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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 -
Archives of Dermatological Research Mar 2023Treatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis,... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Treatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis, across the spectrum of ichthyosis, suggesting that targeting this pathway might broadly reduce disease severity.
OBJECTIVE
To determine whether secukinumab, an IL-17A inhibitor, can improve ichthyosis across several congenital ichthyosis subtypes.
DESIGN
Exploratory 16-week double-blind, randomized, placebo-controlled trial comparing secukinumab 300 mg every 4wks to placebo (1:1 randomization) in adults with the four major congenital ichthyosis subtypes (NCT03041038), followed by a 16-week open-label phase to evaluate response of the placebo-first group and a 20-week extension for safety. Significant differences in secukinumab- vs. placebo-treated subjects at Wk16 in the Ichthyosis Area Severity Index (IASI) score and lack of increased mucocutaneous bacterial and/or fungal infections were the co-primary efficacy and safety endpoints, respectively.
SETTING
Two tertiary referral centers: Northwestern University Feinberg School of Medicine, Chicago, and Mount Sinai Icahn School of Medicine, New York.
PARTICIPANTS
Twenty subjects ≥ 18 yo with genotype-confirmed epidermolytic ichthyosis, Netherton syndrome, lamellar ichthyosis, or congenital ichthyosiform erythroderma with at least moderate erythroderma.
RESULTS
IL-17A inhibition did not significantly reduce severity or increase mucocutaneous infections among the 18 who completed the 16-week double-blind phase. Five patients with 29-50% clinical improvement at Wk32 requested drug continuation. Th17-related biomarkers were not significantly reduced vs. baseline or placebo-treated levels.
LIMITATIONS
Small sample size; heterogeneous ichthyosis subsets.
CONCLUSION
IL-17 inhibition with secukinumab is safe, but not efficacious across the spectrum of adult ichthyoses.
GOV REGISTRATION NUMBER
NCT03041038; first posted on 02/02/2017.
Topics: Adult; Humans; Ichthyosis, Lamellar; Antibodies, Monoclonal; Interleukin-17; Ichthyosis; Psoriasis; Ichthyosiform Erythroderma, Congenital; Severity of Illness Index; Double-Blind Method; Treatment Outcome
PubMed: 35218370
DOI: 10.1007/s00403-022-02325-3 -
Developmental Medicine and Child... Feb 2007Sjögren-Larsson syndrome is a recessively inherited syndrome caused by deficiency of fatty aldehyde dehydrogenase. The most common symptoms and signs are described,... (Review)
Review
Sjögren-Larsson syndrome is a recessively inherited syndrome caused by deficiency of fatty aldehyde dehydrogenase. The most common symptoms and signs are described, especially ichthyosis, spastic diplegia, and severe learning difficulties; but also other less frequent ones. Special investigations include sensory evoked potentials, electromyography, and proton magnetic resonance spectroscopy. Post-mortem examination shows, in particular, an accumulation of lipid substances in specific regions of the brain. The diagnosis depends on the measurement of fatty aldehyde dehydrogenase in cultured fibroblasts from skin biopsies, and by identifying known mutations by allele-specific polymerase chain reaction assay. Prenatal diagnosis is possible by using the same technique. The disorder is located on gene 17, and many mutations have been identified. Most mutations are unique to an affected family, but clinical variations may be due to unknown genetic and environmental factors. The deficiency of the enzyme impairs the oxidation of medium and long chain fatty aldehydes, and this may explain the link between the brain and skin disorders. The treatment of affected children needs input from a number of specialists, and their contributions are discussed.
Topics: Humans; Sjogren-Larsson Syndrome
PubMed: 17254005
DOI: 10.1111/j.1469-8749.2007.00152.x -
The Pan African Medical Journal 2021
Topics: Collodion; Humans; Ichthyosis; Ichthyosis, Lamellar; Infant
PubMed: 34804344
DOI: 10.11604/pamj.2021.40.77.26789 -
The Turkish Journal of Gastroenterology... Jan 2019Chanarin Dorfman syndrome is a multisystem, very rare, autosomal recessive lipid storage disorder, characterized by the accumulation of lipid vacuoles in neutrophils,...
