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1.
Andes Pediatr ; 95(3): 236-243, 2024 Jun.
Article in Spanish | MEDLINE | ID: mdl-39093208

ABSTRACT

Atopic dermatitis (AD) is a chronic, non-infectious inflammatory dermatosis, with increasing prevalence in recent decades. Due to its chronic and recurrent nature, it diminishes the quality of life of patients and their families. In recent years, advances in the understanding of AD's pathophysiology have driven the development of targeted therapies such as monoclonal antibodies (mAbs) and Janus kinase inhibitors (JAKis) which modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. Four targeted therapies have been approved in the USA for the treatment of severe/refractory cases: dupilumab, tralokinumab, abrocitinib, and upadacitinib. This manuscript aims to present an update on the pathophysiology of AD, describe the new treatments available, and provide an analysis of the initial results of the use of these treatments in the pediatric population. We concluded that the high cost of these treatments often limits their prescription to situations where cases of atopic dermatitis are resistant to other conventional therapeutic options or when the disease reaches a severe degree. This underscores the importance of careful and accurate decision-making in the medical management of AD to ensure the efficient use of these therapeutic resources.


Subject(s)
Dermatitis, Atopic , Precision Medicine , Dermatitis, Atopic/drug therapy , Humans , Child , Janus Kinase Inhibitors/therapeutic use , Severity of Illness Index , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Molecular Targeted Therapy/methods , Pyrimidines , Sulfonamides
3.
Cells ; 13(16)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39195286

ABSTRACT

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.


Subject(s)
Dermatitis, Atopic , Interleukin-22 , Interleukins , Dermatitis, Atopic/pathology , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/immunology , Humans , Interleukins/metabolism , Animals , Keratinocytes/metabolism , Skin/pathology , Skin/metabolism , Microbiota
4.
Mar Drugs ; 22(8)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39195470

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Cytokines , Dermatitis, Atopic , Immunosuppressive Agents , Phaeophyceae , Staphylococcus aureus , Dermatitis, Atopic/drug therapy , Animals , Mice , Phaeophyceae/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Staphylococcus aureus/drug effects , Cytokines/metabolism , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/isolation & purification , Immunosuppressive Agents/chemistry , Disease Models, Animal , Esters/pharmacology , Esters/chemistry , Female , Mice, Inbred BALB C , Aquatic Organisms , Keratinocytes/drug effects
5.
J Drugs Dermatol ; 23(8): 669-673, 2024 08 01.
Article in English | MEDLINE | ID: mdl-39093654

ABSTRACT

Atopic Dermatitis (AD) is a common chronic inflammatory skin condition, with high prevalence in children. Sun protection is important for children with eczema and AD-prone skin, yet many sunscreens can cause skin irritation due to their formulations. In this study, we evaluated the safety and tolerance of an SPF 50 sunscreen in ethnically diverse children with a history of AD over 4 weeks of product use. A total of 45 children from diverse racial/ethnic backgrounds, aged 3 to 12 years old with skin phototypes I-VI, plus a history of eczema and perceived sensitive skin completed the study. All participants applied sunscreen daily on the face and body, at least 15 minutes prior to sun exposure and as needed. After 4 weeks, evaluations were performed by a dermatologist and by participants for tolerability. Product performance questionnaires were also completed by parents/guardians of pediatric participants. After 4 weeks of sunscreen application, tolerability assessments of skin dryness, peeling, erythema, and edema were all absent in children participants. Parent/guardian evaluations of sunscreen tolerability for their child also revealed no perceived skin issues. These results were consistent with no adverse event being observed throughout the study. Parents/guardians reported that sunscreen application on children was smooth and even, with the absence of a white cast appearance on children with skin of color. We conclude from this study that this SPF 50 sunscreen is safe to use in ethnically diverse children with a history of AD and sensitive skin. J Drugs Dermatol. 2024;23(8):669-673.  doi:10.36849/JDD.8282.


