Yoshinori Umezawa

Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan

Oculocutaneous albinism (OCA) is a complex genetic disease with great clinical heterogeneity. Four different types of OCA have been reported to date (OCA1, OCA2, OCA3, and OCA4). MATP was recently reported in a single Turkish OCA patient as the fourth pathological gene, but no other patients with OCA4 have been reported. Here, we report the mutational profile of OCA4, determined by genetic analysis of the MATP gene in a large Japanese population with OCA. Of 75 unrelated patients that were screened, 18 individuals (24%) were identified as having OCA4; they harbored seven novel mutations, including four missense mutations (P58S, D157N, G188V, and V507L) and three frameshift mutations (S90CGGCCA-->GC, V144insAAGT, and V469delG), showing that MATP is the most frequent locus for tyrosinase-positive OCA in Japanese patients. We discuss the functional melanogenic activity of each mutant allele, judging from the relationship between the phenotypes and genotypes of the patients. This is the first report on a large group of patients with OCA4.

Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity.

Generalized pustular psoriasis (GPP) is a rare but notoriously recalcitrant cutaneous diseases. Therefore, there have been few reports of more than ten patients with GPP who were treated at the same institution. The severity of this disease and its response to each therapeutic modality vary among patients. In some GPP is life-threatening, but in others it may show a benign, chronic course for a long period of time. Before starting treatment, a knowledge of the therapeutic efficacy and side effects of each drug used in the treatment of GPP is necessary. In our multicenter study, we compared the effectiveness of and adverse reactions to several systemically administered drugs. Following the development of a unique classification of the disease severity based on scoring the clinical symptoms and the laboratory findings, we propose here therapeutic guidelines for the treatment of GPP.

Optimal time for therapeutic drug monitoring of cyclosporine microemulsion in patients with psoriasis.

Backgroundu2002 The clinical usefulness of cyclosporine in patients with psoriasis has generally been established; however, modification of the dosage on the basis of therapeutic drug monitoring is needed to prevent potential adverse reactions. The area under the drug concentration–time curve from 0 to 4 h after treatment (AUC0−4), used to assess the pharmacokinetics of cyclosporine microemulsion, correlates with clinical symptoms and adverse reactions.

Preprandial vs. postprandial pharmacokinetics of cyclosporine in patients with psoriasis.

Backgroundu2002 Cyclosporine is usually administered after meals. Preprandial administration of cyclosporine has been shown to enhance drug absorption in patients with nephritic syndrome.

Seborrheic keratosis that follows Blaschko's lines

A 66‐year‐old Japanese man had skin lesions on the left side of his trunk and the left upper extremity for approximately 10 years. The skin lesions were asymptomatic but increased gradually, which brought the patient to our hospital. On the initial examination, we noticed 5 mm × 5 mm to 15 mm × 5 mm, round or oval, light to dark brown keratotic papules on the left side of chest and abdomen and the left upper extremity. The papules were aligned in an S‐shaped line on the trunk and in a straight line on the upper extremity. Clinical and histopathological findings led to a diagnosis of seborrheic keratosis that followed Blaschkos lines. To our knowledge, no such a case has been reported previously. Our case supports the hypothesis that seborrheic keratosis can be associated with genetic mosaicism.

Generalized Pustular Psoriasis in a Child: Observation of Long-Term Combination Therapy with Etretinate and Calcipotriol for 16 Years

Abstract:u2002 Generalized pustular psoriasis (GPP) is a rare condition in young children. It is difficult to treat and may require long‐term systemic therapy. We report the long‐term course of a 3‐year‐old boy whose onset of psoriasis dated to age 7u2003months. He was treated with etretinate and psoralen plus ultraviolet A therapy initially and then with etretinate alone, and at age 12, topical calcipotriol was added. At the age of 19, he had been taking oral retinoids for 16u2003years, with a mean dose of etretinate of 0.22u2003mg/kg per day, a total amount of approximately 37 g, without evidence of stunted growth, ligamentous calcification, hyperostosis, or hepatic toxicity.

A case of blastic NK-cell lymphoma.

