Yozo Ishiuji - Academia.edu (original) (raw)

Papers by Yozo Ishiuji

Journal of Dermatological Science, Mar 1, 2014

[2] Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. Stat3 links activated ke... more [2] Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11:43–9. [3] Nakajima K, Kanda T, Takaishi M, Shiga T, Miyoshi K, Nakajima H, et al. Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol 2011;186:4481–9. [4] Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD, et al. Interleukin (IL)19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 2006;15:991–1004. [5] He M, Liang P. IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis. J Immunol 2010;184: 1793–8. [6] Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent [10] Cai Y, Shen X, Ding C, Qi C, Li K, Li X, et al. Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity 2011;35:596–610.

Journal of Dermatological Science, Feb 1, 2016

Journal of The American Academy of Dermatology, Nov 1, 2007

Although patients with rosacea often complain of increased skin sensitivity, there has been no qu... more Although patients with rosacea often complain of increased skin sensitivity, there has been no quantitative sensory testing of this phenomenon. Furthermore, cutaneous blood flow in these patients has not been assessed using state-of-the-art laser Doppler imaging (LDI). To assess heat pain thresholds and skin blood flow using quantitative thermal sensory testing and LDI in patients with untreated rosacea. Of the total 24 subjects enrolled, 8 had papulopustular rosacea (PPR), 8 had erythematotelangiectatic rosacea (ETR) and 8 were control subjects. Subjective burning perception, heat pain threshold, skin blood flow, and skin temperature was assessed in all subjects. In the ETR and PPR groups, two areas were compared: affected and nonaffected. Heat pain thresholds of areas affected by rosacea were lower than those of nonaffected areas. In addition, subjective burning perception was increased in rosacea patients when compared with control subjects. Although PPR-affected skin had elevated skin blood flow when compared with nonaffected skin, this was not significant for ETR-affected skin. The small number of subjects enrolled was the main limitation. This study showed enhanced sensitivity to noxious heat stimuli in rosacea-affected skin, which was more prominent in the PPR group.

The Japanese journal of dermatology, Apr 1, 2015

European Journal of Dermatology, Mar 1, 2014

Journal of Dermatology, Aug 24, 2017

Biochemical and Biophysical Research Communications, 2021

In the present study, we demonstrated that there is a direct relationship between scratching beha... more In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of DFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of DFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress.

Acta dermato-venereologica, 2021

International Journal of Dermatology, Aug 12, 2015

Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision... more Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision with tumor-free margins is the standard treatment strategy. However, surgical excision is not an option for lesions near critical anatomical structures, such as those on the face. We report the case of a patient with retiform hemangioendothelioma that responded to non-surgical treatments. We describe the case of a 72-year-old male patient with a retiform hemangioendothelioma on the face that responded to a combination of pulsed dye laser, local corticosteroid injection, and application of imiquimod cream. In addition, we reviewed past case reports of patients with retiform hemangioendothelioma. Thirty-five cases that describe the management of RH, including the present case, have been reported. Review of the cases indicate a relatively low disease-free survival rate in cases that underwent surgical excision as the initial therapy for retiform hemangioendothelioma. Surgical excision might not be the best therapeutic option. Local control with conservative therapy is an acceptable strategy for lesions in anatomical regions including the face.

Japanese Society of Allergology, Aug 27, 2020

Springer eBooks, Dec 11, 2009

ABSTRACT Autoimmune diseases are a collection of more than 80 individual diseases that are estima... more ABSTRACT Autoimmune diseases are a collection of more than 80 individual diseases that are estimated to affect more than 3% of the U.S. population.1 Underlying this diverse group of diseases is one common pathology: the malfunction of the immune system, resulting in the destruction of self-tissue. The etiology of autoimmune diseases is thought to have both genetic and environmental contributions.

Medicine, May 1, 2019

Rationale: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (P... more Rationale: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (PCI) are rare abdominal diseases and the pathological mechanisms have not been fully elucidated. Systemic sclerosis (SSc), which is characterized by the progressive sclerotic changes of skin and internal organs, is a refractory collagen disease and is frequently associated with digestive disorders including CIPO. Patient concerns: A 68-year-old woman who has been well managed for SSc over the long term, who presented with abdominal fullness for the first time. Diagnoses: Abdominal X-ray and computed tomography (CT) images showed PCI with pneumoperitoneum findings. Based on the diagnosis of CIPO, we evaluated the intestinal peristalsis of the patient by using cine magnetic resonance imaging (MRI). Interventions: Oral medications of 15 g/d of Daikenchuto, 750 mg/d of Metronidazole and Sodium Picosulfate were started for improving the bowel peristaltic movement and decreasing intestinal gas production. Outcomes: A great improvement of CIPO and PCI by multidrug therapy without any surgical treatments for such an unusual case. Lessons: This case indicates that SSc can be accompanied with not only CIPO but also PCI as digestive disorders and that cine MRI, which is a definitely beneficial imaging modality, can intelligibly visualize the peristalsis of the intestines and lead to successful medical control by noninvasive treatment.

