Lamellar Ichthyosis Research Articles

Mucous Membrane Graft for Cicatricial Ectropion in Lamellar Ichthyosis: An Approach Revisited

A 26-year-old woman with congenital lamellar ichthyosis presented with bilateral cicatricial ectropion of the upper and lower eyelids. There was severe exposure keratopathy with corneal perforation in the left eye. The generalized skin involvement necessitated the use of an alternative to correct the cicatricial ectropion. Mucous membrane graft harvested from the oral cavity was used to correct the cicatricial ectropion of upper and lower eyelid of both eyes. Six months after treatment, the mucous membrane graft was keratinized and a significant reduction in lagophthalmos was seen. Mucous membrane graft offers a promising alternative to correct cicatricial ectropion in lamellar ichthyosis.

Prevalence of autosomal recessive congenital ichthyosis: A population-based study using the capture-recapture method in Spain

Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete. We sought to describe the prevalence of ARCI. We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method. We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association. The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries. The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study.

Congenital Lamellar Icthyosis (Collodion Baby)

Lamellar ichthyosis, also known as ichthyosis lammellaris and nonbullous congenital ichthyosis, is a rare inherited skin disorder, affecting around 1 in 600,000 people the images of this rare variety of skin disorder has been presented here. DOI: http://dx.doi.org/10.3126/jnps.v31i3.3769 J Nep Paedtr Soc 2011;31(3): 257

Lipid transport by mammalian ABC proteins

ABC (ATP-binding cassette) proteins actively transport a wide variety of substrates, including peptides, amino acids, sugars, metals, drugs, vitamins and lipids, across extracellular and intracellular membranes. Of the 49 hum an ABC proteins, a significant number are known to mediate the extrusion of lipids from membranes or the flipping of membrane lipids across the bilayer to generate and maintain membrane lipid asymmetry. Typical lipid substrates include phospholipids, sterols, sphingolipids, bile acids and related lipid conjugates. Members of the ABCA subfamily of ABC transporters and other ABC proteins such as ABCB4, ABCG1 and ABCG5/8 implicated in lipid transport play important roles in diverse biological processes such as cell signalling, membrane lipid asymmetry, removal of potentially toxic compounds and metabolites, and apoptosis. The importance of these ABC lipid transporters in cell physiology is evident from the finding that mutations in the genes encoding many of these proteins are responsible for severe inherited diseases. For example, mutations in ABCA1 cause Tangier disease associated with defective efflux of cholesterol and phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1 (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency associated with a loss in secretion of the lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal degenerative disease linked to the reduced clearance of retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis, skin diseases associated with defective lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective phospholipid and sterol transport respectively. This chapter highlights the involvement of various mammalian ABC transporters in lipid transport in the context of their role in cell signalling, cellular homoeostasis, apoptosis and inherited disorders.

Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects

Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.

Pediatric dermatology emergencies

The purpose of this review is to summarize recent advances in the diagnosis and treatment of several severe skin diseases seen in children. Several articles published recently added significantly to our understanding of drug reaction with eosinophilia and systemic symptoms (DRESS), eczema herpeticum, staphylococcal scalded skin syndrome and inherited ichthyosis. A review of 60 patients with DRESS showed 80% with hepatic involvement, 40% with renal involvement, 33% with pulmonary involvement and 50% with hematologic abnormalities. A review on eczema herpeticum describes several clinical scenarios in which it is vital to keep that diagnosis in mind. Another review on severe staphylococcal skin infections reminds us of the importance of covering for methicillin-resistant Staphylococcus aureus in all such cases until cultures and sensitivities show otherwise. The results of an international consensus conference on ichthyosis published this year will help all of us to better characterize these complicated patients. Additionally, the first case of hypothyroidism associated with a collodion baby was reported, as was the finding of an increased incidence of atypical nevi in patients with inherited ichthyosis. Although all of the conditions discussed in this article are relatively rare, it is important that they be kept on the differential diagnosis for sick infants and children with cutaneous findings, as early diagnosis and treatment of some of these conditions can be life saving.

Bébé collodion et syndrome de détresse respiratoire

The congenital ichthyosis appears mainly in the form of collodion baby. This one can be suspected in case of polyhydramnios associated with a snowy aspect of the amniotic liquid in the antenatal echography. The reported four cases of collodion baby were premature children having presented a respiratory distress syndrome of variable gravity. The pulmonary disease was of multifactorial origin. The outcome was favorable for four children.

