Pediatric Atopic Dermatitis Research Articles

Impact of the Family and Household Environment on Pediatric Atopic Dermatitis in Japan.

Pediatric atopic dermatitis (AD) can negatively impact the family quality of life (QoL). We report data from the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE) study in Japanese pediatric patients, focusing on disease impact on family QoL. Children and adolescents aged 6 months to <18 years completed an online survey between September 2018-December 2019. The impact of disease severity on family QoL and its effect on parents' time were assessed using the dermatitis family impact (DFI) questionnaire. The impact of a family history of allergic conditions, current residency, second-hand smoke exposure, and household pets on AD prevalence and severity was also assessed. Family QoL decreased as AD severity increased, particularly in families with children aged <6 years; but had the greatest impact on sleep and tiredness in families with children aged <12 years. Parents spent at least 4.6 h/week caring for children <6 years, including those with mild symptoms. Most children (>80%) had a family history of allergic conditions; AD prevalence was increased in those exposed to second-hand smoke or household pets. This study demonstrated that pediatric AD in Japanese individuals has negative impacts on family QoL and that family and household environments can influence pediatric AD prevalence.

476 High loading-dose of dupilumab rapidly controls pruritus in pediatric atopic dermatitis patients

476 High loading-dose of dupilumab rapidly controls pruritus in pediatric atopic dermatitis patients

Pathogenic role of the staphylococcal accessory gene regulator quorum sensing system in atopic dermatitis.

The skin is home to various bacteria, archaea, fungi, and viruses, collectively referred to as the skin microbiota. Patients with certain skin diseases reportedly have unique skin "dysbiosis," a condition involving imbalanced microbiota, suggesting that dysbiosis in the skin may be either causal or a consequence of specific skin diseases. Atopic dermatitis (AD) is the most common allergic skin disease that affects 15-20% of children and 2-10% of adults worldwide. Both intrinsic genetic factors, such as susceptibility to type 2 inflammation or skin barrier dysfunction, and extrinsic environmental factors, such as air pollen and skin microbiota, contribute to AD. Staphylococcus aureus, which does not often colonize the skin of healthy individuals, is commonly identified in the lesional skin of patients with AD and is correlated with the disease flare. However, the role of S. aureus in the pathogenesis of AD has not been elucidated. Here, we discuss the pathological behavior of S. aureus, focusing on accessory gene regulator (Agr) quorum sensing, which is a fundamental bacterial cell-to-cell interaction mechanism that affects the behavior of S. aureus and other members of the microbial community. Importantly, beyond bacteria-bacteria interactions, the Agr quorum sensing system also regulates various virulence factors, which induce type 2 and IL-17-dependent skin inflammation in the host. Furthermore, the colonization of Agr-positive S. aureus in early life accelerates the development of pediatric AD. Finally, we aim to highlight the current efforts to establish novel therapeutic methods to ameliorate or prevent AD through Agr-targeted intervention.

Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis

Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children with early-onset moderate-to-severe AD, we investigated the effect of coding variation in FLG and 13 other genes with epidermal barrier or immune function through the use of targeted amplicon sequencing and genotyping. A FLG loss-of-function variant (Arg501Ter, Ser761fs, Arg2447Ter, or Ser3247Ter) was identified in 20 of 140 patients showing higher transepidermal water loss values than patients without these variants. Total FLG loss-of-function variant frequency (7.14%) was significantly higher than in the general Finnish population (2.34%). When tested separately, only Arg2447Ter showed a significant association with AD (P= 0.003104). In addition, a modest association with moderate-to-severe pediatric AD was seen for rs12730241 and rs6587667 (FLG2:Gly137Glu). Loss-of-function variants, previously reported pathogenic variants, or statistically significant enrichment of nonsynonymous coding region variants were not found in the 13 candidate genes studied by amplicon sequencing. However, higher IgE and eosinophil counts were found in carriers of potentially pathogenic DOCK8 missense variants, suggesting that the role of DOCK8 variation in AD should be further investigated in larger cohorts.

