This case series from Japan describes three patients with generalized pustular psoriasis who required additional biologic therapies after initial treatment with spesolimab because of persistent erythematous lesions. While spesolimab rapidly resolved pustules and systemic symptoms, complete disease control could not be achieved with acute-phase spesolimab treatment alone, underscoring the need for further data on long-term management strategies.

Psoriasis vulgaris is a persistent inflammatory skin disease that often necessitates long-term biologic therapy to maintain symptom control and prevent flares. Interruptions in biologic treatment are sometimes unavoidable due to individual health concerns or external circumstances, but the impact of repeated, extended gaps in therapy remains insufficiently understood. We describe a case involving a woman with moderate-to-severe psoriasis vulgaris who achieved sustained remission using tildrakizumab, even after multiple treatment interruptions, each lasting over a year. The patient initially received various conventional and biologic treatments before transitioning to tildrakizumab. Despite prolonged discontinuations prompted by personal concerns, she consistently regained complete skin clearance within months of restarting therapy. No therapy-related adverse events were recorded during any biologic treatment period. This case emphasizes the potential resilience of tildrakizumab efficacy in the setting of intermittent administration, suggesting its suitability for patients who may face unavoidable gaps in care. Further research is warranted to evaluate immunogenicity risks and long-term effectiveness in larger, diverse patient populations.

Introduction Cell transplantation therapy has emerged as a promising approach in regenerative medicine for treating neurological diseases. Neural stem/progenitor cell (NS/PC) transplantation has demonstrated therapeutic efficacy; however, its potential remains limited by suboptimal differentiation and insufficient secretion of pro-healing growth factors. Trehalose, a glucose disaccharide, has been shown to exert neuroprotective effects by inducing autophagy and stabilizing cellular structures. Recent studies suggest that trehalose can modulate growth factor secretion through the CDKN1A/p21 pathway. However, its impact on human induced pluripotent stem cell-derived NS/PCs (hiPSC-NS/PCs) remains unclear. This study investigates the effect of trehalose on neuronal differentiation, cell viability, and growth factor expression in hiPSC-NS/PCs to explore its potential in enhancing transplantation therapy. Methods hiPSC-NS/PCs were cultured as neurospheres and treated with trehalose (10 mg/ml or 40 mg/ml) for 7 days. Cell viability was assessed using CellTiter Glo® assay. Gene expression analysis was conducted via qRT-PCR and RNA-seq, particularly focusing on CDKN1A, VEGFA, FGF2, and BDNF. Protein expression of SOX2 was analyzed via western blotting. Neurite outgrowth was evaluated using MAP2 immunostaining following differentiation. Statistical significance was set at p < 0.05. Results Treatment with 10 mg/ml trehalose upregulated CDKN1A expression and promoted neuronal differentiation, as evidenced by reduced SOX2 expression and enhanced neurite outgrowth. RNA-seq analysis revealed the activation of growth factor-related pathways, including VEGFA upregulation, which persisted even after trehalose withdrawal (p = 0.016). However, high concentration (40 mg/ml) significantly reduced cell viability (p = 0.032), suggesting dose-dependent cytotoxicity. Conclusion Trehalose enhances neuronal differentiation and VEGFA secretion in hiPSC-NS/PCs, potentially augmenting the efficacy of transplantation therapy. These findings suggest that trehalose may serve as a valuable adjunct for neural regeneration, though optimal dosing must be determined to balance differentiation enhancement and cell viability. Further in vivo studies are warranted to validate its clinical applicability.

Myositis-specific autoantibodies found in dermatomyositis (DM) are associated with clinical symptoms and responses to therapy and are useful for diagnosis, treatment selection, and prognostication. Although the prevalence of anti-small ubiquitin-like modifier-activating enzyme (anti-SAE) antibodies in DM patients is low, clinical features such as skin symptoms preceding muscle symptoms and a higher incidence of dysphagia and malignancy have been reported. Herein, we present a case of anti-SAE antibody-positive DM in which panniculitis of the lower legs, a rare dermatological manifestation of DM, preceded muscle symptoms by 2 months. This case was associated with cervical cancer; however, the clinical course of DM was favourable with glucocorticoid monotherapy. Anti-SAE antibody-positive DM needs to be considered as a differential diagnosis of unexplained panniculitis without muscle symptoms.

