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Psoriasiform drug eruption is defined as condition similar to psoriasis triggered by drug administration, including de novo development of psoriasis or exacerbation of pre-existing psoriasis. Herein, we describe a 52-year-old Japanese woman, who developed disseminated psoriasiform lesions following administration of temozolomide, a remedy for glioblastoma, although cutaneous adverse events by this drug was very rare. In addition, we assume that altered inflammatory signals associated with psoriasis, such as activation of signal transducer and activator of transcription 3 (STAT3), might be involved in the underlying pathomechanism of drug eruption caused by temozolomide. [ABSTRACT FROM AUTHOR]

Objective: Systemc sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Recently, it has been shown that leucine-rich α-2 glycoprotein (LRG) functions as a modulator of transforming growth factor-β (TGF-β) signaling in fibrosis. We aimed to characterize the effect of LRG in SSc model and SSc patients. Methods: Histological analysis was performed on LRG knockout (KO) and wild type (WT) mouse in the skin and the lung after bleomycin administration. Serum LRG levels were measured during the injection period. Gene expression analysis of the skin and lung tissue from LRG KO and WT mice was performed. In addition, serum LRG levels were determined in SSc patients and healthy controls. Results: LRG KO mice display an inhibition of fibrosis in the skin in association with a decrease of dermal thickness, collagen deposition, and phospho-Smad3 expression after bleomycin. Serum LRG concentration significantly increased in WT mice after bleomycin. There was also a suppression of inflammation and fibrosis in the LRG KO mouse lung indicated by a reduction of lung weight, collagen content, and phospho-Smad3 expression after bleomycin. Gene expressions of TGF-β and Smad2/3 were significantly reduced in LRG KO mice. Serum LRG levels in SSc patients were significantly higher than those in controls. Conclusion: LRG promotes fibrotic processes in SSc model through TGF-β-Smad3 signaling, and LRG can be a biomarker for SSc in humans and also a potential therapeutic target for SSc. [ABSTRACT FROM AUTHOR]

Objectives: von Willebrand factor (vWF) has prognostic value in patients with heart failure (HF) and in those with liver disease. Liver congestion, due to right-sided HF (RHF), is one of the major clinical pathophysiologic manifestations in adults with congenital heart disease (ACHD). The present study's purpose was to clarify the prognostic value of plasma levels of vWF antigen (vWF:Ag) in ACHD.Methods: We measured vWF:Ag (%) in 382 consecutive patients (20 unrepaired cyanotic ACHD, 172 Fontan patients and 190 ACHD after biventricular repair) and compared the results with the clinical profiles and prognosis.Results: The plasma vWF:Ag level was 130±53 (normal range: 55%-190%), and 48 patients (13%) showed high levels of vWF:Ag (≥190%). Older age, Fontan circulation, higher central venous pressure, lower arterial oxygen saturation and lower plasma levels of albumin were independently associated with high log (vWF:Ag) (p<0.05-0.0001). During the follow-up of 2.4±1.4 years, 15 patients died. High log (vWF:Ag) predicted the all-cause mortality (HR 1.63 per 0.1, 95% CI 1.40 to 1.96, p<0.0001). Specifically, patients with high vWF:Ag (≥165%) had a substantially higher risk of all-cause mortality (HR 56.4, 95% CI 11.4 to 1020, p<0.0001), and this prognostic value was independent of plasma levels of brain-type natriuretic peptide.Conclusions: High vWF:Ag may reflect RHF severity and related liver dysfunction with a strong prognostic value of all-cause mortality in ACHD. Thus, vWF:Ag might be an excellent biomarker for monitoring ACHD with RHF. [ABSTRACT FROM AUTHOR]

