A Successful Switch From Ustekinumab to an Extended Dosing Interval of Guselkumab Without Induction in a Patient With Psoriasis Vulgaris.

Psoriasis vulgaris, also known as plaque-type psoriasis, is the most common form of psoriasis. It is characterized by erythematous plaques covered with scales. Among the available treatments, the fully human monoclonal antibodies ustekinumab (UST) and guselkumab (GUS) have low immunogenicity. Additionally, GUS has not been found to have a significant risk of inducing the development of clinically relevant neutralizing antibodies. Therefore, we sometimes consider switching to GUS when UST is insufficiently effective. However, switching to another biological agent usually requires an induction phase, potentially incurring additional costs. We herein present the first case of a successful transition from UST 90 mg to an extended dosing interval of GUS without an induction phase. This approach may be a viable and cost-saving option, especially for patients with relatively low disease activity.

Effects of hot bath therapy on cholinergic urticaria with hypohidrosis or anhidrosis.

Cholinergic urticaria with hypohidrosis or anhidrosis (CUHA) can impair quality of life due to itching, tingling, and reduced sweating. Current treatment options for CUHA include antihistamines, pulsed steroids, and sweat-promoting therapies such as exercise or hot baths. However, the efficacy of these therapies, particularly hot bath therapy, has yet to be established. We evaluated the efficacy of hot bath therapy in patients with CUHA. We enrolled eight patients who underwent hot bath therapy between January 2010 and August 2022. Patients had a half-body bath in a bathtub filled with hot water (40-43°C) for 30-60 minutes daily for 3-7 days. After treatment, pain improved in three (42.9%) patients, urticaria improved in four (50%) patients, and anhidrosis improved in five (62.5%) patients without any severe adverse events. Because hot bath therapy is easily performed, it should be considered a treatment option for patients with CUHA.

A fluorescence imaging technique suggests that sweat leakage in the epidermis contributes to the pathomechanism of palmoplantar pustulosis.

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.

Flare-up of generalized pustular psoriasis combined with systemic capillary leak syndrome after coronavirus disease 2019 mRNA vaccination.

Generalized pustular psoriasis (GPP) is characterized by acute flare-ups induced by various factors, but few reports have described GPP onset or flare-up induced by vaccination. To our knowledge, only three such cases following coronavirus disease 2019 (COVID-19) vaccination have been reported. We herein report a case of GPP flare-up after COVID-19 mRNA vaccination. A 65-year-old man with GPP controlled by infliximab presented with widespread pustular erythema, fever, and malaise following his second COVID-19 mRNA vaccination. A skin eruption was apparent at the injection site. He also exhibited systemic capillary leak syndrome (SCLS), which responded rapidly to secukinumab and systemic corticosteroids. Two biopsies, one of which was of the injection site, revealed not only findings typical of GPP, but also a dermal mixed-cell infiltration with eosinophils, and microthrombi in the small dermal vessels. The latter findings have been observed in cutaneous lesions induced by both COVID-19 infection and vaccination. This is the first case of a GPP flare-up accompanied by SCLS induced by a COVID-19 mRNA vaccine. Also, this is the first flare-up induced by the second vaccine dose, and the first such report including detailed histological data, including for the injection site.

NIR-II-Excitable Dye-Loaded Nanoemulsions for Two-Photon Microscopy Imaging of Capillary Blood Vessels in the Entire Hippocampal CA1 Region of Living Mice.

