IMPETIGO KONTAGIOSA BERAT PADA ANAK DENGAN ATOPI: LAPORAN KASUS DENGAN TINJAUAN FARMAKOLOGI

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

The skin microbiome is different in pediatric versus adult atopic dermatitis

Skin microbiome correlates with disease severity for lesional and nonlesional skin, indicating a global influence of atopic dermatitis (AD). A relation between skin microbiome and filaggrin gene (FLG) mutations proposes a possible association between skin microbiome and host genetics. To assess skin and nasal microbiome diversity and composition in patients with AD and compare with healthy controls, and to investigate the microbiome in relation to disease severity and FLG mutations in patients with AD. An observational case-control study of 45 adult healthy controls and 56 adult patients with AD was carried out from January 2015 to June 2015 in a tertiary referral center, Department of Dermatology, Bispebjerg Hospital, Denmark. Bacterial swabs were taken from patients with AD (lesional skin, nonlesional skin, and anterior nares) and from healthy controls (nonlesional skin and anterior nares). Eczema severity was assessed and FLG mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA regions amplified with PCR. Samples were analyzed at Statens Serum Institut September 2015 to September 2016. Bioinformatics analyses of the microbiome were analyzed using R statistical software (version 3.3.1, R Foundation Inc). Skin microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA. Microbiome alpha diversity was lower in patients with AD compared with healthy controls in nonlesional skin (effect size, 0.710; 95% CI, 0.27-1.15; P = .002), lesional skin (effect size, 0.728; 95% CI, 0.35-1.33; P = .001), and nose (effect size, 1.111; 95% CI, 0.48-0.94; P < .001). Alpha diversity was inversely correlated with disease severity for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P = .02) and nonlesional skin (effect size, 0.451; 95% CI, 0.04-2.44; P = .04) in patients with AD. Microbiome composition in AD nonlesional skin was linked to FLG mutations. An altered microbiome composition in patients with AD in nonlesional skin, lesional skin, as well as nose, suggests a global influence of AD. Microbiome composition in AD nonlesional skin is associated with FLG mutations, proposing a possible association between the skin microbiome and host genetics.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease affecting ~10–20% of the general population. AD is characterized by disturbances in epidermal barrier function and hyperactive immune response. Recently, changes in the skin and intestinal microbiome have been analyzed in more detail. The available data suggest a link between disturbed skin microbiome and course of the disease. Flares of the disease are associated with an expansion of Staphylococcus aureus on lesional skin and a substantial loss of biodiversity in skin microbiome. Staphylococci exoproteins and superantigens evoke inflammatory reactions in the host. Skin microbiome includes superficial stratum corneum that is affected by environmental factors such as exposure to germs and cleansing. Available evidence argues for a link between epidermal barrier impairment and disturbances in skin microbiome in AD. In contrast to skin microbiome, intestinal microbiome seems to become stabilized after infancy. There is also a significant heritable component for intestinal microbiome. The microbial taxa, relative percentages and quantities vary remarkably between the different parts of the intestinal tract. Early intestinal microbial colonization may be a critical step for prevention of further development of AD. Skin barrier-aimed topical treatments help to develop a neo-microbiome from deeper compartments. Probiotics, prebiotics and synbiotics have been investigated for the treatment of AD, but further investigations are needed. Targeted treatment options to normalize skin and intestinal microbiome in AD are under investigation.

Dupilumab in HIV-positive patients: A case series report of 4 patients

Skin microbiome in atopic dermatitis: New insights from clinical trials.

