTION OF KETOPROFEN AND PARACETAMOL IN THE TREATMENT OF TENSION-TYPE HEADACHE

Background: Headaches are one of the commonly reported issues throughout the world population. Globally, Tension-type headache is a more common problem. Individuals facing long occurring and more severe headaches may go for care from the medical facility. However, most of the individuals do not do so which usually consequences in inappropriate and inadequate management of this problem.&#x0D; Objective: The aim of the present study is to compare the effectiveness of ketoprofen IV injection and paracetamol IV injection in the treatment of tension-type headache.&#x0D; Methodology: A validated questionnaire was designed to conduct this study. Certain inclusion and exclusion criteria were established to select the participants. Patients having the age between 20 to 40 years were treated with paracetamol and ketoprofen and their responses were recorded and evaluated.&#x0D; Results: Our results suggest that paracetamol has more vital signs stability when compared with ketoprofen and is safer in terms of drug-induced allergic reaction and injection site reaction. However, ketoprofen has a faster onset of action when compared with paracetamol.&#x0D; Conclusion: Management of tension-type headache is neglected most of the time which affects the quality of life and productivity in the affected population. Development and update of existing guidelines for tension-type headache are essential in managing this issue. Both ketoprofen and paracetamol are effective in treating this issue but both have some side effects. Future studies are still desired to further evaluate their effects.&#x0D; Keywords: Tension-type headache, Headache, analgesics, Ketoprofen, Paracetamol

The Translational Relevance of Human Circulating Memory Cutaneous Lymphocyte-Associated Antigen Positive T Cells in Inflammatory Skin Disorders.

Circulating memory T cells are heterogeneous in their tissue tropism. The skin-seeking T cell subset expresses the cutaneous lymphocyte-associated antigen (CLA) on their surface. CLA+ memory T cells not only migrate from blood to skin but also recirculate between blood and skin. Studying CLA+ memory T cells in cutaneous diseases has allowed a better understanding of immune-inflammatory mechanisms that take place. The analysis of the phenotypical features of these cells, their antigen specificity, cytokine production profile, and changes in relationship to clinical status and therapies among other characteristics have led to the concept that they constitute peripheral cellular biomarkers in T cell-mediated cutaneous conditions. CLA+ memory T cells are of relevance in the pathogenesis of several cutaneous diseases, such as psoriasis (PSO), atopic dermatitis, vitiligo, and drug-induced allergic reactions, to name a few. The interaction of circulating CLA+ T cells with skin-resident cells has been investigated in different ex vivo coculture models made out of clinical samples. Interestingly, microbes that are present in the skin or related with human skin diseases are preferentially recognized by CLA+ T cells. Thus, the interaction of Streptococcus pyogenes with CLA+ T cells in PSO is providing novel concepts that help to understand disease immunopathogenesis. The goal of this review is to present latest results in the field of CLA+ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology.

Novel method to analyze cell kinetics for the rapid diagnosis and determination of the causative agent in allergy.

Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively). HiSAT analyzes the cell kinetics as an index against chemotactic factors in a patient’s serum, as different from the diagnosis using conventional methods. Once allergy has occurred, HiSAT can be used to determine the causative medicine using culture supernatants incubated with the subject’s lymphocytes and the test allergen. This test is more efficient (60%) than the lymphocyte transformation test (20%). Furthermore, in HiSAT, cell mobility significantly increases in a dose-dependent manner against supernatant incubated with lymphocytes from a subject with pollinosis collected at a time when the subject is without allergic symptoms and the antigen. The result demonstraed that HiSAT might be a promising method to rapidly diagnose DIA or to determine with high accuracy the antigen causing allergy.

