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Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase‐4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i‐related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i‐unrelated BP, 17 patients with DPP4i‐related BP, and 13 healthy controls were analyzed. Patients with DPP4i‐related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)‐erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti‐BP180 antibody than patients with DPP4i‐unrelated BP. The serum interleukin (IL)‐6 level was significantly higher in patients with DPP4i‐related BP than in healthy controls (P = 0.0037). The serum IL‐10 level was significantly higher in patients with DPP4i‐related BP than in patients with DPP4i‐unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI‐blister/erosions score (r = 0.757, P = 0.001), BPDAI‐erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI‐total score (r = 0.833, P < 0.001) in patients with DPP4i‐related BP. In conclusion, patients with DPP4i‐related BP had increased serum levels of IL‐6 and IL‐10 compared with healthy controls and positive correlations between the serum IL‐10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL‐10 level is a potential objective biomarker of disease severity in patients with DPP4i‐related BP. [ABSTRACT FROM AUTHOR]

Recent studies indicate that hepatic diseases are associated with psoriasis. Non‐invasive tests, including the Fibrosis‐4 (FIB‐4) index, which can confidently rule out the presence of advanced fibrosis, are currently receiving attention. However, data on the FIB‐4 index in psoriasis patients and the effects of biologics on the FIB‐4 index are limited. We investigated the relationships between the FIB‐4 index and demographic or clinical characteristics as well as the effects of biologics on the FIB‐4 index in psoriasis patients. Psoriasis patients aged 36–64 years, whose treatment was initiated with interleukin (IL)‐17 inhibitors or IL‐23 inhibitors for psoriasis from May 2015 to December 2022, were consecutively included. Data were collected retrospectively from the patients' charts. A total of 171 psoriasis patients were included in this study. Thirty‐four, 43, 21, 32, and 41 psoriasis patients were treated with secukinumab, ixekizumab, brodalumab, guselkumab, or risankizumab, respectively. In biologics‐naïve patients, a significant but weak positive correlation was observed between the FIB‐4 index and age (r = 0.3246, p = 0.0018). There was no significant correlation between the FIB‐4 index and other demographic or clinical characteristics. Regarding the effects of biologics on the FIB‐4 index, no significant change was observed in psoriasis patients treated with any biologics. However, in psoriasis patients with a baseline FIB‐4 index of >1.3, patients treated with guselkumab and those treated with either IL‐23 inhibitor showed significantly decreased FIB‐4 index scores 6 months after initiating the biologics (p = 0.0323, p = 0.0212). In contrast, no change was observed in FIB‐4 index scores in patients treated with IL‐17 inhibitors. In conclusion, our study revealed that the FIB‐4 index was correlated with age in psoriasis patients. Furthermore, IL‐23 inhibitors (but not IL‐17 inhibitors) decreased the FIB‐4 index score at 6 months in psoriasis patients with elevated FIB‐4 index scores at baseline. Further studies are needed to clarify whether IL‐23 inhibitors improve liver fibrosis physiologically and functionally. [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]

It has recently been revealed that mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)‐36 receptor antagonist (IL‐36Ra), which has antagonistic roles against IL‐36α, ‐36β, and ‐36γ. Previously, sanger sequencing performed in 62 Chinese GPP patients to identify IL36RN mutations revealed a new variant, c.245C>T (p.Pro82Leu), in a single heterozygous state in a patient with adult‐onset GPP with psoriasis vulgaris. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris or control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses. Meanwhile, Sorting Intolerant From Tolerant and PolyPhen‐2, pathogenicity prediction tools, predict this variant as tolerated and benign. To date, its pathogenicity is unknown. We experienced a patient with GPP harboring the p.Pro82Leu variant, and investigated mRNA and protein expressions of IL‐36Ra. Polymerase chain reaction conducted on hair follicle samples obtained from the scalp of the patient with GPP harboring the p.Pro82Leu using primers to detect mRNA of exons 2 and 5 in IL36RN demonstrated mRNA expression of IL36RN. Immunohistochemical staining revealed IL‐36Ra expression in the keratinocytes of the patient with GPP harboring the p.Pro82Leu as in those of a GPP patient without the mutation (positive control). Furthermore, quantitative analysis of the immunofluorescent staining by ImageJ revealed that the expression level of IL‐36Ra in the keratinocytes of the patient with GPP harboring p.Pro82Leu was higher than that in the healthy control and not lower than that in the GPP patients without the mutation. Our results indicate no aberrant splicing in this variant. In addition, according to the 1000 Genomes Project, this variant could be a founder mutation. Considering these factors together, this variant is unlikely to be associated with the development of GPP. [ABSTRACT FROM AUTHOR]

