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Psoriasis is an immune-mediated chronic inflammatory disease that predominantly affects the skin and joints. Systemic therapies are required for patients with moderate-to-severe psoriasis, and biologics can provide significant symptomatic improvement. Computed tomography (CT) analysis is recommended before and after biologic therapy to exclude the possibility of comorbid infections and malignancies; incidental findings are often detected in asymptomatic patients. In this study, we analyzed the common incidental findings on CT in 227 patients with psoriasis on biologic therapy and 219 living-kidney transplant donors at our hospital. Incidental findings on CT were observed in 176 (77.5%) patients with psoriasis. The most common were fatty liver (82 patients, 36.1%), urolithiasis (54 patients, 23.8%), pulmonary lesions (47 patients, 20.7%), gallstones or postoperative gallstones (38 patients, 16.7%), liver cysts (36 patients, 15.9%), renal cysts (33 patients, 14.5%), and colonic diverticulum (22 patients, 9.7%), which were observed in 38 (17.4%), eight (3.7%), 68 (31.1%), 12 (5.5%), 58 (26.5%), 88 (40.2%), and 10 (4.6%) donors, respectively. The prevalence of fatty liver, urolithiasis, gallstones, and postoperative gallstones was significantly higher in patients with psoriasis. Multivariate logistic regression showed that psoriasis was a risk factor for fatty liver disease, urolithiasis, and gallstones. Currently, incidental findings on CT in patients with psoriasis have not been well studied. The results of this survey will lead to increased awareness of the incidental findings on CT as a complication of psoriasis., (© 2023 Japanese Dermatological Association.)

This real-world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1-, 2-, 3-, and 4-year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%)., (© 2023 Japanese Dermatological Association.)

Objective: The 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations provide an evidence-based guide for selecting therapy based on the individual's disease features. Beyond the disease features and associated conditions (eg, uveitis and inflammatory bowel disease), comorbidities play an important role in selecting therapy for an individual patient., Methods: We performed a systematic literature review. We examined the available evidence to inform treatment selection based on the presence or absence of comorbidities in psoriatic arthritis (PsA)., Results: Common comorbidities in PsA that may affect treatment selection include presence of baseline cardiovascular disease (CVD) or high risk for CVD, obesity and metabolic syndrome, liver disease, mood disorders, including depression in particular, chronic infections, malignancies, osteoporosis, and fibromyalgia and/or central sensitization., Conclusion: Comorbidities may influence both the effectiveness of a given therapy but also the potential for adverse events. It is important to assess for the presence of comorbidities prior to therapy selection., (Copyright © 2023 by the Journal of Rheumatology.)

The population-based Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey was designed to better understand patient and dermatologist perceptions of the disease burden of psoriasis (PsO) and their treatment expectations. UPLIFT was a cross-sectional, quantitative, online survey conducted in Europe, North America, and Japan between 2 March and 3 June 2020. In Japan, 391 patients reporting a diagnosis of PsO and/or psoriatic arthritis (PsA) were surveyed (75% had PsO alone, 23% had PsO and PsA, and 2% had PsA alone). Self-reported body surface area (BSA) data were available for 309 Japanese patients, with the majority (80%) reporting PsO-involved BSA ≤3 palms. Current symptoms of PsO were rated as moderate or severe by 43% of Japanese patients with BSA ≤3 palms, and severe by 44% of patients with BSA 4-10 palms. PsO frequently occurred in ≥1 special areas, most commonly the scalp in 76% of Japanese patients with BSA ≤3 palms, and ≥90% of those with BSA ≥4 palms. Furthermore, musculoskeletal symptoms in 42% of patients with PsO alone were suggestive of PsA. Whereas Japanese patients with BSA ≤3 palms mainly reported receiving topical therapy alone (34%) or no treatment (32%), 64% patients with BSA 4-10 palms reported receiving systemic therapy. Overall, 21% of Japanese patients with self-perceived mild symptoms of PsO and 48% of patients with special area involvement experienced at least a moderate impact of disease on quality of life (Dermatology Life Quality Index score >5). Moreover, patients and dermatologists differed in their perceptions of determinants of PsO severity and treatment, and office visit discussions. In general, these findings from the Japanese subgroup of the UPLIFT survey demonstrated that a high proportion of patients perceived their symptoms to be moderate or severe irrespective of the level of skin involvement, suggesting a persistent unmet treatment need., (© 2022 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing COVID-19 pandemic has affected both daily life and medical care; therefore, the aim of this study was to analyze the use of biologics for inflammatory skin diseases during the COVID-19 pandemic in our hospital. The observation period was between 1 January 2020 and 23 February 2021. In this study, we enrolled 227 patients with psoriasis, six patients with palmoplantar pustulosis (PPP), 69 patients with atopic dermatitis (AD), and five patients with hidradenitis suppurativa (HS). Bioswitch was performed in 25 patients with psoriasis (11.0%). Biologics were discontinued in 14 patients with psoriasis (6.2%), 10 patients with AD (14.5%), and four patients with HS (80.0%); they were not discontinued in patients with PPP. The introduction of biologics was observed in 27 patients with psoriasis (11.9%), four patients with PPP (66.7%), 33 patients with AD (47.8%), and two patients with HS (40.0%). The use of telephone consultations was observed in four patients with psoriasis and two patients with AD. One patient, who received adalimumab for the treatment of psoriatic arthritis, suffered from COVID-19 and recovered after a mild course. In conclusion, we report our experience regarding the use of biologic drugs for inflammatory skin diseases. The use of biologics seemed safe for use amidst COVID-19 infection during the observation period; however, further observation on a larger number of patients is required to confirm the risks and benefits of biologic use in the COVID-19 era., (© 2021 Japanese Dermatological Association.)

