-
American Journal of Clinical Dermatology Feb 2018Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. Syndromic as well as... (Review)
Review
Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. Syndromic as well as nonsyndromic forms of ichthyosis exist. Irrespective of etiology, virtually all types of ichthyosis exhibit a defective epidermal barrier that constitutes the driving force for hyperkeratosis, skin scaling, and inflammation. In nonsyndromic forms, these features are most evident in severe autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis, but to some extent also occur in the common type of non-congenital ichthyosis. A correct diagnosis of ichthyosis-essential not only for genetic counseling but also for adequate patient information about prognosis and therapeutic options-is becoming increasingly feasible thanks to recent progress in genetic knowledge and DNA sequencing methods. This paper reviews the most important aspects of nonsyndromic ichthyoses, focusing on new knowledge about the pathophysiology of the disorders, which will hopefully lead to novel ideas about therapy.
Topics: Administration, Cutaneous; Administration, Oral; Dermatologic Agents; Genetic Counseling; Genetic Testing; Genetic Therapy; Humans; Ichthyosis; Keratins; Microscopy; Mutation; Permeability; Retinoids; Skin; Skin Transplantation
PubMed: 28815464
DOI: 10.1007/s40257-017-0313-x -
International Journal of... 2023Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40... (Review)
Review
Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.
Topics: Female; Humans; Omalizumab; Netherton Syndrome; Tumor Necrosis Factor Inhibitors; Treatment Outcome; Severity of Illness Index; Double-Blind Method
PubMed: 37200480
DOI: 10.1177/03946320231172881 -
JCI Insight Feb 2024Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. Patients with AD are at heightened risk for Staphylococcus...
Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. Patients with AD are at heightened risk for Staphylococcus aureus infection. Group 2 innate lymphoid cells (ILC2s) are mainly activated by epithelial cell-derived cytokines IL-33 and involved in the pathogenesis of AD. However, little is known about the effect of skin delipidization on the epithelial cell-derived cytokines and dermal ILC2s in AD. In our study, we investigated the mechanism by which S. aureus infection modulates and exacerbates the pathogenesis of dry skin, leading to type 2 inflammation in the context of innate immunity. In vivo, we found that S. aureus infection aggravated delipidization-induced dermal IL-33 release and dermal ILC2 accumulation, which exacerbated skin inflammation. We also noticed that Il33fl/fl K14cre mice and Tlr2-/- mice exhibited attenuated skin inflammation. In vitro, treatment with necroptosis inhibitors reduced IL-33 release from S. aureus-infected keratinocytes. Mechanistically, we observed an increase in the necroptosis-associated kinases, MLKL and RIPK3, in S. aureus-infected mice, indicating that IL-33 release was associated with necroptotic cell death responses. Our results reveal that S. aureus infection-elicited keratinocyte necroptosis contributes to IL-33-mediated type 2 inflammation, which exacerbates the pathogenesis of dry skin.
Topics: Humans; Mice; Animals; Immunity, Innate; Staphylococcus aureus; Interleukin-33; Necroptosis; Lymphocytes; Dermatitis, Atopic; Inflammation; Cytokines; Staphylococcal Infections; Ichthyosis; Receptor-Interacting Protein Serine-Threonine Kinases; Protein Kinases
PubMed: 38319737
DOI: 10.1172/jci.insight.166821 -
Revista Chilena de Pediatria 2016Hereditary ichthyoses are a group of genetic disorders of cornification, which are characterised by hyperkeratosis and scaling. The new classification identifies 36... (Review)
Review
Hereditary ichthyoses are a group of genetic disorders of cornification, which are characterised by hyperkeratosis and scaling. The new classification identifies 36 types of ichthyosis, which are subdivided according to their frequency, pattern of inheritance and extracutaneous involvement. The diagnosis is mainly based on clinical features, since genetic studies are not available in our setting. Treatment is symptomatic and management should be performed by a multidisciplinary team. In this article, the diagnostic and therapeutic aspects of different types of ichthyosis are reviewed, taking into account the nomenclature and modifications presented in the new classification.
Topics: Humans; Ichthyosis; Patient Care Team; Terminology as Topic
PubMed: 26471314
DOI: 10.1016/j.rchipe.2015.07.025 -
Clinical and Experimental Dermatology Dec 2022For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids...
For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids (acitretin, isotretinoin and alitretinoin) has been shown to be effective in reducing disease severity; however, potentially rare adverse effects (AEs) may occur, including hyperostotic skeletal changes. The true prevalence of this AE in adult patients administered life-long therapy is unknown. We identified 3 of 127 (2.4%) patients (with ichthyosis or Darier disease) who had been prescribed isotretinoin with or without acitretin, and who developed radiological signs and clinical symptoms of hyperostosis and ligamentous ossification. This clinical review highlights the significance of retinoid-induced skeletal hyperostosis in patients prescribed long-term, high-dose retinoid therapy for disorders of keratinization. Patients commencing systemic retinoid therapy, particularly women of childbearing age, should be counselled about this important and potentially serious AE, especially if long-term treatment is indicated.