Apremilast is an anti-psoriatic medicine that works intracellularly by inhibiting phosphodiesterase 4 (PDE4), thereby blocking the degradation of cyclic adenosine monophosphate (cAMP), leading to its elevation (1, 2). The inhibition of PDE4 results in modification of the immune system, i.e. decreased expression of proinflammatory mediators, and increased anti-inflammatory mediators, such as IL-10 (1-3). A recent double-blind, placebo-controlled, randomized study demonstrated that apremilast may have a beneficial role in the treatment of palmoplantar psoriasis (4). Given that psoriasis has recently been defined as an autoimmune disease, apremilast may play a role in attenuating not only immune skewing, but also epidermal abnormalities. Therefore, in the current study, apremilast was administered to 6 patients with intractable palmoplantar keratoderma (PPKs) that resulted from psoriasis or other dermatodes, including pityriasis rubra pilaris (PRP), congenital ichthyosiform erythroderma (CIE) and acquired PPK. Surprisingly, all 6 patients showed favourable responses to apremilast within 4 months. Thus, the current study highlights the beneficial clinical effect of apremilast on PPKs in a variety of skin diseases. It also suggests the possibility that an inhibitory effect of apremilast on keratinocyte proliferation may ameliorate hyperkeratosis lesions in PPK. [ABSTRACT FROM AUTHOR]

Background: Despite the pathogenetic potential of human polyomavirus 6 (HPyV6) and human polyomavirus 7 (HPyV7), they have been found in the normal skin of healthy individuals. However, little is known about the prevalence, infection levels, and geographical variations of these polyomaviruses in the skin.Methods: Using skin swabs from 470 participants aged 2-98 years, we estimated the prevalence of copy numbers of HPyV6 and HPyV7 with respect to age and ethnicity. Phylogenetic analyses were conducted based on viral sequences obtained from Asian and white populations.Results: This study provides the first analyses of the age-specific prevalence and levels of HPyV6 and HPyV7 infections in normal skin. Comparisons of age groups revealed that the prevalence and viral loads were significantly higher in elderly persons. Phylogenetic analyses demonstrated the existence of Asian/Japanese-specific strains genetically distinct from strains prevalent in the skin of the white population studied.Conclusions: This large study suggests that HPyV6 and HPyV7 infections in the skin are highly prevalent in elderly adults. Further research is warranted to understand whether persistent infection with high viral loads in the skin could be a risk factor for the development of HPyV6- and HPyV7-associated skin disorders. [ABSTRACT FROM AUTHOR]

Livedo reticularis occurs when there is increased visibility of the venous plexus, often caused by reduced arterial inflow or venodilation.1 Although livedo reticularis has been reported in patients with COVID-19,2,3 it has also been reported following COVID-19 vaccination.4. [ABSTRACT FROM AUTHOR]

Background: Despite the oncogenic potential of Merkel cell polyomavirus (MCPyV), it has been found in the normal skin of healthy individuals; however, little is known about geographical variations in the ecology of MCPyV in this tissue.Methods: This study included 284 Japanese participants. Sun-unexposed arm and sun-exposed forehead skin swab samples were obtained and analyzed for MCPyV infection, using quantitative polymerase chain reaction. Phylogenetic analyses were also conducted, based on the full-length genes encoding MCPyV large T antigen and viral protein 1.Results: This study provides the first analyses of the age-specific prevalence and levels of MCPyV infection in normal skin. Steep increases in prevalence and viral load were observed in individuals aged >40 years. MCPyV infections with a high viral load were predominantly observed in the foreheads of subjects aged >60 years, among whom a high burden of MCPyV tended to persist. Phylogenetic analyses showed that all of the gene sequences obtained in this study clustered in a major clade, suggesting the existence of an Asian/Japanese genotype.Conclusions: This large study suggests that MCPyV infection with high viral loads is prevalent in the sun-exposed skin of elderly adults, making it necessary to follow up this cohort for possible transformation of MCPyV to a pathogenetic form. [ABSTRACT FROM AUTHOR]

The article describes a case study concerning a 67-year-old Japanese woman with clinically and immunologically typical paraneoplastic pemphigus (PNP) who benefited from plasma exchange (PE) therapy. Topics discussed include PNP's distinct features from classical pemphigus, extensive ulcerative oral mucosal lesions, and the absence of acantholysis. Also mentioned are PNP's development of autoreactive T lymphocytes and PE's removal of cytokines more efficiently than plasmapheresis.