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 , , , , and .

Children with atopic dermatitis show increased activity of β-glucocerebrosidase and stratum corneum levels of glucosylcholesterol that are strongly related to the local cytokine milieu.

Background: Atopic dermatitis (AD) is characterized by immune dysregulations and an impaired skin barrier, including abnormalities in lipid organization. In the stratum corneum (SC), β-glucocerebrosidase (GBA) mediates transformation of glucosylceramide (GlcCER) into ceramide (CER) and cholesterol into glucosylcholesterol (GlcChol). Alteration in GBA activity might contribute to skin barrier defects in AD.

binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis.

colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that interacts with the host protein corneodesmosin.

Changes in nano-mechanical properties of human epidermal cornified cells in children with atopic dermatitis.

 Impaired skin barrier is an important etiological factor in atopic dermatitis (AD). The structural protein filaggrin (FLG) plays a major role in maintenance of the competent skin barrier and its deficiency is associated with enhanced susceptibility to mechanical injury. Here we examined biomechanical characteristics of the corneocytes in children with AD and healthy controls.

The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab.

Background: The immune abnormalities underlying the ichthyoses are poorly understood.

Objective: To determine the immunophenotype of an ichthyosis resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin gene (DSP) and target therapy on the basis of molecular pathogenesis.

Methods: Immunophenotyping was performed by using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy.

Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis.

skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum.

Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations.

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci).

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations.

Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown.

Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin.

Background: Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 gene (DSG1). To date, only 3 families have been reported.

Objective: We studied a new case of SAM syndrome known to have no mutations in DSG1 to detail the clinical, histopathologic, immunofluorescent, and ultrastructural phenotype and to identify the underlying molecular mechanisms in this rare genodermatosis.

Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis.

Background: Loss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP).

Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease.

Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling. In more than 80% of cases, IP is due to recurrent or nonrecurrent deletions causing loss-of-function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion.

High-density genotyping study identifies four new susceptibility loci for atopic dermatitis.

Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency.

The multifunctional role of filaggrin in allergic skin disease.

Filaggrin is a major structural protein in the stratum corneum of the epidermis. Mutations in the filaggrin gene are the most significant known genetic risk factor for the development of atopic dermatitis. Mutations in the human filaggrin gene (FLG) also confer risk for the associated allergic diseases of food allergy, asthma, and allergic rhinitis.

A study investigating patients' experience of hospital and home iontophoresis for hyperhidrosis.

Iontophoresis is an effective and safe treatment for hyperhidrosis. We investigated patients' experiences with the Idrostar® home iontophoresis unit (STD Pharmaceuticals, Hereford, UK) considering compliance and efficacy.

Papulopustular rosacea: prevalence and relationship to photodamage.

Background: The prevalence and pathogenesis of rosacea is uncertain. Previously, studies used varying definitions of disease and have not explored the relationship of its prevalence to ultraviolet (UV) exposure or photodamage.

Objectives: We investigated the prevalence of papulopustular rosacea (PPR) and its relationship to UV radiation exposure in 1000 randomly selected Irish individuals.