For in vivo two-photon fluorescence microscopy (2PM) imaging, the development of techniques that can improve the observable depth and temporal resolution is an important challenge to address biological and biomedical concerns such as vascular dynamics in the deep brain (typically the hippocampal region) of living animals. Improvements have been achieved through two approaches: an optical approach using a highly tissue-penetrating excitation laser oscillating in the second near-infrared wavelength region (NIR-II, 1100-1350 nm) and a chemical approach employing fluorescent probes with high two-photon brightness (characterized by the product of the two-photon absorption cross section, σ2, and the fluorescence quantum yield, Φ). To integrate these two approaches, we developed a fluorescent dye exhibiting a sufficiently high σ2Φ value of 68 Goeppert-Mayer units at 1100 nm. When a nanoemulsion encapsulating >1000 dye molecules per particle and a 1100 nm laser were employed for 2PM imaging, capillary blood vessels in almost the entire hippocampal CA1 region of the mouse brain (approximately 1.1-1.5 mm below the surface) were clearly visualized at a frame rate of 30 frames s-1 (averaged over eight frames, practically 3.75 frames s-1). This observable depth and frame rate are much higher than those in previous reports on 2PM imaging. Furthermore, this nanoemulsion allowed for the visualization of blood vessels at a depth of 1.8 mm, corresponding to the hippocampal dentate gyrus. These results highlight the advantage of combining bright probes with NIR-II lasers. Our probe is a promising tool for studying the vascular dynamics of living animals and related diseases.

A Case of Eosinophilic Pustular Folliculitis since Birth.

A newborn male infant presented with multiple pustules and erosions with erythema involving his scalp and forehead at birth. One week after birth, new pustules continued to appear, forming crusted, ring-shaped plaques with pigmentation. Tests for possible pathogens were negative. Tzanck smear and skin biopsy revealed pustules beneath the stratum corneum at sites corresponding to hair follicles, which contained eosinophils and neutrophils. Taken together, a diagnosis of eosinophilic pustular folliculitis (EPF) was made. The pustules on the head disappeared rapidly with topical corticosteroid treatment, although new eruptions were still observed on the trunk about one month after birth. To our knowledge, only two cases of EPF since birth have been reported to date. Here, we also discuss the differential diagnosis of noninfectious pustular diseases at birth, including erythema toxicum neonatorum and transient neonatal pustular melanosis. These diseases, and EPF, may present with very similar clinical symptoms at birth, and the Tzanck test or biopsy may be required for differential diagnosis.

High-quality Fluorescence Imaging of the Human Acrosyringium Using a Transparency: Enhancing Technique and an Improved, Fluorescent Solvatochromic Pyrene Probe.

Two-photon, excitation fluorescent microscopy featuring autofluorescence or immunofluorescence, combined with optical clearance using a transparency-enhancing technique, allows deep imaging of three-dimensional (3D) skin structures. However, it remains difficult to obtain high-quality images of individual cells or 3D structures. We combined a new dye with a transparency-enhancing technology and performed high-quality structural analysis of human epidermal structures, especially the acrosyringium. Human fingertip skin samples were collected, formalin-fixed, embedded in both frozen and paraffin blocks, sliced, stained with propidium iodide, optically cleared using a transparency-enhancing technique, and stained with a new fluorescent, solvatochromic pyrene probe. Microscopy revealed fine skin features and detailed epidermal structures including the stratum corneum (horny layer), keratinocytes, eccrine sweat glands, and peripheral nerves. Three-dimensional reconstruction of an entire acrosyringium was possible in one sample. This new fluorescence microscopy technique yields high-quality epidermal images and will aid in histopathological analyses of skin disorders.

Case of thymoma-associated cutaneous graft-versus-host disease-like disease successfully improved by narrowband ultraviolet B phototherapy.

Thymoma-associated graft-versus-host disease (GVHD)-like disease is a rare paraneoplastic disease seen in patients with thymoma. Here, we describe the first case of thymoma-associated GVHD-like disease localized to the skin that was successfully improved by a combination of systemic corticosteroids and whole-body narrowband ultraviolet (UV)-B phototherapy. The patient had developed toxic epidermal necrolysis-like erosive skin lesions over the whole body. Although systemic corticosteroids were effective up to a point, we were unable to begin the steroid taper. The addition of systemic narrowband UV-B phototherapy improved the skin manifestation of this disease, allowing corticosteroids to be reduced to a third of the original dose. Histopathologically, it was confirmed that the proportion of Foxp3-positive lymphocytes in the skin increased after narrowband UV-B irradiation. We propose that whole-body narrowband UV-B phototherapy is a good therapeutic option for the skin manifestation of thymoma-associated GVHD-like disease.