The Enhancement of Regulatory T Cell Maturation and Th1/Th2 Balance through FOXP3 Expression by Lactobacillus paracasei in an Ovalbumin-Induced Allergic Skin Animal Model.

Chronic allergic skin conditions, including atopic dermatitis (AD), are characterized by pruritus, erythema, xerosis, desquamation, and inflammation, significantly impacting quality of life. Long-term steroid use, while common in treatment, carries the risk of adverse effects. Previous studies have demonstrated the potential of Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) in alleviating AD symptoms from a preventive perspective. This study, however, focuses on exploring NTU 101's therapeutic potential by investigating its effects on regulatory T cell (Treg) maturation and Th1/Th2 balance. The results revealed that NTU 101 administration effectively reduced serum IgE levels and inflammatory cell infiltration in the skin, leading to a significant improvement in both epidermal and dermal thickness in the AD model. Additionally, NTU 101 modulated the immune response by increasing the proportion of CD4+/IL-4+ (Th2) cells in the spleen and concurrently enhancing FOXP3 expression in CD4+/CD25+ cells, which is critical for Treg cell development. This immune modulation was further associated with a rebalancing of the Th1/Th2 ratio, achieved by increasing the proportion of CD4+/IFN-γ+ (Th1) cells. Moreover, NTU 101 influenced the proportion of CD4+IL-17+ (Th17) cells, thereby supporting neutrophil maturation and promoting allergen clearance, ultimately mitigating AD symptoms. These findings underscore the potential of NTU 101 not only in managing AD symptoms but also in modulating key immune pathways involved in the pathogenesis of the disease, offering a promising alternative or adjunct to conventional steroid therapies.

Resolution of Molluscum Contagiosum After Discontinuation of Topical Corticosteroids During Dupilumab Therapy for Atopic Dermatitis: A Case Report.

A 35-year-old male patient with atopic dermatitis (AD) was referred to our department for exacerbated AD lesions. His sudden discontinuation of topical corticosteroid had induced erythroderma on his face, extremities, and trunk. Additionally, he presented small multiple whitish papules, mainly on the trunk and thighs, diagnosed as molluscum contagiosum (MC). Dupilumab was initiated in combination with a topical corticosteroid (0.05% betamethasone butyrate propionate). After four weeks, the AD symptoms substantially improved, while MC showed no changes. After 11 weeks of dupilumab therapy, he abruptly stopped topical corticosteroid treatment, and the MC lesions completely resolved in two weeks.

Human Beta Defensin-2 mRNA and Proteasome Subunit ß Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients.

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human ß-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies.

Co-Expression Network and Machine Learning Analysis of Transcriptomics Data Identifies Distinct Gene Signatures and Pathways in Lesional and Non-Lesional Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin condition with complex origins. Current treatments often yield suboptimal results due to an incomplete understanding of its underlying mechanisms. This study aimed to identify pathway and gene signatures that distinguish between lesional AD, non-lesional AD, and healthy skin. METHOD: We conducted differential gene expression and co-expression network analyses to identify differentially co-expressed genes (DCEGs) in lesional AD vs. healthy skin, lesional vs. non-lesional AD, and non-lesional AD vs. healthy skin. Modules associated with lesional and non-lesional AD were identified based on the correlation coefficients between module eigengenes and clinical phenotypes (|R| ≥ 0.5, p-value < 0.05). Subsequently, we employed Ingenuity Pathway Analysis (IPA) on the identified DCEGs, followed by machine learning (ML) analysis within the pathway expression framework. The ML analysis of pathway expressions, selected by IPA and derived from gene expression data, identified relevant pathway signatures, which were validated using an independent dataset and correlated with AD severity measures (EASI and SCORAD). RESULTS: We identified 975, 441, and 40 DCEGs in lesional vs. healthy skin, lesional vs. non-lesional, and non-lesional vs. healthy skin, respectively. IPA and ML analyses revealed 25 relevant pathway signatures, including wound healing, glucocorticoid receptor signaling, and S100 gene family signaling pathways. Validation confirmed the significance of 10 pathway signatures, which were correlated with the AD severity measures. DCEGs such as MMP12 and S100A8 demonstrated high diagnostic efficacy (AUC > 0.70) in both the discovery and validation datasets. CONCLUSIONS: Differential gene expression, co-expression networks and ML analyses of pathway expression have unveiled relevant pathways and gene signatures that distinguish between lesional, non-lesional, and healthy skin, providing valuable insights into AD pathogenesis.

