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Nature Reviews. Disease Primers Jan 2023The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation... (Review)
Review
The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype-genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.
Topics: Humans; Quality of Life; Ichthyosis; Eye; Genetic Association Studies
PubMed: 36658199
DOI: 10.1038/s41572-022-00412-3 -
Italian Journal of Dermatology and... Jun 2023Keratosis pilaris (KP) is a common, hyperkeratotic skin condition characterized by small, folliculocentric papules with variable perifollicular erythema. We provide an... (Review)
Review
Keratosis pilaris (KP) is a common, hyperkeratotic skin condition characterized by small, folliculocentric papules with variable perifollicular erythema. We provide an updated review on the pathogenesis, clinical manifestations, and management of this common, and often annoying, finding. KP represents a family of follicular disorders, of which KP simplex is by far the most common. Other variants and rare subtypes include keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Inherited mutations of the FLG gene and ABCA12 gene have been implicated etiologically. KP may be associated with ichthyosis vulgaris and palmar hyperlinearity, but less likely atopic dermatitis. Some potential differential diagnoses for KP include lichen spinulosus, phrynoderma, ichthyosis vulgaris, and trichostasis spinulosa. General cutaneous measures such as hydrating skin, avoiding long baths or showers, and using mild soaps or cleansers should be recommended. Topical keratolytic agents are first-line therapy, followed by topical retinoids and corticosteroids. Recent options include a variety of lasers and microdermabrasion if the patient is refractory to topical therapy.
Topics: Humans; Ichthyosis Vulgaris; Darier Disease; Skin; Abnormalities, Multiple
PubMed: 37166753
DOI: 10.23736/S2784-8671.23.07594-1 -
International Journal of Molecular... May 2022The discovery in 2006 that loss-of-function mutations in the filaggrin gene () cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the... (Review)
Review
The discovery in 2006 that loss-of-function mutations in the filaggrin gene () cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.
Topics: Dermatitis, Atopic; Filaggrin Proteins; Humans; Ichthyosis Vulgaris; Intermediate Filament Proteins; Water
PubMed: 35628125
DOI: 10.3390/ijms23105318 -
Orphanet Journal of Rare Diseases Jul 2022Ichthyosis covers a wide spectrum of diseases affecting the cornification of the skin. In recent years, new advances in understanding the pathophysiology of ichthyosis... (Review)
Review
Ichthyosis covers a wide spectrum of diseases affecting the cornification of the skin. In recent years, new advances in understanding the pathophysiology of ichthyosis have been made. This knowledge, combined with constant development of pathogenesis-based therapies, such as protein replacement therapy and gene therapy, are rather promising for patients with inherited skin diseases. Several ongoing trials are investigating the potency of these new approaches and various studies have already been published. Furthermore, a lot of case series report that biological therapeutics are effective treatment options, mainly for Netherton syndrome and autosomal recessive congenital ichthyosis. It is expected that some of these new therapies will prove their efficacy and will be incorporated in the treatment of ichthyosis.
Topics: Humans; Ichthyosis; Netherton Syndrome; Skin; Skin Neoplasms
PubMed: 35840979
DOI: 10.1186/s13023-022-02430-6 -
JAMA Dermatology Nov 2022
Topics: Humans; Netherton Syndrome; Dermatitis, Exfoliative; Dermoscopy
PubMed: 36169939
DOI: 10.1001/jamadermatol.2022.3796 -
Current Opinion in Pediatrics Aug 2023This review focuses on the presentation and management of ichthyoses and highlights recent advances in treatment that hold promise for better targeted therapy. (Review)
Review
PURPOSE OF REVIEW
This review focuses on the presentation and management of ichthyoses and highlights recent advances in treatment that hold promise for better targeted therapy.
RECENT FINDINGS
The ichthyoses are a group of rare genetic diseases with a wide phenotypic spectrum, characterized most often by generalized hyperkeratosis and scaling with variable erythema. The highly visible scaling and frequent itch contribute to decreased quality of life. Management for ichthyosis focuses on symptomatic relief and scale reduction with emollients, keratolytics, and retinoids. Recent advances in immune profiling and genotype-phenotype mapping have increased understanding of ichthyosis and shifted focus to pathogenesis-based targeted therapies with emerging biologics, small molecular inhibitors, and gene therapy.
SUMMARY
This article discusses clinical assessment and genotyping to make the diagnosis of specific forms of ichthyosis, provides guidance for management, and reviews new treatment options with systemic agents.
Topics: Humans; Quality of Life; Ichthyosis; Retinoids; Diagnosis, Differential; Genetic Therapy
PubMed: 37345742
DOI: 10.1097/MOP.0000000000001264 -
Nature Reviews. Disease Primers Jan 2023
Topics: Humans; Ichthyosis; Ichthyosis, Lamellar
PubMed: 36658163
DOI: 10.1038/s41572-023-00419-4 -
Dermatologie (Heidelberg, Germany) Apr 2023Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority... (Review)
Review
Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority of genodermatoses are autosomal or X‑linked inherited, but mosaic forms are also observed. Genodermatoses comprise various phenotypes ranging from limited cutaneous disease to severe cutaneous and extracutaneous involvement and may also be early warning signs of a multisystemic disorder. Despite recent advances in genetic technology and skin imaging modalities, dermoscopy can be useful for screening, diagnosis, and treatment follow-up. In ectopic mineralization and lysosomal storage disorders (pseudoxanthoma elasticum and Fabry disease, respectively), cutaneous manifestations may indicate involvement of other organs. In keratinization diseases (e.g., ichthyoses) and acantholytic skin fragility disorders (e.g., Darier and Hailey-Hailey disease), dermoscopy may help to assess treatment response by visualizing background erythema, hyperkeratosis, and interkeratinocyte space prominence. Dermoscopy is a noninvasive, easily accessible, useful, in vivo assessment tool that is well established in dermatology to recognize characteristic features of genodermatoses.
Topics: Humans; Dermoscopy; Skin; Ichthyosis; Keratosis; Pemphigus, Benign Familial
PubMed: 36882583
DOI: 10.1007/s00105-023-05124-7 -
Experimental Dermatology Oct 2019
Topics: Connective Tissue Diseases; Ectodermal Dysplasia; Epidermolysis Bullosa; Humans; Ichthyosis; Rare Diseases; Skin Diseases
PubMed: 31663654
DOI: 10.1111/exd.14035 -
JAMA Dermatology Feb 2023
Topics: Humans; Ichthyosis, Lamellar; Ectropion
PubMed: 36576743
DOI: 10.1001/jamadermatol.2022.5112