Junko Sowa-Osako

Pemphigoid with antibodies to laminin γ1, BP180 and BP230, associated with psoriasis vulgaris: Successful disease control with cyclosporin

Both anti‐laminin γ1 pemphigoid and bullous pemphigoid are autoimmune subepidermal blistering diseases. The former is rare and characterized by autoantibodies to laminin γ1, a 200‐kDa dermal protein, while the latter is common among the elderly and characterized by autoantibodies to BP180 and BP230, both of which are hemidesmosomal proteins. We experienced a 69‐year‐old Japanese male patient with blister formation secondary to erythrodermic psoriasis, which was successfully treated with cyclosporin. The histopathology of erythema corresponded with psoriasis and that of a blistering lesion showed infiltration of neutrophils and eosinophils in and around the subepidermal blisters. Patient immunoglobulin G antibodies labeled both the epidermal and dermal sides of 1 mol/L NaCl‐split human skin by indirect immunofluorescent microscopy and recognized laminin γ1, BP180 and BP230 by immunoblotting. To the best of our knowledge, this is the first report of coexistence of psoriasis and atypical pemphigoid with these three autoantibodies.

Severe stomatitis with a deep buccal ulcer associated with an allergic reaction to methyl methacrylate used for dental treatment: SEVERE STOMATITIS CAUSED BY MMA

A 54-year-old woman was referred by a local dentist to our dermatology clinic for evaluation of severe stomatitis and a painful ulcer. Physical examination showed erosions of the upper palate and bilateral buccal mucosa. A deep ulceration with erythema in the right buccal mucosa was also noted (Fig. 1). The patient was otherwise healthy and free from systemic symptoms indicating Behçet disease or Crohn’s disease. Nine days earlier she underwent dental treatment with ‘acrylic resin A’ as a temporary filling for a right maxillary molar tooth. On her way home, she felt a stinging sensation in the oral cavity, and found that the right labial angle was eroded. On day 4, the dentist covered the ‘acrylic resin A’ with ‘acrylic resin B’. On day 5, the mucosal epithelium of the entire palate detached, and subsequently the patient experienced severe pain when swallowing. Therefore, all of the sealing products were removed, and ‘acrylic resin C’ was used as a temporary dental crown. However, the pain worsened, and on day 6 the ‘acrylic resin C’ was removed.

Allergic contact dermatitis caused by the preservative 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one in black trousers

Ayano Umekoji1, Kazuyoshi Fukai1, Junko Sowa-Osako1, Marina Manabe1, Maki Kikugawa2, Kyoko Ishii3, Kazumi Sasaki3 and Daisuke Tsuruta1 1Department of Dermatology, Osaka City University, Graduate School of Medicine, Osaka, 545-8585, Japan, 2Consumer Product Safety Technology Division, National Institute of Technology and Evaluation, Product Safety Technology Centre, Osaka, 559-0034, Japan, and 3Biosafety Analysis Division, National Institute of Technology and Evaluation, Biological Resource Centre, Tokyo, 151-0066, Japan

Repeated myiasis in a female vulvar squamous cell carcinoma caused by Lucilia sericata and Sarcophaga crassipalpis.

Dear Editor, Myiasis, the infestation of tissues by larvae (maggots) of dipterous insects, is rarely reported in Japan. Here, we describe a case of a 66-year-old woman with recurrent vulvar squamous cell carcinoma (SCC) who presented with two independent episodes of myiasis within a few days. This patient was initially referred to our dermatology department in June 2014. She reported that something was creeping on her vulva and it occasionally caused mild pain. She had removed three maggots at home before visiting our hospital. Upon physical examination in lithotomy position, we observed papilloma-like tumors covering the whole vulva, with several whitish maggots (Fig. 1a,b). Using forceps, we removed 12 maggots with body lengths of 8–10 mm (Fig. 1c). After confirming that all maggots were removed, we washed the area with saline. Three days later, the patient noticed new maggots on her vulva, removed six of them and returned to our hospital. We examined and cared for her in the same manner (Fig. 1d,e). This time, we removed 17 maggots with body lengths of 3–5 mm (Fig. 1f). To identify the species of maggots obtained during the patient’s first and second visits, some of the maggots were raised and metamorphosed into pupa and adults to allow observation of their morphological features. Other maggot samples were frozen to extract DNA for cytochrome oxidase c subunit 1 (COI) analysis. Both morphological taxonomy and

Presymptomatic genetic diagnosis of two siblings with hereditary angioedema, presenting with unusual normal levels of serum C4