Successful Treatment with Topical N‐Acetylcysteine in Urea in Five Children with Congenital Lamellar Ichthyosis

We reported the efficacy of topical cutaneous N-acetylcysteine in children with type I lamellar ichthyosis. The drug was applied on predetermined body surface areas two times a day for 6 weeks, followed by a daily maintenance application. During the first 2 weeks of treatment, a significant improvement occurred. After 4 months of maintenance application, a marked overall improvement occurred in all the treated areas. Only two patients showed mild adverse effects such as light burning, pruritus, and irritation. Even though a larger group of patients should be necessary to confirm the data, topical 10% N-acetylcysteine emulsion prepared in urea 5% seems to be a valuable and safe therapeutic option for lamellar ichthyosis in children, with benefit not only for skin lesions but also for ectropion avoiding a surgical procedure.

Collodion baby: a rare occurrence but a great teacher at each presentation!

Collodion is a rare(1:200 000) congenital condition linked to gene mutation mostly and sometimes can be autosomal recessive. Babies appear to have an extra layer tight shiny skin (sausage skin...

A rare case of lamellar ichthyosis

The authors describe a case of a relatively rare form of dermatosis - lamellar ichthyosis being an autosomal recessive disease - in a female patient aged 22. The population frequency of lamellar ichthyosis is from 1:200 000 to 1:300 000 newborns. The authors summarized data about the clinical picture and described problems with treatment of the disease.

Dorfman-Chanarin syndrome in two female siblings: A case report and discussion on approach & management

Dorfman-Chanarin syndrome (DCS) is a very rare disorder of lipid metabolism that exhibits an autosomal recessive pattern of inheritance. Besides ichthyosis, systemic manifestations may be present. We report two female siblings with DCS who presented with non-bullous ichthyosiform erythroderma (NBIE). A peripheral blood smear demonstrated Jordan anomaly. This case emphasizes the need for peripheral blood smear screening in patients with congenital ichthyosis.A 2½-year-old female child and her 1-month-old sibling presented with generalized erythema and scaling, which was suggestive of NBIE. Hepatomegaly and ectropion were seen in the older sibling. A peripheral blood smear of both the patients revealed Jordan anomaly. Serum biochemistry revealed abnormal liver function tests, abnormal lipid profile, and elevated muscle-derived enzymes. A diagnosis of Dorfman-Chanarin syndrome was made in both the siblings. Screening for Jordan anomaly in the family members including the parents and maternal and paternal grandmothers was negative.The peculiarities in our case include the presence of this disorder in both female siblings along with alopecia in the younger sibling. Hyperlipidemia, noted in one of our cases, is also not a common association. Diagnosing DCS is fairly simple and a high index of suspicion may lead to higher rates of detection of this rare disorder.

The roles of ABCA12 in keratinocyte differentiation and lipid barrier formation in the epidermis

ABCA12 is a member of the large superfamily of ATP-binding cassette (ABC) transporters, which bind and hydrolyze ATP to transport various molecules across limiting membranes or into vesicles. The ABCA subfamily members are thought to be lipid transporters. ABCA12 is a keratinocyte transmembrane lipid transporter protein associated with the transport of lipids in lamellar granules to the apical surface of granular layer keratinocytes. Extracellular lipids, including ceramide, are thought to be essential for skin barrier function. ABCA12 mutations are known to underlie the three main types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations lead to defective lipid transport via lamellar granules in the keratinocytes, resulting in malformation of the epidermal lipid barrier and ichthyosis phenotypes. Studies of ABCA12-deficient model mice indicate that lipid transport by ABCA12 is also indispensable for intact differentiation of keratinocytes.

Treatment of rare keratinization disorders: what’s new?

Disorders of keratinization encompass a wide variety of monogenic skin diseases characterized by inheritable disturbances in the differentiation of epidermal keratinocytes leading to hyperkeratosis and/or epidermal fragility. Over the last decade, many new etiologies have been found for these diseases, but until recently this has not been paralleled by a similar good progress in therapy. The purpose of this article is to review the treatment of three groups of disorders of keratinization: congenital ichthyoses due to autosomal-recessive inheritance (e.g., lamellar ichthyosis and ichthyosiform erythroderma); keratinopathies due to dominant-negative keratin mutations (epidermolytic ichthyosis, epidermolysis bullosa simplex and pachyonychia congenita); and acantholytic diseases due to autosomal-dominant disorders of cell adhesion (Darier–White and Hailey–Hailey diseases). Recent advances in the use of keratolytic agents, retinoids, botulinum toxin and molecular biology techniques are discussed. In conclusion, there is reason for optimism among patients with keratinization disorders as there are now an increasing number of improved therapeutic strategies.