Clinical Aspect of Pruritus in Pediatric Atopic Dermatitis: A Study from Western India

Introduction: Atopic dermatitis (AD) is one of the most common dermatoses in the pediatric population and pruritus is its leading symptom; however, the clinical aspect of pruritus has not been studied much. The aim of the study was to explore clinical aspect of pruritus in pediatric AD and to analyze correlation of intensity of pruritus to the severity of AD. Methods: A hospital-based cross-sectional study of 106 pediatric patients of AD, between the age group of 6 months and 16 years was conducted. Diagnosis was made using the UK Working Party’s Diagnostic Criteria for AD. The severity of pruritus and sleep disturbances were assessed using the Numerical Rating Scale, and the severity of AD was assessed using SCORing of AD index. Results: Mean age at onset was 4.73 years and the mean duration of disease was 1.07 years. Pruritus was localized in 66.03%, intermittent in 89.7%, and continuous in 10.3%. Winter aggravation was observed in 36.8% and sleep disturbances were observed in 39.62%. “Pruritus intensity” was moderate or severe in 92% of patients and had significant correlation to the duration and severity of the disease, sleep disturbances, and coexistence of other atopic diseases. Conclusion: A pediatric patient with AD usually presents with localized or generalized, moderate or severe pruritus, and with sleep disturbances. Exacerbation of pruritus was the most common in winter and due to woolen garments and sweating. The intensity of pruritus was in direct proportion with the duration and severity of AD and coexistence of other atopic diseases.

Obesity and the microbiome in atopic dermatitis: Therapeutic implications for PPAR-γ agonists

Atopic dermatitis (AD) is an inflammatory skin disease characterized by epidermal barrier disruption, Th2 immune responses to skin allergens and microbial dysbiosis within affected lesions. Studies within the past decade have revealed genetic and environmental factors contributing to AD in children. Obesity is a metabolic disorder that often manifests early in life and is associated with reduced bacterial diversity, leading to skin colonization with lipophilic bacteria and intestinal colonization with pro-inflammatory species. These changes impair epithelial barriers and promote Th17 responses, which may worsen the severity of AD symptoms. While few studies have examined the contribution of microbiota in obesity-induced allergies, there is emerging evidence that PPAR-γ may be an effective therapeutic target. This review discusses the microbiome in pediatric AD, treatment with probiotics, how disease is altered by obesity and potential therapeutic effects of PPAR-γ agonists. While healthy skin contains diverse species adapted for specific niches, lesional skin is highly colonized with Staphylococcus aureus which perpetuates the inflammatory reaction. Treatments for AD should help to restore microbial diversity in the skin and intestine, as well as epithelial barrier function. Pre-clinical models have shown that PPAR-γ agonists can suppress Th17 responses, IgE production and mast cell function, while improving the epidermal barrier and microbial homeostasis. Overall, PPAR-γ agonists may be effective in a subset of patients with AD, and future studies should distinguish their metabolic and anti-inflammatory effects in order to inform the best therapies.

Economic and Humanistic Burden in Paediatric Patients with Atopic Dermatitis.

Data concerning the economic and humanistic burden in patients with paediatric atopic dermatitis (AD) and their families are scarce. This retrospective study investigated these burdens in paediatric patients with AD using maintenance treatment with topical corticosteroids and/or conventional systemic immunosuppressants. Patient-reported outcomes regarding quality of life, AD severity, and parental work-related impairment were completed at inclusion. Data on healthcare resource utilization and medication prescription were collected retrospectively over the previous 12 months. Patients were categorized into mild, moderate or severe AD, based on Eczema Area and Severity Index score and medication use. Costs per patient per year per AD severity category were calculated. A total of 101 patients (median age 11.0 years (interquartile range 7.5-14.0), 47.5% men) were included, of whom 38 had mild AD, 37 moderate AD, and 26 severe AD. Mean ± standard deviation (SD) total costs patient per year for mild, moderate and severe AD were €1,812 ± €1,280, €2,680 ± €3,127, and €5,861 ± €3,993, respectively. Highest total direct and indirect costs were found in patients with severe AD, mainly due to higher healthcare and medication costs. Highest humanistic burden was found in patients with moderate AD. For example, the median (interquartile range) Patient-Oriented Eczema Measure score was significantly higher in these patients compared with mild and severe AD (19.0 (15.0-24.0) vs 12.0 (8.8-15.0) and 17.0 (9.5-22.0), respectively). AD in paediatric patients incurs considerable direct and indirect costs, especially in patients with severe AD. The high humanistic burden in patients with moderate AD underlines the need for effective and safe new treatment options for children with AD.