A case report of uveitis secondary to dupilumab treatment for atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant patient and population burden. It has been observed that obesity is associated with a higher risk of AD. However, the underlying mechanisms are not clear. The purpose of this thesis is to assess the relationship of AD and obesity in a general adult population cohort and explore possible underlying mechanistic links. Specifically, there are five different aims to determine epidemiological associations, skin physiology differences, skin microbiome diversity, serum inflammatory biomarkers profile and genomic associations between AD and obesity. These are specifically to address the various hypotheses based on our current understanding of AD’s pathophysiological mechanisms. Participants of the Health for Life in Singapore (HELIOS) study cohort, aged 30 to 85 years old from the general population, were included in the analysis. Participants were screened for AD using the modified UK Working Party criteria and obesity classified according to anthropometric, bio-impedance and dual x-ray absorptiometry measures. Skin physiology parameters such as trans epidermal water loss (TEWL), skin surface moisture and pH were also measured for all participants. In addition, skin microbiome profiling and serum inflammatory biomarkers proteomics analysis were performed in 300 selected Chinese participants (150 AD participants age and gender matched in a 1:1 ratio with healthy controls). Genetic associations and the concept of Mendelian randomisation (MR) were also used to explore causal relationship between obesity, and AD using genetic data published in public domain. Finally, analysis was performed to integrate results from the skin microbiome and serum proteomic studies to evaluate interactions between the various omics platforms. A total of 5560 participants were recruited from initiation till January 2020. About 8.8% of participants had AD while 40.2% were overweight or obese. Participants with higher visceral fat mass were more likely to have AD after adjusting for age, gender and ethnicity (Odds Ratio (OR): 1.52; p=0.028). Skin physiology, skin microbiome and serum proteomic profile related to AD were found to be significant with increasing body mass index (BMI). Obese participants (BMI ≥ 30 kgm-2 had a significantly higher trans-epidermal water loss (TEWL) values (Beta=0.059 p < 0.001) while having a lower skin surface hydration (Beta= - 0.047 p = 0.003). Serum proteomic analysis revealed that levels of 98 specific serum biomarkers were significantly different with increasing BMI. Known biomarkers of obesity such as serum leptin and IL6 and several AD related chemokines such as CCL17, CCL20, CCL3 and CCL4 were among these significantly different serum biomarkers. The IL18 family of cytokines, previously hypothesized to play a role in initiating AD like dermatitis, were also found to be significantly elevated with increasing BMI. While the diversity of the skin microbiome was similar between the obese and the lean, there were increased proportions of Corynebacterium species, Staphylococcus hominis and Malassezia globosa and reduced proportions of Propionibacterium (Cutibacterium) acnes in participants with increasing BMI. Finally, with MR analysis, it has been observed that genetically determined increase in obesity is associated with increased risk of AD (OR of AD 1.08; p = 0.015). This study provided new evidence to improve our understanding of how obesity is associated with the risk of AD. Obesity, particularly abdominal/visceral obesity was associated with an increased risk of AD. It was established by the MR analyses that the direction of this relationship likely reflects an effect of obesity on the risk of developing AD. This was further reinforced by the observations that obese participants exhibited features of skin barrier dysfunction. Serum proteomic and skin microbiome analyses also revealed unique profile among obese participants. These findings provided basis for future studies to evaluate possible underlying mechanistic pathways of this relationship.

Investigation of changes in the skin microbiome following treatment of atopic dermatitis (AD) with dupilumab may provide valuable insights into the skin microbiome as a therapeutic target. The aim of this study is to assess changes in the AD skin microbiome following treatment of AD with dupilumab (n = 27). E-swabs were collected from nose, lesional, and nonlesional skin before and after 16 weeks of dupilumab therapy, and the microbiome was analyzed by 16S rRNA and tuf gene sequencing. Data for 17 patients with milder disease receiving treatment with non-targeted therapies are also presented. The results show that both groups experienced clinical improvement (p < 0.001) following dupilumab therapy and that Shannon diversity increased and bacterial community structure changed. The relative abundance of the genus Staphylococcus (S.) and S. aureus decreased, while that of S. epidermidis and S. hominis increased. No significant changes were observed for patients receiving non-targeted treatments. The increases in S. epidermidis and S. hominis and the decrease in S. aureus correlated with clinical improvement. Furthermore, changes in S. hominis and S. epidermidis correlated inversely with S. aureus. In conclusion, treatment with dupilumab significantly changed the skin microbiome and decreased S. aureus. Our results suggest a favorable role of commensal staphylococci in AD.

