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.

Clinical assessments (SCORAD, PASI, VAS), QoL and adherence to the treatment were evaluated at baseline and after 4 weeks.

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.

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.

Atopic dermatitis (AD) is a highly prevalent disease in Canada with significant patient burden. Treatment guidance for topical therapy (the mainstay of AD management), with particular consideration of emerging treatments, may further improve patient care. Here, we aim to provide healthcare professionals with AD treatment recommendations from the perspective of 10 Canadian dermatologists with expertise in managing AD.

The panel of dermatologists conducted a systematic literature review and leveraged their clinical experience to develop generally accepted principles, consensus statements, and a treatment algorithm using an iterative consensus process.

The panel collectively developed six generally accepted principles, 10 consensus statements, and a treatment algorithm. The guidance notes that assessment of disease severity should encompass both physician-rated measures and patient-reported outcomes. Disease education, lifestyle-based strategies (e.g., trigger avoidance), and supportive measures (e.g., moisturizers) can help reduce signs and symptoms of AD. Choice of therapy should consider disease-, patient-, and treatment-related factors. Although topical corticosteroids (TCS) are often used as first-line treatment in AD, they should be limited to intermittent short-term use. Noncorticosteroid topical therapies (e.g., topical calcineurin inhibitors; topical phosphodiesterase-4 inhibitors; and topical Janus kinase inhibitors) can be used for widespread involvement of AD according to approved use. Once treatment goals are achieved, noncorticosteroid topical maintenance therapy should continue to prevent flares and reduce the need for TCS.

Guidance reflecting the benefits and limitations of topical AD treatments in conjunction with patient understanding of treatment goals supports robust shared decision-making in the management of AD.

Despite significant progress observed in the treatment of atopic dermatitis (AD), a considerable number of patients with severe disease are undertreated and have inadequate symptom control. This may be due to several reasons, such as underestimation of the implications of the disease on patients, families, and society, as well as inconsistent access to effective treatment. The multidimensional disease burden of AD includes other atopic comorbidities, sleep disturbance, and functional impairment and secondary consequences, including neuropsychiatric issues (anxiety and depression) and reduced health-related quality of life.

MEASURE-AD was a global, cross-sectional observational study in adolescents and adults with moderate-to-severe AD, conducted to describe disease burden, treatment patterns, and healthcare resource utilization.

The results concerning patients from Portugal and Greece indicate moderate-to-severe disease for most of the population with frequent disease flares. The quality of life of both adolescents and adults was greatly affected, mainly owing to itch. One out of five patients perceived that their treatment was not effectively controlling AD. Disease resulted in important out-of-pocket expenses and loss of productivity.

Understanding and recognizing the complex burden of moderate-to-severe AD is required to encourage and guide changes in public policy for the effective management of patients.

Background: Although itch is the universal symptom of atopic dermatitis (AD), little is known about its clinical phenotypes in AD. Objective: To examine the relationships of itch characteristics and patterns with AD severity, mental health, sleep, and quality of life (QOL). Methods: We conducted a prospective study of 456 adult patients with AD using validated questionnaires and skin examinations. Thirteen itch characteristics were assessed with the Patient-Reported Outcomes Measurement Information System Itch-Quality. Multivariable regression models evaluated the associations of itch characteristics, severity, or patterns with outcomes. Results: A total of 283 (62%) patients described their itch with ≥1 descriptor-most commonly, stinging (29%), tingling (24%), burning (23%), and painful (23%). The number of itch characteristics reported and endorsement of at least one itch quality were associated with greater AD and itch severity, history of anxiety and depression, active symptoms of clinical depression, sleep impairment, and QOL decrement. Reporting ≥1 itch characteristic remained associated with anxiety, active depression, sleep disturbance, and QOL impact independent of itch severity. All 13 itch descriptors were associated with worse sleep and QOL even after controlling for itch severity. Dermatitis affecting the face, eyelids, hands, or feet was each associated with distinct patterns of itch qualities. Latent class analysis identified three phenotypes of itch, which correlated with AD and itch severity, active symptoms of depression, and QOL decrement. Conclusion: Adults with AD commonly describe their itch heterogeneously using pain-related sensory descriptors. The quality of itch may independently predict mental health outcomes, sleep impairment, and QOL impact.

There are conflicting data on a potential association between atopic dermatitis (AD) and cardiovascular diseases (CVD). The aim of this study was to further explore this connection and whether there are biomarkers indicating the risk for CVD in AD patients.

We included 677 AD patients and 79 nonatopic controls from an observational multicenter case-control study (ProRaD: Prospective longitudinal study investigating the remission phase in patients with atopic dermatitis and other allergy-associated diseases). AD severity and atopic, metabolic, and cardiovascular conditions as well as risk factors were assessed. Serum samples were analyzed with targeted proteomics (cardiometabolics panel, Olink).