Topics: Adult; Humans; Female; Acitretin; Isotretinoin; Alitretinoin; Hyperostosis; Ichthyosis
PubMed: 35988035
DOI: 10.1111/ced.15382 -
The Indian Journal of Medical Research Aug 2016
Topics: Humans; Hyperkeratosis, Epidermolytic; Male; Middle Aged
PubMed: 27934814
DOI: 10.4103/0971-5916.195059 -
The Journal of Clinical Investigation Sep 2020The biology of harlequin ichthyosis (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly understood, and to date, no...
The biology of harlequin ichthyosis (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly understood, and to date, no satisfactory treatment has been developed. We sought to investigate pathomechanisms of HI that could lead to the identification of new treatments for improving patients' quality of life. In this study, RNA-Seq and functional assays were performed to define the effects of loss of ABCA12 using HI patient skin samples and an engineered CRISPR/Cas9 ABCA12 KO cell line. The HI living skin equivalent (3D model) recapitulated the HI skin phenotype. The cytokines IL-36α and IL-36γ were upregulated in HI skin, whereas the innate immune inhibitor IL-37 was strongly downregulated. We also identified STAT1 and its downstream target inducible nitric oxide synthase (NOS2) as being upregulated in the in vitro HI 3D model and HI patient skin samples. Inhibition of NOS2 using the inhibitor 1400W or the JAK inhibitor tofacitinib dramatically improved the in vitro HI phenotype by restoring the lipid barrier in the HI 3D model. Our study has identified dysregulated pathways in HI skin that are feasible therapeutic targets.
Topics: ATP-Binding Cassette Transporters; Amidines; Benzylamines; Cell Culture Techniques; Cells, Cultured; Drug Delivery Systems; Gene Knockdown Techniques; Humans; Ichthyosis, Lamellar; Inflammation; Interleukin-1; Loss of Function Mutation; Models, Biological; Nitric Oxide Synthase Type II; Piperidines; Pyrimidines; STAT1 Transcription Factor
PubMed: 32544098
DOI: 10.1172/JCI132987 -
Indian Journal of Dermatology,... 2016
Topics: Bone Density; Humans; Ichthyosis, Lamellar; Infant; Vitamin D; Vitamin D Deficiency
PubMed: 27088925
DOI: 10.4103/0378-6323.179750 -
Clinical Journal of the American... Jul 2021Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney...
BACKGROUND AND OBJECTIVES
Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney transplantation due to restoration of kidney function.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We leveraged a two-center prospective study of 1298 kidney transplant candidates and 521 recipients (May 2014 to March 2020). Symptom scores (0-100) at evaluation and admission for transplantation were calculated using the Kidney Disease Quality of Life Short-Form Survey, where lower scores represent greater burden, and burden was categorized as very high: 0.0-71.0; high: 71.1-81.0; medium: 81.1-91.0; and low: 91.1-100.0. We estimated adjusted waitlist mortality risk (competing risks regression), change in symptoms between evaluation and transplantation (=190), and post-transplantation symptom score trajectories (mixed effects models).
RESULTS
At evaluation, candidates reported being moderately to extremely bothered by fatigue (32%), xeroderma (27%), muscle soreness (26%), and pruritus (25%); 16% reported high and 21% reported very high symptom burden. Candidates with very high symptom burden were at greater waitlist mortality risk (adjusted subdistribution hazard ratio, 1.67; 95% confidence interval, 1.06 to 2.62). By transplantation, 34% experienced an increased symptom burden, whereas 42% remained unchanged. The estimated overall symptom score was 82.3 points at transplantation and 90.6 points at 3 months (10% improvement); the score increased 2.75 points per month (95% confidence interval, 2.38 to 3.13) from 0 to 3 months, and plateaued (-0.06 points per month; 95% confidence interval, -0.30 to 0.18) from 3 to 12 months post-transplantation. There were early (first 3 months) improvements in nine of 11 symptoms; pruritus (23% improvement) and fatigue (21% improvement) had the greatest improvements.
CONCLUSIONS
Among candidates, very high symptom burden was associated with waitlist mortality, but for those surviving and undergoing kidney transplantation, symptoms improved.
Topics: Adult; Aged; Fatigue; Female; Humans; Ichthyosis; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Myalgia; Postoperative Period; Preoperative Period; Prospective Studies; Pruritus; Quality of Life; Risk Assessment; Symptom Assessment; Waiting Lists
PubMed: 34597266
DOI: 10.2215/CJN.19031220 -
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