Form Of Ichthyosis Research Articles

Molecular Heterogeneity of Blistering Disorders: The Paradigm of Epidermolysis Bullosa

Molecular Heterogeneity of Blistering Disorders: The Paradigm of Epidermolysis Bullosa

Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

BackgroundArsenic is a ubiquitous environmental toxicant, and abnormalities of the skin are the most common outcomes of long-term, low-dose, chronic arsenic exposure. If the balance between keratinocyte proliferation, differentiation, and death is perturbed, pathologic changes of the epidermis may result, including psoriasis, atopic dermatitis, and certain forms of ichthyosis. Therefore, research investigations using in vitro human epidermal cells could help elucidate cellular and molecular processes in keratinocytes affected by arsenic. Data from such investigations could also provide the basis for developing cosmetic intervention for skin diseases caused by arsenic.MethodsThe viability of HaCaT keratinocyte cultures with or without prior exposure to low-dose arsenic trioxide was compared for varying concentrations of arsenic trioxide over a time course of 14 days because in untreated control cultures, approximately 2 weeks is required to complete cell differentiation. Long-term cultures were established by culturing HaCaT cells on collagen IV, and cells were subsequently exposed to 0 parts per million (ppm), 1 ppm, 5 ppm, 7.5 ppm, 10 ppm, and 15 ppm of arsenic trioxide. The percentages of viable cells as well as DNA damage after exposure were determined on Day 2, Day 5, Day 8, and Day 14.ResultsUsing both statistical and visual analytics approaches for data analysis, we have observed a biphasic response at a 5 ppm dose with cell viability peaking on Day 8 in both chronic and acute exposures. Further, a low dose of 1 ppm arsenic trioxide enhanced HaCaT keratinocyte proliferation, whereas doses above 7.5 ppm inhibited growth.ConclusionThe time course profiling of arsenic trioxide cytotoxicity using long-term HaCaT keratinocyte cultures presents an approach to modeling the human epidermal cellular responses to varying doses of arsenic trioxide treatment or exposure. A low dose of arsenic trioxide appears to aid cell growth but concomitantly disrupts the DNA transcription process.

Banding Pattern on Polarized Hair Microscopic Examination and Unilateral Polymicrogyria in a Patient With Steroid Sulfatase Deficiency

Several forms of ichthyosis are associated with neurologic manifestations, including Sjögren-Larsson syndrome, Refsum disease, and mental retardation-enteropathy-deafness-neuropathy-ichthyosis-keratoderma (MEDNIK) syndrome. We report a case of X-linked steroid sulfatase deficiency, ichthyosis, seizures, abnormal hair banding pattern, and unilateral polymicrogyria. A 3-year-old Caucasian male with a history of ichthyosis since birth presented with generalized tonic seizures. Findings from a physical examination were remarkable for thin hair, retinitis pigmentosa, and poor dentition. Polarized light microscopic examination of all the hair samples demonstrated a banding pattern. Magnetic resonance imaging of the brain revealed left hemispheric polymicrogyria with decreased sulcal pattern and stable asymmetric dilation of the left lateral ventricle. Constitutional microarray revealed the typical approximately 1.5-Mb deletion of the steroid sulfatase gene. Steroid sulfatase deficiency is a cause of X-linked ichthyosis; however, our patient also had retinitis pigmentosa, seizures, and abnormal hair findings. The presence of abnormal hair with a banding pattern on polarized microscopy may be helpful for diagnosis; however, this pattern is not specific to this disease. In addition, to our knowledge, the presence of a malformation of cortical development has not been previously reported in patients with steroid sulfatase deficiency.

Hiperceratose epidermolítica: um seguimento de 23 anos de uso de retinoides orais

Epidermolytic hyperkeratosis is a form of ichthyosis normally resistant to topical treatments. Female patient monitored since 1978 diagnosed with epidermolytic hyperkeratosis. Clinical examination showed generalized hyperkeratosis and scaling. Given that no other treatments were available at the time, the patient was initially treated with keratolytic, systemic vitamin A and moisturizers, with no improvement. In 1986, with the development of oral retinoids, etretinate was introduced. In 1998 this was replaced by acitretin. The patient is receiving 25 mg/day after 23 years of using oral retinoids. Significant improvement of the condition and patient's quality of life has been noted.

