Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arte...Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arteriosclerosis obliterans (ASO) and/or thromboangiitis obliterans (TAO) by unclarified mechanisms other than vasculitis and thrombosis. This study evaluated the radiological imaging in patients with digital gangrene associated with collagen disease and compared the images with those of PAD based on the results of laboratory and histopathological examinations. Methods: Angiography, MR angiography and/or CT angiography were performed on 6 patients with refractory gangrene or extensive ulcers accompanied by scleroderma-spectrum disorders;3 with diffuse systemic sclerosis, 1 with limited systemic sclerosis, 1 with overlap syndrome and 1 with Sj?gren’s syndrome. Results: Although the vascular alterations in collagen diseases were similar to those in PAD, the abnormal image findings (occlusion or stenosis of the arteries with smooth vessel walls) found in collagen diseases did not include atheromatous plaque, which are worm-like vessels that are characteristic of those observed in PAD. Conclusions: Some cases of digital gangrene seen in collagen diseases show similar vascular imaging patterns to those of PAD and comprehensive examinations including arterial imaging can be useful for the diagnosis of these unrecognized vascular changes other than vasculitis or digital thrombosis.展开更多
Background: Although vitiligo shows a similar clinical picture to other disorders in which patients exhibit depigmented spots, there are few reports on the differentiation of these conditions from each other. Purpose:...Background: Although vitiligo shows a similar clinical picture to other disorders in which patients exhibit depigmented spots, there are few reports on the differentiation of these conditions from each other. Purpose: We aimed to investigate the differences and similarities between vitiligo and nevus depigmentosus in children based on the clinical course and characteristics. Materials and Methods: We conducted an examination of the disease type, treatment, progress, and differentiation of 85 cases of vitiligo and nevus depigmentosus that developed before 15 years of age among patients who visited the Osaka University Department of Dermatology with a chief complaint of white patches from January 2010 to March 2017. Results: The median age at the onset of symptoms of 79 patients with vitiligo was 4.5 years and while that of 6 patients with nevus depigmentosus was 0.8 years, indicating that the onset of nevus depigmentosus occurred earlier. While vitiligo often developed in the head and neck regions, with a tendency for depigmented spots in multiple regions, nevus depigmentosus did not show this tendency in these regions. Upon performing Wood’s lamp observation in 38 cases of vitiligo, 35 cases were found to be fluorescent chalky white and in 3 cases histologically diagnosed as vitiligo, no clear fluorescent color was observed. All 6 patients diagnosed with nevus depigmentosus exhibited a non-fluorescent off-white color under a Wood’s lamp. Conclusions: This study indicates that non-invasive observation using a Wood’s lamp is useful in the differential diagnosis of pediatric leukoderma, in addition to the subsequent clinical course, such as the presence or absence of lesional repigmentation and/or enlargement.展开更多
We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional borde...We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.展开更多
Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy again...Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy against various soft tissue sarcomas. However, its extravasation causes serious complications, such as tissue necrosis and a delay in the treatment of underlying diseases. Methods: We experienced a rare case in which trabectedin extravasation caused severe pectoralis major muscle necrosis. A 45-year-old man with multiple lung metastases of follicular dendritic cell sarcoma received 2.15 mg of trabectedin totally through a central venous access device (CVAD) system in the right precordium. Computed tomography showed extensive turbidity of subcutaneous fatty tissue and swelling of the pectoralis major muscle to the upper margin of the liver, and the creatine kinase level was elevated to 759 U/L (reference value from 54 to 286). We performed surgical debridement twice, and the CVAD was concomitantly removed;thereafter, the skin defect was reconstructed with a split skin mesh graft. Results: Histopathology showed extreme degeneration of striated muscle and fatty tissue. Unfortunately, disability of the right arm abducens persisted after treatment because of debridement around the right humerus muscle. Discussion: Several reports have described cases of the extravasation of trabectedin. A few have mentioned severe muscular degeneration similar to that shown in the present case. Because trabectedin is a strong vesicant cytotoxic agent, it is principally administered through a CVAD rather than peripheral vessels and is continued during the nighttime;this can lead to a delay in patients or attending doctors noticing any extravasation. We need to spread appropriate knowledge of this drug and make an effort to prevent severe complications like in the present case.展开更多