Effect of Paediatric Atopic Dermatitis on Parental Sleep Quality.

Data on the impact of paediatric atopic dermatitis on parental sleep are scarce. The aim of this study was to examine the effects of paediatric atopic dermatitis on the quality of parents' sleep. This cross-sectional study included parents of patients with atopic dermatitis and parents of healthy children who completed validated Pittsburgh Sleep Quality Index questionnaires. The study and control groups were compared, as were results for mild and moderate atopic dermatitis with severe atopic dermatitis, mothers and fathers, and different ethnic groups. A total of 200 parents were enrolled. Sleep latency was significantly longer in the study group compared with the control group. Sleep duration was shorter in the parents of the mild AD group compared with the moderate-severe and control groups. Parents in the control group reported more daytime dysfunction than parents in the AD group. Fathers of children with AD reported more sleep disturbance than mothers.

Peripheral Blood Gene Expression Profile of Infants with Atopic Dermatitis

To enhance the understanding of molecular mechanisms and mine previously unidentified biomarkers of pediatric atopic dermatitis, PBMC gene expression profiles were generated by RNA sequencing in infants with atopic dermatitis and age-matched controls. A total of 178 significantly differentially expressed genes (DEGs) (115 upregulations and 63 downregulations) were seen, compared with those in healthy controls. The DEGs identified included IL1β, TNF, TREM1, IL18R1, and IL18RAP. DEGs were validated by real-time RT- qPCR in a larger number of samples from PBMCs of infants with atopic dermatitis aged <12 months. Using the DAVID (Database for Annotation, Visualization and Integrated Discovery) database, functional and pathway enrichment analyses of DEGs were performed. Gene ontology enrichment analysis showed that DEGs were associated with immune responses, inflammatory responses, regulation of immune responses, and platelet activation. Pathway analysis indicated that DEGs were enriched in cytokine‒cytokine receptor interaction, immunoregulatory interactions between lymphoid and nonlymphoid cells, hematopoietic cell lineage, phosphoinositide 3-kinase‒protein kinase B signaling pathway, NK cell‒mediated cytotoxicity, and platelet activation. Furthermore, the protein‒protein interaction network was predicted using the STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database and visualized with Cytoscape software. Finally, on the basis of the protein‒protein interaction network, 18 hub genes were selected, and two significant modules were obtained. In conclusion, this study sheds light on the molecular mechanisms of pediatric atopic dermatitis and may provide diagnostic biomarkers and therapeutic targets.

Sleep Disturbances in Children With Atopic Dermatitis: A Scoping Review.

Atopic dermatitis (AD) is associated with various quality of life concerns including poor sleep. Sleep impairments in children with AD are associated with increased risk of short stature, metabolic syndrome, mental illness and neurocognitive dysfunction. Although the association between AD and sleep disturbance is well established, the specific types of sleep disturbance in pediatric AD patients and their underlying mechanisms are not fully understood. A scoping literature review was performed to characterize and summarize the types of sleep disturbance in children (less than 18 years of age) with AD. 31 papers met inclusion criteria and extracted data were analyzed in an iterative manner. Two types of sleep disturbances were found to be more prevalent in pediatric AD patients in comparison to controls. One category was related to loss of sleep (increased frequency or duration of awakenings, increased sleep fragmentation, delayed sleep onset, decreased total sleep duration, and decreased sleep efficiency). Another category was associated with unusual behaviors during sleep (restlessness/limb movement/scratching, sleep-disordered breathing including obstructive sleep apnea and snoring, nightmares, nocturnal enuresis and nocturnal hyperhidrosis). Some mechanisms underlying these sleep disturbances include pruritus and induced scratching and increased proinflammatory markers induced by sleep loss. Sleep disturbance appears to be associated with AD. We recommend clinicians to consider interventions that may reduce sleep disturbances in children with AD. Further investigation of these sleep disturbances is needed to elucidate pathophysiology, develop additional treatments, and reduce negative impacts on the health outcomes and quality of life in pediatric AD patients.

