Search Results (568)

Background: Iodinated contrast media are essential for oncologic imaging but raise specific safety concerns because cancer patients are often exposed to repeated contrast-enhanced computed tomography, nephrotoxic drugs, immune-modulating therapies, and, in selected cases, radioiodine-dependent diagnostic or therapeutic pathways. Methods: We performed a narrative review based on an exploratory search followed by a focused search targeting iodinated contrast use in oncology-related settings. Studies were included if they addressed renal risk and post-contrast acute kidney injury, hypersensitivity and acute adverse reactions, or thyroid dysfunction with radioiodine-related implications. We also considered clinically relevant studies on drug interactions, isotope studies, and laboratory confounding. Results: The evidence base was methodologically heterogeneous, with renal safety as the predominant domain. Kidney injury after contrast-enhanced imaging in cancer patients appeared frequently multifactorial, supporting the broader concept of post-contrast acute kidney injury rather than automatic attribution to contrast alone. Hypersensitivity reactions to modern nonionic iodinated contrast media were generally uncommon, with severe reactions rare, although immune-modulating therapies may alter risk. Thyroid-related effects were usually transient but relevant in patients with thyroid autonomy and in differentiated thyroid carcinoma, where contrast exposure may affect scintigraphy and radioiodine planning. Conclusions: In oncology, iodinated contrast use requires individualized, field-specific risk stratification instead of reflexive avoidance. Full article

Background: Kounis syndrome is an acute coronary syndrome triggered by hypersensitivity reactions, which may result in coronary vasospasm, thrombosis, or stent-related complications. Case Summary: A 64-year-old male smoker with dyslipidemia and recently diagnosed urothelial carcinoma presented with exertional angina and underwent coronary angiography. Percutaneous coronary intervention was performed for a critical proximal–mid left anterior descending artery lesion using a drug-eluting stent. Immediately after stent deployment, the patient developed diffuse multivessel coronary vasospasm involving the left main stem, left anterior descending, and left circumflex arteries, accompanied by slow-flow/no-reflow phenomena and subsequent acute in-stent thrombosis. The clinical course rapidly progressed to ventricular arrhythmias and cardiogenic collapse. Despite transient return of spontaneous circulation after cardiopulmonary resuscitation, the patient developed fatal asystole during a repeat angiographic attempt. No cutaneous or respiratory allergic manifestations were observed. The abrupt onset of diffuse coronary dysfunction immediately following contrast exposure was suggestive of suspected Kounis syndrome, although mechanical causes and chemotherapy-related vasospasm could not be entirely excluded. Conclusions: Diffuse coronary vasospasm with multivessel dysfunction occurring abruptly after contrast exposure should raise suspicion for Kounis syndrome, even in the absence of overt allergic manifestations. Early recognition is essential to avoid misattribution to procedural complications and may be particularly important in patients with malignancy undergoing invasive coronary procedures. Full article

Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use has increased exponentially as studies show significant benefits in cardiovascular and renal diseases and obesity. Accessibility to the public also increased after compounding pharmacies began direct-to-consumer distribution. Gastrointestinal side effects are common; however, hypersensitivity reactions are rare. Case Presentation: A 50-year-old female with a history of obesity, hypertension, and lisinopril-induced angioedema presented to the Emergency Department with swelling of the lips, tongue, and throat developing four hours after her first injection of compounded semaglutide for weight loss. She was treated with epinephrine, corticosteroids, and antihistamines, but due to progressive airway edema, she required intubation and mechanical ventilation for four days. After extubation, she reported accidentally injecting a ten-fold higher dose (2 mg) of semaglutide than was appropriate for the first dose. The hospitalization was complicated by hypoglycemia requiring dextrose infusion, but was otherwise unremarkable, and she was discharged home on day 7. Based on the temporal onset after semaglutide injection, this presentation was most consistent with GLP-1 RA-induced angioedema. While she also had a history of lisinopril-induced angioedema five years earlier, and had been taking valsartan for hypertension, the remoteness of the lisinopril exposure made this less likely. Conclusions: Semaglutide use may be associated with severe angioedema within hours of administration. Given the overlapping indications and patient populations, angioedema appearing in patients taking both GLP-1 RAs and ACE inhibitors may become increasingly common and present a diagnostic dilemma. Diagnosis of hypersensitivity to GLP-1 RAs can be supported with history and positive skin testing. Clinicians should be aware that inexperienced patients are at the highest risk of dosing errors. Full article