Pleomorphic Ichthyosis: Proposed Name for a Heterogeneous Group of Congenital Ichthyoses with Phenotypic Shifting and Mild Residual Scaling

Congenital ichthyosis is often associated with typical neonatal phenotypes, "Collodion baby" and "Harlequin foetus", later transforming into severe lamellar or erythrodermic ichthyosis. However, in a minority of cases the skin condition will improve spontaneously after birth, although slight scaling, xerosis, hypohidrosis and keratoderma usually persist. Some of these patients will eventually be diagnosed as suffering from self-improving collodion ichthyosis, ichthyosis prematurity syndrome, or other, even rarer, forms of ichthyosis also characterized by a phenotypic shift in early childhood. This paper summarizes newly described aetiologies for some of these diseases and discusses difficulties encountered when trying to distinguish them clinically from other types of autosomal recessive congenital ichthyosis. To remind health providers about this heterogeneous group of partially transient disorders of cornification, a new umbrella term, "pleomorphic ichthyosis", is proposed.

Ichthyosis cribriformis: A new entity?

A 22-year-old woman had an unusual congenital skin disorder in the form of ichthyosis characterized by innumerable keratotic plugs, resulting in a peculiar sievelike appearance. On histopathologic examination the epidermis showed a pronounced orthohyperkeratosis. The keratotic plugs seemed to emerge from the infundibular region of hair follicles. Immunohistochemical characterization revealed a normal keratin and filaggrin expression. Oral treatment with isotretinoin resulted in a reduction of the hyperkeratosis. Because we could not find any previously reported similar case, we propose the new name "ichthyosis cribriformis," which means "sievelike ichthyosis."

Hepoxilin A 3 (HXA 3) synthase deficiency is causative of a novel ichthyosis form

Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar ichthyosis (LI) are characterized by mutations in 12 R-lipoxygenase (12 R-LOX) and/or epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3 lacks oxygenase activity, but is capable of forming hepoxilin-type products from arachidonic acid-derived hydroperoxide from 12 R-LOX, termed 12 R-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12 R-HpETE). Mutations in either of two enzymes lead to NCIE or LI. Moreover, 12 R-LOX-deficient mice exhibit severe phenotypic water barrier dysfunctions. Here, we demonstrate that 12 R-HpETE can also be transformed to 8 R-HXA 3 by hepoxilin A 3 (HXA 3) synthase (12-lipoxygenase), which exhibits oxygenase activity. We also presented a novel form of ichthyosis in a patient, termed hepoxilin A 3 synthase-linked ichthyosis (HXALI), whose scales expressed high levels of 12 R-LOX, but were deficient of HXA 3 synthase.

Emerging drugs for ichthyosis

The ichthyoses constitute a large and heterogeneous group of disorders characterised by varying degrees of skin scaling. Most forms are rare but between them, they affect tens of thousands of people worldwide. Treatment presently consists primarily of topical keratolytic agents, aimed at removing the ichthyotic scales, and emollients. If an ichthyosis cannot be controlled by topical therapy alone, retinoids can be used. Although effective in several forms of ichthyosis, side effects and teratogenicity severely limit their use. The recent development of retinoic acid metabolism blocking agents (RAMBAs) offers new possibilities. With these drugs, retinoid effects may be obtained with less side effects and a shorter post-treatment teratogenicity period. This review discusses the RAMBAs that are now in clinical trials and outlines possible future developments.

