Search Results (355)

Nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate urticaria and/or angioedema in up to 30% of patients with chronic urticaria (CU), representing a distinct subtype characterized by heightened inflammation and leukotriene-driven pathophysiology. MicroRNAs (miRNAs) are post-transcriptional regulators that modulate immune and inflammatory responses. This study aimed to identify differentially expressed miRNAs (DEMs) according to NSAID hypersensitivity status and to elucidate their molecular networks in CU. Serum miRNA profiles were analyzed in 14 NSAID-exacerbated CU (NECU) and 16 NSAID-tolerant CU (NTCU) patients using an Affymetrix GeneChip^® miRNA 4.0 Array. DEMs were identified (fold difference > 1.5, p < 0.05), and validated targets were retrieved from the multiMiR database for network construction and Gene Ontology enrichment analyses. NECU patients exhibited a higher frequency of angioedema and systemic corticosteroid use than NTCU patients. Eight DEMs were identified, including upregulated miR-5001-5p, miR-4270, and miR-6869-5p, and downregulated miR-6511b-5p, miR-2277-5p, and miR-378h in NECU. Network integration revealed AGO2-BTG2-LMNB2, NFIC-ZZZ3, and NUFIP2-GLG1 as central clusters, implicating dysregulation of mRNA decay and inflammatory signaling pathways. Reduced miR-6511b-5p expression may derepress BRG1, enhancing chromatin accessibility for inflammatory and leukotriene-synthetic genes. Distinct miRNA signatures differentiate NECU from NTCU, implying a miR-5001-5p/miR-6511b-5p–mRNA decay axis that links impaired post-transcriptional regulation with leukotriene-driven inflammation in CU. These findings highlight candidate miRNAs as potential biomarkers for disease endotyping and therapeutic stratification. Full article

Background/Objectives: Acute generalized exanthematous pustulosis (AGEP) is a severe drug-induced cutaneous reaction characterized by the abrupt onset of sterile pustules, fever, neutrophilia, and a T cell-mediated type IVd hypersensitivity response. This narrative review synthesizes current evidence on pharmacological triggers, immunopathogenic mechanisms, diagnostic criteria, and differential diagnosis to provide a clinically oriented framework. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and SpringerLink for studies published between 2000 and 2025, complemented by selected clinical reference sources. Studies addressing clinical features, immunological pathways, pharmacovigilance signals, and diagnostic tools for AGEP were included. Synthesis of Evidence: β-lactam antibiotics remain the most frequent triggers, while increasing associations have been reported with hydroxychloroquine, targeted therapies, immune checkpoint inhibitors, psychotropic agents, and vaccines. Immunopathogenesis is driven by IL-36 activation, CXCL8/IL-8–mediated neutrophil recruitment, and IL36RN mutations, explaining overlap with pustular psoriasis. Diagnostic accuracy improves through integration of drug latency, clinical morphology, histopathology, biomarkers, and standardized tools such as the EuroSCAR score. Conclusions: AGEP is a complex pustular reaction induced by diverse drugs and amplified by IL-36-mediated inflammation. Accurate diagnosis requires a multidimensional approach supported by structured algorithms and robust pharmacovigilance to identify evolving drug-associated patterns. Full article

The Mas-related G protein-coupled receptor (MRGPR) X2 is expressed on skin mast cells and can be stimulated by an unusually broad spectrum of ligands, including specific drugs and even endogenous peptides. MRGPRX2 activation can induce mast cell degranulation and consequently mediator release, leading to inflammatory and hypersensitivity reactions. In addition, MRGPRX2 mediates pain and itching sensations, leading to increased efforts to identify MRGPRX2 inhibitors, including plant-derived compounds. Components within oat extracts have been shown to mediate anti-inflammatory and itch-relieving properties, but a possible inhibitory effect on MRGPRX2 activation has not yet been investigated. We aimed to fill this gap and explored whether an oat kernel extract can modulate MRGPRX2 activation. For this purpose, we established a mast cell model with the human LAD2 cell line and used it to investigate the consequences of exposure to oat extract. While we did not observe any influence on cell viability, we analyzed the impact of oat extract on MRGPRX2-mediated mast cell activation and degranulation initiated by the three confirmed MRGPRX2 ligands c48/80, substance P, and cortistatin 14. Exposure to oat extract resulted in a significant reduction in mast cell degranulation for all three ligands, as assessed by the release of β-hexosaminidase, tryptase, cell surface expression of CD63 and CD107a, and phosphorylation of ERK. All results were confirmed with primary human mast cells. Thus, we demonstrated for the first time that oat extract leads to a significant reduction in MRGPRX2 activation, pointing to a previously unrecognized capacity of natural compounds to modulate this pathway. Full article

