Ichthyosiform Erythroderma Research Articles

Identification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families.

Non-bullous congenital ichthyosiform erythroderma (NCIE) is characterized by skin scaling with erythema. In this study, two Pakistani families with NCIE are genetically characterized through Whole Exome and Sanger sequencing to identify molecular basis of the disease. We identified a nonsense homozygous c.2026C>T mutation of ALOXE3, causing premature termination of the eLOX3 protein (p.Q676X). In silico studies predicted impaired enzymatic activity of the premature truncated eLOX3, leading to abnormal synthesis of specific hepoxilin derivatives, essential for epidermal barrier formation. It is the first ever study reporting homozygotes of p.Q676X mutation in ethnically distinct two Pakistani families; otherwise, heterozygotes of the said mutation have been reported in South Asian population only. Hence, mutation seems to be region-specific and may be useful for molecular diagnosis of NCIE. Moreover, our findings should help in genetic counseling and career screening.

Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents

BackgroundChanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by ichthyosiform non-bullous erythroderma and variable involvement of the liver and the neuromuscular system. In CDS patients, the accumulation of neutral lipids inside cytoplasmic lipid droplets has been demonstrated in different tissues. To date, ninety families with this disease have been described worldwide; most of them are from Mediterranean countries.Case presentationIn this report, we describe a consanguineous Turkish family with typical features of CDS. The parents are first cousins and are both diseased. At the age of eight, their child presented CDS with non-bullous congenital ichthyosiform erythroderma, hepatosteatosis, hepatomegaly and ectropion. Electromyographic examination is compatible with myopathy. A five-year-old cousin of the child is also affected by CDS. She was born to non-affected consanguineous parents. Mutation analysis of the ABHD5 gene revealed the previously reported mutation, N209X, which is the most frequent in Turkish patients. Lipid vacuoles, also known as Jordan’s anomaly, are detectable in their leucocytes.ConclusionsTo the best of our knowledge, this is the first report of a CDS family in which both parents and their child are affected by CDS. To date, the child does not present a more severe clinical phenotype compared with those of his relatives or other CDS patients of the same age. These findings suggest that high levels of triacylglycerol accumulation, that may be supposed to be present in high amount inside the ooplasm, did not affect embryo development and foetal growth.

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotypingof ichthyotic skin could suggest much-needed pathogenesis-based therapy. We sought to profile the molecular fingerprint of the most common orphan ichthyoses. Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n=9; lamellar ichthyosis, n=8; epidermolytic ichthyosis, n=8; and Netherton syndrome, n=4), as well as age-matched healthy control subjects (n=14), patients with psoriasis (n=30), and patients with atopic dermatitis (AD; n=16). Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with TH1/IFN-γ, OASL, and TH2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P<.05). Ichthyoses lacked the epidermal differentiation and tight junction alterations of patients with AD (loricrin, filaggrin, and claudin 1) but showed characteristic alterations in lipid metabolism genes (ELOVL fatty acid elongase 3 and galanin), with parallel reductions in extracellular lipids and corneocyte compaction in all ichthyoses except epidermolytic ichthyosis, suggesting phenotypic variations. Transepidermal water loss, a functional barrier measure, significantly correlated with IL-17-regulated gene expression (IL17F and IL36A/IL36B/IL36G). Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data supportthe testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.

Mindfulness-Based Cognitive Hypnotherapy and Skin Disorders

Mindfulness-based cognitive hypnotherapy integrates mindfulness, cognitive-behavioral therapy, and hypnotherapy to improve physical, emotional, mental, and/or spiritual aspects of skin disorders. Meditation, including mindfulness meditation, and hypnosis both utilize trance phenomena to help produce focalization and specific improvements in skin disorders through psycho-neuro-endocrine-immunologic mechanisms. Hypnosis, cognitive hypnotherapy, focused meditation, and mindfulness meditation are discussed with respect to improving various skin disorders including acne, acne excoriée, alopecia areata, atopic dermatitis, congenital ichthyosiform erythroderma, dyshidrotic dermatitis, erythema nodosum, erythromelalgia, furuncles, glossodynia, herpes simplex, hyperhidrosis, ichthyosis vulgaris, lichen planus, neurodermatitis, nummular dermatitis, postherpetic neuralgia, prurigo nodularis, pruritus, psoriasis, rosacea, trichotillomania, urticaria, verruca vulgaris, and vitiligo. Their integration into mindfulness-based cognitive hypnotherapy is then discussed and illustrated with improvement in a patient with systemic lupus erythematosus.

