Ichthyosis Vulgaris Research Articles

Ichthyosis vulgaris successfully treated with individualised homoeopathic medicine Dulcamara 200C – An evidence-based case report

Ichthyosis vulgaris successfully treated with individualised homoeopathic medicine Dulcamara 200C – An evidence-based case report

Memory, mood and associated neuroanatomy in individuals with steroid sulphatase deficiency (X-linked ichthyosis).

Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and steroid (sulphate) levels correlate with mood and age-related cognitive decline. In animals, STS inhibition or deletion of the associated gene, enhances memory/neuroprotection and alters hippocampal neurochemistry. Little is known about the consequences of constitutive STS deficiency on memory-related processes in humans. We investigated self-reported memory performance (Multifactorial Memory Questionnaire), word-picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X-linked ichthyosis (XLI; n = 41) and in adult female carriers of XLI-associated genetic variants (n = 79); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, n = 98) or recruited from the general population (n = 250)]. Using the UK Biobank, we compared mood/memory-related neuroanatomy in carriers of genetic deletions encompassing STS (n = 28) and non-carriers (n = 34,522). We found poorer word-picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI-associated variant carriers and individuals with IV reported more adverse mood symptoms, reduced memory contentment and greater use of memory aids, compared with general population controls. Mood and memory findings appeared largely independent. Neuroanatomical analysis only indicated a nominally-significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non-carriers. In humans, constitutive STS deficiency appears associated with mood-independent impairments in memory but not with large effects on underlying brain structure; the mediating psychobiological mechanisms might be explored further in individuals with XLI and in new mammalian models lacking STS developmentally.

Clinical Spectrum of Congenital Ichthyosis in Pediatric Age Group from a Tertiary Care Center in India

Objective: Ichthyosis is a disorder of cornification, which can be acquired or inherited, and encompasses various forms of generalized scaling and superficial roughness of the skin secondary to impaired skin barrier. It can be often associated with systemic manifestations. There is a paucity of Indian studies assessing the clinical and demographic profile of children with inherited ichthyosis. Hence, we conducted this study with the primary objective of assessing the clinical and epidemiological profile of children with congenital ichthyosis (CI). Materials and Methods: The study was conducted over 1 year. All children aged up to 18 years of age, with the clinical diagnosis of CI, were evaluated for epidemiological profile and clinical features. Results: A total of 32 children with CI presented with a mean age of 6 ± 4.81 years. The most common phenotype was ichthyosis vulgaris, seen in 13 (40.6%) children, while X-linked recessive ichthyosis was present in 6 (18.75%) children. Epidermolytic ichthyosis (EI) was also seen in 6 (18.75%) children, out of which 5 were diagnosed with generalized EI and 1 was diagnosed with superficial EI. Lamellar ichthyosis was seen in 4 (12.5%) children. Sjogren–Larsson syndrome (SLS), harlequin ichthyosis, and Netherton syndrome were present in 1 (3.1%) case each. Various extracutaneous abnormalities detected were ectropion (9.3%), lagophthalmos (3.1%), and refractive error with stye (3.1%) on ophthalmological evaluation, gross development delay (8.75%), and neurological involvement in the form of spastic quadriplegia (one patient with SLS). Conclusions: CI comprises various skin diseases and can range from mild to very severe presentation with systemic involvement. Identification of the phenotypic expression of ichthyosis is a prerequisite for making prognostic predictions, therapeutic decisions, and offering genetic counseling.

Clinico-Epidemiologic Profile of Non-Syndromic Congenital Ichthyosis - A Retrospective Chart Review of 107 Patients.

Congenital ichthyoses are a rare Mendelian group of disorders affecting the integument with a heterogeneous clinical presentation amongst which scaling is a constant feature. There is scanty epidemiologic data regarding the clinical profile and histologic patterns of inherited ichthyosis from resource-poor countries. The study was aimed at assessing the clinic-epidemiologic characteristics associated with the different forms of non-syndromic congenital ichthyosis. This was a retrospective chart review of ichthyosis patients that presented between July 2016 and Jun 2020. Details including demographic profile, clinical characteristics along with any relevant investigations done were included. During the study period of 4 years, 107 patients with congenital non-syndromic ichthyosis were seen. The most frequent diagnosis was of common ichthyoses, followed by autosomal recessive congenital ichthyosis, epidermolytic ichthyosis and erythrokeratoderma, in decreasing order. Important clinical findings like erythema and the type of scales as well as histological differences including an absent or reduced granular layer in ichthyosis vulgaris can help differentiate among the clinical phenotypes of inherited non-syndromic ichthyosis especially in resource-poor settings. Also, there is a high prevalence of vitamin D deficiency and hence a need for screening for the same in all patients of congenital ichthyosis including the milder phenotypes.