Biologics for pediatric atopic dermatitis: A protocol of a systematic review and meta-analysis.

Atopic dermatitis is a chronic pruritic inflammatory skin disease commonly occurring in children. The objective of this study is to evaluate the treatment of pediatric atopic dermatitis with biologics, as they have displayed immense promising results in several recent clinical trials on atopic dermatitis (AD). We will conduct an extensive search for RCTs in several databases, including Embase, Cochrane Library, Web of Science, and PubMed, from the inception of the study till 15th May 2022. The primary outcomes will be the proportion of patients with EASI 75/90/100 after 12-16 weeks of treatment. The secondary outcomes will include the Numerical Rating Scale (NRS), Investigator Global Assessment (IGA)0-1, body surface area (BSA), Dermatology Life Quality Index (DLQI) scores, and incidence of adverse reactions. All studies will be screened by two independent researchers. They will assess the risk of bias in the included studies according to the RCTs bias risk evaluation tool in Cochrane System Review Manual 5.1.0. Meta-analysis will be performed using RevMan V.5.3.0 software. The research results will provide a reference for the clinical application of biological agents in pediatric atopic dermatitis. We aim to evaluate the efficacy and safety of biologics in pediatric atopic dermatitis cases and provide evidence-based data for easy clinical application. CRD42022319052 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).

Differences in prescriptions for systemic medications and nonsteroidal topicals among children with atopic dermatitis.

Nonsteroidal topicals and systemic therapies are often utilized for atopic dermatitis (AD) in children with inadequate response to topical corticosteroids. We sought to characterize patient factors associated with prescriptions for nonsteroidal topical (tacrolimus, pimecrolimus, crisaborole), systemic immunosuppressant (methotrexate, mycophenolate, cyclosporine, azathioprine), and systemic corticosteroid therapy among children with AD. In a cross-sectional study of patients <18 years old with AD seen at a large children's hospital between 2009 and 2017, we found that nonsteroidal topical and systemic medication prescriptions were associated with older age of the patient, male sex, comorbid atopy, greater healthcare utilization, specialist care, and race/ethnicity. Compared to White patients, Black and Hispanic patients were less likely to be prescribed nonsteroidal topicals and non-White patients were less likely to be prescribed systemic medications, suggesting that further examination of potential disparities in pediatric AD treatment is needed.

285 Performance metrics of a soft wearable acousto-mechanic sensor for measuring itch in children and adults with atopic dermatitis

