Seborrheic Dermatitis Treatment Using a Standardized Medical Insurance-Approved Korean Medicine: a case report.

Background: Conventional treatments for seborrheic dermatitis often lead to a recurring cycle of symptom improvement and worsening, resulting in chronic conditions. Thus, safer and more effective alternatives are needed. In Korean medicine, Hwangryunhaedok-tang tablets, targeted at treating the fire-heat syndrome, offer a more fundamental approach to manage seborrheic dermatitis. Clinical Features and Outcomes: In this study, we monitored the changes in the symptoms of two patients with seborrheic dermatitis who were treated with Hwangryunhaedok-tang tablets. The patients were administered this medication during the treatment period. The effectiveness of the treatment was assessed by visually recording changes in the affected skin areas using photographs and evaluating symptoms such as heat, itching, and stinging in these areas using a visual analog scale (VAS). Visible improvements in the patients' skin conditions were observed after taking Hwangryunhaedok-tang tablets. Following treatment, VAS scores for subjective symptoms such as heat sensation, itching, and stinging in the affected areas decreased. Conclusion: This study offers evidence of a potential alternative approach for treating seborrheic dermatitis using Kyungbang Hwangryunhaedok-tang tablets. However, it highlights the necessity for further research on the appropriate dosage, side effects, and long-term effectiveness of this treatment.

Atopy and asthma in children born to mothers at risk of gestational diabetes mellitus: a follow-up study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring's risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring. METHODS: The follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother-child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children's serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0). RESULTS: According to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08-20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03-9.63, p = 0.045). Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04-7.31, p = 0.041). CONCLUSION: Among pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases.

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis.

BACKGROUND: Abrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated. CASE PRESENTATION: A 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship. CONCLUSIONS: The present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

Superficial Conjunctival Cells from Dupilumab-treated Atopic Dermatitis Patients with Ocular Adverse Events Display a Transcriptomic Psoriasis Signature.

Dupilumab has demonstrated efficacy in the treatment of atopic dermatitis (AD). However, a subset of patients experiences ocular adverse events (OAE), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of AD patient conjunctival cells collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in two groups according to their ophthalmological status at M4: 12 with OAE (OAE+) and 24 without (OAE-). The analysis revealed 52 differentially expressed genes (DEG) between OAE+ and OAE- patients at M0, and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. Additionally, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 DEG selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ vs OAE- patients, validating the psoriasis signature, while MUC-7 was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some AD patients to develop OAE upon dupilumab treatment.

Epidermal renewal during the treatment of atopic dermatitis lesions: A study coupling line-field confocal optical coherence tomography with artificial intelligence quantifications: LC-OCT reveals new biological markers of AD.

OBJECTIVE: This study explores the application of Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging coupled with artificial intelligence (AI)-based algorithms to investigate atopic dermatitis (AD), a common inflammatory dermatosis. MATERIALS AND METHODS: AD acute and chronic lesions (ADL) were compared to clinically healthy-looking skin (ADNL). LC-OCT was used noninvasively and in real-time to image the skin of AD patients during flare-ups and monitor remissions under topical steroid treatment for 2 weeks. Quantitative parameters were extracted from the images, including morphological and cellular-level markers of epidermal architecture. A novel cellular-level parameter, nuclei "atypia," which quantifies the orderliness of epidermal renewal, was used to highlight abnormal maturation processes. RESULTS: Compared to healthy skin, AD lesions exhibited significant increases in both epidermal and stratum corneum (SC) thickness, along with a more undulated dermo-epidermal junction (DEJ). Additionally, keratinocyte nuclei (KN) were larger, less compact, and less organized in lesional areas, as indicated by the atypia parameter. A higher degree of atypia was observed in chronic lesions compared to acute ones. Following treatment, all the parameters normalized to levels observed in healthy skin within 2 weeks, mirroring clinical improvements. CONCLUSION: This study provides insights into the quantification of epidermal renewal using a noninvasive imaging technique, highlighting differences between ADL/ADNL and acute/chronic lesions. It also presents the AD treatment mechanism, paving the way for future investigations on AD and other skin barrier function-related conditions.