Background: Molar–Incisor Hypomineralization (MIH) represents a developmental enamel defect of systemic origin, typically affecting the first permanent molars and often the incisors. Within the limitations of this study, several associations were observed between perinatal factors and MIH-related outcomes. However, most of these connections were not retained in adjusted analyses. Febrile illness during the first year of life showed a significant association with hypersensitivity. Methods: A structured 30-item questionnaire was distributed to mothers of 50 children diagnosed with MIH between February and March 2024. Data was analyzed using chi-square tests, with p < 0.05 considered significant, and univariate and multivariate logistic regressions at 95% confidence interval. Clinical diagnosis followed the Weerheijm (EAPD) criteria. Results: Maternal medication during pregnancy (antibiotics, antiepileptics, asthma drugs) was significantly associated with preterm birth (p = 0.01). Low birth weight correlated with tooth eruption disorders (p = 0.009) and perinatal complications such as hypoxia and respiratory distress (p = 0.0001). Fluoride application demonstrated a protective effect against discolorations (p = 0.005), caries (p = 0.002), and hypersensitivity (p = 0.01). In the multivariate model, febrile illness during the first year of life may be associated with hypersensitivity in MIH-affected teeth (aOR = 5.71, 95% CI: 1.01–32.27, p = 0.049). Conclusions: Maternal medication and perinatal complications, particularly low birth weight, were associated with MIH occurrence. Preventive strategies emphasizing maternal health, early screening, and remineralization-based therapies can mitigate long-term oral health impacts. Full article

Background/Objectives: Drug hypersensitivity reactions (DHRs) are an important cause of morbidity in hospitalized patients, but their epidemiology and management in the inpatient setting are not well defined. Mislabeling of drug allergies may lead to inappropriate treatment and reduced antimicrobial stewardship. This study aimed to characterize the clinical profile, diagnostics, and management of inpatients referred for suspected drug allergy in a tertiary care hospital. Methods: We retrospectively reviewed all adult inpatients (≥18 years) at Luigi Sacco Hospital (Milan, Italy) who received allergology consultation between 1 June 2022 and 31 May 2025. Data on demographics, reaction type, culprit drugs, investigations, and management were collected. Immediate reaction severity was graded using the United States Drug Allergy Registry (USDAR) scale; delayed reactions were classified as severe cutaneous adverse reactions (SCARs) or non-SCARs. Logistic regression identified predictors of severity. Results: Among 35,438 admissions, 334 patients (0.9%) were evaluated; median age was 65 years, 51.2% were female, 67.4% had atopic comorbidities, and 55.1% reported prior drug allergy. Immediate reactions occurred in 49.1%, delayed in 43.7%. Cutaneous involvement was present in 86.8%, anaphylaxis in 6.6%, and SCARs in 3.9%. Antibiotics—particularly β-lactams—were most often implicated. In multivariate analysis, antibiotic exposure and older age were linked to more severe immediate reactions, while the absence of atopy predicted SCARs. Desensitization was successfully performed in 16.2% of patients. Conclusions: DHRs in inpatients are frequent and often involve high-risk drugs. Structured inpatient allergology services and an “allergy stewardship” approach may reduce DHR-related risks, support optimal therapy, and improve antimicrobial use strategies in tertiary care settings. Full article

