RESUMEN
In defying conventional views that dismissed itch as trivial, I persisted in studying basophils and ILC2s in human skin and atopic dermatitis. My research on JAK inhibitors for itch ultimately led to FDA-approved drugs. This is my story of disregarding categories and definitions-a story about an unconventional path in science that emphasizes innovation over conformity.
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Dermatitis Atópica , Modelos Animales de Enfermedad , Prurito , Humanos , Animales , Ratones , Dermatitis Atópica/patología , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Historia del Siglo XX , Historia del Siglo XXI , Basófilos/metabolismo , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/farmacología , Piel/patología , Piel/metabolismoRESUMEN
Contact dermatitis (allergic and irritant) occurs when the skin encounters haptens that elicit a T cell-mediated hypersensitivity reaction (allergic) or a nonimmunologic, toxic reaction (irritant). Patch testing is the reference standard for diagnosing allergic contact dermatitis (ACD), although positive results are not always relevant. Therefore, the definitive diagnosis of ACD requires an astute clinician able to connect the results of patch testing appropriately with the clinical history and the cutaneous examination findings. Comorbid conditions such as atopic dermatitis can confound the accurate diagnosis of ACD because of the similarities in clinical presentation. Furthermore, both extremes of age can further challenge the diagnostic specificity of ACD owing to the maturing immune system and the space limitations present when the very young are patch tested. The goal of this Continuing Medical Education article is to discuss the challenges of diagnosing ACD in patients with unique comorbidities such as atopic dermatitis, given the morphologic similarities, and when to patch test these patients. Diagnosis of ACD will also be discussed in very young patients with a focus on patch test allergen selection despite the limited geographic space. The most common allergens reported in very young and old patients will also be discussed.
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Alérgenos , Comorbilidad , Dermatitis Alérgica por Contacto , Dermatitis Atópica , Dermatitis Irritante , Pruebas del Parche , Humanos , Dermatitis Atópica/epidemiología , Dermatitis Atópica/diagnóstico , Alérgenos/inmunología , Dermatitis Irritante/epidemiología , Dermatitis Irritante/diagnóstico , Dermatitis Irritante/inmunología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Alérgica por Contacto/inmunología , Factores de EdadAsunto(s)
Aminopiridinas , Benzamidas , Ciclopropanos , Dermatitis Atópica , Inhibidores de Fosfodiesterasa 4 , Humanos , Dermatitis Atópica/tratamiento farmacológico , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Aminopiridinas/administración & dosificación , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Ciclopropanos/uso terapéutico , Ciclopropanos/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/farmacología , Ciclopropanos/farmacocinética , Benzamidas/efectos adversos , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Crema para la Piel/administración & dosificación , Administración CutáneaAsunto(s)
Dermatitis Atópica , Exones , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Humanos , Dermatitis Atópica/genética , Dermatitis Atópica/diagnóstico , Proteínas de Filamentos Intermediarios/genética , Exones/genética , Masculino , Femenino , Mutación con Pérdida de Función , Adulto , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Reports regarding the correlation and effect size of change of the full spectrum of quality of life and disease severity measures applied in-person to patients with atopic dermatitis are scarce. OBJECTIVES: To assess quality-of-life with 3 different instruments and to evaluate disease severity indices and to determine their correlation and effect size of change between two measurements. MATERIALS AND METHODS: Patient-level data were obtained through two in-person visits. Sociodemographic information and data related to disease distribution, severity (through the BSA, EASI, SCORAD, POEM, and itching scales), and the impact of atopic dermatitis on quality of life using the DLQI and Skindex-29, and EQ-5D, were assessed. The correlation between change in quality-of-life scores and disease severity scores in addition to the standardized effect size were also evaluated. RESULTS: Only 139 out of 212 patients completed the follow-up visit. BSA highly correlated with SCORAD and EASI, and the lowest correlation was found with POEM. The best correlation of pruritus VAS was found with sleep disturbance. The SCORAD score highly correlated with EASI, and the lowest correlation was found with POEM. The magnitude of the effect at initiation of the study vs follow-up was in average moderate to important. CONCLUSIONS: Patients with atopic dermatitis experience a substantial burden on quality of life. Disease activity correlates better with quality-of-life measurements when the disease is less severe after starting therapy. POEM and Skindex-29 seem to be optimal to determine disease severity and quality of life in adults with atopic dermatitis.