We did not find an overall association between AD and CVD. However, AD patients without atopic comorbidities (pure AD) showed a significantly higher CVD prevalence than AD patients with atopic comorbidities (ADAC) (28.2% [37/131] vs. 14.7% [80/546], p < 0.001). Yet, this association could not be confirmed when controlling for cardiovascular risk factors. In pure AD, patients with CVD showed a more severe AD than those without CVD (median EASI [Eczema Area and Severity Index] 12.9 vs. 4.0, p < 0.001). In this subgroup of patients, EASI remained a significant predictor of CVD even in the adjusted model (adjusted odds ratio [aOR] = 1.05, p = 0.040). Forty serum cardiometabolic proteins were upregulated in AD patients compared with nonatopic controls. CC-chemokine ligand 18 (CCL18) was upregulated in both AD (p < 0.001) and CVD (p < 0.001) and its increase correlated with AD severity.

Our study does not suggest an overall association between AD and CVD, but a more complex relation between the two conditions. Disease severity may be a risk factor for CVD in pure AD patients, but not in those with atopic comorbidities. CCL18 may be a biomarker for CVD.

Topical application of mesenchymal stem/stromal cell (MSC) exosomes have yielded encouraging results in the treatment of psoriasis in pre-clinical studies. The safety of topical applications of MSC exosome in ointment has not yet been determined in human subjects.

To assess the safety and tolerability of an MSC exosome ointment, PTD2021P, for topical application in healthy adult volunteers.

Ten healthy adult volunteers were enrolled. All subjects received topical treatment with PTD2021P immediately followed by Vesiderm liposome cream ter in die (TID) (thrice a day) on the forearm with a gap of 4 hours between doses for 20 days and underwent another round of screening procedure at end of study (Day 21 + 3 days). Screening procedures included vital signs, blood examinations, photographs and visual assessment of the area of application. All through the treatment period, the subjects completed the daily Subject Diary to capture adverse events, concomitant medications, and time of study product application.

One subject was reported with 1 treatment-emergent adverse event (TEAE) of COVID-19 infection during the study. The TEAE was moderate in severity and unlikely related to the study drug. This TEAE was resolved and the subject recovered fully. No subject was reported with clinically significant abnormality for laboratory parameters. As per the visual assessment of the area of application, no subject had dryness, itch, oozing/crusting, redness, scratch marks, skin thickening, sleeplessness, or swelling at the area of application of skin.

PTD 2021P was well tolerated for topical application. There were no serious adverse events (SAEs) or TEAEs related to the treatment, and no subject discontinued the study. No clinically significant abnormality was reported for laboratory parameters and vital signs. No abnormality was reported for visual assessment of the area of application of exosome ointment. This ointment could be an alternative therapeutic option for patients who are refractory to current first line therapy.

The prevalence and burden of atopic dermatitis (AD) are disproportionately high in people with skin of colour. Previous research has shown that the risk of xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, no patient-reported instruments have been developed specifically for these disease sequelae in patients with skin of colour.

To develop and perform content validation of patient-reported outcome (PRO) questionnaires to assess AD-related xerosis and dyspigmentation in patients with skin of colour.

A targeted literature review was conducted to understand and identify AD-related disease sequelae and quality-of-life impacts relevant to patients with skin of colour and any instruments used to assess AD in the target population. Two draft PRO questionnaires assessing xerosis (X-AD) and dyspigmentation (D-AD) were developed and refined following advice meetings with three clinical experts. Questionnaire content validity was explored during hybrid concept elicitation and cognitive debriefing interviews with 15 adult and adolescent patients with skin of colour who have moderate-to-severe AD.

Ten concept-focused articles, 3 websites, 17 labels, 1 U.S. Food and Drug Administration compendium and 1 clinical trial confirmed that xerosis and dyspigmentation are important AD-related disease sequelae. Patients with skin of colour [47% girls/women; mean (SD) age 33.3 (21.2) years] reported that the questionnaires were relevant to their AD experience in an appropriate recall timeframe and were readily understood, and that meaningful responses were easy to select. The final X-AD consisted of one 11-point numerical rating scale (NRS) assessing xerosis severity and two items assessing the level of bother associated with xerosis appearance and feeling over the past week (0-4 verbal rating scale). The final D-AD consisted of two 11-point NRS items assessing dyspigmentation severity and two items assessing the level of bother associated with how dyspigmentation looked over the past week.

The X-AD/D-AD questionnaires were well understood and effective in capturing the experiences of xerosis and dyspigmentation in the target population in an appropriate and comprehensive way. This study supports the initial development of the questionnaires in accordance with regulatory guidelines and best practices; however, psychometric validation is required to evaluate the properties of each questionnaire and develop score interpretation guidelines.