Predictive Factors for Long-Term High Responders to Upadacitinib Treatment in Patients with Atopic Dermatitis.

Background: Upadacitinib, a Janus kinase 1 inhibitor, is an effective medicine for moderate-to-severe atopic dermatitis (AD). Identifying long-term responders to upadacitinib is crucial for optimal treatment strategies in real-world clinical practice. To identify predictive factors for long-term high responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥2-point improvement from baseline IGA at week 48. Methods: A retrospective study was conducted from August 2021 to September 2023 on 63 AD patients treated with upadacitinib 15 mg and 31 patients with 30 mg. Patients of each group were categorized into long-term high responders (achievers of IGA 0/1 at week 48) and low responders (non-achievers). We compared baseline values of clinical indexes and laboratory parameters between long-term responders and nonresponders. Results: In 15 mg group, long-term high responders showed lower rate of bronchial asthma (BA), lower values of baseline eczema area and severity index (EASI) of head and neck, IgE, and systemic inflammatory response index (SIRI) compared with low responders. In 30 mg group, long-term high responders showed lower baseline levels of IgE compared with low responders. Conclusion: Patients with lower baseline EASI of head and neck, IgE, or SIRI or without BA and those with lower baseline IgE may have a higher potential to become long-term high responders to upadacitinib 15 mg and 30 mg treatment, respectively.

Moving beyond biology: the critical role of social and structural determinants in atopic dermatitis.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease with a substantial global burden and negative impact on quality of life. While genetics and pathophysiology are key to understanding AD, emerging evidence indicates that social and structural determinants of health (SDOH and StDOH) strongly influence the condition's onset, severity, and outcomes. SDOH, such as economic stability, education quality and access, healthcare quality and access, neighborhood environment, and social/community context, shape individual risk and disease experience. StDOH, including government processes, economic policies, social/public policies, and cultural/societal values, further act as upstream forces that directly and indirectly influence AD outcomes. In this review, we synthesize current knowledge on the impacts of SDOH and StDOH on AD incidence, severity, and disparities. Embracing a biopsychosocial model is crucial to elucidate the etiology, epidemiology, and optimal management of AD. Future research should adopt a holistic approach, moving beyond a purely biological perspective to consider the intricate interplay of social and structural determinants in understanding and managing AD.

Sex-Specific and Long-Term Trends of Asthma, Allergic Rhinitis, and Atopic Dermatitis in South Korea, 2007-2022: A Nationwide Representative Study.

INTRODUCTION: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic. METHODS: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007-2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or ß-coefficients for these factors across multiple categories. RESULTS: During the study period (2007-2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3-21.3), while among males, it was 15.6% (13.8-17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5-3.2] in 2007-2009 to 4.7% [3.9-5.4] in 2022; AR: from 11.7% [11.1-12.4] in 2007-2009 to 17.4% [16.0-18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese. CONCLUSIONS: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma.

Cannabidiol modulation of immune cell function: in vitro insights and therapeutic implications for atopic dermatitis.

Introduction: Cannabidiol (CBD) exhibits neuroprotective, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for addressing inflammatory skin disorders like atopic dermatitis. Aim: This study aimed to (i) investigate CBD's impact on lymphocyte proliferation and lymphocyte viability; (ii) assess in vitro cytotoxicity U937 cells (a human promonocytic cell line) of CBD/cytotoxicity of CBD on U937 cells; (iii) provide insights into CBD immunomodulatory potential, and (iv) evaluate suitability of CBD for treating inflammatory skin conditions. Material and methods: To this aim PBMCs from healthy donors were cultured with mitogen and two different CBD doses (0.1 and 1 mg/ml), assessing B and T cell proliferation through flow cytometry. CBD inhibited mitogen-induced lymphocyte proliferation, reducing the percentage of proliferating T and B cells. Notably, both CBD doses did not exhibit cytotoxicity on lymphocytes as revealed by viability assessment. We also analysed the effect of CBD on U937 cells using an optical microscopy approach. Interestingly, the higher dose of CBD exerted a cytotoxic effect on U937 cells, while the lower dose was well tolerated. Results: We analysed the effect of an adjuvant treatment for atopic dermatitis with a CBD-containing cleansing cream in reducing itch. Notably, the treatment with the CBD-containing cleansing cream significantly reduced itch in patients suffering from atopic dermatitis. Conclusions: These findings affirm CBD's immunomodulatory characteristics, emphasizing its potential therapeutic application in inflammatory skin disorders.