X‐linked ichthyosis without STS deficiency: Clinical, genetical, and molecular studies

We report on a Sardinian pedigree with congenital ichthyosis associated with normal levels of steroid sulfatase and a normal molecular pattern, as detectable with a cDNA probe for the steroid sulfatase (STS) gene. Though the pattern of transmission of the disease is consistent with X-linked recessive inheritance, this form of ichthyosis was found to segregate independently of genetic polymorphisms detected by probes of the region Xp22.3, where the STS locus has been mapped. The search for close genetic linkages with other polymorphic markers scattered along the entire X chromosome has so far been fruitless. For the time being, the main conclusion derived from these data is that STS deficiency is not a sine qua non for X-linked ichthyosis which may also result from a mutational event at an X-chromosomal site genetically unlinked to the STS locus.

Functional state of endocrinic system in patients with various forms of ichthyosis

The increased content of AKTG, renin in blood serum and progesterone in men is cha- recteristic of all forms of ichthyosis. The decrease of the level of somototropin, prolactin. aldosterone in blood serum and testosterone in men is revealed in all forms of ichthyosis.

Barrier function parameters in various keratinization disorders: transepidermal water loss and vascular response to hexyl nicotinate

In this study, we characterized the stratum corneum barrier function in 39 patients with various keratinization disorders (autosomal dominant ichthyosis vulgaris [ADI] [n = 7], X-linked recessive ichthyosis [XRI] [n = 6], autosomal recessive congenital ichthyosis [CI] [n = 10], dyskeratosis follicularis [Darier's disease; DD] [n = 8], erythrokeratoderma variabilis [EKV] [n = 8]), and 21 healthy volunteers, using two non-invasive methods: transepidermal water loss (TEWL) measuring outward transport of water through the skin by evaporimetry, and the vascular response to hexyl nicotinate (HN) penetration into the skin as determined by laser-Doppler flowmetry. Significantly increased TEWL values were found on the volar forearm in all three forms of ichthyosis, compared with the healthy control group, with the highest TEWL values in the CI group. The penetration of HN on the volar forearm was accelerated in patients with ADI, XRI and CI, as indicated by a shorter lag time (t0) between HN application and initial vascular response. However, differentiation between CI and the other ichthyoses was not possible by this method. When using both methods in DD and EKV, no differences compared with the healthy controls could be detected on the volar forearm, where the skin was principally unaffected; only the measurements from the affected skin on alternative sites demonstrated significantly increased TEWL values. In ADI and CI, however, normal-appearing skin also showed impaired values. We conclude that both TEWL and the vascular response to penetration of HN are suitable methods to monitor the skin barrier function in keratinization disorders, and are helpful in discriminating between these disorders.

Epidermal Growth Factor Receptors in Genetically Induced Hyperproliferative Skin Disorders

The presence and morphologic distribution of epidermal growth factor receptor (EGF-R) were investigated in a variety of genetic disorders that affect human epidermis. These diseases included various forms of ichthyoses as well as restrictive dermopathy and the CHILD syndrome (congenital hemidysplasia-ichthyosiform erythroderma-limb defects). The distribution of EGF-R was detected by immunohistochemical techniques. Increased staining of immunoreactive EGF-R was frequently, but not always, seen in lesions with experimental or clinical evidence of hyperproliferation, suggesting an increased potential to respond to endogenous levels of either transforming growth factor-alpha or EGF. The finding that EGF-R levels are not always increased in congenital epidermal disorders indicated that the presence of this receptor pathway is not simply a marker for aberrant epidermis.

Topical retinoids: In vivo predictive assays

Vitamin A is important for epithelial cell proliferation and differentiation and therefore has been used as a therapy for a variety of skin diseases. Synthetic vitamin A derivatives, called retinoids, have been used to treat a number of clinical skin conditions, including cystic acne and various forms of ichthyosis, Darier's disease, and psoriasis. Because of the toxicity of existing retinoids, newer vitamin A derivatives have been synthesized and must be evaluated in preclinical assays. Retinoids have profoundly differing biologic properties that can be evaluated selectively by studying their efficacy in different in vivo animal assays. This review will discuss some of the assays that may be useful predictors of retinoid efficacy.

Autosomal dominant lamellar ichthyosis.

Five members of two generations of one family were affected with lamellar ichthyosis, suggesting autosomal dominant transmission. The clinical and histopathological characteristics of the cases described here are similar to those reported by Traupe et al. (1984) as autosomal dominant lamellar ichthyosis and thus confirm the existence of this new form of ichthyosis.