Severe asthma and moderate-to-severe atopic dermatitis can significantly impact the lives of children and adolescents. However, real-world data on pediatric patients' perceptions of their medication are limited.

This non-interventional cross-sectional study at a university hospital explored patients' perceptions. We included patients aged between 6 and 17 with severe asthma and/or moderate-to-severe atopic dermatitis. For patients treated with dupilumab, a minimum dupilumab treatment duration of 16 weeks was required. We conducted one structured interview per patient, based on a questionnaire consisting of open questions and ratings on 6-point Likert scales (response scale range: "0: not at all" to "5: very strongly").

The study included 57 participants (severe asthma: n = 31; moderate-to-severe atopic dermatitis: n = 21; both: n = 5) who reported a "rather moderate" burden of asthma (median: 2; Q25/Q75: 0.3/2.8) or atopic dermatitis (3; 1.5/3.5). They experienced their current medications as "rather helpful" (asthma: 4; 3/5; atopic dermatitis: 4; 3/5). Twelve of the participants (21%) reported refusing to take their medication because of reluctance, but all resumed treatment. All participants receiving dupilumab therapy (n = 16) reported an improvement in their disease within a maximum of 2.5 months after starting treatment. The median fear of injection decreased from 3 (0/5) before the first injection to 0.5 (0/1) at the time of the survey.

In this real-world, interview-based study, we found that pediatric patients perceived treatment as highly beneficial for asthma and atopic dermatitis. Furthermore, pediatric patients seemed to respond well to dupilumab therapy in terms of both disease improvement and less fear of injection.

DRKSID DRKS00028092.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2024. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In the revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Patient- and investigator-reported outcome measures are used in research and clinical practice to assess the severity and impact of atopic dermatitis (AD). Initial validation studies of the most commonly used outcome measures for AD underrepresent patients with skin of color or fail to report race, ethnicity, and skin color altogether. Various adaptations have been proposed. Upgrading the erythema score by 1 when using the Eczema Area and Severity Index in patients with skin of color has been suggested but has not yet been validated. However, the use of a "grey scale" in place of the erythema component has been reported to improve inter-rater reliability. Patients of different ethnicities or with skin of color may be impacted in different ways by AD. The pooling of patient-reported outcome measures is therefore not recommended. The Patient-orientated SCORing for Atopic Dermatitis tool for Black skin is an example of a patient-reported outcome measure specifically adapted and validated for Black skin. Novel methods for assessing AD severity include biomarker assessment using tape strips, photonic testing, and measuring subepidermal low echogenic band thickness. In this article, we review the common and novel AD outcome measures in patients with skin of color to highlight best practices and where further research to develop, adapt, and validate outcome measures will be of benefit to patients with AD with skin of color or from minoritized ethnic groups.

The need for alternative therapies for atopic dermatitis (AD) has emerged due to the side effects of conventional therapies. Biodegradable microneedle acupuncture (BMA) is a novel medical device that overcame the shortcomings of traditional intradermal acupuncture (IDA), such as foreign body feeling and allergic dermatitis. This study aimed to evaluate the efficacy and safety of BMA for patients with Mild to Moderate AD compared with the IDA.

An assessor-blinded, parallel, non-superiority, randomized controlled pilot trial was conducted. Thirty adult participants were recruited from a single hospital and were equally divided into the experimental or control group. They were treated with BMA or IDA on both sides of LI11, ST36, and PC6 for four hours. Over four weeks, both interventions were performed eight times in total. The primary endpoint was the objective scoring AD (O-SCORAD) index. The secondary endpoints were visual analog scale (VAS) for itch and sleep disturbance, dermatology life quality index (DLQI), skin hydration, and transepidermal water loss (TEWL).

Enrolled thirty participants completed the trial. After the trial, all endpoints remarkably improved compared with the baseline in both groups, except for the TEWL. Between the two interventions, there were no remarkable differences in the fourth week, except for the VAS score for itch and DLQI. No serious adverse events occurred during the study period.

Both BMA and IDA were effective in improving Mild to Moderate AD, and they were safe. BMA can be an alternative to conventional acupuncture for patients with sensitive skin, including metal allergies.

Off-label treatment is the use of a drug approved for marketing, outside the registration in terms of indication, age group, dose or route of administration. Despite the constant appearance of new preparations on the market, treatment outside the SmPCs guidelines is a current clinical problem. It is believed that it is based on the needs of patients unmet by classical therapy methods. This work focuses on off-label treatment in inflammatory dermatoses such as atopic dermatitis, psoriasis, acne vulgaris and rosacea. Publications on this subject, available on PubMed, Google Scholar and the Cochrane Library, were analyzed in the form of a review, taking into account the mechanisms of action, efficacy and safety of preparations. Based on the literature analysis, it can be concluded that the use of drugs outside the SmPC indications is a common situation in dermatology. However, it is difficult to determine its exact frequency-there is a lack of data on the prevalence of off-label appliances in inflammatory dermatoses from a European perspective. Publications demonstrate varying effectiveness and safety of this form of therapy, depending on the specific preparation. Off-label treatment in dermatology remains an important and current clinical issue that should be explored in further research.