A 58-year-old woman complicated with autoimmune diseases of myasthenia gravis (MG), rheumatoid arthritis, and systemic lupus erythematosus noticed an irregular black macule on her bilateral major labia, which was diag...A 58-year-old woman complicated with autoimmune diseases of myasthenia gravis (MG), rheumatoid arthritis, and systemic lupus erythematosus noticed an irregular black macule on her bilateral major labia, which was diagnosed as malignant melanoma. The melanoma lesion involving the vagina, uterus, and ventral side of rectum was not operable and was treated with nivolumab and concurrent radiotherapy with good control of the MG. This resulted in remarkable tumor shrinkage, possibly due to synergistic effects of both treatments. To our knowledge, few reports have described the effectiveness of combination therapy with nivolumab and radiation for malignant melanoma. The present case showed an enhanced anti-tumor effect with combination therapy.展开更多
Although the administration of systemic steroid for nonsegmental vitiligo in the progressive stage is a recommended treatment according to guidelines, the clinical efficacy of this regimen has not been fully establish...Although the administration of systemic steroid for nonsegmental vitiligo in the progressive stage is a recommended treatment according to guidelines, the clinical efficacy of this regimen has not been fully established. In this study, we evaluated the clinical efficacy of half-dose steroid treatment and stratified the evidence regarding its usefulness in progressive vitiligo patients. Half-dose steroid pulse therapy (500 mg/day of methylprednisolone for three sequential days) was administered intravenously three times monthly in five vitiligo patients. The visual changes in vitiligo lesions were evaluated on photographs and quantified using a spectrophotometer. As results, all patients completed three cycles of treatment without severe adverse events. Three of the five patients achieved disease arrest with decrease in white contrast. Therefore, short-term and halfdose steroid therapy is well tolerated and effective for achieving disease arrest in progressive nonsegmental vitiligo. The whiteness assessed by a spectrophotometer is possibly associated with therapeutic response to steroid therapy.展开更多
Background: Vitiligo is an autoimmune disorder related to melanocyte loss;however, the exact interplay between antigen-specific autoimmunity and local oxidative stress remains unclear. Recently, the migration ability ...Background: Vitiligo is an autoimmune disorder related to melanocyte loss;however, the exact interplay between antigen-specific autoimmunity and local oxidative stress remains unclear. Recently, the migration ability and number of Foxp3-expressing regulatory T cells (Tregs) in lesional skin was found to be reduced in vitiligo patients. Objectives: We aimed to clarify the T cell anergy status of melanocytes by focusing on the impaired equivalence of peripheral melanocyte-specific cytotoxic T cells and functional Tregs in patients with progressive vitiligo. Materials and methods: Ten progressive vitiligo patients and 10 age-matched healthy individuals were enrolled in this study. We analyzed the number of functional Tregs in progressive vitiligo patients and compared the findings with those of controls. Next, to assess the suppressive activity of Tregs on melanocyte-specific T lymphocytes, we strictly purified the functional Tregs fraction and Melan-A-specific CD8+ T cells and co-cultured these cells with each other. The number of Melan-A-specific CD8+ T cells was then counted by FACS. In addition, the expression of the representative exhaustion markers PD-1 and CTLA-4 on functional Tregs was assessed in vitiligo patients and normal controls. Results: The number of functional Tregs itself was not significantly decreased in the blood of vitiligo patients compared to healthy controls. However, the cytotoxic T cell (CTL) proliferation was significantly decreased after cultivation with Tregs from healthy individuals (p < 0.01), and this decrease in CTLs was less marked after cultivation with Tregs from vitiligo patients. Conclusions: We demonstrated a reduced suppressive function of activated Tregs on Melan-A-specific CTLs in the circulating cells of vitiligo patients compared with healthy controls. This result suggests that T cell anergy with Tregs dysfunction may participate in the immune response to melanocytes in vitiligo patients.展开更多