Finding Homes for Orphan Cytochrome P450s: CYP4V2 and CYP4F22 in Disease States

The cytochrome P450 (CYP) 4 family of enzymes contains several recently identified membersthat are referred to as “orphan P450s” because their endogenous substrates are unknown.Human CYP4V2 and CYP4F22 are two such orphan P450s that are strongly linked to ocular andskin disease, respectively. Genetic analyses have identified a wide spectrum of mutations in the CYP4V2gene from patients suffering from Bietti’s crystalline corneoretinal dystrophy, and mutations in theCYP4F22 gene have been linked to lamellar ichthyosis. The strong gene–disease associations provideunique opportunities for elucidating the substrate specificity of these orphan P450s and unraveling thebiochemical pathways that may be impacted in patients with CYP4V2 and CYP4F22 functional deficits.

Dermatophytosis and Sjögren-Larsson syndrome: Foe or friend?

We report the patchy normalization of lamellar ichthyotic skin in Sjögren-Larsson syndrome (SLS) following a cutaneous Trichophyton rubrum infection. The dermatophytosis was pruritic and pustular, requiring treatment which was followed by the return of the lamellar ichthyosis. We discuss the possible mechanism of this clinical observation, which in turn may direct future therapy for difficult to treat ichthyotic skin seen in conditions such as SLS.

Collodion baby: Presentation of a clinical case with good outcome

Collodion baby: Presentation of a clinical case with good outcome

Expedient Treatment of a Collodion Baby

Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term “collodion baby” refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children develop signs of one of several types of ichthyosis, which gives the skin the appearance of “fish scales.” We report a unique case of a Caucasian male that was born as a Collodion baby at the University of Kentucky Children's Hospital in Lexington, Kentucky. Although the impairment of the skin barrier function put the patient at risk for a number of complications, he improved significantly after being treated with emollients and antibiotics. In contrast to previous findings, we found that skin emollients were beneficial and did not increase the risk of infection.

A report of two cases of TGM1 mutations in Iranian patients with lamellar ichthyosis.

Objective Autosomal Recessive Congenital Ichthyosis (ARCI) is a rare, heterogenous keratinization disorder of the skin, classically divided into two clinical subtypes, Lamellar Ichthyosis (LI) and Nonbullous Congenital Ichthyosi-formis Erythroderma (NCIE). Lamellar Ichtyosis is caused by mutations in the TGM1 gene that encodes transglutaminase 1 enzyme, which is critical for the assembly of the cornified cell envelope in terminally differentiating keratinocytes. TGM1 is a complex enzyme existing as both cytosolic and membrane-bound forms. Moreover, TGM1 is proteolytically processed, and the major functionally active form consists of a membrane-bound 67/33/10-kDa complex with a myristoylated and palmitoylated amino-terminal 10-kDa membrane anchorage fragment. In this study, all 14 coding exons of TGM1 gene were investigated using PCRsequencing method in three Iranian patients with different phenotypes which are often caused by homozygote or compound heterozygote mutations and a homozygote mutation (G218S) in exon 4 and three heterozygote mutations (R37K, D58N, D86N) in exon 2 were observed. The mutation (D86N) was seen in two patients simultaneously. Key words: TGM1gene, mutation, ARCI, lamellar, ichthyosis, sequencing.

Improvement of Nonbullous Congenital Ichthyosiform Erythroderma Following Functional Endoscopic Sinus Surgery

We report the case of a child with congenital nonbullous ichthyosiform erythroderma on long-term isotretinoin who developed progressively worsening ichthyosis along with recurrent bouts of sinusitis. Endoscopic sinus surgery revealed osteophytes, most likely an isotretinoin-related adverse event, and post operatively the patient's sinus disease and skin disease both dramatically improved. This case represents the first report, to our knowledge, of ichthyosis improving after endoscopic sinus surgery.

Expedient Treatment of a Collodion Baby

Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term “collodion baby” refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children develop signs of one of several types of ichthyosis, which gives the skin the appearance of “fish scales.” We report a unique case of a Caucasian male that was born as a Collodion baby at the University of Kentucky Children's Hospital in Lexington, Kentucky. Although the impairment of the skin barrier function put the patient at risk for a number of complications, he improved significantly after being treated with emollients and antibiotics. In contrast to previous findings, we found that skin emollients were beneficial and did not increase the risk of infection.