Search Results (157)

Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to the contact allergen. This delayed response to the contact allergen is seen during patch testing, where allergen-naïve, unaffected skin of allergic individuals is exposed to the contact allergen. However, in daily life and in certain occupational settings, allergic individuals often experience rapid flare-ups/exacerbations with intensely itching erythema, oedema, and often vesicles within hours after re-exposure to the specific contact allergen. These rapid flare-ups only develop at skin sites previously exposed to the contact allergen. Thus, it is important to distinguish between the rapid-onset reaction typically experienced by the allergic individual and the delayed-type reaction typically seen after patch testing. This review summarizes current insights into the immunopathology of rapid- versus delayed-type ACD reactions and outlines potential therapeutic opportunities, as well as their current limitations, against rapid-onset ACD, including modulation of cytokine signaling, T cell survival, checkpoint pathways, and redox balance. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

Background/Objectives: Natural products with claimed adaptogenic and/or immunomodulatory effects are widely used in traditional medicine systems across Eurasia. These include herbal remedies (e.g., Panax ginseng), fungi (e.g., Ganoderma lucidum), and animal-derived substances (e.g., propolis from Apis mellifera). Despite their popularity, the safety profiles of these products—particularly concerning adverse events (AEs) and serious adverse events (SAEs)—remain insufficiently understood. This study aimed to assess the safety profiles of adaptogenic and immunomodulatory natural products through a scoping review of published human studies and an analysis of individual case safety reports (ICSRs) from the WHO-UMC VigiBase database. Methods: A scoping review was conducted using PubMed (1980–2024) in line with PRISMA-ScR guidelines. Eligible studies included randomized and non-randomized clinical trials and case reports in humans focused on safety outcomes. Data extraction followed the Joanna Briggs Institute (JBI) standardized template. ICSRs from VigiBase were analyzed by product type, AE type and seriousness, and demographic characteristics. The data were further organized to highlight the 15 most frequently reported products and their top five System Organ Classes (SOCs) and Preferred Terms (PTs). Results: The scoping review identified 51 natural products with reported adaptogenic and/or immunomodulatory properties. This included 285 clinical trials and 119 case studies on single-ingredient products and 54 clinical trials and 21 case studies on multi-ingredient preparations. Common AEs included gastrointestinal, dermatological, hepatic, cardiovascular, and immunological reactions. SAEs were rare but reported for Echinacea purpurea, Silybum marianum, and Camellia sinensis. From Vigibase, 45,042 ICSRs were retrieved for 49 natural products: 10,702 for single-ingredient and 34,340 for multi-ingredient products. Among 7856 reports listing a single-ingredient product as the sole suspect, 15.8% were SAEs, including eight fatal cases. However, the causality remained unclear due to insufficient data. Ganoderma lucidum, Viscum album, and Silybum marianum were most frequently associated with SAEs. In multi-ingredient products, propolis was frequently linked to hypersensitivity and skin reactions. Conclusions: This study provides a comprehensive overview of the safety profiles of adaptogenic and immunomodulatory natural products. Variability in product composition, lack of standardization, incomplete reporting in clinical studies, and underreporting in pharmacovigilance databases complicate accurate risk assessment. For multi-ingredient products, attributing specific AEs to specific components remains difficult. Further high-quality clinical research and improved pharmacovigilance are needed, along with clear safety warnings to reduce risks for consumers. Full article