Introducción: La información publicada sobre la correlación entre la magnitud del efecto de todo el espectro de la calidad de vida y la gravedad de la enfermedad en pacientes con dermatitis atópica es escasa. Objetivos: Evaluar la calidad de vida con tres instrumentos diferentes y los índices de gravedad de la enfermedad en pacientes con dermatitis atópica para determinar su correlación y el tamaño del efecto del cambio. Materiales y métodos: Los datos de los pacientes se obtuvieron a partir de dos visitas. Se evaluó la información sociodemográfica y los datos relacionados con la distribución y la gravedad de la enfermedad (mediante de las escalas BSA, EASI, SCORAD, POEM, prurito) y el impacto de la dermatitis atópica en la calidad de vida utilizando el Dermatology Life Quality Index, Skindex-29 y EQ-5D. También se evaluó la correlación entre el cambio en las puntuaciones de calidad de vida y las de gravedad de la enfermedad, además del tamaño del efecto estandarizado. Resultados: Solo 139 de los 212 pacientes completaron la visita de seguimiento. El área de superficie corporal se correlacionó fuertemente con el SCORAD y el EASI, y la correlación más débil fue con el POEM. La mejor correlación del prurito medido con la escala visual análoga se halló con la alteración del sueño. El puntaje SCORAD se correlacionó altamente con el EASI mientras que la correlación más baja se encontró con el POEM. La magnitud del efecto al inicio del estudio respecto al seguimiento fue en promedio de moderada a importante. Conclusiones: Los pacientes con dermatitis atópica experimentan una carga sustancial en la calidad de vida. La actividad de la enfermedad se correlaciona mejor con las mediciones de calidad de vida cuando esta es menos grave, después de comenzar la terapia. Los índices POEM y Skindex-29 parecen ser óptimos para determinar la gravedad de la enfermedad y la calidad de vida en adultos con dermatitis atópica.
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Dermatitis Atópica , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/psicología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Prurito/etiología , Adulto JovenAsunto(s)
Dermatitis Atópica , Melatonina , Índice de Severidad de la Enfermedad , Calidad del Sueño , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). METHODS: We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. RESULTS: The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. CONCLUSION: Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.
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Teorema de Bayes , Dermatitis Atópica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Microbiota , Polimorfismo de Nucleótido Simple , Humanos , Microbiota/genética , Dermatitis Atópica/microbiología , Dermatitis Atópica/genética , Piel/microbiología , Rosácea/microbiología , Rosácea/genética , Enfermedades de la Piel/microbiología , Enfermedades de la Piel/genética , Psoriasis/microbiología , Psoriasis/genéticaRESUMEN
Clinical research has revealed that inflammatory skin diseases are associated with dyslipidaemia. Modulating lipids is also a rising potential treatment option. However, there is heterogeneity in the existing evidence and a lack of large-scale clinical trials. Observational research is prone to bias, making it difficult to determine causality. This study aimed to evaluate the causal association between lipid-lowering drugs and inflammatory skin diseases. A drug target Mendelian randomisation (MR) analysis was conducted. Genetic targets of lipid-lowering drugs, including proprotein convertase subtilis kexin 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, were screened. Common inflammatory skin diseases, including psoriasis, allergic urticaria, rosacea, atopic dermatitis, systemic sclerosis and seborrhoeic dermatitis, were considered as outcomes. Gene-predicted inhibition of PCSK9 was causally associated with a decreased risk of psoriasis (ORIVW [95%CI] = 0.600 [0.474-0.761], p = 2.48 × 10-5) and atopic dermatitis (ORIVW [95%CI] = 0.781 [0.633-0.964], p = 2.17 × 10-2). Gene-predicted inhibition of HMGCR decreased the risk of seborrhoeic dermatitis (ORIVW [95%CI] = 0.407 [0.168-0.984], p = 4.61 × 10-2) but increased the risk of allergic urticaria (ORIVW [95%CI] = 3.421 [1.374-8.520], p = 8.24 × 10-3) and rosacea (ORIVW [95%CI] = 3.132 [1.260-7.786], p = 1.40 × 10-2). Among all causal associations, only PCSK9 inhibition demonstrated a robust causal effect on psoriasis after a more rigorous Bonferroni test (p < 4.17 × 10-3, which is 0.05/12). Modulating lipids via PCSK9 inhibition may offer potential therapeutic targets for psoriasis and atopic dermatitis. Given the potential cutaneous side effects associated with HMGCR inhibitors, PCSK9 inhibitors could be considered viable alternatives in lipid-lowering medication.
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Análisis de la Aleatorización Mendeliana , Humanos , Inhibidores de PCSK9 , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proproteína Convertasa 9/genética , Hidroximetilglutaril-CoA Reductasas/genética , Psoriasis/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Dermatitis Atópica/tratamiento farmacológicoRESUMEN
BACKGROUND: Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. METHODS: We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. RESULTS: Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. CONCLUSION: Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.