Journal of Dermatology, Nov 7, 2018

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a ... more The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4 + T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4 + T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT + cells among CD4 + T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT + cells among CD4 + T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4 + T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4 + T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.

Journal of Investigative Dermatology, Feb 1, 2019

Clinical & Experimental Allergy, Dec 16, 2022

Experimental Dermatology, Sep 30, 2019

Itch is a multidimensional experience involving various brain regions associated with sensory per... more Itch is a multidimensional experience involving various brain regions associated with sensory perception and emotion, as well as an urge to scratch employing the motor system. Scratch temporarily relieves itch sensation in healthy subjects. However, in patients with chronic itch, rather than inhibit, scratch may aggravate itch. Patients with chronic itch, such as those with atopic dermatitis, experience severe itch and a strong desire to scratch. This urge to scratch is the driving force underlying the formation of the itch-scratch-cycle, an addictive and vicious cycle in chronic itch patients. This vicious itch-scratch behaviour and various types of addiction (henceforth, including recreational drug use) were shown to share common sensory mechanisms. Abnormalities have been observed in central neural circuits, including the reward, motivation/drive, control and learning/memory circuits, as well as other brain systems. Reward systems, including the ventral tegmental area (VTA), nucleus accumbens (NAc) and striatum, are important for brain processing of both addiction and itch. In addition to reward, addicted individuals can experience severe disruptions in motor control, cognitive awareness, executive function, learning/memory and even emotional functions. Findings showing that addiction and itch share a common neurobiological foundation could have important mechanistic and therapeutic implications. Here we propose that similar neuroadaptations exist in addiction and chronic itch patients.

Journal of Dermatology, Jul 9, 2013

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and... more Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.

Acta dermato-venereologica, 2021

To date, the relationship between the 2 different types of severity-indicating parameters (i.e. b... more To date, the relationship between the 2 different types of severity-indicating parameters (i.e. between subjective and objective severity-indicating parameters) in patients with atopic dermatitis has not been sufficiently elucidated. This study elucidates the relationship between the subjective and objective severity-indicating parameters in atopic dermatitis. Eosinophil relative count in the peripheral blood is considered to correlate with degree of itch in patients with atopic dermatitis, while neutrophil-to-lymphocyte ratio in the peripheral blood is considered to correlate with the degree of inflammation and the area of the affected region. Eosinophil relative count and neutrophil-to-lymphocyte ratio may be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis. The aim of this study is to elucidate the relationship between 2 different types of severity-indicating parameters (i.e. between subjective and objective severityindicating parameters in patients with atopic dermatitis. The disease severity of 55 patients with atopic dermatitis was assessed using 7 subjective parameters indicating severity, including visual analogue scale for itch, Patient-Oriented Eczema Measure, 5-D itch scale, Dermatology Life Quality Index, Eczema Area and Severity Index, body surface area, and Investigator Global Assessment, and 8 objective parameters indicating severity, including eosinophil relative count, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and thymus and activation-regulated chemokine. Five subjective parameters reflecting itch correlated significantly with eosinophil relative count, but not with neutrophil-to-lymphocyte ratio. In contrast, 2 subjective parameters, mainly reflecting the degree of inflammation and area of affected regions, correlated significantly with neutrophil-to-lymphocyte ratio. The eosinophil relative count may correlate with the degree of itch, while the neutrophil-to-lymphocyte ratio may correlate with the degree of inflammation and the area of the affected region. The eosinophil relative count and neutrophil-to-lymphocyte ratio may thus be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis.

Medicine, Sep 18, 2020

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces t... more Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-a antibody dupilumab in clinical trials and a real-Ethics approval and consent to patients: All investigators involved in this study shall carry out this study in accordance with the latest editions of the Declaration of Helsinki and "Ethical Guidelines for Medical and Health Research involving Human Subjects" of the Ministry of Health, Labour and Welfare, Japan. The study protocol has been approved by the Clinical Research Network Fukuoka Certified Review Board (CRB7180004). This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000037307). Access to the final trial dataset: Masutaka Furue and Takeshi Nakahara are finally responsible for accessing the final dataset. After investigators' meeting, we will decide how to report the obtained conclusion. This investigator-sponsored (Kyushu University) study received funding from Sanofi Genzyme and Regeneron (SGZ-2018-11996) to Masutaka Furue (Research contact person) and Takeshi Nakahara (Public contact person). The authors have no conflicts of interest to disclose. Trial registration: This trial has been registered with the University Hospital Medical Information Network Clinical Trials Registry (identifier: UMIN000037307) (registered on July 8th, 2019) (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042536). We expect to finish the enrollment until May 31, 2021. The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

Journal of Dermatological Science, Mar 1, 2014

[2] Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. Stat3 links activated ke... more [2] Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11:43–9. [3] Nakajima K, Kanda T, Takaishi M, Shiga T, Miyoshi K, Nakajima H, et al. Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol 2011;186:4481–9. [4] Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD, et al. Interleukin (IL)19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 2006;15:991–1004. [5] He M, Liang P. IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis. J Immunol 2010;184: 1793–8. [6] Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent [10] Cai Y, Shen X, Ding C, Qi C, Li K, Li X, et al. Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity 2011;35:596–610.

