Collodion Membrane Research Articles

A founder DBR1 variant causes a lethal form of congenital ichthyosis.

DBR1 encodes the only known human lariatdebranching enzyme and its deficiency has been found to cause an autosomal recessive inborn error of immunity characterized by pediatric brainstem viral-induced encephalitis (MIM 619441). We describe a distinct allelic disorder caused by a founder recessive DBR1 variant in four families (DBR1(NM_016216.4):c.200A > G (p.Tyr67Cys)). Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. Patient-derived fibroblasts displayed the characteristic accumulation of intron lariats in their RNA as revealed by targeted and untargeted analysis, in addition to a marked reduction of DBR1 on immunoblot analysis. We propose a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility and highlight the apparent lack of correlation with the degree of DBR1 deficiency.

Familial Lamellar Ichthyosis in 6 Years Old and 2 Years Old Children: A Rare Case Report

Background: Lamellar ichthyosis (LI) is a rare non-syndromic congenital ichthyosis and is autosomal recessive. LI patients are generally born with abnormalities of keratinization, then develop into lamellar scales and persist into adulthood. This study aimed to describe cases of lamellar ichthyosis and provide appropriate management to prevent worsening patient prognosis.
 Case presentation: A 6-year-old girl and her younger brother, 2-year-old have been complaining of scaly skin all over their bodies since birth. Both patients were born with a history of being covered by a collodion membrane. On physical examination, thick and wide lamellar scales were seen with an erythematous base and palmoplantar hyperkeratosis. Ectropion of the eyelids, eclabium in the mouth area, and microtia in the ears were seen. The results of the dermoscopy examination showed brownish quadrilateral structures with white scales forming a lamellar pattern. Laboratory examination showed vitamin D insufficiency. Both patients were referred to the Pediatric Polyclinic regarding insufficiency and developmental complaints. Patients received therapy in the form of moisturizers, artificial eye drops, topical urea as a keratolytic, and oral vitamin D 2,000 IU per day. There was a clinical improvement after 3 months of treatment.
 Conclusion: Lamellar ichthyosis is an autosomal recessive congenital ichthyosis with clinical manifestations limited to the skin. In a minority of cases, LI can be inherited in an autosomal dominant manner. Thorough management is necessary to prevent a poor prognosis in patients.

Birth incidence and outcome of harlequin ichthyosis and collodion membrane in the UK and Ireland: a national 2-year prospective surveillance study.

Collodion membrane covers a heterogeneous group of ichthyoses with disparate outcomes. In this large, prospective birth-cohort study we show that babies with non-syndromic collodion membrane are born in good condition and in 40% the ichthyosis resolves within a year. Our data challenges existing guidelines and supports expectant management.

Successful Treatment of an Adult with Atopic Dermatitis and Lamellar Ichthyosis Using Dupilumab

Lamellar ichthyosis (LI) is a rare autosomal cornification disorder, with most cases due to a mutation in the transglutaminase-1 (TGM1) gene on chromosome 14. Patients with LI usually present with a collodion membrane and mild erythroderma at birth, with the collodion membranes shedding within the first weeks of life and being replaced by a generalized scale. Typically, LI is managed with oral retinoids, emollients, and keratolytic agents, eg, lactic acid. We report an LI case associated with atopic dermatitis and asthma that showed a marked improvement with dupilumab treatment. This finding is highly significant as it may represent a breakthrough in the treatment of LI, thus more research is needed to investigate the potential benefits of dupilumab for the treatment of ichthyosis, such as the effects observed in our patient.

Proposal for a 6-step approach for differential diagnosis of neonatal erythroderma.

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.

Erythroderma in a neonate

Erythroderma in a neonate

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal-recessive congenital ichthyosis.

Autosomal-recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self-improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non-SICI patients (nSICI, n = 60) by their ARCI phenotype. Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi-squared and t-Tests. The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo-/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo-/anhidrosis or vitamin D levels and monitored for changes in quality of life.

