Anti-atopic dermatitis effect of fraxinellone via inhibiting IL-31 in vivo and in vitro.

Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. Anti-IL-31 receptor α (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.; however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD.

Prevalence, severity, and risk factors of eczema among young children and adolescents in Saudi Arabia: A national cross-sectional study, 2019.

Background: Eczema is a common inflammatory skin disease with a significant global health burden. Eczema has a significant impact on quality of life. Objective: We aimed to estimate the prevalence, severity, and risk factors associated with eczema among schoolchildren in Saudi Arabia. Methods: The standardized Global Asthma Network questionnaires and methodology were used to conduct a nationwide cross-sectional study across 20 regions in Saudi Arabia between March and April 2019. Data were collected from 137 primary schools and 140 intermediate schools by using a multistage stratified cluster sampling method. Results: The study included 3614 young children aged 6 to 7 years and 4068 adolescents aged 13 to 14 years. Current eczema was prevalent among 4.5% of the children and 5.1% of the adolescents. Severe eczema was reported in 0.8% and 0.9% of the young children and adolescents, respectively. Several factors showed significant association with eczema. Among the children, eczema was linked positively to having a history of chest infections and wheezing in early life, as well as to ever attending day care and current exposure to cats. Among the adolescents, the main potential risk factors included paracetamol use in the previous year, adherence to a lifestyle of vigorous physical activity, and current exposure to cats. Conversely, high consumption of nuts was found to be negatively associated with eczema. Conclusion: The prevalence of eczema in schoolchildren in Saudi Arabia is lower than the global average but within the average range for the Eastern Mediterranean region. Further studies in Saudi Arabia should be conducted to identify variation among different regions.

A Fleshy Mystery: Prurigo Nodularis.

Prurigo nodularis is a chronic dermatologic condition typically presenting as firm, dome-shaped pruritic nodules of various sizes that are often symmetrically distributed on extensor surfaces of the extremities. The diagnosis is clinical and based on a history of chronic, severe pruritis in the setting of characteristic, excoriated lesions. Treatment is difficult and aimed at reducing skin irritation and pruritus. Quality of life is impacted due to the chronic, intractable, and relapsing nature of the disease. Here, we report a case of prurigo nodularis diagnosed in the outpatient clinic setting. This paper aims to report the patient's clinical history, presentation, and histopathologic findings, as well as present a literature review to determine the significance of this case and the approach to ongoing management.

Decreased expression of galectin-3 in the epidermis of psoriasis patients.

Conventional histopathological features of psoriasis and atopic dermatitis often overlap. We aimed to investigate Galectin-3 (Gal-3) expression in psoriatic skin lesions and its potential as an immunohistochemical marker for distinguishing between psoriasis and atopic dermatitis on a pathological basis. Based on immunohistochemical analysis, we assessed Gal-3 expression in formalin-fixed, paraffin-embedded tissue sections from 21 patients with psoriasis and 15 patients with atopic dermatitis. Quantitative analysis of expression intensity was performed using the average density (average optical density) method. We analysed the relationship between Gal-3 expression and clinical characteristics, as well as conventional histopathological features. Patients with psoriasis exhibited significantly decreased Gal-3 expression in the epidermis (0.11±0.05) compared to the atopic dermatitis group (0.36±0.15) and healthy controls (0.49±0.13) (p<0.0001). Reduction in Gal-3 expression in the psoriatic epidermis around areas of neutrophil aggregation was more pronounced than around areas of non-neutrophil aggregation (0.07±0.02 vs 0.16±0.05, p<0.01). In both psoriasis (r=-0.48, p<0.05) and atopic dermatitis groups (r=-0.70, p<0.01), Gal-3 expression negatively correlated with epidermal thickness. When epidermal thickness was matched between the two groups, the decrease in epidermal Gal-3 expression remained significant in the psoriasis group compared to the atopic dermatitis group (0.14±0.05 Vs 0.30±0.07, p<0.01). Patients with psoriasis show specific downregulation of epidermal Gal-3, correlating with epidermal thickness and neutrophil-related factors. Gal-3 may serve as an auxiliary discriminative marker between psoriasis and atopic dermatitis, potentially associated with keratinocyte proliferation and neutrophil function.

A Case of Pseudomonas straminea Blood Stream Infection in an Elderly Woman with Cellulitis.

Here, we report the simultaneous isolation of Pseudomonas straminea from blood cultures and from a skin ulcer in an elderly woman who suffered from atopic dermatitis and psoriasis and developed acute cellulitis of both arms requiring hospital treatment. To the best of our knowledge, P. straminea has not been previously reported to cause invasive infections in humans. This case highlights how chronic diseases and older age increase the susceptibility to bacterial infections with environmental bacteria of low virulence. Our study describes the microbiological identification of the blood culture isolate, including morpho-molecular characterization and virulence demonstration in a Galleria mellonella model.