Adverse drug reactions (ADRs) remain a major clinical challenge and a leading cause of morbidity and mortality worldwide. Among them, severe cutaneous adverse drug reactions (SCARs), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), represent life-threatening immune-mediated hypersensitivity responses strongly associated with specific human leukocyte antigen (HLA) alleles. Despite well-established pharmacogenetic associations, current diagnostic strategies remain largely retrospective and lack predictive capability for novel drug–HLA risk pairs. Here, we present an integrative network-informed machine learning framework for predicting HLA-associated SCAR risk by combining pharmacogenomic features, drug chemical structure, and topological descriptors derived from drug–drug and drug–symptom interaction networks. An Extreme Gradient Boosting (XGBoost) classifier trained on integrated HLA allele and drug features, labeled using curated HLA–SCAR associations, achieved an accuracy of 0.860 ± 0.005, an F1-score of 0.689 ± 0.010, with an area under the receiver operating characteristic curve (AUROC) of 0.922 ± 0.003 and an area under the precision–recall curve (AUPRC) of 0.768 ± 0.007. Notably, several predicted positive associations absent from the training data corresponded to biologically plausible and literature-supported cases, including carbamazepine—HLA-B*15:11, supporting the model’s ability to generalize beyond known associations. Molecular docking provides structural evidence for the predicted associations, highlighting allele-specific binding patterns underlying these results. Overall, our results demonstrate that network-informed machine learning provides a proactive and integrative approach to SCAR risk prediction and may support early risk stratification and personalized drug safety assessment in precision medicine. Full article

Background/Objective: The present case demonstrates the successful preservation of a severely inflamed dental pulp despite uncontrolled bleeding occurring during pulpotomy. This novel therapeutic approach was developed when a 7-year-old boy presented for endodontic treatment one week after sustaining a crown-root fracture in an immature incisor. The tooth exhibited slight hypersensitivity to cold testing, with no tenderness to percussion or palpation. An exposed pulp was present; however, when he could avoid contact with the exposed pulp tissue, the patient reported no symptoms. Methods: The critical determinant of success when uncontrolled pulpal bleeding occurred following pulpotomy was the stepwise treatment in two visits and the bacteria-tight seal of the access cavity. The seal was achieved through the incremental application of the temporary filling material. A calcium hydroxide preparation was applied as interappointment topical pulp dressing. Four weeks after the initial visit the pulpotomy could be accomplished. Results: During 3.5 years of follow-up, the patient remained without symptoms and the tooth showed ongoing root growth in length and width combined with positive reaction to electric pulp testing. Conclusions: In summary, this case demonstrates that, despite persistent bleeding following pulpotomy, pulpal vitality can be preserved, thereby promoting continued root development. Full article