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.

The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4+/CD8+ and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+/CD8+ T cells, with inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell activation, respectively. We compared peripheral blood from 47 patients with ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical measures included the ichthyosis severity score, with subsets for erythema and scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive inducible co-stimulator molecule activation (P<0.001), particularly epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22-producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper 2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-γ frequencies (P > 0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with clinical measures, whereas IFN-γ clustered with age. Our data show peripheral blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical measures. Targeted therapies should dissect the relative contribution of polar cytokines to disease pathogenesis.

Analysis of keratin 1 gene mutation and phenotypes in a pair of twins with bullous congenital ichthyosiform erythroderma

Objective To identify mutations in keratin genes (KRT1 and KRT10) in a pair of twins with bullous congenital ichthyosiform erythroderma (BCIE) , and to explore the relationship between the causative genes and phenotypes. Methods Clinical data were collected from a pair of twins with BCIE and their family members. Peripheral blood samples were obtained from the twins, their old brother and parents, and DNA was extracted from these blood samples. Polymerase chain reaction (PCR) was performed to amplify all the coding exons and their flanking sequences of the KRT1 and KRT10 genes, and 100 unrelated healthy persons served as controls. Results The 11-year-old male proband presented with recurrent blisters, hypertrophy and desquamation all over the body for 11 years. His twin brother had similar skin lesions. Skin examination of the proband showed diffuse erythema covered with thick scaly crusts on the trunk and extremities. Blisters, bullae and erosions due to ruptured blisters were observed locally with tenderness on palpation. There were obvious hyperkeratotic and hard lesions on the big joints of the extremities. Diffuse hyperkeratosis could be seen on the palms and soles. A mutation c.591 + 1G > A was identified at position 1 in intron 1 of the KRT1 gene in the twins, but not in the 3 healthy family members or the 100 unrelated healthy controls. Conclusion The mutation c.591 + 1G > A at position 1 in intron 1 of the KRT1 gene may contribute to the clinical phenotype of the twins with BCIE. Key words: Ichthyosiform erythroderma, congenital; Keratin-1; Keratin-10; DNA mutational analysis

Case report of adolescent male with non-bullous congenital ichthyosiform erythroderma visiting dermatology clinic of King Fahad Military Hospital, Jeddah, Saudi Arabia, 2017

Non-bullous congenital ichthyosiform erythroderma (NBCIE) is an inherited disease with autosomal recessive form. It is considered as an extremely rare skin disorder that estimated to occur in 1/300,000 births, characterized by abnormal scaling of the skin with underlying redness. This is a case report study design with detailed history, examination and genetic analysis of 17 years old male with Non-bullous congenital ichthyosiform erythroderma (NBCIE).

Recurrent terbinafine resistant Trichophyton rubrum infection in a child with congenital ichthyosis

Dermatophytosis in children caused by Trichophyton rubrum is preferably treated with topical or systemic terbinafine. We report the first case of terbinafine resistance in a child with recurrent T. rubrum dermatophytosis and congenital ichthyosiform erythroderma.

Ocular complications of lamellar ichthyosis

Ichthyosis is a rare heterogeneous cutaneous disorder characterized by hyperkeratinization of the skin. They may be inherited or acquired following malnutrition, malignancy, or autoimmune disorders. Common forms of ichthyosis include lamellar ichthyosis (LI), X-linked ichthyosis, bullous ichthyosiform erythroderma, and ichthyosis vulgaris. LI may be associated with ectropion and eclabion and if poorly managed could result in vision loss. The case of a 7-month-old girl who presented with bilateral keratitis, panophthalmitis, and perforated right cornea is reported in this communication.

ROC analysis of selected matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in psoriatic patients.

