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The British Journal of Dermatology Oct 2022The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections....
BACKGROUND
The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored.
OBJECTIVES
To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes.
METHODS
Body site-matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis.
RESULTS
Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and Corynebacterium genera, as well as shifts in fungal species, including Malassezia. Malassezia globosa was reduced at all body sites, whereas M. sympodialis was reduced in the ichthyotic upper arm and upper buttocks. Malassezia slooffiae, by contrast, was strikingly increased at all body sites in participants with congenital ichthyosiform erythroderma (CIE) and lamellar ichthyosis (LI). A previously undescribed Trichophyton species was also detected as sporadically colonizing the skin of patients with CIE, LI and epidermolytic ichthyosis subtypes.
CONCLUSIONS
The ichthyosis skin microbiome is significantly altered from healthy skin with specific changes predominating among ichthyosis subtypes. Skewing towards the Th17 pathway may represent a response to the altered microbial colonization in ichthyosis. What is already known about this topic? The skin microbiome of congenital ichthyoses is largely unexplored. Microbes play an important role in pathogenesis, as infections are common. The relative abundances of staphylococci and corynebacteria is increased in the cutaneous microbiome of patients with Netherton syndrome, but extension of these abundances to all congenital ichthyoses is unexplored. What does this study add? A common skin microbiome signature was observed across congenital ichthyoses. Distinct microbiome features were associated with ichthyosis subtypes. Changes in microbiome may contribute to T helper 17 cell immune polarization. What is the translational message? These data provide the basis for comparison of the microbiome with lipidomic and transcriptomic alterations in these forms of ichthyosis and consideration of correcting the dysbiosis as a therapeutic intervention.
Topics: Adult; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Ichthyosis, Lamellar; Lipids; Microbiota; Skin
PubMed: 35633118
DOI: 10.1111/bjd.21687 -
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 American Academy of... Sep 2013Skin toxicities are the most common side effects associated with the epidermal growth factor receptor inhibitor erlotinib, occurring in most patients receiving the drug.... (Review)
Review
Skin toxicities are the most common side effects associated with the epidermal growth factor receptor inhibitor erlotinib, occurring in most patients receiving the drug. Clinical trials evaluating erlotinib for the treatment of non-small cell lung cancer have reported a range of skin disorders, the most common being acneiform rash, xeroderma (dry skin), pruritus, and paronychia. Although in the majority of cases these effects are mild and transient, they can have a considerable impact on a patient's quality of life and, if particularly severe and persistent, may necessitate treatment interruption or cessation and compromise treatment outcome. This coupled with recent evidence to suggest a positive correlation between the incidence and severity of rash and clinical outcome among erlotinib-treated patients with advanced or metastatic non-small cell lung cancer highlights the importance of adequately managing epidermal growth factor receptor inhibitor--related skin disorders. Clear treatment strategies are therefore necessary to ensure the prevention and optimal management of erlotinib-related skin toxicities thereby enabling patients to continue erlotinib treatment. In this review we present a practical approach for the treatment of erlotinib-related cutaneous side effects in Japanese patients with advanced non-small cell lung cancer providing details of specific treatment interventions, according to symptom severity, for each of the common skin disorders. In addition, the importance of preventive skin care measures--namely maintaining cleanliness, moisturization, and protection from external stimuli--in preventing the development of serious skin disorders is discussed and guidelines for the practice of proper skin care are presented.
Topics: Acneiform Eruptions; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Eruptions; Erlotinib Hydrochloride; Humans; Ichthyosis; Lung Neoplasms; Paronychia; Patient Education as Topic; Pruritus; Quinazolines
PubMed: 23602600
DOI: 10.1016/j.jaad.2013.02.025 -
Dermatology Online Journal Dec 2005A 6-year-old African boy with a history of a collodion membrane presented with scale in a generalized distribution and flexural accentuation. Large, brown, polygonal...
A 6-year-old African boy with a history of a collodion membrane presented with scale in a generalized distribution and flexural accentuation. Large, brown, polygonal scales were present on the forehead, lateral aspects of the face, and extremities. The nature of the scales and the lack of erythroderma in this patient are consistent with a mild form of lamellar ichthyosis (LI). LI and nonbullous congenital ichthyosiform erythroderma (NBCIE) represent phenotypes at the poles of the autosomal recessive ichthyosis spectrum. Mutations in genes encoding transglutaminase 1 (TGM1), the ABCA12 transporter (ABCA12), ichthyin, lipoxygenase 3 (ALOXE3), and 12(R)-lipoxygenase (ALOX12B) have been shown to underlie both NBCIE and LI.
Topics: Child; Humans; Ichthyosis, Lamellar; Male; Skin
PubMed: 16403385
DOI: No ID Found -
The FEBS Journal Jul 2007The recent convergence of genetic and biochemical evidence on the activities of lipoxygenase (LOX) enzymes has implicated the production of hepoxilin derivatives (fatty... (Review)
Review
The recent convergence of genetic and biochemical evidence on the activities of lipoxygenase (LOX) enzymes has implicated the production of hepoxilin derivatives (fatty acid epoxyalcohols) in the pathways leading to formation of the water-impermeable barrier of the outer epidermis. The enzymes 12R-LOX and eLOX3 are mutated in a rare form of congenital ichthyosis, and, in vitro, the two enzymes function together to convert arachidonic acid to a specific hepoxilin. Taken together, these lines of evidence suggest an involvement of these enzymes and their products in skin barrier function in all normal subjects. The natural occurrence of the specific hepoxilin products, and their biological role, whether structural or signaling, remain to be defined.
Topics: Animals; Epidermis; Humans; Hydroxyeicosatetraenoic Acids; Ichthyosis; Intramolecular Oxidoreductases; Lipoxygenase; Signal Transduction
PubMed: 17608720
DOI: 10.1111/j.1742-4658.2007.05909.x -
Biochimica Et Biophysica Acta Mar 2014Fatty acids in the epidermis can be incorporated into complex lipids or exist in a free form, and they are crucial to proper functions of the epidermis and its... (Review)
Review
Fatty acids in the epidermis can be incorporated into complex lipids or exist in a free form, and they are crucial to proper functions of the epidermis and its appendages, such as sebaceous glands. Epidermal fatty acids can be synthesized de novo by keratinocytes or taken up from extracutaneous sources in a process that likely involves protein transporters. Several proteins that are expressed in the epidermis have been proposed to facilitate the uptake of long-chain fatty acids (LCFA) in mammalian cells, including fatty acid translocase/CD36, fatty acid binding protein, and fatty acid transport protein (FATP)/very long-chain acyl-CoA synthetase. In this review, we will discuss the mechanisms by which these candidate transporters facilitate the uptake of fatty acids. We will then discuss the clinical implications of defects in these transporters and relevant animal models, including the FATP4 animal models and ichthyosis prematurity syndrome, a congenital ichthyosis caused by FATP4 deficiency. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
Topics: Animals; Aniridia; Biological Transport, Active; Disease Models, Animal; Fatty Acid Transport Proteins; Fatty Acids; Female; Humans; Ichthyosis; Infant, Premature, Diseases; Kidney; Male; Psychomotor Disorders; Skin
PubMed: 24120574
DOI: 10.1016/j.bbalip.2013.09.016 -
Molecular Genetics & Genomic Medicine Dec 2023Very long-chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are...
BACKGROUND
Very long-chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt-like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single-nucleotide variants.
METHODS
We performed clinical exome sequencing on probands from four unrelated families with neuro-ichthyosis.
RESULTS
We identified three novel homozygous ELOVL4 variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in ELOVL4, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three.
CONCLUSION
Our study expands the allelic spectrum of ELOVL4-related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation.
Topics: Humans; Mutation; Macular Degeneration; Retina; Ichthyosis; Ichthyosis, Lamellar; Carbon; Eye Proteins; Membrane Proteins
PubMed: 37592902
DOI: 10.1002/mgg3.2256 -
Anais Brasileiros de Dermatologia 2015Epidermolytic hipercetarose is a rare genodermatosis, with a prevalence of 1:100.000 to 1:300.000, with autosomal dominant inheritance. We report the case of a 5 year...
Epidermolytic hipercetarose is a rare genodermatosis, with a prevalence of 1:100.000 to 1:300.000, with autosomal dominant inheritance. We report the case of a 5 year old girl who presented an hypertrophic verrucous plaques in the neck, under arm, buttocks, knees, pelvis, legs, dorsum of the right foot and elbows. Histological examination of the skin lesions showed typical changes of epidermolytic hyperkeratosis. Because it is an autosomal dominant disorder with complete penetrance, the individual carrying the mutation will necessarily develop the disease. However, in 50% of cases postzygotic mutation occur. The case report emphasizes early diagnosis and differential diagnoses with ichthyosis and other bullous diseases of childhood, as well as discussing the therapeutic possibilities.
Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Skin; Skin Diseases, Vesiculobullous
PubMed: 26734873
DOI: 10.1590/abd1806-4841.20153966 -
Seminars in Perinatology Feb 2013The ichthyoses encompass a variety of genetic disorders marked by abnormal epidermal differentiation. The neonatal period is critical for patients with ichthyosis... (Review)
Review
The ichthyoses encompass a variety of genetic disorders marked by abnormal epidermal differentiation. The neonatal period is critical for patients with ichthyosis because of the risk for significant associated morbidity and mortality, with the majority of complications arising as a result of impaired barrier function. This article reviews presentations of ichthyosis in the neonate, outlines risks and complications, and provides strategies for management.
Topics: Dehydration; Diagnosis, Differential; Directive Counseling; Ectropion; Female; Humans; Ichthyosis, Lamellar; Infant, Newborn; Male; Netherton Syndrome; Pain; Parents; Risk Factors; Sjogren-Larsson Syndrome; Staphylococcal Scalded Skin Syndrome; Stevens-Johnson Syndrome; Trichothiodystrophy Syndromes
PubMed: 23419760
DOI: 10.1053/j.semperi.2012.11.001 -
Indian Journal of Pathology &... 2022Harlequin ichthyosis (HI) is the most severe type of congenital ichthyosis. It is extremely rare with very few cases reported in India. It is inherited in an autosomal...
Harlequin ichthyosis (HI) is the most severe type of congenital ichthyosis. It is extremely rare with very few cases reported in India. It is inherited in an autosomal recessive fashion. The importance of antenatal diagnosis by ultrasonography, DNA-based molecular studies on chorionic villus sampling, and amniocentesis has been emphasized. We report a new case of HI in an infant, diagnosed postnatally by correlation of clinical and histopathological features on skin biopsy. The infant succumbed on the second day of birth despite intensive supportive care. A short review of the literature regarding the condition is also presented.
Topics: Biopsy; Female; Humans; Ichthyosis, Lamellar; Infant; Pregnancy; Prenatal Diagnosis; Skin
PubMed: 35435396
DOI: 10.4103/IJPM.IJPM_1150_20