Search Results (168)

Background and Clinical Significance: Infective endocarditis (IE) is a serious condition with rising incidence, frequently caused by Staphylococcus aureus. However, cases involving rare congenital anomalies such as Gerbode’s defect are uncommon. Case Presentation: This report presents the first documented case of IE in a patient with a congenital Gerbode defect complicated by DRESS syndrome—a severe, drug-induced hypersensitivity reaction typically triggered by antibiotics like oxacillin. A 65-year-old woman developed infective endocarditis involving vegetations on the cardiac device lead, the tricuspid valve, and adjacent to a Gerbode defect. The diagnosis was confirmed by positive blood cultures and echocardiographic findings. She received treatment with oxacillin. Subsequently, she exhibited clinical features consistent with DRESS syndrome, including rash, eosinophilia, and multi-organ involvement. Rapid recognition and management, including corticosteroid therapy and antibiotic modification, led to clinical improvement. Conclusions: This case highlights the importance of vigilance for DRESS syndrome in prolonged antibiotic therapy for IE, especially in the context of rare congenital cardiac anomalies. In addition, guidelines are needed to optimize the diagnosis and treatment of this potentially lethal complication. 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

Herein, we present scanning electron microscopy imagery of Demodex folliculorum on the eyelashes of a patient with a two-year history of dry, burning, and watery eyes. Demodex mites are part of the normal human skin flora, inhabiting hair follicles and sebaceous glands. However, in some individuals, they may contribute to ocular surface diseases, including blepharitis and dry eye disease. Symptoms often include itching, photophobia, and a foreign body sensation. The pathogenic role of Demodex is not fully understood but may involve microabrasions, gland obstruction, hypersensitivity reactions, and bacterial dysbiosis. The presence of collarettes at the base of eyelashes is a diagnostic hallmark. Although optimal treatment remains debated, options include topical tea tree oil, ivermectin, and a recently FDA-approved drug lotilaner. Our patient responded favorably to a two-month regimen of tea tree oil-based eyelid wipes. This case underscores the clinical relevance of Demodex infestation in chronic ocular discomfort and highlights the importance of diagnostics. Full article

A 10-year-old male neutered British Shorthair cat with diabetes mellitus presented with an acute onset of unilateral swelling, erythema, alopecia and coalescing ulcerations of the face and periocular skin. Initial clinical differential diagnoses were trauma, infections (including feline respiratory viruses), arthropod bites, and eosinophilic dermatoses such as eosinophilic granuloma complex, mosquito-bite hypersensitivity and cutaneous adverse drug reaction. Histopathology revealed fulminant furunculosis with abundant eosinophils and vasculitis. Initial topical glucocorticoid treatment partially improved the clinical signs but severely raised serum glucose levels. As a result, systemic glucocorticoids and ciclosporin were not considered optimal treatments, and the off-label and short-term use of oclacitinib was chosen with the owner’s informed consent. This treatment induced fast remission of clinical signs with no recurrence for 17 months. Secondary fusion of the eyelids caused by cicatrization was surgically reconstructed to restore full function. Full article

Lamotrigine is the drug of choice for the treatment of depressive episodes in bipolar disorder (BD). Despite its generally favorable tolerability profile, lamotrigine use is associated with a risk of Cutaneous Adverse Drug Reactions (cADRs), including Stevens–Johnson Syndrome (SJS) and Lyell’s syndrome, also known as toxic epidermal necrolysis (TEN). Genetic markers HLA and, in particular, HLA-B 15:02 and HLA-A 31:01 are crucial in predicting individuals’ susceptibility to developing the symptoms. The symptoms are triggered by type IV hypersensitivity developing because of CTL and NK cell activation, leading to keratinocyte apoptosis, epidermal necrosis and skin detachment. The exact pharmacotherapy that should be widely utilized in treating affected patients has not yet been established. New therapies including JAK inhibitors or cyclosporine show potential in improving outcomes by reducing mortality and enhancing the period of recovery. Key factors in preventing cADRs may include adequate patient observation, gradual titration of the patient’s dose, and reduction of risk factors through screening for HLA polymorphisms. When the initial symptoms of cADR are identified, it is imperative to make an immediate decision to discontinue treatment, as this can significantly reduce the risk of progression to SJS/TEN and systemic complications. The purpose of this review is to identify a significant correlation between lamotrigine use in BD and the occurrence of SJS by showing the risk factors, neuropharmacological mechanisms, immune response and correctness of pharmacotherapy. Full article