Hand eczema (HE) is common among individuals with atopic dermatitis (AD), yet data on its prevalence and predictors in this population remain limited.

A prospective, dermatology practice-based study was performed in adult patients with AD to determine the prevalence of HE and associations with HE severity. AD severity was assessed using Investigator's Global Assessment (IGA), body surface area (BSA), Eczema Area and Severity Index (EASI), Scoring AD (SCORAD), objective component of SCORAD (O-SCORAD), Patient-reported Global AD severity (PtGA) and Patient-Oriented Eczema Measure (POEM).

Active HE was observed in 135 (45.9%) patients, including 83 (61.5%) with mild, 43 (31.9%) with moderate and 9 (6.7%) with severe HE. Lesions affected the dorsal hands or digits in 231 (78.6%), wrists in 69 (51.1%), palmar hands or digits in 113 (38.4%), with nail dystrophy present in only 7 (5.2%). There were no significant associations of HE severity with demographics or self-reported history of atopic disease. However, in bivariable and multivariable logistic regression models, HE severity was associated with moderate and severe IGA, BSA, EASI, SCORAD, O-SCORAD, PtGA and POEM.

HE was highly prevalent in adult patients with AD treated in the dermatology setting, particularly among patients with moderate-severe AD.

Biallelic variants in diacylglycerol acyltransferase 1 (DGAT1) genegene have been implicated congenital diarrhea and protein-losing enteropathy. Insights into the immunopathologic features of this ultrarare disorder remain scarce, with only one cohort published to date.

To delineate the clinical presentations, laboratory and immunologic profiles, and therapeutic responses associated with DGAT1 deficiency and identify prognostic indicators that affect survival rates.

In this multicenter retrospective analysis of a comprehensive cohort of nine patients carrying seven novel variants, each displaying distinct phenotypic features, we recorded clinical, immunologic, and laboratory data of patients and evaluated the impact of various factors on prognosis.

A total of 67% of patients (n = 6) exhibited symptoms during the first month of life, whereas one demonstrated symptom onset after 6 months. Moreover, 78% of patients (n = 7) presented with diarrhea, all of whom all had vomiting, failure to thrive, hypoalbuminemia, and hypogammaglobulinemia as the advent of protein-losing enteropathy. Patients with reduced CD4+ T-cell frequency (n = 2) exhibited severe infections with unexpected bacteria during the follow-up. Despite immunoglobulin replacement therapy, 45% of patients (n = 4) died of infective complications. A decreased CD4+/CD8+ T-cell ratio was observed in all deceased patients whose colon biopsy samples showed marked inflammation or apoptosis. Early fat-restricted nutrition extended survival, whereas early symptom onset, recurrent severe infections, and a reduced CD4+/CD8+ T-cell ratio were associated with less favorable outcomes.

Our findings advocate early fat restriction as a critical therapeutic strategy. Given the heightened risk of severe infections, antibiotic prophylaxis can be recommended in addition to immunoglobulin replacement therapy for DGAT1-deficient patients exhibiting lymphopenia or diminished CD4+ T cells.

Limited by the specific location of atopic facial dermatitis, treatment options for atopic dermatitis are limited. Our previous research confirms that BiShengZhiYan cream (BSZY cream) can reconstruct the damaged skin barrier and strengthen the repair ability of skin. However, little evidence of its efficacy and safety for the treatment of atopic facial dermatitis is available.

A protocol for a randomised, double-blind, controlled trial of BSZY cream is designed for patients with mild-to-moderate atopic facial dermatitis. We will recruit 130 patients with mild-to-moderate atopic facial dermatitis from the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The participants will be assigned to the BSZY cream group (treatment group) or the emulsion matrix group (control group) randomly. The intervention period will be 4 weeks, once daily in the morning and once in the evening. The primary outcome is the Scoring Atopic Dermatitis Scale. The Clinical Dermatologist Evaluation Form, Patient Self-Assessment Questionnaire and Safety Indicators will be evaluated as secondary outcomes. The follow-up will be conducted at week 8±3 days. The skin condition is assessed by a clinical dermatologist at week 0±3 days, week 2±3 days and week 4±3 days.

The protocol has been approved by Shanghai University of Traditional Chinese Medicine's Yueyang Hospital ethics committee (No. 2023-024). All participants will be asked to sign an informed consent in compliance with the Declaration of Helsinki. On completion of the trial, we plan to disseminate the results through peer-reviewed publications and present the findings at relevant scientific conferences. Data will be provided on reasonable request under participant confidentiality and data privacy regulations.