Association between single nucleotide polymorphisms of interleukin-35 genes and atopic dermatitis.

Introduction: The pathogenesis of atopic dermatitis (AD) involves complex interactions between environmental factors, the skin microbiome, epidermal barrier defects, and altered immune responses that develop on a not fully understood specific genetic background. Aim: We aimed to evaluate the contribution of single nucleotide polymorphisms (SNPs) in the IL-35 genes (IL-12A and EBI3) towards AD susceptibility and clinical characteristics of AD in the Polish population. Two SNPs (rs568408, rs582054) in IL-12A and one SNP (rs428253) in EBI3 were selected. Material and methods: Blood samples were collected from 202 AD patients and 178 healthy individuals. SNPs in IL-35 genes were analysed by the polymerase chain reaction with sequence-specific primers (SSP-PCR) method. Results: For IL-12A rs568408, the AA genotype was significantly linked to increased odds of AD (OR = 34.61; 95% CI: 2.06-579.97, p = 0.0137) and marginally associated with normal total serum IgE levels (OR = 2.82; 95% CI: 0.97-8.16; p = 0.05), while the GA genotype showed significantly reduced odds of AD (OR = 0.53; 95% CI: 0.34-0.81; p = 0.0035). In the context of IL-12A rs582054, TT genotype carriers had increased odds of AD (OR = 2.05; 95% CI: 1.08-3.85; p = 0.03). Patients with the GG genotype of EBI3 rs428253 had decreased odds of high total serum IgE levels (OR = 0.42; 95% CI: 0.20-0.86; p = 0.02) and milder pruritus severity compared to CC genotype carriers (4.12 vs. 7.50; p = 0.02). Conclusions: IL-35 genetic variations appear to play a role in AD pathogenesis.

Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.

Protease-activated receptor-2 (PAR2) is a class-A G protein-coupled receptor (GPCR) activated by serine proteases and is expressed by multiple tissues, including the skin. PAR2 is involved in the skin inflammatory response, promoting Th2 inflammation, delaying skin barrier repair, and affecting the differentiation of keratinocytes. It also participates in the transmission of itch and pain sensations in the skin. Increasing evidence indicates that PAR2 plays an important role in the pathogenesis of inflammatory skin diseases such as acne vulgaris, rosacea, psoriasis, and atopic dermatitis. Additional focus will be placed on potential targeted therapies based on PAR2. The Goal of this review is to outline the emerging effects of PAR2 activation in inflammatory skin disease and highlight the promise of PAR2 modulators.

Effect of Staphylococcus aureus colonization and immune defects on the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.

Saikosaponin A Recovers Impaired Filaggrin Levels in Inflamed Skin by Downregulating the Expression of FRA1 and c-Jun.

