Compound heterozygosity for novel splice site mutations of ITGA6 in lethal junctional epidermolysis bullosa with pyloric atresia.

Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a rare congenital bullous disease with gastrointestinal disturbance that has been associated with mutations in ITGA6 or ITGB4 encoding the α6 or β4 subunit of integrin, respectively. Only six ITGA6 mutations in PA-JEB have been reported while many ITGB4 mutations have been identified, and all the ITGA6 mutations were homozygous. Here, we report a case of lethal type PA-JEB, in which immunofluorescence showed the lack of both α6 and β4 integrins resulting from compound heterozygous splice site mutation in ITGA6, c.

The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report.

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment.

[Dermatomycoses and medically important fungi that are necessary subjects of study for dermatology specialists -a personal experience].

Among the numerous skin diseases, dermatomycosis is the one caused by fungus (parasite) infecting the skin (host) . Once diagnosis is made, dermatomycosis can be cured with the use of appropriate anti-fungal drugs. Therefore, it is a much more easily treatable disease compareds with intractable skin diseases.

Unilateral bullous pemphigoid without erythema and eosinophil infiltration in a hemiplegic patient.

In this report, we describe an 88-year-old male stroke patient with unilateral bullous pemphigoid limited to the hemiplegic side. Physical examinations revealed multiple tense bullae with clear and/or bloody contents without apparent erythema on the right thigh and lower leg, accompanied by erosions on the right chest. Histopathologically, no eosinophils were infiltrated into and around the subepidermal bullae.

Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris.

Background: An active disease mouse model of pemphigus vulgaris (PV) was developed using the adoptive transfer of splenocytes from Dsg3(-/-) mice with a mixed C57BL/6J (B6) and 129/Sv genetic background into B6-Rag2(-/-) mice. Further immunological investigation is needed to resolve the genetic mismatch between host and recipient mice. The B6-Dsg3(-/-) mice did not grow old enough to provide splenocytes, probably due to severe oral erosions, with resulting inhibition of food intake.

Antigen-independent development of Foxp3+ regulatory T cells suppressing autoantibody production in experimental pemphigus vulgaris.

The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play suppressive roles in various types of autoimmunity. It has been reported that Tregs develop in the thymus after high-affinity interaction of their TCR with self-peptide/MHC ligands mostly utilizing TCR-transgenic system. In this study, we examined whether the specific antigen is involved in the development of polyclonal Tregs in pemphigus vulgaris (PV), an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies, as a model system.

A randomized double-blind trial of intravenous immunoglobulin for pemphigus.

Background: Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a placebo group, appropriate treatment often must be provided when the disease flares.

Objective: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of a single cycle of high-dose intravenous immunoglobulin (400, 200, or 0 mg/kg/d) administered over 5 consecutive days in patients relatively resistant to systemic steroids.

Autoreactive B-cell elimination by pathogenic IgG specific for the same antigen: implications for peripheral tolerance.

Harmful pathogenic IgG auto-antibodies are produced against desmoglein 3 (Dsg3) in pemphigus vulgaris, an autoimmune blistering disease. Dsg3 is a cadherin-type cell adhesion molecule expressed in desmosomes of the skin and mucous membranes. In AK7-transgenic mice expressing non-pathogenic AK7 IgM against Dsg3, autoreactive transgenic B cells escape from the deletion or inactivation and exist in the periphery.

G-protein-coupled receptor GPR49 is up-regulated in basal cell carcinoma and promotes cell proliferation and tumor formation.

The significance of Hedgehog (HH) signaling in the development of basal cell carcinoma (BCC) has been established. Although several target genes of HH signaling have been described previously, their precise role in tumorigenesis and cell proliferation is not yet known. To identify genes responsible for tumor formation in BCC, we screened a DNA microarray database of human BCC cases; the orphan G-protein-coupled receptor GPR49 was found to be up-regulated in all cases.

Pemphigus mouse model as a tool to evaluate various immunosuppressive therapies.

Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by immunoglobulin G (IgG) autoantibodies against desmoglein 3 (Dsg3). We have generated an active disease mouse model for PV by adoptive transfer of Dsg3(-/-) lymphocytes. In this study, we investigated the benefits and limitations of this model as a tool to evaluate various immunosuppressive therapeutic strategies.

Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris.

Autoreactive T cells are thought to be involved in the pathogenesis of autoimmune diseases, but evidence for their direct pathogenicity is almost lacking. Herein we established a unique system for evaluating the in vivo pathogenicity of desmoglein 3 (Dsg3)-reactive T cells at a clonal level in a mouse model for pemphigus vulgaris (PV), an autoimmune blistering disease induced by anti-Dsg3 autoantibodies. Dsg3-reactive CD4(+) T cell lines generated in vitro were adoptively transferred into Rag-2(-/-) mice with primed B cells derived from Dsg3-immunized Dsg3(-/-) mice.

Abnormal keratin expression in circumscribed palmar hypokeratosis.

Background: Circumscribed palmar or plantar hypokeratosis (CPH) is a rare skin disorder only recently described.

Objective: To determine the diagnostic features and to provide insight into the pathogenesis of CPH, with analysis of two new Japanese cases.

Methods: Dermoscopy, immunohistochemistry, electron microscopy, polymerase chain reaction amplification for human papillomavirus (HPV) DNA and 16S microbial rRNA gene profiling were conducted.

Dose-finding comparative study of 2 weeks of luliconazole cream treatment for tinea pedis--comparison between three groups (1%, 0.5%, 0.1%) by a multi-center randomised double-blind study.