In addition to therapeutic options such as steroid ointment, immunosuppressive drug and ultraviolet phototherapy, recent reports have demonstrated the clinical efficacy of topical vitamin D3 for vitiligo vulgaris. How...In addition to therapeutic options such as steroid ointment, immunosuppressive drug and ultraviolet phototherapy, recent reports have demonstrated the clinical efficacy of topical vitamin D3 for vitiligo vulgaris. However, there seems to be little clinical effect of vitamin D3 without UV exposure. In the present study, we evaluated the clinical difference of sun irradiation vs. narrowband UVB in combination with tacalcitol assessing the change of lesion size and color tone by a spectrophotometer. Thirty-three vitiligo patients were composed of 19 treated with sun illumination and 14 treated with narrowband UVB in combination with topical use of tacalcitol. The mean % size reduction was higher in the group of sunbathing than narrowband UVB (29% vs. 23%). Delta L score, which represented the difference of whiteness between lesional and perilesional skin, was significantly improved after treatment in the group of sun irradiation instead of narrowband UVB (p = 0.0023). Therefore, we consider that sun illumination along with tacalcitol may be able to induce natural repigmentation and be an alternative therapeutic option for vitiligo vulgaris.展开更多
Objective:To study the effect of Jumihaidokuto(Shi-Wei-Bai-Du-Tang,十味败毒汤)in the management of chronic spontaneous urticaria.Methods:A randomized two-arm,parallel group study was conducted to compare the effect of...Objective:To study the effect of Jumihaidokuto(Shi-Wei-Bai-Du-Tang,十味败毒汤)in the management of chronic spontaneous urticaria.Methods:A randomized two-arm,parallel group study was conducted to compare the effect of Jumihaidokuto(6 g daily)with a control for 8 weeks.Concomitant therapy(e.g.,antihistamines)was continued.Twenty?one subjects with severe chronic urticaria were enrolled in this study.The primary treatment outcome was the severity score proposed by the Japanese Dermatological Association.Secondary outcomes were quality of life(Skindex-16),itch intensity(Visual Analogue Scale),and patients'subjective disability due to wheal or itch.After the subjects were randomly assigned to groups by block randomization,10 received Jumihaidokuto,and 11 did not.All subjects had already taken antihistamines.Results:Improvement was significant when comparing the severity score of the Jumihaidokuto group with that of the control group(P<0.01).Skindex-16 values for both groups gradually decreased in the same fashion.Conclusion:Concomitant use of Jumihaidokuto with antihistamine was more effective than antihistamine alone in the management of chronic idiopathic urticaria.展开更多
文摘Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arteriosclerosis obliterans (ASO) and/or thromboangiitis obliterans (TAO) by unclarified mechanisms other than vasculitis and thrombosis. This study evaluated the radiological imaging in patients with digital gangrene associated with collagen disease and compared the images with those of PAD based on the results of laboratory and histopathological examinations. Methods: Angiography, MR angiography and/or CT angiography were performed on 6 patients with refractory gangrene or extensive ulcers accompanied by scleroderma-spectrum disorders;3 with diffuse systemic sclerosis, 1 with limited systemic sclerosis, 1 with overlap syndrome and 1 with Sj?gren’s syndrome. Results: Although the vascular alterations in collagen diseases were similar to those in PAD, the abnormal image findings (occlusion or stenosis of the arteries with smooth vessel walls) found in collagen diseases did not include atheromatous plaque, which are worm-like vessels that are characteristic of those observed in PAD. Conclusions: Some cases of digital gangrene seen in collagen diseases show similar vascular imaging patterns to those of PAD and comprehensive examinations including arterial imaging can be useful for the diagnosis of these unrecognized vascular changes other than vasculitis or digital thrombosis.
