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Cells May 2019Atopic dermatitis (AD) is characterized by dry and itchy skin evolving into disseminated skin lesions. AD is believed to result from a primary acquired or a... (Review)
Review
Atopic dermatitis (AD) is characterized by dry and itchy skin evolving into disseminated skin lesions. AD is believed to result from a primary acquired or a genetically-induced epidermal barrier defect leading to immune hyper-responsiveness. Filaggrin (FLG) is a protein found in the cornified envelope of fully differentiated keratinocytes, referred to as corneocytes. Although null mutations are strongly associated with AD, they are not sufficient to induce the disease. Moreover, most patients with ichthyosis vulgaris (IV), a monogenetic skin disease characterized by homozygous, heterozygous, or compound heterozygous null mutations, display non-inflamed dry and scaly skin. Thus, all causes of epidermal barrier impairment in AD have not yet been identified, including those leading to the Th2-predominant inflammation observed in AD. Three dimensional organotypic cultures have emerged as valuable tools in skin research, replacing animal experimentation in many cases and precluding the need for repeated patient biopsies. Here, we review the results on IV and AD obtained with epidermal or skin equivalents and consider these findings in the context of human in vivo data. Further research utilizing complex models including immune cells and cutaneous innervation will enable finer dissection of the pathogenesis of AD and deepen our knowledge of epidermal biology.
Topics: Cells, Cultured; Dermatitis, Atopic; Filaggrin Proteins; Humans; Hypersensitivity; Ichthyosis Vulgaris; Inflammation; Intermediate Filament Proteins; Models, Biological; Mutation; Skin
PubMed: 31121896
DOI: 10.3390/cells8050489 -
JAMA Dermatology Jan 2022Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more...
IMPORTANCE
Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish.
OBJECTIVE
To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis.
MAIN OUTCOMES AND MEASURES
Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations.
RESULTS
Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery.
CONCLUSIONS AND RELEVANCE
This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.
Topics: Cohort Studies; Female; Genomics; Humans; Ichthyosis; Ichthyosis, Lamellar; Male; Phenotype
PubMed: 34851365
DOI: 10.1001/jamadermatol.2021.4242 -
Journal of Inherited Metabolic Disease Nov 2018Congenital disorders of glycosylation (CDG) have a broad spectrum of clinical manifestations. They can affect multiple organ systems, including skin and subcutaneous...
Congenital disorders of glycosylation (CDG) have a broad spectrum of clinical manifestations. They can affect multiple organ systems, including skin and subcutaneous tissue. We report on an infant with severe ichthyosis caused by MPDU1 mutations. The case illustrates that skin manifestations are an important feature of CDG syndromes. Therefore, metabolic investigations should be included in the workup of infantile ichthyosis disorders.
Topics: Congenital Disorders of Glycosylation; Female; Humans; Ichthyosis; Infant; Mutation; Repressor Proteins; Skin; Exome Sequencing
PubMed: 29721919
DOI: 10.1007/s10545-018-0189-9 -
Allergologia Et Immunopathologia 2014Atopic eczema (AE) affects approximately 20% of children in Northern countries. Onset during early infancy is common and is characterised by altered skin barrier,...
BACKGROUND
Atopic eczema (AE) affects approximately 20% of children in Northern countries. Onset during early infancy is common and is characterised by altered skin barrier, increased water loss and defective lipid layer. Restoration of skin barrier by emollients and/or oil baths is an important part of AE treatment, but its role in preventing xerosis and AE is unknown. The present pilot study aimed to assess if xerosis, and possibly AE, could be reduced at six months of age by early introduction of frequent oil baths/facial fat cream in infants with dry skin.
METHODS
A controlled intervention pilot study included 56 six-week-old infants with xerosis, but not AE. Skin quality score ranging from 0 (normal skin) to 4 (probable AE), was assessed at inclusion, three and six months of age, with skin quality at six months as main outcome. One well baby clinic was recruited for intervention, frequent skin care (oil bath (0.5 dl) and facial fat cream, five well baby clinics recruited for observation only.