NCT05792826.

Since the early introduction of peanut to prevent IgE-mediated peanut allergy, other case series have suggested an increased incidence of peanut-triggered Food Protein Induced Enterocolitis Syndrome (FPIES). Data on the prevalence of peanut-induced FPIES in prospective cohorts are lacking.

The PeanutNL cohort is a prospective cohort that included infants at risk of peanut allergy (n = 706) as well as infants with reactions to peanut at home after early introduction (n = 186). They all introduced peanut before the age of 12 months. Oral food challenges were performed to introduce peanut or to evaluate reactions to peanut at home.

Of the 706 infants that were included for first introduction of peanut, 2 had reactions with a phenotype compatible with FPIES (0.3%). Of the 186 infants with reactions to peanut at home, 6 were diagnosed with FPIES (3.2%). Seven out of 8 cases had ingestions of peanut without reactions at home or during clinical introduction before FPIES became apparent. During a 3-year follow-up, six infants (75%) were shown to be tolerant to peanut before the age of 3 years.

The prevalence of challenge-proven peanut-induced FPIES in a Dutch cohort of atopic infants that introduced peanut between the ages of 4 and 11 months is 0.3%. The majority of cases were tolerant to peanut before the age of 3 years. When introducing peanut in the first year of life, physicians should be aware of FPIES reactions, but it should not be a reason to avoid early introduction of peanut.

Itch and pain are both mediated by small sensory fibres. Atopic dermatitis (AD) patients usually report stress-induced flares, but the impact of stress on sensory fibres in lesional and non-lesional skin remains inconclusive. This observational study assessed the effect of acute stress on sensory profiles in subjects with AD (n = 18) and healthy controls (HC, n = 21). Participants completed clinical and psychological questionnaires, and quantitative sensory testing was performed on lesional and non-lesional skin in AD and healthy skin in HC. Assessments were done before and after the Montreal Imaging Stress Task, an acute stress protocol. Stress responses were evaluated by anxiety ratings, heart rate (HR) and salivary cortisol (CORT). Cortisol binding globulin (CBG) was quantified as an indirect measure for circulating CORT. AD participants reported higher anxiety, depression and stress perception than HC. HR was similar between groups, but AD participants showed a blunted CORT response post-stress and lower CBG levels, suggesting altered stress regulation. Acute stress reduced cold sensitivity in HC and non-lesional AD skin but had no effect on lesions. These findings indicate that the effects of stress on small fibres depend on the condition of the skin and emphasise the sensory alterations experienced by AD patients.

Atopic dermatitis (AD) is a common inflammatory skin disease, for which dysbiosis of the skin mycobiome is considered a triggering factor. The aim of this study was to explore the skin mycobiome of AD patients and healthy volunteers (HV). The study included 50 AD patients and as many HV. Culture-based species identification involved a battery of conventional phenotypic tests and PCR sequencing of the internal transcribed spacer (ITS) 1 and 2 regions within the rDNA cluster. Culture-independent, metataxonomic sequencing was performed with ITS1 as the target region. The overall culture-positive rate was higher in AD patients than in HV (74% vs 28%). Among the former, Rhodotorula spp. dominated, followed by Candida spp., Malassezia spp. and Naganishia albida. The congruence between PCR sequencing and phenotyping was 68.6%. Upon metataxonomy of AD samples, 33 (66%) demonstrated close clustering with HV samples ('control-like' AD), while 17 (34%) displayed a remarkably different mycobiome composition ('AD-specific'), with Cladosporium, Malassezia, Candida, Diplodia, Saccharomyces, Penicillium and Aspergillus genera showing increased abundance. Patients with 'AD-specific' mycobiomes were more commonly exposed to air-conditioning compared to 'control-like' AD patients (p = 0.030). A subset of patients with AD has a different cutaneous mycobiome make-up dominated by environmental moulds, and Malassezia and Candida yeasts. Anthropogenic factors may affect the cutaneous mycobiome composition in AD and should be taken into account in microbiome studies.

In recent years, several targeted therapeutic options have become available for the management of atopic dermatitis in children. In this systematic review and meta-analysis, we assessed the efficacy and safety of systemic targeted therapies for atopic dermatitis in children.

A systematic review of literature available in CENTRAL, MEDLINE, Embase, and ICHUSHI databases until January 7, 2023, was performed. Randomized controlled trials of systemic targeted therapies (biologics and small molecules) on children aged 18 years or younger with atopic dermatitis were included. The primary outcomes were the eczema area and severity index (EASI) and adverse events. Other efficacy and safety outcomes were also used for meta-analysis and risk of bias analysis.