IntroductionLesional skin of atopic dermatitis (AD) is often colonised by Staphylococcus aureus and the bacterial abundance increases during a flare. However, the role of S. aureus and the skin microbiome...

Purpose Atopic dermatitis (AD), psoriasis and xerosis are characterized by alterations in the skin barrier leading to symptoms that severely impair patients’ quality of life (QoL). This multicenter, prospective study evaluated the benefits of a 4-week ceramide-containing regimen on the symptoms and QoL of patients with AD, psoriasis, or xerosis. Materials and methods Clinical assessments (SCORAD, PASI, VAS), QoL and adherence to the treatment were evaluated at baseline and after 4 weeks. Results A total of 312 patients (109 AD, 97 psoriasis and 106 xerosis) participated in the study; 59.3% female, mean age 42.4 years, no family history of AD, psoriasis or xerosis in ∼70% of patients. Significant clinical improvements after 4 weeks were reported: 61.2% reduction in SCORAD in AD; 65.5% reduction in PASI in psoriasis; and reductions in VAS for dryness, erythema and other symptoms in xerosis patients. QoL improved in all groups (67.2% AD, 64.7% psoriasis, 77.3% xerosis), with a significant proportion of patients reducing their concomitant treatments. Most patients adhered to the regimen, and no adverse reactions were reported. Conclusions A ceramide-containing regimen reduced the symptoms commonly associated with AD, psoriasis, and xerosis and improves patients’ QoL. Limitations include the lack of control group and limiting conclusions about ceramides’ contribution on effectiveness.

BackgroundEczema is a common skin inflammatory disorder during infancy. An increasing number of studies have shown an association between eczema and skin microbiome fluctuations. Skin dysbiosis was reported to precede...

The pathogenesis of atopic dermatitis (AD) has not been fully elucidated, which may be mainly associated with abnormality of immunity, dysfunction of skin barrier and environmental factors. The main symptom of AD is severe pruritus, which can greatly affect the life quality of patients. The management of AD in clinical practice is still a big challenge. Most patients can achieve improvement through avoidance of provocative factors, basic skin care and topical application of anti-inflammatory agents. However, a few patients with generalized lesions are resistant to conventional therapy, and systemic therapy is needed. Biological agents have been widely used in patients with moderate and severe AD. This review summarizes advances in the medications for AD. Key words: Dermatitis, atopic; Therapies, investigational; Biological therapy

Possible Involvement of Antigen-Presenting Cells Expressing the Macrophage Galactose-Type C-Type Lectin in Inflammatory Skin Diseases

Atopic dermatitis (AD) is a complex, chronic skin disorder with a broad spectrum of clinical aspects, characterized by abnormal skin barrier function. This has a significant impact on patients' quality of life (QoL), which represents a crucial parameter for their wellbeing. This study assessed the QoL of patients with AD by following parameters such as itching, disturbance of sleep, disturbance of play activity, and community activities. The study included 64 patients clinically diagnosed with AD, aged 0 to 16 years. QoL of patients with AD was measured by evaluating the QoL indices for infants and young children (IDQoL-Infants' Dermatitis Quality of Life Index) and the QoL for children over 4 years (CDQoL-Children's Dermatology Life Quality Index). The severity of the disease was also monitored by evaluating the SCORAD index. The major symptom for atopic dermatitis, pruritus, was found most frequently in our study and influenced patients' QoL. The study showed that the above questionnaires are efficient tools for correlating AD severity with QoL even in younger patients and could be included in current guidelines. This is the first study that analyzed the QoL of pediatric patients with atopic dermatitis in Romania and can constitute the basis for elaborating a more comprehensive disease management guidelines.