Abstract Pruritus is a prominent symptom in many systemic (e.g. renal failure, cholestasis) and dermatologic (e.g. urticaria, xerosis) conditions. Atopic dermatitis (AD) is characterized by the itch-scratch cycle, whereby the reflexive scratching leads to greater skin inflammation and worsens pruritus. Itch in AD has also been associated with certain stages of the circadian rhythm. Therefore, an objective method of measuring nocturnal scratching behaviour as a proxy for itch symptom severity would prove useful and insightful in the management of a patient’s AD. The purpose of this study is to validate the performance of a novel wearable sensor, the advanced acousto-mechanic (ADAM) device, in regard to the detection of nocturnal scratching behaviour in paediatric and adult populations with AD. The sensor is able to detect both the accelerometer data (movement in space) and acoustic data generated by finger and wrist movements in scratching. Performance metrics used to evaluate the sensor include sensitivity, specificity, positive predictive value (PPV) and F1 score (combination of precision and recall). The sensor’s performance was compared to video recordings, the gold standard for objectively measuring scratch. A total of 60 healthy adult subjects (22 males and 38 females) were recruited and asked to perform a series of scratching behaviours and non-scratching behaviours while wearing the ADAM sensor on their dorsal hand using a one-use adhesive in a controlled environment. The data were used to create a machine-learning algorithm for scratch detection and validation in both a paediatric and adult AD cohort. Individuals with mild-to-severe AD were recruited to monitor their nocturnal scratching behaviour in the home environment. An infrared camera was provided for each subject to record the patient’s scratching and compared it to data collected by the ADAM sensor worn on the subject’s dominant dorsal hand. Video recordings were graded for scratching activity by at least two graders; scratch was defined as lasting at least 4.5 s. The scratch algorithm’s classification of scratch and non-scratch was then compared to the gold standard video recording and generated performance metrics. The initial scratch algorithm yielded sensitivity of 88%, specificity of 88% and F1 score of 90% when cross-validated with data from 10 healthy adult subjects. When cross-validated with data from all 60 healthy adult subjects, the algorithm yielded a sensitivity of 92%, specificity of 98% and F1 score of 95%. A total of 11 paediatric AD subjects (1 : 3 male-to-female ratio, ages 10.5 ± 9.1) and 46 nights of data were collected in the home setting, yielding a total of 378.4 h of video. The scratch algorithm was able to detect scratching behaviour with sensitivity of 84%, specificity of 99% and F1 score of 83% in the paediatric cohort. In the adult cohort, a total of 11 adults with atopic dermatitis (two males and nine females, ages 29 ± 13) and 73 nights of data were collected, resulting in a total of 457.7 h of video. When the data was applied to the scratch algorithm, the algorithm yielded a sensitivity of 93%, specificity of 100% and F1 score of 91%. The use of a flexible wearable sensor on the dorsal hand for detection of nocturnal scratching behaviour in both paediatric and adult subjects with atopic dermatitis can provide valuable information regarding the degree of scratching and severity of pruritus the wearer is experiencing when compared to video recording. Its ability to serve as an accurate objective measure of itch may be helpful in drug development and can help serve as a tool to guide the clinical management of symptoms.

Association Between Staphylococcus Aureus Colonization and Pediatric Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Atopic dermatitis is a chronic inflammatory skin condition common in early childhood. Acute exacerbation is frequently associated with Staphylococcus aureus colonization. This study aims to explore the relationship between S. aureus skin and nasal colonization with pediatric atopic dermatitis. A systematic review and meta-analysis were conducted by comparing atopic dermatitis patients aged ≤18 years and nondiseased controls. A random-effects model was used to obtain the pooled prevalence and odds ratio of S. aureus colonization at eczematous skin, nonlesional skin, and nasal cavity. Subgroup analyses for colonization with methicillin-resistant S. aureus were also evaluated. A total of 2,670 cases and 1,224 controls from 26 studies were included in the meta-analysis. S. aureus colonization at eczematous skin and nasal cavity is significantly higher in atopic dermatitis compared to control with odds ratios of 10.55 (95% confidence interval [CI]; 4.85-22.92, P < .001) and 2.38 (nasal cavity; 95% CI; 1.46-3.90, P < .001), respectively. The pooled prevalence of skin and nasal colonization were 55.0% (eczematous skin; 95% CI; 38.3-71.7), 23.3% (nonlesional skin; 95% CI; 12.6-33.9), and 56.3% (95% CI; 43.2-69.4), respectively. Methicillin-resistant S. aureus strain was obtained from the nares and eczematous skin with rates of 11.6% (95% CI; 6.5-16.7) and 8.5% (95% CI; 4.3-12.8), respectively. Children with atopic dermatitis are more prone to skin and nasal colonization by S. aureus compared to nondiseased individuals.

Estimating the Frequency of Hanifin and Rajka’s Minor Criteria among Paediatric Atopic Cases at a Tertiary Care Hospital in Western Tamil Nadu, India- A Cross-sectional Study