Background/Objectives: Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM), both immediate and non-immediate, pose clinical challenges despite using low-osmolality agents. This review aims to summarize current diagnostic approaches, cross-reactivity patterns, and the debated role of premedication. Methods: A narrative review was conducted using PubMed (2014–2024), selecting studies on ICM-related HSRs, focusing on skin and in vitro testing, drug provocation tests (DPTs), cross-reactivity, and premedication. Results: Skin tests show limited sensitivity, especially for non-immediate reactions. Cross-reactivity among ICMs is common but unpredictable. DPTs are the diagnostic gold standard but lack standardized protocols. Premedication is frequently used, though its efficacy remains uncertain. Conclusions: The management of ICM hypersensitivity is limited by diagnostic gaps and insufficient evidence on premedication. Standardized protocols and prospective studies are needed to improve patient safety and guide clinical decisions. Full article

Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. In eligible patients, hypomethylating agents are used as a bridge for allogeneic stem cell transplantation, currently the only curative approach in these malignancies. The most common side effects of hypomethylating agents are myelosuppression, cutaneous injection site reactions (when azacitidine is given subcutaneously), and gastrointestinal symptoms. Uncommon, disabling, and long-lasting side effects represent a threat to effective treatment in this group of patients. Case Presentation: We describe the case of a 49-year-old male patient with IPSS-M intermediate-risk MDS, intended to receive first-line treatment with azacitidine followed by allogeneic stem cell transplantation. The first, late-onset azacitidine reaction was observed 48 h after the first exposure, with cutaneous and respiratory toxicity, followed by the late-onset recurrence of symptoms after azacitidine withdrawal and decitabine introduction. Conclusions: This case highlights atypical, disabling, and long-lasting drug reactions to two hypomethylating agents, with the persistence of hypersensitivity manifestations months after medication withdrawal. Full article

Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs. Full article

Background and Objectives: Drug provocation tests (DPTs) diagnose drug hypersensitivity reactions (DHRs) and identify safe alternatives. DHRs contribute to patient anxiety. The aim of this study was to evaluate anxiety and hopelessness levels before and after DPT and to examine patients’ avoidance characteristics of the tested drugs. Materials and Methods: Patients undergoing DPT were included. The State–Trait Anxiety Inventory (STAI) assessed anxiety, and the Beck Hopelessness Scale measured hopelessness. Demographic and clinical data, pre- and post-DPT scores, the status of using the medication provided after DPT, and the reason for not using it were analyzed. Results: Seventy-nine patients (60 female, 75.9%) participated. Patients’ Beck Hopelessness Scale, STAI–State, and STAI–Trait scores decreased significantly after the DPT compared to the initial scores. Among the patients who developed a reaction during the drug provocation test, the rate of those whose scale scores increased was significantly higher than the rate of those who did not develop a reaction. A total of 42 patients (53.2%) did not use the alternative safe drug. Of these, six (14.3%) reported that their reluctance stemmed from a fear of experiencing a reaction similar to their initial adverse event. Patients with concomitant allergic diseases were less likely to use alternative safe drugs. Conclusions: DPT reduces long-term anxiety and hopelessness. However, one in seven patients avoids the prescribed safe drug due to fear of recurrence. Effective communication, especially with patients who have allergic conditions or experience a reaction during DPT, and psychological support may improve adherence to the tested medication. Full article

