Search Results (64)

Background/Objectives: Cutaneous adverse drug reactions (CADRs) represent the most common manifestations of drug-induced allergy, with most unfavorable clinical outcomes seen in severe cutaneous adverse reactions (SCARs). To manage SCARs immediate cessation of the offending drug is needed; therefore, it is crucial to identify the list of medications associated with SCARs in real-world clinical practice. The objective of this study was to evaluate the structure of drugs associated with SCARs and to analyze drug-induced SCAR signals by calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR) based on spontaneous reports extracted from the Russian national pharmacovigilance database. Methods: A retrospective, descriptive pharmacoepidemiological analysis of spontaneous reports (SRs) registered in the pharmacovigilance database from 1 April 2019 to 31 March 2025. Results: A total of 7011 SRs with SCARs were finally revealed, with 907 identified drug triggers. The most frequently reported were antibacterial drugs for systemic use (22.8%), antineoplastic agents (17.8%), and antiepileptics (6.0%). The top five drugs involved in SCARs were dupilumab (2.14%, n = 244), piperacillin and beta-lactamase inhibitor (2.0%, n = 227), pembrolizumab (1.98%, n = 225), levofloxacin (1.95%, n = 222), and linagliptin (1.93%, n = 220). The strongest signals were detected for linagliptin (PRR = 15.37, 95% CI: 13.54–17.44; ROR = 17.24, 95% CI: 14.95–19.88), followed by clindamycin (PRR = 12.44, 95% CI: 10.89–14.21; ROR = 13.62, 95% CI: 11.77–15.77) and by piperacillin and beta-lactamase inhibitor (PRR = 10.02, 95% CI: 8.86–11.43; ROR = 10.81, 95% CI: 9.42–12.40). Conclusions: Pharmacovigilance databases facilitate the identification of diverse phenotypes of SCARs and the list of culprit drugs. The accumulated data serve as a valuable tool to enhance clinical practice outcomes and strengthen overall healthcare monitoring. Full article

Autophagy is a conserved process that involves the degradation of damaged proteins and organelles to restore cellular homeostasis. Autophagy plays a critical role in cell differentiation, immune responses, and protection against pathogens, as well as the development and progression of allergic inflammation. Crosstalk between autophagy and signaling pathways modulates immune responses to inflammatory signals. Here, we discuss the regulatory roles of autophagy in allergic inflammation. Autophagy can promote allergic inflammation by enhancing the secretion of inflammatory mediators. Impaired autophagy resulting from the accumulation of autophagosomes can exacerbate allergic inflammation. Mast cell degranulation and activation require energy provided by mitochondrial respiration. Mast cell activation is accompanied by morphological changes and mitochondrial fragmentation. Mitochondrial fragmentation (mitophagy) induced by oxidative stress involves the degradation of defective mitochondria. Therefore, we discuss the relationship between mitophagy and allergic inflammation. Targeting autophagy and oxidative stress can be a strategy for developing anti-allergy therapeutics. In this review, we also discuss future research directions to better understand allergic diseases with respect to autophagy and develop effective anti-allergy drugs. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause hypersensitivity reactions and lead to anaphylactic shock. These drugs also act as cofactors in allergic reactions. Lipid transfer proteins (LTPs), found in plants, represent a unique group of allergens in which cofactors play a crucial role. This case report describes a 26-year-old female who developed anaphylactic symptoms after ingesting grapes and taking ketoprofen. The patient experienced swelling of the lips, tongue, and throat, as well as shortness of breath, dizziness, and loss of consciousness, after consuming grapes and taking ketoprofen. She had previously used ketoprofen and acetylsalicylic acid without issues but had developed urticaria on several occasions after consuming multi-ingredient dishes. Skin prick tests showed positive results for peanut and orange allergens. Further testing using the ALEX multiparametric test detected antibodies to several LTP allergens. Intradermal tests with ketoprofen yielded a positive result, although irritant reactions could not be ruled out. A provocation test with acetylsalicylic acid (ASA) showed no adverse reactions. Skin tests with ibuprofen were negative, and provocation tests confirmed its tolerance. A diagnosis of LTP allergy and selective ketoprofen allergy was made, with the recommendation to avoid ketoprofen and follow a diet excluding foods from the LTP group. Full article