The peeling skin syndrome

A unique form of congenital ichthyosis in two unrelated patients is described and characterized histologically by separation of the epidermis between the stratum corneum and the stratum granulosum. The clinical history, genetics, serially performed skin biopsies, and biochemical studies are reviewed. This form of ichthyosis is different from previously described entities. Lifelong peeling of the general body epidermis, pruritus, short stature, easily removed anagen hairs, and the ability to easily mechanically separate stratum corneum from the rest of the epidermis characterize the syndrome. In two families with this disorder, autosomal recessive inheritance is suggested. A low plasma tryptophan level as present in two patients with this disease. This inherited disorder of the epidermis was first described in 1924 before the genetics and histology of ichthyosis were extensively studied and is a distinct genetic and clinical entity to be considered in unusual cases of ichthyosis.

Bilateral Corneal Opacities

Congential unilateral ichthyosiform erythroderma was first described in 1963. 1 All reported cases have been associated with other congenital anomalies. Although there has been no successful treatment of this condition, because of the preliminary success of oral isotretinoin for other forms of ichthyosis, our patient was given a trial of this drug. The treatment was a failure, and a complication of reversible corneal deposits occurred. Report of a Case A 14-month-old girl, the product of a full-term pregnancy and normal vaginal delivery, was seen and hospitalized at the Albany (NY) Medical Center in January 1977 for evaluation of multiple congenital abnormalities. There was no family history of anomalies. The mother had taken only the normal medications permitted during pregnancy. On physical examination, the child had a lobster-claw deformity of the left hand as well as a malformed left lower extremity. A well-demarcated, crusted, scaling erythroderma extended from the anterior midline

Hyperkeratosis of Nipple and Areola

Hyperkeratosis of the nipple and areola is a rare condition that may occur in association with various forms of ichthyosis or as the result of extension of an epidermal nevus. The nevoid form is extremely rare and appears most commonly in women in their second or third decade of life. It is characterized by verrucous thickening and brownish discoloration of both nipples and areolae. Thirteen cases of this type have been reported. We are describing two additional cases to bring the total to 15 instances.

Disc-electrophoretic separation of water soluble proteins from scales of different forms of ichthyosis.

In extracts of scales of different forms of ichthyosis, disc-electrophoretic separation of water soluble proteins was performed. Number and position of the protein bands correspond with number and position of the bands of extracts of normal keratin and psoriatic scales. However, in comparison to normal keratin, all examined forms of ichthyosis showed in zone II the enriched bands Nos. 6 and 7. This permits a distinct differentiation from psoriasis in which in zone II the bands Nos. 9 and 10 are enriched. In congenital ichthyosiform erythroderma and in ichthyosis combined with atopic dermatitis, in zone III the bands, containing gamma globulins, are enriched as an expression of the concomittant exudative process. The protein content of scale extracts of ichthyosis is 2 to 5 times lower than the one of psoriasis.

Management and treatment of ichthyosis.

ICHTHYOSIS is the term used to describe a group of hereditary disorders in which the outer horny layer of the skin is abnormal and has been likened in appearance to the scales of lower vertebrates.Many patients experience lifelong disfigurement as well as considerable discomfort from the abnormally thickened horny layer. In addition, thermal regulation, water balance and growth and development may be adversely affected, depending on the type and severity of the disease. The principal features of these disorders are outlined in Table 1. Although knowledge of the fundamental defects in the various forms of ichthyosis is incomplete, there have . . .

THE MITOTIC RATE AND DURATION IN LESIONS OP PSORIASIS AND ICHTYOSIS*

SUMMARY. The epidermal mitotic rate in psoriatic lesions is 3 or 4 times greater than that in normal epidermis as established by using 0.5% colcemid effective during a 5 hr. period. The mitotic duration in psoriasis is about 4 hr. compared with the normal 11/2hr. The colcemid mitotic rate in various forms of ichthyosis was found to be within the range of normal.