A novel ELISA method to determine human MrgX2 in chronic urticaria

BackgroundMas-related G-protein coupled receptor member X2 (MrgX2) directly mediates drug-induced pseudo allergic reactions. Skin mast cell MrgX2 is upregulated in severe chronic urticaria (CU). Mast cells and leukocytes are key effector cells in allergic reactions and undergo degranulation upon stimulation. It is unknown whether circulating MrgX2 expression can be detected occurs in the whole blood of CU patients and reflects pseudo-allergic reaction. There is no effective method for its detection. Therefore, an enzyme-linked immuno-sorbent assay (ELISA) for MrgX2 was developed.MethodsMonoclonal and polyclonal MrgX2 specific antibodies were obtained from rabbits and mice immunized by MrgX2 peptides prepared. Indirect ELISA and Dot blot were used to determine antibody titers before a sandwich ELISA for MrgX2 was established. The whole blood from healthy subjects and CU patients was used to detect MrgX2 concentrations. The use of feasibility of this MrgX2-ELISA as a clinical detection tool was explored and diagnostic purposes was assessed.ResultsThe sandwich antibody ELISA method for MrgX2 was established with good linearity regression (R2 = 0.9910). The lowest detection limit was 3.125 ng/mL. The quantification limit was 6.25 ng/mL. The sandwich ELISA for MrgX2 have good stability and high specificity. The initial truncation value of MrgX2 was 60.91 ng/mL (95% confidence interval). The whole blood MrgX2 concentrations in CU patients (median 98.01 ± 4.317 ng/mL, n = 75) was significantly increased compared to healthy subjects (58.09 ± 1.418 ng/mL, n = 75), with significant difference (p < 0.0001) and higher accuracy of (AUC = 0.8795). Comprehensive the frequency analysis of MrgX2 expression in 75 CU patients reference frequency distribution and ROC curve analysis, determined the threshold for CU patients as 71.23 ng/mL, with 81.33% sensitivity and 90.67% specificity.ConclusionMrgX2-ELISA provides a useful and convenient method for detecting MrgX2 in whole blood samples. The MrgX2-ELISA will help improve the understanding of the role of MrgX2 in regulating chronic urticaria.

A Comprehensive Study on Some Reported Polyherbal Formulation with Potential Antihistaminic activity

The polyherbalism that is a combination of two or more herbs expresses the fundamental aspect of Ayurvedic/herbal drug formulation. As per the many pieces of evidence shows the various herbal formulation with different potency acts by a unique mechanism. By which the Polyherbal formulation today make the choice for threatened disease or disorder rather than single one, to gain synergistic therapeutic application. The allergens produce immunoglobulin E (IgE)-mediated immune response and instant hypersensitivity reaction result in asthma, hay fever, atopic dermatitis, allergic rhinitis, food, and drug-induced allergies. Taking into consideration the etiology of upper respiratory tract infection, nowadays antihistamines are the choice of drug for the treatment of viral infections of the upper respiratory tract can be practice to stop complex inflammatory mediated reaction mainly effective in adult patients. The different plant species are discovered and applied over various clinical manifestations related to an allergic response. According to the traditional system of medicine, common plant species with their plant part used in some Antihistaminic Polyherbal formulation were assessed by Animal model work on the allergic response which includes HK-07, Unani eye drop, Bharangyadi, Ashmi, Pentapala-04. This study proved that many herbs combination has anti-histaminic and anti-allergic activity.

Quinolone Allergy.

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available.

Use of an electric toothbrush in patients affected by autoimmune desquamative gingivitis: evaluation of biological parameters

