CD25 expression could be a prognostic marker of bexarotene monotherapy for cutaneous T-cell lymphomas.

Bexarotene is often administered to phototherapy-resistant early cutaneous T-cell lymphoma (CTCL) patients as one of the first-line therapies in real-world practice. Since bexarotene reduces the expression of CCR4 in CTCL cells and CCL22 to decrease serum CCL22 levels, bexarotene inhibits the migration of CTCL cells, as well as other CCR4+ cells, such as cytotoxic T cells and regulatory T cells, in the lesional skin of CTCL. In this report, the efficacy of bexarotene in 28 cases of CTCL, as well as its correlations with immunohistochemical profiles of tumour-infiltrating leucocytes (TILs), was retrospectively investigated. The overall response rate at 1 and 4 months for the total cohort was 70.8% (95% CI, 50.6%-86.3%) and 47.8% (95% CI, 29.2%-67.0%), respectively. The disease control rate for the total cohort at 4 months was 65.2% (95% CI, 44.8%-81.3%). The mean event-free survival for all patients was 4.1 months (0.3-68.5 months). In addition, the immunoreactive cells were calculated using digital microscopy, suggesting that the ratio of CD25+ cells among TILs was significantly increased in patients who responded to bexarotene (p = 0.0209), whereas there were no significant differences in the ratios of CD8+ cells, granulysin+ cells, and Foxp3+ cells among TILs between responder and non-responder patients. Collectively, the ratio of CD25 expression among TILs might be a predictive biomarker for the efficacy of bexarotene.

Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet. OBJECTIVE: Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis. METHODS: Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5. RESULTS: Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes. CONCLUSION: Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis.

Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study.

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20-80 mg/day), methotrexate (6-10 mg/week), cyclosporin (100-150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.

Diagnostic criteria, severity classification and guidelines of localized scleroderma.

We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma.

Diagnostic criteria, severity classification and guidelines of eosinophilic fasciitis.

We established diagnostic criteria and severity classification of eosinophilic fasciitis because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for eosinophilic fasciitis, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of eosinophilic fasciitis.

Diagnostic criteria, severity classification and guidelines of lichen sclerosus et atrophicus.

We established diagnostic criteria and severity classification of lichen sclerosus et atrophicus, because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there is no clinical guideline for lichen sclerosus et atrophicus in Japan, so we proposed its clinical guideline. The clinical guidelines were formulated by clinical questions and recommendations on the basis of evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guidelines easy to use and reliable including the newest evidence, and to present guidance for various clinical problems in treatment of lichen sclerosus et atrophicus.

The wound/burn guidelines - 3: Guidelines for the diagnosis and treatment for diabetic ulcer/gangrene.

We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence-based recommendations for clinical judgments by incorporating various viewpoints.

The wound/burn guidelines - 6: Guidelines for the management of burns.

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.

A case of scleredema adultorum successfully treated with narrow-band ultraviolet B phototherapy.

Scleredema adultorum, also known as scleredema of Buschke, is a rare connective tissue disease with unknown etiology, which is characterized by diffuse skin induration of face, neck, upper chest, back, shoulders and arms. Although there is no established treatment for this disease, the efficacy of phototherapy has been reported. We herein describe a case of scleredema adultorum successfully treated with narrow-band ultraviolet B and discuss a potential mechanism explaining its efficacy for fibrotic skin diseases.

Effects of the immunosuppressant rapamycin on the expression of human α2(I) collagen and matrix metalloproteinase 1 genes in scleroderma dermal fibroblasts.

BACKGROUND: Rapamycin has been shown to exert an anti-fibrotic effect on skin fibrosis in a certain subset of patients with systemic sclerosis (SSc) and in bleomycin-treated animal models. OBJECTIVES: To investigate the mechanism responsible for the anti-fibrotic effect of rapamycin especially by focusing on human α2(I) collagen (COL1A2) and matrix metalloproteinase 1 (MMP1) genes in normal and systemic sclerosis (SSc) dermal fibroblasts. METHODS: The expression levels of type I procollagen and MMP1 proteins were analyzed by immunoblotting and the mRNA levels of COL1A2 and MMP1 genes were evaluated by quantitative real-time RT-PCR. The activities of COL1A2 and MMP1 promoters were determined by reporter analysis. RESULTS: Rapamycin significantly decreased the levels of type I procollagen protein and COL1A2 mRNA, while significantly increasing the levels of MMP1 protein and mRNA in normal dermal fibroblasts. Similar effects of rapamycin were also observed in SSc dermal fibroblasts. Importantly, the inhibitory and stimulatory effects of rapamycin on the mRNA levels of COL1A2 and MMP1 genes, respectively, were significantly greater in SSc dermal fibroblasts than in normal dermal fibroblasts. In SSc dermal fibroblasts, rapamycin affected the expression of COL1A2 gene at the post-transcriptional level. In contrast, rapamycin altered the expression of MMP1 gene at the transcriptional level through the JNK/c-Jun signaling pathway in those cells. CONCLUSION: Rapamycin has a potential to directly regulate the deposition of type I collagen in extracellular matrix through inhibiting type I collagen synthesis and promoting its degradation by MMP1, suggesting that this drug is useful for the treatment of SSc.