IL-22 in Atopic Dermatitis.

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating the underlying mechanisms of the disease has facilitated the identification of new potential therapeutic targets and promising drug candidates. In this review, we summarize the newest data, considering multiple connections between IL-22 and AD. The presence of circulating IL-22 has been found to correlate with the severity of AD and is identified as a critical factor driving the inflammatory response associated with the condition. Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD.

Antibacterial and Immunosuppressive Effects of a Novel Marine Brown Alga-Derived Ester in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin condition that is characterized by dysregulated immune responses and a heightened risk of Staphylococcus aureus infections, necessitating the advancement of innovative therapeutic methods. This study explored the potential of (6Z,9Z,12Z,15Z)-(2R,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl octadeca-6,9,12,15-tetraenoate (HSN-S1), a compound derived from the marine alga Hizikia fusiformis, which shows anti-inflammatory, antimicrobial, and immunomodulatory properties. HSN-S1 was isolated and characterized using advanced chromatographic and spectroscopic methods. Its efficacy was evaluated via in vitro assays with keratinocytes, macrophages, and T cells to assess cytokine suppression and its immunomodulatory effects; its antibacterial activity against S. aureus was quantified. The in vivo effectiveness was validated using a 2,4-dinitrochlorobenzene-induced AD mouse model that focused on skin pathology and cytokine modulation. HSN-S1 significantly reduced pro-inflammatory cytokine secretion, altered T-helper cell cytokine profiles, and showed strong antibacterial activity against S. aureus. In vivo, HSN-S1 alleviated AD-like symptoms in mice and reduced skin inflammation, transepidermal water loss, serum immunoglobulin-E levels, and Th2/Th17 cytokine outputs. These findings suggest HSN-S1 to be a promising marine-derived candidate for AD treatment, as it offers a dual-target approach that could overcome the limitations of existing therapies, hence warranting further clinical investigation.

Budget impact and cost per responder analysis of upadacitinib for the treatment of moderate to severe atopic dermatitis from the perspective of the social security and the private sector in Argentina.

OBJECTIVES: Our study assessed the budget impact and cost per responder of upadacitinib15mg and 30 mg for moderate to severe atopic dermatitis (MS-AD) treatment from social security and private health sector perspective in Argentina. METHODS: A budget impact model was adapted to depict clinical and economic aspects of treatment over a 5-years horizon time. Scenario analyses and deterministic sensitivity analyses were performed. A 16-weeks cost per responder model was adapted based on a network meta-analysis. Primary analyses assessed the cost per Eczema Area and Severity Index 50, 75 and 90 at week 16. RESULTS: The inclusion of upadacitinib 15 mg and 30 mg in the biological treatment mix for MS-AD was associated with an average budget saving per-member per-month ofU$S0.062 (social security) and U$S0.064 (private sector). Percentage of patients with access to treatment, acquisition cost of upadacitinib 30 mg and prevalence of MS-AD were the most influential parameters in the budget impact results. At week 16, upadacitinib 30 mg was associated with the lowest number needed to treat and the lowest cost per responder for all outcomes. CONCLUSION: The introduction of upadacitinib in MS-AD treatment was associated with modest savings for the social security and private payer budget in Argentina.

Prevalence of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Background: Atopic dermatitis (AD) negatively affects quality of life and places a substantial financial burden on health care systems due to treatment costs and increased demand for services. Objective: To estimate the worldwide prevalence of AD, the proportion of severe cases worldwide and explore sources of heterogeneity. Methods: We searched MEDLINE, Embase, and Global Index Medicus from January 2012 up until August 30, 2022. We included primary prevalence studies published from 2012 onward. Study selection was conducted by two reviewers independently. One reviewer performed data extraction and assessed risk of bias using the JBI Critical Appraisal Checklist for Prevalence Studies, with independent checking by a second reviewer. Random-effects meta-analyses were conducted to pool results; subgroup analyses were conducted to evaluate potential modifiers. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Main outcomes were point prevalence and proportion of severe cases. Results: We identified 12,774 unique references and assessed 1029 full texts, ultimately resulting in the inclusion of 310 studies with 25.5 million individuals. Point prevalence was 11.1% (95% CI 9.4-13.1; 123 studies; 12,776,910 individuals; moderate certainty of evidence) in children and adolescents, and 6.3% (95% CI 5.0-7.8; 59 studies; 12,794,260 individuals; moderate certainty of evidence) in adults. Relatively similar results were observed for studies with low risk of bias. Proportion of severe cases varied from 1.9 to 7.2% in children and adolescents and 2.8% to 15.6% in adults. Conclusions: These findings may underpin effective health care policies, research initiatives, and clinical decision-making.