Subject(s)
Dermatitis, Atopic , Sunscreening Agents , Humans , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/ethnology , Child , Female , Male , Child, Preschool , Sunscreening Agents/administration & dosage , Sunscreening Agents/adverse effects , Ethnicity , Administration, Cutaneous , Skin/drug effects , Skin/pathology , Surveys and Questionnaires
6.
Int J Cosmet Sci ; 46(4): 516-525, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39113306

ABSTRACT

OBJECTIVE: Atopic dermatitis (AD) is characterized by compositional and structural changes to the skin at lesional sites. Alteration to the levels and organization of both protein and lipid components are associated with disease status and lead to impaired barrier and hydration. Corneodesmosin (CDSN) and the arrangement and length of the intercellular lipid lamellae (ICLL) are altered in disrupted skin states. The aim of this research was to profile the distribution of CDSN and the ICLL in the stratum corneum (SC) at lesional and non-lesional sites in AD-prone skin and to investigate the impact of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. METHODS: An IRB-approved study was conducted with participants with active AD. From a small subset of participants, tape strips were collected from lesional and non-lesional sites on the arm, prior to and after twice daily application, over 4 weeks of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Fluorescent antibody staining was used to investigate the distribution of CDSN. Transmission electron microscopy (TEM) was used to characterize the ICLL. RESULTS: The distribution/coverage of CDSN was similar between lesional and non-lesional sites at baseline; application of the lotion resulted in a more defined honeycomb/peripheral distribution. Normalized ICLL (nICLL) was lower in baseline samples from lesional sites relative to non-lesional sites. Application of the lotion increased this parameter by the end of the study at all sites. CONCLUSION: The eczema calming lotion containing petroleum jelly, fatty acids and colloidal oatmeal provided changes in corneodesmosomal proteins distribution and ICLL, consistent with improvements in corneocyte maturation and improved barrier function in the skin of individuals with atopic dermatitis.


OBJECTIF: La dermatite atopique (DA) est caractérisée par des modifications de la composition et de la structure de la peau au niveau des sites lésionnels. L'altération des taux et de l'organisation des composants protéiques et lipidiques est associée au statut de la maladie, et entraîne une altération de la barrière et de l'hydratation. La cornéodesmosine (CDSN), et la disposition et la longueur des lamelles lipidiques intercellulaires (LLIC) sont altérées dans les états cutanés perturbés. L'objectif de cette étude était d'établir le profil de la distribution de la CDSN et des LLIC dans la couche cornée (CC) au niveau des sites lésionnels et non lésionnels dans la peau sujette à la DA, et d'étudier l'impact d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. MÉTHODES: Une étude approuvée par un CPP a été menée auprès de participants atteints de DA active. Dans un petit sous­ensemble de participants, des bandes adhésives ont été prélevées sur des sites lésionnels et non lésionnels du bras, avant et après l'application deux fois par jour pendant 4 semaines d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. Une coloration par anticorps fluorescents a été utilisée pour étudier la distribution de la CDSN. La microscopie électronique en transmission (MET) a été utilisée pour caractériser les LLIC. RÉSULTATS: La distribution/couverture de la CDSN était similaire entre les sites lésionnels et non lésionnels à l'entrée dans l'étude; l'application de la lotion a entraîné une distribution en nid d'abeille/périphérique plus définie. Le taux normalisé de LLIC (LLICn) était plus faible dans les échantillons prélevés à l'entrée dans l'étude au niveau des sites lésionnels par rapport aux sites non lésionnels. L'application de la lotion a augmenté ce paramètre à la fin de l'étude pour tous les sites. CONCLUSIONS: La lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale a entraîné des changements dans la distribution des protéines cornéodesmosomales et des LLIC, ce qui correspond à des améliorations de la maturation des cornéocytes et de la fonction de barrière de la peau des personnes atteintes de dermatite atopique.


Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Adult , Male , Female , Glycoproteins/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Lipids/chemistry , Eczema/drug therapy , Eczema/pathology , Eczema/metabolism , Skin Cream , Young Adult , Epidermis/metabolism , Epidermis/drug effects , Epidermis/pathology , Middle Aged
8.
Arch Dermatol Res ; 316(8): 557, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177922

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by increased sensitivity to environmental allergens and irritants. Icariin, a natural compound extracted from the herb Epimedium, has been traditionally used for its potential anti-inflammatory and antioxidant properties. This study aimed to investigate the regulatory effects of icariin on AD-like symptoms and to elucidate its underlying mechanisms. The effects of icariin on TNF-α/IFN-γ-induced HaCaT cell injury were assessed using various assays, including cell counting kit-8 for cell viability, flow cytometry for reactive oxygen species (ROS) levels, and colorimetric assays for malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. In addition, the study performed enzyme-linked immunosorbent assays to assess cytokines (IL-1ß, IL-6, and IL-8) and chemokines (MDC, TARC, and RANTES) levels. Flow cytometry was used to quantify apoptotic rate, while a wound-healing assay was conducted to assess cell migration. The expression of WT1 associated protein (WTAP) and serpin family B member 4 (SERPINB4) at the mRNA and protein levels was determined using qRT-PCR and western blotting, respectively. The associations between WTAP and SERPINB4 were analyzed using RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. Icariin treatment significantly mitigated TNF-α/IFN-γ-induced oxidative stress, inflammatory response, and apoptosis in HaCaT cells, while also reversing the inhibitory effect on cell migration. Icariin reduced the expression of WTAP in TNF-α/IFN-γ-stimulated HaCaT cells. Overexpression of WTAP reversed the effects of icariin in TNF-α/IFN-γ-stimulated HaCaT cells. WTAP silencing inhibited the mRNA stability of SERPINB4 through the m6A modification. SERPINB4 overexpression attenuated the effects of WTAP silencing on oxidative stress, inflammatory response, apoptosis, and migration of TNF-α/IFN-γ-stimulated HaCaT cells. Icariin treatment downregulated SERPINB4 expression by regulating WTAP in TNF-α/IFN-γ-stimulated HaCaT cells. Icariin ameliorated TNF-α/IFN-γ-induced human immortalized epidermal cell injury through the WTAP/SERPINB4 axis, highlighting the potential for targeted interventions in AD pathogenesis.


Subject(s)
Apoptosis , Dermatitis, Atopic , Flavonoids , HaCaT Cells , Interferon-gamma , Oxidative Stress , Tumor Necrosis Factor-alpha , Humans , Flavonoids/pharmacology , Oxidative Stress/drug effects , Apoptosis/drug effects , Tumor Necrosis Factor-alpha/metabolism , Interferon-gamma/metabolism , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Dermatitis, Atopic/metabolism , Serpins/metabolism , Keratinocytes/drug effects , Keratinocytes/metabolism , Cell Survival/drug effects , Signal Transduction/drug effects , Reactive Oxygen Species/metabolism , Cell Movement/drug effects , Antioxidants/pharmacology , Anti-Inflammatory Agents/pharmacology , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cytokines/metabolism
9.
Int J Mol Med ; 54(4)2024 Oct.
Article in English | MEDLINE | ID: mdl-39129316

ABSTRACT

Topical therapy remains a critical component in the management of immune­mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid­free therapeutic alternatives. Despite their potential for skin­selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier­based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti­inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these 'hard­to­formulate' macromolecules in the context of psoriasis and atopic dermatitis.


Subject(s)
Calcineurin Inhibitors , MTOR Inhibitors , Humans , Calcineurin Inhibitors/therapeutic use , Animals , MTOR Inhibitors/therapeutic use , Administration, Topical , Nanotechnology/methods , Dermatitis, Atopic/drug therapy , Nanoparticles/chemistry , Tacrolimus/therapeutic use , Tacrolimus/administration & dosage , Tacrolimus/pharmacology , Sirolimus/therapeutic use , Sirolimus/pharmacology , Drug Delivery Systems/methods
10.
Biomolecules ; 14(8)2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39199350

ABSTRACT

Graphene oxide (GO), a carbon-based material with oxygen-containing functional groups, can be applied in biomedicine for drug delivery, cancer therapy, and tissue regeneration. We have previously shown that nanoscale-sized graphene oxide (NGO), an oxidized graphene derivative, exhibits effective anti-inflammatory activity in a murine model of sepsis mediated by T helper (Th)1-promoting cytokines such as IFNγ and TNFα. However, whether NGO influences Th2-induced skin inflammation remains unclear. To address this issue, we employed an ovalbumin (OVA) plus aluminum hydroxide (Alum)-induced Th2-mediated skin inflammation model in conjunction with OVA-specific DO11.10 T cell receptor transgenic Balb/c mice. In vivo NGO injection upon OVA/Alum sensitization down-regulated OVA-elicited antigen-specific Th2 cells and GATA3-expressing Th2-type regulatory T cells. Next, we examined the effect of NGO injection on OVA/Alum-induced atopic dermatitis (AD)-like skin inflammation. NGO-injected mice exhibited significantly decreased Th2 disease phenotypes (e.g., a lower clinical score, decreased epidermal thickness and Th2 cell differentiation, and fewer infiltrated mast cells and basophils in skin lesions) compared with vehicle-injected control mice. Overall, our results suggest that NGOs are promising therapeutic materials for treating allergic diseases such as AD.