Event Abstract Back to Event Use of an electric toothbrush in patients affected by autoimmune desquamative gingivitis: evaluation of biological parameters Giuli Antonucci1, Alessio Gambino1*, Paola Carcieri1, Marco Cabras1, Roberto Broccoletti1 and Paolo Giacomo Arduino1 1 University of Turin, Department of Surgical Sciences, Italy Aim. According to the current classification of periodontal diseases (classification of periodontal and peri-implant diseases and conditions 2017), desquamative gingivitis is included in "gingival disorders not induced by dental biofilm". The gums are usually erythematous, very sore, sometimes bleeding, with areas of atrophy, ulceration and / or presence of vesiculo-bullous lesions. It appears to be the gingival manifestation of different systemic conditions, such as oral disimmune diseases, but also as consequence of drug-induced injuries or allergic reactions to chemicals and food. Oral lichen planus (OLP), pemphigus vulgaris (PV), and mucous membranes pemphigoid (PMM) account for between 88 and 98% of total cases. The desquamative gingivitis treatment’s goal is to control the progression of the lesions and to reduce symptoms perceived, although a complete recovery may be quite difficult. The pharmacological treatment should be accompanied by a strict plaque control with home and professional proper oral hygiene procedures. This study aims to evaluate the effectiveness of the Oral-B Smart 4 electric toothbrush in association with the "Sensitive Clean" head and the "Sensitive Teeth" mode for home oral hygiene in patients with desquamative gingivitis. The study was carried out through the estimation of periodontal biological parameters, concerning the development of the pathology and parameters related to the comfort perceived by the patient, comparing their previous use of a manual toothbrush. Materials and Methods. The propose protocol consisted of 5 appointments. In the initial appointment (T0), clinical parameters were recorded such as pocket depth, recessions, plaque index (FMPS) and bleeding index (FMBS) through the compilation of a periodontal charting; a complete photographic status was also performed, and the severity of the clinical signs evaluated with the use of the Desquamative Gingivitis Clinical Score (DGCS), the severity of pain with the use of the VAS scale, and the comfort with the use of the Oral Health Impact Profile. In the next appointment (T1), a week apart, the plaque index (PI) was recorded with the help of the Tri Plaque ID Gel plaque detector; in the meantime, a frontal photo was acquired and a professional oral hygiene session were performed. In this session, the patients were instructed to use the electric toothbrush. The two following appointments (T2 and T3), one month after T1, repeated the same steps of instruction and motivation of the T1. In the last two appointments (T4 and T5), two months after T2 and T3, the same indices evaluated during the first session were examined again. Results. Fourteen patients were recruited, with an average age of 65.85 years and with an average of 25 dental elements. In the sample, 7 patients had OLP, 4 had PMM and 3 had PV. The plaque and bleeding index showed a statistically significant reduction (p<0.05) between the first and last appointments, unlike the DGCS. Discussion. According to literature data, the electric toothbrush evaluated appeared to be a valid substitute for the manual toothbrush. Our work revealed statistically significant differences in terms of plaque reduction and bleeding, thus being in line with previous studies establishing a correlation between desquamative gingivitis and plaque-induced gingivitis. The DGCS index showed a susceptibility from T0 to T5 in almost all patients, with a worsening of clinical signs detected in patients with OLP, instead of those with PMM and PV. This result may be partly explained due to the sporadic usage of immunosuppressants in patients with symptomatic OLP, being instead a steady, although low-dosage, treatment among individuals with bullous disease. The main limitation of the present protocol is represented by the small size of the sample. However, such limit must be put in perspective, considering that the limited number of patients recruited is an inevitable consequence of the sample inclusion criteria, which had to be so strictly arranged in order to minimize the weight of a steady high-dosage corticosteroid therapy as confounding factor. Further studies will be needed to increase as much as possible the size of the sample, aiming to obtain the most applicable results for the population. Plaque and tartar control through a protocol that provides professional oral hygiene sessions and oral home health motivation plays a key role in the clinical management of these patients. Oral hygiene in patients with desquamative gingivitis for autoimmune diseases are able to provide long-term benefits from their gingival health, if the same patients have previously been through a drug therapy.

DIAGNOSIS OF DELAYED DRUG ALLERGIC REACTIONS

Mechanisms of delayed druginduced allergies (DDIA), individual features of the immune response to the drug, influence of various cofactors (concomitant pathology, viral infection, insolation, etc.) create difficulties in diagnostics of drug allergy (DA). Identification and elimination of a causative drug allows to prevent the development of severe allergic reactions. Verification of DA diagnosis during the survey allows to avoid the unreasonable lifelong ban on application of certain drug, which often leads to decreasing of treatment efficiency and increasing its cost. In vitro diagnostic tests are safe, but laborious and expensive. This article will provide the review of literature, reflecting a modern view on the diagnosis of DDIA.

