Hyperhidrosis is a common condition associated with a substantial negative impact on the quality of life. Several studies have described the clinical characteristics and disease burden of patients with hyperhidrosis in Japan. However, comparable real-world clinical data on hyperhidrosis from Hokkaido remain limited. We therefore evaluated real-world clinical practice patterns at our institution before and after the establishment of a specialized outpatient clinic for hyperhidrosis. In this retrospective study, we analyzed the data of 144 patients who presented with hyperhidrosis between November 2013 and March 2025. Patient characteristics, pathways to care, treatment modalities, and treatment continuation were evaluated using data from electronic medical records. The sex distribution, age at presentation, and subtype distribution of hyperhidrosis in our cohort were largely consistent with those reported in a prior nationwide survey. Primary axillary and/or palmar hyperhidrosis accounted for 87.5% of all cases. After launching a specialized clinic in April 2023, we observed a substantial increase in the number of patients who consulted for hyperhidrosis during visits for other dermatologic conditions; this finding may suggest the presence of previously unrecognized patients. However, changes in hospital access policies may also have influenced consultation patterns. The treatment continuation rates for axillary and palmar hyperhidrosis were both approximately 40%. Among the treatments for axillary hyperhidrosis, sofpironium bromide gel was prescribed most frequently, whereas glycopyrronium tosylate hydrate wipes showed a higher treatment continuation rate. In conclusion, the presence of a specialized outpatient clinic may improve access to care for patients with primary focal hyperhidrosis and facilitate the identification of previously unrecognized patients. However, treatment continuation remained suboptimal, highlighting the importance of improving continuity of care in hyperhidrosis management at our institution.

Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by chronic and relapsing eruptions of multiple sterile pustules on the palms and soles, which subsequently crust and desquamate. In addition to pustules, vesicles and pustulo-vesicles are often observed simultaneously. It is more prevalent among Japanese individuals, and the number of affected patients in Japan is estimated to be approximately 140,000 based on national health insurance claims data in Japan. Sterile osteitis occurs in 10%-30% of patients with PPP or a history of PPP, a condition referred to as pustulotic arthro-osteitis. Because it has become evident that focal infections act as triggering factors in approximately 80% of both conditions, their therapeutic algorithms differ fundamentally from those for psoriasis. The aim of the Treatment Guidance for Palmoplantar Pustulosis 2022 was to clarify the clinical manifestations and histopathological findings supporting the diagnosis of PPP, and to explain treatment algorithms and recommendation grades based on differences in triggering factors and pathophysiology between PPP and psoriasis. Although the level of evidence is limited due to the ethical and practical difficulties in conducting rigorous double-blinde clinical trials to evaluate the efficacy of focal infection treatment, the treatment recommendations were determined through expert consensus based on extensive clinical experience accumulated in Japan, together with relevant basic research findings.

Among the relatively common manifestations of dermatomyositis (DM), "mechanic's hands" refer to symmetric hyperkeratotic erythematous lesions on the ulnar aspect of the thumbs and the radial aspect of the index and middle fingers. The "pseudocheckerboard pattern" is a distinct histopathological finding associated with mechanic's hands. This pattern consists of vertical keratotic columns in the stratum corneum, some of which display a striped appearance characterized by alternating bands of orthokeratosis and parakeratosis in both vertical and horizontal orientations. Although this phenomenon is well documented, its underlying mechanism remains poorly understood. In this study, we collected tissue samples from 14 patients with DM accompanied by mechanic's hands and reviewed their clinical presentations and histopathological features. We identified several common histopathological findings of DM, including the characteristic pseudocheckerboard pattern associated with these lesions. Parakeratotic foci of the pseudocheckerboard pattern were observed within the stratum corneum, corresponding to the suprapapillary epidermis, where both CD4- and CD8-positive lymphocytes infiltrated the papillary dermis and suprapapillary epidermis. A portion of these lymphocytes expressed interleukin (IL)-17, and the number of IL-17-positive cells was comparable to that in psoriatic skin lesions. The inflammatory response was relatively confined to the papillary dermis and suprapapillary epidermis, suggesting that Th17-mediated epidermal hyperplasia may be involved in the pathogenesis of mechanic's hands.