Exploring novel drug targets for atopic dermatitis through plasma proteome with genome.

Atopic dermatitis (AD) is a chronic inflammatory disease with a complex and heterogeneous clinical presentation, leading to treatment limitations. Therefore, there is an urgent demand for new therapeutic drug targets. This study utilized Summary-data-based Mendelian randomization (SMR) to identify potential drug targets for AD. Summary statistics for 2,940 human plasma proteins were obtained from the UK Biobank, while AD statistics came from the Early Genetics and Epidemiology of Life Processes consortium and the FinnGen consortium. Furthermore, subsequent colocalization analyses confirmed the causal roles of candidate proteins. Moreover, Phenome-Wide Association Studies (PheWAS), protein-protein interaction (PPI), enrichment analysis, and single cell-type expression analysis provided additional insights. Additionally, drug prediction, druggability prediction, and molecular docking informed the discovery of novel drug targets. SMR analysis showed that eight plasma proteins were causally associated with AD: PVALB and TST were associated with a reduced risk of AD, while CA14, ECM1, IL22, IL6R, IL18R1, and MMP12 were associated with an increased risk of AD. Colocalization analysis confirmed significant associations for TST, IL22, and CA14. PheWAS further revealed that candidate drug targets were mainly linked to other allergic diseases. The corresponding protein-coding genes are predominantly expressed in melanocytes, T cells, and macrophages in skin tissue. Importantly, these proteins were identified to be involved in cytokine-cytokine receptor interaction, Th17 cell differentiation, and the JAK-STAT signaling pathway. All of these proteins are druggable, and six of them show great potential as drug targets. In conclusion, this study identified eight plasma proteins causally associated with AD and provided new insights into the etiology and potential drug targets for AD.

Recent prevalence of allergic rhinitis caused by house dust mites among the pediatric population in Fukui, Japan.

Background: Allergic rhinitis (AR) is an IgE-mediated type I allergic chronic nasal disease common among all age groups, including the pediatric population. House dust mites (HDMs) are globally ubiquitous and the most important indoor aeroallergen. However, the recent prevalence of HDM-caused AR (AR-HDM) in Japan remains unknown, especially after the COVID-19 pandemic. Objective: The objective of this study was to investigate the current prevalence of AR-HDM, its clinical features, and the current status of medical examinations in elementary school students. Methods: A survey of 41,000 elementary school students was conducted during July 2021 in Fukui Prefecture, Japan. Parents were asked to complete a questionnaire that examined allergic disease history and clinical background. Results: A total of 17,974 subjects were analyzed in the study. The results showed that the current prevalence of AR-HDM in elementary school children is 18.8%. We found that AR-HDM had already developed before entrance into elementary school in 68.3% of affected subjects. Among these subjects, 82.3% had received some form of treatment, such as prescription medications, whereas 4.2% were treated by allergen immunotherapy. Multiple logistic regression analysis of the onset of AR-HDM revealed that male sex, being the first-born child, comorbidity of bronchial asthma, atopic dermatitis, food allergy, and allergic conjunctivitis are associated with development of AR-HDM. Conclusions: The present study revealed the prevalence of AR-HDM in elementary school children. The results emphasize the importance of appropriate diagnosis and treatment from infancy through early childhood.

A randomized controlled trial comparing tacrolimus versus hydrocortisone for the treatment of atopic dermatitis in children: new perspectives on interferon gamma-induced protein and growth-related oncogene-α.

Introduction: Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children. Aim: To investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children. Patients and methods: This clinical randomized investigation included 100 children with AD who met the eligibility criteria. AD patients were recruited from Tanta University's Dermatology Department and divided into two groups (n = 50)., For four months, group 1 (the hydrocortisone group) received topical hydrocortisone cream. Group 2 received topical tacrolimus for four months. A dermatologist evaluated the patients at the start and four months after the treatment had been initiated to measure serum concentrations of neutrophil chemoattractant growth-related oncogene-α (GRO-α), interferon gamma induced protein 10 (IP-10), tumor necrosis factor alpha (TNF-α), vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1). All patients were examined using the modified Eczema Area and Severity Index (mEASI) score. Results: Tacrolimus group showed a significant reduction in serum levels of all measured biomarkers (p < 0.05) when compared to its baseline and when compared to the hydrocortisone group. Both groups displayed a significant decline in mEASI score in comparison with their baseline values (p < 0.05). Conclusion: In children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone, suggesting its potential as a more effective treatment option. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05607901.