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Asma , Índice de Masa Corporal , Ganancia de Peso Gestacional , Hipersensibilidad , Humanos , Embarazo , Femenino , Asma/epidemiología , Asma/inmunología , Preescolar , Masculino , Estudios Prospectivos , Hipersensibilidad/epidemiología , Hipersensibilidad/inmunología , Adulto , Inmunoglobulina E/sangre , Lactante , Dermatitis Atópica/epidemiología , Dermatitis Atópica/inmunología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inmunología , Encuestas y Cuestionarios , Estudios de Cohortes , Cohorte de Nacimiento , Recién NacidoRESUMEN
The experience of itch and its associated chronic conditions (i.e., atopic dermatitis) form a significant burden of disease. Knowledge of how the brain processes itch, that might occur uniquely for chronic itch populations, could be used to guide more effective psychotherapeutic interventions for these groups. To build the evidence base for such approaches, we conducted a series of coordinates-based fMRI analyses, to identify the shared neural mechanisms for itch across the published literature. Upon so doing, we identified a core "itch network" that spans the Basal Ganglia/Thalamus, Claustrum and Insula. Additionally, we found evidence that the Paracentral Lobule and Medial Frontal Gyrus, regions associated with cognitive control and response inhibition, deactivate during itch. Interestingly, a separate analysis for chronic itch populations identified significant recruitment of the Left Paracentral Lobule, potentially suggesting the recruitment of cognitive control mechanisms to resist the urge to scratch. We position these results in light of further integrative studies that could use neuroimaging alongside clinical studies, to explore how transdiagnostic psychological approaches-such as mindfulness and compassion training-might help to improve quality of life for individuals who experience chronic itch.
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Encéfalo , Imagen por Resonancia Magnética , Prurito , Prurito/psicología , Prurito/fisiopatología , Humanos , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Masculino , Femenino , Adulto , Dermatitis Atópica/psicología , Dermatitis Atópica/fisiopatología , Dermatitis Atópica/terapiaRESUMEN
Ruxolitinib cream 1.5% was first approved by the US Food and Drug Administration (FDA) in 2011. Opzelura™ cream was introduced by Incyte Dermatology in 2021 for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients aged ≥12 years, whose clinical manifestations are not controlled with prescribed topical therapies, such as topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase-4 ( PDE4) inhibitors, or when such therapies are not advisable. Ruxolitinib is a Janus kinase (JAK) inhibitor that addresses inflammation in AD. It selectively inhibits JAK1 and JAK2, blocking JAK and activating signal transducer and activator of transcription (STAT), thereby interrupting the cytokine pathways responsible for cutaneous inflammation. The targeted downstream cytokines include Interleukin- 4 (IL-4), IL-13, IL-31, and cytokine thymic stromal lymphopoietin (TSLP), which play pivotal roles in the itching and inflammation experienced by AD patients. Ruxolitinib cream is directly applied as a thin layer over AD lesions twice daily up to 20% body surface area (BSA) using no more than 60 g per week. It can be used for up to 8 weeks on delicate or thin skin surfaces.
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Dermatitis Atópica , Nitrilos , Pirazoles , Pirimidinas , Humanos , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Nitrilos/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Crema para la Piel , Administración Cutánea , Citocinas/metabolismoRESUMEN
Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.
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Dermatitis Atópica , Hemo-Oxigenasa 1 , Nanopartículas del Metal , Molibdeno , Factor 2 Relacionado con NF-E2 , FN-kappa B , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inducido químicamente , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Hemo-Oxigenasa 1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Molibdeno/farmacología , Molibdeno/química , Humanos , Ratones , Nanopartículas del Metal/química , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Células HaCaT , Antioxidantes/farmacología , Ratones Endogámicos BALB C , Nanopartículas/química , Línea Celular , Piel/efectos de los fármacos , Piel/metabolismo , Proteínas de la MembranaRESUMEN
Atopic dermatitis (AD) is the most common chronic inflammatory dermatitis in developed countries, and has a major impact on those affected. Little is known about AD in elderly patients. This prospective multicentre observational study described the clinical characteristics and burden of AD in elderly subjects ≥ 65 years, as well as the therapeutic options chosen for this population in routine care, and compared findings with those in young adults with AD < 30 years. Cohort data from adult patients with moderate-to-severe AD enrolled in a French national prospective registry (December 2020 to May 2023) were analysed. Patients ≥ 65 years made up 12.5% of the total adult cohort and presented less head-and-neck and extremity involvement, and were less affected by generalized forms than young adult patients. Elderly patients predominantly had late-onset AD and had similar disease severity to younger adults. Although the overall impact of AD appeared to be lower in elderly patients and treatment was initially less used in this age group, the substantial impact on sleep and psychiatric comorbidities was similar in older and younger adult patients. Better understanding of AD in elderly patients and the establishment of age-specific treatment guidelines may help dermatologists manage the disease in older people.
