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Abstract Janus kinase (JAK) inhibitors are efficacious for atopic dermatitis (AD). However, some patients receiving JAK inhibitors develop acne, especially younger patients, or herpes zoster, especially elderly patients, and desire to switch to dupilumab. We experienced two patients with immediate exacerbation of AD after switching from upadacitinib to dupilumab, and herein report these cases. This phenomenon is attributed to the difference in elimination half‐life of the two drugs and a slower onset of efficacy of dupilumab than upadacitinib. When switching from a JAK inhibitor to dupilumab, short‐term concomitant use, intensifying topical treatment, and/or rescue with cyclosporine should be considered.

Abstract Dupilumab was approved for treating adult patients with atopic dermatitis (AD) refractory to topical therapy in Japan in April 2018, and self‐injection of dupilumab has been available since May 2019. Subcutaneous self‐injection of medication has benefits for patients and the healthcare system. However, anxiety about self‐injection, lack of confidence, and the complicated procedure could prevent initiating self‐injection. In this study, we assessed the experience of AD patients treated with dupilumab before and after introducing self‐injection, utilizing the Self‐Injection Assessment Questionnaire (SIAQ). Adult AD patients who received dupilumab by self‐injection and had been treated for more than 3 months after initiating self‐injection in our hospital from March 1, 2020, to June 19, 2021, were included in this study. Patients rated their perceptions about self‐injections using the SIAQ before the first self‐injection and 3 months after initiating self‐injection. Data were collected retrospectively from their charts. Data on 36 patients were analyzed. The mean age was 34.1 ± 11.5 years. Twenty patients used a prefilled auto‐injector, and the others used a prefilled syringe. Scores on self‐confidence and satisfaction with self‐injection significantly improved after introducing self‐injection. Feelings about injections improved in patients over 40 years and in those who felt anxious about self‐injection. A strong correlation in scores between satisfaction with self‐injection and the ease of use was observed. The results were not affected by clinical severity, gender, or device. Our results could encourage patients who dither to introduce self‐injection of dupilumab due to anxiety and/or lack of self‐confidence about self‐injection to initiate self‐injection.

Dupilumab, an anti‐interleukin (IL)‐4 receptor α‐antibody, was approved in 2018 for the treatment of moderate‐to‐severe atopic dermatitis (AD) in Japan. Although real‐world data have accumulated on the effectiveness and safety of dupilumab in patients with AD in the short term, real‐world data on its long‐term use are limited. In this study, we retrospectively investigated its effectiveness, safety and laboratory data in patients with AD who received dupilumab for 3 years. All adult patients with moderate‐to‐severe AD who were administered dupilumab between June 2018 and December 2020 and were treated with dupilumab for more than 3 years were included in this study. Sixty Japanese patients with AD (male, 48; female, 12) were included in this study. Their mean age was 36.6 ± 11.0 (standard deviation) years. The mean Eczema Area and Severity Index (EASI) was 29.9 ± 9.2. The clinical severity scales, including Investigator's Global Assessment (IGA), EASI and affected body surface area (BSA), and patient‐reported outcomes, such as Dermatology Quality Life Index (DLQI), Patient‐Oriented Eczema Measure (POEM) and visual analogue scale (VAS) of pruritus, significantly improved at 3 months, and at 1, 2 and 3 years after initiating dupilumab. The total EASI score significantly decreased by a mean of 66.8% at 3 months, 81.0% at 1 year, 85.3% at 2 years and 90.0% at 3 years after initiating dupilumab. The serum levels of thymus and activation‐regulated chemokine (TARC), immunoglobulin E (IgE) and lactate dehydrogenase (LDH) significantly decreased at 1, 2 and 3 years. A slight decrease in circulating neutrophils was observed in patients with AD treated with dupilumab over periods from 3 months to 3 years. The number of circulating eosinophils significantly decreased at 2 and 3 years after initiating dupilumab. The most common adverse event was ocular disorders observed in 23 patients (38.3%). Our study shows the sustained effectiveness and tolerable safety of 3‐year usage of dupilumab in Japanese patients with atopic dermatitis. Furthermore, dupilumab decreased neutrophil values at 3 months and later, and reduced the number of circulating eosinophils after long‐term use (≧ 2 years). [ABSTRACT FROM AUTHOR]

Abstract Dupilumab demonstrated high efficacy and tolerable safety profiles in moderate‐to‐severe atopic dermatitis (AD) patients in clinical trials; however, certain patients suffer from facial redness, while obtaining good responses on the trunk and limbs to dupilumab in the real‐world setting. In our study, we investigated the effectiveness of tacrolimus ointment on facial lesions refractory to topical corticosteroid in patients with AD receiving dupilumab. This study included Japanese adult patients with moderate‐to‐severe AD who developed facial lesions during dupilumab treatment and whose facial lesions became refractory to topical corticosteroid treatment. Nine patients (one female, eight males) were included in this study. One patient newly developed facial erythema after initiating dupilumab. Facial lesions were refractory to dupilumab treatment in the other patients. Five of the nine patients showed improvement in EASI scores of head and neck by switching the facial treatment from topical corticosteroid to tacrolimus ointment. The patient who developed newly facial erythema showed improvement after applying tacrolimus ointment. Although we explored the predictors of effectiveness of tacrolimus ointment in patients with facial lesions during dupilumab treatment, no significant differences were observed in age, duration of dupilumab prior treatment, or prior head and neck EASI between patients who showed improvement after changing to tacrolimus and those who did not. Tacrolimus ointment is worth trying if facial lesions are refractory to topical corticosteroid.

