Hiromitsu Shimada

Association between HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303 alleles and lamotrigine-induced cutaneous adverse drug reactions. A pilot case-control study from Japan

BACKGROUND Human leukocyte antigen (HLA) genotypes in lamotrigine -induced (LTG-induced) cutaneous adverse drug reactions (cADRs) have been described in several reports but controversy remains even for a given ethnic group. We attempted to clarify a possible association between LTG-induced cADRs and HLA alleles in Japanese patients. METHOD Sixteen subjects, including eight patients with LTG-induced cADRs and eight LTG-tolerant controls were included in this study. All eight patients with LTG-induced cADRs gave positive results in a drug-induced lymphocyte stimulation test (DLST) with LTG. We performed HLA-typing for HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1, using PCR with sequence-specific oligonucleotide probes and multiple analyte profiling (xMAP) technology (Luminex System; Luminex Corporation, Austin, TX). We examined differences between allele frequencies in our two groups of subjects and the allele frequencies in the general Japanese population. RESULTS The frequencies of HLA-DRB1*0405, and HLA-DQB1*0401 alleles were higher in our LTG-cADRs patients than the reference frequencies in the general Japanese population. We also detected HLA-DQA1*0303 frequently in our LTG-cADRs patients, but data for this allele in the Japanese population was not available. Our observation was presumably due to the linkage disequilibrium among the three alleles. The haplotype frequency of HLA-DRB1*0405, DQB1*0401 and DQA1*0303 in our LTG-cADRs subjects was also different from the corresponding haplotype frequency in the database for the Japanese population and the difference was statistically significant. One patient with the HLA-DRB1*0405, -DQB1*0401 and DQA1*0303 haplotype was safely re-treated with LTG after results of a DLST with LTG ceased to be positive about 4 months after discontinuation of LTG. LIMITATIONS Our analysis included only 16 patients. Associations between LTG-induced cADRs and specific HLA loci will have to be confirmed in larger studies. CONCLUSIONS LTG-induced cADRs are associated with HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303.

A case of concurrent pemphigoid vegetans and pemphigus vegetans resolving without oral corticosteroid

of jet injector and the parameters used among various studies. The amount of pain can be reduced with the use of appropriate parameters. Pain severity correlates with the jet’s depth of penetration. We have observed that low driving pressure, low volume per spurt, smaller nozzle diameter and a longer distance (2–3 mm) between the tip of the nozzle and skin surface allow more superficial penetration of the jet into the skin. A low-pressure jet injector provides rapid, adequate and painless anaesthesia for a variety of dermatological procedures. The lack of needle use and the rapidity of the procedure reduce apprehension in the needle-phobic patient. For needle-phobic patients, the direct injection of BTX-A into the palms with the needle-free injector is also a justifiable option despite a 5–10% waste of BTX-A occurring through splash and splatter. Traditional jet injectors, such as Dermojet , have fixed driving pressures due to their spring-loaded mechanism. They are high-pressure devices with driving pressure varying between 1400 and 2000 psi. These devices do not work universally on different areas of the body and some manufacturers even warn against their use on the hands and fingers. Driving pressures used in our practice do not usually exceed 140 psi, which is at least 10 times lower than the driving pressure used in traditional jet injectors. Complications with higher-pressure traditional injectors include pain and considerable harm to vital nerves and vessels. The disadvantages of jet injection with the lowest possible pressure (140 psi) capable of inducing a subepidermal weal are minimal. The risk of infection is low with disposable anticontaminant devices and spacers combined with the use of advanced sterilization techniques. Soaking the hands in lukewarm water for 5–10 min helps induce a subepidermal weal with lower pressures. The driving pressure should be increased only when the weal fails to appear. At that time, it can be increased by increments of 10 psi until the anaesthetic weal becomes visible or a tiny blood spot appears into which BTX-A can be injected in a painless manner. The versatility of the pressure settings is because the new jet injectors are powered by carbon dioxide, which allows delivery of the injectate at the desired depth. Using a sterile jet injector on each patient avoids transmission of infection between patients. Because needle phobia is prevalent and has remained a therapeutic challenge, the importance of embracing needle-free injection systems in dermatology cannot be overemphasized.

Cutaneous horn malignant melanoma

A 73-year-old Japanese woman presented with cutaneous horn on the right cheek. The resected tumor was 9 mm in diameter, with 14 mm protrusion, and showed exophytic growth with marked papillomatosis. Histopathology showed proliferation of atypical melanocytes with melanin pigments in the epidermis and dermis under the cutaneous horn. These cells were confined to the base of the cutaneous horn, and did not spread to the surrounding epidermis. The final diagnosis was cutaneous horn malignant melanoma. This pathological entity is considered a specific form of verrucous melanoma, and might be added to the list of cutaneous horn-forming lesions.