Nanopore Sequencing Enables Allelic Phasing of FLG Loss-of-Function Variants, Intragenic Copy Number Variation, and Methylation Status in Atopic Dermatitis and Ichthyosis Vulgaris

Nanopore Sequencing Enables Allelic Phasing of FLG Loss-of-Function Variants, Intragenic Copy Number Variation, and Methylation Status in Atopic Dermatitis and Ichthyosis Vulgaris

Surgical Site Infection After Cesarean Section in a Patient with Ichthyosis Vulgaris

Surgical Site Infection After Cesarean Section in a Patient with Ichthyosis Vulgaris

Filaggrin gene variants among Saudi patients with ichthyosis vulgaris

Ichthyoses are a heterogeneous group of cornification disorders. The most common form of ichthyoses is ichthyosis vulgaris (IV) ([OMIM] #146,700), which can be inherited as autosomal semi-dominant mutation in the filaggrin gene (FLG). We present the findings of a study involving 35 Saudi patients with a clinical diagnosis of ichthyosis vulgaris. For identifying the pathogenic mutation of their disease, we used Sanger sequencing analysis of the extracted DNA samples. We also identified the underlying 22 FLG variants, which have been seen before. However, the detected mutations do not involve the common p.R501* c. 2282del4 mutations reported in European populations. Indeed, we did not identify any statistical influence of the homozygous or heterozygous genotypes on the phenotype severity of the disease.

A Case Report on Ichthyosis Vulgaris; Ayurvedic View and Management

Ichthyosis are a heterogeneous group of Hereditary and acquired disorders of keratinization characterized by the presence of visible scales on skin surface. The word is derived from Greek root for fish – icthys. There are two major types of ichthyosis that is Congenital and Acquired. Ichthyosis vulgaris one among congenital ichthyosis is the most common with an estimated incidence rate of 1 in 250 births, with an onset in early childhood characterized by fine, whitish scales which often sheds off. The severity of symptoms can vary enormously from mildest, most common types such as Ichthyosis vulgaris, up to life threatening condition such as Harlequin Ichthyosis. In general all types of Ichthyosis has been identified as rare disease by National Organization for Rare Disorders (NORD). There is currently no cure for ichthyosis only symptomatic management is done. Topical application is the major treatment according to modern medicine, which should be used daily In Ayurveda skin diseases have been described under the heading Kushta; which is again classified into Mahakushta and Kshudrakushta. Ekakushta, one among Kshudrakushta having Dosa predominance of Vata Kapha shares features more or less similar to ichthyosis vulgaris. Ayurvedic management aims at clearing the Srotas and providing internal and external Snehana has produced a markable change in a case of congenital ichthyosis.

BG11 Palmoplantar keratoderma with mutations in filaggrin and desmoglein-1 genes

Abstract Hereditary palmoplantar keratoderma (PPK) has many forms, and genetic testing can help distinguish diagnoses. This case demonstrates a presentation of PPK with an altered phenotype caused by a mutation in FLG. The patient was a 23-year-old woman referred with PPK since the age of 6 years. She reported dry skin on the back of her hands from infancy and no other dermatological conditions. She denied plantar pain except when there were fissures in the callus. There was no relevant past medical history, but a significant family history of individuals with PPK and curly hair, and sudden infant death (SID) in two siblings. Physical examination revealed focal plantar keratoderma bilaterally, curly hair, mild tongue leukokeratosis and generally dry skin on both legs. She had palmar hyperlinearity, small calluses on the palms and normal nails. She declined a skin biopsy. The patient was referred to cardiology to rule out cardiomyopathy associated with a desmoplakin variant. She had an unremarkable transthoracic echocardiography and cardiac magnetic resonance imaging. Twelve-lead electrocardiography showed sinus rhythm with biphasic T-wave in V2 and inverted V1. Clinically arrhythmogenic right ventricular cardiomyopathy (ARVC) was ruled out; however, given her significant family history of SID and PPK, panel testing for genes associated with ARVC was performed, which revealed a heterozygous variant of uncertain significance in MYBPC3 (p.Val639lle). This variant did not explain the patient’s PPK; therefore, a PPK panel was performed. Next-generation sequencing identified a heterozygous DSG1 [c430A>T p.(Arg.144*)] pathogenic variant and a heterozygous FLG [c2282_2285del p.(Ser761Cysfs*36)] pathogenic variant. The patient’s PPK was more severe on the plantar surface of the feet than one might expect with a DSG1 variant. This case demonstrates the interaction between two genetic variants known to be associated with skin conditions. Ichthyosis vulgaris is caused by FLG variants. Patients with heterozygous FLG variants are less severely affected and have reduced penetrance compared to homozygotes. Meanwhile, heterozygous pathogenic variants in DSG1 are associated with keratosis palmoplantaris striata I (MIM148700). We hypothesize that the coexistence of FLG and DSG1 variants may contribute to a more extensive keratoderma phenotype than usually seen with DSG1 variants. This case contributes to our understanding of PPK, demonstrates the value of genetic testing in dermatological conditions and describes a unique phenotype in the presence of multiple genetic variants. Further research is required to better understand the interaction between variants in PPK pathogenesis.

