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1.
Cureus ; 16(2): e55171, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38558626

RESUMO

Atopic dermatitis (AD) has become a global health concern due to an increase in its frequency over the past few decades. This illness not only reduces the quality of life but also imposes a considerable financial burden due to the increased risk of skin infections. This case report explores the presentation of a four-month-old male infant with a personal history of atopic dermatitis that developed yellow scaly lesions on the scalp, which were assumed to be cradle cap. However, there was a clinical worsening of the cutaneous lesions, with the appearance of vesicles, so he was referred to the Pediatric Emergency Room after an urgent dermatology appointment. A blood test was performed, which revealed severe eosinophilia and a slightly increased total IgE. Considering the patient's past medical record of atopic dermatitis and the observable characteristics of the skin rash, there was a strong suspicion of eczema herpeticum (EH). Consequently, intravenous acyclovir treatment was initiated, along with an antibiotic, as there were concerns about a potential secondary infection. He was followed up with a pediatric and dermatology appointment, with a resolution of skin lesions after six weeks. EH is a rare clinical entity, usually caused by herpes simplex virus (HSV) types 1 and 2. It is a clinical entity that, while being uncommon, is one of the few dermatological emergencies responsible for a high morbidity rate, associated with the systemic spread of the viral infection.

2.
Front Microbiol ; 15: 1349674, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559353

RESUMO

Introduction: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear. Methods: 16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC-MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples. Results: Samples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC-MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways. Discussion: We suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.

3.
Am J Ophthalmol Case Rep ; 34: 102045, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38559364

RESUMO

Purpose: To determine the characteristics of an eye that developed acute hydrops while being treated for infectious keratitis. Observation: A 35-year-old man presented with pain and blurred vision in his left eye. He had undergone cataract surgery seven years earlier and was being treated for poorly controlled atopic dermatitis. The decimal best-corrected visual acuity (BCVA) of the left eye was 0.01. Slit-lamp microscopy showed conjunctival injection, corneal opacification, and a corneal ulcer. The patient was diagnosed with infectious keratitis and was treated with topical and systemic antibiotics. During the hospitalization, the patient was noted to rub his eyes frequently and vigorously. Five days after the first visit, the cornea protruded markedly, and the stroma surrounding the ulcerated area was edematous. These findings led to a diagnosis of acute hydrops.Penetrating keratoplasty was performed to prevent corneal perforation. Histopathological study of the excised cornea showed stromal edema, infiltration of leukocytes, and a tear in Descemet's membrane. Unfortunately, the patient developed endophthalmitis the day after the surgery. The anterior chamber was irrigated with antibiotics, and antibiotics were also injected into the vitreous. The endophthalmitis gradually subsided, and two years after the surgery, the patient's decimal BCVA had improved to 0.6. Conclusion and importance: Vigorous eye rubbing in cases of infectious keratitis can induce acute hydrops, and timely surgical intervention is recommended.

4.
Drug Des Devel Ther ; 18: 941-951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560522

RESUMO

Atopic dermatitis (AD), a common pruritic and chronic inflammatory skin disease, has a major impact on a patient's quality of life. It is characterized by dry, itchy, and eczema-like rashes. AD is more prevalent in young children and has been linked to a variety of other allergy disorders. Traditional drug therapy has certain limitations for treating young children with AD. However, biologics have good clinical application prospects in the medical treatment of young patients. Dupilumab, a fully human monoclonal antibody, specifically binds to the IL-4 Rα subunit, inhibiting IL-4 and IL-13 signaling and blocking the occurrence of type 2 inflammatory response. It has a good effect on treating infants and children with moderate-to-severe AD. This review explores the safety and efficacy of dupilumab in the treatment of AD in infants and children and the impact of early intervention on AD progression, with the aim of informing clinical practice in the use of dupilumab for the treatment of young patients with AD.


