Novel and recurrent mutations in keratin 10 causing bullous congenital ichthyosiform erythroderma

Bullous congenital ichthyosiform erythroderma (BCIE) is a dominantly inherited keratinizing disorder characterized by erythroderma and blistering in neonates and generalized epidermolytic hyperkeratosis (EH) in adulthood. Previously, it has been shown that BCIE can be caused by mutations in either of the genes encoding K1 or K10, the keratins predominantly expressed in suprabasal layers of the epidermis. Using direct sequencing of genomic PCR fragments, we have analyzed 4 British families with BCIE, all of whom were found to carry mutations in K10. In 1 family, the affected person was found to have an unusual dinucleotide transversion mutation, 2138CC-->AA, causing two amino acid substitutions, D155E and R156S, also in the 1A domain of the K10 polypeptide. In 2 further kindreds, the previously reported "hotspot" mutations 2139C-->T and 2140G-->A were found. These mutations predict amino acid substitutions in the helix 1A domain of K10, designated R156C and R156H respectively. The proband in the fourth family was found to carry a novel mutation 4724T-->C, predicting the amino acid change L452P in the helix 2B domain of K10. All mutations were confirmed in the affected persons and were excluded from a population of 50 normal, unrelated individuals by restriction enzyme analysis. The location of these mutations in the highly conserved helix boundary motif sequences of K10 are consistent with previously reported dominant negative mutations in K10 and other keratins. Despite the unusual nature of two of these mutations, in particular the double missense mutation, the phenotypes of the affected individuals in these 4 families were entirely typical of BCIE.     

红皮病120例病因分析

目的：探讨红皮病的病因及并发感染的情况。方法：回顾性分析120例红皮病患者的临床资料。结果：120例患者中73．3％红皮病继发于原有皮肤病,其他致病原因依次为药物过敏、肿瘤,部分原因不明。28．3％并发感染的红皮病患者中,41～60岁组和〉60岁年龄组的感染率高于≤40岁年龄组,差异有统计学意义（P均〈0．05）;血浆白蛋白降低组患者感染率高于血浆白蛋白正常组患者,差异亦有统计学意义（P〈0．01）。结论：红皮病病因多种多样,不能忽视非常见病因的存在。随着年龄的增长和血浆白蛋白的降低,红皮病患者的感染率增加,应注意皮肤护理及早期支持治疗。     

Warfarin‐induced erythroderma

Erythroderma is a potentially serious and life‐threatening skin disease with a number of possible aetiologies. Drug reactions are well‐documented causes, with carbamazepine, penicillin and allopurinol being the most commonly implicated. This case describes a unique presentation of warfarin‐induced erythroderma in a 78‐year‐old female patient.     

The development of manifest psoriatic lesions is linked with the invasion of CD8+ T cells and CD11c+ macrophages into the epidermis

Koebner response was studied in 35 psoriatic patients. Two punch biopsies per patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7 days, 14 days and 21 days after, tape stripping. Alterations in the numbers of CD1+ Langerhans cells, CD4+ and CD8+ T cells and CD11c+ macrophages were mapped morphometrically. Results were compared with lesional and non-lesional psoriatic skin, and control skin. Nine of 35 patients were Koebner-positive. No statistically significant differences were noted between non-lesional psoriatic and control skin. CD4+ T cells increased in number 2 days after trauma in both the epidermis and the dermis, whereas epidermal CD8+ T cells and CD11c+ macrophages increased only in the Koebner-positive lesional skin after 7 days. The changes in lesions induced by tapestripping resembled those seen in lesional psoriatic skin (mature plaques). The number of CD1+ cells increased in mature psoriatic lesions only. It seems possible that trauma per se stimulates the accumulation of CD4+ T cells at the site of injury, but the development of manifest psoriatic lesions correlates with invasion of CD8+ T cells and CD11c+ macrophages into the epidermis.     

Intra- and inter-individual variations in cornified envelope peptide composition in normal and psoriatic skin

Summary Cornified envelopes from the stratum corneum of healthy volunteers and from the involved and uninvolved skin of psoriatic patients were electrophoretically purified, and their peptide composition analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) after cyanogen bromide cleavage. The resulting envelope peptide patterns (EPPs) were compared. In normal subjects, mainly quantitative minor differences in the EPPs were observed between different individuals. In the same individual, palms and soles could be distinguished from other body sites by their EPPs. The palm and sole samples presented identical patterns which were different from the patterns found with samples from other body sites. In psoriatic patients, EPPs of uninvolved skin resembled closely those of healthy epidermis, but showed striking differences from those of lesional skin. The EPPs of psoriatic lesional skin showed a characteristic accumulation of small peptides with molecular weights of 3–11 kDa. The EPP of lesional skin returned to normal during PUVA therapy, indicating that the changes in the biochemical composition of the cornified envelope are correlated with the clinical status of the disease.     

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.     

PROLIFERATION OF HIV IN LYMPHOCYTE – ASSOCIATED MACROPHAGES WITH CYTOPATHIC CHANGES IN AIDS ERYTHRODERMA.

Latency of the Human Immunodeficiency Virus (HIV) has been demonstrated in both helper T-Lymphocytes and cells of the macrophage/monocyte series. Although mitogen-dependent amplification of HIV infection within lymphocytes and monocytes/macrophages has been demonstrated to occur in vitro, in vivo evidence of such a phenomenon has been lacking. We have performed electron microscopic and immunocytochemical evaluation of skin biopsies from a patient with the Acquired Immunodeficiency Syndrome (AIDS) with chronic erythroderma. These biopsies provided evidence of proliferation of HIV in macrophages interacting with activated lymphocytes (CD3+). These macrophages were undergoing morphologic changes characteristic of cytopathicity and contained numerous viral particles, many of which were actively budding from plasma membranes. Cutaneous macrophages which were not interacting with lymphocytes did not demonstrate cytopathicity or evidence of viral multiplication. These in vivo data substantiate the concept that activation of cells which harbour latent HIV promotes viral replication as well as subsequent cytopathicity.     

Congenital ichthyosiform erythroderma: particulate staining pattern of TGK

A case of late onset non-bullous congenital ichthyosiform erythroderma (CIE) was studied. This patient was not born as a collodion baby and did not have skin abnormalities until 9-10 years of age. She gradually developed erythroderma and fine scales, callosities of her feet, and a mild ectropion. Since recent work has revealed that in the majority of CIE patients, transglutaminase (TGK) is distributed in the cytoplasm of granular cells and horny cells (11), TGK was studied in our case. It was found that TGK was distributed along the cell periphery of horny cells and also in the cytoplasm of granular cells. In the control skins, TGK was stained along the cell periphery of horny cells and granular cells. The marginal band formation was normal. Involucrine and loricrin, the building materials of the marginal band whose-cross-linking is mediated by TGK, were normally stained in the upper epidermis. Cytoplasmic TGK of granular cells and normal development of the marginal band may serve as a helpful diagnostic marker of CIE, particularly because the often confusing collodion baby of lamellar ichthyosis may lack TGK staining and the marginal band altogether.