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.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Novel insights into immune checkpoints in psoriasis and atopic dermatitis: From expression and function to treatments.

Psoriasis and atopic dermatitis (AD) are both chronic inflammatory skin diseases, which are common and difficult to cure. Currently, the emerging biologics have demonstrated outstanding efficacy, but not all patients are able to benefit from them, and traditional systemic treatments come with many severe side effects. The emergence of immune checkpoints brings new hope to solve this problem. Immune checkpoints regulate T cell activation. Upon damage to the co-inhibitory molecules, the inhibition on T cells is removed, leading to the excessive activation of T cells. In this review, we delineate and highlight the expression and function of immune checkpoint molecules (CTLA-4, PD-1, TIM-3, TIGIT, VISTA, LAG-3, OX40, GITR) in psoriasis and AD. We provide preclinical and clinical studies supporting a potential therapeutic approach of targeting these checkpoints for inflammatory skin diseases. Moreover, the complexity of immune checkpoints and safety of clinical application are discussed.

Effect of a topical traditional Chinese herbal medicine on skin microbiota in mouse model of atopic dermatitis.

This study aims to explore the impact of the herbal ointment Chushi Zhiyang Ruangao (CSZYRG) on the skin's microecological environment in a mouse model of atopic dermatitis (AD) and to understand the underlying mechanisms involved. The AD model was established in C57 mice using calpolitol (a hypocalcemic analog of vitamin D3; MC903). Medication-free matrix ointment, CSZYRG, and mometasone furoate cream (positive control group) were applied to the injured areas. The skin lesions of AD model mice were photographed. Skin lesions were applied for the hematoxylin and eosin (H&E) staining to observe any pathological changes. Serum immunoglobulin IgE was detected by enzyme-linked immunosorbent assay (ELISA). The changes in the expression of inflammation-related factors TNF-α, IL-1ß, and IL-6 in mice were detected using ELISA and qRT-PCR. Skin microflora samples were taken for 16S rDNA sequencing and analyzed for changes in the skin flora diversity, abundance, and dominant flora in mice. It was concluded that CSZYRG effectively alleviates skin lesions, serum IgE, and levels of TNF-α, IL-1ß, and IL-6 in AD model mice. However, CSZYRG did not affect the skin microbial diversity of AD model mice but could exert an effect on the skin microbial community in AD mice and the relative abundance of the dominant microflora. CSZYRG may play a therapeutic role in AD by affecting the skin microbial community and relative abundance of dominant microflora in AD mice.

The Rare Adverse Effect of Myalgia After Dupilumab Biologic Therapy for Refractory Atopic Dermatitis.

Dupilumab, a systemic injectable biologic, can be prescribed to patients with atopic dermatitis who do not respond to topical treatments. Atopy can frequently subside by blocking inflammatory pathways, such as interleukin-4 (IL-4) and interleukin-13 (IL-13) in the immune system. Dupilumab is generally well-tolerated and mild; the most common adverse reactions listed are arthralgia, back pain, and conjunctivitis, which clears upon cessation or finalization of dupilumab therapy. This case report describes a patient experiencing severe myalgia - a rare adverse effect. The patient's atopic dermatitis was refractory toward topical treatments, but within one month of starting dupilumab, he experienced severe myalgias and muscle spasms, which prompted cessation of dupilumab despite it working well for his atopic dermatitis.

Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review.

Importance: Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges. Objective: To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents. Evidence review: On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents. Findings: A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic. Conclusions and relevance: Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.

Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.

Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG, and RARRES1. Also, inflammation-related SAA1 was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6, or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. SERPINF1, FKBP5, IFIT1/3, DDX58) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. ACOT4, S1PR3), keratinization (e.g. LCE5A, KRT5/7/16), neutrophil degranulation, and antimicrobial peptides (e.g. LTF, DEFB4A, S100A7-9). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.

A Mouse Model for Eosinophilic Esophagitis (EoE).

Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE. Despite this, a robust mouse model that mimics human disease is still crucial for both understanding disease pathogenesis and as a preclinical model for testing future therapeutics. Herein, we describe a highly reproducible and robust model of EoE that can be performed using wild-type mice by ear sensitization with oxazolone (OXA) followed by intraesophageal challenges. Experimental EoE elicited by OXA mimics the main histopathological features of human EoE, including intraepithelial eosinophilia, epithelial and lamina propria thickening, basal cell hyperplasia, and fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of EoE in mice using oxazolone Support Protocol 1: Preparing the mouse esophagus for histological analysis Support Protocol 2: Assessment of epithelial and lamina propria thickness using H&E staining Support Protocol 3: Assessment of eosinophilic infiltration using anti-MBP and basal cell proliferation using anti-Ki-67 staining Support Protocol 4: Flow cytometry of mouse esophageal samples Support Protocol 5: ELISA on protein lysates of esophageal samples.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Ozonated Sunflower Oil (OSO) Alleviates Inflammatory Responses in Oxazolone-Induced Atopic Dermatitis (AD)-Like Mice and LPS-Treated RAW 264.7 Cells.

Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1ß and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1ß, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.

Is corticophobia spreading among pediatricians?-Insights from a self-efficacy survey on the management of pediatric atopic dermatitis.

Background: Atopic dermatitis (AD) is a chronic dermatological condition, often diagnosed and managed by pediatricians. However, pediatricians have difficulties with adhering to guidelines, which recommend the use of topical corticosteroids (TCS) as a first-line treatment and oral corticosteroids (OCS) for resistant cases. Our aim was to assess pediatricians' self-confidence in using steroids in the management of pediatric AD, and investigate which characteristics are related to high self-confidence in prescribing corticosteroids (CS). Methods: We conducted a cross-sectional questionnaire study among Israeli pediatricians between April 2022 and June 2022. Participants were asked to answer questions dealing with self-assessment of prescribing CS in the management of AD. Results: A total of 171 residents and pediatricians participated in the survey; 86.6% and 28.1% admitted feeling either average or below-average confidence in the prescription of OCS and TCS, respectively. Physicians who were exposed to higher AD patients (P=0.048) and worked at the clinics (88.2% vs. 60.4%, P<0.001) had high self-confidence in treating AD with TCS. Males (20.3% vs. 8%, P=0.03), and having gone to medical school outside Israel (22.2% vs. 10.4%, P=0.09) were all related to high self-efficacy in prescribing OCS. In total, 11.7% of participants confessed to refraining from prescribing steroids because of fear of side effects. Conclusions: Most pediatricians have below-average confidence in prescribing OCS for the treatment of AD. Males, working in a community setting, and previous exposure improve the confidence level and can be easily considered in future pediatric training programs.

Heat shock protein 90 (Hsp90) inhibitor STA-9090 (Ganetespib) ameliorates inflammation in a mouse model of atopic dermatitis.

Molecular chaperones belonging to the heat shock protein 90 (Hsp90) family are implicated in inflammatory processes and described as potential novel therapeutic targets in autoimmune/inflammatory skin diseases. While the pathological role of circulating Hsp90 has been recently proposed in patients with atopic dermatitis (AD), a chronic inflammatory skin disease characterized by intense itching and recurrent skin lesions, studies aimed at investigating the role of Hsp90 as a potential target of AD therapy have not yet been conducted. Here, the effects of the Hsp90 blocker STA-9090 (Ganetespib) applied systemically or topically were determined in an experimental mouse model of dinitrochlorobenzene (DNCB)-induced AD. Intraperitoneal administration of STA-9090 ameliorated clinical disease severity, histological epidermal thickness, and dermal leukocyte infiltration in AD mice which was associated with reducing the scratching behavior in DNCB-treated animals. Additionally, topically applied STA-9090 led to lowered disease activity in AD mice, reduced serum levels of IgE, and up-regulated filaggrin expression in lesional skin samples. Our observations suggest that Hsp90 may be a promising therapeutic target in atopic dermatitis and potentially other inflammatory or autoimmune dermatoses.