Biologics are essential for treating psoriasis; however, secondary failure, often due to the development of anti-drug antibodies, is a significant concern. This study aimed to evaluate the relationship between secondary failure and the production of anti-drug antibodies in a real-world setting. Serum levels of anti-adalimumab and anti-secukinumab antibodies were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. A retrospective analysis was conducted on 85 patients with psoriasis, focusing on cases in which dermatologists identified secondary failure during biologic therapy. In the adalimumab group, eight patients were identified as having secondary failure. Among them, two showed high titers of anti-drug antibodies, and one showed a low titer. In the secukinumab group, four cases were judged to have secondary failure, but none had elevated antibody titers. The results of this study indicate that the mechanisms underlying secondary failure in real-world settings may vary depending on the drug. The secondary failure of adalimumab, a drug with high immunogenicity, is primarily attributed to the production of anti-drug antibodies. In contrast, for secukinumab, which has low immunogenicity, extending the dosing interval may lead to reduced serum drug levels and an increased risk of secondary failure.

BACKGROUND: Palmoplantar Pustulosis (PPP) is a chronic inflammatory skin disease that presents as pustules on the palms and soles. There are no oral medications for patients with mild PPP, with apremilast, a new oral PDE4 inhibitor, indicated for moderate to severe cases of the disease. We previously reported that antimicrobial therapy improved PPP symptoms according to dermatological assessment (improvement or not), with a negative correlation between lymphocyte-to-monocyte ratio (LMR) and improvement of symptoms. However, the correlation between PPP area-and-severity index (PPPASI) and LMR could not be evaluated. METHODS: Herein, we used the PPPASI to evaluate the effect of antimicrobial therapy and investigate whether LMR, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), which reflect inflammation, could be used as indicators of treatment efficacy. Eleven patients who were administered an antimicrobial agent were enrolled. Treatment efficacy was measured by PPPASI 25 and PPPASI symptom subscales. Treated patients were compared with six control patients who had no change in PPP therapy during the observation period. In addition, the improvement in LMR, PLR, and NLR with antimicrobial treatment was analyzed and correlated with PPPASI. RESULTS: The antimicrobial drug treatment group was more likely to achieve PPPASI 25 than the control group. PPPASI symptoms subscale for erythema and desquamation were improved compared to those in the control group. There was a correlation between changes in PPPASI correlated with LMR, PLR, and NLR from antimicrobial treatment. CONCLUSIONS: Our results suggest antimicrobial drug treatment as therapy for mild PPP. In addition, LMR, PLR, and NLR are potential biomarkers of antimicrobial drug treatment. TRIAL REGISTRATION: This study is not considered a clinical trial because it is observational.

Background Pseudo-Kaposi sarcoma (PKS) is a rare vascular proliferative disease, caused by arteriovenous malformation (AVM) and chronic venous insufficiency. The lesions are characterized by purple or reddish-brownish papules, plaques, and nodules. Although benign, it is clinically similar to Kaposi's sarcoma (KS), a malignant disease, and must be differentiated by histopathological examination. We report a rare case of PKS with chronic limb-threatening ischemia (CLTI).Case presentation An 83-year-old man with diabetes mellitus (DM) presented to a local dermatology department with a complaint of a right second toe ulcer and was, thereby, referred to our department due to arterial bleeding during skin biopsy to exclude malignant diseases. Although the pulsation of dorsalis pedis artery of the affected limb was palpable, the skin perfusion pressure was only 20 and 30 mmHg on the dorsum and planter surface, respectively, indicating severe ischemia of toe and forefoot. Ultrasonography and computed tomography revealed an AVM around the right second metatarsophalangeal joint and occlusion of the right dorsalis pedis artery in the middle, indicating CLTI in the background. Pathological findings of the skin biopsy found capillary blood vessel proliferation, hemosiderin deposition, and extravascular red blood cell leakage in the dermal layer, which could be found in KS. However, CD34 was normally stained in the vascular endothelium, and human herpesvirus-8 staining was negative, resulting in the pathological diagnosis of PKS, a proliferative vascular lesion associated with AVM. The ulcer was spontaneously epithelialized, but 2 years later the ulcer recurred and infection developed, necessitating treatment for abnormal blood flow. Transarterial embolization using N-butyl 2-cyanoacrylate for the AVM controlled abnormal perfusion once; however, the procedure exacerbated perfusion of the toe, resulting in foot ulcer progression. Forefoot amputation with surgical excision of AVM was performed, and thereby, wound healing was achieved.Conclusion This is a rare case of PKS with CLTI complicated with AVM. As there is currently no established consensus on the treatment of PKS, the approach to treatment strategy should be tailored to the specific condition of each patient.