Case of malignant melanoma that developed the ability to secrete granulocyte colony-stimulating factor.

tory of erosion on her left nipple. Physical examination revealed a reddish nodule measuring 10.7 mm 9 9.8 mm 9 8.0 mm with an erosive surface on her left nipple (Fig. 1a). Breast palpation failed to reveal any masses except for the nodule on her nipple. However, magnetic resonance imaging revealed limited dilation of lactiferous ducts in the upper medial part of her left breast, which was separated from her nipple. A biopsied specimen from her nipple revealed an ill-defined dermal tumor composed of a collection of ductal structures of varying shapes and sizes (Fig. 1b,c). These structures were lined with two distinct types of epithelial cells: myoepithelial cells lining the outer edge of the ductal structure, and cuboidal cells facing the lumen with frequent apocrine snouts. Mild atypia, with variation in size and shape, and hyperchromatic nuclei with prominent nucleoli were observed (Fig. 1c). Immunohistochemically, more than half the tumor cells were positive for 5-hmC (73.0 3.9%) (Fig. 1d). We diagnosed it as EAN and performed a tumor resection with preservation of her left nipple. Mild atypicality was also found in a vacuum-assisted biopsy specimen from the dilated lactiferous ducts. Wide local excision was performed. Histopathologically, mildly atypical epithelial cells formed a cribriform architecture within the ductal structure (Fig. 1e). The ratio of 5-hmC-positive cells was less than 10% (Fig. 1f). We diagnosed it as ductal carcinoma in situ (DCIS). In case 2, a 44-year-old Japanese woman had a 4-month history of bloody discharge from her left nipple. Physical examination revealed a well-defined erosion without induration (Fig. 1g). A biopsied specimen showed ductal structures consisting of two cell types: myoepithelial cells and epithelial luminal cells (Fig. 1h). Immunohistochemically, more than the tumor cells were positive for 5-hmC (83.5 2.9%). We diagnosed it as EAN and performed a tumor resection with preservation of her left nipple. Erosive adenomatosis of the nipple is a benign mammary proliferation that may be misdiagnosed as breast cancer, especially DCIS. DCIS is a malignant proliferation of cells within the basement membrane-bound structures. Immunostaining of several proteins, including carcinoembryonic antigen, vimentin and muscle-specific actin, has been used to aid diagnosis. The results of this staining are reliable, but not absolute. Levels of 5-hmC are dramatically reduced in a broad spectrum of human cancers. Immunohistochemically, fewer than 10% of tumor cells in breast cancer are 5-hmC-positive (Prof. Ken-ichi Ito, 2015, unpubl. data). We noted a clear difference in the proportion of 5-hmC-positive tumor cells between EAN and DCIS, implying that the presence of 5-hmC will be useful for the diagnosis of EAN.

Lichen planus pemphigoides concomitant with rectal adenocarcinoma: fortuitous or a true association?

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease with clinical and histopathological features of lichen planus and bullous pemphigoid [1]. LPP has a benign course and does not need aggressive therapy, particularly in younger patients. LPP is more frequently idiopathic and it is known to be associated with drug intake or infections, but rare case associated with neoplasmshave also been reported [1, 2]. We report a case of LPP in association with rectal adenocarcinoma.An 81-year-old [...]

Pustular psoriasis occurring after total colectomy for ulcerative colitis and relieved by administration of infliximab

Shin-ichi ANSAI, Shiho HASHIZUME, Seiji KAWANA, Chiharu TATEISHI, Hiroshi KOGA, Takashi HASHIMOTO Division of Dermatology, Nippon Medical School Musashi Kosugi-Hospital, Kawasaki, Department of Dermatology, Nippon Medical School, Tokyo, Department of Dermatology, Osaka City University School of Medicine, Osaka, and Department of Dermatology, Kurume University School of Medicine, and Kurume Univerisity Institute of Cutaneous Cell Biology, Kurume, Japan

Blistering disease associated with diffuse large B-cell lymphoma but without autoantibodies.

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A case of cutaneous tuberculosis: a clue to diagnosing miliary tuberculosis

The incidence of tuberculosis in Japan remains higher than in western countries and more than 20,000 new patients were registered with this disease in Japan in 2011 [1]. We report the case of an 84-year-old female who presented with a subcutaneous nodule in her nose that provided a clue to diagnosing miliary tuberculosis.In September 2014, the patient complained of a symptomless nodule on the left side of the root of her nose. She had suffered from rib caries when she was 28 years old. She had lost [...]

CRTC1-MAML2 gene fusion in G-CSF-secreting mucoepidermoid carcinoma: an indicator of favourable prognosis?

Mucoepidermoid carcinoma (MEC) is histologically characterised as low-, intermediate-, and high-grade [1]. Low-grade tumours rarely transform into high-grade tumours (dedifferentiation) [2, 3] and the latter very rarely produce granulocyte colony stimulating factor (G-CSF) [4, 5]. MEC harbours a characteristic t(11;19)(q21;p13) translocation; this rearrangement results from the fusion between exon 1 of the gene for CRTC1 (cyclic AMP/cyclic AMP-responsive element-binding protein-regulated transcription [...]

Comparative analysis of mamushi (Gloydius blomhoffii) bite patients indicates that creatinine kinase levels/white blood cell count trends reflect severity

There has been no indicator that allows an early quantitative evaluation of the severity of a mamushi snake (Gloydius blomhoffii) bite. Because the number of severe mamushi bite cases is much fewer than non‐severe cases, a formal case–control study is difficult. Therefore, we tried to generate a preliminary quantitative, real‐time index for its severity by referring to published reports of severe mamushi bite cases.