Background: Anti-MRSA agents are essential for treating severe infections, yet their use is constrained by distinct toxicity profiles. However, comparative real-world data remain scarce. Methods: This nationwide pharmacovigilance study used the Japanese Adverse Drug Event Report (JADER) database (2004–2025). Disproportionality analyses (proportional reporting ratio [PRR]) were performed at the Standardized MedDRA Query and Preferred Term levels, complemented by Weibull-based time-to-onset modeling, to characterize AE patterns associated with vancomycin (VCM), teicoplanin (TEIC), arbekacin (ABK), daptomycin (DAP), linezolid (LZD), and tedizolid (TZD). Results: Distinct agent-specific AE profiles were observed. VCM showed disproportionate reporting of acute renal failure (PRR 6.66) and severe cutaneous reactions. TEIC displayed fewer renal signals but relatively higher reporting of hematologic events (PRR 3.51). ABK demonstrated high disproportionality in acute and chronic renal failure, reflecting aminoglycoside nephrotoxicity. DAP showed a high reporting signal for eosinophilic pneumonia (PRR 23.30), interstitial lung disease, and creatine kinase elevation/rhabdomyolysis, with wear-out hazard patterns suggesting a possible time-dependent reporting tendency. LZD exhibited hematopoietic signals (PRR 6.13) and additional associations with hyponatremia, lactic acidosis, and optic neuropathy, consistent with marrow suppression and mitochondrial toxicity. Weibull analysis indicated cumulative “wear-out” risks for renal, hepatic, and hematologic events, whereas hypersensitivity and many pulmonary events followed random-failure patterns. Conclusions: This large-scale JADER analysis delineated the distinct safety profiles of the six anti-MRSA agents. The key findings included DAP pulmonary and muscle toxicities, LZD hematological events, and VCM nephrotoxicity. Time-to-onset modeling indicates potential cumulative versus random risk patterns, suggesting the need for individualized monitoring and cross-validation. Full article

Kounis syndrome (KS) describes the occurrence of acute coronary syndromes precipitated by allergic, hypersensitivity, or anaphylactic reactions and represents a unique intersection between immunologic activation and cardiovascular disease. The epidemiology of KS is likely underestimated due to diagnostic overlap with other cardiac and allergic conditions and limited awareness across medical specialties. This narrative review focuses on the distinctive features of KS in special populations, emphasizing how patients’ age, comorbidities, immune status, and vascular substrate modify presentation, diagnosis, and outcomes. In elderly patients, polypharmacy, increased plaque vulnerability, and endothelial dysfunction favor Type II and III KS. Pediatric cases, although rare, are predominantly Type I and strongly associated with food allergies, insect stings, vaccines, and antibiotics, with under-recognition driven by diagnostic bias and ethical concerns surrounding invasive testing. Patients with coronary stents, cardiac devices, chronic kidney disease, and those receiving dialysis exhibit heightened susceptibility due to chronic inflammation, foreign-body hypersensitivity, and prothrombotic states. Pregnancy and the peripartum period represent a unique immuno-hemodynamic milieu in which Th2 immune shift, increased coronary vasoreactivity, and obstetric triggers can compromise both maternal and fetal perfusion. Additional risk modulation is observed in atopic individuals, asthmatics, patients with autoimmune, inflammatory, oncologic, psychiatric, and neurodevelopmental conditions, as well as in COVID-19 and post-infectious states. We propose a host-modified framework for KS that complements traditional classification by integrating immune phenotype and vascular substrate, enabling improved risk stratification and personalized preventive strategies. Full article

Cross-reactivity among nonsteroidal anti-inflammatory drugs (NSAIDs) creates a significant clinical difficulty, especially in patients with NSAID hypersensitivity. These reactions are based on cyclooxygenase-1 (COX-1) inhibition and non-immunoglobulin E (IgE)-mediated reactions. COX-1 inhibition leads to dysregulation of arachidonic acid metabolism, with decreased prostaglandin synthesis and increased leukotriene production. Clinically, cross-intolerant reactions manifest in different phenotypes, including NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), and NSAID-exacerbated cutaneous disease (NECD). In contrast, true allergic reactions—such as single-NSAID-induced urticaria/angioedema and anaphylaxis (SNIUAA) and single-NSAID-induced delayed hypersensitivity reactions (SNIDHR)—are immunologically mediated and drug-specific. These phenotypes differ in underlying conditions, clinical manifestations, and patterns of NSAID tolerance. Paracetamol is generally considered a safer alternative due to its weak COX-1 inhibition; however, reactions may still occur, particularly at higher doses. Selective COX-2 inhibitors are usually better tolerated, however their safety should be confirmed, preferably through controlled drug provocation testing due to sporadic reactions in cross-intolerant patients. Understanding the distinction between pharmacologically mediated cross-intolerance and true allergic reactions is essential for accurate diagnosis, risk stratification, and therapeutic decision-making. This review summarizes current evidence on the mechanisms underlying NSAID hypersensitivity, analyzes the tolerability of paracetamol and alternative analgesics, and discusses practical management strategies to reduce the risk of adverse reactions. Full article

