This multicentre study compares four immunoassays for detecting antilaminin 332 IgG in mucous membrane pemphigoid. The keratinocyte footprint assay showed the highest diagnostic accuracy, while the laminin 332 Biochip (R) provided excellent specificity as a standardized and widely accessible diagnostic option.

BACKGROUND:X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by pathogenic variants in the Bruton tyrosine kinase ( BTK ) gene, leading to severe B-cell maturation defects and pan-hypogammaglobulinemia. Botryomycosis is a rare chronic bacterial infection, typically caused by Staphylococcus aureus ( S. aureus ), characterized by suppurative and chronic inflammation and grape-like bacterial clusters in tissue. CASE PRESENTATION:We report 2 adult male siblings with previously undiagnosed XLA who presented with cutaneous botryomycosis. Case 1, aged 20 years, developed painless perianal nodules and plaques; laboratory tests revealed markedly decreased IgG, IgM, and IgA. Deep tissue cultures grew methicillin-resistant S. aureus , Streptococcus agalactiae , and Peptoniophilus species. Case 2, his elder brother, aged 21 years, had recurrent pneumonia and persistent verrucous nodules on both lower extremities; methicillin-resistant S. aureus was cultured from a localized abscess. Both siblings carried the same BTK pathogenic variant (c.1760T > C; p.Met587Thr). Skin lesions in both patients resolved with systemic antibiotics and subcutaneous immunoglobulin replacement therapy. HISTOPATHOLOGY:Biopsies revealed chronic inflammation with scattered neutrophils, fibrosis, and capillary proliferation centered on the hair follicle. Follicular infundibulum contained grape-like clusters of cocci, occasionally forming tetrads, without Splendore-Hoeppli phenomenon. The organisms were Gram-positive and nonspecifically Gomori methenamine silver-positive. Immunohistochemistry confirmed S. aureus as the causative pathogen. CONCLUSIONS:These sibling cases highlight cutaneous botryomycosis as an under-recognized but clinically relevant manifestation of XLA. Awareness of this association can facilitate earlier diagnosis of the underlying immunodeficiency through integration of clinical history, microbiology, immunohistochemistry, and histopathology.

Background: In the diagnosis of linear IgA bullous dermatosis (LABD), detection of IgA at the epidermal basement membrane zone and circulating IgA autoantibodies are essential. The disease has two subtypes, lamina lucida-type and sublamina densa-type, with 120 kDa LAD-1 and 97 kDa LABD97 as major autoantigens for lamina lucida-type. Normal human epidermal keratinocytes (NHEK) and HaCaT cells are widely used for immunoblotting (IB) in the diagnosis process, but they do not provide high sensitivity and semiquantitative analysis. Objective: To develop a more sensitive and convenient method for detecting IgA antibodies in lamina lucida-type LABD patients. Methods: The expressions of LAD-1 and LABD97 in lysates and culture supernatants from Ker-CT, HaCaT, DJM-1, and NHEK were compared. The sensitivity of IBs using concentrated culture supernatants of HaCaT and Ker-CT and ELISAs using several recombinant proteins (RPs) corresponding to BP180 ectodomain were compared using 55 sera from LABD patients. Results: In culture supernatant, Ker-CT expressed higher amounts of LAD-1 and LABD97. IBs using concentrated culture supernatant of HaCaT and Ker-CT showed 43 % and 46 % positivity to sera from LABD patients, respectively. In ELISAs, the RP of amino acids 490-1421 of BP180 showed the highest positivity (80.0 %) among several proteins. Additionally, this ELISA showed reduced OD values in LABD and related diseases patients' sera at remission. Conclusion: The ELISA using the RP coding amino acids 490-1421 of BP180 is useful for identifying IgA antibodies and monitoring disease activity in lamina lucida-type LABD patients. (c) 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Mucous membrane pemphigoid (MMP) is an autoimmune subepithelial/subepidermal blistering disease characterized by linear deposition of immunoglobulin G (IgG), IgA, and/or C3 in the basement membrane zone (BMZ) and predominant mucosal lesions involving the oral cavity and conjunctivae. Here, we describe a case of a 58-year-old Japanese man with MMP. Intraoral examination revealed desquamative gingivitis in the upper and lower gingivae. No conjunctival or cutaneous lesions were observed. Histopathological examination revealed a subepithelial split with inflammatory cell infiltration of the epithelial and connective tissues. Direct immunofluorescence revealed a linear deposition of C3 in the BMZ. IgG autoantibodies against BP230 were detected using an enzyme-linked immunosorbent assay. Indirect immunofluorescence using 1mol/L NaCl-split skin sections revealed no reactivity for serum IgG or IgA. Immunoblotting using normal human epidermal extract as a substrate did not detect IgG reactivity against the 230-kDa antigen. Based on the above results, the definitive diagnosis of MMP with anti-BP230 antibody alone was established. Our case was categorized as low-risk MMP. The patient was treated with 0.1% triamcinolone acetonide ointment, oral minocycline, and oral nicotinamide, which improved the oral erosions. However, the mechanism underlying IgG autoantibody production against intracellular BP230 remains unclear. Further research and more such case studies are necessary to elucidate the mechanism of anti-BP230 antibody production and the clinical feature of anti-BP230 type MMP.

