Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model of climacterium.

Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on so-called dry skin. However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at premenopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause. Hydration of the SC, recovery of the permeability barrier function, integrity and cohesion of the SC, and irritant dermatitis were analysed in mice that underwent ovariectomy with or without replacement of 17ß-estradiol. In ovariectomized mice, hydration of the SC was reduced, recovery of permeability barrier function after acute disruption was impaired, and integrity of the SC was weakened and was associated with increased cohesion and increased levels of irritant dermatitis. Oestrogen replacement treatment restored all changes. Immunohistochemistry revealed reduced levels of expression of desmoglein-1 and differentiation markers of epidermis in ovariectomized mice compared with control mice and mice with oestrogen replacement treatment. These changes might be directly associated with weakened integrity and impaired permeability barrier function of the SC in ovariectomized mice. This study results reveal that so-called dry skin at menopause is caused by not only lower hydration of the SC but also complicated structural and functional changes in the SC and skin.

Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by an acquired impairment in total body sweating despite exposure to heat or exercise. Severe cases may result in heatstroke. Most cases of AIGA have been reported in Asia, especially in Japan. However, there is limited information on the epidemiology of this condition, and no diagnostic criteria or appropriate treatment options have been established. This guideline was developed to fill this gap. It contains information on the etiology, diagnosis, evaluation of disease severity and evidence-based recommendations for the treatment of AIGA. Appropriate treatment according to disease severity may relieve the clinical manifestations and emotional distress experienced by patients with AIGA.

Long-term treatment outcome after only popliteal lymph node dissection for nodal metastasis in malignant melanoma of the heel: the only "interval node" dissection can be an adequate surgical treatment.

We present a patient with malignant melanoma on his heel. Wide local excision was performed, along with sentinel lymph node biopsy of the inguinal and popliteal lesions. The primary site was clear of tumor at all margins; the inguinal nodes were negative, but the popliteal node was positive for metastatic melanoma. Only radical popliteal lymph node dissection was performed. The patient went on to receive adjuvant chemoimmunotherapy. There was no recurrence or complication until the long-term followup. Popliteal drainage from below the knee is uncommon, and the rate of popliteal-positive and inguinal-negative cases is estimated to be less than 1% of all melanomas. There is no established evidence about how to treat lymph nodes in these cases. Because we considered popliteal nodes as a regional, not interval, lymph node basin, only popliteal lymph node dissection was performed, and good postoperative course was achieved. The first site of drainage is the sentinel node, and the popliteal node can be a sentinel node. The inguinal node is not a sentinel node in all lower extremity melanomas. This case illustrates the importance of individual detailed investigation of lymphatic drainage patterns from foot to inguinal and popliteal nodes.

Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior.

Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.

Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation.

Tim-3 is a cell surface molecule preferentially expressed in Th1 and Th17 cells. Galectin-9 is a ligand for Tim-3 and the binding of galectin-9 to Tim-3 induces apoptosis. We recently developed a stable form of galectin-9 (sGal-9) by partial deletion of the linker peptide. In this study, we characterized the therapeutic effects of sGal-9 on inflammatory reactions in contact hypersensitivity and IL-23-induced psoriatic mouse models. In contact hypersensitivity in mice, the ear swelling response was suppressed by sGal-9. In vitro treatment with sGal-9 resulted in cell apoptosis of CD4, CD8, and hepatic NK cells. sGal-9-treated mice had decreased IFN-gamma- and IL-17-producing T cells. Similarly, sGal-9 reduced epidermal thickness and dermal cellular infiltrate levels in IL-23-induced psoriasis-like skin inflammation. This was accompanied by decreased skin lesion levels of IL-17 and IL-22. sGal-9 may be a unique and useful therapeutic tool for the treatment of Th1- and/or Th17-mediated skin inflammation.

Airborne contact dermatitis due to Japanese cedar pollen.

Contact dermatitis caused by airborne antigen is a well-recognized problem. Previously, airborne contact dermatitis after contact with Japanese cedar pollen [Japanese cedar pollen dermatitis (JCPD)] has been reported in Japan. However, there is still no diagnostic test to evaluate contact dermatitis due to Japanese cedar pollen. Skin tests with Japanese cedar pollen have been used to investigate these patients. A histological analysis was also conducted to clarify the mechanism of JCPD. We performed a scratch-patch test, scratch test and assays for total immunoglobulin E (IgE) and specific IgE in 13 patients suspected to have skin symptoms from Japanese cedar pollen, 5 patients with Japanese cedar pollinosis and 15 control normal subjects. All subjects were tested with Japanese cedar pollen allergen extract. A skin biopsy was performed from a Japanese cedar pollen-scratch-patch-test positive in patients with JCPD. The result after 48 hr of scratch-patch test was compared with the patient's history and the findings of corresponding scratch test and specific IgE. 100% of the 13 patients with JCPD showed a positive scratch-patch-test reaction to Japanese cedar pollen extract. However, 20% of the patients with the Japanese cedar pollinosis without any eruptions showed a positive scratch-patch-test reaction. The percentage of positive results for specific IgE and the scratch test did not differ substantially between Japanese cedar pollionosis patients with a history of chronic erythema after contact with Japanese cedar pollen and those without such a history. No side-effects were observed regarding the scratch-patch test. Control subjects showed 7% positive reaction. Histological examination showed that eczematous change (spongiosis, intracellular oedema and acanthosis), and infiltration of lymphocytes and eosinophils were all observed at the scratch-patch-test-positive sites. We therefore concluded that the use of the scratch-patch test with Japanese cedar pollen extract was useful for accurately diagnosing JCPD.

Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of atopy patch testing and histological examination.

Atopy patch testing with Japanese cedar pollen extract has been used to investigate patients with atopic dermatitis whose condition is exacerbated by contact with Japanese cedar pollen. Comparative atopy patch testing, scratch tests, and assays for total IgE and specific IgE were performed in 74 patients with atopic dermatitis, 5 patients with Japanese cedar pollinosis and 15 control subjects. A skin biopsy was performed on any sites that were positive to Japanese cedar pollen patch test. The results after 48 h of atopy patch testing were compared with the patient's history, skin scratch test and specific IgE. Twenty-two of the 74 patients (30%) had a history of exacerbation every spring after contact with Japanese cedar. Of these patients 68% showed a positive reaction to Japanese cedar pollen extract, as did 21% of patients with atopic dermatitis without a history of exacerbation by Japanese cedar pollen, 20% of patients with Japanese cedar pollinosis without eruption and 7% of control subjects. A histological examination revealed eczematous changes and infiltration of lymphocytes and eosinophils in atopy patch testing positive sites. In conclusion, atopy patch testing with Japanese cedar pollen extract is a useful method for investigating trigger factors for eczematous skin lesions in a subgroup of patients with atopic dermatitis.