Background: Drug allergies constitute a significant health concern among the elderly, with beta-lactam (BL) antibiotics among the most frequently implicated agents. Nevertheless, data regarding the safety and efficacy of BL allergy de-labeling in this population remain scarce. This study aimed to evaluate the safety and efficacy of BL allergy assessment in a cohort of geriatric patients carrying BL allergy labels. Methods: We conducted a retrospective study, including patients aged >65 years who were referred for BL allergy evaluation at the Allergy Unit of Meir Medical Center. Patients underwent comprehensive anamnesis, skin testing, and, when indicated, oral challenge. Those successfully de-labeled were followed longitudinally to assess subsequent BL use and clinical outcomes. Results: Between 2009 and 2019, 166 elderly patients with suspected BL allergies were evaluated. A BL allergy was ruled out in 145 patients (87.3%). Sixteen patients (9.6%) were diagnosed with immediate-type hypersensitivity, 2.4% of patients had severe delayed-type hypersensitivity reactions, and one patient (0.6%) had a benign rash. The evaluation process was safe, with no severe reactions occurring during oral challenges, and no patient required hospitalization or epinephrine administration. A long-term follow up was available for 106 patients; among them, 38 (35.8%) received subsequent treatment with the previously suspected BL agent, without any reports of immediate or severe delayed reactions. Conclusions: Beta-lactam allergy de-labeling is safe and effective in the elderly and supports the critical role of allergy evaluation in this population. Enhanced awareness and implementation of de-labeling protocols in geriatric patients are warranted. Full article

Nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, has been associated with rare but potentially serious pulmonary toxicity, which can present in acute, subacute, or chronic forms. Acute toxicity typically manifests in the form of hypersensitivity pneumonitis, which is characterized by fever, dyspnea, and eosinophilia, often resolving rapidly after drug discontinuation. However, chronic toxicity can lead to interstitial lung disease with progressive fibrosis, causing significant and sometimes irreversible pulmonary impairment. The pathophysiology of nitrofurantoin-induced lung injury is thought to involve oxidative stress, immune-mediated mechanisms, and direct cytotoxic effects; however, the exact pathways remain incompletely understood. Clinical diagnosis is challenging due to nonspecific symptoms that often resemble other respiratory conditions, leading to delays in recognition and treatment. Radiographic findings vary, with acute cases showing diffuse ground-glass opacities, while chronic cases may demonstrate reticular interstitial changes and fibrosis. The discontinuation of nitrofurantoin is the primary intervention, but corticosteroids may be beneficial, particularly in chronic cases with persistent inflammation or fibrosis, though their efficacy remains uncertain. Given the risk of long-term respiratory complications, heightened awareness among healthcare providers is essential for early diagnosis and intervention. Future research is needed to better define risk factors, improve diagnostic criteria, and explore alternative treatment strategies that mitigate the potential for pulmonary toxicity while maintaining effective antimicrobial therapy. This review explores the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for nitrofurantoin-induced pulmonary toxicity. Full article

Background/Objectives: Diseases associated with inflammatory processes continue to grow steadily throughout the world. Unfortunately, prolonged use of drugs induces adverse effects ranging from hypersensitivity reactions to damage to the digestive system. These negative effects open the possibility of continuing the search for anti-inflammatory compounds with less toxicity. The aim of this research was to isolate and evaluate the anti-inflammatory activity of a mixture of two enantiomeric labdanes isolated from Gymnosperma glutinosum by in vivo, in vitro, and in silico methods. Methods: A brief description of the main methods or treatments applied. This can include any relevant preregistration or specimen information. The structure of the labdanes enantiomers was elucidated by X-ray crystallography and spectroscopies methods. The anti-inflammatory effect was evaluated on a mouse model of ear edema induced with 12-O-tetradecanoyl phorbol-13-acetate; the pro-inflammatory mediators, nitric oxide (NO) and interleukin (IL-6), were quantified on macrophages stimulated with lipopolysaccharide, and the interaction between labdanes and diana was studied by molecular docking. Results: We identified the chemical structures of two new labdane enantiomers: a-gymglu acid and b-ent-gymglu acid. The enantiomer mixture, named gymglu acid, diminished ear edema at doses of 1 and 2 mg/ear by 36.07% and 41.99%, respectively. A concentration of 155.16 µM of gymglu acid inhibited the production of NO by 78.06% and IL-6 by 71.04%. The in silico results suggest two routes by which these labdanes reduce inflammation: partial agonism toward the corticosteroid receptors and inhibition of nitric oxide synthases. Conclusions: These results show that the gymglu acid enantiomers have promising anti-inflammatory activity. Full article