Psoriasis is characterized by increased dermal vascularity, indicating that aberrant angiogenesis is associated with the pathogenesis of psoriasis. Data on angiogenesis‐related factors in psoriasis patients are limited. We explored serum levels of angiogenesis‐related factors in patients with psoriasis, and investigated their association with clinical severity and laboratory data. Psoriasis patients visiting our hospital from April 2013 to April 2018 and healthy controls were included in this study. Serum levels of angiopoietin‐1, fibroblast growth factor (FGF)‐basic, epidermal growth factor (EGF), platelet endothelial cell adhesion molecule (PECAM)‐1, placental growth factor, and vascular endothelial growth factor (VEGF) were measured by LEGENDplex. Serum samples obtained from 10 healthy controls, 18 patients with psoriasis vulgaris (PsV), 24 patients with psoriatic arthritis (PsA), and 13 patients with generalized pustular psoriasis (GPP) were analyzed. The serum angiopoietin‐1 level was elevated in the PsV, PsA, and GPP patients. GPP patients had a higher serum VEGF level than healthy controls. In contrast, serum levels of EGF and PECAM‐1 were lower in the PsV, PsA, and GPP patients than in healthy controls. The serum FGF‐basic level was lower in the PsA and GPP patients than in healthy controls. Serum levels of FGF‐basic in PsA and GPP patients, PECAM‐1 in PsA patients, and VEGF in GPP patients became closer to the respective levels in healthy controls after systemic therapy. The serum FGF‐basic level was positively correlated with the psoriasis area and severity index and the number of circulating eosinophils in GPP patients. The serum VEGF level was correlated positively with the serum C‐reactive protein (CRP) level and erythrocyte sedimentation rate, and negatively with the serum albumin level in GPP patients. In conclusion, our exploratory study revealed that psoriasis affects serum levels of certain angiogenesis‐related factors. Some of these factors could be biomarkers of treatment outcomes, clinical severity, and systemic inflammation. [ABSTRACT FROM AUTHOR]

The impact of the COVID‐19 pandemic on biologic treatment for psoriasis in Japan remains to be elucidated. This study aimed to investigate changes in biologic treatment and patients' behavior of visiting our department, especially in psoriasis patients treated with biologics before and during the pandemic. Data were collected from medical records retrospectively. The numbers of new psoriasis patients before (2019) and during (2020) the pandemic were compared. Patients' behavior of visiting our department was evaluated. The number of new psoriasis patients who visited our department in 2020 decreased by 35.7% compared with that in 2019. The reduction rate of new patients with psoriasis vulgaris was 49.3%, whereas the numbers of new patients with psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP) were almost the same in 2019 and 2020. The number of patients who newly initiated biologics did not decrease in 2020 compared with that in 2019. As of January 1, 2020, 215 psoriasis patients were treated with biologics. Six patients (2.8%) discontinued biologics treatment possibly due to COVID‐19 in 2020. Among 212 patients with good adherence to visiting our department in the previous year, 24 patients (11.3%) refrained from their visits for at least 1 month. In most cases, refrainment was observed in April and May when the first state of emergency was in effect in Japan. In conclusion, the COVID‐19 pandemic hindered patients from visiting our department. However, its impact on patients who needed intensive care, such as patients with PsA and GPP, and psoriasis patients treated with biologics, was limited. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in the cranial nerve or dorsal root ganglia, with spread of the virus along the sensory nerve to the dermatome. Postherpetic neuralgia is a feared complication of HZ and impairs patients' quality of life enormously. However, there is no predictor of the duration of neuralgia. Our objective was to investigate whether there are correlations between the duration of neuralgia and serum levels of potential biomarkers in order to find practical predictors of the duration of neuralgia. Patients who were diagnosed with HZ at our hospital from April 2013 to January 2014 were included in this study. Serum levels of cytokines and other biomarkers were measured using commercial enzyme‐linked immunosorbent assay kits. Thirty patients (15 men and 15 women) with HZ were enrolled in this study. The mean age was 66.1 ± 9.2 (standard deviation) years (range, 51–84 years). Four patients were evaluated as having mild, 19 as having moderate, and seven as having severe HZ. Patients with severe HZ suffered from neuralgia for a significantly longer period of time than patients with mild‐to‐moderate HZ (9.86 ± 8.25 months vs. 2.01 ± 2.68 months, severe vs. mild‐to‐moderate, p = 0.0021). The serum interleukin (IL)‐10 level was significantly higher in patients with severe HZ than in those with mild‐to‐moderate HZ (12.93 ± 3.27 pg/mL vs. 6.74 ± 3.72 pg/mL; severe vs. mild‐to‐moderate; p = 0.0487). Furthermore, the serum IL‐10 level was significantly correlated with the duration of neuralgia (r = 0.5193, p = 0.0111). Lastly, the serum IL‐10 level significantly decreased after treatment in comparison with that before treatment (from 8.15 ± 4.46 pg/mL to 4.32 ± 11.83 pg/mL, p < 0.0001). In conclusion, these results suggest that the serum IL‐10 level is an objective biomarker of the severity of HZ, and that the serum IL‐10 level can be a practical predictor of the duration of neuralgia. [ABSTRACT FROM AUTHOR]