A case of autosomal recessive congenital ichthyosis with a novel mutation identified in the TGM1 gene by whole exome sequencing

Background: The &amp;quot;autosomal recessive congenital ichthyosis (ARCI)&amp;quot; refers to a group of rare, heterogeneous, and non-syndromic disorders of keratinization, represented as abnormal scales over the entire body and attributable to defective epidermal keratinocyte differentiation and lipid metabolism. ARCI is caused by mutations in a wide variety of genes, including ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4, TGM1, CERS3, PNPLA1, CASP14, SDR9C7, and SULT2B1. The most common cause of ARCI is a TGM1 gene mutation, which is strongly associated with a collodion membrane at birth. Case presentation: A 15-year-old male patient presented with extensive scaling over the entire body since birth. His history revealed that he was born ash-colored in a membrane, kept in an incubator for one month, and clinically diagnosed with ichthyosis at birth. The patient, who had undergone no previous genetic testing, was subjected to whole exome sequencing with the preliminary diagnosis of autosomal recessive/X-linked recessive congenital ichthyosis. The analysis identified a homozygous c.1020delG change in the TGM1 gene in the form of a frameshift mutation that is classified as pathogenic according to the American College of Medical Genetics criteria. Conclusion: Next-generation sequencing technologies employing whole-exome sequencing enable the sequencing of all protein-coding DNA regions in a single run.

The Genomic and Phenotypic Landscape of Ichthyosis

Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish. To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations. This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis. Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations. Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery. This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.

Report of a Novel ALOX12B Mutation in Self-Improving Collodion Ichthyosis with an Overview of the Genetic Background of the Collodion Baby Phenotype.

Collodion baby is a congenital, transient phenotype encountered in approximately 70–90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. Genetic mutations of components of the epidermal lipoxygenase pathway have been implicated in the majority of self-improving collodion ichthyosis (SICI). In SICI, the shedding of the collodion membrane reveals clear skin or only mild residual manifestation of ichthyosis. Here we report the case of a girl born with a severe form of collodion baby phenotype, whose skin almost completely cleared within the first month of life. At the age of 3 years, only mild symptoms of a keratinization disorder remained. However, the severity of erythema and scaling showed mild fluctuations over time. To objectively evaluate the skin changes of the patient, we assessed the ichthyosis severity index. Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation, c.1607G>A (p.Trp536Ter) with the recurrent, heterozygous mutation c.1562A>G (p.Tyr521Cys). Thereby, our findings expand the genotypic spectrum of SICI. In addition, we summarize the spectrum of further genetic diseases that can present at birth as collodion baby, in particular the SICI.

Visual Diagnosis: Unusual Skin Findings in a Premature Infant.

1. Sneha Butala, MD* 2. Lauren Pronman, DO*,† 3. Michelle Baechtold, MD‡ 4. Timmie R. Sharma, MD‡ 5. Rebecca Fish, MD§ 6. Qin Yao, MD§ 1. *Department of Pediatrics and 2. §Division of Neonatology and Perinatal Medicine, Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH 3. †Department of Genetics and Genomics and 4. ‡Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH A 24-year-old gravida 2 para 1 woman presents at 32 weeks’ gestation with vaginal bleeding concerning for placental abruption. The prenatal history is unclear because the mother obtained most of her prenatal care in Mexico. She precipitously gives birth to a female infant via breech vaginal delivery. On delivery, the infant is intubated and given 1 dose of surfactant due to respiratory failure. Apgar scores are 2 and 3 at 1 and 5 minutes, respectively. The birthweight is 1,900 g. A chest radiograph demonstrates diffuse severe alveolar opacity in bilateral lung fields consistent with severe respiratory distress syndrome. The infant is transported to a tertiary center and develops worsening hypoxia requiring 100% oxygen. The blood gas on admission reveals severe mixed respiratory and metabolic acidosis. The infant receives additional doses of surfactant and a prolonged period of respiratory support. The severity of the infant’s respiratory distress syndrome is disproportionate to the degree of prematurity. Pertinent physical examination findings include mottling of the skin with thick white scale. The scale is symmetrical, involving the scalp, shoulders, and extremities (Figs 1 and 2). External ear canals are not visible; they may be absent or occluded by the scale, which is also found around the nares. Thin erosions in rectangular shapes on her abdomen are noted where cardiac leads have been placed. Erosions are also found on the right side of the face near the endotracheal tube securement device and on the bilateral dorsum of feet. Auscultation of the lungs reveals coarse breath sounds and diffuse crackles bilaterally, without increased work of breathing, retractions, or nasal flaring. There is no collodion membrane, ectropion (outturning of the eyelids), or eclabium (outturning of the lips) present. Figure 1. Thick adherent scales and erosions on day 1. Figure 2. Thick adherent scales and erosions at 4 weeks. The complete blood …