Eczematous paradoxical reactions are commonly associated with anti-interleukin-17A (anti-IL-17A) antibodies. However, IL-23 p19 inhibitors can also cause similar cutaneous manifestations. We present a case of a 77-year-old Japanese woman with palmoplantar pustulosis (PPP), who developed eczematous lesions on her face, neck, and dorsum of the hands 10 weeks after initiating guselkumab treatment. Patch tests revealed a positive reaction to Chrysanthemum flowers and leaves, confirming a diagnosis of contact dermatitis. This was notable, as the patient had routine contact with Chrysanthemum every morning for years without prior allergic reactions, until after initiating anti-IL-23 p19 antibody treatment. Given the temporal association and potential causal link with guselkumab administration, the treatment was discontinued, and avoiding contact with the plant improved the contact dermatitis eruptions. Concurrently, PPP lesions remained unchanged. IL-23 inhibition is known to skew the IL-12/T-helper 1 (Th1) axis, resulting in increased interferon-γ (IFN-γ) production, a cytokine implicated in the early sensitization phase of allergic contact dermatitis (ACD). Despite prior tolerance, this case report highlights the importance of considering drug-induced ACD in patients presenting with new-onset eczema while on biologic therapy, particularly in susceptible individuals.

The diagnosis of systemic amyloidosis relies on the detection of amyloid deposition in the tissue, often utilizing biopsy specimens from the abdominal skin owing to their minimal invasiveness. Several amyloid staining methods, including Congo Red, Direct Fast Scarlet (DFS), and Thioflavin T (ThT), have been employed for visualization. Lipomembranous fat necrosis (LFN) is a non-specific reaction pattern of adipose tissue to injury, typically derived from blood insufficiency across a wide range of clinical conditions or diseases. It is characterized by the presence of eosinophilic, crenulated, and/or serpiginous membranes in fat lobules. We encountered a patient in whom ThT yielded suspiciously positive results in amyloidosis screening tests. Furthermore, our retrospective observations suggested that ThT staining was positive for LFN, whereas DFS and Congo red staining yielded negative results. The awareness that LFN can result in false-positive ThT staining during amyloid screening is crucial to avoiding the misdiagnosis of systemic amyloidosis. Furthermore, skin samples should not be collected from areas prone to developing lipomembranous changes. The use of more than two different stains for skin biopsy specimens is recommended.