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints., (Copyright © 2021 by The Journal of Rheumatology.)

This is a Japanese retrospective single-center study carried out between 1 January 2010 and 21 November 2018 at the Department of Dermatology in Jichi Medical University Hospital. The drug survival rate for six biologic agents used for the treatment of psoriasis was investigated. We reviewed the clinical records of 315 treatment series of 205 patients with moderate to severe psoriasis treated with adalimumab (103 cases), infliximab (70 cases), ustekinumab (66 cases), secukinumab (38 cases), brodalumab (12 cases) and ixekizumab (26 cases). In our study, ustekinumab revealed a trend towards higher drug survival among the six biologic agents. Ustekinumab had a higher drug survival rate than infliximab and secukinumab with significant differences by log-rank test among all patients and among biologic-naive (bio-naive) patients. There was no significant difference in drug survival between bio-naive and biologic-experienced (non-naive) patients in the treatment courses with adalimumab, infliximab, ustekinumab, secukinumab and ixekizumab. The dose augmentation therapy in infliximab-treated patients was associated with longer drug survival. Of all patients, 25 cases with generalized pustular psoriasis (GPP) were included, who functioned as the negative predictor for drug persistence with a hazard ratio of 1.87 (95% confidence interval, 1.12-3.11; P = 0.016). Our results reveal that ustekinumab had a superior drug survival, which is supported by the previous studies. Further studies are needed to clarify the efficacy of biologic agents on patients with GPP., (© 2019 Japanese Dermatological Association.)

Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.

Apremilast is a novel oral phosphodiesterase-4 inhibitor approved for treatment of plaque psoriasis and psoriatic arthritis in Japan in December 2016. We have treated a substantial number of patients with psoriasis with apremilast and investigated the length of the treatment period with apremilast (drug survival of apremilast) in 138 patients with psoriasis who were treated at the Department of Dermatology in Jichi Medical University Hospital from 1 March 2017 to 31 August 2018 using the Kaplan-Meier survival curve. The drug survival rate of apremilast at 1 year was 53.4%. The median length of the drug survival period was 453 days. There were no statistical differences in the drug survival rate in terms of the type of psoriasis, previous systemic treatment or presence of one or more adverse events. Drug efficacy was investigated in 115 patients who were followed for more than 16 weeks. There was no correlation between drug efficacy and sex, previous systemic treatment or presence of one or more adverse events; however, there was a correlation between drug efficacy and plaque size (P < 0.01, rs = -0.29). The result of our study indicates that apremilast is effective regardless of the history of prior systemic treatment, and it supports our previous finding that small plaque-type psoriasis is more sensitive to treatment with apremilast., (© 2019 Japanese Dermatological Association.)