Filaggrin (FLG) is an essential structural protein expressed in differentiated keratinocytes. Insufficient FLG expression contributes to the pathogenesis of chronic inflammatory skin diseases. Saikosaponin A (SSA), a bioactive oleanane-type triterpenoid, exerts anti-inflammatory activity. However, the effects of topically applied SSA on FLG expression in inflamed skin remain unclear. This study aimed to evaluate the biological activity of SSA in restoring reduced FLG expression. The effect of SSA on FLG expression in HaCaT cells was assessed through various biological methods, including reverse transcription PCR, quantitative real-time PCR, immunoblotting, and immunofluorescence staining. TNFα and IFNγ decreased FLG mRNA, cytoplasmic FLG protein levels, and FLG gene promoter-reporter activity compared to the control groups. However, the presence of SSA restored these effects. A series of FLG promoter-reporter constructs were generated to investigate the underlying mechanism of the effect of SSA on FLG expression. Mutation of the AP1-binding site (mtAP1) in the -343/+25 FLG promoter-reporter abrogated the decrease in reporter activities caused by TNFα + IFNγ, suggesting the importance of the AP1-binding site in reducing FLG expression. The SSA treatment restored FLG expression by inhibiting the expression and nuclear localization of FRA1 and c-Jun, components of AP1, triggered by TNFα + IFNγ stimulation. The ERK1/2 mitogen-activated protein kinase signaling pathway upregulates FRA1 and c-Jun expression, thereby reducing FLG levels. The SSA treatment inhibited ERK1/2 activation caused by TNFα + IFNγ stimulation and reduced the levels of FRA1 and c-Jun proteins in the nucleus, leading to a decrease in the binding of FRA1, c-Jun, p-STAT1, and HDAC1 to the AP1-binding site in the FLG promoter. The effect of SSA was evaluated in an animal study using a BALB/c mouse model, which induces human atopic-dermatitis-like skin lesions via the topical application of dinitrochlorobenzene. Topically applied SSA significantly reduced skin thickening, immune cell infiltration, and the expression of FRA1, c-Jun, and p-ERK1/2 compared to the vehicle-treated group. These results suggest that SSA can effectively recover impaired FLG levels in inflamed skin by preventing the formation of the repressor complex consisting of FRA1, c-Jun, HDAC1, and STAT1.

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation on Clinical Outcome of Atopic Dermatitis in Children.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while others show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA from fish oil in combination with gamma-linolenic acid (GLA) from blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period throughout autumn, winter, and spring, avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing a specific blend of omega-3 and omega-6 fatty acids or placebo. The primary outcomes were changes in severity of AD measured using SCORing Atopic Dermatitis (SCORAD), patient-oriented SCORAD (PO-SCORAD) and the difference in topical corticosteroid (TCS) use. The secondary outcomes were changes in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving the active product, intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and the use of topical corticosteroids (from median 30 to 10 mg/month, p < 0.001), but also significant improvements in itch, sleep quality, and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D may decrease symptoms and were associated with an improvement clinical picture of AD in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that may significantly reduce the severity of AD in pediatric patients.

The Skin Histopathology of Pro- and Parabiotics in a Mouse Model of Atopic Dermatitis.

As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics.

Preventive and Therapeutic Effects of Lactiplantibacillus plantarum HD02 and MD159 through Mast Cell Degranulation Inhibition in Mouse Models of Atopic Dermatitis.

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3+ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.

Single cell sequencing delineates T-cell clonality and pathogenesis of the parapsoriasis disease group.

BACKGROUND: Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is often underdiagnosed in early stages due to similarities with benign dermatoses such as atopic dermatitis (AD). Furthermore, the delineation from so-called "parapsoriasis en plaque," a disease that can appear either in a small- or large-plaque form, is still controversial. OBJECTIVE: To characterize the parapsoriasis disease spectrum. METHODS: We performed single-cell RNA sequencing of skin biopsies from patients within the parapsoriasis-to-early-stage MF spectrum, stratified for small and large plaques, and compared them to AD, psoriasis and healthy control skin. RESULTS: 6 out of 8 large-plaque lesions harbored either an expanded alpha/beta or gamma/delta T-cell clone with downregulation of CD7 expression, consistent with a diagnosis of early-stage MF. By contrast, 6 out of 7 small-plaque lesions were polyclonal in nature thereby lacking a lymphomatous phenotype, and also revealed a less inflammatory microenvironment than early-stage MF or AD. Of note, polyclonal small- and large-plaque lesions characteristically harbored a population of NPY+ innate lymphoid cells and displayed a stromal signature of complement upregulation and antimicrobial hyperresponsiveness in fibroblasts and sweat gland cells, respectively. These conditions were clearly distinct from AD or psoriasis, which uniquely harbored CD3+CRTH2+ IL13-expressing "Th2A" cells or strong type 17 inflammation, respectively. CONCLUSION: These data position polyclonal small- and large-plaque dermatitis lesions as a separate disease entity, that characteristically harbors a so far undescribed ILC population. We thus propose the new term "polyclonal parapsoriasis en plaque" to this kind of lesions, as they can be clearly differentiated from early and advanced-stage MF, psoriasis and AD on several cellular and molecular levels.