The Journal of DermatologyEarly View LETTER TO THE EDITOR A Japanese patient with hereditary angioedema caused by deep intron variation in the SERPING1 gene Tokimasa Hida, Tokimasa Hida orcid.org/0000-0003-3662-0095 Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorAki Ishikawa, Aki Ishikawa Department of Medical Genetics, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorMasae Okura, Masae Okura Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorMari Kishibe, Mari Kishibe orcid.org/0000-0002-2966-1756 Department of Dermatology, Asahikawa Medical University, Asahikawa, JapanSearch for more papers by this authorHisashi Uhara, Corresponding Author Hisashi Uhara [email protected] orcid.org/0000-0001-5391-3397 Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan Correspondence Hisashi Uhara, Department of Dermatology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan. Email: [email protected]Search for more papers by this author Tokimasa Hida, Tokimasa Hida orcid.org/0000-0003-3662-0095 Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorAki Ishikawa, Aki Ishikawa Department of Medical Genetics, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorMasae Okura, Masae Okura Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, JapanSearch for more papers by this authorMari Kishibe, Mari Kishibe orcid.org/0000-0002-2966-1756 Department of Dermatology, Asahikawa Medical University, Asahikawa, JapanSearch for more papers by this authorHisashi Uhara, Corresponding Author Hisashi Uhara [email protected] orcid.org/0000-0001-5391-3397 Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan Correspondence Hisashi Uhara, Department of Dermatology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan. Email: [email protected]Search for more papers by this author First published: 08 May 2023 https://doi.org/10.1111/1346-8138.16817Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – the 2021 revision and update. Allergy. 2022; 77: 1961– 90. 2Iwamoto K, Morioke S, Yanase Y, Uchida K, Hide M. Tissue factor expression on the surface of monocytes from a patient with hereditary angioedema. J Dermatol. 2014; 41: 929– 32. 3Vatsiou S, Zamanakou M, Loules G, Psarros F, Parsopoulou F, Csuka D, et al. A novel deep intronic SERPING1 variant as a cause of hereditary angioedema due to C1-inhibitor deficiency. Allergol Int. 2020; 69: 443– 9. 4Drouet C, López-Lera A, Ghannam A, López-Trascasa M, Cichon S, Ponard D, et al. SERPING1 variants and C1-INH biological function: a close relationship with C1-INH-HAE. Front Allergy. 2022; 3:835503. 5Hujová P, Souček P, Grodecká L, Grombiříková H, Ravčuková B, Kuklínek P, et al. Deep intronic mutation in SERPING1 caused hereditary angioedema through pseudoexon activation. J Clin Immunol. 2020; 40: 435– 46. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Epidermolysis Bullosa Simplex generalized severe (EBS-gen sev) is a hereditary blistering disease, mainly caused by keratin (K) 5 and K14 mutation. The mutational hotspot identified as K14 p.R125C/H missense mutation is located at the helix initiation motif, presumably impairing keratin polymerization with a dominant-negative effect. In the past, we found a Japanese family with EBS-gen sev which carries a novel heterozygous for K14 p.G364Rfr*118 mutation that leads to a frameshift and encodes an elongated protein due to a delayed terminal codon. Because differences in K14 mutations may lead to differences in pathogenesis, we hypothesized that a pathophysiology-based treatment strategy might be beneficial for EBS. To investigate the pathogenic impact of the K14 mutation, we generated three HaCaT cell lines, K14 wild-type (WT), the hotspot mutation K14 R125C, and K14 G364Rfr*118, in a doxycycline-inducible manner and compared cytological impact between the cell lines. Initially, we found that K14 G364Rfr*118-transfected keratinocytes had significantly more prominent and more numerous intracytoplasmic keratin aggregates and intracytoplasmic vacuoles compared to K14 wild type (WT) and R125C cells (P<0.01) and disrupted the distribution of tubulin filament. These findings suggest that the novel K14 mutation could make the cell structure more fragile than the hotspot mutation. Next, we tried to see whether removing the abnormal keratin aggregates could resolve the fragility of the cytoskeleton. Rapamycin-induced autophagy reduced the size of keratin aggregates in the cytosol of K14 G364Rfr*118 cells, whereas it did not alter that of K14R125C. Finally, therapeutic experiments showed that topical sirolimus gel slightly improved the healing of our patient's eruption. Treatment options based on underlying pathogenetic mechanisms may promote precision medicine for EBS and improve patients' quality of life.

Background: Lamellar granules (LGs) are essential cell organelles secreted extracellularly and contribute to skin barrier function. Our previous 3D electron microscopy (EM) studies revealed that LGs remains in the cytoplasm in the 3rd layer from the surface of the epidermal granule layer, SG3, and that secretion toward the surface layer begins in the 2nd layer, SG2, with all granules secreted in the 1st layer, SG1. However, the details of the regulatory mechanism of secretion still need to be fully elucidated. Aim: To clarify the secretory regulation mechanism of LGs. Materials & Methods: Healthy human skin samples were subjected to 2D transmission EM (TEM) and 3DEM. For the latter, we used serial section scanning electron microscopy (SEM), which uses imaging of resin-embedded thin sections on glass slides. We cut 300 serial sections of 100 nm thickness and examined them by SEM. Granular cells, nuclei, and extracellular LGs were segmented, and 3D images were reconstructed. Results: 2DEM showed that when SG2 cells are in contact with multiple SG1 cells, the LG secretion does not occur uniformly on the underside of all SG1 cells in contact. In 2DEM, however, cellular phenomena are not always correctly reflected in a particular cross-section, and the positional relationship of multiple SG1 cells is uncertain. 3DEM revealed that if an SG2 cell faced two or more SG1 cells, secretion of LGs can be limited on the underside of a particular SG1 cell, that was located closer to the stratum corneum than the other SG1 cells. Conclusion: Granule cells may be able to sense the degree of cell differentiation with which they are in contact. 3DEM can be a powerful tool for unraveling skin biology.

Autoimmune diseases triggered by coronavirus disease 2019 (COVID-19) mRNA vaccination have been emerging. Here, we report the case of a 27-year-old Japanese man with autoimmunity-related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjogren syndrome after the second dose of the Pfizer/BioNTech COVID-19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo-epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new-onset of SLE after COVID-19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti-SS-A/SS-B antibodies. COVID-19 mRNA vaccination can induce the production of type-I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity-related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme-like lesions.