IntroductionInherited ichthyoses are caused by mutations in various genes important for keratinocyte differentiation and epidermal barrier function. Although ichthyoses are rare disorders, they require costly long-term medical management, and thus there is a need for efficient preventive and therapeutic strategies.AimWe performed a retrospective study to determine the frequency, types, clinical presentation and associated genomic errors of primary hereditary ichthyoses in Egyptian patients and their relatives consulting the Genetics Clinic, Pediatric Hospital, Ain Shams University.Material and methodsThe outpatient log books of patients between January 2000 and December 2014 were reviewed, and diagnosis of new patients was confirmed through examination by a dermatologist. All epidemiologic, demographic, and clinical data were extracted and recorded in especially designed data collection forms.ResultsThe occurrence rate of primary hereditary ichthyoses in our study was 25.7% of genodermatosis patients attending the genetics clinics and 1 per 2359 patients attending the Pediatric Hospital. The commonest type of ichthyosis in our study was Lamellar ichthyosis (38%), followed by congenital ichthyosiform erythroderma (26.8%). Consanguineous marriage was reported among the parents of 79% of patients and positive family history was reported in 72% of patients.ConclusionsTo the best of our knowledge, this preliminary study is the first report on the clinico-epidemiological features of primary hereditary ichthyoses in Egypt. The high rate of prenatal consanguinity among parents of our patients may account for the high frequency of these genodermatoses in Egypt. This highlights the importance of genetic counselling and prenatal diagnosis in Egypt.

Досвід лікування новонароджених з іхтіозіформною еритродермією

Досвід лікування новонароджених з іхтіозіформною еритродермією

Infantile erythrodermic psoriasis: A case report and review of the literature

Erythroderma in infants can be attributed to plenty of causes, the more common ones being nonbullous congenital ichthyosiform erythroderma, lamellar ichthyosis, bullous congenital ichthyosiform erythroderma, severe atopic dermatitis, etc., However, there can be circumstances where infantile psoriasis can present to us with erythroderma; this may be a diagnostic challenge to the clinician. Hereby, we present a case of a young boy with recurrent erythroderma.

Invasive ocular surface squamous neoplasia in congenital ichthyosiform erythroderma

We report an invasive type of ocular surface squamous neoplasia (OSSN) in a patient with congenital ichthyosiform erythroderma. A male patient aged 44 years, with ichthyosis presented with progressively growing right corneal mass, with decreasing vision. He was clinically diagnosed as OSSN and treated with local excision, conjunctival cryotherapy, and ocular surface reconstruction with amniotic membrane graft. Histopathological examination of the excised specimen confirmed the mass as a well-differentiated squamous cell carcinoma with invasion into the corneal stroma. Postoperatively, ocular surface reconstruction was achieved, and visual acuity improved from only perception of light to counting fingers one meter due to dense corneal scar. Postoperative central corneal scar with thinning was noted. Early age of onset and progression of OSSN in such patient with ichthyosis, recommend the need for screening in patients with congenital ichthyosis. Early treatment can prevent visual disability and permanent sequelae due to corneal scar.

Collodion Baby: Case Report

The purpose of this work is to analyse the present data concerning epidemiological aspects, therapeutic possibilities as well as prenatal diagnosis of collodion baby. We report the case a woman, having a case index in the family and that consulted for a threat of premature childbirth to 29 weeks of amenorrhoea. Following have been marked by a premature childbirth of masculine sex newborn, presenting dermatological lesions typical of collodion baby, whose evolution was quickly fatal since first hours of life. Collodion baby is a severe form of congenital ichthyosis presents at birth. The clinical table is often characteristic. The prognosis depends on the management in the early neonatal period. This disorder usually evolves into a nonbullous congenital ichthyosiform erythroderma. Thanks to techniques of molecular biology, the prenatal diagnosis is given back possible since the 10-12 weeks of amenorrhoea, permitting a genetic counseling.

A Case Report on Congenital Ichthyosis - Collodion Baby

Collodion baby describes a highly characteristic clinical entity in newborns encased in a yellowish translucent membrane resembling collodion. In most cases the condition either precedes the development of one of a variety of ichthyoses, the commonest of which are lamellar ichthyosis and non-bullous ichthyosiform erythroderma, or occasionally represents an initial phase of other ichthyoses such as ichthyosis vulgaris. In at least 10% of all cases of collodion baby, the condition is followed by a mild ichthyosis of lamellar type, so mild as to be considered more or less normal, so-called self-healing collodion baby or 'lamellar ichthyosis of the newborn'. In this report, we present a severe form of ichthyosis.Faridpur Med. Coll. J. Jan 2016;11(1): 39-42

An IL-17–dominant immune profile is shared across the major orphan forms of ichthyosis

The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking because the underlying molecular basis is poorly understood. We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n=6; lamellar ichthyosis, n=7; epidermolytic ichthyosis, n=5; and Netherton syndrome, n=3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and T-cell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1β), and some TH1/interferon (IFN-γ) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-α levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patients with psoriasis and those with AD. Expression of TH2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17-related genes or markers synergistically induced by IL-17 and TNF-α (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P<.05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A (r=0.74, P<.001) and IL-17/TNF-synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. Our data associate a shared TH17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies.