Thymus and activation‐regulated chemokine (TARC) is designated as a T‐helper 2‐type chemokine and its expression is upregulated in patients with atopic dermatitis. Previous studies reported that serum TARC levels in patients with psoriasis vulgaris (PsV) were comparable with those in healthy controls. However, the association of clinical severity of psoriasis with serum TARC levels and serum TARC levels in patients with psoriatic arthritis (PsA) or generalized pustular psoriasis (GPP) have never been reported. We investigated the association of serum TARC level with psoriasis by the type of psoriasis, and examine correlations of serum TARC levels with clinical severity scores and other results of blood tests. Data on 75 patients (51 men and 24 women; PsV, 30 patients; PsA, 29 patients; GPP, 16 patients) were analyzed. The serum TARC level was significantly higher in patients with GPP than in patients with PsV and patients with PsA. There was a positive correlation between serum TARC level and Psoriasis Area and Severity Index score (r = 0.3499, P = 0.0030). The serum TARC levels decreased after treatment in GPP patients. Our study revealed that the serum TARC level can potentially be one of the biomarkers reflecting the severity or systemic inflammation caused by psoriasis in patients with psoriasis, although not as much as in patients with atopic dermatitis. Furthermore, serum TARC levels were high in patients with GPP. Those were decreased by treatment, suggesting that serum TARC levels could be utilized as an objective biomarker to evaluate a therapeutic effect in individual GPP patients. Further accumulation of cases and further research are needed to elucidate the role of TARC in psoriasis. [ABSTRACT FROM AUTHOR]

Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12 months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients' charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12 months after initiating dupilumab but not at 1 month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6 months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1 month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases. [ABSTRACT FROM AUTHOR]

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid‐stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C‐reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = −0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a T‐helper (Th)1/Th17‐mediated, chronic inflammatory dermatitis that is commonly treated with topical corticosteroids and vitamin D3 analogs. The combination of a topical corticosteroid and vitamin D3 analog showed superior efficacy to each alone in clinical trials; however, the mechanisms by which the topical corticosteroid and vitamin D3 analog exert their effects on lesional skin in combination and each alone remain unknown. In this study, we examined the effects of combined calcipotriol (Cal)/betamethasone dipropionate (BD) ointment on psoriasis in vivo, utilizing imiquimod (IMQ)‐induced murine psoriasiform skin inflammation, compared with each alone. Vehicle, Cal/BD, Cal or BD was applied on the shaved back skin for 3 consecutive days. Then, IMQ was applied for 6 consecutive days. Twenty‐four hours after the last IMQ treatment, the murine skin was evaluated clinically and pathologically. mRNA expressions were examined by quantitative polymerase chain reaction. All ointments alleviated IMQ‐induced psoriasiform skin inflammation clinically in comparison with vehicle application. Cal/BD suppressed mRNA expressions of cytokines involved in psoriasis pathogenesis such as interleukin (IL)‐17A and IL‐22 efficiently. Cal alone induced IL‐10 expression, whereas BD alone reduced IL‐6 mRNA expression and the number of phosphorylated signal transducer and activator of transcription 3‐positive cells in lesional skin. Our study revealed that Cal and BD have different effects on IMQ‐induced psoriasiform skin. Some of the immune effects of Cal and BD may be additive or synergistic, which may account for the superior clinical efficacy of their combination. [ABSTRACT FROM AUTHOR]