Journal of Dermatological Science, Feb 1, 2016

Journal of The American Academy of Dermatology, Nov 1, 2007

Although patients with rosacea often complain of increased skin sensitivity, there has been no qu... more Although patients with rosacea often complain of increased skin sensitivity, there has been no quantitative sensory testing of this phenomenon. Furthermore, cutaneous blood flow in these patients has not been assessed using state-of-the-art laser Doppler imaging (LDI). To assess heat pain thresholds and skin blood flow using quantitative thermal sensory testing and LDI in patients with untreated rosacea. Of the total 24 subjects enrolled, 8 had papulopustular rosacea (PPR), 8 had erythematotelangiectatic rosacea (ETR) and 8 were control subjects. Subjective burning perception, heat pain threshold, skin blood flow, and skin temperature was assessed in all subjects. In the ETR and PPR groups, two areas were compared: affected and nonaffected. Heat pain thresholds of areas affected by rosacea were lower than those of nonaffected areas. In addition, subjective burning perception was increased in rosacea patients when compared with control subjects. Although PPR-affected skin had elevated skin blood flow when compared with nonaffected skin, this was not significant for ETR-affected skin. The small number of subjects enrolled was the main limitation. This study showed enhanced sensitivity to noxious heat stimuli in rosacea-affected skin, which was more prominent in the PPR group.

The Japanese journal of dermatology, Apr 1, 2015

European Journal of Dermatology, Mar 1, 2014

Journal of Dermatology, Aug 24, 2017

Biochemical and Biophysical Research Communications, 2021

In the present study, we demonstrated that there is a direct relationship between scratching beha... more In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of DFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of DFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress.

Acta dermato-venereologica, 2021

International Journal of Dermatology, Aug 12, 2015

Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision... more Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision with tumor-free margins is the standard treatment strategy. However, surgical excision is not an option for lesions near critical anatomical structures, such as those on the face. We report the case of a patient with retiform hemangioendothelioma that responded to non-surgical treatments. We describe the case of a 72-year-old male patient with a retiform hemangioendothelioma on the face that responded to a combination of pulsed dye laser, local corticosteroid injection, and application of imiquimod cream. In addition, we reviewed past case reports of patients with retiform hemangioendothelioma. Thirty-five cases that describe the management of RH, including the present case, have been reported. Review of the cases indicate a relatively low disease-free survival rate in cases that underwent surgical excision as the initial therapy for retiform hemangioendothelioma. Surgical excision might not be the best therapeutic option. Local control with conservative therapy is an acceptable strategy for lesions in anatomical regions including the face.

Japanese Society of Allergology, Aug 27, 2020

Springer eBooks, Dec 11, 2009

ABSTRACT Autoimmune diseases are a collection of more than 80 individual diseases that are estima... more ABSTRACT Autoimmune diseases are a collection of more than 80 individual diseases that are estimated to affect more than 3% of the U.S. population.1 Underlying this diverse group of diseases is one common pathology: the malfunction of the immune system, resulting in the destruction of self-tissue. The etiology of autoimmune diseases is thought to have both genetic and environmental contributions.

Medicine, May 1, 2019

Rationale: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (P... more Rationale: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (PCI) are rare abdominal diseases and the pathological mechanisms have not been fully elucidated. Systemic sclerosis (SSc), which is characterized by the progressive sclerotic changes of skin and internal organs, is a refractory collagen disease and is frequently associated with digestive disorders including CIPO. Patient concerns: A 68-year-old woman who has been well managed for SSc over the long term, who presented with abdominal fullness for the first time. Diagnoses: Abdominal X-ray and computed tomography (CT) images showed PCI with pneumoperitoneum findings. Based on the diagnosis of CIPO, we evaluated the intestinal peristalsis of the patient by using cine magnetic resonance imaging (MRI). Interventions: Oral medications of 15 g/d of Daikenchuto, 750 mg/d of Metronidazole and Sodium Picosulfate were started for improving the bowel peristaltic movement and decreasing intestinal gas production. Outcomes: A great improvement of CIPO and PCI by multidrug therapy without any surgical treatments for such an unusual case. Lessons: This case indicates that SSc can be accompanied with not only CIPO but also PCI as digestive disorders and that cine MRI, which is a definitely beneficial imaging modality, can intelligibly visualize the peristalsis of the intestines and lead to successful medical control by noninvasive treatment.