108 Targeting the toll-like receptor pathway to treat scaling in the autosomal recessive congenital ichthyoses

Autosomal recessive congenital ichthyosis (ARCI) represents a group of non-syndromic ichthyoses, which include a range of ichthyoses such as congenital ichthyosiform erythroderma, lamellar ichthyosis and harlequin ichthyosis, resulting from gene mutations in at least 9 different genes. They are characterized by a hyperkeratotic epidermis, resulting in varying severities of scaling and erythroderma. The current first-line treatment is with oral retinoids although the mechanism of action is not well understood. Although retinoids are effective in treating skin scaling they have a number of side effects that limits treatment to certain individuals. New treatments based on an understanding of the mechanisms of hyperkeratosis have the potential to treat the majority of ARCI individuals regardless of genotype. Hyperkeratotic skin displays elevated keratin 1 (K1) expression and interleukin 1-alpha (IL1a) signalling. We have previously identified the NFkB/IL1a pathway as being the key innate immune pathway that leads to hyperkeratosis. We show here that the upstream effector of hyperkeratosis is the innate immune receptor, toll-like receptor 1/2 (TLR1/2). Agonists of this receptor upregulate K1 and IL1a, and are sufficient to induce hyperkeratosis in organotypic culture models. Therefore, we sought to target this pathway using a novel small molecule inhibitor that targets TLR1/2, in our Arachidonate 12-lipoxygenase and Transglutaminase1 shRNA knockdown ARCI cell culture model and human ARCI patient cells. Here we show K1 and IL1a are upregulated in knockdown cells compared to scrambled controls and that treatment with a TLR1/2 inhibitor rapidly reduces K1 protein expression levels and IL1a signalling. This therefore indicates that the use of this inhibitor in ARCI individuals, as well as other skin diseases with a scaling hyperkeratotic phenotype, could provide a more targeted treatment for hyperkeratosis with a reduced side-effect profile compared to retinoids.

Cutaneous verruciform xanthoma

Verruciform xanthoma is an uncommon verruciform or cauliflower-like benign hyperplastic disease that occurs most frequently in the oral cavity and sometimes outside it. The lesions of verruciform xanthomacan be solitary or multiple, and grow slowly with no subjective symptoms. Histopathological manifestations are important evidence for final diagnosis, and are characterized by the presence of a large number of foam cells in the dermal papilla. The pathogenesis of verruciform xanthoma is still unclear, and is mainly associated with stimulation, trauma, inflammation, lymphedema, heredity, and so on. Verruciform xanthoma can occur alone or together with other diseases, such as discoid lupus erythematosus, lichen planus, lichen sclerosus et atrophicus, arteriovenous hemangioma, lymphedema, graft-versus-host disease, congenital hemidysplasia with ichthyosiform erythroderma and limb defects, dystrophic epidermolysis bullosa, capillary leak syndrome, etc. Key words: Skin; Xanthomatosis; Infection; Heredity; Immunity; Pathology

Inherited ichthyosis: Non-syndromic forms.

Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non-syndromic ichthyoses and ichthyosis syndromes. Non-syndromic ichthyoses are characterized by the phenotypic expression of the disorder being seen only in the skin. Non-syndromic ichthyoses include ichthyosis vulgaris, recessive X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis and other forms. This review focuses on updates for each type of non-syndromic ichthyosis, highlighting molecular mechanisms and phenotype/genotype correlations. Included in autosomal recessive congenital ichthyosis are three of the major phenotypes (harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma) and three of the minor subtypes (self-healing collodion baby, acral self-healing collodion baby and bathing suit ichthyosis). Keratinopathic ichthyosis is proposed as an umbrella term for ichthyoses caused by mutations in keratin genes. Next-generation sequencing technologies have become powerful tools for the diagnosis of inherited ichthyoses and the discovery of their genetic causes. This article reviews the current understanding of molecular pathomechanisms for non-syndromic ichthyoses and explores future perspectives.

A rare case of bullous congenital ichthyosiform erythroderma in a newborn

Bullous congenital ichthyosiform erythroderma is a rare disorder of keratinization. It is associated with defective keratinization leading to skin fragility, blistering and hyperkeratosis. This condition was difficult to distinguish from staphylococcal scalded skin syndrome. We report a case of Bullous congenital ichthyosiform erythroderma in a 72 hour old male baby and discussed the differential diagnosis and management of the disease.