Background: Fixed drug eruption (FDE) is a non-immediate, CD8+ T cell–mediated hypersensitivity reaction characterized by well-demarcated erythematous–violaceous plaques that recur at the same site after re-exposure to the causative drug. Although NSAIDs and antibiotics are the most common triggers, various other medications may induce FDE, and genetic susceptibility has been linked to specific HLA alleles. Methods: We conducted a clinical evaluation supported by patch testing, oral drug provocation, and assessment of therapeutic alternatives to identify the causative agent and confirm delayed-type hypersensitivity. Results: We report the case of a 53-year-old woman with essential hypertension, autoimmune thyroiditis, and renal lithiasis who developed well-demarcated erythematous plaques with central vesiculation and moderate pruritus on the dorsal hand and posterior calf approximately 8 h after ingestion of a 60 mg etoricoxib tablet. Patch testing was negative, while oral challenge confirmed etoricoxib-induced FDE; celecoxib was subsequently evaluated as a potential safe alternative. Conclusions: This case underscores the importance of an integrated diagnostic approach—including careful history, clinical examination, and confirmatory testing—to accurately diagnose delayed cutaneous drug reactions and to identify safe therapeutic options for patients. Full article

Background: Adverse reactions to tattoo pigments are increasingly recognized, yet severe systemic complications remain rare and poorly characterized. Red tattoo ink, in particular, is associated with delayed hypersensitivity reactions, but widespread manifestations affecting multiple organ systems have not been documented. This case report aims to describe an unusual constellation of erythroderma, alopecia universalis, anhidrosis, and vitiligo triggered by red tattoo ink and to highlight the diagnostic and therapeutic challenges associated with such reactions. Case presentation: This case report describes a 36-year-old Caucasian male who developed erythroderma, alopecia, anhidrosis, and vitiligo as complications of a red ink tattoo, marking a rare and previously unreported case of such extensive reactions. Four months after getting the tattoo, the patient began to develop itchy eczematous changes, which progressed to erythroderma over several months, along with alopecia universalis and anhidrosis. Results: After months of ineffective treatment with glucocorticosteroids, cyclosporine, methotrexate, and acitretin, patch tests confirmed hypersensitivity to possible components of the red tattoo ink, prompting surgical removal of the inflamed tattoo fragments. Unfortunately, aside from resolving the erythroderma, this did not improve the patient’s clinical condition, and he developed vitiligo. Only after the complete removal of the red tattoo ink from the same series that caused the sensitization and the use of immunosuppressive and immunomodulatory drugs, including JAK inhibitors, was hair growth restored and the progression of vitiligo halted, but with no effect on anhidrosis. Conclusions: This case highlights the challenges in managing systemic reactions to tattoo ink and the importance of thorough evaluation and treatment strategies. Full article

Polyethylene glycol (PEG) has been extensively utilized in drug formulations due to its multifunctional properties, i.e., hydrophilicity and biocompatibility. The roles played by PEG (as a drug delivery carrier and a solubilizer) improve the dissolution profile of several active pharmaceutical ingredients (APIs), leading to an improved absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile. Moreover, PEG aids in upgrading the existing mechanical properties (as a binding agent, a plasticizer, etc.). Furthermore, PEG, due to its unique ability to provide “stealth” properties, is a valuable tool in pharmaceutical nanotechnology. Exploiting physicochemical variables, PEG acts as a coating/conjugation component of nanocarriers for ameliorating permeability and enhancing in vivo circulation without clearance by the body’s immune system. Additionally, PEG’s presence at the target site decreases external interactions and enhances the pharmacological attributes in terms of loading efficiency and controlled release. Nevertheless, cases of hypersensitivity or allergy, as well as anaphylactic shocks and allergic reactions, have been detected. The topic of this article is the exploitation of PEG’s physicochemical properties in the study of drug delivery, focusing on solid dosage forms and nanovesicles, along with the evaluation of its contribution to the fabrication of safe delivery and theragnostic systems. Full article