Background/Objectives: Hypersensitivity to iodinated contrast media (ICM) agents is a significant concern in clinical practice, potentially limiting their use in essential medical imaging studies and interventions. This cohort study reflects real-world clinical settings, with the aim of characterizing patients with a history of an ICM allergy and to analyze the potential cross-reactivity between different ICM agents. Methods: We conducted a retrospective review of patients with a documented history of an allergy to ICM. Data were collected from a six-year period, (2018 to 2023), and included a total of 26,465 procedures carried out with contrast. Data on patient demographics, reaction characteristics, culprit ICM agents, and outcomes of re-exposure were analyzed. Results: One hundred and eighty-three patients were identified as being allergic to at least one type of ICM. The majority of reactions were immediate (60.7%) versus delayed (39.3%). The most common culprit agent was Ioversol (3.84%) and related to the total time used. Among those who were ever exposed to more than one agent, the highest rate of recurrent hypersensitivity reactions was observed between Iohexol and Iodixanol (three out of six cases) and between Iopromide and Iopamidol (one out of two cases). No recurrent hypersensitivity reaction rate was observed between Iodixanol and Iopamidol (0 out of 12 cases). The highest proportion of severe allergies among those with allergic reactions was 3/15 (20%) for Iodixanol. Conclusions: Allergic reactions to ICM are uncommon and mostly non-severe. Although our findings do not confirm immunologic cross-reactivity, the occurrence of recurrent reactions to different ICMs in certain cases underscores the need for careful clinical judgment when selecting appropriate agents. 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

Type I allergies are triggered by immunoglobulin E (IgE)-mediated hypersensitivity reactions upon allergen exposure. Dogs are diagnosed with allergic dermatitis based on history, clinical signs, and allergen-specific IgE detection. Using the multiple allergen simultaneous test (MAST)–immunoblot assay, this study measured IgE concentrations and analyzed the proportion of dogs showing allergen-specific IgE positivity, and IgE concentrations of environmental and food allergens in South Korea. We examined data from canine serum using the MAST assay in 2023; the allergen panel included 130 allergens. Data were analyzed, with results greater than zero regarded as positive for the prevalence measurements and concentrations compared among subgroups. Overall, 2663 samples were evaluated to assess the proportion of dogs showing allergen-specific IgE positivity and mean concentrations of environmental and food allergens. Among the environmental allergens, Alternaria spp. had the highest IgE prevalence, whereas Japanese cedar had the highest mean IgE concentration. Allergen-specific differences were observed among subgroups categorized by age, sex, and breed. To our knowledge, this research is the first large-scale study to analyze canine serum using a MAST assay to assess the IgE prevalence of allergen-specific IgE positivity and concentration and to examine data by age, sex, and breed. These findings provide information for diagnosis and management of canine allergies. Full article

Allergic diseases represent a major and growing global health concern, with increasing prevalence among both children and adults. This manuscript presents an extensive review of allergy mechanisms, epidemiology, diagnostics, and clinical challenges, highlighting the complex interplay between immune system dysregulation and environmental exposures. The authors provide a structured analysis of hypersensitivity types, with particular focus on IgE-mediated responses, and emphasize the role of immune barrier defects, epigenetics, and the microbiota in allergic pathogenesis. This manuscript explores diagnostic limitations, including test sensitivity, specificity, and the presence of hidden allergens, as well as challenges in identifying food-related or atypical allergic reactions. A novel and valuable aspect is the discussion of allergy as a potential clinical manifestation of primary immunodeficiencies, such as selective IgA deficiency, Wiskott–Aldrich syndrome, hyper-IgE syndrome, and Netherton syndrome. This review also outlines challenges in treatment, especially among polysensitized patients, and examines the psychosocial burden and complications of allergic diseases, including mental health, nutritional deficiencies, and impaired sleep. This comprehensive synthesis underscores the need for early diagnosis, multidisciplinary management, and personalized therapeutic strategies to improve quality of life of allergic patients. 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

Background/objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in treating type 2 diabetes and obesity, offering established metabolic and cardiovascular benefits. Emerging evidence suggests these agents also exert direct dermatologic effects. This systematic review categorizes these effects and explores their role in inflammatory skin diseases. Methods: A comprehensive literature search was performed across EMBASE, PubMed, Web of Science, and Google Scholar for studies published from 2014 to 2025. Inclusion criteria were English-language, peer-reviewed original research involving human subjects that linked GLP-1RAs to dermatologic effects. Animal and in vitro studies were excluded. PRISMA guidelines were followed. Results: Fifty-one studies met inclusion criteria. Thirty-four reported adverse effects, including hypersensitivity, injection-site reactions, pruritus, urticaria, angioedema, and immune-mediated conditions like bullous pemphigoid. Seventeen studies described beneficial outcomes, such as improvements in psoriasis, reduced hidradenitis suppurativa flares, enhanced wound healing, anti-aging potential, and decreased inflammation. GLP-1RAs showed cytokine modulation in psoriasis, though their role in hidradenitis suppurativa remains uncertain. Cosmetic concerns, such as “Ozempic Face” due to rapid weight loss, were also noted. Conclusions: GLP-1RAs have a broad spectrum of dermatologic effects, from immunomodulatory benefits to adverse cutaneous reactions. Their impact on inflammatory skin disorders suggests a novel therapeutic avenue. However, adverse reactions and aesthetic changes warrant vigilance. Future research should focus on mechanistic studies, long-term safety, and identifying biomarkers to predict dermatologic responses, ultimately guiding personalized treatment approaches. Full article