Introduction: Hypoglossal nerve stimulation (HNS) “Inspire_© therapy” has garnered popularity among obstructive sleep apnea (OSA) patients seeking an alternative to continuous positive airway pressure (CPAP) therapy. The growth in HNS has been particularly high in older adults living with OSA. Consistent and proper use of HNS in the geriatric population faces unique age-associated barriers: a high rate of multiple chronic conditions (MCC) and polypharmacy (being on five or more drugs). Early recognition and patient-centered management of these barriers will allow older patients to obtain maximum benefits from HNS. HNS has distinct advantages in the geriatric population because it overcomes many concerns related to CPAP therapy adherence, such as mechanical limitations due to manual dexterity, maxillofacial anatomy, dental issues such as usage of dentures, allergy/otolaryngology-related disorders, and pre-existing post-traumatic stress disorder-related claustrophobia. This paper describes how we worked with older patients with OSA and their care partners to overcome these barriers so patients can continue to derive cardiovascular, neurologic, and quality of life benefits resulting from optimal OSA management. These benefits are especially important in the older population because of higher rates of comorbidities (dementia, coronary artery disease, and atrial fibrillation) exacerbated by sub-optimally treated OSA. In this article, we describe our clinical experience with elderly patients on Inspire_© therapy, with a focus on the everyday difficulties faced by these patients and the measures implemented to address and mitigate these barriers. Methods: A retrospective chart review was conducted to identify patients aged 65 and above who underwent hypoglossal nerve stimulator insertion. Experiences of older patients during and after the insertion procedure were documented and compared to a younger population of patients on HNS therapy. We specifically collected information on difficulties encountered during activation or follow-up visits and compared them between the different age groups. Using this information, we identified areas to improve treatment adherence from the patients’ perspectives. Results: We identified 43 geriatric (65 to 86 years old) patients who received the Inspire implant at a tertiary academic medical center and compared them to a younger population of 23 patients. Most common challenges noted—with a potential to impact adherence—included orofacial and lingual neuropraxia (ischemic or demyelination-induced neuropathy) at activation, cognitive dysfunction (memory problems), preexisting anxiety, and insomnia. Other difficulties that are less commonly reported but equally important to consistent and proper use of HNS included headaches, concerns of device malfunction, change in comfort levels after cardiac procedures, and general intolerance of the device. The older patient population had a statistically significant higher incidence of cognitive difficulties (30.2% vs. 4.4%) and a smaller social support system (62.8% vs. 91.3%) affecting device usage compared to the younger population. There were no statistically significant differences in the rates of other more commonly reported adverse effects such as headaches, dry mouth, and anxiety between the two age groups. Conclusion: Despite several challenges faced by geriatric patients, Inspire_© hypoglossal nerve stimulation remains a viable, alternative treatment option for OSA with improved tolerance and adherence compared to CPAP. After identifying less commonly reported barriers such as cognitive decline, sensory deficits, and decreased social support systems, minor adjustments and appropriate education on use allows older patients to correctly use and benefit from Inspire_© device therapy, with subsequent improvement in sleep and overall quality of life. Full article

Background/Objectives: Docetaxel is a potent anti-cancer agent capable of treating various types of cancer. However, it often induces a range of adverse reactions when used with its standard solubilizer, Tween-80, necessitating allergy prophylaxis with dexamethasone prior to administration. To mitigate the risk of allergic reactions, with nanomicelles garnering significant interest due to their enhanced solubility and thermodynamic stability. Methods: In this research, a mPEG-PLA-Lys(Fmoc) micellar carrier with m = 45 and n = 10 was engineered to encapsulate docetaxel, and its self-assembly into micelles was investigated. Additionally, allergic reaction studies were conducted on animals. Results: The findings indicated that the formulation did not cause hemolysis, vascular, or muscle irritation in rabbits, nor did it elicit an allergic response in guinea pigs. Conclusions: These results suggest that nanomicelle-encapsulated docetaxel can diminish the allergic reactions associated with docetaxel injections, offering a novel approach to enhance the therapeutic utility of this outstanding anti-cancer drug. Full article