The combination of BRAF inhibitor and MEK inhibitor is one of the first‐line treatments for unresectable BRAF‐mutant melanoma or as an adjuvant therapy. However, some patients who received the combination of dabrafenib and trametinib (CombiDT) or the combination of encorafenib and binimetinib (CombiEB) had adverse events (AEs) including pyrexia. We herein report a patient with BRAF‐mutated melanoma who repeatedly developed elevated levels of D‐dimer and pyrexia after CombiDT and CombiEB treatments. Moreover, concomitant edoxaban prevented these AEs, enabling the patient to continue receiving CombiEB. [ABSTRACT FROM AUTHOR]

Rhododendrol (RD), 4‐(4‐hydroxyphenyl)‐2‐butanol, inhibits melanin synthesis and had been used in skin‐whitening cosmetic products until 2013. However, some individuals developed leukoderma on the skin where RD had been applied and have suffered from refractory depigmentation even after discontinuing RD application. Bimatoprost is a prostaglandin F2α analog and is often used for eyelash growth for cosmetic reasons as well as in the treatment of glaucoma. It was reported that bimatoprost induced skin pigmentation in addition to iris pigmentation as adverse effects. Therefore, we conducted an open‐label single‐center pilot study to evaluate the effectiveness of bimatoprost on refractory RD‐induced leukoderma. Eleven Japanese female patients with skin type III who developed leukoderma on the exact or slightly extended area of skin where RD had been applied and gained a halt of enlargement of leukoderma or repigmentation on a part of the affected skin after discontinuation of RD were enrolled. Bimatoprost 0.03% solution was applied on the leukoderma once daily for 3 months, and then the frequency of application was increased to twice daily for the subsequent 3 months. Ten patients completed the 6‐month course of bimatoprost application. In four patients, bimatoprost application brought slight improvement in RD‐induced refractory leukoderma by dermatologists' evaluation. Because the number of enrolled patients was limited, further larger studies are necessary to better assess the effectiveness of bimatoprost in inducing repigmentation in patients with RD‐induced refractory leukoderma. [ABSTRACT FROM AUTHOR]

Abstract: Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)‐4 inhibitors have become commonly used to treat diabetes. As DPP‐4 inhibitors are more commonly prescribed for diabetes, BP related to DPP‐4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP‐4 inhibitor‐related BP (nine patients; median age, 85 years) in comparison with non‐DPP‐4 inhibitor‐related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP‐4 inhibitor‐related BP patients and non‐DPP‐4 inhibitor‐related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP‐4 inhibitor‐related BP patients and non‐DPP‐4 inhibitor‐related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti‐BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor‐related BP than in patients with non‐DPP4 inhibitor‐related BP. Our results showed that DPP‐4 inhibitor‐related BP has some distinct pathological characteristics from BP not associated with DPP‐4 inhibitor. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that presents with erythema and sterile pustules, pathologically characterized by Kogoj's spongiform pustules. GPP is sometimes accompanied by mucosal involvement, and the most common lesion is on the tongue. IL36RN mutation was found to contribute to the pathogenesis of GPP especially in patients who develop GPP without a past medical history of psoriasis vulgaris. The association of IL36RN mutation with mucosal involvement in GPP is controversial. We herein report a 60‐year‐old male GPP patient with no past history of plaque psoriasis presenting with not only severe skin lesions and arthritis but also severe mucosal involvements of pharyngeal and gastrointestinal lesions, which led to gastrointestinal bleeding. Our case did not have any mutation in the IL36RN gene. We should be aware that severe GPP can cause gastrointestinal bleeding. The relevancy of IL36RN mutation with mucosal involvement in GPP remains to be elucidated. [ABSTRACT FROM AUTHOR]