We included 10 studies reported in 11 articles involving three agents (dupilumab, abrocitinib, and upadacitinib) and 1760 children. Systemic targeted therapies significantly improved eczema severity with an EASI-75 response (risk ratio, 2.99; 95 % confidence interval [CI], 2.66-3.37). However, systemic targeted therapies were associated with treatment-emergent adverse events (risk difference, 0.05; 95 % CI, 0.01-0.09), particularly among small molecules in subgroup analysis, while no such trend was observed with biologics. Systemic targeted therapy also significantly improved other efficacy outcomes, and no significant association was found in the other safety outcomes. There was no risk of bias in any of the outcomes.

Our findings indicate that systemic targeted therapies are effective and relatively safe for treating atopic dermatitis in children, although small molecules may pose a slightly higher risk of adverse events.

Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases. Among diseases with type 2 Inflammation, this concept is novel and currently most advanced in asthma. This new paradigm has been developed based on a better understanding of the pathophysiology of type 2 inflammation and the advent of highly effective drugs selectively interfering with type 2 pathways. Here, we review the evolution of the new remission concepts in type 2 inflammatory diseases and discuss associated challenges and future research needs.

None.

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs, such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment, have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In these revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

In skin lesions of atopic dermatitis (AD), a chronic inflammatory skin disease, mast cells beyond other immune cells are present in increasing numbers. Upon activation, mast cells release a plethora of mediators, in particular histamine and leukotrienes, as well as chemokines and cytokines, which modulate the immune response of cells in their microenvironment and may influence mast cells in an autocrine loop. This study investigated the effects of histamine and TH2 cytokines on the biosynthesis of cysteinyl leukotrienes (CysLTs) as well as CysLT receptor expression on human mast cells from healthy volunteers and patients with AD.

Human mast cells were generated from CD34+ progenitor cells from peripheral blood. The cultured mast cells were stimulated with IL-4, IL-13, histamine and different histamine receptor selective ligands. Expression of enzymes in the biosynthesis of leukotrienes and expression of CysLT receptors were quantified by real-time PCR. The release of CysLTs was measured by ELISA.

Mast cells from AD patients showed higher expression of 5-Lipoxygenase (5-LO) and 5-Lipoxygenase activating protein (FLAP) compared to mast cells from healthy volunteers at baseline and in presence of histamine and TH2 cytokines. Expression of leukotriene C4 synthase (LTC4S), the biosynthesis of CysLTs, and mRNA expression of both CysLT receptors were induced by histamine and TH2 cytokines in mast cells from healthy volunteers and AD patients.

We provide evidence that in an acute allergic situation histamine and TH2 cytokines may activate the biosynthesis of pro-allergic cysteinyl leukotrienes and up-regulation of CysLT receptor expression in human mast cells. This suggests a novel mechanism for sustaining mast cell activation through a possible autocrine signalling loop under these conditions.

SCORring atopic dermatitis (SCORAD) is widely used to assess the severity of atopic eczema, but score systems based on the entire body may be limited in effective monitoring and intervention. It is crucial to monitor moisture levels in each affected body part, but empirical research is still lacking. The objective of this study was to analyze the levels of stratum corneum hydration (SCH) and transepidermal water loss (TEWL) in atopic dermatitis (AD) patients, focusing on the presence and location of atopic lesions at different body sites. The levels of TEWL and SCH were measured using the AF200 AquaFlux and the Corneometer, respectively, at 15 body sites. 98 children under the age of 10 were measured, including 83 AD patients and 15 in the control group. Patients were also assessed with SCORAD and for the presence of atopic lesions at each body site. 58.7% of AD patients had lesions in the antecubital fossa and popliteal fossa, with corresponding low SCH levels and high TEWL in the upper body. The differences in TEWL between the control group and AD patients were confirmed significant in the neck and antecubital fossa regions, while differences in SCH were identified in the face, antecubital fossa, and popliteal fossa regions. A higher TEWL was found among AD patients with atopic lesions in the face and ankle. This study suggests that continuous monitoring of SCH and TEWL levels at specific body sites can provide insights into identifying vulnerable body areas to AD and supplement the SCORAD system for more effective clinical intervention and prevention strategies.

The Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account. Currently, there is insufficient knowledge about the modulating variables of the PBI and whether it can complement the assessment of the DLQI. In a longitudinal cohort study, 82 patients with PSO were assessed before and up to sixteen weeks after a new treatment episode. The PBI was compared with patients with atopic dermatitis (AD) (n = 61). The effects of gender, age, type of therapy, improvement in body surface area (BSA), anxiety/depression, DLQI and individual coping were assessed. "Getting better skin quickly" was most important in PSO. Improved BSA, anxiety/depression, DLQI, male gender and initiation of biological therapy had the most positive effects. Partial mediation was found for the reduction of anxiety/depression and improved coping. The PBI may be considered an appropriate outcome measure of treatment success in PSO, complementing the DLQI. Patients with clinically relevant anxiety/depression and inadequate coping should be offered adjuvant psychosomatic treatment.

