Search Results (33)

Background/Objectives: We aimed to evaluate the etiologic distribution of markedly elevated IgE (≥2000 IU/mL) and the association of parasitic infections with longitudinal IgE dynamics and National Institutes of Health Hyper-IgE Syndrome (NIH-HIES) score trajectories in pediatric patients. Methods: We retrospectively enrolled 127 pediatric patients with IgE ≥2000 IU/mL and ≥1 year of longitudinal follow-up at a tertiary allergy clinic (2019–2024). The primary outcome was the IgE reduction percentage difference between parasitic and non-parasitic groups. Results: Atopic sensitization was identified in 81.0% of tested patients; genetic evaluation was performed in 40 patients (31.5%), with confirmed IEI in one patient (0.8% of the cohort; 2.5% of those evaluated). Parasitic infections were present in 24.4% of patients (n = 31; intestinal parasites 15.7%, scabies 8.7%, hydatid cyst 1.6%; two patients had concurrent intestinal parasitosis and scabies). Median IgE reduction was 63.8% vs. 27.0% in parasitic versus non-parasitic groups (p < 0.001), persisting after multivariable adjustment (p < 0.001). Parasitic infection independently predicted IgE normalization below 2000 IU/mL (OR = 8.26; 95% CI: 2.76–24.68; p < 0.001). All three NIH-HIES inflammatory components (IgE, eosinophilia, eczema) regressed more often in the parasitic group (all p ≤ 0.01); no patient reached the ≥40-point HIES threshold. Conclusions: Parasitic infections produce a clinical phenotype overlapping with hyper-IgE syndrome, constituting a reversible phenocopy of primary immune dysregulation. In populations with substantial parasitic prevalence, parasitological evaluation may be a useful consideration in children with markedly elevated IgE and indeterminate clinical scores; however, this approach should complement rather than replace comprehensive clinical assessment. Full article

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which persistence of immunological memory underlies disease recurrence and progression toward atopic comorbidities. Evidence indicates that pathogenic tissue-resident memory T cells (TRM), including Th2- and Th22-skewed subsets, among others, persist in both lesional and clinically resolved skin and rapidly re-initiate inflammation through production of IL-4, IL-13, IL-22 and IL-31, promoting barrier dysfunction and pruritus. In parallel, circulating CLA⁺ memory T cells retain skin-homing capacity and contribute to flare reactivation, while IgG1⁺CD23 IL-4Rα⁺ type-2 memory B cells (MBC2) constitute a reservoir for high-affinity IgE production, linking cutaneous inflammation with allergic comorbidities. These adaptive memory compartments are sustained by epithelial alarmins, dendritic cell–derived chemokines such as CCL17, CCL22 and CCL18, and the OX40/OX40L costimulatory pathway, which promotes differentiation, survival and tissue retention of memory T cells. Clinical and transcriptomic studies show how, although IL-4/IL-13 blockade reduces circulating type-2 responses, Th2A cells, Tc2 cells and activated dendritic cells can persist in clinically resolved skin, providing a mechanistic basis for relapse after treatment withdrawal. Together, these findings support the relevance of targeting memory-imprinting pathways as a promising mechanism to achieve durable disease modification in AD. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction and susceptibility to Staphylococcus aureus colonization. Biofilm formation modifies antibiotic resistance and the host immune response. This longitudinal study analyzed antimicrobial susceptibility and biofilm formation in 136 S. aureus isolates obtained over 18 months from lesional, nonlesional, and nasal samples of 26 pediatric patients with moderate-to-severe AD. Antimicrobial susceptibility testing was determined by the disk diffusion method, and biofilm production was quantified using a crystal violet microtiter assay. Clinical parameters, including disease severity, treatment response, and the administration of dilute bleach baths, were evaluated in relation to bacterial characteristics. Overall, 60.2% of isolates exhibited moderate-to-strong biofilm production, significantly associated with severe AD at baseline (p = 0.01), lack of clinical improvement (p = 0.04), and persistent moderate-to-severe disease (p = 0.01). Resistance rates for penicillin, gentamicin, clindamycin, and erythromycin exceeded 15%. Isolates from patients using dilute bleach baths showed greater resistance to ciprofloxacin (p < 0.0001) and exhibited constitutive or inducible macrolide–lincosamide–streptogramin B (MLS_B) resistance, with ermA detected in 80% of inducible cases. In conclusion, S. aureus biofilm formation is linked to disease severity and treatment failure in pediatric AD, underscoring the importance of culture-guided, targeted therapeutic strategies. Full article