The role of nemolizumab in the treatment of atopic dermatitis for the adult population.

Atopic dermatitis (AD) often requires long-term treatment that may be associated with adverse effects. This review aims to characterize nemolizumab as a treatment for AD in adults. A literature search was performed to assess nemolizumab's role in moderate-to-severe AD in adults. Currently, clinical trials are being conducted to evaluate the clinical efficacy, safety profile and optimal dosing of nemolizumab for adults with moderate-to-severe AD. The most common adverse effects include nasopharyngitis, AD exacerbation and increased blood creatinine phosphokinase. Recent data from clinical trials suggest nemolizumab may be an acceptable treatment in adults with moderate-to-severe AD.

Atopic dermatitis, also known as eczema, is a long-lasting skin condition that is difficult to treat. Symptoms include itching, redness, dryness and pain. Various eczema treatments are available to help patients based on how severe their symptoms are. Nemolizumab is a treatment that blocks immune system pathways involving itching and inflammation. This review describes nemolizumab as a treatment option for moderate-to-severe eczema in adults. We completed a literature search to understand nemolizumab's role in eczema treatment. Nemolizumab has decreased itchiness in adults with moderate-to-severe eczema in clinical trials. The most common side effects of nemolizumab treatment were the common cold, worsening of eczema and an increased muscle marker (creatinine phosphokinase). Nemolizumab appears to be an effective treatment for moderate-to-severe eczema in adults with bearable side effects.

Unraveling the complexity - Insights and interventions of refractory vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses. Lack of responsiveness to a drug or treatment is relatively common in VKC and it is not only due to corneal involvement, which is considered the main sign of severity. The concept of refractory may be relative to multiple factors including the clinical condition, systemic co-morbidities, previous or concomitant drugs or regiments, compliance, patient's psychological condition or expectations, type of exposome and environmental conditions, doctor's experience and expectations, or timing of clinical evaluation. In this narrative review, the authors propose a definition of refractory VKC based on revised literature and clinical experience and consider potential new treatments for refractory patients and surgical management in case of complications.

The role of excimer light in dermatology: a review.

Excimer light is a subtype of NB-UVB that emits a 308 nm wavelength, and can provide targeted phototherapy treatment. The absorption of 308 nm light by skin cells leads to therapeutic response in various common and ultraviolet-responsive skin diseases, such as psoriasis and vitiligo, and photo-resistant skin diseases such as prurigo nodularis, localized scleroderma, genital lichen sclerosis, and granuloma annulare, cutaneous T-cell lymphomas, among others. Excimer light has few adverse reactions and overall is well tolerated by patients, furthermore, it can be performed in places that are difficult to access. This article aims to explain the therapeutic bases and applications of excimer light in current dermatology.

More Time Spent with Clear Skin and No Itch with Upadacitinib versus Dupilumab for Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD. METHODS: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up. RESULTS: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab. CONCLUSIONS: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).

Treatment of moderate-to-severe canine atopic dermatitis with modified-release mycophenolate (OKV-1001): A pilot open-label, single-arm multicentric clinical trial.

BACKGROUND: Mycophenolate is an immunomodulating agent successfully used for the treatment of moderate-to-severe atopic dermatitis (AD) in people. Mycophenolate is an effective steroid-sparing treatment option for use in dogs with inflammatory skin diseases. OBJECTIVE: To evaluate whether once-daily modified-release mycophenolate (OKV-1001) is safe and effective for treating moderate-to-severe canine AD. ANIMALS: Client-owned atopic dogs (n = 9) were enrolled. MATERIALS AND METHODS: In an open-label multicentre pilot study, OKV-1001 (30 mg/kg every 24 h) was given orally for ≤84 days. Concomitant tapering doses of glucocorticoids were administered up to Day (D)28. Clinicians assessed Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) on D0, D14, D28, D56 and D84. Body weight and clinical pathological parameters were measured at baseline and at the end of the study. RESULTS: Treatment with OKV-1001 combined with glucocorticoids significantly reduced the severity of AD within two weeks in seven of nine (77.8%) dogs. The mean percentage change from baseline in the CADESI-04 score was 29% (p = 0.009) at D14 (n = 9), 39% (p = 0.008) at D28 (n = 9) and 49% (p = 0.03) at D56 (n = 7) at which point glucocorticoids had been withdrawn. In two dogs the improvement in CADESI-04 was 62% and 23% (respectively) on D84. No significant adverse events including clinical pathological findings were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Modified-release mycophenolate (OKV-1001) may represent a promising alternative treatment option for dogs with moderate-to-severe AD. The safety and efficacy profile of OKV-1001 will need to be established in larger, placebo-controlled clinical trials.