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

Background: Hypersensitivity reactions to antineoplastic agents are an increasing clinical challenge due to their rising incidence and potential severity. Early allergological assessment and tailored drug re-exposure strategies may allow continuation of essential therapies, although real-world data remain limited. Methods: We conducted a monocentric retrospective observational study including adult oncologic patients with suspected chemotherapy-induced hypersensitivity reactions. Clinical features, allergological work-up, and management strategies were analyzed. The primary outcome was the success rate of drug reintroduction using desensitization or enhanced premedication. Secondary outcomes included skin test positivity rates and the association between cumulative chemotherapy exposure and anaphylaxis. Results: Forty-two patients were included (95% female; median age 57.5 years). Re-exposure was required in 18 patients, and was successful in all patients undergoing desensitization and in 92% of those managed with enhanced premedication. Skin testing was positive in 71% of suspected platinum reactions, 30% of taxanes, and 40% of biologic agent reactions. Anaphylaxis occurred in 26.2% of patients, and a trend toward an association with cumulative chemotherapy exposure was observed; each additional cycle was associated with a 28% increase in the odds of anaphylaxis (adjusted OR 1.28; 95% CI, 1.00–1.63). Conclusions: Desensitization and enhanced premedication allow safe reintroduction of antineoplastic agents. Cumulative chemotherapy exposure is associated with an increased risk of anaphylaxis. Full article

Etoposide is a key component of many frontline and salvage chemotherapy regimens in pediatric oncology. However, its clinical use may be complicated by acute hypersensitivity reactions, which can disrupt treatment continuity and compromise therapeutic efficacy. Recent pediatric studies indicate that the incidence of etoposide-associated hypersensitivity is higher than historically reported and varies according to disease type and administration conditions. This narrative review provides a comprehensive overview of etoposide hypersensitivity in children, integrating clinical, immunological, and pharmaceutical perspectives. Current evidence suggests that true IgE-mediated type I hypersensitivity is uncommon in pediatric patients, whereas most reactions are consistent with non-IgE-mediated mechanisms, often related to formulation excipients such as polysorbate 80 and ethanol. We discuss the clinical features and differential diagnosis of acute reactions associated with etoposide administration, including hypersensitivity reactions and infusion-related reactions, such as ethanol-related toxicity. In addition, modifiable risk factors, preventive measures, and management strategies—such as infusion optimization, alternative formulations, and rapid desensitization protocols—are critically reviewed. A mechanism-based approach to etoposide hypersensitivity is essential to ensure patient safety while maintaining treatment intensity in pediatric cancer care. Full article