Isosorbide fatty acid diesters constitute a novel class of bioactive compounds with emerging therapeutic applications in inflammatory and barrier-compromised disorders. Among them, isosorbide dicaprylate (IDC) and isosorbide di-linoleate/oleate (IDL) synergistically strengthen epidermal barrier integrity, enhance stratum corneum hydration, regulate keratinocyte differentiation, suppress proinflammatory signaling, and beneficially modulate the skin microbiome. Randomized, double-blind clinical trials in both pediatric and adult populations with atopic dermatitis (AD) demonstrate that topical IDC + IDL formulations significantly reduce pruritus, corticosteroid dependence, and Staphylococcus aureus colonization while improving sleep quality, disease severity scores, and overall quality of life. Extending applications within and even beyond dermatology, isosorbide dimethyl fumarate (IDMF)—a next-generation fumarate derivative designed to mitigate sensitization risk—exhibits potent anti-inflammatory and antioxidant activities through NRF2 activation and NF-κB/IRF1 suppression. Preclinical studies in psoriasis and neuroinflammatory models, including multiple sclerosis, reveal robust modulation of oxidative stress and immune pathways with improved safety and mechanistic precision compared to conventional fumarates, although its systemic use remains exploratory and requires clinical validation. Collectively, isosorbide diesters emerge as multifunctional therapeutic agents offering barrier repair, immune modulation, and inflammation control, representing promising alternatives to corticosteroids and systemic immunosuppressants across dermatologic and systemic inflammatory disorders. Full article

Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions. Full article

Eosinophilic esophagitis (EoE) is a chronic disease which clinically presents with symptoms related to esophageal dysfunction, while pathologically it is characterized by eosinophilic infiltration of esophageal epithelium. Most patients with EoE present with food and/or inhalant allergy symptoms. The results of animal model studies and genetic studies, as well as the efficacy of elimination diets in managing the symptoms, suggest an atopic background of the disease. The aim of this study was to evaluate the prevalence of EoE in a group of patients with upper gastrointestinal symptoms and food and/or inhalant allergies and to assess the influence of drugs used in type I allergies on the results of endoscopic, histopathological, and immunohistochemical tests. Methods: This was a prospective observational study. Patients with inhalant/food allergies and upper esophageal symptoms constituted the study group while patients without allergies who were diagnosed with dyspepsia or irritable bowel syndrome constituted the control group. All study group subjects underwent allergy testing, including prick testing and blood tests. All participants underwent a gastroscopy with specimen collection. Esophageal specimens were stained for eotaxin-1 and desmoglein-1. Results: Based on histopathology results, eosinophilic esophagitis was found in 9 of the 73 patients from the study group. All patients with EoE presented with multimorbidity and were diagnosed with at least one allergic disease in addition to EoE. Positive staining for CCL-11 was found in 56 (78%) patients in the study group, including all patients with EoE while only 3 (17%) individuals from the control group showed positive staining. The presence of DSG-1 in esophageal specimens was detected in 6 (7%) subjects from the study group in contrast to 14 (78%) subjects from the control group. DSG-1 was not found in any of the specimens of patients diagnosed with EoE. Conclusions: EoE is a rare disease, usually accompanied by allergic multimorbidity. Positive staining for eotaxin-1 and negative staining for desmoglein-1 in patients with esophageal symptoms and allergies but who did not meet EoE diagnostic criteria could be indicative of subclinical course of the disease or a masking effect of corticosteroids. It is now vitally important for both researchers and practicing clinicians to recognize that eosinophilic esophagitis (EoE) is not a homogeneous disease but rather consists of multiple subtypes (phenotypes). The so-called “classic” form of EoE—defined by current diagnostic criteria as the presence of more than 15 eosinophils per high power field on histopathological examination—appears to represent only the tip of the iceberg. There is an urgent need for further research in order to refine endoscopic techniques, expand the scope of histopathological assessments, and identify novel biomarkers to better define the distinct phenotypes of eosinophilic esophagitis. Full article

Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child’s life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: “the impact of intestinal microbiota on the development of immune diseases and asthma”, “intestinal microbiota and allergic diseases”, “the impact of intrauterine microbiota on the development of asthma”, “intrauterine microbiota and immune diseases”, “intrauterine microbiota and atopic dermatitis”, “intrauterine microbiota and food allergies”, “maternal microbiota”, “fetal microbiota” and “neonatal microbiota”. The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect. Full article

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments. Full article

Geological hazards in Xinxian County, Xinyang City, Henan Province, are characterized by their small scale, wide distribution, and significant influence from regional tectonics. This study focuses on collapses and landslide hazards within the area, selecting twelve evaluation factors: aspect, slope shape, normalized difference vegetation index (NDVI), topographic relief, distance from geological structure, slope, distance from roads, land use cover type, area of land change (2012–2022), average annual rainfall (2012–2022), and river network density. Utilizing data from historical disaster sites across the region, the information quantity method and hierarchical analysis method are employed to ascertain the information quantity and weight of each factor. Subsequently, a random forest model is applied to perform susceptibility zoning of geological hazards in Xinxian County and to examine the characteristics of these geological disasters. The results show that in the study area, the primary factors influencing the development of geohazards are the distance from roads, rock groups, and distance from geological structure areas. A comparison of the susceptibility results obtained through two methods, the analytic hierarchy process information quantity method and the random forests model, reveals that the former exhibits a higher accuracy. This model categorizes the geohazard susceptibility in the study area into four levels: low, medium, high, and very high. Notably, the areas of very high and high susceptibility together cover 559.17 km², constituting 35.99% of the study area’s total area, and encompass 57 disaster sites, which represent 72.15% of all disaster sites. Geological hazards in Xinxian County frequently manifest on steep canyon inclines, along the curved and concave banks of mountain rivers, within watershed regions, on gully inclines, atop steep cliffs, and on artificially created slopes, among other sites. Areas with very high and high vulnerability to these hazards are mainly concentrated near the county’s geological formations. The gneiss formations are widely exposed in Xinxian County, and the gneisses’ strength is significantly changed under weathering, which makes the properties of the different degrees of weathering of the rock and soil bodies play a decisive role in the stability of the slopes. This paper provides a basis for evaluating and preventing geologic hazards in the Dabie mountainous area of the South Henan Province, and the spatial planning of the national territory. Full article

Introduction: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). Methods: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. Results: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. Conclusion: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin. Full article

Erythroderma is a condition characterized by erythema affecting at least 90% of the skin surface area. It can be caused by various underlying conditions. Due to nonspecific clinical and laboratory findings, determining the cause may pose a challenge. In the retrospective study, we identified 212 patients hospitalized for erythroderma in the Department of Dermatology, Venereology, and Allergology at Wroclaw Medical University between January 2012 and March 2022. Clinical, laboratory, and histopathological features, as well as the management of patients, were studied. The median age of adults was 61 years (IQR = 47–68). The most common causes of erythroderma were psoriasis (n = 49, 24.01%), followed by atopic dermatitis (AD) (n = 27, 13.23%), and cutaneous T-cell lymphomas (CTCL) (n = 27, 13.23%). Despite laboratory tests and histopathological examination, the etiology of erythroderma remained undetermined in 39 cases (19.12%). In 70.59% of patients, it was the first episode of erythroderma, while 29.41% experienced a recurrent episode. Regardless of the etiology of erythroderma, patients were most frequently treated with systemic antihistamines (146 cases, 71.57%) and systemic steroids (132 cases, 64.71%). Patients with idiopathic erythroderma constitute the greatest diagnostic and therapeutic challenge, requiring particularly thorough evaluation. Full article

Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases whose prevalence has increased worldwide in recent decades. These disorders contribute to patients’ decreased quality of life (QoL) and constitute a socioeconomic burden. New therapeutic options for AD and psoriasis based on natural compounds are being investigated. These include resveratrol (3,5,40-trihydroxystilbene) and its derivatives, which are produced by many plant species, including grapevines. Resveratrol has gained interest since the term “French Paradox”, which refers to improved cardiovascular outcomes despite a high-fat diet in the French population, was introduced. Resveratrol and its derivatives have demonstrated various health benefits. In addition to anti-cancer, anti-aging, and antibacterial effects, there are also anti-inflammatory and antioxidant effects that can affect the molecular pathways of inflammatory skin disorders. A comprehensive understanding of these mechanisms may help develop new therapies. Numerous in vivo and in vitro studies have been conducted on the therapeutic properties of natural compounds. However, regarding resveratrol and its derivatives in treating AD and psoriasis, there are still many unexplained mechanisms and a need for clinical trials. Considering this, in this review, we discuss and summarize the most critical research on resveratrol and its derivatives in animal and cell models mimicking AD and psoriasis. Full article