Luliconazole is a newly developed imidazolyl antifungal agent. A randomised double-blind comparative study was designed to assess the efficacy and safety of 1% luliconazole cream (group A), 0.5% cream (group B) and 0.

A history of Japanese dermatology: past, present and future.

On the occasion of the 14th Korea-Japan joint meeting of dermatology, the founding of the Japanese Dermatological Association, its activities and relationship to neighboring societies were presented to let both Korean and Japanese participants know the current status of Japanese dermatology. It is felt that one central meeting in Asia will be necessary to make a strong impact on not only Asian but also Western colleagues. We should make more of an effort to get used to our common international language, English, so that we can communicate with other Asian colleagues more closely and in more depth in this era of increasing globalization.

T helper type 2-biased natural killer cell phenotype in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoantibody-mediated bullous disease, but the role of natural killer (NK) cells in its pathogenic process has never been examined in detail. Circulating CD56+ CD3- NK cells as well as CD69+-activated NK cells were increased in PV patients compared with healthy controls and patients with other autoantibody-mediated autoimmune diseases, including immune thrombocytopenic purpura and myasthenia gravis. Gene expression analysis of highly purified NK cells demonstrated an increased expression of IL-10 and decreased expression of IL-12Rbeta2, perforin, and granzyme B ex vivo in PV patients versus healthy controls.

A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis.

The aim of the study was to compare the efficacy and safety of luliconazole 1% cream and bifonazole 1% cream as applied in the treatment of tinea pedis (interdigital-type and plantar-type). A multi-clinic, randomised single-blind, parallel group study with 34 hospitals and 11 clinics formed the study design. Five hundred and eleven patients with mycologically confirmed tinea pedis were included.

Tolerance induction by the blockade of CD40/CD154 interaction in pemphigus vulgaris mouse model.

Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by IgG autoantibodies against desmoglein 3 (Dsg3). We have recently developed an active disease mouse model for PV by adoptive transfer of splenocytes from Dsg3(-/-) mice. The purpose of this study was to determine the role of CD40/CD154 interaction in the pathogenic antibody production and development of the disease in PV model mice.

Additive contribution of multiple factors in the development of pneumatosis intestinalis: a case report and review of the literature.

We describe a 53-year-old patient with dermatomyositis, who developed pneumatosis intestinalis (PI) accompanied by pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema of the neck. The development of PI in our patient was possibly attributed to the effect of factors such as dermatomyositis, corticosteroids, methotrexate, and alpha-glucosidase inhibitor (AGI). The coexistence of multiple factors associated with PI might enhance the risk of developing PI, even though each of them alone is not sufficient to induce it.

Skin diseases described in Japan 2004.

During the last century of modern dermatology, more than 30 skin diseases have been described first by physicians from Japan. Many of those conditions were disorders of pigmentation and keratinization, which are quite common in Oriental patients. Since the late 1940s, a number of skin diseases first reported in Japan have gained attention internationally among them being Kimura disease, hypomelanosis of Ito, Kawasaki disease, adult T-cell leukemia/ lymphoma, eosinophilic pustular folliculitis, prurigo pigmentosa, and Ofuji's papuloerythroderma.

Detection of potentially novel bacterial components of the human skin microbiota using culture-independent molecular profiling.

Although the micro-organisms forming the cutaneous microbiota are considered to play important roles in the modification and prevention of skin diseases, a comprehensive analysis of their composition has not yet been carried out because of difficulties in determining yet-to-be-cultured micro-organisms in the samples. Swab-scrubbed forehead skin samples of five healthy volunteers were analysed by profiling 16S rRNA genes, as well as by conventional culture methods, to provide a profile of the cutaneous microbiota that included yet-to-be-cultured bacteria from normal human skin. Cluster analyses of the 16S rRNA gene sequences indicated a marked increase in diversity compared with that derived from the culture methods.

Systemic sclerosis with unusual panniculitis and overlying discoid lupus erythematosus-like lesions.

A 33-year-old men presented with systemic sclerosis accompanied by both unusual panniculitis and overlying discoid lupus erythematosus (DLE)-like skin changes on the left buttock. The lesion did not completely match either lupus erythematosus profundus or morphea profunda but featured clinical and pathological findings halfway between the two entities. No case report of co-existence of systemic sclerosis and morphea profunda was found in the literature, but there are three case reports of patients with systemic sclerosis and lupus erythematosus profundus.

Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene.

Background: Mucormycosis is an invasive opportunistic infection caused by fungi belonging to the order Mucorales. Due to the lack of laboratory tests, the diagnosis of mucormycosis is notoriously difficult. Added with its rapid progression as well as the debilitated state of the patients who contract the disease, mortality is extremely high.

Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy.

Background: Pemphigoid gestationis (PG) is a rare pregnancy-associated subepidermal immunobullous disease that targets hemidesmosomal proteins, particularly BP180. Clinically, PG can resemble the eruption known as polymorphic urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation between these 2 pruritic pregnancy dermatoses has important implications for fetal and maternal prognoses. Results of epitope mapping studies show that IgG autoantibodies in up to 90% of PG serum samples target the well-defined membrane-proximal NC16a domain of BP180.

Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis.

Objective: To identify novel autoantibodies specific for dermatomyositis (DM), especially those specific for clinically amyopathic DM (C-ADM).

Methods: Autoantibodies were analyzed by immunoprecipitation in 298 serum samples from patients with various connective tissue diseases (CTDs) or idiopathic pulmonary fibrosis (IPF). Antigen specificity of the sera was further examined by immunoblotting and indirect immunofluorescence (IF).