A Case of Mediterranean Spotted Fever Misdiagnosed as Drug Allergy

Skin rashes are observed in about 2-3% of patients taking medication for any reason. Since the cutaneous manifestations are also common in viral exanthemas, rickettsial-bacterial infections and rheumatologic diseases, it is important to exclude other conditions that may mimic drug-induced allergic reactions in patients having skin rashes. Here, we report a patient of Mediterranean Spotted Fever (MSF) who was initially misdiagnosed as a drug eruption. The clinician should take into account the skin manifestations that can also be seen in the course of infectious diseases and they should consider the possibility of various infections in the diagnosis of drug allergy such as a Mediterranean Spotted Fever.

Immune pathogenesis of heparin-induced thrombocytopenia.

The immune response to heparin is one of the most common drug-induced allergies, and yet, atypical for a drug hypersensitivity reaction. Whereas most drug-induced allergies are rare, idiosyncratic and life-long, the allergic response to heparin is common, predictable in certain clinical settings and transient. Advances in the last decade with regards to structural characterisation of the PF4/heparin antigenic complex, contributions of innate immunity and development of animal models have provided insights into the distinctive features of the HIT immune response. Recent descriptions of the crystal structure of the PF4/heparin complex, alongside other biophysical studies, have clarified the structural requirements for immunogenicity and heparin-dependency of antibody formation. Studies of interactions of PF4 with bacterial cell walls as well as epidemiologic associations of anti-PF4/heparin antibody formation and infection suggest a role for immune priming and explain the rapid evolution of an isotype-switched immune response in sensitised patients. Murine models have greatly facilitated investigations of cellular basis of the HIT response and identified a major role for T-cells and marginal zone B-cells, but key findings have yet to be validated in human disease. This chapter will summarise recent investigations of the HIT immune response in the context of major pathways of immune activation and identify areas of uncertainty.

Study of association of concomitant diseases with chemotherapy tolerability in children with active tuberculosis: results of a retrospective cohort research

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

Eosinophilic colitis in 36 years old female: a case presentation with review of literature

&lt;p class="abstract"&gt;&lt;span lang="EN-US"&gt;Eosinophilic Colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with prevalence in neonates and young adults. EC condition is less understood as compared to the recognized eosinophilic esophagitis. Clinically EC presents as highly variable disease and it is based according to mucosal, transmural, or serosal predominance of inflammation. EC has a vast range of differential diagnosis because eosinophilia of colon occurs in many conditions like parasitic infection, Inflammatory Bowel Disease (IBD), drug-induced allergic reactions and various connective tissue disorders and so it require to rule out these causes by thorough searching for secondary causes which can be treated with antibiotics or dietary and drug elimination before we start the EC treatment. EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics. Here we present a case of EC in a 36 years old female with pain in abdomen and bloody diarrhoea.&lt;/span&gt;&lt;/p&gt;

Drug-Induced Anaphylaxis in Latin American Countries

Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P < .01). Severe DIA was less frequent with underlying asthma (N = 22 vs 35 [38.6% vs 61.4%], P < .05) or atopy (N = 62 vs 71 [43% vs 59% ], P < .01). Nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 178 [57.8%]), beta-lactam antibiotics (N = 44 [14.3%]), and other antibiotics (N = 16 [5.2%]) were the most frequently implicated drug classes. Anaphylaxis was rated as severe in N = 133 (50.4%) and anaphylactic shock (AS) was present in N = 90 (34.1%). Epinephrine was only used in N = 73 (27.6%) overall, but in N = 70 (77.8%) of patients with AS. In Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA.

Dexamethasone disrupts cytoskeleton organization and migration of T47D Human breast cancer cells by modulating the AKT/mTOR/RhoA pathway.

Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/ mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.