RESULTS
The intervention group (n=24) had more often normal skin (75%) at six months than the observation group (37.5%) (p<0.001), and less often probable AE (4.0 vs. 19.0%, respectively, ns). Oil baths were performed regularly, 2-4 up to 5-7 times/week in the intervention group, vs. fewer oil baths with sparse volume of oil in the observation group. No adverse reactions were reported.
CONCLUSION
Regular oil baths in infants seem to reduce xerosis and may possibly reduce atopic eczema.
Topics: Dermatitis, Atopic; Female; Follow-Up Studies; Humans; Ichthyosis; Infant; Male; Oils; Pilot Projects; Skin; Skin Care; Skin Cream
PubMed: 25201763
DOI: 10.1016/j.aller.2014.06.003 -
Pediatrics and Neonatology Nov 2022
Topics: Humans; Infant, Newborn; Ichthyosis, Lamellar
PubMed: 35659753
DOI: 10.1016/j.pedneo.2022.04.006 -
International Journal of Nursing Studies Apr 2016Maintaining and improving skin health of patients and long-term care receivers is a widely agreed upon goal in health and nursing care. Care dependent and aged persons...
BACKGROUND
Maintaining and improving skin health of patients and long-term care receivers is a widely agreed upon goal in health and nursing care. Care dependent and aged persons have a high predisposition to develop dry skin conditions.
OBJECTIVES
The aim of this study was to estimate the prevalence and severity of skin dryness in hospitals and nursing homes and to identify person- and health-related variables associated with this skin condition.
DESIGN
The study was part of a bigger annual multicentre descriptive cross-sectional prevalence study of health problems.
SETTINGS/PARTICIPANTS
Fourteen nursing homes and six hospitals in Germany participated in this study in 2014. A total of 1710 subjects (n=1091 long-term care residents and n=619 in-patients) were included.
METHODS
Skin assessments were conducted and skin dryness was measured using the Overall Dry Skin Score. Mobility was measured using the respective item of the Care Dependency Scale. Demographic, functional and physiological parameters were compared between subjects with and without dry skin. A logistic regression model predicting skin dryness was created.
RESULTS
The prevalence of skin dryness was 48.8% (95% CI 46.5-51.2). Nursing home residents were most often affected (52.6%; 95% CI 49.6-55.6) compared to in-patients (42.2%; 95% CI 38.3-46.1). The skin of feet and legs were most often affected by skin dryness (42.9%) compared to other skin areas. Being older (OR 1.01; 95% CI 1.01-1.02), having pruritus (OR 14.21; 95% CI 8.00-22.95), oncological (OR 1.95; 95% CI 1.30-2.91), musculoskeletal diseases (OR 1.31; 95% CI 1.04-1.64), being skin care independent (OR 0.48; 95% CI 0.32-0.70) were the strongest covariates for the presence of dry skin in the multivariate model.
CONCLUSIONS
Based on a large sample results indicate that approximately every second nursing home resident and hospital in-patient are affected by dry skin. Severe forms occur more often in hospital in-patients compared to nursing home residents. Skin care interventions to tackle dry skin are recommended particularly for hospital patients and nursing home residents who are affected by pruritus or oncological diseases, who are in need of washing/bathing assistance, and who have musculoskeletal diseases.
Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Germany; Hospitals; Humans; Ichthyosis; Inpatients; Male; Nursing Homes; Prevalence
PubMed: 26810458
DOI: 10.1016/j.ijnurstu.2016.01.003 -
The Journal of Investigative Dermatology Jul 2021The Mendelian disorders of cornification consist of a highly heterogeneous group of diseases, and the majority of nonsyndromic cases belong to the family of autosomal...