Abstract Background Empathy, which involves understanding another person’s experiences and concerns, is an important component for developing physicians’ overall competence. This longitudinal study was designed to test the hypothesis that medical students’ empathy can be enhanced and sustained by Humanitude Care Methodology, which focuses on perception, emotion and speech. Methods This six-year longitudinal observational study examined 115 students who entered Okayama University Medical School in 2013. The study participants were exposed to two empathy-enhancing programs: (1) a communication skills training program (involving medical interviews) and (2) a Humanitude training program aimed at enhancing their empathy. They completed the Jefferson Scale of Empathy (JSE) seven times: when they entered medical school, before participation in the first program (medical interview), immediately after the first program, before the second program (Humanitude exercise), immediately after the second program, and in the 5th and 6th year (last year) of medical school. A total of 79 students (69% of the cohort) completed all seven test administrations of the JSE. Results The mean JSE scores improved significantly after participation in the medical interview program (p

This case report describes a 44‐year‐old male patient with atopic dermatitis who developed malignant lymphoma (diffuse large B‐cell lymphoma) during the dupilumab treatment.

Psossibility and appropriate timing of discontinuation of dupilumab for atopic dermatitis (AD) remain unclear. We explored the possibility of patients, who could maintain remission with topical therapy alone after withdrawing dupilumab in the real world. Furthermore, we identified their characteristics. All adult AD patients who initiated dupilumab from June 2018 to July 2022 and were treated with dupilumab for more than 3 months at our hospital were included in this study. The observation period was from June 2018 to July 2023. In 138 patients, 58 (42.0%) discontinued dupilumab at least once. Among them, 18 (13.0%) discontinued dupilumab but reinitiated dupilumab later due to exacerbation. Only seven patients (5.1%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM, VAS of pruritus, serum levels of TARC and LDH, and neutrophil counts at baseline, and those of longer duration of dupilumab until its discontinuation (24.0 ± 13.3 vs. 12.8 ± 7.3 months) and lower EASI and affected BSA at the discontinuation of dupilumab. In 118 patients treated with dupilumab for at least 1 year, 38 patients (32.2%) discontinued at least once. Only four patients (3.4%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM at baseline and lower EASI at the discontinuation of dupilumab. In conclusion, maintaining remission after withdrawing dupilumab is challenging. Discontinuation of dupilumab may be considered in patients with low baseline POEM, after more than 2 years of dupilumab treatment, with a substantial decrease in EASI. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis (PPP) is relatively rare and recognition of PPP is different in different countries. Therefore, real‐world data are limited. Local phototherapy for the palms and the soles is commonly used to treat PPP due to tolerable safety. However, data on the effectiveness of 308‐nm excimer light are limited. In our study, we retrospectively investigated the effectiveness of treatments for PPP, especially phototherapy (308‐nm excimer light), in our department. In addition, we examined whether smoking status and focal infection affected responsiveness to treatment of PPP. Patients who were diagnosed with PPP by board‐certified dermatologists and visited our hospital from April 2015 to August 2018 were analyzed in this study. We collected data on PPP area severity index (PPPASI) before treatment. We also collected data on PPPASI in May to August 2018 as "after treatment" from all patients. Patients who received any treatment for less than 3 months were excluded. Nineteen patients (16 women and three men) were analyzed in this study. In patients treated with phototherapy (n = 12), PPPASI significantly decreased from a mean ± SD of 16.5 ± 10.3 to 4.5 ± 3.6 (p = 0.004), whereas it did not in patients treated without phototherapy (n = 7). Patients who quit smoking showed a significant decrease in PPPASI after treatment (16.8 ± 12.7 to 2.4 ± 2.9, p = 0.008). Regarding focal infection, in patients treated without phototherapy, the reduction rate of PPPASI was significantly lower in patients with focal infection than in those without focal infection (17.7 ± 21.5%, 71.1 ± 19.3%, p = 0.035), indicating that focal infection is associated with intractability. Meanwhile, in patients treated with phototherapy, PPPASI decreased regardless of the presence or absence of focal infection. In conclusion, our study demonstrated the effectiveness of local phototherapy consisting of 308‐nm excimer light, regardless of focal infection. Patients who quit smoking were responsive to any treatment, indicating the importance of smoking cessation. [ABSTRACT FROM AUTHOR]

This Article reports on the influence of light irradiation on the stability of emulsions prepared using a photoresponsive gemini surfactant (C7-azo-C7) having an azobenzene skeleton as a spacer. When mixtures of trans C7-azo-C7 aqueous solution and n-octane are homogenized, stable emulsions are obtained in a specific region of weight fraction and surfactant concentration. Fluorescence microscopy observations using a small amount of fluorescent probes show that the stable emulsions are oil-in-water (O/W)-type. UV irradiation of stable O/W emulsions promotes the cis isomerization of trans C7-azo-C7 and leads to the coalescence of the oil (octane) droplets in the emulsions, that is, demulsification. While the equilibrated interfacial tension (IFT) between aqueous trans C7-azo-C7 solution and octane is almost the same as that between aqueous cis C7-azo-C7 and octane, the occupied area per molecule for C7-azo-C7 at octane/water interface decreases with the cis photoisomerization of trans isomer. Dynamic IFT measurement shows that UV irradiation to the interface between aqueous trans C7-azo-C7 solution and octane brings about an increase in the interfacial tension, indicating that the Gibbs free energy at the interface increases. From these results, the cis isomerization of trans C7-azo-C7 molecules at the O/W interface due to UV irradiation leads to direct contact between the water and octane phases, because of the reduction of molecular area at the interface, and subsequently makes the emulsions demulsified.

Small-molecule compounds strongly affecting osteogenesis can form the basis of effective therapeutic strategies in bone regenerative medicine. A cell-based high-throughput screening system might be a powerful tool for identifying osteoblast-targeting candidates; however, this approach is generally limited with using only one molecule as a cell-based sensor that does not always reflect the activation of the osteogenic phenotype. In the present study, we used the MC3T3-E1 cell line stably transfected with the green fluorescent protein (GFP) reporter gene driven by a fragment of type I collagen promoter (Col-1a1GFP-MC3T3-E1) to evaluate a double-screening system to identify osteogenic inducible compounds using a combination of a cell-based reporter assay and detection of alkaline phosphatase (ALP) activity. Col-1a1GFP-MC3T3-E1 cells were cultured in an osteogenic induction medium after library screening of 1280 pharmacologically active compounds (Lopack1280). After 7 days, GFP fluorescence was measured using a microplate reader. After 14 days of osteogenic induction, the cells were stained with ALP. Library screening using the Col-1a1/GFP reporter and ALP staining assay detected three candidates with significant osteogenic induction ability. Furthermore, leflunomide, one of the three detected candidates, significantly promoted new bone formation in vivo. Therefore, this double-screening method could identify candidates for osteogenesis-targeting compounds more reliably than conventional methods.

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

Dupilumab was approved for treating adult patients with atopic dermatitis (AD) refractory to topical therapy in Japan in April 2018, and self‐injection of dupilumab has been available since May 2019. Subcutaneous self‐injection of medication has benefits for patients and the healthcare system. However, anxiety about self‐injection, lack of confidence, and the complicated procedure could prevent initiating self‐injection. In this study, we assessed the experience of AD patients treated with dupilumab before and after introducing self‐injection, utilizing the Self‐Injection Assessment Questionnaire (SIAQ). Adult AD patients who received dupilumab by self‐injection and had been treated for more than 3 months after initiating self‐injection in our hospital from March 1, 2020, to June 19, 2021, were included in this study. Patients rated their perceptions about self‐injections using the SIAQ before the first self‐injection and 3 months after initiating self‐injection. Data were collected retrospectively from their charts. Data on 36 patients were analyzed. The mean age was 34.1 ± 11.5 years. Twenty patients used a prefilled auto‐injector, and the others used a prefilled syringe. Scores on self‐confidence and satisfaction with self‐injection significantly improved after introducing self‐injection. Feelings about injections improved in patients over 40 years and in those who felt anxious about self‐injection. A strong correlation in scores between satisfaction with self‐injection and the ease of use was observed. The results were not affected by clinical severity, gender, or device. Our results could encourage patients who dither to introduce self‐injection of dupilumab due to anxiety and/or lack of self‐confidence about self‐injection to initiate self‐injection. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors are efficacious for atopic dermatitis (AD). However, some patients receiving JAK inhibitors develop acne, especially younger patients, or herpes zoster, especially elderly patients, and desire to switch to dupilumab. We experienced two patients with immediate exacerbation of AD after switching from upadacitinib to dupilumab, and herein report these cases. This phenomenon is attributed to the difference in elimination half‐life of the two drugs and a slower onset of efficacy of dupilumab than upadacitinib. When switching from a JAK inhibitor to dupilumab, short‐term concomitant use, intensifying topical treatment, and/or rescue with cyclosporine should be considered. [ABSTRACT FROM AUTHOR]

High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions.

Abstract is missing (Short communication)