Introduction: Atopic Dermatitis (AD) is a common relapsing inflammatory disorder, among the paediatric population clinically, characterised by pruritus and recurring eczematous skin lesions and a host of other cutaneous changes. Diagnosis is done on the basis of clinical findings with the usage of Hanifin and Rajka’s criteria which includes 4 major and 23 minor criteria. Geographical, climatic factors and other population factors have been reported to influence the occurrence of minor criteria. Aim: To estimate the frequency of Minor criteria among paediatric atopic dermatitis in Western Tamil Nadu, India. Materials and Methods: This cross-sectional observational study was done by including 110 atopic children attending Paediatric and Dermatology Outpatient Departments (OPD) of KMCH IHSR, Coimbatore, Western Tamil Nadu, India, between March 2022 to August 2022. The clinical and ophthalmological findings were documented. Categorical variables were presented as frequency and percentages, Continuous variables were presented as Mean±Standard deviation. The data was entered in excel and was analysed using statistical package for social sciences (SPSS) version 27. Results: Among the total study population of 110, 53 (48.2%) were males and the rest 57 (51.8%) were females. The mean age was 24.73±5.18 years with a range of 2-15 years. Early age of onset was seen in 73.6% of study population. Hyperlinear palms were found in 70% of the study patients. 68.2% had Dennie Morgan infraorbital fold, 64.5% had xerosis, 61% had pityriasis alba and 60% had a family history of atopy. Conclusion: Certain minor manifestations of AD like xerosis, icthyosis, hyprerlinear palms, and perifollicular accentuation were more common in the present study. Western Tamil Nadu having a tropical semi-arid climate tempered by higher altitude could explain the differences noted in the frequency of certain minor criteria.

A Qualitative Study on Dupilumab's Impact on Atopic Dermatitis Among Adolescent and Adult Patients.

Atopic dermatitis (AD) is the most common inflammatory skin disease and dupilumab is US Food and Drug Administration-approved in both adult and pediatric AD patients. To qualitatively assess the life experiences and impact of treatment in adult and adolescent patients with AD being treated with dupilumab. Sixteen semi-structured interviews were conducted with adult (n=9) and adolescent (n=7) participants who had received a diagnosis of AD between 1/1/2017 and 1/1/2022 after they had received treatment with dupilumab. Results were analyzed using qualitative research methods. Most participants reported frustration with daily topical medications and starting dupilumab after exhausting other treatment options. Before treatment, participants described severe AD, social anxiety, and decreased self-esteem. Although most participants did not experience complete resolution of AD after treatment, all participants described a profound decrease in the physical and psychosocial burden of their disease. Participant satisfaction was high with dupilumab treatment. Injection-related pain was commonly reported as the most negative aspect of treatment. AD was physically and psychosocially debilitating in our cohort. Dupilumab offered an efficacious treatment for these patients and helped improve the physical and psychosocial burden of their disease. J Drugs Dermatol. 2023;22(2):148-153. doi:10.36849/JDD.7053.

A Cross-Sectional Study Comparing Application of Hanifin and Rajka Criteria in Indian Pediatric Atopic Dermatitis Patients to that of Other Countries.

Hanifin and Rajka criteria are considered to be the gold standard for atopic dermatitis diagnosis. However, the exhaustive nature limits its use in clinical settings. To determine the frequency of Hanifin and Rajka criteria commonly found in Indian pediatric atopic dermatitis patients and variation from the findings of other studies. An observational, descriptive study with a sample size of 52 pediatric atopic dermatitis patients. Patients were divided into infantile, childhood, and adolescent. Overall, xerosis, early age of onset, Dennie-Morgan fold, aggravation because of environmental factors, palmar hyper-linearity, ichthyosis vulgaris, keratosis pilaris, pityriasis alba, and orbital darkening were found in more than 50% of patients. Dennie-Morgan fold was more commonly found in Indian pediatric atopic dermatitis patients. Peri-follicular accentuation was less prevalent in Indian patients as compared to other Asian studies. None of the parents reported food intolerance, which was seen in studies from other countries. A small sample size and ophthalmological evaluation was not performed in all patients. The frequency of different Hanifin and Rajka minor criteria varies widely among different study populations. Hence, the criteria specifically applicable to the Indian population need to be derived for ease of diagnosis.

Alterations of Epidermal Lipid Profiles and Skin Microbiome in Children With Atopic Dermatitis.