Assuntos
Dermatite Atópica , Criança , Lactente , Humanos , Pré-Escolar , Dermatite Atópica/tratamento farmacológico , Qualidade de Vida , Interleucina-4 , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Método Duplo-Cego
5.
Cureus ; 16(2): e55282, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38562266

RESUMO

The role of diet in the development of skin disorders is well-established, with nutritional deficiency often identified as a risk factor for skin diseases. Imbalances in the skin can be caused by nutritional deficiencies, excessive intake, insufficient nutrients, and hazardous ingredients. Patients frequently inquire about the impact of dietary patterns on skin health when consulting dermatologists in clinical settings. Simultaneously, the popularity of using nutritional supplements containing vitamins, minerals, and nutraceutical blends has been on the rise. It is crucial for dermatologists, primary care physicians, and other healthcare providers to be acquainted with evidence-based dietary interventions, distinguishing them from those that are more market-driven than truly efficacious. This review explores the modification of diet, encompassing both dietary exclusion and supplementation, as a therapeutic approach for conditions such as psoriasis, atopic dermatitis, bullous disease, vitiligo, and alopecia areata. A comprehensive literature search, utilizing the PubMed/Medline, Google Scholar, and Medscape databases, was conducted to investigate the relationship between each nutrient and various inflammatory skin diseases. The findings emphasize the significance of a well-balanced and thoughtfully planned diet in supplying adequate amounts of proteins, vitamins, and minerals to support optimal skin health. Additionally, this comprehensive review navigates through various dietary recommendations, offering insights into their multifaceted impacts on the immune system, gut microbiome, and skin health. The goal is to pave the way for informed and targeted dietary interventions for individuals dealing with food allergies and associated skin conditions.

6.
Cureus ; 16(3): e55393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38562326

RESUMO

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.

7.
Postgrad Med J ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565127

RESUMO

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

9.
Allergy ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563683

RESUMO

BACKGROUND: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD. METHODS: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. RESULTS: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL-37, and S100A8) toward non-lesional expression. CONCLUSION: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non-lesional levels, further highlighting the key role of IL-13 in the pathogenesis of AD. CLINICAL TRIAL REGISTRATION: NCT03131648, NCT03587805.

10.
J Dermatolog Treat ; 35(1): 2338280, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38569598

RESUMO

For individuals with atopic dermatitis (AD), interpreting scientific papers that present clinical outcomes including the Eczema Area and Severity Index (EASI) and Investigators Global Assessment may be difficult. When compared to tabulated data and graphs, images from before and after treatment are often far more meaningful to these patients that ultimately will be candidates for the treatment. This systematic review focused on determining the frequency of clinical image sharing in AD research.Conducted in accordance with PRISMA guidelines, the review concentrated on randomized controlled trials that investigated predefined and available systemic treatments for AD. The search was performed in the MEDLINE database for studies published from the inception until 21 December 2023.The review included 60 studies, encompassing 17,799 randomized patients. Across these studies, 16 images representing 6 patients were shared in the manuscripts, leading to a sharing rate of 0.3‰.The almost missing inclusion of patient images in clinical trial publications hinders patient understanding. Adding images to scientific manuscripts could significantly improve patients' comprehension of potential treatment outcomes. This review highlights the need for authors, the pharmaceutical industry, study sponsors, and publishers to enhance and promote patient information through increased use of visual data.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Administração Cutânea , Índice de Gravidade de Doença
11.
Intern Med ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599864

RESUMO

Atopic dermatitis is common in children and often treated with topical corticosteroids (TCs). A boy in his late teens who had been using TCs for atopic dermatitis was diagnosed with liver damage during a health checkup. A medical examination revealed severe steatotic liver disease and elevated liver enzyme levels despite the absence of typical symptoms such as central obesity. After discontinuation of TCs, an improvement in liver enzyme levels was observed, leading to the diagnosis of drug-induced steatohepatitis. This case underscores the potential liver risks associated with prolonged TC use in children, highlighting the need for parental education.

12.
Artigo em Alemão | MEDLINE | ID: mdl-38600365

RESUMO

The term prevention includes measures that are used to avoid illnesses or damage to health as well as to reduce the risk of illness or to delay its occurrence. Preventive measures can be classified based on various criteria: temporal differentiation (primary, secondary, and tertiary prevention), context (behavioral and relational prevention), and recipient (general and individual prevention). Health promotion is used when appropriate measures are intended to strengthen and increase human health potential and resources. This includes, among other things, measures to develop health-promoting behavior (empowerment) and measures regarding the planning and implementation of health-promoting behavior (participation). One goal of these measures is generally to increase health literacy. This article describes examples of prevention and health promotion measures for occupational skin cancer (counseling approach for individual sun protection for outdoor workers; "individuelle Lichtschutzberatung" [ILB]) as well as occupational hand eczema within the meaning of German occupational disease number 5101 (outpatient and inpatient individual prevention measures). These are supplemented by the example of outpatient age-adapted small group trainings for patients with atopic dermatitis according to the multicenter evaluated concept of AGNES e. V. ("Arbeitsgemeinschaft Neurodermitisschulung") and ARNE ("Arbeitsgemeinschaft Neurodermitisschulung im Erwachsenenalter"). These examples also address aspects of sustainability and digitalization (eHealth, eLearning) in the areas of prevention and health promotion.

13.
J Dtsch Dermatol Ges ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600890
14.
Artigo em Inglês | MEDLINE | ID: mdl-38594991

RESUMO

Background Atopic dermatitis (AD) is a common skin condition that occurs due to a combined effect of immune dysregulation, skin barrier dysfunction, changes in the cutaneous microbiome, and genetic factors. Recent data from both clinical trials and real-world studies indicate that dupilumab, a biological agent that inhibits interleukin 4 receptor-α is an effective drug in the treatment of AD, which further suggests the important role of IL-13 and IL-4 in the pathogenesis of AD. Objectives To assess the association between gene polymorphisms of IL-13, IL-13 receptor, IL-4, and IL-4 receptor and susceptibility to AD. Methods The single nucleotide polymorphisms (SNPs) of the above-mentioned genes were detected by single base extension (SNaPshot) assay. The association between these SNPs and AD risk was analysed using SPSS software. Results Two hundred and seventy-one subjects including 130 patients with AD and 141 healthy controls were enrolled. There were statistical differences between AD patients and controls in genotype distribution at rs2265753, rs6646259, and rs2254672 of the IL-13 receptor gene (P all < 0.001). Subjects with CG at rs2265753, AG at rs6646259 and TG at rs2254672 had increased risks for AD (P all < 0.001), and subjects with GG at rs2265753, rs6646259, and rs2254672 had reduced risks for AD (P all < 0.001). Limitation This was a single-centre and single-race study, with a relatively small sample size. Conclusions Findings from this study show that rs2265753, rs6646259 and rs2254672 of the IL-13 receptor gene are associated with susceptibility to AD.

15.
J Am Acad Dermatol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588818

RESUMO

BACKGROUND: Dupilumab, a human monoclonal antibody targeting the IL4 alpha receptor, is used for treatment of moderate to severe atopic dermatitis (AD). Previous studies have reported diagnoses of cutaneous T cell lymphoma (CTCL) after dupilumab use. OBJECTIVE: Investigate the risk of CTCL after dupilumab use in patients with AD. METHODS: Using the TrinetX database, incidence of cutaneous and lymphoid malignancies including CTCL was compared between a cohort of patients with AD who used dupilumab and a cohort of patients with AD who never used dupilumab. A second analysis excluding prior DMARD use was performed. Propensity score matching was performed to control for covariates. RESULTS: An increased risk of CTCL was found in the cohort of AD patients who used dupilumab (OR 4.1003, 95% CI 2.055-8.192). The increased risk persisted after exclusion of prior DMARD use. Risk was not increased for other cutaneous or lymphoid malignancies. Most (27/41) cases of CTCL were diagnosed more than one year after dupilumab use. LIMITATIONS: There is potential for misclassification in the database. Severity of atopic dermatitis could not be assessed. Association between dupilumab and CTCL does not prove causality. CONCLUSION: Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38591168