Dear Editor, Hereditary angioedema (HAE) is a rare autosomal dominant disorder, characterized by episodes of angioedema of various body parts, abdominal pain, nausea and vomiting. A sudden attack of HAE is unpredictable, and swelling of the airway can potentially lead to death. Most cases of HAE are classified into type I and type II with heterozygous deficiencies of the C1 inhibitor (C1-INH) gene (SERPING1), but the genotype–phenotype relationship of them has not been reported. The administration of compliment C1-INH, which is available as Berinert P (CSL Behring, Tokyo, Japan) in Japan, reduces the symptoms when administrated shortly after the onset of each attack. Therefore, presymptomatic genetic diagnosis of HAE is beneficial. As such, we conducted genetic counseling and the DNAbased diagnosis of a family. The proband was a 30-year-old woman who experienced recurrent episodes of angioedema. The low level of both C1INH activity and protein concentration, along with the low C4 level, suggested that she had HAE type I. DNA analysis revealed that she has a heterozygous splice site mutation (g.1820G>A, c.51+1G>A) of the C1-INH gene. This mutation has already been reported as a pathological mutation in HAE type I of Hungarian patients, but this is the first report of the same mutation in an individual of Japanese heritage. The proband has three daughters. At the time of the study, all of them were free of angioedema and their serum C4 levels were normal (Table 1). However, the second and third daughters showed slightly low levels of C1-INH activity and protein concentration, as well as C1q. These test results raised the possibility that two of the daughters also have HAE. To confirm this, we conducted genetic counseling and presymptomatic genetic diagnosis of HAE in all three daughters. DNA tests revealed that the second (a 2-year-old) and third (a 1-year-old) daughters have the same heterozygous splice site mutation of the C1-INH gene. The first daughter does not carry the mutation. All study protocols were approved by the institutional review board of the Ethical Committee for Human Genome Research of Hiroshima University (Gen-M114-9) and the Osaka City University Graduate School of Medicine (#2986) before the genetic analysis. The proband provided written informed consent. Based on the diagnosis of HAE, we clarified for this family which hospital to visit in case of a sudden attack. According to Ohsawa et al., the sensitivity and specificity of low C4 for HAE were 95.6% and 93.8%, respectively. In Ohsawa et al.’s case series, only one of 23 HAE patients showed a normal level of C4. However, the second measurement during an attack exhibited a low C4 level. Therefore, normal C4 levels in the present cases may be attributable to the lack of the attacks of angioedema so far. Thus, although it has been generally agreed that low serum levels of C4 are a useful marker for HAE, normal serum C4 levels do not exclude the possibility of HAE. This underscores the importance of DNA-based diagnosis of HAE, particularly for presymptomatic young children who may be prone to atypical laboratory tests for C4.

Onychocytic matricoma as an underrecognized benign mimicker of subungual malignant melanoma and Bowen's disease

Figure 1. (a) The nail plate of the ring finger with non-homogeneous brown pigmentation. (b) Dermoscopic findings: vague irregular longitudinal lines over a light brown background, nail scales (dashed blue circle), white dots (yellow circles) and splinter hemorrhage (red arrow). (c) Gross view of the specimen. (d–g) Histopathological findings. (d) Scan magnification: apparent acanthosis of the nail matrix and the nail bed. The blue box indicates the location of (e), the yellow box (f) and the red box (g) (hematoxylineosin [HE], original magnification 910). (e) Thickened nail plate with parakeratosis (HE, 9100). (f) Squamous eddy-like structures in pre-keratogenous zone (PKZ) cells (HE, 9200). (g) A keratinous cyst-like structure formed by a nest of pre-keratogenous and keratogenous zone (KZ) in concentric arrangements with nail plate in the center (HE, 9200).

Case of facial pyoderma gangrenosum

1 Cox NH, Jorizzo JL, Bourke JF, Savage COS. Vasuculitis, neutrophilic dermatoses and related disorders. In: Tony B, Breathnach S, Cox N, Griffiths C, eds. Rooks Textbook of Dermatology, 8th edn. Oxford: Wiley-Blackwell, A John Wiley & Sons Ltd, 2012; 74–75. 2 Rochet NM, Chavan RN, Cappel MA et al. Sweet syndrome: clinical presentation, association and response to treatment in 77 patients. J Am Acad Dermatol 2013; 69: 557–564. 3 Richetts JR, Rothe MJ, Grant-Keis JM. Cutaneous stimulants of infectious disease. Int J Dermatol 2011; 50: 1043–1057. 4 Coelho JF, Lourrenҫo S, Marques J, Mendonҫa P, Malhado JA. Neutrophilic dermatosis of the dorasal hands associated with chronic hepatitis C virus infection. Indian J Dermatol Venereol Leprol 2008; 74: 478–480. 5 Yong AS, Lee KY, Murphy J, Phillips M, Rushbrook S, Garioch JJ. Acute febrile neutrophilic dermatosis (Sweet’s disease) in a patient with biliary sepsis. Postgrad Med J 2013; 89: 731–732.

