Toshihisa Hamada

Confocal laser scanning microscopic observation of glycocalyx production by Staphylococcus aureus in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus

Summary Background Glycocalyx collapses during dehydration to produce electron‐dense accretions. Confocal laser scanning microscopy (CLSM) may be used to visualize fully hydrated microbial biofilms.

Bullous Systemic Lupus Erythematosus as an Initial Manifestation of SLE

Bullous systemic lupus erythematosus (BSLE) is a rare subset of systemic lupus erythematosus that is often associated with autoimmunity to type VII collagen. We describe a 45‐year‐old woman with BSLE who presented with vesiculobullous lesions as an initial manifestation of SLE. The patient first noticed a widespread urticarial, erythematous eruption associated with tense blisters, erosions, and crusting. She was diagnosed with bullous pemphigoid and underwent a one‐month course of treatment with betamethazone. Because of the appearance of marked proteinuria, a subsequent renal biopsy, and serological tests, the patient was diagnosed with rapidly progressive glomerulonephritis and systemic lupus erythematosus. The patients IgG circulating antibodies labeled the dermal floor of salt‐split skin and recognized type VII collagen in immunoblot studies. Although methylprednisolone pulse therapy for glomerulonephritis did not alleviate the vesicullobullous eruption, treatment with dapsone resulted in dramatic disappearance of the lesions. Cessation of dapsone therapy due to hemolysis with Heinz‐body formation did not aggravate the bullous disease. Our case illustrates that a generalized vesiculobullous eruption can be the sole presenting manifestation of SLE. It also emphasizes the close temporal relationship between BSLE and lupus nephritis.

Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance

Background  Antidesmoglein (anti‐Dsg) 3 serum antibody titres are usually correlated with the disease activity of pemphigus vulgaris (PV), but some patients retain high titres even in remission.

Retrospective analysis of 133 patients with cutaneous lymphomas from a single Japanese medical center between 1995 and 2008

In 2008, a revised World Health Organization (WHO) system of hematological neoplasm classification was promulgated. Between January 1995 and December 2008, 133 new patients with cutaneous lymphomas were seen at the dermatology clinic of Okayama University Hospital. All patients were re‐classified according to the revised WHO system. The incidence rates were analyzed and the survival was estimated. Of 133 patients, 106 (79.7%) had primary cutaneous lymphomas (PCLs) and 27 (20.3%) were skin invasion from extracutaneous origin of systemic lymphoma. Compared with several reports from western countries, “mature T‐cell and NK‐cell neoplasms” was frequent in this study (87% vs. 77 or 72%) because of the occurrence of adult T‐cell leukemia/lymphoma (ATLL) and “extranodal NK/T cell lymphoma, nasal type”, with less frequent occurrence of “mature B‐cell neoplasms” (13% vs. 23 or 28%). Estimated survival of patients with mycosis fungoides was favorable (5‐year survival rate 90.6%), but that of the patients with primary cutaneous anaplastic large cell lymphoma (C‐ALCL) was extremely less favorable than previously reported (5‐year survival rate of 47.4%).

Cutaneous lymphoma in Japan: A nationwide study of 1733 patients

Types of cutaneous lymphoma (CL) and their incidences may vary among geographic areas or ethnic groups. The present study aimed to investigate the incidences of various CL in Japan, using epidemiological data from a nationwide registration system for CL. Between 2007 and 2011, 1733 new patients with CL were registered from over 600 dermatological institutes in Japan. The 1733 patients registered included 1485 (85.7%) patients with mature T‐ and natural killer (NK)‐cell neoplasms, 224 (12.9%) with B‐cell neoplasms and 24 (1.4%) with blastic plasmacytoid dendritic cell neoplasm. Mycosis fungoides (MF) is the most common CL subtype in the present study (750 patients, 43.3%). The proportion of MF patients with early‐stage disease was 73%, similar to that of previous studies from other cohorts. The incidence rates of adult T‐cell leukemia/lymphoma and extranodal NK/T‐cell lymphoma, nasal type were 16.7% and 2.0%, respectively, which may account for the higher incidence of mature T‐ and NK‐cell neoplasms in Japan, as compared with that in the USA and Europe. A male predominance was observed in most types of CL, except for several CL subtypes such as subcutaneous panniculitis‐like T‐cell lymphoma.