Collodion babies: A 15-year retrospective multicenter study in The Netherlands—Evaluation of severity scores to predict the underlying disease

To the Editor: The clinical phenotype of a collodion baby can be caused by many ichthyosis subtypes of different severities. When genetic analysis is not possible or when diagnosis is unknown, clinical evaluation is essential to identify the more severe syndromic subtypes of ichthyosis in which other organ systems besides skin can be affected. Rubio-Gomez et al1 proposed a clinical scoring system based on collodion penotype based on 15 characteristics and concluded that an extensive collodion membrane was predominantly related to a nonsyndromic ichthyosis.

Ichthyoses in everyday practice: management of a rare group of diseases.

Ichthyoses comprise a heterogeneous group of hereditary disorders of keratinization characterized by a highly varied clinical picture. A distinction is made between common hereditary ichthyoses (ichthyosis vulgaris and X-linked ichthyosis), which usually manifest themselves in the first year of life, and rare, sometimes severe congenital ichthyoses. Patients with very mild symptoms often do not even realize they have ichthyosis. The diagnosis is usually based on clinical evaluation. Molecular genetic testing as well as histological and electron microscopic studies may aid in confirming the diagnosis. Mapping a family tree is also diagnostically useful. Besides skin manifestations, important aspects of the clinical examination and history include disease onset, presence of a collodion membrane at birth as well as the presence of hair anomalies and extracutaneous signs and symptoms. Rigorous hydration of the skin (several times a day) and balneotherapy are the mainstay of ichthyosis treatment. For patients with severe disease, systemic acitretin treatment should be considered on a case-by-case basis. While ichthyoses are generally limited to the skin, there are syndromic forms that may affect other organs and that require interdisciplinarity cooperation. Although ichthyoses remain incurable, they can be managed well with symptomatic treatment. However, such treatment is frequently time consuming and expensive. In the future, novel therapeutic approaches might include enzyme replacement and gene therapies as well as antiinflammatory drugs.

Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis.

BackgroundAutosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations.MethodsGenomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families.ResultsGenetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic.ConclusionOur findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI.

Collodion baby-congenital ichthyosis: clinical review

Collodion baby is a rare form of congenital ichthyosis in which the entire body is covered by a parchment-like membrane. These neonates are at the risk of dehydration, sepsis, electrolyte disturbances, and temperature instability. It is inherited in autosomal recessive manner. We report a case of Collodion baby, born of a consanguineous marriage. Here, we present a short review of this condition and the various methods available for the prenatal diagnosis. A literature search was done using PubMed, Medline, and Google Scholar databases using the mesh terms “Ichthyosis”, “collodion baby”, “collodion membrane”, “Congenital ichthyosiform erythroderma”, and “Lamellar ichthyosis”.

Infant skin care: updates and recommendations.