The Eczema Area and Severity Index is an investigator-assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus-based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments.

Background: Atopic dermatitis (AD) is a chronic skin condition that weakens the skin barrier, leading to increased trans-epidermal water loss and reduced skin moisture. Understanding how these changes in the skin barrier relate to AD severity in Mongolian children may offer insights that could apply to other regions facing similar environmental challenges. Methods: A cross-sectional study was conducted at the National Dermatology Center of Mongolia, involving 103 children with AD. Severity was assessed using the SCORAD index, and skin barrier function was measured through TEWL, skin moisture, and pH. Linear regression analyses were conducted, adjusting for age, skin physiological parameters, AD severity characteristics, and total IgE levels. Results: Among the participants, 48.54% were classified as having moderate AD, while 34.95% had severe AD. The mean SCORAD index was 43.19 ± 17.11. In the final adjusted regression analysis, higher TEWL was significantly associated with greater AD severity (non-lesional: B = 0.328, p = 0.004; lesional: B = 0.272, p = 0.007), while skin moisture showed an inverse association (non-lesional: B = -0.771, p < 0.001; lesional: B = -0.218, p < 0.001). The total IgE level was significantly higher in the severe AD group (p = 0.013). Although skin pH initially correlated with AD severity, it did not remain significant in multivariate analysis. Conclusions: This study emphasizes the role of skin barrier function, particularly increased TEWL and reduced moisture, in AD severity among Mongolian children.

Early life infections (ELIs), encompassing both viral and bacterial types, occur within the first six months of life. Influenced by genetic host factors and environmental conditions, the relationship between ELIs and subsequent allergic manifestations, particularly cow's milk protein allergy (CMPA) and atopic dermatitis (AD), is complex and not fully understood.

The aim of the current study was to examine the potential interplay between nutrition, infections, and allergic manifestations in the first six months of life in infants with a family history of allergies, who were either exclusively breastfed (EBF) or fed a combination of breast milk and standard (SF) or partially hydrolyzed infant formula (pHF).

The Allergy Reduction Trial (ART) is a multicenter, randomized controlled trial involving 551 participants. From birth, these participants were divided into three groups: Exclusive Breastfeeding (EBF), Partially Hydrolyzed Formula (pHF), and Standard Formula (SF). ELIs, defined as viral and bacterial infections occurring during the first 6 months, and outcomes (AD, CMPA) were recorded through questionnaires (i.e., SCORAD and CоMiSS) and clinical assessments.

The relative risk (RR) for CMPA in infants with ELIs was 0.20 (95% CI: 0.07-0.58), highlighting a protective effect of ELIs against CMPA development. Notably, the incidence of CMPA was significantly lower in infants who experienced ELIs compared to those without (3% vs. 13.4%, p = 0.001), with no cases of CMPA observed at 6 months in exclusively breastfed (EBF) infants with ELIs. For AD, a trend was observed where the incidence was lower in infants with ELIs who were fed with pHF at 6.5%, compared to those fed with SF at 18.2% (p = 0.092), suggesting a potential protective effect of ELIs in the pHF group against AD development.

The study highlights a potential protective role of ELIs in reducing the risk of CMPA, particularly in EBF infants. Furthermore, it suggests a trend towards lower AD incidence in infants fed with pHF, highlighting the complex interplay between early microbial exposures, feeding practices, and immune development. Further research is warranted to unravel this challenging relationship and appropriately inform early life allergy prevention strategies.

Previous studies have shown efficacy of early introduction of peanut to prevent peanut allergy. It is currently unknown which diagnostic pathway is optimal after parental-reported reactions to peanut at home after early introduction.

The PeanutNL cohort study included high-risk infants who were referred for early introduction of peanut. A subgroup of 186 infants with reactions to peanut at home underwent peanut skin prick tests and a supervised open oral food challenge (OFC) at a median age of 8 months. After a negative OFC, peanut was introduced at home.

Sensitization to peanut was detected in 69% of 186 infants, of whom 80% had >4 mm wheals in skin prick tests. An OFC with a cumulative dose of 4.4 g of peanut protein was performed in 163 infants with Sampson severity score grade I-III reactions at home; 120 challenges were negative. Peanut was subsequently introduced at home in infants with a negative challenge outcome. After 6 months, 96% were still eating peanut and 81% ate single portions of 3.0 g of peanut protein. One patient was considered to be peanut allergic after reintroduction of peanut at home.

These data show that 65% of infants with reported reactions to peanut at home have negative OFCs. In those children, peanut could be introduced safely, and 96% were able to consume peanut regularly without reactions. Challenging infants younger than 12 months prevents the misdiagnosis of peanut allergy and enables safe continued exposure to peanut and the induction of long-term tolerance.

