The Journal of dermatology最新文献

Vitiligo is an acquired autoimmune disease characterized by depigmented macules resulting from melanocyte loss. It is a complex multifactorial disorder in which genetic predisposition is combined with environmental factors; however, its detailed etiology remains unclear. Although Janus kinase (JAK) inhibitors have recently emerged as a therapeutic option, the range of available molecularly targeted drugs is limited compared to those for atopic dermatitis or psoriasis, necessitating an urgent elucidation of its pathogenesis. The pathogenesis of vitiligo is centrally mediated by cytotoxic CD8⁺ T cells (CTLs) specific for melanocyte antigens and their production of interferon-gamma (IFN-γ). In recent years, however, the involvement of other immune cells, such as resident memory T cells and regulatory T cells, innate immune cells, and non-immune cells including keratinocytes and fibroblasts has also garnered attention. Furthermore, pathogenic alterations are also present in clinically normal-appearing non-lesional skin, indicating that this tissue is "primed" for disease development. This finding supports a paradigm shift toward viewing vitiligo as a systemic disease rather than a localized skin disorder. Herein, this review summarizes the current knowledge on the factors leading to the onset and progression of non-segmental vitiligo, while also briefly addressing segmental vitiligo.

Multifocal venous malformation (VM) is a rare vascular disorder characterized by multiple cutaneous and visceral venous malformations caused by somatic variants in the TEK gene, which encodes the TIE2 receptor. We report a 30-year-old man presenting with multiple subcutaneous nodules and oral lesions. MRI revealed multiple masses around the left scapula. A biopsy from a lumbar lesion showed dilated venous channels, and immunohistochemistry was positive for CD31. There was no evidence of anemia. Genetic analysis using next-generation sequencing of both skin and blood identified two somatic TEK variants, p.(Tyr897Cys) and p.(Arg918His), restricted to the lesion tissue. Bulk phasing analysis revealed that Y897C and R918H existed both as single variants and as double variants in cis. The absence of these variants in blood confirmed their somatic origin. Based on clinical and pathological findings, the patient was diagnosed with multifocal VM. Clinically, this case resembled multifocal sporadic VM; however, the genetic profile was consistent with blue rubber bleb nevus syndrome, suggesting this case may represent an intermediate phenotype between the two entities. The involvement of the PI3K/AKT/mTOR signaling pathway implies potential therapeutic benefit from mTOR inhibitors, such as sirolimus. Close follow-up is ongoing due to progressive oral involvement.

Atopic dermatitis (AD) essentially exhibits dysbiosis of skin fungal microbiome, mycobiome, characterized by depletion of Malassezia. The effects of recent systemic therapies for AD on skin mycobiome were not understood enough. We examined changes of skin mycobiome before and after systemic treatments with anti-IL-4Rα antibody (dupilumab: DUP) and calcineurin inhibitor (cyclosporine, CyA). Swab samples from postauricular areas in 19 AD patients treated with dupilumab (n = 13) and cyclosporine (n = 6) were collected before and 4-8 weeks after starting each treatment. Fungal DNA was amplified from the samples and sequenced with ITS1 metagenomic analysis, and taxonomic classification was performed. Fungi belonging to total 89 genera were detected. The share of the fungus was most occupied by Malassezia (81.3%), followed by Aspergillus (3.7%), and Trametes (1.1%) before DUP and CyA treatment, and occupied by Malassezia (87.3%), followed by Aspergillus (1.9%), and Candida (1.7%) after treatment. Three AD patients whose ratio of Malassezia in the skin mycobiome was under 50%, showed an exploratory increase of Malassezia after treatments (before 17.3%, after 67%). Analysis of the Malassezia species revealed an increase in M. restricta (before 70.5%, after 79.5%) and a decrease in M. globosa (before 23.9%, after 16.1%). No consistent patterns distinguishing DUP and CyA were observed. Systemic treatment with DUP and CyA was associated with shifts toward higher Malassezia abundance and modulation between M. restricta and M. globosa. These findings are exploratory and require validation in larger controlled studies.

Tinea corporis, a superficial fungal skin infection of the trunk and extremities, typically presents as scaly, erythematous plaques with an active border. However, atypical presentations, especially those caused by uncommon dermatophytes, can complicate diagnosis. Here, we report an unusual case presenting with an oyster-like (rupioid) lesion on the right shoulder, a presentation not previously documented. Molecular analysis of the internal transcribed spacer (ITS) region of ribosomal DNA identified Nannizzia incurvata, a rare dermatophyte within the Nannizzia gypsea complex. The patient was successfully treated with a four-week course of oral itraconazole and topical terbinafine. This case underscores the importance of recognizing unusual clinical presentations and using molecular techniques for accurate pathogen identification. Understanding the characteristics and clinical significance of this uncommon pathogen in human infections will contribute to better diagnosis and management strategies.

Ocular mucous membrane pemphigoid (MMP) presents a significant diagnostic challenge because of the typically low positivity rate of serum antibody. While direct immunofluorescence (DIF) of conjunctival biopsies yields a high positivity rate, its invasiveness limits routine application. To address this, we explored tear fluid-which contains detectable immunoglobulin G (IgG) and can be collected safely and minimally invasively-as an alternative sample source for immunological testing. This pilot study reports the first case of tear fluid-based indirect immunofluorescence (IIF) using oral mucosal tissue to evaluate disease activity in ocular MMP. A man in his 60s presented with ocular pain, conjunctival hyperemia, and erosions. He had a prior MMP diagnosis based on low-titer serum anti-BP180NC16a antibody, histopathology, DIF, and serum IIF. During the second exacerbation, serum anti-BP180NC16a antibody was negative, and serum-based IIF showed no linear deposition of IgG and C3. Tear fluid testing revealed linear IgG deposition along the basement membrane zone (BMZ) of oral mucosa, with titers of 1:20 (left eye) and 1:320 (right eye), correlating with clinical asymmetry. Control testing yielded negative results. Following remission, tear fluid-based IIF showed no IgG reactivity, indicating a correlation with disease activity. Notably, serum-based IIF using oral mucosa was negative, while tear fluid-based IIF demonstrated clear IgG positivity, suggesting higher sensitivity in detecting ocular disease. In conclusion, tear fluid-based IIF using oral mucosa represents a novel and potentially more sensitive method for evaluating ocular MMP, warranting further validation.