Neonatal skin acclimates rapidly to dry, aerobic conditions at birth and skin function gradually matures throughout infancy. Gentle skin care practices support the ongoing development and function of newborn skin. This article reviews research updates and current skin care recommendations for full-term infants, premature infants, and infants born with severe cutaneous manifestations of genetic skin disorders. Although safe early bathing of full-term infants with environmental controls is possible, delaying the first newborn bath for 12-24 h of life offers benefits of increased parental bonding and breastfeeding success. Swaddled bathing every 4 days is an effective bathing strategy for premature neonates. Among infants with a family history of atopic dermatitis, regular application of bland skin moisturizers reduces their risk of developing the disease. For newborns with erosive or blistering genetic skin conditions, use of specialized wound dressings and emollients promotes wound healing and helps limit skin damage. Environmental control with humidified incubators helps prevent life-threatening hypernatremic dehydration among babies born with collodion membranes; however, affected infants can tolerate breaks outside of the humidifier to promote parent-infant bonding. This article reviews infant skin care recommendations relevant to pediatric practice. Research to further optimize newborn skin care is ongoing, particularly, for the special populations of premature neonates and infants born with severe skin disease.

LAMELLAR ICHTHYOSIS: ONE CASE REPORT

Introduction: Ichthyosis is a heterogeneous group of skin disease characterized by generalized scaling. Lamellar ichthyosis is an autosomal recessive disorder with a mutation in the TGM 1 gene encodes the transglutaminase I protein was found. The scales reflect changes in epidermal differentiation. Lamellar ichthyosis is the one of the rarest form of ichtyosis where the infant is usually born with a collodion membrane. Case: A 10-year-old girl was consulted by the ophthalmologic department with a chief complaint of generalized scales on the body since birth. Both patients also complained of sore eyes because they can not close tightly. According to the parent, at the time of birth the patient was enveloped by membranes where the eyes could not close tightly. The patient was also unable to breastfeed. Physical examination showed ichtyiosiform scales arranged lamellar in a mosaic pattern throughout the body, Eclabium on the lips and ectropion on the eyes were found. Histopathological examination results support the diagnosis of lamellar ichthyosis. The patient was given emollient and supportive therapy. A good improvement shown by markedly diminished scales and skin stiffness was seen after six weeks of treatment. Conclusion: Lamellar ichthyosis is a rare type of ichtyosis. Treatment aims to prevent excessive transepidermal water loss, prevent complications such as secondary infections and to reduce clinical symptoms.

Collodion baby treated at a tertiary hospital in Tanzania: a case report

BackgroundThe term “collodion baby” is used to describe a newborn covered with a translucent, parchment-like skin sheet. It is an extremely rare condition with an estimated incidence of 1 in 300,000 live births. Clinically, the baby will present with a collodion membrane with fissures, ectropium, eclabium, and hypoplastic digits. Shedding of the membrane increases risk of dehydration and infection.Case presentationWe present the case of an African baby girl, who died when she was 7-months old, who presented with features of collodion membrane at birth. She later developed hypernatremic dehydration and a constricted band on her lower limb that required urgent surgical release. She stayed in our hospital for 35 days; she was then discharged home after improvement for 6 months of follow-up clinics at Muhimbili National Hospital: neonatal; dermatology; ear, nose, and throat; and physiotherapy units. She died at 7 months of age.ConclusionDespite limited resources, the early survival of these babies can be improved by providing basic care.

Ichthyosis Vulgaris

Ichthyosis Vulgaris

CuS nanoflowers/semipermeable collodion membrane composite for high-efficiency solar vapor generation

The ever-dwindling freshwater sources and ever-increasing need for freshwater resources are regarded as two important concerns for current society. Solar vapor generation has proven to be an effective and reliable solar-driven technology to overcome these concerns. However, it is a big challenge to prepare low-cost and high-efficiency solar absorber for solar vapor generation. Herein, we report a novel structurally integrated solar absorber composed of CuS nanoflowers and semipermeable collodion membrane (SCM). Three-dimensional (3D) covellite CuS nanoflowers composed of nanosheets have been synthesized with a facile hydrothermal route and their morphology and structure are investigated with various analytical techniques. High solar vapor generation efficiencies of 68.6% and 81.2% were achieved with CuS/SCM under 1 and 4 sun irradiation, respectively, much higher than that of the CuS nanofluid. A stable solar vapor generation performance has been demonstrated over 20 cycles. These results display a promising potential of CuS/SCM as a solar-absorber for efficient solar vapor generation.