© 2007 The International Society of Dermatology 722 The patient was a 64-year-old Japanese man. He first visited our department on April 23, 2004 with an eruption on his anterior chest of 2 months’ duration as the chief complaint. The visit was preceded by consultation with a local physician who took a skin biopsy when the eruption gradually increased in size. On the basis of the pathologic findings, the patient was diagnosed with cutaneous malignant lymphoma and, as a result, was referred to our department for further testing and treatment. The patient presented with a semicircular, purplish-red lesion measuring approximately 5 cm in diameter, with a clear border, on the anterior chest. Irregularities of up to several millimeters in size were observed on the surface of the lesion, which appeared mostly glossy (Fig. 1a). In addition, diffuse, partially fused, semicircular erythematous patches accompanied by reddish to reddish-brown discoloration were present on the face and extending to the upper body (Fig. 1b). The cervical and supraclavicular lymph nodes were swollen. Hematologic findings on admission (Table 1) revealed a differential peripheral white blood cell count of 1.0% lymphoma-like cells and slightly elevated lactate dehydrogenase (LDH) levels of 238 U/L. Levels of LDH2 and LDH3 were elevated at 41.0 and 28.0%, respectively. Furthermore, the level of interleukin-2R (IL-2R) was elevated at 610 U/mL. The patient had a history of Epstein–Barr (EB) virus infection. The results of various tests (Table 2) showed bilateral enlargement of the posterior cervical, supraclavicular, cervical, axillary, portal, and inguinal lymph nodes. No tumor was seen from the nose to the neck. Gallium scintigraphy showed no accumulation. A skin biopsy of the lesion on the anterior chest was performed, with histopathologic evidence indicating the existence of a tumor exhibiting a Grenz zone and infiltration into all dermis layers. The tumor consisted of large blastoid atypical lymphocytes (Fig. 2a,b). The results of a biopsy of a semicircular erythematous patch on the right upper arm were similar. Immunohistological staining with in situ hybridization showed that the tumor cells were CD4-positive, CD56-positive, CD34-negative, CD68-negative, myeloperoxidase (MPO)negative, terminal deoxynucleotidyl transferase (TdT)negative, and EB-negative. Rearrangement of the T-cell receptor (TCR) Cβ1 and IG(H)JH genes was not observed in dermal tissue. The cervical lymph nodes were biopsied and flow cytometry was conducted. Tumor cells in the lymph nodes were CD4positive and CD56-positive. Bone marrow biopsies confirmed the diagnosis: CD4-positive, CD56-positive, CD34-negative, and CD13-negative. On the basis of the aforementioned clinical and histopathologic findings, the patient was diagnosed with blastic natural killer (NK)-cell lymphoma. One week after hospitalization, the lesion on the anterior chest and the erythematous patches from the face to the chest exacerbated, and the patient was placed on a hyper-CVAD regimen (300 mg/m of cyclophosphamide, 2 mg of vincristine, 25 mg/m of doxorubicin, 40 mg of dexamethasone, 1000 mg/m of methotrexate, and 1000 mg/m of cytarabine), with the lesion and erythematous patches mostly disappearing after two cycles of the regimen (Fig. 3). Blackwell Publishing Ltd Oxford, UK IJD nternational Jour al of Dermatology 0011-9059 , 2006 45 Morphology

Relationship between lymphocyte cyclosporin sensitivity and clinical progress of psoriasis

Cyclosporin (CYA) is a therapeutic agent used in the treatment of psoriasis vulgaris. However, the effectiveness of CYA therapy varies among patients. In the present study, due to the fact that CYA mainly acts on lymphocytes, we hypothesized that a measurement of the sensitivity of lymphocytes to CYA in vitro (IC50) could be applied to patients with psoriasis vulgaris to determine therapeutic success. We measured IC50 levels of 32 patients presenting with psoriasis prior to CYA administration, and classified them into three groups according to IC50 levels: favorable, moderate and low sensitivity. CYA sensitivity levels were correlated with the degree of improvements in psoriasis area and severity index (PASI) scores, CYA dosage and occurrence of side-effects (hepatopathy and nephropathy). Results showed the degree of improvement in PASI scores differed significantly between the favorable and low sensitivity groups (P < 0.05). Furthermore, CYA dosage was lowest in the favorable sensitivity group and highest in the low sensitivity group. Moreover, hepatopathies and nephropathies were detected in the low and moderate sensitivity groups, but not in the favorable sensitivity group. These results suggest that the effectiveness of CYA therapy as a treatment of psoriasis vulgaris is affected by the sensitivity of lymphocytes in each patient.

A case of implantation dermatosis that formed a tumor

A 51‐year‐old man visited our hospital complaining of a tumor located above his lip. He had been hit on his upper left lip by a chopstick holder 2 months previously. The lesion turned into a tumor and gradually enlarged. The tumor was well circumscribed, smooth and covered with reddish, partially milk‐white skin. During surgery to remove the tumor, a piece of a chopstick was found in the subcutaneous tissue, and a diagnosis of implantation dermatosis (ID) was made. On histology, the tumor appeared as an abscess that had increased fibroblasts, small vessels and a large number of neutrophils. In the Japanese published work, we found 86 cases of ID; three were similar to our case and had been clinically diagnosed as adnexal tumors. There were also six cases that showed abscess formation similar to our case on histology. In a survey of the published work from other countries, there were 44 ID cases. There were no common features found among the cases reported in the published work.