Ichthyosis: A Road Model for Skin Research

Abstract

Ichthyosis refers to skin diseases with scaling somewhat reminiscent of fish scales (Greek: ichthus=fish). There are more than 50 genetic types of, mostly non-syndromic, ichthyosis, ranging in severity and frequency from mild and common (prevalence < 1%) to severe and rare (< 0.001%). In the latter case, babies are often born with a thick horny layer (collodion), dermal inflammation and impaired skin barrier function, requiring intensive medical care. Nearly all patients with ichthyosis require daily applications of cream, sometimes complemented with retinoid tablets. This review highlights recent progress in the understanding of the causes and consequences of ichthyosis, which may lead to better care and treatments. The understanding of monogenetic disorders of cornification, including the group of diseases called ichthyoses, has expanded greatly in recent years. Studies of the aetiology of more than 50 types of ichthyosis have almost invariably uncovered errors in the biosynthesis of epidermal lipids or structural proteins essential for normal skin barrier function. The barrier abnormality per se may elicit epidermal inflammation, hyperproliferation and hyperkeratosis, potentially contributing to the patient's skin symptoms. Despite this and other new knowledge about pathomechanisms, treatment of ichthyosis often remains unsatisfactory. This review highlights a series of approaches used to elucidate the pathobiology and clinical consequences of different types of ichthyosis, and related diseases with the ultimate goal of finding new and better treatments.

Knockdown of SDR9C7 Impairs Epidermal Barrier Function

“…The final step of subsequent covalent binding to CE is catalyzed either by TGase-1 or the alternative pathway via SDR9C7 that produces 13ketone from the oxidated linoleate molecule. Therefore, there is the absence of CLEs on electron microscopic examination of ARCI patients with SDR9C7 deficiency (Vahlquist and Torma, 2020;Takeichi et al, 2020). Also, epidermal barrier dysfunction was recently demonstrated in a mouse Sdr9c7 -/knockout model due to a severe reduction of the covalently bound ceramides and failure to form the CLE (Takeichi et al, 2017).…”

Mammalian Epidermis: A Compendium of Lipid Functionality

“…The relative abundance of different lipid species changes across the various layers of the epidermis, underscoring how the correct establishment of a functional barrier requires tightly controlled regulation of lipid production ( Lampe et al, 1983 ). Indeed, dysregulation of the lipid balance can cause a number of pathological conditions, notably ichthyoses ( Akiyama, 2017 ; Vahlquist and Törmä, 2020 ).…”

Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: genotype–phenotype correlation

“…A major characteristic of ARCI is partially overlapping phenotypes and genotypes between LI and CIE [ 20 ] (Table 1 ). Therefore, it would be difficult to determine the specific genetic background for each form.…”