文摘Background: Although vitiligo shows a similar clinical picture to other disorders in which patients exhibit depigmented spots, there are few reports on the differentiation of these conditions from each other. Purpose: We aimed to investigate the differences and similarities between vitiligo and nevus depigmentosus in children based on the clinical course and characteristics. Materials and Methods: We conducted an examination of the disease type, treatment, progress, and differentiation of 85 cases of vitiligo and nevus depigmentosus that developed before 15 years of age among patients who visited the Osaka University Department of Dermatology with a chief complaint of white patches from January 2010 to March 2017. Results: The median age at the onset of symptoms of 79 patients with vitiligo was 4.5 years and while that of 6 patients with nevus depigmentosus was 0.8 years, indicating that the onset of nevus depigmentosus occurred earlier. While vitiligo often developed in the head and neck regions, with a tendency for depigmented spots in multiple regions, nevus depigmentosus did not show this tendency in these regions. Upon performing Wood’s lamp observation in 38 cases of vitiligo, 35 cases were found to be fluorescent chalky white and in 3 cases histologically diagnosed as vitiligo, no clear fluorescent color was observed. All 6 patients diagnosed with nevus depigmentosus exhibited a non-fluorescent off-white color under a Wood’s lamp. Conclusions: This study indicates that non-invasive observation using a Wood’s lamp is useful in the differential diagnosis of pediatric leukoderma, in addition to the subsequent clinical course, such as the presence or absence of lesional repigmentation and/or enlargement.
文摘We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.
文摘Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy against various soft tissue sarcomas. However, its extravasation causes serious complications, such as tissue necrosis and a delay in the treatment of underlying diseases. Methods: We experienced a rare case in which trabectedin extravasation caused severe pectoralis major muscle necrosis. A 45-year-old man with multiple lung metastases of follicular dendritic cell sarcoma received 2.15 mg of trabectedin totally through a central venous access device (CVAD) system in the right precordium. Computed tomography showed extensive turbidity of subcutaneous fatty tissue and swelling of the pectoralis major muscle to the upper margin of the liver, and the creatine kinase level was elevated to 759 U/L (reference value from 54 to 286). We performed surgical debridement twice, and the CVAD was concomitantly removed;thereafter, the skin defect was reconstructed with a split skin mesh graft. Results: Histopathology showed extreme degeneration of striated muscle and fatty tissue. Unfortunately, disability of the right arm abducens persisted after treatment because of debridement around the right humerus muscle. Discussion: Several reports have described cases of the extravasation of trabectedin. A few have mentioned severe muscular degeneration similar to that shown in the present case. Because trabectedin is a strong vesicant cytotoxic agent, it is principally administered through a CVAD rather than peripheral vessels and is continued during the nighttime;this can lead to a delay in patients or attending doctors noticing any extravasation. We need to spread appropriate knowledge of this drug and make an effort to prevent severe complications like in the present case.
文摘A 58-year-old woman complicated with autoimmune diseases of myasthenia gravis (MG), rheumatoid arthritis, and systemic lupus erythematosus noticed an irregular black macule on her bilateral major labia, which was diagnosed as malignant melanoma. The melanoma lesion involving the vagina, uterus, and ventral side of rectum was not operable and was treated with nivolumab and concurrent radiotherapy with good control of the MG. This resulted in remarkable tumor shrinkage, possibly due to synergistic effects of both treatments. To our knowledge, few reports have described the effectiveness of combination therapy with nivolumab and radiation for malignant melanoma. The present case showed an enhanced anti-tumor effect with combination therapy.
文摘Although the administration of systemic steroid for nonsegmental vitiligo in the progressive stage is a recommended treatment according to guidelines, the clinical efficacy of this regimen has not been fully established. In this study, we evaluated the clinical efficacy of half-dose steroid treatment and stratified the evidence regarding its usefulness in progressive vitiligo patients. Half-dose steroid pulse therapy (500 mg/day of methylprednisolone for three sequential days) was administered intravenously three times monthly in five vitiligo patients. The visual changes in vitiligo lesions were evaluated on photographs and quantified using a spectrophotometer. As results, all patients completed three cycles of treatment without severe adverse events. Three of the five patients achieved disease arrest with decrease in white contrast. Therefore, short-term and halfdose steroid therapy is well tolerated and effective for achieving disease arrest in progressive nonsegmental vitiligo. The whiteness assessed by a spectrophotometer is possibly associated with therapeutic response to steroid therapy.
