Plastic surgery for the management of palmoplantar keratodermia (Palmoplantoneoplasty)

Keratodermia is an incurable genetic and regional disease located in the palmar and plantar regions. The author reports his experience with five cases of palmoplantar keratodermia that were treated by grafting onto the soles and the palms skin taken from the calves and the thighs.     

The molecular basis for inherited bullous diseases

In the past 5 years enormous progress have been made in our understanding of the molecular basis for a number of inherited skin diseases characterized by easy blistering of the skin and the mucous membranes after minor physical trauma. This increased fragility of the skin or its appendages is due to molecular defects in genes coding for different intra- and extracellular structural proteins which are responsible for mechanical strength at their sites of expression. These diseases encompass the group of epidermolysis bullosa and disorders of cornification such as bullous forms of ichthyosis, palmoplantar keratoderma, and pachyonychia congenita. On the basis of clinical, morphological, and ultrastructural observations the epidermolysis bullosa group has been divided into three major categories. In epidermolysis bullosa simplex blister formation appears within the basal cell layer of the epidermis, and many mutations have been found in the genes of keratin 5 and 14 which are both expressed in basal keratinocytes. Epidermolytic hyperkeratosis leads to an epidermal separation in the suprabasal cell layers. In these patients numerous point mutations have now been described in the suprabasally expressed genes of keratin 1 and 10. In ichthyosis bullosa of Siemens blisters occur in the more upper suprabasal epidermis coincidental with the expression of keratin 2e, and mutations have been detected in the corresponding gene. In epidermolytic palmoplantar hyperkeratosis the suprabasal epidermal splitting is restricted to palms and soles of the patient. In keratin 9, which reveals such an exclusive expression pattern, molecular defects have indeed been recognized. Most recently in two different clinical subtypes of pachyonychia congenita, which is characterized by defective nails and focal palmoplantar hyperkeratosis, point mutations have been found in the genes coding for keratins 6, 16, and 17. In junctional epidermolysis bullosa the separation takes place within the dermal-epidermal basement membrane at the level of the lamina lucida, and mutations have been found in three genes coding for different laminin chains, in the ₄ gene of ₆₄ integrin, and in the gene of collagen XVII. In dystrophic epidermolysis bullosa the tissue separation occurs beneath the basement membrane within the papillary dermis at the level of the anchoring fibrils, and several mutations have been identified in the collagen VII gene. The rapid unraveling of molecular defects in these disabling or even lethal inherited skin diseases makes possible a more precise and earlier prenatal diagnosis, creates new options for suitable therapeutic regimens, and even offers the hope of curing these diseases by means of somatic cell gene therapy.Abbreviations BM Basement membrane - BPAg Bullous pemphigoid antigen - DEB Dystrophic epidermolysis bullosa - EB Epidermolysis bullosa - EBS Epidermolysis bullosa simplex - EHK Epidermolytic hyperkeratosis - EPPK Epidermolytic palmoplantar keratoderma - IBS Ichthyosis bullosa of Siemens - JEB Junctional epidermolysis bullosa - KIF Keratin intermediate filaments - NC Noncollagenous domain - NEPPK Nonepidermolytic palmoplantar keratoderma - PC Pachyonychia congenita     

Ichthyosis associated with widespread tinea corporis: report of three cases

Ichthyoses are a common group of keratinization disorders. A non-inflammatory generalized persistent skin desquamation is observed. It is characterized by increased cell turnover, thickening of the stratum corneum and functional changes of sebaceous and sweat glands. All of these favor fungal proliferation. Dermatophytes may infect skin, hair and nails causing ringworm or tinea. They have the ability to obtain nutrients from keratinized material. One of its most prevalent genera is Trichophyton rubrum. Although tineas and ichthyoses are quite common, the association of the two entities is rarely reported in the literature. Three cases of ichthyosis associated with widespread infection by T. rubrum are presented. Resistance to several antifungal treatments was responsible for worsening of ichthyosis signs and symptoms.     

Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology

Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.     