We aimed to investigate epidermal lipid profiles and their association with skin microbiome compositions in children with atopic dermatitis (AD). Specimens were obtained by skin tape stripping from 27 children with AD and 18 healthy subjects matched for age and sex. Proteins and lipids of stratum corneum samples from nonlesional and lesional skin of AD patients and normal subjects were quantified by liquid chromatography tandem mass spectrometry. Skin microbiome profiles were analyzed using bacterial 16S rRNA sequencing. Ceramides with nonhydroxy fatty acids (FAs) and C18 sphingosine as their sphingoid base (C18-NS-CERs) N-acylated with C16, C18 and C22 FAs, sphingomyelin (SM) N-acylated with C18 FAs, and lysophosphatidylcholine (LPC) with C16 FAs were increased in AD lesional skin compared to those in AD nonlesional skin and that of control subjects (all P < 0.01). SMs N-acylated with C16 FAs were increased in AD lesional skin compared to control subjects (P < 0.05). The ratio of NS-CERs with long-chain fatty acids (LCFAs) to short-chain fatty acids (SCFAs) (C24-32:C14-22), the ratio of LPC with LCFAs to SCFAs (C24-30:C16-22) as well as the ratio of total esterified omega-hydroxy ceramides to total NS-CERs were negatively correlated with transepidermal water loss (rho coefficients = -0.738, -0.528, and -0.489, respectively; all P < 0.001). The proportions of Firmicutes and Staphylococcus were positively correlated to SCFAs including NS ceramides (C14-22), SMs (C17-18), and LPCs (C16), while the proportions of Actinobacteria, Proteobacteria, Bacteroidetes, Corynebacterium, Enhydrobacteria, and Micrococcus were negatively correlated to these SCFAs. Our results suggest that pediatric AD skin shows aberrant lipid profiles, and these alterations are associated with skin microbial dysbiosis and cutaneous barrier dysfunction.

Metabolic Comorbidities in Pediatric Atopic Dermatitis: A Narrative Review.

Atopic dermatitis (AD) is an itchy dermatitis with multifactorial aetiology, chronic-recurrent course, and typical distribution of lesions according to the age, affecting the 10-20% of pediatric population. Patients with AD, including children, suffer from many metabolic comorbidities, including metabolic syndrome, being overweight, obesity, dyslipidaemia, and arterial hypertension, all of which had a prevalence that was demonstrated to be higher than in healthy patients. The association between AD and metabolic comorbidities is multifactorial and involves the deregulation of immune system. In fact, hypertrophic adipose tissue produces soluble adipokines involved in inflammation and immunity, which stimulate the production of pro-inflammatory cytokines, responsible for a chronic low-grade inflammatory state and a higher predisposition to hypersensitivity reactions. Especially in pediatric population with AD, these metabolic disorders are usually underestimated and are associated with long term sequelae and an increased risk of a cardiovascular event, which may also occur later in adult age. Therefore, metabolic comorbidities should be carefully evaluated and early treated in children with AD, to minimize the long-term risk of cardiovascular events.

Modern Interventions for Pediatric Atopic Dermatitis: An Updated Pharmacologic Approach.

Pediatric atopic dermatitis (AD) has historically challenged dermatologists given the variable response of patients to treatment and limited available therapeutic options, often with significant potential side effects. Over the last decade, targeted treatments including dupilumab and Janus kinase (JAK) inhibitors have emerged as significant treatment advances. An updated therapeutic approach for incorporating these new practice-changing medications can help clinicians manage these challenging patients. In this review, we discuss emerging topical and systemic (oral and injectable) treatments in pediatric AD, including topical PDE4 inhibitors and tapinarof, oral JAK inhibitors, and injected biologics including IL-4Rα inhibitor dupilumab, IL-13 inhibitor tralokinumab, IL-13Rα inhibitor lebrikizumab, IL-31Rα inhibitor nemolizumab, and IL-5Rα inhibitor benralizumab. We also review experimental agents in early clinical trials, such as targeted microbiome transplant lotions/antimicrobials, which may gain relevance in AD treatment. Finally, we propose a therapeutic approach for pediatric AD that incorporates newer therapies including dupilumab and JAK inhibitors, recognizing that these agents may not be universally available or approved. Further trials that include pediatric patients, especially head-to-head studies among therapeutic classes, are needed to clarify the role of emerging treatments.