Journal of Dermatology, Nov 7, 2018

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a ... more The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4 + T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4 + T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT + cells among CD4 + T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT + cells among CD4 + T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4 + T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4 + T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.

Journal of Investigative Dermatology, Feb 1, 2019

Clinical & Experimental Allergy, Dec 16, 2022

Experimental Dermatology, Sep 30, 2019

Itch is a multidimensional experience involving various brain regions associated with sensory per... more Itch is a multidimensional experience involving various brain regions associated with sensory perception and emotion, as well as an urge to scratch employing the motor system. Scratch temporarily relieves itch sensation in healthy subjects. However, in patients with chronic itch, rather than inhibit, scratch may aggravate itch. Patients with chronic itch, such as those with atopic dermatitis, experience severe itch and a strong desire to scratch. This urge to scratch is the driving force underlying the formation of the itch-scratch-cycle, an addictive and vicious cycle in chronic itch patients. This vicious itch-scratch behaviour and various types of addiction (henceforth, including recreational drug use) were shown to share common sensory mechanisms. Abnormalities have been observed in central neural circuits, including the reward, motivation/drive, control and learning/memory circuits, as well as other brain systems. Reward systems, including the ventral tegmental area (VTA), nucleus accumbens (NAc) and striatum, are important for brain processing of both addiction and itch. In addition to reward, addicted individuals can experience severe disruptions in motor control, cognitive awareness, executive function, learning/memory and even emotional functions. Findings showing that addiction and itch share a common neurobiological foundation could have important mechanistic and therapeutic implications. Here we propose that similar neuroadaptations exist in addiction and chronic itch patients.

Journal of Dermatology, Jul 9, 2013

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and... more Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.

Acta dermato-venereologica, 2021

To date, the relationship between the 2 different types of severity-indicating parameters (i.e. b... more To date, the relationship between the 2 different types of severity-indicating parameters (i.e. between subjective and objective severity-indicating parameters) in patients with atopic dermatitis has not been sufficiently elucidated. This study elucidates the relationship between the subjective and objective severity-indicating parameters in atopic dermatitis. Eosinophil relative count in the peripheral blood is considered to correlate with degree of itch in patients with atopic dermatitis, while neutrophil-to-lymphocyte ratio in the peripheral blood is considered to correlate with the degree of inflammation and the area of the affected region. Eosinophil relative count and neutrophil-to-lymphocyte ratio may be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis. The aim of this study is to elucidate the relationship between 2 different types of severity-indicating parameters (i.e. between subjective and objective severityindicating parameters in patients with atopic dermatitis. The disease severity of 55 patients with atopic dermatitis was assessed using 7 subjective parameters indicating severity, including visual analogue scale for itch, Patient-Oriented Eczema Measure, 5-D itch scale, Dermatology Life Quality Index, Eczema Area and Severity Index, body surface area, and Investigator Global Assessment, and 8 objective parameters indicating severity, including eosinophil relative count, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and thymus and activation-regulated chemokine. Five subjective parameters reflecting itch correlated significantly with eosinophil relative count, but not with neutrophil-to-lymphocyte ratio. In contrast, 2 subjective parameters, mainly reflecting the degree of inflammation and area of affected regions, correlated significantly with neutrophil-to-lymphocyte ratio. The eosinophil relative count may correlate with the degree of itch, while the neutrophil-to-lymphocyte ratio may correlate with the degree of inflammation and the area of the affected region. The eosinophil relative count and neutrophil-to-lymphocyte ratio may thus be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis.

Medicine, Sep 18, 2020

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces t... more Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-a antibody dupilumab in clinical trials and a real-Ethics approval and consent to patients: All investigators involved in this study shall carry out this study in accordance with the latest editions of the Declaration of Helsinki and "Ethical Guidelines for Medical and Health Research involving Human Subjects" of the Ministry of Health, Labour and Welfare, Japan. The study protocol has been approved by the Clinical Research Network Fukuoka Certified Review Board (CRB7180004). This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000037307). Access to the final trial dataset: Masutaka Furue and Takeshi Nakahara are finally responsible for accessing the final dataset. After investigators' meeting, we will decide how to report the obtained conclusion. This investigator-sponsored (Kyushu University) study received funding from Sanofi Genzyme and Regeneron (SGZ-2018-11996) to Masutaka Furue (Research contact person) and Takeshi Nakahara (Public contact person). The authors have no conflicts of interest to disclose. Trial registration: This trial has been registered with the University Hospital Medical Information Network Clinical Trials Registry (identifier: UMIN000037307) (registered on July 8th, 2019) (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042536). We expect to finish the enrollment until May 31, 2021. The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.