Work-related skin conditions, including work-related irritant and allergic contact dermatitis, rank as the second most prevalent among work-related diseases. The most commonly reported manifestation of these conditions is hand eczema, which develops due to exposure to various substances in the workplace. Understanding the origins and triggers of eczema and contact dermatitis enables healthcare professionals to educate themselves and their patients about effective preventive measures, such as avoiding specific irritants and allergens, using protective equipment, and maintaining proper skincare hygiene. Additionally, this knowledge facilitates the development of new recommendations to enhance skin protection in work-related settings, regulate the use of substances known to cause work-related skin diseases, and provide healthcare practitioners with the necessary training to recognize and manage these conditions. Given that approximately one in every five healthcare workers is considered to have hand eczema, the objective of this study was to review the existing literature regarding the characteristics of eczema in healthcare workers. Furthermore, this study aimed to comprehensively investigate environmental and constitutional factors (including years of work experience involving exposure to skin hazards, frequent glove use, regular handwashing and water contact, frequent use of disinfectants and detergents, and a history of previous allergies and atopic dermatitis) that influence the occurrence and progression of eczema. Full article

cAMP response element binding protein (CREB) functions as a prototypical stimulus-inducible transcription factor (TF) that initiates multiple cellular changes in response to activation. Despite pronounced expression in mast cells (MCs), CREB function is surprisingly ill-defined in the lineage. Skin MCs (skMCs) are critical effector cells in acute allergic and pseudo-allergic settings, and they contribute to various chronic dermatoses such as urticaria, atopic dermatitis, allergic contact dermatitis, psoriasis, prurigo, rosacea and others. Using MCs of skin origin, we demonstrate herein that CREB is rapidly phosphorylated on serine-133 upon SCF-mediated KIT dimerization. Phosphorylation initiated by the SCF/KIT axis required intrinsic KIT kinase activity and partially depended on ERK1/2, but not on other kinases such as p38, JNK, PI3K or PKA. CREB was constitutively nuclear, where phosphorylation occurred. Interestingly, ERK did not translocate to the nucleus upon SCF activation of skMCs, but a fraction was present in the nucleus at baseline, and phosphorylation was prompted in the cytoplasm and nucleus in situ. CREB was required for SCF-facilitated survival, as demonstrated with the CREB-selective inhibitor 666-15. Knock-down of CREB by RNA interference duplicated CREB’s anti-apoptotic function. On comparison with other modules (PI3K, p38 and MEK/ERK), CREB was equal or more potent at survival promotion. SCF efficiently induces immediate early genes (IEGs) in skMCs (FOS, JUNB and NR4A2). We now demonstrate that CREB is an essential partaker in this induction. Collectively, the ancient TF CREB is a crucial component of skMCs, where it operates as an effector of the SCF/KIT axis, orchestrating IEG induction and lifespan. Full article

Atopic dermatitis (AD) is classified as a type 2 disease owing to the majority of type 2 lymphocytes that constitute the skin-infiltrating leukocytes. However, all of the type 1–3 lymphocytes intermingle in inflamed skin lesions. Here, using an AD mouse model where caspase-1 was specifically amplified under keratin-14 induction, we analyzed the sequential changes in type 1–3 inflammatory cytokines in lymphocytes purified from the cervical lymph nodes. Cells were cultured and stained for CD4, CD8, and γδTCR, followed by intracellular cytokines. Cytokine production in innate lymphocyte cells (ILCs) and the protein expression of type 2 cytokine IL-17E (IL-25) were investigated. We observed that, as inflammation progresses, the cytokine-producing T cells increased and abundant IL-13 but low levels of IL-4 are produced in CD4-positive T cells and ILCs. TNF-α and IFN-γ levels increased continuously. The total number of T cells and ILCs peaked at 4 months and decreased in the chronic phase. In addition, IL-25 may be simultaneously produced by IL-17F-producing cells. IL-25-producing cells increased in a time-dependent manner during the chronic phase and may work specifically for the prolongation of type 2 inflammation. Altogether, these findings suggest that inhibition of IL-25 may be a potential target in the treatment of inflammation. Full article