A longitudinal study of a harlequin infant presenting clinicallyas non-bullous congenital ichthyosiform erythroderma

Over the past 8 years, we have followed a child born as a harlequin baby, who survived due to treatment with retinoids. His condition evolved clinically towards the erythrodermic form of lamellar ichthyosis (non-bullous congenital ichthyosiform erythroderma, NBCIE). According to ultrastructural and biochemical criteria, our patient originally presented with type II harlequin ichthyosis. Investigations showed an abnormal keratinosome structure and extrusion, a keratin pattern characteristic for epidermal hyperproliferation, and an absence of conversion of profilaggrin to filaggrin. Persisting keratinocyte hyperproliferation, associated with the presence of a dermal infiltrate, is in agreement with the present clinical picture of severe NBCIE. However, abnormal lamellar body production and defective filaggrin processing, which is not one of the diagnostic criteria of NBCIE, persist in the patient's skin. Further studies of the epidermal lipid composition, and of possible mutations of the keratinocyte transglutaminase gene performed on epidermal cell cultures of harlequin ichthyosis, will be necessary before type II harlequin ichthyosis can be accepted as an extremely severe form of NBCIE.     

Multiple aggressive squamous skin cancers in association with nonbullous congenital ichthyosiform erythroderma

Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.     

先天性大疱性鱼鳞病样红皮病角蛋白10的新发突变

目的: 检测1例先天性大疱性鱼鳞病样红皮病患者KRT1和KRT10基因突变.方法: 提取患者及其家人外周血DNA,PCR扩增KRT1和KRT10基因编码区的全部外显子及其侧翼序列并测序,以100名正常人作对照.结果: 该患者KRT10基因第1号外显子中的第466位碱基发生C→T杂合突变(c.C466T),导致其编码第156位氨基酸发生错义突变(p.R156C),患者父母、妹妹及正常对照均未发现该突变,提示其为新发突变.结论: KRT10基因的c.C466T错义突变可能为引起该患者临床表型的病因.     

Bullous and non-bullous ichthyosiform erythroderma associated with generalized pustular psoriasis of von Zumbusch type

Bullous ichthyosiform erythroderma (BIE) and non-bullous ichthyosiform erythroderma (NBIE) are rare congenital ichthyoses. Generalized pustular psoriasis (GPP) of von Zumbusch type is a rare and severe form of psoriasis marked by desquamative and pustular erythroderma associated with fever and altered general conditions. We report two adults with an ichthyosis typical of BIE in the first case and NBIE in the second, without any previous history of psoriasis, who presented with a severe and relapsing GPP of von Zumbusch type. Using current knowledge of the genetic relationship between psoriasis and congenital ichthyoses, we discuss the possibility of a common physiopathological link between congenital ichthyoses and GPP, and examine the possible therapeutic problems resulting from this pathological association, especially in BIE.     

表皮松解性角化过度型鱼鳞病一家系K10基因突变的研究

目的:检测一表皮松解性角化过度型鱼鳞病家系K10基因突变位点.方法:提取该家系成员的外周血DNA,采用聚合酶链反应(PCR)及DNA直接测序方法,检测患者角蛋白1(K1)及K10的基因突变.结果:该家系2例患者存在K10基因的杂合点突变,即在K10基因第2140位G→A,导致其第156位的精氨酸变为组氨酸(R156H).结论:K10 R156H是导致该家系2例患者临床表型的特异突变,进一步证实K10基因第156位密码子是突变热点.     

先天性大疱性鱼鳞病样红皮病一例KRT1及KRT10基因突变检测

目的：对先天性大疱性鱼鳞病样红皮病一例散发患者进行KRT1及KRT10基因的突变分析。方法：收集临床资料,提取外周血DNA,采用PCR技术扩增KRT1及KRT10基因的编码区及侧翼序列,用Sanger法测序检测潜在的基因突变,选取与患者无亲缘关系的100名健康人作为对照。结果：该患者KRT10检测出第1号外显子中第467位碱基发生G→A杂合突变（c.467G>A）,导致其编码的第156号氨基酸发生错义突变（p.R156H）。患者父母及正常对照均未发现该突变。KRT1基因未检测到突变。结论：KRT10基因的错义突变c.467G>A可能与该患者发病有关。     

Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma

We report novel mutations in the transglutaminase (TGase) 1 gene (TGM1) in a Japanese boy with non-bullous congenital ichthyosiform erythroderma (NBCIE). The patient showed fine, grey or light-brown scales on an erythematous skin. An in situ TGase activity assay detected markedly reduced TGase activity in the patient's epidermis. Electron microscopy revealed incomplete thickening of the cornified cell envelope during keratinization in the epidermis. Sequencing of the entire exons and exon-intron borders of TGM1 revealed that the proband was a compound heterozygote for two novel mutations, 9008delA and R388H. In lamellar ichthyosis, most previously reported TGM1 mutations have been located in the central core domain or upstream of the TGase 1 molecule. In the present NBCIE patient, the frameshift mutation 9008delA resulting in a premature termination codon at the tail of the TGase 1 peptide was in the beta-barrel 2 domain (C-terminal end domain) of the peptide, far from the active sites of the TGase 1 molecule, and the mis-sense mutation R388H was in the core domain.     

Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythroderma

A 3-year-old boy with nonbullous congenital ichthyosiform erythroderma with a four-month history of scabies was treated with a single dose of lindane cream. In a 48-hour period, he developed nausea and vomiting and also suffered from an epileptiform convulsion and muscular spasms. Seventy-two hours after application of the cream, his blood lindane level was 54 ng/mL. Caution should be exercised when using lindane in patients with compromised epidermal barrier function.     

Cushing's syndrome induced by topical steroids used for the treatment of non-bullous ichthyosiform erythroderma

Two children are reported who had the autosomal recessive type of ichthyosis, non-bullous ichthyosiform erythroderma, and who were treated with topical steroids. Both developed features of Cushing's syndrome, which disappeared when topical steroid therapy was discontinued and emollients were used. We believe topical steroid therapy is contra-indicated in this condition.     

异维A酸治疗先天性非大疱性鱼鳞病样红皮病一例

患者男,16岁,因全身皮肤粗糙、鳞屑16年,皮肤发红15年入我院.患者早产,出生时全身覆一层肥皂沫样膜,1个月后经清洗退去,发现患者皮肤粗糙、干燥,有细碎鳞屑,未曾出现过水疱.1岁左右全身皮肤发红,鳞屑逐渐增多、变大,4～5岁时鳞屑为蚕豆至钱币大小,中央固着,边缘游离,并出现裂隙,四肢重于躯干.随着年龄增长病情逐渐加重.病情冬重夏轻,无睑外翻、脱发、视力异常、隐睾,四肢活动稍受限.父母否认近亲结婚,否认类似疾病家族史.体检:各系统检查未见异常.皮肤科检查:全身皮肤发红、干燥、变硬,覆蚕豆至钱币大小皮色或淡白色广泛厚而大的鳞屑,鳞屑以四肢、躯干下半部分、手足为重(图1).掌跖角化过度.双眼闭合正常.口腔黏膜未受累.双手指间关节活动轻度受限,肘、膝关节活动正常.指甲见横脊.辅助检查:血尿粪常规、血生化检查正常,X线胸片、心电图、腹部B超无明显异常.皮损组织病理:角化过度,角质层凹陷处角化不全,表皮见空泡化细胞,棘层肥厚,乳头瘤样增生,表皮突延长;真皮浅层血管周围淋巴细胞浸润.诊断:先天性非大疱性鱼鳞病样红皮病.