Vernix caseosa reveals mechanistic clues linking maternal obesity to atopic dermatitis pathogenesis.

BACKGROUND: Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix caseosa (VC) is a proteolipid material covering the fetus produced during skin development. However, whether maternal prepregnancy weight excess influences fetal skin development is unknown. Characterizing the VC of newborns from mothers with prepregnancy overweight and obesity might reveal AD-prone alterations during fetal skin development. OBJECTIVE: We sought to explore AD biomarkers and staphylococcal loads in VC from the offspring of mothers who were overweight/obese (O/O) before pregnancy versus in those from offspring of normal weight mothers. METHODS: The VC of newborns of 14 O/O and 12 normal weight mothers were collected immediately after birth. Biomarkers were determined by ELISA and staphylococcal species by quantitative PCR. RESULTS: The VC from the O/O group showed decreased expression of skin barrier proteins (filaggrin and loricrin) and increased levels of proinflammatory biomarkers (IgA, thymic stromal lymphopoietin [TSLP], S100A8, IL-25, and IL-33). No differences in concentrations of antimicrobial peptides and enzymes were detected. The VC from the O/O group had a lower Staphylococcus epidermidis and Staphylococcus hominis commensal bacterial load, whereas Staphylococcus aureus bacterial load was not significantly different between the 2 groups. Maternal body mass index was negatively correlated with VC filaggrin expression and S epidermidis load and was positively associated with TSLP concentration. One-year follow-up established that the offspring of O/O mothers had a higher incidence of AD that was specifically linked with decreased VC filaggrin expression and lower S epidermidis load. CONCLUSIONS: VC from neonates of mothers with prepregnancy overweight and obesity exhibit skin barrier molecular alterations and staphylococcal dysbiosis that suggest early mechanistic clues to this population's increased risk of AD.

Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

BACKGROUND: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. OBJECTIVES: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. METHODS: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). RESULTS: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. CONCLUSIONS: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Association between obesity and atopic dermatitis in children: A case-control study in a high obesity prevalence population.

BACKGROUND/OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Research suggests an association between obesity and AD, although evidence is lacking from Latin American populations. This study evaluated the association of obesity with AD in children from Chile, a country with high obesity prevalence. METHODS: A case-control study was performed in children with active AD (cases) and healthy controls (HCs) from Santiago, Chile. Body mass index was evaluated by z-score (z-BMI), with overweight defined as z-BMI ≥+1 and <+2, and obesity as z-BMI ≥+2. Abdominal obesity was defined by a waist circumference-to-height ratio (WHR) ≥0.5. AD severity was evaluated by Scoring AD (SCORAD) index. RESULTS: A total of 174 children with AD and 101 controls were included. AD patients had similar overweight (27% vs. 28%) and obesity (21% vs. 26%) rates as HCs (p = .65). Abdominal obesity rates were also comparable (64% vs. 62%, p = .81). In sex-specific analyses, girls with AD had higher abdominal obesity rates than HCs (71% vs. 53%, p < .05) while boys with AD had lower abdominal obesity rates than HCs (53% vs. 75%, p = .03). Among children with AD, higher z-BMI or WHR did not correlate with higher SCORAD, eosinophil counts or total IgE. CONCLUSION: In our study, Chilean children with AD had high but similar rates of obesity as HCs, but showed sex-specific associations of abdominal obesity and AD. Further research is needed to evaluate these associations and the roles that weight excess and weight loss could play in the pathogenesis and treatment of AD.

Vitamin D modulates the allergic phenotype of dendritic cells in children with atopic dermatitis.