Background/Objectives: Food hypersensitivity remains an understudied and overlooked subject globally. It is characterized by adverse reactions to dietary substances, potentially triggered by various mechanisms. Food allergy, a subset of food hypersensitivity, denotes an immune response to food proteins categorized into immunoglobulin IgE-mediated or non-IgE-mediated reactions. Conversely, food intolerance, another facet of food hypersensitivity, refers to non-immunological reactions, in which the human body cannot properly digest certain foods or components, leading to gastrointestinal discomfort and other non-immune-related symptoms. The main objective of this study was to determine and differentiate the differences, characteristics, and types of food hypersensitivity. Methods: This study involved a comprehensive review of key research from 1990 onward, including review articles, prospective studies, nested case–control studies, and meta-analyses. Results: Recognizing these differences is essential for healthcare professionals to ensure accurate diagnosis, effective management, and improved patient outcomes, while also aiding dietitians in providing optimal nutritional and dietary guidance. Conclusions: there are big differences between the main characteristics, such as symptoms, complications, and treatments between allergies, and food intolerances. Commonly reported trigger foods include cow milk, gluten, eggs, nuts, and seafood. 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

Atopy is defined as a predisposition to hypersensitivity reactions against a range of antigens. It is characterized by the activation of CD4+ T helper type 2 (Th2) cells and an increased production of immunoglobulin E (IgE). The most common atopic conditions are atopic dermatitis, asthma, allergic rhinitis, food allergies, and atopic ocular diseases. Atopic keratoconjunctivitis (AKC) is a chronic, bilateral inflammatory condition affecting the ocular surface, frequently occurring in conjunction with atopic dermatitis. It is not uncommon for patients to present with multiple conditions simultaneously or in a sequential manner. A comprehensive understanding of the underlying mechanisms of atopic diseases is essential for the effective clinical evaluation and treatment. Recent research has underscored the pivotal role of the microbiota in the pathogenesis of atopic dermatitis and atopic eye diseases, with alterations in microbial composition (dysbiosis) being linked to a spectrum of atopic conditions. Probiotics are currently being investigated as a potential treatment option for restoring microbial balance and alleviating disease symptoms. This review examines the relationship between atopic dermatitis, atopic keratoconjunctivitis, and the microbiota, evaluating the current evidence and exploring the potential of probiotics as a novel therapeutic approach. Full article

Kounis syndrome (KS) is a rare condition where hypersensitivity reactions trigger coronary vasospasm, destabilization of atherosclerotic plaques, or stent thrombosis, posing diagnostic and therapeutic challenges due to its overlap with acute coronary syndrome (ACS) and the absence of specific guidelines. This study reviews cases of KS from the Institute of Cardiovascular Disease to highlight clinical presentations, triggers, and treatment strategies. We analyzed four cases of KS treated at our institution between 2019 and 2024. Detailed clinical histories, laboratory findings, imaging studies, and treatment plans were reviewed. Patients were classified by KS subtype based on coronary anatomy and pathophysiological mechanisms. Management strategies were tailored to each subtype, combining myocardial revascularization, antiplatelet therapy, and treatment for allergic reactions. The series included two cases of Type I KS in patients with structurally normal coronary arteries and two cases of Type II KS involving pre-existing atherosclerosis. No Type III KS was observed. Triggers included insect stings, antibiotics, iodinated contrast agents, and anesthetics. Coronary angiography confirmed the diagnosis in all cases. Treatments included percutaneous coronary interventions, dual antiplatelet therapy, and prophylactic antihistamines or corticosteroids. All patients experienced favorable outcomes, although diagnostic delays were noted in cases with atypical presentations. KS remains underdiagnosed, especially in emergency settings where it mimics ACS. Early recognition and multidisciplinary management involving allergology and cardiology are crucial. Future research should focus on safer diagnostic tools, understanding the pathophysiology, and developing evidence-based preventive strategies. Increasing the awareness of KS and its inclusion in ACS differentials are essential to improving patient outcomes and preventing recurrences. Full article

