Shigenori Muramatsu

Amnia for intractable skin ulcers with recessive dystrophic epidermolysis bullosa : Report of three cases

Recessive dystrophic epidermolysis bullosa (RDEB) is a disease characterized by recurrent blistering and chronic ulceration of the skin. In these patients, recurrent blisters frequently result in intractable skin ulcers due to impaired wound healing caused by mutations in the type VII collagen gene and malnutrition as well as by increased collagenase activity. To evaluate the efficacy of amnia for intractable ulcers in RDEB, we treated RDEB patients with amnia. The amniotic membrane was simply placed on the cleansed wound surface. The procedure was repeated once a week for up to 10 weeks. As a result, wound conditions improved remarkably after treatment with amnia for 2–10 weeks in all the patients, resulting in total re‐epithelization of the ulcers. Amnia could be an effective therapy for intractable skin ulcers in RDEB patients, and should be considered as a re‐emerging therapeutic option for the disease.

An allogeneic cultured dermal substitute suitable for treating intractable skin ulcers and large skin defects prior to autologous skin grafting: three case reports.

Intractable skin ulcers that arise as secondary lesions from disease and full‐thickness skin defects that result from skin tumor excision often need autologous skin grafting to close the wound. We developed an allogeneic cultured dermal substitute (CDS) to shorten the time needed to prepare a wound bed suitable for autologous skin grafting. The CDS was prepared by plating normal human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelo‐collagen. The allogeneic CDS was then placed on the rinsed wound surface. This procedure was repeated twice a week for up to five weeks, until the wounds were closed by autologous skin grafting. In all three cases, after CDS treatment for two to five weeks, the wound conditions became suitable for skin grafting; these conditions had not been improved by conventional topical treatments, including topical basic fibroblast growth factor (bFGF). Healthy granulation tissue developed rapidly, concomitant with wound size reduction. The present results indicate that CDS is an excellent biological wound dressing for improving wound conditions so that they are suitable for subsequent autologous skin grafting as well as for shortening the treatment duration for skin ulcers and full‐thickness skin defects.

Intractable venous leg ulcer treated successfully with allogeneic cultured dermal substitute.

Venous leg ulcers are resistant to various treatments, including autologous skin grafting. We applied an allogeneic cultured dermal substitute in a patient with such a wound, and the wound improved, healthy granulation tissue formed, and the size of the wound was reduced.

A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene

We report a 6‐month‐old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cows milk and egg IgE antibodies by radioallergosorbent tests. Trypsin‐like hydrolytic activity in the patients lesional stratum corneum showed an activity seven times higher than that in age‐matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G→C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.

Psoriasiform and palmoplanter pustular lesions induced after Kawasaki disease

A 7‐month‐old boy was referred to us because of psoriatic lesions on the bilateral cheeks and on the extensor region of the left upper arm at the same site of his vaccination for tuberculosis 4 months previously ( Fig. 1a,b ). He also presented with small pustules scattered on the palms and soles ( Fig. 1c ).

A case of diffuse plane normolipemic xanthomatosis associated with pancytopenia and monoclonal gammopathy.

We report a case of diffuse plane normolipemic xanthomatosis (DPNX) which showed poorly demarcated, uncommon, yellow macules symmetrically distributed on the nape, axillae and inguinal folds accompanied by severe, persistent itching. Histopathological and ultrastructural studies of skin biopsy specimens revealed the existence of some foamy cells and the deposition of neutral fat in the upper papillary dermis. Laboratory investigations and bone marrow aspirate smears showed that our patient had myelodysplastic syndrome (MDS) associated with pancytopenia and monoclonal gammopathy of undetermined significance. Because our patient had neither a malignant hematological disorder nor a severe systemic disease, monoclonal gammopathy might explain the pathogenesis of DPNX in the present case.

Recurrent E413K Mutation of hHb6 in a Japanese Family with Monilethrix

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. This disorder has been reported to be caused by mutations in the helix termination motif of two type II cortex keratins, hHb1 and hHb6. Here we describe a Japanese monilethrix family that has the most frequent mutation, the E413K mutation in hHb6, so far found in 26 families. Genotype/phenotype correlation was not obvious in our case or in the previously reported cases.

Differentiation-specific expression and localization of an autophagosomal marker protein (LC3) in human epidermal keratinocytes

Fig. 1 Western-blot and immunohistochemical analyses o cultured human keratinocytes. (A) The top panel shows the the arrows) in the whole-keratinocyte extracts obtained from differentiation in the presence of E64d and pepstatin A (10 mg/ expression during keratinocyte differentiation. Keratin 10 wa weight markers are indicated on the left. (B) The upper (a—c tochemical staining on days 0 and 7 after calcium-induced dif show the pattern of immunohistochemical staining with anti-LC with FITC (green); (c) and (f) show overlays of (a) and (b), and undifferentiated (day 0) and differentiated (day 7) keratin keratinization. In the merged images (Merge), the red color represents the fluorescence of anti-keration 10 antibody, and magnification shows the LC3 distribution in the cytoplasm of around the nuclei of the normal human keratinocyte cells (p immunofluorescence image of differentiated keratinocytes o Macintosh Power PC G4 using the ImageJ software (http://rsb. line square in (a). Note the presence of LC3-positive rings in aggregation of keratin filaments, and formation of the cornified cell envelope. Therefore, cellular homeostasis of keratinocytes requires a constant balance to be maintained between biosynthetic and catabolic processes. In regard to the catabolic processes, recent studies have revealed that all eukaryotic cells primarily use two distinct mechanisms for large-scale degradation; one mediated by the proteasome [1], and the other involving autop-

R156C mutation of keratin 10 causes mild form of epidermolytic hyperkeratosis

A 37‐year‐old Japanese male presented to us with persistent asteatotic skin with mild erythema on the trunk and extremities. Skin biopsy from the left knee showed marked epidermal acanthosis and hyperkeratosis, and milder granular degeneration. Ultrastructural analysis revealed clumping of the keratin filaments within suprabasal keratinocytes of the epidermis. Following direct sequencing, we found a single nucleotide substitution in one allele at the residue position 466 of the 1A rod domain segment (CGC to TGC, arginine to cysteine; R156C) in keratin 10. Clinical manifestations and molecular analysis indicated that R156C mutation in keratin 10 gene (KRT10) causes a mild form of epidermolytic hyperkeratosis (EHK) in the presented case.

A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome.

We report a 6‐day‐old Japanese girl showing generalized erythroderma accompanied by yellowish, exfoliative scaling that was accentuated on the face and scalp. Histological analysis showed psoriasiform dermatitis with acanthotic epidermis and premature shedding of the stratum corneum. Measurement of trypsin‐like hydrolytic activity in SC showed six‐fold greater activity compared with age‐matched controls. DNA analysis revealed two mutations, 375delAT and 966insC, in exons 5 and 11, respectively, of the SPINK5 gene. Although at 4 weeks the child was still too young to display characteristic hair abnormalities or atopic diathesis, we diagnosed Netherton syndrome based on enzyme assay and DNA analysis.