Background/Objectives: Asparaginase (ASP)-based chemotherapy has substantially improved clinical outcomes in Epstein–Barr virus (EBV)-positive NK/T-cell lymphomas (NKTCL). However, as a bacterial-derived enzyme, ASP is frequently associated with immune-mediated adverse events, particularly hypersensitivity reactions (HSRs), which may compromise both treatment efficacy and patient safety. This report presents a case of an ASP-related HSR and reviews the incidence within our institutional cohort. Detailed Case Description: A 60-year-old female presented an immediate Grade 2 HSR during her second PEG-asparaginase infusion, with pruritus, vomiting, and presyncope. The infusion was discontinued, and she was subsequently transitioned to crisantaspase—an alternative formulation—which was well tolerated without further adverse events. She remains disease-free to date. A retrospective review of institutional records (2015–2025) identified six patients with NKTCL treated with ASP-containing chemotherapy. The incidence of HSRs in this cohort was 1 of 6 (16.7%). Conclusions: As in acute lymphoblastic leukemia, HSRs to asparaginase remains a major challenge in the management of NKTCL with potential implications for treatment safety and efficacy. The establishment of standardized, consensus-based criteria for the diagnosis, classification, and management of ASP-related HSRs is urgently needed to optimize patient outcomes. Full article

Allergic bronchopulmonary aspergillosis (ABPA) is mediated by hypersensitivity reactions to Aspergillus fumigatus, which is ubiquitous in the environment. People with Cystic Fibrosis (PwCF) are at an increased risk for developing ABPA, which can lead to frequent pulmonary exacerbations and progressive decline in lung function. In the age of highly effective modulator therapies (HEMT), PwCF have improved clinical outcomes and overall life expectancy, but they continue to suffer from comorbidities such as ABPA, which may be difficult to diagnose and treat. Establishing the diagnosis of ABPA in PwCF requires high clinical suspicion due to similarities in symptoms with the underlying disease. First-line treatment involves corticosteroids and anti-fungals, which have multiple side effects and drug interactions, especially with HEMT. Given this challenge, biologics have gained attention as potential agents directly targeting the Th-2 inflammatory pathway of ABPA with good tolerability and without significant drug interactions with HEMT. In this review, we discuss the diagnostic process and management of ABPA in PwCF, including a brief overview of the current literature on biologic agents. Full article

Background: Iodinated contrast agents are widely used in computed tomography (CT) imaging; however, they can cause adverse drug reactions (ADRs) ranging from mild hypersensitivity to severe anaphylaxis. While several clinical risk factors have been identified, large–scale studies incorporating environmental variables remain limited. This study aimed to assess the prevalence and predictors of contrast agent-related ADRs over a 10-year period. Methods: We retrospectively analyzed 221,962 adult outpatients who underwent contrast-enhanced CT between January 2014 and December 2023 at a single tertiary center: Patient characteristics, clinical conditions (e.g., hypertension, allergy history), contrast agent types, premedication status, seasonal trends, temperature, and humidity were examined. ADRs were categorized as mild, moderate, or severe based on American College of Radiology (ACR) guidelines. Logistic regression was used to identify independent predictors. Results: The overall prevalence of ADRs was 0.64% (1423 cases). ADRs were more frequent in females, younger patients, and those receiving premedication. Seasonal and environmental patterns were evident: higher ADR rates occurred in summer and autumn, with positive correlations to ambient temperature and humidity. Among contrast agents, Ioversol (1.4%) and Iomeprol (1.2%) showed the highest ADR rates. The prevalence of mild ADRs increased in the post–COVID-19 period, while that of moderate reactions declined. Conclusions: This real–world study identified multiple clinical and environmental factors associated with ADRs to iodinated contrast agents in CT imaging. The findings suggest the importance of individualized risk assessment and the consideration of environmental factors when planning contrast administration. Full article

