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Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were −73.5% at week 4, −81.7% at week 28, and −81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%–95.2%). Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. Methods: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019–2022. We extracted SRs’ bibliographical data and appraised SRs’ methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. Results: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. Conclusions: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users. [ABSTRACT FROM AUTHOR]

Impaired skin barrier is one of the hallmarks of atopic dermatitis (AD), with abnormalities in the cornified envelope, lipid lamellae, tight junctions and cutaneous microbiome. These findings are also present in nonlesional skin of AD individuals, suggesting that epidermal barrier defects may be the initial step towards the development of AD and eventually other atopic diseases (atopic march). It is currently known that pathophysiology of AD involves an interplay between this dysfunctional skin barrier and a predominantly type 2 skewed innate and adaptive immune responses, which further disrupt the skin barrier through type 2 cytokines. In this setting, there is enhanced penetration of environmental and food allergens through a deficient barrier, leading to an increased susceptibility to sensitization. During the sensitization process, thymic stromal lymphopoietin (TSLP) polarizes skin dendritic cells to a T-helper 2 response, and TSLP seems to be a key cytokine in the sensitization of food allergy, allergic asthma and rhinitis. In this review, the authors describe the current knowledge of the pathophysiology of the epidermal barrier, its disruption in AD and how it may be involved in the development of atopic comorbidities and the role of barrier repair therapy on the prevention of the atopic march progression. [ABSTRACT FROM AUTHOR]

Introduction. Grover’s disease is characterized by pruriginous polymorphic rash with a variable course and duration. Although the etiology is still unknown, the disease is often associated with other dermatoses, malignant diseases, use of certain medications, as well as immunosuppression. Case Report. We report a case of a 70-year-old male patient who was referred for examination to the Clinic of Dermatovenereology Diseases, Clinical Center of Vojvodina, due to a rash that lasted for nine months. The first lesions on the skin appeared around the nipples as exudative eczematous plaques. A few months later, identical lesions appeared on the lower legs. During treatment with systemic anti-histamines and topical corticosteroids, there were episodes of transient improvements and re-exacerbations. In the meantime, erythematous brownish, round and oval papules appeared on the abdomen and the back, accompanied by intense itch. Laboratory findings revealed eosinophilia and elevated serum immunoglobulin E levels. A skin biopsy of the back lesion was performed and the histopathological examination confirmed the diagnosis of Grover’s disease. After the systemic treatment using corticosteroids and antihistamines, with gradual dose reduction and application of topical corticosteroids and emollients, complete regression of the skin lesions was achieved. Conclusion. Since the clinical manifestations of the disease may be nonspecific and discrete, dermatopathological analysis is of crucial importance in making the correct diagnosis. In patients with atopy, the treatment with systemic corticosteroids, antihistamines and topical agents may lead to regression of skin lesions with a significant improvement in the quality of life. [ABSTRACT FROM AUTHOR]

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers. [ABSTRACT FROM AUTHOR]

Background/Aim. Atopic diseases such as atopic dermatitis, allergic rhinitis and asthma have had increased prevalence during the past decade and nowadays occur in every third child in developed countries. The aim of the study was to determine frequency and type of atopic diseases at the age of two, as well as the importance the total IgE antibodies concentrations have in diagnosis and prognosis of the disease. Methods. The study involved 175 children up to two years of age. Allergy-like symptoms were found after surveying their parents and pediatric medical records. Using the fluorescence immunossay (FIA) method, total IgE antibodies concentrations and specific IgE antibodies (Phadiatop infant) were determined on an Immunocap 100 Dyagnostic System. Results. One or more allergy-like symptoms accounted for 57.7% of findings in children under the age of two, whilst in 19.4% the existence of IgE-related allergic diseases was found. Atopic diseases usually have clinical manifestations of atopic dermatitis (11.4%), IgE-bound wheezing/asthma (10.8%) and food allergies (7.4%), and to much lesser extent those of allergic rhinitis (3.4%) and urticaria (1.7%). The significantly higher total IgE antibodies concentrations were found in children with allergy-like symptoms (p < 0.0005) (cut-off 15.15 kU/L, sensitivity 76.5% specificity 71.6%). Conclusion. Almost 20% of two-year-old children have any of clinically manifested allergic diseases, with atopic dermatitis and IgE wheeze/asthma being predominant. The higher total IgE antibodies concentration is a good marker for sensitization in children with allergy-like symptoms. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria–host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This study examined whether infants aged 0–3 months exhibited long-term effects of using a moisturizer skincare intervention and whether a short-term skin problem resulted in the subsequent development of food allergies or atopic dermatitis (AD) until the age of 2 years. Methods: This study was a follow-up of a completed randomized control trial (RCT) of moisturizer skincare for infants aged 0–3 months. A self-reported questionnaire was mailed to the parents of children aged 1–2 years who had participated in the RCT. Data were analyzed using a Chi square test, by intention to treat analysis, and by multiple logistic regression. Results: Of 155 infants, 22 (14.2%) and 28 (18.1%) had food allergies and AD/eczema until 2 years of age, respectively. No significant difference was seen in food allergies or AD between the group that received moisturizer skincare intervention and the control group. On the contrary, food allergies until 2 years of age were significantly associated with short-term (4–7 days) and long-term (more than 7 days) body skin problems occurring in the first 3 months of life, a family history of AD, and the time of starting complementary food. High value of face transepidermal water loss at 3 months of age was also associated with food allergies. Moreover, a short duration of severe diaper dermatitis during the first 3 months, a family history of AD, and being male were significantly associated with AD/eczema until the age of 2 years. Conclusions: After adjusting for family history of AD, a short-term skin problem in the first 3 months of life was significantly associated with the development of food allergies or AD/eczema until the age of 2 years. Prevention or prompt treatment of skin problems in newborns is essential for preventing future allergic diseases. Trial registration This was a follow-up study conducted 2 years after the completed RCT of a moisturizer skincare intervention for early infants, which was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013260) [ABSTRACT FROM AUTHOR]