Subject(s)
Graphite , Mice, Inbred BALB C , Ovalbumin , Th2 Cells , Animals , Graphite/chemistry , Th2 Cells/immunology , Th2 Cells/drug effects , Mice , Alum Compounds/chemistry , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/pathology , Dermatitis, Atopic/immunology , Female , Inflammation/drug therapy , Inflammation/pathology , Inflammation/chemically induced , Down-Regulation/drug effects , Skin/drug effects , Skin/pathology , Skin/immunology , Nanoparticles/chemistry
11.
Int J Mol Sci ; 25(16)2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39201579

ABSTRACT

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD.


Subject(s)
Agrimonia , Dermatitis, Atopic , Plant Extracts , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Mice , Agrimonia/chemistry , Disease Models, Animal , Calcium Release Activated Calcium Channels/metabolism , Calcium Release Activated Calcium Channels/antagonists & inhibitors , Humans , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Calcium Signaling/drug effects , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , T-Lymphocytes/immunology
12.
Curr Allergy Asthma Rep ; 24(9): 485-496, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39105881

ABSTRACT

PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.


Subject(s)
Dermatitis, Atopic , Janus Kinase Inhibitors , Humans , Dermatitis, Atopic/drug therapy , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/administration & dosage , Child , Adolescent , Purines/therapeutic use , Administration, Oral , Azetidines/therapeutic use , Azetidines/administration & dosage , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Pyrimidines/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Treatment Outcome
13.
J Appl Microbiol ; 135(8)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39090975

ABSTRACT

As our understanding of dermatological conditions advances, it becomes increasingly evident that traditional pharmaceutical interventions are not universally effective. The intricate balance of the skin microbiota plays a pivotal role in the development of various skin conditions, prompting a growing interest in probiotics, or live biotherapeutic products (LBPs), as potential remedies. Specifically, the topical application of LBPs to modulate bacterial populations on the skin has emerged as a promising approach to alleviate symptoms associated with common skin conditions. This review considers LBPs and their application in addressing a wide spectrum of dermatological conditions with particular emphasis on three key areas: acne, atopic dermatitis, and wound healing. Within this context, the critical role of strain selection is presented as a pivotal factor in effectively managing these dermatological concerns. Additionally, the review considers formulation challenges associated with probiotic viability and proposes a personalised approach to facilitate compatibility with the skin's unique microenvironment. This analysis offers valuable insights into the potential of LBPs in dermatological applications, underlining their promise in reshaping the landscape of dermatological treatments while acknowledging the hurdles that must be overcome to unlock their full potential.


Subject(s)
Probiotics , Skin , Probiotics/therapeutic use , Humans , Skin/microbiology , Acne Vulgaris/microbiology , Acne Vulgaris/therapy , Acne Vulgaris/drug therapy , Wound Healing , Dermatitis, Atopic/microbiology , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/therapy , Microbiota , Skin Diseases/microbiology , Skin Diseases/drug therapy , Skin Diseases/therapy , Biological Products/therapeutic use
14.
Eur J Dermatol ; 34(4): 361-370, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39193672

ABSTRACT

Atopic dermatitis (AD) is associated with chronic inflammation and an altered skin barrier. Lipids of the stratum corneum of AD patients are known to differ substantially in composition from those of healthy subjects. A reconstructed human epidermis (RHE) model has been developed in vitro in order to mimic the characteristics of AD. In this study, using this model, we compared lipid profile modifications between control RHE and RHE treated with Th2 cytokines in order to mimic AD. We focused particularly on the lipid profile of the ceramide subclasses: non-hydroxy sphingosine (NS) and esterified ω-hydroxy sphingosine (EOS), which have been reported to be clearly modified in atopic skin. RHE lipids were extracted and analysed using high-performance liquid chromatography coupled to high-resolution mass spectrometry. The following lipid profile changes were observed in Th2-cytokine-treated RHE: (i) an increase in ceramide NS composed of an unsaturated fatty acid chain; (ii) an increase in saturated ceramide NS with small total carbon content (≤40 carbon atoms), whereas NS with a higher total carbon content (≥42 carbon atoms) was decreased; and (iii) a decrease in ceramide EOS. These results are in accordance with reported lipid profiles of human atopic skin in vivo. Moreover, the in vitro model represents a useful tool to better understand the pathogenesis of AD which may be used for future screening of new effective treatments.


