Nobuyasu Mayuzumi

A case of chromomycosis caused by Fonsecaea pedrosoi and a review of reported cases of dematiaceous fungal infection in Japan

We report a case of chromomycosis caused by Fonsecaea pedrosoi that developed in the left buttock of a 63‐year‐old female farmer. About 4 years ago, the patient developed erythema in the left buttock, which gradually spread. At the first consultation, we noted a well‐defined, red‐brown, infiltrated erythematous plaque (8 × 6 cm). Histopathological examination revealed a granulomatous lesion, containing sclerotic cells, associated with giant cells in the upper dermis. The causative fungus was difficult to identify due to low conidiogenesis, but was eventually identified by slide culture as F. pedrosoi. Excision and skin graft were performed, and no recurrence has been observed after 2 years. In Japan, 212 cases of dematiaceous fungal infection were reported in the period from 1982 to 2001. The causative fungus was F. pedrosoi in the majority of cases (126/212; 66%), followed by Exophiala jeanselmei (36/212; 19%). Similar incidence of dematiaceous fungal infection was reported in male and female patients. The upper limbs were affected most frequently in both male and female patients. Ten cases were associated with visceral lesions.

Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1

Summary  Background  Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases.

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes

Background  Dariers disease (DD) and Hailey–Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids.

A Japanese case of de novo dominant dystrophic epidermolysis bullosa

Summary We report a Japanese case of dominant dystrophic epidermolysis bullosa with a de novo mutation in the triple‐helical domain of the type VII collagen. Mutation detection revealed a glycine → aspartic acid substitution at amino acid position 2012 in exon 73 (G2012D). This previously unreported mutation underlies a clinical phenotype of moderately severe, localized skin blistering.

SCCA2-transfected human keratinocytes show increased secretion of IL-1α and IL-6, but not of TNF-α

Psoriasis is a common skin disease characterized by epidermal hyperproliferation, capillary dilatation, and the presence of acute and chronic inflammatory cells in both the dermis and epidermis [1, 2]. A unifying hypothesis that accounts for the wide range of clinical characteristics of psoriasis highlights the role of cytokines in the etio-pathophysiology of this disease [8]. Epidermal cells, particularly keratinocytes, may play a central role in transmitting pro-inflammatory signals by the secretion of cytokines and growth factors [7]. The production of these factors, in particular IL-1 is usually very low, but can be induced significantly by various injurious agents, such as endotoxin, virus particles, tumor promoter or UV light [6, 7]. Both IL-1a and c are expressed in human keratinocytes, although the major isotype secreted is IL-1a [6]. IL-1 and TNF-a in their turn act with an autocrine mechanism on keratinocytes to induce the release of a cascade of other cytokines with pro-inflammatory or chemotactic activity (IL-6, IL-8) [3]. All of these mentioned cytokines have been detected in psoriatic lesions. In addition to these observations, Takeda et al. [11] reported that SCCA2, the member of serine proteinase inhibitor family (serpin) is the major inducible SCCA in psoriatic skin. They found that SCCA2 was expressed in stratum corneum, subset of spinous layer cells and dermal infiltrated cells [11]. The level of SCCA2 is significantly increased in the sera of psoriatic patients, compared with non-psoriatic individuals [4], and probably be due, at least in part, to the production of cytokines in psoriatic tissues. Moreover, recent study suggested that the expression of SCCA in keretinocytes may be participated in the growth of keratinocytes and their differentiation [11]. Since keratinocytes can secrete TNF-a, IL-1a, and IL-6, and since these molecules have been detected in psoriatic skin, the goal of this study was to test whether the expression of SCCA2 in human keratinocytes plays a role in modulating expression of these cytokines. Commercially available human epidermal keratinocytes (Kurabo, Japan) were grown in supplemented low calcium medium and were sub-cultured at 60–70% confluence to avoid differentiation. A SCCA2 construct consisting of the SCCA2 coding region cloned in to the p3XFLAG-myc-CMV-26 vector (Sigma) has been described elsewhere [12]. The vector [p3XFLAG-mycCMV-26 (Sigma)] without SCCA2 was transfected into the keratinocytes as a control. The SCCA2 construct or the control vector was transfected into human keratinocytes using lipofectamine reagent (Sigma) according to the manufacturer’s instructions. TNF-a, IL-1a, and IL-6 concentrations in the culture media were measured by using ELISA kits (R&D Systems Inc., USA) according to the manufacturer’s instructions. SCCA2 expression in transfected cell was determined by Western blot analysis using anti-SCCA antibody (Sigma). The statistical analysis was performed using Student’s t test, and P<0.05 was considered to be significant. The results are shown as mean ± standard deviation (SD). To show SCCA2 expression in cells transfected with the SCCA2 construct, cell lysates were subjected to Western blot analysis. SCCA2 expression was detected in cells transfected with the SCCA2 construct (Fig. 1a, lane 1) but not in cells transfected with vector alone (Fig. 1a, lane 2). Figure 2b shows a control blot using non-immunized mouse IgG. There is no conflict of interest in this manuscript.

Recurrent R156H mutation of KRT10 in a Japanese family with bullous congenital ichthyosiform erythroderma

Recently, mutations of keratin 1 gene (KRT1) and keratin 10 gene (KRT10) have been reported in various patients with bullous congenital ichthyosiform erythroderma (BCIE). The substitution of arginine (R) to histidine (H) at amino acid residue 156 (R156H) of coiled 1A region is one of the most frequent mutations of KRT10. In this study, we searched for a mutation in KRT1 and KRT10 in a Japanese family with BCIE and detected mutation R156H in KRT10. Our search led to the detection of R156H. This mutation was not detected in 50 normal individuals. These results confirmed that codon 156 is a frequently mutated site, and that R156H in KRT10 is likely also to be a mutation hotspot in Japanese patients with BCIE.

Immunoglobulin A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in a patient with atypical bullous pemphigoid.

Bullous pemphigoid is an autoimmune subepidermal blistering disease associated with autoantibodies against BP180 and BP230. We report herein a rare case of bullous pemphigoid with newly formed annular erythematous lesions when bullous skin lesions were in remission. Various immunological studies revealed immunoglobulin (Ig)A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in addition to IgG antibodies against BP180 and BP230. These clinical and immunological changes in a patient are a rare event, suggesting an epitope‐spreading phenomenon.