The Mendelian disorders of cornification consist of a highly heterogeneous group of diseases, and the majority of nonsyndromic cases belong to the family of autosomal recessive congenital ichthyosis. Mutations in SDR9C7 have been associated with autosomal recessive congenital ichthyosis, and clinical manifestations include mild to moderately dry, scaly skin with or without hyperkeratosis, palmoplantar keratoderma, and erythroderma. SDR9C7, with short-chain dehydrogenase and/or reductase activity, is known as nicotinamide adenine dinucleotide‒ or nicotinamide adenine dinucleotide phosphate‒dependent oxidoreductase and has been shown to be involved in the final step of epidermal lipid barrier formation by covalent binding of acylceramide to the cornified envelope. In this study, we present the clinical and molecular description of 19 patients with autosomal recessive congenital ichthyosis in five consanguineous families with SDR9C7 mutations. We also downregulated the expression of SDR9C7 in keratinocytes using the small interfering RNA technique in three-dimensional organotypic skin constructs. Our results demonstrated morphological and histological abnormalities in these constructs ex vivo, similar to those observed in patients with ichthyosis. Moreover, the results from keratinocyte migration and epidermal dye penetration assays provided evidence for the role of SDR9C7 in the disease pathomechanism. Collectively, our results indicate that SDR9C7 deficiency by itself is sufficient to disrupt epidermal barrier function leading to ichthyotic phenotype.
Topics: Cell Movement; Consanguinity; Epidermis; Female; Gene Knockdown Techniques; HaCaT Cells; Humans; Ichthyosis; Male; Oxidoreductases; Pedigree; Water Loss, Insensible
PubMed: 33422619
DOI: 10.1016/j.jid.2020.11.030 -
International Journal of Molecular... Sep 2021Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus....
Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus. Here, we investigated the effects of a novel emollient containing H.ECM liposome, which contains a soluble proteoglycan in combination with hydrolyzed collagen and hyaluronic acid. A prospective, single-arm study was conducted on 25 participants with mild atopic dermatitis or dry skin to assess the hydration and anti-inflammatory effect of the novel emollient applied daily over four weeks. All efficacy parameters, including itching severity, transepidermal water loss, and skin hydration, improved significantly after four weeks. The in vitro and ex vivo studies confirmed the restoration of the skin's barrier function. The study revealed the clinical and laboratory efficacy of H.ECM liposome in reducing itching and improving the skin's barrier integrity. Thus, the use of H.ECM liposome can be considered a therapeutic option for dry and eczema-prone skin.
Topics: Administration, Topical; Adult; Animals; Anti-Inflammatory Agents; Cell Line; Collagen; Dermatitis, Atopic; Eczema; Emollients; Female; Humans; Hyaluronic Acid; Ichthyosis; Liposomes; Male; Mice; Middle Aged; Pilot Projects; Proteoglycans; Pruritus; RAW 264.7 Cells; Severity of Illness Index; Skin; Water Loss, Insensible; Young Adult
PubMed: 34638528
DOI: 10.3390/ijms221910189 -
Journal of the European Academy of... Jul 2022The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the... (Review)
Review
The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.
Topics: Dermatitis, Exfoliative; Diagnosis, Differential; Humans; Ichthyosis; Ichthyosis, Lamellar; Infant, Newborn; Netherton Syndrome; Severe Combined Immunodeficiency
PubMed: 35238435
DOI: 10.1111/jdv.18043 -
Journal of Obstetrics and Gynaecology... Apr 2020Keratitis-ichthyosis-deafness (KID) syndrome is a congenital ectodermal disorder characterized by keratitis, ichthyosis, and deafness. This syndrome affects multiple...
BACKGROUND
Keratitis-ichthyosis-deafness (KID) syndrome is a congenital ectodermal disorder characterized by keratitis, ichthyosis, and deafness. This syndrome affects multiple systems and can be fatal.
CASE
A 34-year-old G2, P1 woman was admitted to the Ege University School of Medicine in Izmir, Turkey because of a rapid increase in abdominal circumference at 32 weeks gestation. Fetal anatomic screening revealed complete chorioamniotic separation, hypoplasia of the cerebellar vermis, and dysmorphic facial findings such as frontal bulging. After the delivery, the baby's whole body had granular thickened skin. Bilateral dry eye, corneal edema, and bilateral retinopathy of prematurity were diagnosed.
CONCLUSION
This case report highlights the importance of prenatal diagnosis through ultrasonography and magnetic resonance imaging. This is the first case report that has antenatal ultrasonographic features in the literature.
Topics: Adult; Deafness; Female; Humans; Ichthyosis; Infant, Newborn; Keratitis; Magnetic Resonance Imaging; Pregnancy; Prenatal Diagnosis; Turkey; Ultrasonography
PubMed: 31421982
DOI: 10.1016/j.jogc.2019.06.005