Vitamin D (VD) deficiency has been associated with increased incidence and severity of atopic dermatitis (AD), but the mechanisms through which VD may ameliorate AD are unclear. We compared the phenotypic characteristics of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs, respectively) of children with AD vs healthy controls (HC) and evaluated if VD can modulate the allergic phenotype of circulating DCs in AD patients. Although there was no difference in frequency of circulating DCs between groups, among children with AD there was an inverse correlation between SCORAD and circulating total DCs and mDCs. In AD, serum IgE concentration correlated with FcεRI and surface-bound IgE expression on mDCs and pDCs; pDCs expressing FcεRI and IgE were significantly increased compared to HC. Ex vivo, 1,25(OH)2 D3 significantly decreased FcεRI expression on mDCs and surface-bound IgE on mDCs and pDCs. Oral VD supplementation reduced expression of surface-bound IgE on pDCs in children with AD. In summary, VD decreases the allergic phenotype of circulating DCs in children with AD, a potential mechanism for how VD supplementation may improve AD severity. Future studies are needed to further assess the role of VD supplementation as an immunomodulatory therapy for AD.

Agreement between dermatologic and pediatric researchers in scoring of atopic dermatitis in children.

The Scoring of Atopic Dermatitis (SCORAD) index is a widely applied instrument for measuring the severity of atopic dermatitis (AD), but few studies have evaluated the interobserver agreement between different disciplines. A cross-sectional study of 21 children with AD evaluated by dermatology and pediatric researchers found excellent agreement between the SCORAD, the objective SCORAD, and the Three Item Severity score, confirming the applicability of these scores by nondermatologists.

Humoral and Cellular Autoreactivity to Epidermal Proteins in Atopic Dermatitis.

Atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, is an important public health concern affecting 10-20 % of children worldwide. The etiology and pathogenesis of AD involve the interplay of genetic and environmental factors, including abnormalities in skin integrity and a skewed immune system usually driven by a Th2 phenotype in childhood with a switch to Th1 in the chronic phase of disease. Children and adults with AD commonly have elevated IgE levels directed to multiple different antigens, including aeroallergens, food allergens, and microbial proteins. IgE targeting self-antigens from epidermal proteins have been detected in up to 91 % of patients, particularly in severe persistent AD. It has been suggested that the occurrence of autoreactivity develops in early childhood. However, it is not clear yet if autoreactive IgEs in patients with AD are pathogenic or just an epiphenomenon. The fact that these autoantibodies are associated with severity and are not present in other allergic or skin diseases favors the pathogenicity of IgE-mediated autoreactivity in AD. In this review, we evaluate the pathogenesis of AD and the emerging role of autoreactivity to various keratinocyte antigens involving both the humoral and cellular components of the immune system.

Buscando la mejor evidencia en dermatología / Searching for the best evidence in dermatology

En los últimos años han ocurrido grandes cambios en la generación y divulgación de la información biomédica. Gracias al desarrollo y la importancia dada a la Medicina basada en evidencia, más de una década después de su introducción en el quehacer médico, contamos con múltiples fuentes de información de gran calidad, para el manejo de nuestros pacientes. En el presente artículo hacemos una revisión de las fuentes de información basadas en evidencia, con énfasis a aquellas de mayor relevancia a la dermatología

In the lad few years main changes have taken place in the way that biomedical information is developed and spread. The credibility and importance gwer to evidence based medicine, after a decade of its introduction in the medical task, have made available lost of sources of high quality information. In this paper we review these sources of information, emphasizing those most relevant for the dermatology price

Dermatología Basada en Evidencia: ¿un enfoque posible? / Evidence based dermatology: a possible approach?

La Medicina Basada en Evidencia (MBE) es una herramienta de gran utilidad para la resolución eficiente de situaciones clínicas, que involucra los conocimientos derivados tanto de la experiencia clínica, como de los estudios clínicos. La aplicación de la MBE en la toma de decisiones en pacientes con enfermedades cutáneas, es lo que conocemos como Dermatología Basada en Evidencia. En este artículo revisamos los conceptos fundamentales de la MBE, las principales críticas surgidas desde su introducción, las ventajas que nos entrega y el primer paso para su ejecución, la formulación de preguntas clínicas

Evidence Based Medicine (EBM) is a useful tool for the efficient resolutipn of clinical situations, which involves the knowledge derived from the clinical experience, and derivative from clinical trials. The application of EBM in the decisions-making process with dermatology patients is what we know as Evidence Based Dermatology. In this article we chek the fundamental concepts of the EBM, the controversial aspects since its introduction, its advantages, and the first step for its execution, the formulation of clinical questions