In accordance with the advancement of therapies for skin malignancies, the Japanese Dermatological Association and Japanese Skin Cancer Society updated guidelines for skin malignancies to reflect current clinical practices. Basal cell carcinoma (BCC) is one of the most ordinary malignant cutaneous tumors and its incidence continues to grow in many countries. Clinically, BCCs in East Asian populations are usually pigmented, and 88.3% of total BCCs in Japanese patients are pigmented. However, a low proportion of BCCs in Western populations are pigmented. Therefore, diagnosis and tumor border evaluation of BCCs in Western populations are relatively difficult. From these characteristics, clinical guidelines for East Asian BCCs should differ from those for Western BCCs. This revised Japanese clinical guideline for BCC was also undertaken by a committee comprising experts across relevant fields who meticulously reviewed and systematized a wide range of literature on BCC to develop comprehensive, evidence-based guidelines. Literature searches were conducted by the Japan Medical Library in accordance with the Minds Clinical Practice Guideline Creation Manual 2020, ver. 3.0. Four clinical questions (CQs) were established, and corresponding recommendation statements were provided for each CQ. There are about the reduced margin resection for pigmented BCCs, the radiotherapy for the recurrent BCCs, the topical immune response modifiers, and the systemic therapy using immune checkpoint inhibitors. This Japanese clinical guideline for BCC will help clinicians select suitable therapies for BCCs in East Asia.

Extramammary Paget disease (EMPD) is a rare malignancy that primarily arises in apocrine gland-bearing areas such as the genital, perianal, and axillary regions. The clinical and biological heterogeneity of EMPD, together with a lack of evidence from large-scale studies, has made it difficult to establish standardized approaches to diagnosis and treatment. To address these issues, the 2025 Japanese Guidelines for the Management of EMPD were developed, providing evidence-based recommendations tailored to the healthcare context in Japan. These guidelines were constructed using the Minds Guideline Development Manual 2020 (ver. 3.0), adhering to systematic review principles and incorporating both Japan and international research findings. A multidisciplinary panel of dermatologists, oncologists, surgeons, and other specialists developed the guidelines through a consensus-based process, which included structured discussions and grading of evidence. The primary focus of this condensed version is on six critical clinical questions, which address key aspects of EMPD management, including the role of mapping biopsy in diagnosis, the use of sentinel lymph node biopsy in cases of suspected dermal invasion, the efficacy of nonsurgical therapies when surgery is not an option, the efficacy of lymph node dissection for multiple regional lymph node metastases, the efficacy of radiation therapy after regional lymph node dissection, and systemic treatment options for advanced disease. The recommendations aim to improve diagnostic accuracy, optimize therapeutic approaches, and support clinical decision-making by providing a clear framework for the management of EMPD. By focusing on these critical areas, the guidelines strive to enhance patient outcomes and contribute to the advancement of evidence-based care for this rare and challenging malignancy.

Patients with autoimmune bullous disease have their quality of life (QOL) affected by both the disease and its treatment burden. While QOL assessment is clinically important, it is often hindered by limited time in clinical practice, highlighting the need for accurate and efficient QOL evaluation tools. However, no validated QOL questionnaires are currently available in Japan. This study evaluated the validity and reliability of the Japanese versions of the Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires, as well as their practical application in clinical settings. The original questionnaires were forward and back-translated into Japanese by certified translators according to established guidelines, then their validity and reliability were evaluated using data from 147 patients with autoimmune bullous diseases. Validity was evaluated via confirmatory and exploratory factor analyses, cross-cultural validation, hypothesis testing, and convergent validity. Reliability was evaluated via test-retest and internal consistency. Although confirmatory factor analysis showed a weak fit and factor structures slightly differed from the original versions, internal consistency was cross-culturally valid. Also, the Japanese version cohort showed lower mean scores and better QOL outcomes compared with other language versions for similar cohorts. Hypothesis testing revealed a significant positive correlation between ABQOL scores and subjective disease severity; TABQOL scores were significantly correlated with steroid dosage. The mucosal subscale of the ABQOL showed a significant difference based on mucosal lesion status. Bland-Altman plots confirmed approximate agreement between the two sets of measurements: Cronbach's alpha coefficients were 0.872 for ABQOL and 0.903 for TABQOL, verifying reliability. Finally, an expert panel reviewed and agreed on the target population, timing, methods for using the scales, and considerations for scale evaluation. The Japanese versions of the ABQOL and TABQOL are expected to be implemented in clinical practice as reliable and validated tools in Japan.