RESUMO

Summary: Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

17.
Lab Anim Res ; 40(1): 13, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38582857

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). RESULTS: The paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage. CONCLUSIONS: Our results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

18.
World Allergy Organ J ; 17(4): 100890, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585333

RESUMO

Background: There are few studies concerning the impact of serum vitamin D status on the risk of allergen sensitization and atopic dermatitis (AD) during early childhood. Method: Children with AD and age-matched healthy controls (HC) were prospectively enrolled at age 0.5, 2, and 4 years. Serum 25-hydroxyvitamin D (25[OH]D) level was measured using Elecsys Vitamin D Total assay. The study utilized the ImmunoCAP assay to analyze specific IgE for food and inhalant allergens, along with total serum IgE levels. It explored the connection between vitamin D levels and allergen sensitization, as well as their influence on AD at different ages. Results: A total of 222 children including 95 (59 AD and 36 HC), 66 (37 AD and 29 HC), and 61 (32 AD and 29 HC) children were classified at age 0.5, 2, and 4 years, respectively. In children with AD, there was a significantly lower vitamin D level at age 2 and 4, but a significantly higher prevalence of food and mite sensitization at all ages in comparison with HC (P < 0.001). Vitamin D level was found to be inversely related to the prevalence of allergen sensitization at age 4 (P < 0.05). However, vitamin D level appeared to have high importance for allergen sensitization at all ages and AD at age 2 and 4 years. Conclusion: Vitamin D deficiency is strongly associated with heightened prevalence of allergen sensitization, potentially increasing the susceptibility to AD in early childhood.

19.
J Asthma Allergy ; 17: 305-311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585501

RESUMO

Atopic dermatitis (AD) may sometimes be comorbid with alopecia areata (AA). However, traditional treatments for AA show limited efficacy. New treatment options, such as dupilumab and Janus kinase inhibitors, have proven efficacy in addressing both AD and AA. This article highlights the challenging case of a 12-year-old boy experiencing severe refractory AD and comorbid AA treated with oral abrocitinib after dupilumab failure with 1-year follow-up. After 3 months of treatment, his skin manifestations improved and the hair completely regenerated. No adverse reactions were observed during the 1-year follow-up period. This case provides evidence of the efficacy and safety of using abrocitinib to treat pediatric patients with both AD and AA.

20.
Front Immunol ; 15: 1354128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558806

RESUMO

Importance: Disease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied. Objective: To investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients. Design: This study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score ≥3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman's rank correlation coefficients were calculated between metabolites and cytokines. Setting: Patients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center. Participants: The study included 20 atopic dermatitis patients and 24 healthy control patients. Main outcomes and measures: Fold changes of metabolites in AD vs healthy control plasma. Results: In patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values<0.0001) compared to healthy controls. Enriched metabolites were involved in branched-chain amino acid (valine, leucine, and isoleucine) degradation, catecholamine biosynthesis, thyroid hormone synthesis, threonine metabolism, and branched and long-chain fatty acid metabolism. Dysregulated metabolites in AD were positively correlated cytokines TARC and MCP-4 and negatively correlated with IL-1a and CCL20. Conclusions and relevance: Our study characterized novel dysregulated circulating plasma metabolites and metabolic pathways that may be involved in the pathogenesis of AD. These metabolic pathways serve as potential future biomarkers and therapeutic targets in the treatment of AD.


Assuntos
Dermatite Atópica , Humanos , Citocinas/metabolismo , Isoleucina , Prurido , Valina , Treonina
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