Background/Objectives: An optimal physical condition has beneficial effects in adults at risk of chronic diseases. However, research data on how adverse reactions to food (ARFSs) are linked to physical performance are lacking. The aims of this study were (a) to investigate the prevalence of ARFS according to age; (b) to analyze physical performance level according to the type of ARFS; and (c) to determine the probability of having a positive ARFS according to physical performance levels. Methods: A cross-sectional study with 254 Spanish adults (61% women; mean age 43.7 ± 13 y) scoring ≥ 6 in PSIMP-ARFSQ-10 (pathologies and symptomatology questionnaire associated with adverse reactions to foodstuffs) was conducted in the region of Madrid, Spain, following the ALASKA study protocol. Immune-mediated variables used to measure ARFS were sIgE and sIgG₄ antibody reactions (AbR) (type 1 and type 2 food hypersensitivities, respectively); non-immune-mediated variables used to measure ARFS were lactose intolerance and fructose malabsorption. Physical performance variables were body balance, leg power, sit-to-stand speed, resting heart rate, handgrip strength, and cardiorespiratory fitness. Statistical significance was set at 0.05. Results: The most prevalent sIgE- and sIgG₄-mediated ARFSs were against legumes (53% and 46%; 60% and 68% in subjects with ≤45 y and >45 y, respectively). Handgrip strength was significantly lower in subjects positive for lactose intolerance compared to subjects negative for lactose intolerance (p < 0.05). Both the positive mean sIgE and sIgG₄ AbR were significantly associated with high physical performance (p < 0.05). Subjects with high physical performance showed a 1.5-fold increase in the odds of the positive mean total sIgE and positive sIgG₄ AbR against legumes. Conclusions: In conclusion, subjects aged 45 or younger had a higher prevalence of total type 1 and type 2 food hypersensitivities than subjects older than 45 y. Positive lactose intolerance was linked to lower values of handgrip strength. Subjects with high physical performance, whether male or female, aged ≤45 years, or with a BMI of ≥25, showed significant odds of experiencing type 1 food hypersensitivity to nuts. Full article

Pseudomonas cannabina pv. alisalensis (Pcal) causes bacterial blight on cabbage. In a previous study, we screened for reduced virulence using Tn5 transposon mutants and identified a LysR-type transcriptional regulator (LTTR) as a potential virulence factor in Pcal. However, the role of LTTR in Pcal virulence has not been thoroughly investigated. In this study, we demonstrated that the Pcal NN14 mutant (with Tn5 insertion in the LTTR-encoding gene) showed reduced disease symptoms and bacterial populations in cabbage, indicating that LTTR contributes to Pcal virulence. RNA-seq analysis identified 39 LTTR-dependent genes. Genes associated with 13 of the type three secretion system (T3SS), two of flagellar apparatus, ABC transporters, and transcription factors were expressed at lower levels in the NN14 mutant compared to the wild type. Conversely, tssH and hcp, type six secretion system (T6SS)-related genes, showed higher expression in NN14. Furthermore, these differences in gene expression were observed in minimal medium, but not in nutrient-rich medium, suggesting that LTTR acts as a global regulator responsive to nutrient conditions. Additionally, LTTR activated the expression of T3SS-related genes during Pcal infection. We also demonstrated that NN14 showed a reduced ability to induce hypersensitive reaction (HR) cell death in non-host plants. Collectively, these results suggest that LTTR contributes to Pcal virulence by regulating T3SS in response to environmental changes. Full article