Chikako Nishigori

Langerhans Cells Serve as Immunoregulatory Cells by Activating NKT Cells

Ultraviolet exposure alters the morphology and function of epidermal Langerhans cells (LCs), which play a role in UV-induced immune suppression. It is generally believed that UV exposure triggers the migration of immature LCs from the skin to the draining lymph nodes (LNs), where they induce tolerance. However, because most of the previous studies employed in vitro UV-irradiated LCs, the data generated may not adequately reflect what is happening in vivo. In this study, we isolated migrating LCs from the LNs of UV-irradiated mice and studied their function. We found prolonged LC survival in the LNs of UV-irradiated mice. LCs were necessary for UV-induced immune suppression because no immune suppression was observed in LC-deficient mice. Transferring LCs from UV-irradiated mice into normal recipient animals transferred immune suppression and induced tolerance. We found that LCs colocalized with LN NKT cells. No immune suppression was observed when LCs were transferred from UV-irradiated mice into NKT cell-deficient mice. NKT cells isolated from the LNs of UV-irradiated mice secreted significantly more IL-4 than NKT cells isolated from nonirradiated controls. Injecting the wild-type mice with anti–IL-4 blocked the induction of immune suppression. Our findings indicate that UV exposure activates the migration of mature LC to the skin draining LNs, where they induce immune regulation in vivo by activating NKT cells.

Rapid Desensitization with Autologous Sweat in Cholinergic Urticaria

BACKGROUNDnThe majority of patients with cholinergic urticaria presents with strong hypersensitivity to autologous sweat. Patients with severe cholinergic urticaria are frequently resistant to H(1) antagonists which are used in conventional therapies for various types of urticaria. It has been reported that desensitization using partially purified sweat antigen was effective in a patient with cholinergic urticaria.nnnMETHODSnThe aim of this study is to determine the usefulness of rapid desensitization with autologous sweat in severe cholinergic urticaria, because rapid desensitization has proven to be a quick and effective immunotherapy for allergies to various allergens. Six patients with severe cholinergic urticaria who are resistant to H(1) antagonists and have sweat hypersensitivity were enrolled in a rapid desensitization protocol.nnnRESULTSnIn all six patients, the responses for skin tests with autologous sweat were attenuated after rapid desensitization with autologous sweat. Two of the three cholinergic urticaria patients showed reduced histamine release with autologous sweat after the rapid desensitization with autologous sweat. Further, the rapid desensitization and subsequent maintenance treatment reduced the symptoms in five of the six patients.nnnCONCLUSIONSnThis study provides evidence that rapid desensitization with autologous sweat is beneficial for treating cholinergic urticaria patients resistant to conventional therapy who have sweat hypersensitivity.

Suppressive effect of recombinant human thioredoxin on ultraviolet light-induced inflammation and apoptosis in murine skin.

Thioredoxin (TRX) is a small ubiquitous protein, which regulates cellular redox status and scavenges reactive oxygen species. The present study was conducted to investigate the effect of TRX on ultraviolet (UV)‐B‐mediated inflammatory and apoptotic responses. Ear swelling after UV‐B irradiation was significantly reduced in TRX‐transgenic mice compared to wild‐type mice. Administration i.p. of recombinant human TRX also reduced acute skin inflammatory reaction, such as skin erythema and swelling. Histologically, numbers of inflammatory cells including neutrophils and lymphocytes were significantly reduced and the average size of the caliber of blood vessels were also reduced in recombinant human TRX‐injected mice. The number of apoptotic keratinocytes, in terms of sunburn cells, activated‐caspase‐3‐positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling‐positive cells were all significantly reduced in recombinant human TRX‐injected mice. Immunohistochemical intensity of 8‐hydroxy‐2′‐deoxyguanosine was strikingly reduced in recombinant human TRX‐injected mouse. Western blotting showed that administration of recombinant human TRX attenuated duration of phosphorylation of p38 mitogen‐activated protein kinases and intensity of phosphorylation of c‐Jun N‐terminal kinase in the early phase, which play important roles in inflammatory and apoptotic signaling. Collectively, these findings indicated that recombinant human TRX attenuated inflammatory and apoptotic responses caused by UV‐B. Possible mechanisms for this might be via redox regulation of stress signaling and reduction of reactive oxygen species.

Limited influence of aspirin intake on mast cell activation in patients with food-dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well-known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation.

Non-occupational allergic contact dermatitis from 2-N-octyl-4-isothiazolin-3-one in a Japanese mattress gel-sheet used for cooling.

Atsushi Fukunaga1, Satoshi Nishiyama1, Hideki Shimizu1, Hiroshi Nagai1, Tatsuya Horikawa1, Ayumi Mori2, Noboru Inoue2, Kazumi Sasaki2 and Chikako Nishigori1 1Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan and 2Product Safety Technology Center, National Institute of Technology and Evaluation, 4-1-67 Otemae, Chuo-ku, Osaka-shi, Osaka 540-0008, Japan

Thioredoxin ameliorates cutaneous inflammation by regulating the epithelial production and release of pro-inflammatory cytokines.

Human thioredoxin-1 (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-. It has been demonstrated that systemic administration and transgenic overexpression of TRX ameliorate inflammation in various animal models, but its anti-inflammatory mechanism is not well characterized. We investigated the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX) in a murine irritant contact dermatitis (ICD) induced by croton oil. Topically applied rhTRX was distributed only in the skin tissues under both non-inflammatory and inflammatory conditions, and significantly suppressed the inflammatory response by inhibiting the production of cytokines and chemokines, such as TNF-α, Il-1β, IL-6, CXCL-1, and MCP-1. In an in vitro study, rhTRX also significantly inhibited the formation of cytokines and chemokines produced by keratinocytes after exposure to croton oil and phorbol 12-myristate 13-acetate. These results indicate that TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. As a promising new approach, local application of TRX may be useful for the treatment of various skin and mucosal inflammatory disorders.

Unilateral aquagenic wrinkling of the palms with a peculiar clinical course

ejd.2012.1792 Auteur(s) : Chieko Ibusuki, Masahiro Oka oka@med.kobe-u.ac.jp, Atsushi Fukunaga, Makoto Kunisada, Chikako Nishigori Kobe University School of Medicine, Department of Dermatology, 7-5-1 Kusunoki-cho Chuo-ku, Kobe 650-0017, Japan Aquagenic wrinkling of the palms (AWP) is a rare condition characterized by the rapid development of transient, edematous, white to translucent papules and plaques on the palms after brief exposure to water [1,xa02]. To date, more than 30xa0cases have [...]

Onychomycosis as a warning sign for peripheral arterial disease.

Atsushi Fukunaga, Ken Washio, Kanako Ogura, Kumiko Taguchi, Koji Chiyomaru, Yoshiharu Ohno^, Taro Masaki^, Hiroshi Nagai, Tohru Nagano, Masahiro Oka and Chikako Nishigori Division of Dermatology. Department of Internal Related. Division of Functional and Diagnostic Imaging Research. Department of Radiolog). Kobe University Graduate School of Medicine. 7-5-1 Kusunoki-cho, Chuo-ku. Kobe 650-0017. and ^Department of Dermatology, Nishinomiya Municipal Central Hospital, Nishinomiya, Japan. E-mail: atsushi@med.kobe-u.ae.jp Accepted Dec 3, 2012: Epub ahead of print Mar 25. 2013

Successful treatment with adapalene of cetuximab‐induced acneiform eruptions

shrift and potentially life-threatening conditions such as DIHS are not well recognized. In 2011, Ozeki et al. found that 12 single nucleotide polymorphisms significantly associated with CBZ-induced cADR are located within a 463-kb region on chromosome 6p (21,33). It is notable that this region corresponds to the major histocompatibility complex (MHC) class I region containing the HLA-A locus. The individual HLA-A alleles were genotyped for 61 cases that developed cADR and 376 cases that did not develop cADR with administration of CBZ. It was found that the HLA-A*3101 allele was present in 60.7% (37 ⁄ 61) of the cases with CBZ-induced cADR, but in only 12.5% (47 ⁄ 376) of the CBZ-tolerant controls (odds ratio = 10.8). This implies that the allele has 60.7% sensitivity and 87.5% specificity when applied as a risk predictor for CBZ-induced cADR. This report suggested that for certain drugs, HLA alleles which code MHC class I molecules are significantly associated with cADR with respect to pathogenesis. In therapy for HIV infection, pharmacogenetic tests are useful for preventing specific toxic effects of drugs. If pharmacogenomics tests had been administered for our case in the same manner before onset of disease, other anti-neuralgia agents may have been chosen and the complications would have been avoided. It would be ideal if profiling analysis of HLA alleles could be performed in certain geographical areas on a mass scale and if clinical applications of gene analysis could be generalized from this point forward.

Steroid treatment can improve the impaired quality of life of patients with acquired idiopathic generalized anhidrosis

DEAR EDITOR, Acquired idiopathic generalized anhidrosis (AIGA) is characterized by systemic anhidrosis or hypohidrosis with no identified cause or other autonomic or neurological abnormalities. AIGA is sometimes accompanied by cholinergic urticaria with symptoms of tingling, unpleasant sensation and severe pruritus. Treatment options for AIGA are limited. Most reported cases responded to high-dose systemic corticosteroids including intravenous steroid pulse therapy. AIGA can lead to discomfort, hyperthermia and heat stroke, which may affect the quality of life (QoL) of patients. However, the relationship between the QoL of patients with AIGA and effectiveness of therapy has not been examined. The aim of this study was to examine the impact of AIGA on QoL and the relationship between therapeutic effectiveness and improvement in QoL. Eight male patients and one female patient with AIGA were enrolled in this study. The patient characteristics are described in Table 1. The diagnosis of anhidrosis and the treatment efficacy were assessed by a systemic thermoregulatory sweating test and local sweating test involving intradermal injection of acetylcholine and the starch–iodine test (Minor test). Other diseases with hypohidrosis such as Sj€ ogren syndrome and Fabry disease were excluded. Cholinergic urticaria was observed in seven patients. Histological findings revealed that morphological abnormalities of sweat glands and sweat ducts were absent in all patients, and slight infiltration of lymphocytes around the sweat glands was found in five patients. The mean interval between disease onset and treatment was 27 8 months. Histamine release test with the sweat or skin test using autologous sweat revealed sweat allergy in two of eight tested patients. One course of methylprednisolone pulse therapy (3 days, 1000 mg per day) was given to six patients, two courses were given to one patient and three courses were given to one patient. Sweating improved in all patients after therapy. Adverse effects and recurrence of symptoms were not observed for > 1 year after therapy. In the absence of therapy, anhidrosis remained unchanged in one patient who declined treatment. Skindex-16 inquires about the effect of skin conditions on QoL. Patients respond to questions by choosing one of seven possible response choices, which range from ‘never bothered’ to ‘always bothered’. Skindex responses are reported in three subscales (symptoms, emotions and functioning), which address three domains: symptoms, emotional effects, and effects on social and physical functioning. Scores vary from 0 (minimal effect on QoL) to 100 (significant effect on QoL). The mean Skindex-16 subscale scores before and after therapy are shown in Figure 1. Skindex-16 questions before therapy were carried out from spring to autumn (from May to November). Skindex-16 questions after therapy were performed in September (autumn in Japan). The average September temperature of our facility is 20–30 °C. Sweating tests were also performed alongside the Skindex-16 questionnaire before and after therapy.