文摘Background: Vitiligo is an autoimmune disorder related to melanocyte loss;however, the exact interplay between antigen-specific autoimmunity and local oxidative stress remains unclear. Recently, the migration ability and number of Foxp3-expressing regulatory T cells (Tregs) in lesional skin was found to be reduced in vitiligo patients. Objectives: We aimed to clarify the T cell anergy status of melanocytes by focusing on the impaired equivalence of peripheral melanocyte-specific cytotoxic T cells and functional Tregs in patients with progressive vitiligo. Materials and methods: Ten progressive vitiligo patients and 10 age-matched healthy individuals were enrolled in this study. We analyzed the number of functional Tregs in progressive vitiligo patients and compared the findings with those of controls. Next, to assess the suppressive activity of Tregs on melanocyte-specific T lymphocytes, we strictly purified the functional Tregs fraction and Melan-A-specific CD8+ T cells and co-cultured these cells with each other. The number of Melan-A-specific CD8+ T cells was then counted by FACS. In addition, the expression of the representative exhaustion markers PD-1 and CTLA-4 on functional Tregs was assessed in vitiligo patients and normal controls. Results: The number of functional Tregs itself was not significantly decreased in the blood of vitiligo patients compared to healthy controls. However, the cytotoxic T cell (CTL) proliferation was significantly decreased after cultivation with Tregs from healthy individuals (p < 0.01), and this decrease in CTLs was less marked after cultivation with Tregs from vitiligo patients. Conclusions: We demonstrated a reduced suppressive function of activated Tregs on Melan-A-specific CTLs in the circulating cells of vitiligo patients compared with healthy controls. This result suggests that T cell anergy with Tregs dysfunction may participate in the immune response to melanocytes in vitiligo patients.
文摘In addition to therapeutic options such as steroid ointment, immunosuppressive drug and ultraviolet phototherapy, recent reports have demonstrated the clinical efficacy of topical vitamin D3 for vitiligo vulgaris. However, there seems to be little clinical effect of vitamin D3 without UV exposure. In the present study, we evaluated the clinical difference of sun irradiation vs. narrowband UVB in combination with tacalcitol assessing the change of lesion size and color tone by a spectrophotometer. Thirty-three vitiligo patients were composed of 19 treated with sun illumination and 14 treated with narrowband UVB in combination with topical use of tacalcitol. The mean % size reduction was higher in the group of sunbathing than narrowband UVB (29% vs. 23%). Delta L score, which represented the difference of whiteness between lesional and perilesional skin, was significantly improved after treatment in the group of sun irradiation instead of narrowband UVB (p = 0.0023). Therefore, we consider that sun illumination along with tacalcitol may be able to induce natural repigmentation and be an alternative therapeutic option for vitiligo vulgaris.
文摘Objective:To study the effect of Jumihaidokuto(Shi-Wei-Bai-Du-Tang,十味败毒汤)in the management of chronic spontaneous urticaria.Methods:A randomized two-arm,parallel group study was conducted to compare the effect of Jumihaidokuto(6 g daily)with a control for 8 weeks.Concomitant therapy(e.g.,antihistamines)was continued.Twenty?one subjects with severe chronic urticaria were enrolled in this study.The primary treatment outcome was the severity score proposed by the Japanese Dermatological Association.Secondary outcomes were quality of life(Skindex-16),itch intensity(Visual Analogue Scale),and patients'subjective disability due to wheal or itch.After the subjects were randomly assigned to groups by block randomization,10 received Jumihaidokuto,and 11 did not.All subjects had already taken antihistamines.Results:Improvement was significant when comparing the severity score of the Jumihaidokuto group with that of the control group(P<0.01).Skindex-16 values for both groups gradually decreased in the same fashion.Conclusion:Concomitant use of Jumihaidokuto with antihistamine was more effective than antihistamine alone in the management of chronic idiopathic urticaria.