Subject(s)
Ceramides , Cytokines , Dermatitis, Atopic , Epidermis , Th2 Cells , Humans , Ceramides/metabolism , Ceramides/analysis , Epidermis/metabolism , Epidermis/drug effects , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Cytokines/metabolism , Sphingosine/analogs & derivatives , Interleukin-4/metabolism , Models, Biological , Interleukin-33/metabolism , Thymic Stromal Lymphopoietin
15.
Eur J Dermatol ; 34(4): 409-415, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39193678

ABSTRACT

The therapeutic arsenal for atopic dermatitis (AD) has increased in recent years. The use of biologics or Janus kinase inhibitors (JAKi) is advocated following failure or contraindication to cyclosporine (CSA), however, it is not known whether treatment with CSA can impact the response to biologics or JAKi. The aim of this study was to evaluate the effect of previous treatment with CSA on response to biologics or JAKi in patients with AD. This was a retrospective observational study including patients with AD treated for 16 weeks with a biologic or JAKi, who had previously received cyclosporine for at least four weeks. Thirty patients with AD, with a mean age of 25.07±9.91 years, of whom 18 (60%) were women, were included. The mean duration of CSA treatment was 43.39±31.32 weeks. After 16 weeks of biologic or JAKi treatment, 17 (56.7%) patients achieved EASI75. These patients had a higher cumulative dose of CSA (3,6815 vs.76,993.33 mg; p=0.022) and a longer treatment duration (24.5 vs.57.4 weeks; p=0.003). Additionally, a negative correlation was observed between cumulative dose of CSA and EASI or SCORAD at 16 weeks. Previous cumulative dose and longer duration of CSA treatment does not appear to have a negative impact on response to biologics and JAKi in patients with AD.


Subject(s)
Biological Products , Cyclosporine , Dermatitis, Atopic , Janus Kinase Inhibitors , Humans , Dermatitis, Atopic/drug therapy , Female , Cyclosporine/therapeutic use , Retrospective Studies , Male , Janus Kinase Inhibitors/therapeutic use , Adult , Biological Products/therapeutic use , Young Adult , Adolescent , Severity of Illness Index , Immunosuppressive Agents/therapeutic use , Treatment Outcome
16.
Eur J Dermatol ; 34(4): 416-424, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39193679

ABSTRACT

Atopic dermatitis (AD) is a highly prevalent chronic skin disease. Anti-inflammatory and antipruritic emollients (emollients plus) with excellent cosmetic properties may alleviate AD-related symptoms and reduce the number of exacerbations. To screen for herbal extracts with potent anti-inflammatory and antioxidative potential in human skin cell cultures. Ginger extract and synthetic cannabidiol (CBD) were identified and combined in the cosmetic product BNO 3731, which was evaluated in a randomized clinical trial. Preclinical: anti-inflammatory effects of ginger extract, synthetic CBD and a combination thereof were evaluated in human skin cell cultures by analysing nuclear factor κB activation, release of inflammatory cytokines and endocannabinoid production. Clinical: BNO 3731 was studied in a clinical trial comprising 44 AD patients (adults and children) and compared to a benchmark product over a treatment duration of five days. Symptom severity was evaluated by objective and subjective dermatological assessments as well as physiological skin parameters. Itch intensity was assessed using a numerical rating scale (NRS-11). Preclinical: Ginger extract and synthetic CBD exhibited potent anti-inflammatory and antioxidative effects in vitro which were associated with elevated concentrations of the endocannabinoid, anandamide. Clinical: BNO 3731 significantly alleviated symptoms of AD and improved physiological skin parameters. Itch intensity decreased significantly by 55%, and in 75% of subjects, itch improved ≥2 points on the NRS-11 scale. No adverse events were reported. BNO 3731, containing a unique synergistic combination of ginger extract and synthetic CBD, is an effective and safe treatment option for dry and eczema-prone skin, providing rapid and substantial relief of pruritus.