Background: The clinical intra-anesthetic changes of perioperative hypersensitivity (POH) are not specific and require a thorough differential diagnosis with other mimicking conditions. Biomarkers such as tryptase and histamine provide supportive evidence for POH. From the suggested cutoffs, a common decision threshold has not been validated for use in daily practice. The aim of this systematic review and meta-analysis is to identify biomarkers investigated for POH and to evaluate their diagnostic performance. Methods: This meta-analysis included original diagnostic accuracy studies comparing patients with clinically suspected POH and controls with no signs of intraoperative hypersensitivity reactions, in whom allergy biomarkers were evaluated, aiming to investigate diagnostic performance of the assays. Data was pooled to evaluate sensitivity and specificity. Results: In seven studies on tryptase and three studies on histamine dosing for the diagnosis of POH/POA, different fixed or dynamic thresholds for positivity were proposed. For tryptase, fixed thresholds had 59.8% sensitivity and 95.2% specificity for an optimal cutoff of 12.68 ng/mL, while dynamic thresholds yielded 77.2% sensitivity and 88.5% specificity. For histamine, fixed cutoffs presented 78% sensitivity and 85% specificity, while dynamic thresholds investigated in a single study yielded 78.2% sensitivity and 91.1% specificity. Estimates for histamine are unreliable due to limited data. Conclusions: From published data, tryptase is clearly the most robust biomarker, dynamic thresholds boost sensitivity without major specificity loss and confirm the added diagnostic value of relative changes over fixed absolute cutoffs. Preliminary results suggest that histamine might have optimal diagnostic performance, but estimates are severely limited by small sample sizes. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most consumed drugs worldwide and the main cause of drug hypersensitivity reactions (HSRs). The most common NSAID-HSR class is cross-hypersensitivity (CR), with patients reacting to NSAIDs from different chemical groups without specific immunological recognition, with NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype. Although CR-HSRs are triggered by arachidonic acid (AA) alterations following cyclooxygenase (COX)-1 inhibition and cysteinyl-leukotrienes synthesis by 5-lypoxygenase (5-LO), current evidence supports the participation of additional mechanisms. As COX-1 and 5-LO head oxidative pathways, it is conceivable that enzymes participating in antioxidant control are involved in these mechanisms. In addition, as the CR-HSR susceptibility seems to be influenced by genetic factors, the possibility of genetic variants playing a role in such enzymes should not be excluded. Methods: In this observational case–control study, we analysed for the first time in NIUA the overall genetic variability in key antioxidant defence enzymes genes, including catalase (CAT), glutathione peroxidase (GPX)-1 and 3, and superoxide dismutase (SOD)-1. We selected a set of tagging single nucleotide polymorphisms (tSNPs) in these genes using data from Europeans in the 1000 Genomes Project. Two independent Spanish populations (discovery and replication) of NIUA patients and NSAID-tolerant individuals were included. Results: Twenty-six tSNPs were genotyped in the discovery population, with three that were significantly associated with NIUA: rs3448 (GPX-1), rs3792798 (GPX-3), and rs10432782 (SOD-1). They were then genotyped in the replication group, with rs3792798 being protective and rs10432782 being associated with an increased NIUA risk. Conclusions: Our results suggest that a role for antioxidant enzyme polymorphisms in NIUA is required. Nevertheless, further research is needed to replicate our findings in other populations and their meaning at the molecular level and to investigate the role of such variants in other CR-HSR-induced phenotypes. Full article

Background/Objectives: After several decades of using titrated paclitaxel infusions, our institution adopted non-titrated infusions in April 2023 to streamline infusion workflows. We aimed to evaluate whether this alteration in infusion was associated with a higher incidence of HSRs. Methods: This was a retrospective cohort study of patients receiving paclitaxel with titration versus non-titration from April 2022 through November 2023. Patients diagnosed with gynecologic cancers who presented for their first or second paclitaxel lifetime infusions were included. Results: A total of 150 patients were included in this study, each with one or two infusions, for a total of 282 infusion visits. There were 176 infusions performed with titrated paclitaxel (62.4%), and 106 infusions performed with non-titrated paclitaxel dose (37.6%). HSRs occurred in 20.8% of the non-titrated paclitaxel infusions and in 11.9% of titrated paclitaxel infusions (RR 1.73 (95% CI 1.006–3.006), p = 0.047). Additionally, when stratifying by first- or second-visit infusions, the HSR rate increased significantly for non-titrated infusions to 22.4% during the second visit, while there was a decrease to 8.4% for titrated infusions (RR 2.66 (95% CI 1.105–6.413), p = 0.029). Non-titrated infusion reactions were associated with higher grades of reaction. Conclusions: HSRs occurred more frequently with non-titrated infusions, particularly during the second administration, suggesting that eliminating titration may increase hypersensitivity risk. These findings support a prospective evaluation of titration rates to further refine paclitaxel administration. Full article