Impaired Dermatoscopic Visualization in a Patient With Ichthyosis Vulgaris Undergoing Complete Skin Examination

ABSTRACT Ichthyosis vulgaris is an inherited disease caused by loss of function mutations in the filaggrin encoding gene. This mutation results in decreased skin hydration, elevated skin surface pH, and increased transepidermal water loss. This leads to the characteristic xerosis and scaling seen with the disease. Patients with ichthyosis vulgaris may be at a greater risk for skin cancer, which emphasizes the importance of complete skin examinations in this patient population. Prior literature has not addressed potential challenges that arise when performing complete skin examinations in patients with ichthyosis vulgaris—primarily, that dermatoscopic visualization can be obscured by hyperkeratosis. This case highlights the importance of keratolytic use before skin examinations in patients with ichthyosis vulgaris.

888 FLG allelic and mutation phasing with nanopore sequencing to study phenotypic variability in ichthyosis vulgaris

888 FLG allelic and mutation phasing with nanopore sequencing to study phenotypic variability in ichthyosis vulgaris

Keratosis Pilaris Is a Keratinization of Hair Follicles

Keratosis pilaris is a common dermatological condition and is sometimes considered as a normal variant of the skin. It is also referred to as follicular keratosis. It is multifactorial and innocuous, affecting the extensor surfaces of the proximal extremities. Keratosis pilaris first appears in early childhood and progresses to become extensive during the second decade of life. Keratosis pilaris is also associated with many other conditions, including atopic dermatitis, ichthyosis vulgaris, obesity, diabetes mellitus, and malnutrition, as well as in conjunction with syndromes like Down syndrome and Noonan syndrome. Although the disease may improve over time, there are still some treatments available, including emollients, exfoliants, anti-inflammatory medication, phototherapy, and laser therapy.

Investigations into the FLG Null Phenotype: Showcasing the Methodology for CRISPR/Cas9 Editing of Human Keratinocytes

Ever since the association between filaggrin (FLG) loss-of-function mutations and ichthyosis vulgaris and atopic dermatitis disease onset was identified, filaggrins function has been under investigation. Intra-individual genomic predisposition, immunological confounders, and environmental interactions complicate the comparison between FLG genotypes and related causal effects. Using CRISPR/Cas9, we generated human FLG knockout (ΔFLG) N/TERT-2G keratinocytes. Filaggrin deficiency was demonstrated by immunohistochemistry of human epidermal equivalent (HEE) cultures. Next to (partial) loss of structural proteins (IVL, HRNR, KRT2, and TGM1), the stratum corneum was more dense and lacked the typical basket weave appearance. In addition, electrical impedance spectroscopy and transepidermal water loss analyses highlighted a compromised epidermal barrier in ΔFLG-HEEs. Correction of FLG reinstated the presence of keratohyalin granules in the stratum granulosum, filaggrin protein expression, and expression of aforementioned proteins. The beneficial effects on stratum corneum formation were reflected by normalization of EIS and TEWL. This study demonstrates the causal phenotypical and functional consequences of filaggrin deficiency, indicating filaggrin is not only central in epidermal barrier function but also vital for epidermal differentiation by orchestrating the expression of other important epidermal proteins. These observations pave the way to fundamental investigations into the exact role of filaggrin in skin biology and disease.

Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin.

Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X-linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis. To identify sequence variants involved in different forms of hereditary ichthyoses. We studied eight families with different types of ichthyosis including four families with autosomal recessive congenital ichthyosis and four families with common ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease. In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X-linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted. Gene expression studies have not been performed that would have strengthened the findings of computational analysis. This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.

Variants in the Gene Encoding Filaggrin Cause Autosomal-Dominant Symmetrical Acral Keratoderma

Variants in the Gene Encoding Filaggrin Cause Autosomal-Dominant Symmetrical Acral Keratoderma

Genotype Study of Filaggrin Gene Loss-of-Function Mutations in Central India Population with Atopic Dermatitis and Ichthyosis Vulgaris.