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Dermatitis Atópica , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/terapia , Dermatitis Atópica/epidemiología , Masculino , Estudios Prospectivos , Femenino , Anciano , Adulto , Factores de Edad , Persona de Mediana Edad , Adulto Joven , Francia/epidemiología , Sistema de Registros , Fármacos Dermatológicos/uso terapéutico , Comorbilidad , Anciano de 80 o más Años , Edad de Inicio , Resultado del TratamientoRESUMEN
Lebrikizumab has previously demonstrated efficacy in Phase 3 trials: ADvocate1 and ADvocate2 (as monotherapy), ADhere, and ADhere-J (in combination with topical corticosteroids). Here, the impact of lebrikizumab combined with low- to mid-potency topical corticosteroids on patient-reported outcomes at 16 weeks in Japanese patients with moderate-to-severe atopic dermatitis is evaluated. Eligible patients (n = 286) were randomized 2:2:3 to receive placebo+ topical corticosteroids, 250 mg lebrikizumab every 4 weeks (LEBQ4W+topical corticosteroids, 500 mg loading dose at baseline), or 250 mg lebrikizumab every 2 weeks (LEBQ2W+ topical corticosteroids, 500 mg loading dose at baseline and Week 2) by subcutaneous injection. All PRO endpoints for the study were met; patients in the lebrikizumab in combination with topical corticosteroids groups demonstrated statistically significant and clinically meaningful improvements compared with placebo in combination with topical corticosteroids in Skin Pain NRS, DLQI, POEM, WPAI-AD, and SCORAD scales. Lebrikizumab combined with topical corticosteroids compared with placebo+topical corticosteroids improved patient-reported outcomes in Japanese patients with moderate-to-severe atopic dermatitis.
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Dermatitis Atópica , Quimioterapia Combinada , Medición de Resultados Informados por el Paciente , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , Masculino , Adulto , Femenino , Japón , Resultado del Tratamiento , Método Doble Ciego , Persona de Mediana Edad , Administración Cutánea , Factores de Tiempo , Corticoesteroides/administración & dosificación , Inyecciones Subcutáneas , Adulto Joven , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Pueblos del Este de AsiaRESUMEN
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.
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Dermatitis Atópica , Modelos Animales de Enfermedad , Proteínas Filagrina , Prebióticos , Probióticos , Piel , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Animales , Piel/patología , Piel/inmunología , Ratones , Ratones Endogámicos BALB C , Dinitroclorobenceno , FemeninoRESUMEN
As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3+ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.
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Degranulación de la Célula , Dermatitis Atópica , Modelos Animales de Enfermedad , Mastocitos , Probióticos , Animales , Dermatitis Atópica/terapia , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Mastocitos/efectos de los fármacos , Probióticos/farmacología , Ratones , Degranulación de la Célula/efectos de los fármacos , Inmunoglobulina E/sangre , Ratones Endogámicos BALB C , Lactobacillus plantarum , Pyroglyphidae/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Linfocitos T Reguladores/inmunología , QuimasasRESUMEN
Psossibility and appropriate timing of discontinuation of dupilumab for atopic dermatitis (AD) remain unclear. We explored the possibility of patients, who could maintain remission with topical therapy alone after withdrawing dupilumab in the real world. Furthermore, we identified their characteristics. All adult AD patients who initiated dupilumab from June 2018 to July 2022 and were treated with dupilumab for more than 3 months at our hospital were included in this study. The observation period was from June 2018 to July 2023. In 138 patients, 58 (42.0%) discontinued dupilumab at least once. Among them, 18 (13.0%) discontinued dupilumab but reinitiated dupilumab later due to exacerbation. Only seven patients (5.1%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM, VAS of pruritus, serum levels of TARC and LDH, and neutrophil counts at baseline, and those of longer duration of dupilumab until its discontinuation (24.0 ± 13.3 vs. 12.8 ± 7.3 months) and lower EASI and affected BSA at the discontinuation of dupilumab. In 118 patients treated with dupilumab for at least 1 year, 38 patients (32.2%) discontinued at least once. Only four patients (3.4%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM at baseline and lower EASI at the discontinuation of dupilumab. In conclusion, maintaining remission after withdrawing dupilumab is challenging. Discontinuation of dupilumab may be considered in patients with low baseline POEM, after more than 2 years of dupilumab treatment, with a substantial decrease in EASI.