Atopic dermatitis (AD) is a chronic disease that is increasing in prevalence, particularly in children and people with skin of colour. Current management involves topical treatments, phototherapy and immunosuppressants, as well as newer therapies like dupilumab. Health professionals should also be aware of the specific management considerations for AD in people with skin of colour. This systematic review was conducted to examine global guidelines for the management of AD in children, compare management recommendations, examine specific recommendations for children with skin of colour, and assess the quality of the guidelines. The databases Medline, Embase, CINAHL, Scopus, Guidelines International Network, and Emcare Nursing and Allied Health were searched to identify guidelines or articles relating to the management of AD in children from 1990 to 2023. A grey literature search was also undertaken. The recommendations from the guidelines were extracted and compared, and the quality of the guidelines was assessed using the Appraisal Guidelines for Research and Evaluation (AGREE) II tool. A total of 1644 articles were identified from the initial search. Title and abstract screening, full text screening, and reference checking yielded 28 guidelines for the final appraisal and data extraction. The main variations in management recommendations were the timing of emollients, bleach baths, bath additives, oral antihistamines, and the age cut-offs for topical calcineurin inhibitors. Many guidelines were not updated to reflect newer therapies like dupilumab and topical phosphodiesterase-4 (PDE4) inhibitors. There were minimal recommendations regarding management of skin of colour. Only 12/28 guidelines met the satisfactory cut-off score for the AGREE II appraisal, largely due to a lack of well-documented methodology. This review showed that the recommendations for AD management in skin of colour were consistently lacking. Despite generally consistent management strategies over the last 5 years, less than half of the guidelines met high-quality criteria, emphasising the importance of using tools like AGREE II in future guideline development.

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making.

Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes.

Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model.

Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes.

Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients' well-being.

The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex.

To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics.

Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD™; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups.

Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment.

While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions.

To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites.

An open-label, noncontrolled, nonrandomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-min interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months.

Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥ 2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects.

SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile.

Since 2016, several therapies have been approved for treating atopic dermatitis (AD) in Singapore, including biologics, oral Janus kinase (JAK) inhibitors and topical crisaborole. This study supplements the 2016 Singapore treatment guidelines for AD, focusing on newer therapies for moderate-to-severe disease, while revisiting older treatment regimens to accommodate changes in knowledge and practice.

A modified Delphi panel was held, led by 2 co-chairs. The voting expert panel consisted of 12 dermatologists experienced in managing AD in Singapore. Delphi survey rounds were conducted between 24 July and 27 October 2023. Panellists indicated their agreement with drafted statements using a 5-point Likert scale. Consensus was defined as ≥80% agreement. An expert meeting was held to facilitate the consensus process between rounds 1 and 2 of voting.

All expert panellists participated in both survey rounds, with a 100% response rate. Thirty-nine statements, classified into general principles, conventional treatments, biologics and JAK inhibitors, were proposed. Of these, 27 statements reached consensus at the end of round 1. After the expert meeting, 17 statements were included in round 2, of which 16 statements reached consensus. One statement did not reach consensus. Key updates are the inclusion of dupilumab and JAK inhibitors as potential first-line treatments for moderate-to-severe AD, in certain populations.

This modified Delphi study generated consensus among Singapore dermatology experts, to update treatment guidelines in moderate-to-severe atopic dermatitis. The consensus statements developed are intended to supplement the 2016 Singapore treatment guidelines for AD. Further revisions may be required when new evidence and/or treatments become available.

Introduction. Atopic dermatitis (AD) is the most prevalent inflammatory dermatological disorder, affecting a significant percentage of the global population. This chronic disease has a multifactorial and intricate pathogenesis, influenced by genetic predisposition, skin barrier dysfunction, immune dysregulation, neuroimmune mechanisms, and alterations in the skin microbiome, among other factors. Methods. The treatment of AD has faced significant clinical challenges due to the ineffectiveness of conventional therapies. However, recent advances in understanding its pathophysiology have led to the introduction of new therapeutic options. Recently, the OX40 receptor has been identified as a key factor in the development of AD. Recent studies have demonstrated that blocking the OX40 ligand with monoclonal antibodies significantly and sustainably improves the signs and symptoms of moderate to severe AD. Results. A comprehensive review of the available literature on anti-OX40 treatments in atopic dermatitis that evaluates their mechanism of action, their clinical efficacy, and the prospects of this promising therapeutic option for improving AD management is provided. Conclusions. Anti-OX40 and anti-OX40L blockers are a promising therapeutic alternative for the management of moderate-severe atopic dermatitis. Prospective analytical studies are needed to determine whether this new therapeutic target represents a qualitative advance in modifying the progression of the disease.