Tick-bite hypersensitivity encompasses a range of clinical manifestations, from localized allergic reactions to systemic conditions like alpha-gal syndrome (AGS), an IgE-mediated allergy to galactose-α-1,3-galactose (α-Gal). This study investigated the clinical, molecular, immunological, and genetic features of two hypersensitivity cases. Two cases were analyzed: a 30-year-old woman with fixed drug reaction (FDR)-like hypersensitivity and a 10-year-old girl with AGS exhibiting borderline α-Gal-specific IgE. Diagnostic methods included allergen-specific IgE quantification, HLA genotyping, histopathological examination, and the molecular detection of tick-borne pathogens using microfluidic PCR. Case I demonstrated histopathological features of chronic lymphocytic inflammation and eosinophilic infiltrates, with HLA-B13 and DRB113 alleles indicating genetic susceptibility to hypersensitivity, while histological findings suggested a localized FDR-like reaction. Case II exhibited borderline α-Gal-specific IgE, resolving completely with a mammalian-free diet. The presence of HLA-DRB101 and DQB1*05 in the second patient indicated a genetic predisposition to AGS and other atopic conditions. No infectious etiology was identified in either case. These findings emphasize the heterogeneity of tick-related hypersensitivity and the importance of HLA genotypes in susceptibility. Comprehensive molecular, immunological, and genetic profiling offers valuable insights into the mechanisms of hypersensitivity, supporting personalized approaches for the diagnosis and management of tick-induced allergic conditions. Full article

Anaphylaxis is a potentially life-threatening systemic allergic reaction that can result in fatal outcomes if not promptly and appropriately treated. The diagnosis of the cause of anaphylaxis during anesthesia can be challenging due to the complexity of the perioperative environment. Propofol-induced perioperative anaphylaxis is uncommon, occurring in perioperative anaphylactic shock cases. We present a case of perioperative anaphylactic shock in a patient with no known allergies who had been exposed to the same anesthetic agents, propofol, rocuronium, and remifentanil, three times previously without incident. Cardiac arrest occurred 50 min after induction, which showed pulseless electrical activity with decreasing saturation without bronchial spasm and skin erythema or edema. After prompt and appropriate management including cardiopulmonary resuscitation, the patient recovered without complications. The diagnosis was confirmed as propofol-induced anaphylactic shock by an elevated serum tryptase level, measured in a timely manner, and by skin tests (skin prick test and intradermal test), which revealed strong hypersensitivity to propofol. This case is notable for the cardiovascular collapse that occurred without respiratory symptoms or skin manifestations, as well as the delayed onset of anaphylaxis (>50 min). This case underscores the importance of vigilance for anaphylaxis, even with repeated exposure to previously well-tolerated drugs, as sensitization can lead to more severe reactions. It also highlights the potential for anaphylaxis to occur outside the acute phase and without typical clinical features. Full article

The diagnosis of drug-induced anaphylaxis (DIA) is a serious health problem. The Basophil activation test (BAT) is considered a specific in vitro provocation, and compared to in vivo provocation, it is more convenient, cheaper, and safer for the patient. This study aimed to evaluate the usefulness of the BAT in the diagnosis of DIA. This study included 150 patients referred to a reference allergy clinic with suspected drug allergies. All patients underwent a detailed clinical evaluation supplemented with the BAT. Positive BAT results were obtained in two out of 21 patients who were to receive the COVID-19 vaccine. The sensitivity and specificity of the BAT were 40% and 75% for the COVID-19 vaccine, 67% and 58% for DMG PEG 2000, and 100% and 75% for PEG 4000, respectively. Nine out of 34 patients with suspected antibiotic allergies had positive BAT results with 14 different antibiotics. Positive BAT results were also obtained with NSAIDs in two patients and with local anesthetics in three patients. The confirmation of allergy by the BAT improves the safety profile of the diagnostic work-up as it may defer the need for drug provocation, preventing potential anaphylactic reactions. Full article

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis. Full article

Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE–allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children. Full article

(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level. Full article

Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North Americans and 20% of the world’s population are impacted by some form of allergy and it continues to increase in prevalence, especially among children. Specified IgE antibodies can be found in almost all cases of exposure to seasonal or perennial allergens. Activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins. The release of these factors initiates the recruitment of inflammatory cells in the conjunctival mucosa, which causes the late-phase reaction. Signs and symptoms of ocular allergies include itching, tearing, chemosis, and hyperemia, which can lead to decreased productivity and poor quality of life. Many treatment options are available to improve symptoms, including, mast cell stabilizers, antihistamines, dual-acting agents, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and other off-label treatment modalities. This review article provides an overview of different types of allergic conjunctivitis, its pathology and immunology, and recommended methods of treatment. Full article