Hypersensitized P2X3 receptor signaling has been described to play a role in several disorders, including chronic cough. The goal of our in vitro and in vivo studies was to investigate the biotransformation and the influence of CYP3A4 inhibition on the pharmacokinetics of the selective P2X3 antagonist filapixant. Metabolic turnover of filapixant in human liver microsomes and hepatocytes was moderate to high, indicating a complex metabolic pattern with mainly oxidative biotransformation. In recombinant CYP enzymes, depletion of filapixant was observed mainly with CYP3A4 and, to a significantly lesser extent, with CYP1A1, 2D6, 2J2, and 3A5. Drug depletion of [³H]filapixant and metabolite formation in human liver microsomes was significantly inhibited in the presence of strong CYP3A4 inhibitors, whereas other CYP isoform–selective inhibitors showed no or very minor effects. Co-administration of multiple daily doses of 200 mg itraconazole with 80 mg filapixant in humans increased the AUC and C_max of filapixant to 4.01 and 1.89-fold, respectively, indicating that filapixant is a moderately sensitive CYP3A4 substrate. Co-administration of itraconazole also prolonged the half-life of filapixant from 12.1 h to 22.8 h. Overall, changes in AUC, C_max, and half-life indicate that both the bioavailability and elimination of filapixant were affected. Filapixant was well tolerated alone and in combination with itraconazole. Full article

Serum sickness-like reaction (SSLR) is a rare immune-mediated condition that typically affects the skin and joints after exposure to certain drugs, infections, or vaccines. Although it shares clinical similarities with serum sickness (SS), SSLR differs in its underlying mechanisms, histopathology, and causes. Despite its generally benign and self-limiting nature, SSLR is frequently misdiagnosed and may lead to unnecessary hospitalization. This narrative review summarizes current knowledge on epidemiology, pathophysiology, clinical features, diagnosis, treatment, and long-term considerations related to SSLR. The condition is most often associated with antibiotics, monoclonal antibodies, and vaccines, particularly in pediatric populations. Its pathogenesis remains incompletely understood, but proposed mechanisms include immune complex formation, altered drug metabolism, lymphocyte toxicity, and the development of anti-drug antibodies. Diagnosis is primarily clinical, although novel diagnostic tools are emerging. Management involves discontinuation of the offending agent and supportive care, such as antihistamines or nonsteroidal anti-inflammatory drugs (NSAIDs) in mild cases, and corticosteroids in more severe cases. Long-term management, especially in cases requiring potential re-exposure to the causative agent, remains challenging. Skin testing and graded oral challenges appear promising within a structured clinical framework. Increased awareness of SSLR is essential for timely recognition and appropriate care, and further research is needed to elucidate its mechanisms and inform evidence-based management strategies. Full article

Pharmacist engagement in allergy clarification has demonstrated increased appropriate antibiotic use. The purpose of this study was to determine the knowledge and confidence of pharmacy students in their final professional year regarding beta-lactam (BL) allergies. Students from 5 schools of pharmacy participated in a 22-question survey pertaining to experience with drug allergies, knowledge of BL allergies, and confidence regarding BL allergy management. Data were summarized among all respondents and further analyzed by infectious disease (ID) interest. A total of 160/521 students responded to the survey (31%). Most students (73%) had no course dedicated to drug allergies; however, 84% indicated the topic was taught within the curriculum. Students with an ID interest had a higher perceived knowledge regarding the details of penicillin skin testing (62% vs. 32%), clinical implications of penicillin skin test results (87% vs. 70%), and the principles behind a graded and direct penicillin challenge (64% vs. 41%). These students were more confident in educating patients about a perceived penicillin allergy (34% vs. 15%). Perceived knowledge and confidence of BL allergies were low, especially in high-level interventions. Targeted training in beta-lactam allergy recognition and management within the curriculum should be considered to improve upon these findings. Full article

Sterol biosynthesis is crucial for the function of biological membranes and an important target for anti-protozoan/anti-fungal drugs. In the trypanosomatid parasite Leishmania major, the deletion of sterol C14-demethylase (C14DM) results in hypersensitivity to heat, increased plasma membrane fluidity, profound mitochondrial dysfunctions, and reduced virulence in mice. In this study, we show that C14DM-null mutants are defective in their tolerance to membrane-disrupting agents and osmotic stress and their ability to form autophagosomes. In addition, C14DM-null mutants exhibit a heightened sensitivity to anti-trypanosomatid drugs including antimony, ethidium bromide, and pentamidine. The combination of itraconazole (a C14DM antagonist) and pentamidine synergistically inhibits the growth of Leishmania parasites. These findings reveal new insight into the roles of sterol synthesis in protozoan pathogens and highlight the potential of using drug combinations to achieve better treatment outcomes. Full article