Background Trehalose is a naturally occurring disaccharide found in invertebrates but cannot be synthesized by vertebrates. We previously reported that high-concentration trehalose induces a transient senescent-like state in fibroblasts, leading to cell cycle arrest and growth factor secretion via CDKN1A/p21, and this process promoted keratinocyte proliferation, enhancing capillary formation and wound closure in vivo . Objective This study aimed to investigate the effect of trehalose on human keratinocytes. Methods Previously published RNA-seq data of cytokine-untreated samples from our group of trehalose-treated human keratinocytes were re-analyzed, and an in vitro scratch assay was performed using cells treated with mitomycin C. Results The trehalose-treated group exhibited increased wound closure. A significantly increased secretion of vascular endothelial growth factor (VEGF) was observed in keratinocytes treated with high-concentration trehalose, which is one of the most crucial molecules inducing angiogenesis in the skin. Significant upregulation of mRNA level and protein secretion of VEGF was confirmed using qPCR and ELISA, respectively. Furthermore, treatment with axitinib, a VEGF receptor inhibitor, significantly suppressed trehalose-induced activation of keratinocyte migration. Additionally, the increase in trehalose-induced migration activity was significantly inhibited by the Jun N-terminal kinase (JNK) inhibitor SP600125 and the PI3K inhibitor LY294002. Conclusion Trehalose promotes wound healing via VEGF secretion from keratinocytes and the PI3K and JNK pathways. The findings of this study may lead to the development of novel therapeutic agents that can alter the wound healing process. IMPORTANT GUIDELINES CONTACT The Review Commons office can be contacted directly at: office{at}reviewcommons.org

Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis. At high concentrations, the nonreducing disaccharide trehalose (a-d-glucopyranosyl a-d-glucopyranoside) induces a transient senescence-like state in fibroblasts and promotes wound repair. In this study, we investigated the effect of trehalose on normal human keratinocytes and demonstrated its specific role in the skin barrier. RNA-sequencing analysis revealed that trehalose regulates the expression of many skin barrier-associated genes. T helper 2 cytokines IL-4/IL-13 were observed to downregulate several differentiation markers (FLG, loricrin, keratin 1, and keratin 10) and epidermal antimicrobial proteins in monolayer-cultured keratinocytes and living skin equivalents and impaired skin barrier function in living skin equivalents, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MAPK/extracellular signal-regulated kinase kinase 5-extracellular signal-regulated kinase 5 and suppressing extracellular signal-regulated kinase kinase 1/2-extracellular signal-regulated kinase pathway. It also increased NRF2 activation to trigger antioxidant enzyme production through JNK, thus neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription 3/signal transducer and activator of transcription 6 activation and restored IL-4/IL-13-suppressed skin barrier molecules through IL-33 downregulation and NRF2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in atopic dermatitis.

We comment on the study by Caldarola et al. highlighting the increased risk of eczematous eruptions with ixekizumab in patients with psoriasis, especially those with atopic predisposition. We propose that differences in BIO potency between biologics, such as the higher potency of ixekizumab compared with secukinumab, may underlie this risk. Future large-scale studies involving diverse populations are needed to validate this hypothesis.

BACKGROUND:Bach2 has been suggested to be a risk factor for allergic diseases in previous studies. Because type IV hypersensitivity reactions, including allergic contact dermatitis (ACD), develop through activated T cells, and because the expression of Bach2 is regulated in the development and functional differentiation of T cells, the expression of Bach2 in T cells may be involved in the onset of ACD. However, the role of Bach2 in T cells during ACD development has not yet been determined. OBJECTIVE:We investigated the role of the appropriate expression of Bach2 in T cells in the development and prolongation of ACD. METHODS:We induced ACD in mice by repeatedly applying a hapten and analyzed the expression of Bach2 in the T cells of lesional skin or skin-draining lymph nodes (sdLNs). We performed a phenotypic analysis of the skin and/or sdLNs by comparing mice with T cells overexpressing Bach2 or with Bach2 loss to the control mice. RESULTS:We found that Bach2lo T cells accumulated in the skin and sdLNs as ACD developed. T-cell-specific Bach2-deficient mice showed more severe inflammatory responses to the hapten and had prolonged inflammation with T cells expressing higher levels of IL-13 in the skin and IFN-γ and IL-13 in the sdLNs. In contrast, the mice overexpressing Bach2 in T cells developed almost no symptoms of ACD. CONCLUSION:The appropriate expression of Bach2 in T cells may be a key factor in the resolution of ACD.