Nur77 belongs to the NR4A subfamily of orphan nuclear hormone receptors. It has been shown to play important roles in metabolism, cancer progression, cellular differentiation, and the regulation of immune process. However, there has yet to be research reporting on the role of Nur77 in allergic inflammations such as anaphylaxis. This study aimed to identify molecules that could mediate allergic inflammations. To this end, we performed RNA sequencing analysis employing bone marrow-derived mast cells (BMMCs). Antigen (DNP-HSA) stimulation increased the expression levels of transcription factors such as Nr4a3 (NOR1), Nr4a1 (Nur77), and Nr4a2 (Nurr1). We focused our study on Nur77. Antigen stimulation increased the expression of Nur77 in a time- and dose-dependent manner in rat basophilic leukemia cells (RBL2H3). The downregulation of Nur77 prevented both antigen-induced increase in β-hexosaminidase activity as well as hallmarks of allergic reactions such as HDAC3, COX2, and MCP1 in RBL2H3 cells. Nur77 was necessary for both passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA). TargetScan analysis predicted that miR-21a would be a negative regulator of Nur77. miR-21a mimic negatively regulated PCA and PSA by inhibiting the hallmarks of allergic reactions. ChIP assays showed that c-JUN could bind to the promoter sequences of Nur77. Antigen stimulation increased the expression of c-JUN in RBL2H3 cells. Altogether, our findings demonstrate the regulatory role played by Nur77-miR-21a loop in allergic inflammations such as anaphylaxis, making this the first report to present the role played by Nur77 in an allergic inflammation. Our results suggest that Nur77 and miR-21 might serve as targets for developing anti-allergy drugs. Full article

This study aimed to identify and evaluate drug candidates targeting the kinase inhibitory region of suppressor of cytokine signaling (SOCS) 3 for the treatment of allergic rhinitis (AR). Utilizing an artificial intelligence (AI)-based new drug development platform, virtual screening was conducted to identify compounds inhibiting the SH2 domain binding of SOCS3. Luminescence assays assessed the ability of these compounds to restore JAK-2 activity diminished by SOCS3. Jurkat T and BEAS-2B cells were utilized to investigate changes in SOCS3 and STAT3 expression, along with STAT3 phosphorylation in response to the identified compounds. In an OVA-induced allergic rhinitis mouse model, we measured serum levels of total IgE and OVA-specific IgE, performed real-time PCR on nasal mucosa samples to quantify Th2 cytokines and IFN-γ expression, and conducted immunohistochemistry to analyze eosinophil levels. Screening identified 20 hit compounds with robust binding affinities. As the concentration of SOCS3 increased, a corresponding decrease in JAK2 activity was observed. Compounds 5 and 8 exhibited significant efficacy in restoring JAK2 activity without toxicity. Treatment with these compounds resulted in reduced SOCS3 expression and the reinstatement of STAT3 phosphorylation in Jurkat T and BEAS-2B cells. In the OVA-induced allergic rhinitis mouse model, compounds 5 and 8 effectively alleviated nasal symptoms and demonstrated lower levels of immune markers compared to the allergy group. This study underscores the promising nonclinical efficacy of compounds identified through the AI-based drug development platform. These findings introduce innovative strategies for the treatment of AR and highlight the potential therapeutic value of targeting SOCS3 in managing AR. Full article

Methadone is an effective and long-lasting analgesic drug that is also used in medication-assisted treatment for people with opioid use disorders. Although there is evidence that methadone activates μ-opioid and Toll-like-4 receptors (TLR-4s), its effects on distinct immune cells, including mast cells (MCs), are not well characterized. MCs express μ-opioid and Toll-like receptors (TLRs) and constitute an important cell lineage involved in allergy and effective innate immunity responses. In the present study, murine bone-marrow-derived mast cells (BMMCs) were treated with methadone to evaluate cell viability by flow cytometry, cell morphology with immunofluorescence and scanning electron microscopy, reactive oxygen species (ROS) production, and intracellular calcium concentration ([Ca²⁺]i) increase. We found that exposure of BMMCs to 0.5 mM or 1 mM methadone rapidly induced cell death by forming extracellular DNA traps (ETosis). Methadone-induced cell death depended on ROS formation and [Ca²⁺]i. Using pharmacological approaches and TLR4-defective BMMC cultures, we found that µ-opioid receptors were necessary for both methadone-induced ROS production and intracellular calcium increase. Remarkably, TLR4 receptors were also involved in methadone-induced ROS production as it did not occur in BMMCs obtained from TLR4-deficient mice. Finally, confocal microscopy images showed a significant co-localization of μ-opioid and TLR4 receptors that increased after methadone treatment. Our results suggest that methadone produces MCETosis by a mechanism requiring a novel crosstalk pathway between μ-opioid and TLR4 receptors. Full article