SDR9C7-nonsyndromic epidermal differentiation disorder (nEDD) is a form of ceramide synthesis disorder that is known to confer susceptibility to dermatophytosis. Recurrent widespread tinea corporis developed in a SDR9C7-nEDD patient with homozygosity for the Japanese founder variant (c.826C>T, p.Arg276Cys) during apremilast treatment to improve ectropion. Ceramide analysis of the stratum corneum revealed decreased protein-bound ceramides, indicating skin barrier dysfunction. Based on previous studies of decreased Irf4 mRNA in Sdr9c7-/- mice, IRF4 transcription factor-dependent IL-17 production, and the importance of IL-17A/F in mucocutaneous immunity against Candida albicans, we examined the expression of each molecule using immunofluorescence and found for the first time decreased IRF4 and IL17-A/C/F (which were further decreased by apremilast treatment) in SDR9C7-nEDD epidermis. Although further studies are needed to clarify an evaluation of cytokine profiles in SDR9C7-nEDD, which may have immune profiles different from the previously reported IL-17-dominant immune profiles in the major forms of ichthyosis, these findings might have contributed to susceptibility to dermatophytosis in this patient, and it is suggested that the use of apremilast should be avoided in SDR9C7-nEDD.

Advancements in melanoma management have underscored the need for periodic guideline updates every few years to reflect current clinical practices. Previous versions of melanoma clinical practice guidelines in Japan have primarily aimed to reflect global standards of care. This focus on international benchmarks was largely attributed to the scarcity of high-quality evidence from East Asia, necessitating reliance on Western references. Recent findings indicate differences in melanoma subtypes and drug efficacy between Western and East Asian populations. Therefore, efforts were made to incorporate data from East Asia in this revision, aiming to develop guidelines that better reflect the region's unique characteristics. This revision was commissioned by the Japanese Dermatological Association (JDA) and Japanese Skin Cancer Society (JSCS) and was undertaken by a committee comprising experts across relevant fields who meticulously reviewed and systematized a wide range of literature on melanoma to develop comprehensive, evidence-based guidelines. Literature searches were conducted by the Japan Medical Library Association. The recommendation statements were determined using the GRADE Grid approach. The guideline was developed in accordance with the Minds Clinical Practice Guideline Creation Manual 2020, ver. 3.0. Twelve clinical questions (CQs) were established, and corresponding recommendation statements were provided for each CQ. For several CQs, the inclusion of data from East Asia resulted in recommendations that differed from those in Western guidelines. Considering that the biology of melanoma has been increasingly recognized to vary by subtype and ethnicity, guidelines should be developed independently for each region based on evidence specific to the melanoma characteristics of that region. We firmly believe that this JDA clinical guideline for melanoma will contribute to improving melanoma management in East Asia.

This revision work was commissioned by the Japanese Dermatological Association (JDA) and was undertaken by a committee of experts in related fields. The committee prepared comprehensive, evidence-based guidelines by thoroughly reviewing and systematizing a wide range of literature on cutaneous squamous cell carcinoma. The literature search was conducted by the Japan Medical Library Association. Recommendations were prepared using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scheme. These guidelines were prepared in accordance with the "Minds Clinical Practice Guideline Preparation Manual 2020 ver. 3.0". Six clinical questions were established, and corresponding recommendations were described for each. CQs addressed the following: (1) the treatment of early lesions, (2) the possibility of reduction surgery for primary lesions, (3) the significance of sentinel lymph node biopsy, (4) the possibility of non-surgical treatment as an alternative to surgical treatment, (5) follow-ups after treatment, and (6) drug treatment for advanced stages. We are confident that the JDA Clinical Practice Guidelines for Cutaneous Squamous Cell Carcinoma will contribute to improving the treatment of cutaneous squamous cell carcinoma in Japan and worldwide.