Subject(s)
Anti-Inflammatory Agents , Cannabidiol , Dermatitis, Atopic , Emulsions , Plant Extracts , Zingiber officinale , Humans , Cannabidiol/pharmacology , Zingiber officinale/chemistry , Dermatitis, Atopic/drug therapy , Plant Extracts/pharmacology , Adult , Female , Anti-Inflammatory Agents/pharmacology , Male , Child , Pruritus/drug therapy , Adolescent , Middle Aged , Severity of Illness Index , Antioxidants/pharmacology , Young Adult , Cells, Cultured
17.
Arch Dermatol Res ; 316(8): 521, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136778

ABSTRACT

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.


Subject(s)
Blood Proteins , Dermatitis, Atopic , Proteome , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/blood , Dermatitis, Atopic/genetics , Dermatitis, Atopic/immunology , Blood Proteins/metabolism , Blood Proteins/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Molecular Docking Simulation , Protein Interaction Maps , Molecular Targeted Therapy/methods , Genetic Predisposition to Disease
18.
Sci Rep ; 14(1): 18097, 2024 08 05.
Article in English | MEDLINE | ID: mdl-39103489

ABSTRACT

Observational studies suggest dyslipidemia as an atopic dermatitis (AD) risk factor and posit that lipid-lowering drugs may influence AD risk, but the causal link remains elusive. Mendelian randomization was applied to elucidate the causal role of serum lipids in AD and assess the therapeutic potential of lipid-lowering drug targets. Genetic variants related to serum lipid traits and lipid-lowering drug targets were sourced from the Global Lipid Genetics Consortium GWAS data. Comprehensive AD data were collated from the UK Biobank, FinnGen, and Biobank Japan. Colocalization, Summary-data-based Mendelian Randomization (SMR), and mediation analyses were utilized to validate the results and pinpoint potential mediators. Among assessed targets, only Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) was significantly linked to a reduced AD risk, corroborated across three separate AD cohorts. No association between serum lipid concentrations or other lipid-lowering drug targets and diminished AD risk was observed. Mediation analysis revealed that beta nerve growth factor (b-NGF) might mediate approximately 12.8% of PCSK9's influence on AD susceptibility. Our findings refute dyslipidemia's role in AD pathogenesis. Among explored lipid-lowering drug targets, PCSK9 stands out as a promising therapeutic agent for AD.


Subject(s)
Dermatitis, Atopic , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Proprotein Convertase 9 , Humans , Dermatitis, Atopic/genetics , Dermatitis, Atopic/drug therapy , Proprotein Convertase 9/genetics , Lipids/blood , Genetic Predisposition to Disease , Hypolipidemic Agents/therapeutic use , Dyslipidemias/genetics , Dyslipidemias/drug therapy , Female , Male
19.
Int J Mol Sci ; 25(15)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39126010

ABSTRACT

Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions that significantly impact the quality of life of patients, with diverse treatment options available. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37, in Th1, Th2, and Th17 inflammatory responses, closely associated with the pathogenesis of psoriasis and atopic dermatitis. Hence, IL-18 and IL-37 could potentially become therapeutic targets. This narrative review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to 30 May 2024, underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still's Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis.


Subject(s)
Dermatitis, Atopic , Interleukin-18 , Interleukin-1 , Psoriasis , Humans , Dermatitis, Atopic/immunology , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/etiology , Dermatitis, Atopic/metabolism , Psoriasis/drug therapy , Psoriasis/immunology , Psoriasis/metabolism , Interleukin-18/metabolism , Interleukin-1/metabolism , Interleukin-1/antagonists & inhibitors , Animals , Molecular Targeted Therapy
20.
Multimedia | Multimedia Resources | ID: multimedia-13472

ABSTRACT

Na apresentação, o Dr. Davisson Tavares abordará as doenças alérgicas e discutirá como a terapêutica homeopática pode ser uma alternativa eficaz e segura no tratamento dessas condições.


Subject(s)
Homeopathic Therapeutics , Hypersensitivity/drug therapy , Homeopathic Remedy , Immune System Phenomena/drug effects , Rhinitis, Allergic/drug therapy , Dermatitis, Atopic/drug therapy
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