A genotype study of filaggrin gene loss-of-function mutations in central India can provide valuable insights into the prevalence and association of these mutations with atopic dermatitis (AD) and ichthyosis vulgaris (IV) in the region. The FLG R501X and 2282del4 are both genetic variants in the human gene called filaggrin gene (FLG), which encodes a protein that plays an important role in the formation and maintenance of the skin barrier. In this study, we determined the FLG R501X and 2282del4 variants association with both AD and IV in Central Indian populations. This case-control study was conducted in the Departments of Dermatology and Molecular and Virology Research and Diagnostic Laboratory at Sri Aurobindo Medical College and Post Graduate Institute, Indore (Madhya Pradesh). The study was approved by the Clinical Research and Ethics Committee. A total of 180 patients aged between 3 months - 60 years who attended the skin outpatient department between March-2021 to June-2022 were recruited in this study. Among them, 60 patients were in AD-group, 60 patients in IV-group, and 60 patients were in the healthy control group. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) was used in genotyping for FLG mutations (R501X and 2282del4). The most common FLG mutations were R501X (31.6% and 23.3%) and 2282del4 (18.3% and 13.3%) in AD and IV patients with heterozygous (AT) genotype, respectively. The combined mutation (FLG R501X and 2282del4) association was 10% and 5% in the AD and IV groups with heterozygous (AT) genotype, respectively, and in all the patients of control group with wild genotype (AA). There were no significant (P = 0.09) associations found with 2282del14 genotype. The R501X mutation in the gene encoding filaggrin is one of the robust genetic associations of AD and IV. The 2282del4 polymorphism was marginally less as compared to R501X.

Introduction of modern genetic and instrumental examination methods in patients with ichthyosis vulgaris and atopic dermatitis

Introduction of modern genetic and instrumental examination methods in patients with ichthyosis vulgaris and atopic dermatitis

A Cross-Sectional Study Comparing Application of Hanifin and Rajka Criteria in Indian Pediatric Atopic Dermatitis Patients to that of Other Countries.

Hanifin and Rajka criteria are considered to be the gold standard for atopic dermatitis diagnosis. However, the exhaustive nature limits its use in clinical settings. To determine the frequency of Hanifin and Rajka criteria commonly found in Indian pediatric atopic dermatitis patients and variation from the findings of other studies. An observational, descriptive study with a sample size of 52 pediatric atopic dermatitis patients. Patients were divided into infantile, childhood, and adolescent. Overall, xerosis, early age of onset, Dennie-Morgan fold, aggravation because of environmental factors, palmar hyper-linearity, ichthyosis vulgaris, keratosis pilaris, pityriasis alba, and orbital darkening were found in more than 50% of patients. Dennie-Morgan fold was more commonly found in Indian pediatric atopic dermatitis patients. Peri-follicular accentuation was less prevalent in Indian patients as compared to other Asian studies. None of the parents reported food intolerance, which was seen in studies from other countries. A small sample size and ophthalmological evaluation was not performed in all patients. The frequency of different Hanifin and Rajka minor criteria varies widely among different study populations. Hence, the criteria specifically applicable to the Indian population need to be derived for ease of diagnosis.

Genetic variations of filaggrin encoding gene \(\textit{(FLG)}\) in the Vietnamese population revealed from whole-exome sequencing

Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and maintains skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified to cause ichthyosis vulgaris, increase the risk of atopic dermatitis and other skin diseases. In this study, we established the database of FLG gene obtained by whole-exome sequencing (WES) of 244 Vietnamese. We also estimated allele and genotype frequencies of the FLG gene in this Vietnamese population and predicted the impact of novel variants on protein function using in silico analysis tools. The detected variants included 126 nonsynonymous, six nonsense mutations, six frameshift insertions/deletions, and one non-frameshift deletion, mostly located in exon 3. Of which, there were 11 novel variants have been identified and four of them were predicted as detrimental for encoding protein. Remarkable pathogenic variants were mostly nonsense variants, showing the main genetic factor underlying the pathology of diseases caused by FLG. The results obtained in this study would provide essential information about the genetic characteristics of FLG in the Vietnamese population and the risk of occurrence of diseases related to this gene, which facilitates the development of new specific and accurate diagnosis, treatment, and prevention options for FLG-related diseases, particularly in Vietnamese.

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature.

A 3-year-old boy, firstborn to nonconsanguineous parents, presented with motor development delay and floppiness of bilateral lower limbs since birth. No significant family history presented at time of check-up. He could stand with support, eat with a spoon without spillage, and speak in two-word sentences. There was no history suggestive of cranial nerve impairment. Examination revealed normal head circumference, dry, scaly skin lesions on the trunk, distal weakness with sluggish deep tendon reflexes in bilateral lower limbs, and a high stepping gait. Nerve conduction studies revealed demyelinating polyneuropathy. Brain stem-evoked response audiometry testing revealed auditory neuropathy. Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with a novel variant of 2218C > T in the FLG gene. We have reviewed the available literature for reported associations of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris. This is probably the first reported association of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with bilateral hearing loss.