Chanarin Dorfman syndrome is a multisystem, very rare, autosomal recessive lipid storage disorder, characterized by the accumulation of lipid vacuoles in neutrophils, and was first described by Dorfman in 1974. Due to a mutation in the ABHD5 gene of the short arm of chromosome 3, lipid is stored in the granulocytes at various sites in the human body, such as the muscle, liver, eye, ear, central nervous system, and bone marrow. Clinically, the disease is presented with ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation. A 38-year-old male patient was referred to our Internal Medicine Clinic for consultation with laboratory findings as follows: high aspartate aminotransferase (AST; 203 U/L), alanine aminotransferase (ALT; 151 U/L), gamma-glutamyl transferase (GGT; 167 U/L), creatine kinase (CK; 1127 U/L) levels and low platelet levels (108000). After ultrasonography and gastroscopy, the patient was diagnosed with liver cirrhosis. Bilateral mixed-type hearing loss on audial tests and bilateral punctuate keratopathy, ectropion, and cataract in the left eye on ophthalmological tests were found. For the definitive diagnosis of Chanarin Dorfman syndrome, peripheral blood was examined, which revealed lipid accumulation in the neutrophils (Jordan's anomaly). We emphasize that if a patient has unusual findings, such as ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation, the possibility of Chanarin Dorfman syndrome should be considered.
Topics: Adult; Cataract; Diagnosis, Differential; Fibrosis; Hearing Loss; Hepatomegaly; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Intellectual Disability; Lipid Metabolism, Inborn Errors; Male; Muscular Diseases; Splenomegaly
PubMed: 30457558
DOI: 10.5152/tjg.2018.18014 -
Cold Spring Harbor Perspectives in... Apr 2014The epidermis functions as a physical barrier to the external environment and works to prevent loss of water from the skin. Numerous factors have been implicated in the... (Review)
Review
The epidermis functions as a physical barrier to the external environment and works to prevent loss of water from the skin. Numerous factors have been implicated in the formation of epidermal barriers, such as cornified envelopes, corneocytes, lipids, junctional proteins, proteases, protease inhibitors, antimicrobial peptides, and transcription factors. This review illustrates human diseases (ichthyoses) and animal models in which the epidermal barrier is disrupted or dysfunctional at steady state owing to ablation of one or more of the above factors. These diseases and animal models help us to understand the complicated mechanisms of epidermal barrier formation and give further insights on epidermal development.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Epidermis; Humans; Ichthyosis; Lipid Metabolism; Serine Proteases; Serine Proteinase Inhibitors; Skin Physiological Phenomena; Tight Junctions
PubMed: 24692192
DOI: 10.1101/cshperspect.a018218 -
Biomedical Papers of the Medical... Dec 2020Congenital ichthyoses are a very heterogeneous group of diseases manifested by dry, rough and scaling skin. In all forms of ichthyoses, the skin barrier is damaged to a... (Review)
Review
Congenital ichthyoses are a very heterogeneous group of diseases manifested by dry, rough and scaling skin. In all forms of ichthyoses, the skin barrier is damaged to a certain degree. Congenital ichthyoses are caused by various gene mutations. Clinical manifestations of the individual types vary as the patient ages. Currently, the diagnosis of congenital ichthyoses is based on molecular analysis, which also allows a complete genetic counseling and genetic prevention. It is appropriate to refer the patients to specialized medical centers, where the cooperation of a neonatologist, a pediatric dermatologist, a geneticist and other specialists is ensured.
Topics: Adolescent; Age Factors; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis, X-Linked; Infant; Infant, Newborn; Male; Molecular Biology; Mutation; Symptom Assessment
PubMed: 33087941
DOI: 10.5507/bp.2020.050 -
Ugeskrift For Laeger Apr 2020Ichthyosis – also called fish scale disease – is a group of skin diseases, which are characterised by xerosis and scaling. Most commonly, the diseases are...
Ichthyosis – also called fish scale disease – is a group of skin diseases, which are characterised by xerosis and scaling. Most commonly, the diseases are genetically inherited, but an acquired type also exists. Ichthyosis vulgaris (IV), is the most common type, affecting 1:250 individuals. Diagnosing IV can be challenging, because its clinical features are subject to great variation, ranging from mild cases with slight xerosis to severe cases with marked scaling and formation of fissures. In this review, IV and its most relevant differential diagnoses, X-linked ichthyosis, autosomal recessive congenital ichthyosis and acquired ichthyosis are reviewed.
Topics: Humans; Ichthyosis Vulgaris
PubMed: 32400366
DOI: No ID Found -
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 -
Indian Pediatrics Apr 2024
Topics: Humans; Ichthyosis, Lamellar; Phenotype
PubMed: 38419281
DOI: No ID Found