Hypomyelinating spastic dyskinesia and ichthyosis caused by a homozygous splice site mutation leading to exon skipping in ELOVL1

IntroductionNext generation sequencing technologies allow detection of very rare pathogenic gene variants and uncover cerebral palsy. Herein, we describe two siblings with cerebral palsy due to ELOVL1 splice site mutation in autosomal recessive manner. ELOVL1 catalyzes fatty acid elongation to produce very long-chain fatty acids (VLCFAs; ≥C21), most of which are components of sphingolipids such as ceramides and sphingomyelins. Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies (MIM: 618527) stem from ELOVL1 gene deficiency in human.MethodsWe have studied a consanguineous family with whole exome sequencing (WES) and performed in depth analysis of cryptic splicing on the molecular level using RNA. Comprehensive analysis of ceramides in the skin stratum corneum of patients using liquid chromatography-tandem mass spectrometry (LC–MS/MS). ELOVL1 protein structure was computationally modelled.ResultsThe novel c.376-2A > G (ENST00000372458.8) homozygous variant in the affected siblings causes exon skipping. Comprehensive analysis of ceramides in the skin stratum corneum of patients using LC–MS/MS demonstrated significant shortening of fatty acid moieties and severe reduction in the levels of acylceramides.DiscussionIt has recently been shown that disease associated variants of ELOVL1 segregate in an autosomal dominant manner. However, our study for the first time demonstrates an alternative autosomal recessive inheritance model for ELOVL1. In conclusion, we suggest that in ultra-rare diseases, being able to identify the inheritance patterns of the disease-associated gene or genes can be an important guide to identifying the molecular mechanism of genetic cerebral palsy.     

鱼鳞病合并神经系统疾病

目的 探讨鱼鳞病合并神经系统疾病的临床特征及可能机制。方法 回顾性分析8例鱼鳞病合并神经系统疾病患者的临床资料，并结合文献进行讨论。结果 合并中枢神经系统脱髓鞘疾病3例．癫痫3例，Sojgren-Larsson综合征1例，中枢性尿崩症1例。结论 鱼鳞病可合并神经系统疾病，其机制尚不明了，可能与发生学和遗传学有关。     

表皮松解性角化过度鱼鳞病一例

5岁女性患儿,全身皮肤潮红5年,出现干燥及角化增厚4年。皮损组织病理示:表皮显著角化过度,颗粒层细胞内见不规则的透明角质颗粒呈空泡样变性改变,棘层不规则增厚,真皮浅层血管周围少量炎性细胞浸润。基因突变检测示KRT10位点突变,基因编码区478号碱基由T变为A。诊断:表皮松解性角化过度鱼鳞病。给予局部外用0.1%维A酸乳膏每日2次及皮肤保湿剂治疗,40 d复诊时皮损明显好转,全身皮肤基本正常。     

Effect of cyclosporins A,G, and H on normal and ichthyotic keratinocyte growth in culture

Summary Cyclosporin A (CsA) was first used in organ transplantation and for the treatment of autoimmune disorders because of its strong immunosuppressant properties. Several laboratory studies have demonstrated that CsA exerts an inhibitory action on the growth of various cell types in culture, including human skin cells. Such an influence on epidermal keratinocytes, if not associated with the serious adverse effects of CsA medication, would be of interest for the treatment of hyperproliferative genodermatoses such as non-bullous congenital ichthyotic erythroderma (NBCIE). In our study, we used cyclosporin G (CsG) and H (CsH), analogues CsA, to examine the impact of these three cyclosporins on normal and ichthyotic keratinocyte growth in vitro. Epidermal cells were grown in a low-calcium, serum-free medium in the presence or absence of cyclosporins A, G or H (1–10 g/ml). The effects of a 72-h exposure to the drugs were evaluated by cell counting, ³H-thymidine incorporation and cytofluorimetric analysis of the BrdU-labelled cell suspensions. Our findings indicate a dose-dependent keratinocyte growth inhibition by the three cyclosporins. The data obtained with the three quantitation methods were in agreement and the cyclosporin-mediated effects were observed in both normal and ichthyotic keratinocyte cultures. CsG and CsH proved less effective than CsA, which induced a highly significant reduction even at 1 g/ml. Our results suggest, however, that ichthyotic keratinocytes are more sensitive to CsG and H when compared with normal cells (50% inhibition of ³H-thymidine uptake at significantly lower doses). A possible therapeutic action of non-toxic doses of CsG and CsH on NBCIE and other hyperproliferative epidermal diseases needs to be confirmed clinically.     

Netherton's syndrome in two sisters. A ten year experience of therapy with retinoids

Netherton's syndrome is a recessive autosomal disease associating ichthyosiform dermatosis, hair dysplasia and systemic involvement. (Netherton, 1958, Arch. Dermatol. , Vol. 78, 483–487). We report the observation of two sisters who present the complete form of Netherton's syndrome. Both patients were treated with retinoids for more than ten years.