Alectinib-Induced Erythema Multiforme and Successful Rechallenge with Alectinib in a Patient with Anaplastic Lymphoma Kinase-Rearranged Lung Cancer.

Background: Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. Case Presentation: A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK. The skin reaction was observed on the anterior chest, upper arms, and ear auricles on day 11 of treatment with oral alectinib. The skin event presented as widely distributed erythematous macules that were confluent, indicating a severe and life-threatening form. The skin lesions started to resolve after the initiation of treatment with 40 mg prednisolone. After regrowth of the tumor, she received a rechallenge program for alectinib for 2 weeks; thereafter, alectinib treatment was successfully reinitiated. Conclusion: To the best of our knowledge, we present the first case in which alectinib, which binds to the adenosine triphosphate site of EML4-ALK, induced erythema multiforme. Moreover, successful readministration of alectinib through our rechallenge program has not been reported so far.

Promising therapeutic option for cutaneous plasmacytosis: 308-nm excimer lamp

Figure 1. (a) The patient, a 74-year-old man. On his trunk, 10–15-mm multiple infiltrating erythemas had presented. (b) The 311-nm narrowband ultraviolet B (NBUVB) therapy was performed once a week at an initial irradiation dose of 0.2 J/cm. The dose was gradually increased at each visit, and reached 0.8 J/cm 20 weeks after the start of treatment. In March 2017, the 311-nm NBUVB therapy at a total 58 J/cm showed only a slight effect on the cutaneous plasmacytosis (CP). (c) The 308-nm excimer lamp therapy was performed once a week at an initial irradiation dose of 100 mJ/cm. The dose was gradually increased at each visit, and reached 220 mJ/cm 12 weeks after the start of treatment. In November 2017, the 308-nm excimer lamp therapy at a total of 9 J/ cm showed a full effect on the CP. No obvious adverse events were observed. (d,e) Perivascular, periadnexal and lobular infiltrations of mature plasma cells were observed in the dermis to subcutaneous fat, histopathologically (hematoxylin–eosin, [d] scanning magnification, [e] 9400). (f,g) No light chain restriction was detected by in situ hybridization for Igjand Igk-chain (j/k ratio, 0.6; [f] Igj 9200; [g] Igk 9200).

Case of anaphylaxis caused by black ginger in a dietary supplement

Dear Editor, Black ginger (Kaempferia parviflora) has been used as a nourishing medicinal tonic in Thailand and has recently become a popular ingredient in dietary supplements in Japan. Herein, we report the first case of anaphylaxis caused by black ginger. Black ginger belongs to the family Zingiberaceae, which includes zedoary (Curcuma zedoaria), turmeric (Curcuma longa), wild turmeric (Curcuma aromatica) and ginger (Zingiber officinale). A 54-year-old woman was referred to our department with anaphylactic symptoms, including systemic urticaria, abdominal pain, nausea and dyspnea, which had started 2 h after intake of five kinds of dietary supplements. A skin prick test (SPT) yielded a positive result for Company A’s dietary supplement 1% aqua (aq.), while tests for other dietary supplements yielded negative results. SPT on the ingredients of Company A’s dietary supplement yielded a positive result for black ginger 1% aq., but negative results for the other five ingredients. Therefore, we diagnosed the patient with anaphylaxis caused by black ginger. She ate the causative supplement for the first time. Additionally, positive SPT results were obtained with 1% aq. of C. zedoaria, C. longa, Z. officinale and 10% aq. of C. aromatica. To identify the causative protein, we performed polyacrylamide gel electrophoresis (PAGE) and western blotting in both sodium dodecylsulfate PAGE (Fig. 1a) and 2D-PAGE (Fig. 1b), and identified the positive band at 35 kDa of black ginger. Mass spectrometric analysis using TripleTOF 6600 (ABSCIEX, Framingham, MA, USA) and PROTEINPILOT software version 5.0 (ABSCIEX) against entries in the National Center for Biotechnology Information (NCBI) nr database revealed that