A case of dupilumab combination therapy for exacerbation of atopic dermatitis in a patient with eosinophilic granulomatosis with polyangiitis treated with mepolizumab.

We report a 60-year-old male with eosinophilic granulomatosis with polyangiitis (EGPA) complicated with atopic dermatitis (AD). The patient was initially treated with prednisolone, cyclosporine A, and mepolizumab (MEPO). Due to worsening skin symptoms after prednisolone tapering, dupilumab (DUP) was added as an adjunctive therapy for AD confirmed by skin biopsy. The combination therapy of MEPO and DUP resulted in rapid improvement of skin symptoms, suggesting it may be an effective therapeutic option for patients with EGPA and AD. This case report emphasises the importance of a multidisciplinary approach in treating complex diseases such as EGPA and AD.

Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus.

Background: Chronic scratching imposes a major stress on the skin and can lead to itch intensity worsening, and consequently, patients may enter an itch-scratch cycle. This repetitive mechanical stress can result in lichenification, worsening of epidermal barrier function, and enhanced cutaneous inflammation. Furthermore, a reduction of intraepidermal nerve fibers was previously described in lichenification. Aim: The aim of this study was to investigate the influence of chronic scratching on the epidermal neuroanatomy and on sensory changes, in particular the prevalence of hyperknesis and alloknesis in patients after mechanical, chemical, and electrical stimuli. Methods: Analyses were performed on pruritic lichenified (chronically scratched), pruritic non-lichenified (not chronically scratched), and non-pruritic non-lesional (unaffected) skin areas of patients with inflammatory pruritus, i.e., atopic dermatitis (n = 35), and neuropathic pruritus, i.e., brachioradial pruritus (n = 34) vs. healthy matched controls (n = 64). Our fine-grained spatial skin characterization enabled specifically studying the differential effects of chronic scratching in inflammatory and neuropathic itch. Results: Analysis of intraepidermal nerve fiber density showed rarefaction of fibers in all three skin areas of patients compared with healthy controls in both diagnoses. Even more, the two pruritic areas had significantly less nerve fibers than the unaffected skin, whereas electrically induced itch was massively increased. Epidermal branching of the remaining nerve fibers in lichenified/chronically scratched skin was increased, particularly in patients with brachioradial pruritus, which may contribute to the pronounced local neuronal sensitivity. Hyperknesis and alloknesis were found to increase independently of lichenification. Conclusion: Our results indicate that chronic scratching may not affect intraepidermal nerve fiber density but leads to a stronger branching pattern of intraepidermal nerve fibers, which may contribute to local hypersensitivity. The increased sensitivity in the pruritic areas suggests mechanisms of peripheral sensitization, whereas the increased sensation of electrically and chemically induced itch in unaffected skin indicates central sensitization for itch.

Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications.

Frequent use of hormones and drugs may be associated with side-effects. Recent studies have shown that probiotics have effects on the prevention and treatment of immune-related diseases. Limosilactobacillus reuteri (L. reuteri) had regulatory effects on intestinal microbiota, host epithelial cells, immune cells, cytokines, antibodies (Ab), toll-like receptors (TLRs), tryptophan (Try) metabolism, antioxidant enzymes, and expression of related genes, and exhibits antibacterial and anti-inflammatory effects, leading to alleviation of disease symptoms. Although the specific composition of the cell-free supernatant (CFS) of L. reuteri has not been clarified, its efficacy in animal models has drawn increased attention to its potential use. This review summarizes the effects of L. reuteri on intestinal flora and immune regulation, and discusses the feasibility of its application in atopic dermatitis (AD), asthma, necrotizing enterocolitis (NEC), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), and provides insights for the prevention and treatment of immune-related diseases.