Adalimumab (ADA) is one of the tumor necrosis factor (TNF)-α monoclonal antibodies used for the treatment of psoriasis. In Japan, standard dosing of ADA for adults is an initial s.c. injection of 80 mg, followed by 40 mg every other week. Some patients who initially do not respond to treatment are allowed an increased dose of 80 mg every other week. However, studies on the efficacy and safety of ADA dose escalation to 80 mg every other week are few. In this study, we retrospectively studied 92 patients with psoriasis who received ADA therapy in our hospital. In 45 out of 92 patients, the dose of ADA 80 mg was administrated every other week, and the efficacy was observed within 12 weeks. The most common adverse drug reaction was upper respiratory infection, followed by diarrhea. In three patients, malignancies occurred during the observation period. No deaths or other severe complications were observed. In conclusion, this study showed the efficacy and safety of ADA dose escalation to 80 mg every other week in patients with psoriasis., (© 2019 Japanese Dermatological Association.)

Apremilast is a novel oral phosphodiesterase 4 inhibitor effective for psoriasis. It regulates the production of pro-inflammatory mediators. Apremilast was approved in December 2016 in Japan; however, its efficacy and safety in a real-world setting among Japanese patients have not been reported. We report on 44 patients treated with apremilast between March and October 2017. The median treatment duration was 25 weeks (range, 2-33). Thirty-five patients (79.5%) continued the drug for at least 23 weeks, and five (11.4%) achieved a Psoriasis Area and Severity Index 100 response within 12 weeks. Nine patients discontinued the drug within 24 weeks mainly due to insufficient efficacy (n = 3) and adverse events (n = 4). Seven patients continued their previous systemic therapies such as cyclosporin (n = 1), methotrexate (n = 1), etretinate + methotrexate (n = 1) and biologics (n = 4) combined with apremilast. Of these patients, 55.9% had at least one adverse event although no severe adverse events. The most common adverse event was diarrhea (31.8%), followed by nausea (25.0%), headache (13.6%), abdominal discomfort (6.8%) and vomiting (6.8%). The proportion of diarrhea in our patients was higher than those of previous clinical trials. Among 10 patients with psoriatic arthritis, apremilast did not improve joint pain in nine (90%). To investigate the relationship between treatment efficacy and plaque size, we defined a small plaque as an individual rash diameter of 1 inch or less. The efficacy of apremilast was greater in patients with small plaques than in patients with large plaques., (© 2018 Japanese Dermatological Association.)

We report a case of a 70-year-old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti-tumor necrosis factor (TNF)-α therapy to anti-interleukin-12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo-controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti-TNF-α antibodies that specifically block the interaction of TNF-α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy., (© 2016 Japanese Dermatological Association.)

Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent - treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) - and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3-4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann-Whitney U-test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab., (© 2016 Japanese Dermatological Association.)

Background: Psoriasis features an increased level and activity of tumor necrosis factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV) and psoriatic arthritis in Caucasians., Objective: To examine whether these SNPs are associated with susceptibility to PV in Japanese patients, we investigated the genotype and allele frequencies at each SNP in Japanese PV patients and in controls., Methods: We examined 163 PV patients and 96 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method., Results: No significant association between the genotypes or alleles of these SNPs and susceptibility to PV was observed., Conclusion: These SNPs themselves are not associated with susceptibility to PV in the Japanese., (Copyright 2003 S. Karger AG, Basel)

We examined polymorphisms of vitamin D receptor (VDR) gene in Japanese patients with psoriasis vulgaris (PsV). We also studied the association between VDR gene polymorphisms and the response to vitamin D (VD) topical treatment in psoriatic patients. FokI, BsmI, ApaI and TaqI genotypes were determined by restriction fragment patterns in patients (n = 115) and controls (n = 69). In addition, 54 psoriatic patients were divided into two groups in terms of their response to VD (tacalcitol) topical treatment: non-responsive (n = 30) and responsive (n = 24) patients. The frequencies of B allele and t allele were lower in patients than in controls (9 vs. 19%: p < 0.01, 7 vs. 14%: p < 0.05, respectively). In regard to response to VD treatment, F allele was lower in non-responsive patients than in controls (47 vs. 64%, p < 0.05). We show that polymorphisms of VDR gene are associated with Japanese patients with PsV. Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of PsV., (Copyright 2002 Elsevier Science Ireland Ltd.)

Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance., (Copyright 2002 Elsevier Science Ireland Ltd.)