Background and Objectives: Early-type drug hypersensitivity reactions (DHRs) are observed within the first 1–6 h and most commonly manifest as urticaria and/or angioedema. Detailed anamnesis, skin prick tests (SPTs), intradermal tests (IDTs), and oral/intramuscular/intravenous drug provocation tests (DPTs) can be used to identify the drug responsible. We aimed to evaluate the demographic characteristics, responsible drugs, DHR types, and DPT results used in the diagnosis of drug allergy in patients who presented to our clinic with suspected drug allergies. Materials and Methods: The medical records of patients who presented with a suspicion of an early-type DHR between February 2019 and December 2024 were retrospectively evaluated through the hospital information management system. A total of 188 adults who underwent diagnostic drug testing were included. Results: The diagnosis of drug allergy was confirmed in 51 (27%) patients. In 137 (73%) patients, the diagnosis of drug allergy was excluded after DPTs. In 78 of the 188 patients, there was a DHR to a single suspected drug. The other 110 patients had DHR histories with multiple drugs. The rate of confirmation of a drug allergy from diagnostic tests was higher in those who described a history of multiple drug allergies. Amongst the antibiotics, beta-lactam antibiotics (n = 47) were the most frequently suspected drugs. The rate of positive DPTs (n = 4; 8%) was lower in patients with suspected beta-lactam allergies than other antibiotics (p = 0.002). NSAIDs (n = 60) were the second most common group of suspected drug allergies. With regard to IgE or COX-1-mediated mechanisms, there was no statistically significant difference in DPT positivity among these NSAIDs (p = 0.414). The severity of the initial early-type DHRs were grade 1 (n = 168; 80%), grade 2 (n = 14; 7%), and grade 3 (n = 14; 7%). If the patients had redness, itching, urticaria, angioedema, dyspnea, cyanosis, desaturation, syncope, tachycardia, or hypotension during their initial DHRs, the positive diagnostic drug test rate was statistically significantly higher. However, experiencing diarrhea, nausea, and vomiting were not found to be associated with positive diagnostic drug tests. Drug allergies were confirmed with SPTs or IDTs in all patients in whom adrenaline was used during initial reactions. Conclusions: Contrary to the prevailing notion that drugs (especially beta-lactams) are the predominant cause of allergic reactions, this study demonstrated that the actual prevalence of drug allergies is, in fact, low. 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

In vitro tests of cellular activity form part of the diagnostic algorithm of drug hypersensitivity reactions. Because of the wide range of pharmacological mechanisms, clinical symptoms, genetic components, and laboratory tests involved, it is important to know how a particular test performs in the diagnostic procedure. We carried out a detailed retrospective analysis of more than 6000 measurements of numerous drug compounds tested in 738 serum samples over the past 6 years. Our cell viability-based lymphocyte transformation had a coefficient of variation of 10% and showed similar performance over the whole range of tested ages. With an adequate number of parallel measurements, the test can identify modest increases in stimulation indices with high confidence. Similar percentages of analytically positive responses (11.4%, 13.5%, and 9.7%) were observed for the three most frequently tested drug groups, namely, antibiotics, non-steroid anti-inflammatory agents, and anesthetics. These results confirm that cell viability tests are suitable alternatives for proliferation assays in drug allergy testing. Full article