Guidelines for the management of cutaneous lymphomas (2011): A consensus statement by the Japanese Skin Cancer Society - Lymphoma Study Group

In 2010, the first Japanese edition of guidelines for the management of cutaneous lymphoma was published jointly by the Japanese Dermatological Association (JDA) and the Japanese Skin Cancer Society (JSCS) – Lymphoma Study Group. Because the guidelines were revised in 2011 based on the most recent data, we summarized the revised guidelines in English for two reasons: (i) to inform overseas clinicians about our way of managing common types of cutaneous lymphomas such as mycosis fungoides/Sézary syndrome; and (ii) to introduce Japanese guidelines for lymphomas peculiar to Asia, such as adult T‐cell leukemia/lymphoma and extranodal natural killer/T‐cell lymphoma, nasal type. References that provide scientific evidence for these guidelines have been selected by the JSCS – Lymphoma Study Group. These guidelines, together with the degrees of recommendation, have been made in the context of limited medical treatment resources, and standard medical practice within the framework of the Japanese National Health Insurance system.

Phase II study of i.v. interferon-gamma in Japanese patients with mycosis fungoides

A multisite, open‐label, non‐randomized, single‐arm phase II study was conducted to evaluate the efficacy and safety profiles of interferon‐γ in Japanese patients diagnosed with stage IA–IIIA mycosis fungoides (MF). Interferon‐γ was administrated i.v. to 15 patients at a dose of 2 million Japan reference units once daily over 5 days a week for the first 4 weeks, followed by subsequent intermittent injection. The primary efficacy end‐point was the overall skin response during the study as assessed according to the evaluation criteria for chemotherapeutics for malignant skin carcinomas. Of the 15 patients, 11 (73.3%) achieved the objective response. Of the other four patients, three remained on treatment during study with stable disease and one showed disease progression. The median duration of stable disease was not reached but was 170 days or more (range, 29 to ≥253 days). As assessed according to the modified severity weighted assessment tool, nine patients (60.0%) achieved the objective response. The most common drug‐related adverse event (AE) was influenza‐like illness occurring in all patients enrolled, which did not lead to discontinuation of the study. Two serious AE were reported in two patients: aggravation of MF and aggravation of cataract, neither of which was considered directly related to the study drug. The patient with aggravation of MF died 50 days after the initiation of the study treatment. Another patient was withdrawn from the study due to drug‐related cough, which disappeared after discontinuation of the drug. Overall, interferon‐γ was effective and well‐tolerated in Japanese patients with MF.

Ichthyosiform eruptions in association with primary cutaneous T-cell lymphomas

Background  Malignant lymphoma is occasionally complicated by ichthyosiform eruptions.

Phase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma

A phase I study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of the oral histone deacetylase (HDAC) inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T‐cell lymphoma (CTCL). Six patients received vorinostat (400 mg p.o., once daily). Dose‐limiting toxicities (DLT) were evaluated in all six patients during the 28 days of the first cycle. One of the six patients who received vorinostat developed a DLT (grade 4 thrombocytopenia). The most common drug‐related adverse events included nausea (4/6, 67%), thrombocytopenia (4/6, 67%), hyperbilirubinemia (3/6, 50%) and vomiting (3/6, 50%). Most of these events were reversible and were resolved by supportive care and/or the interruption of vorinostat treatment. The safety and PK profiles of vorinostat in Japanese patients with CTCL did not appear to differ from those previously observed in non‐Japanese and Japanese patients with advanced solid tumors. None of the patients achieved an objective response in this study. However, one unconfirmed partial response and two cases of sustained stable disease for 12 weeks or longer were observed among the six patients in the study. One of the three evaluable patients experienced pruritus relief. Vorinostat was well tolerated at a dose of 400 mg p.o. once daily and showed potential efficacy in Japanese patients with CTCL, warranting further investigation.

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites.

Epstein‐Barr virus (EBV)‐associated T/natural‐killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors.