Hiroyuki Matsue's research while affiliated with Chiba University and other places

Background Few studies have examined the effectiveness of the reciprocity law in ultraviolet excimer therapy. This study aimed to examine the difference in erythematous reaction in human skin when the irradiance of ultraviolet excimer treatment devices differed while the irradiation dose was constant. Materials and methods This study, conducted at the Department of Dermatology, Chiba University, included 15 healthy adults aged 20–65 years (mean age, 46.3 years; seven men). Using ultraviolet excimer treatment devices with different irradiances (50 or 150 mW/cm²), the upper abdomen of each participant was irradiated with ultraviolet light at set irradiation doses (80, 100, 120, 140, 160, 180, and 200 mJ/cm²). The erythema index of each irradiated site was measured using a melanin‐ and erythema‐measuring device, and the difference in erythema index before and 24 h after irradiation was the primary endpoint. Results The change in erythema index was significantly higher for an irradiance of 150 mW/cm². Significant differences (p < 0.05) were observed between these irradiance levels at irradiation doses of 100‒200 mJ/cm². Conclusions Even for the same irradiation dose, stronger erythematous reactions occurred at higher irradiances in ultraviolet excimer treatment. This suggests that the reciprocity law may not always hold true in excimer therapy.

Background In clinical practice, the quality of images may vary depending on the imaging device, and the focus of the dermoscope is on the superficial layer of the lesion. Therefore, it is desirable to have a dermoscopy device that can easily focus on any lesion and clearly show the findings. Objectives We conducted a clinical study to compare dermoscopic images of the same skin tumours obtained using a prototype dermoscopy camera, DZ‐D100 (DD, Casio Computer Co., Ltd.), and three existing dermoscopy imaging devices (Derma9500S®‐GR or DG, Derma Medical Inc.; DELTA 20® T or DT, HEINE Optotechnik; and DermLite Foto II Pro® or DF, DermLite LLC). Methods Dermoscopic images of 117 skin tumours from 94 patients who visited Chiba University Hospital were evaluated by two experts in terms of the focus, and the clarity and presence or absence (the primary endpoint) of seven findings (pigmented lines, shiny white lines, dots/globules, blue‐grey structures, vascular structures, milia‐like cysts and comedo‐like openings). Results No significant differences in the number of cases with each of the seven findings (pigmented lines, shiny white lines, dots/globules, blue‐grey structures, vascular structures, milia‐like cysts and comedo‐like openings) among the four groups were observed. The clarity of focus was significantly better with the DD than with the other three devices (all, p < 0.05). Pigmented lines were significantly clearer with the DD than with the DF and DT (all, p < 0.05). A strong correlation was found between the focus and clarity of pigmented lines/globules, blue‐grey structures and vascular structures (all, p < 0.005). Conclusions DD was less affected by elevated lesions and was considered to be the easiest to focus and recognize brown to black lines and dots/globules. The well‐focused captured images are also expected to be applied to diagnosis by artificial intelligence.

Patients with psoriasis vulgaris have a higher incidence of pemphigoid than the general population. However, there are only a few concise reports on the coexistence of generalized pustular psoriasis (GPP) and pemphigoid. The authors describe a rare case of the simultaneous development of GPP and pemphigoid with multiple autoantibodies (i.e., BP180-C-terminal, 200-kDa protein, and laminin 332 proteins) in a complete responder of immune checkpoint inhibitor (ICI) treatment for lung cancer. Anti-interleukin 17 inhibitors for the GPP and oral corticosteroids at 10 mg/day for the pemphigoid effectively achieved remission in both diseases. It may not be uncommon to detect multiple autoantibodies in patients with pemphigoid; however, the detection of autoantibodies to more than three antigens in a single patient is relatively rare. In the current patient, the severe inflammation of GPP might have generated multiple autoantibodies. In addition, although pembrolizumab achieved a complete response and was discontinued 9 months before the onset of GPP and pemphigoid, the ICI might have affected the development of the two diseases. This case report adds useful information to the limited knowledge regarding the coexistence of GPP and pemphigoid, and aids in a better understanding of the pathological mechanisms and treatment options for such patients. Furthermore, the possibility that more patients may develop multiple autoimmune and autoinflammatory diseases in the era of ICIs should be recognized.

Background: Intravenous immunoglobulin (IVIg) was reported to be an effective treatment for bullous pemphigoid. However, the impact of IVIg approval on real-world outcomes remains unclear. Objectives: To investigate the effect of IVIg approval on patients with bullous pemphigoid using a national inpatient database. Methods: Using the Japanese Diagnosis Procedure Combination database, we identified 14,229 patients hospitalized for bullous pemphigoid and treated with systemic corticosteroids between July 2010 and March 2020. We conducted an interrupted time-series analysis to compare in-hospital mortality and morbidity between the patients before and after the approval of reimbursement of IVIg for bullous pemphigoid in the Japanese universal health insurance system in November 2015. Results: In-hospital mortality was 5.5% before and 4.5% after the approval of IVIg reimbursement. After the IVIg approval, 18% of the patients were treated with IVIg. Based on the interrupted time-series analysis, in-hospital mortality significantly decreased at the time of approval (-1.2% [95% confidence interval, -2.0% to -0.3%], P = .009) and a downward trend was observed after the approval (-0.4% annual rate, [-0.7% to -0.1%], P = .005). In-hospital morbidity also demonstrated a downward trend after the approval. Conclusion: IVIg approval is associated with lower in-hospital mortality and morbidity in inpatients with bullous pemphigoid.

Imiquimod (IMQ) is widely used as animal model of psoriasis, a chronic inflammatory skin disorder. Although topical application of IMQ to back skin causes splenomegaly in mice, how the spleen affects the psoriasis-like phenotype of IMQ-treated mice remains unclear. In this study, we analyzed the cellular composition of spleen and measured metabolites in blood of IMQ-treated mice. We also investigated whether splenectomy influences the degree of skin inflammation and pathology in IMQ-treated mice. Flow cytometry showed that the numbers of CD11b+Ly6c+ neutrophils, Ter119+ proerythroblasts, B220+ B cells, F4/80+ macrophages, and CD11c+ dendritic cells in the spleen were significantly higher in IMQ-treated mice compared to control mice. An untargeted metabolomics analysis of blood identified 14 metabolites, including taurine and 2,6-dihydroxybenzoic acid, whose levels distinguished the two groups. The composition of cells in the spleen and blood metabolites positively correlated with the weight of the spleen. However, splenectomy did not affect IMQ-induced psoriasis-like phenotypes compared with sham-operated mice, although splenectomy increased the expression of interleukin-17A mRNA in the skin of IMQ-treated mice. These data suggest that the spleen does not play a direct role in the development of psoriasis-like phenotype on skin of IMQ-treated mice, though IMQ causes splenomegaly.

IL-17 plays important roles in host defense against Candida albicans at barrier surfaces and during invasive infection. However, the role of IL-17 in host defense after colonization of the epidermis, a main site of C. albicans infection remains poorly understood. Using a murine model of epicutaneous candidiasis without skin abrasion, we found that skin inflammation triggered by epidermal C. albicans colonization was self-limiting with fungal clearance completed by day 7 after inoculation in wild-type mice or animals deficient in IL-17A or IL-17F. In contrast, marked neutrophilic inflammation in the epidermis and impaired fungal clearance was observed in mice lacking both IL-17A and IL-17F. Clearance of C. albicans was independent of Dectin-1, Dectin-2, Card9, TLR2, and Myd88 in the epidermal colonization model. We found that group 3 innate lymphoid cells (ILC3s) and γδT cells were the major IL-17 producers in the epicutaneous candidiasis model. Analyses of Rag2−/− mice and Rag2−/−Il2rg−/− mice revealed that production of IL-17A and IL-17F by ILC3s was sufficient for C. albicans clearance. Finally, we found that depletion of neutrophils impaired C. albicans clearance in the epidermal colonization model. Taken together, these findings indicate a critical and redundant function of IL-17A and IL-17F produced by ILC3s in host defense against C. albicans in the epidermis. The results also suggest that epidermal C. albicans clearance is independent of innate immune receptors or that these receptors act redundantly in fungal recognition and clearance.

Open access article at "DOI: https://doi.org/10.1016/j.jdin.2022.04.007" Background Psoriasis is a known risk factor for acute myocardial infarction (AMI). However, the associations between psoriasis and short-term outcomes of AMI remain controversial. Objective To compare the short-term outcomes of AMI patients with and without psoriasis accounting for patient background characteristics and site-specific effects. Methods We identified patients with AMI between July 2010 and March 2020, using a Japanese national inpatient database. We matched patients with and without psoriasis to generate a 1:10 matched-pair cohort matched for sex, hospital, and fiscal year at admission. Multivariable regression analyses with adjustment for background characteristics including age and Killip class at admission were conducted to compare short-term outcomes of AMI. Results In this study of AMI patients with psoriasis (n = 455) and without psoriasis (n = 438,534), 30-day in-hospital mortality was 5.6%. Patients with psoriasis had higher proportions of comorbidities than patients without psoriasis. Multivariable regression analyses in the matched-pair cohort revealed that psoriasis was significantly associated with decreased 30-day in-hospital mortality (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.85). Limitations Retrospective study design without data on psoriasis severity. Conclusion The matched-pair cohort analyses with adjustment for patient background characteristics and site-specific effects revealed decreased in-hospital mortality in AMI patients with psoriasis.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease associated with arterial and venous thromboembolism (VTE) or recurrent fetal loss in individuals carrying antiphospholipid antibodies (aPL). We report a case of a 76-year-old man with plaque psoriasis who presented with VTE and was diagnosed with APS. APS prevalence in patients with psoriasis is currently unknown; our findings suggest that psoriasis patients with VTE may need to be screened for aPL, because the treatment strategy to prevent thrombosis recurrence is different for aPL-positive patients.

Malignant melanomas often present with irregular shapes and in multiple shades of brown under white light. Dermoscopy is used to diagnose malignant melanomas; nevertheless, it is often difficult to differentiate malignant melanoma from healthy pigmented skin. The DZ‐D100 dermoscope (Casio Computer) is a digital camera equipped with a white light‐emitting diode (LED) and a violet LED, which can capture non‐polarized/polarized conventional dermoscopy images (CDS) as well as violet‐light dermoscopy (VLD) images. Since the absorption wavelength of melanin approaches that of ultraviolet rays, VLD with a wavelength of 405 nm can be used to visualize it. This camera allows three images with the same composition to be captured simultaneously. In this case, we performed dermoscopy with DZ‐D100 to determine the surgical resection margins of a melanoma of the heel in a 76‐year‐old woman. The pale‐colored lesions that were difficult to demarcate by CDS were clearly visible by VLD, presenting as dark areas in the grayscale images. Preoperatively determined lesion boundaries with CDS in combination with VLD were histologically more accurate than those with conventional CDS alone. Therefore, the combination of CDS and VLD may reveal the distribution of subtle pigmentation of fine melanin in the skin, making it easier to distinguish between lesions and healthy skin. As one of the limitations, parts of the heel with thick stratum corneum were also observed to be dark gray in the VLD images. Therefore, the evaluation of pigment lesion should be performed by comparing both CDS and VLD.