ABSTRACT
Pemphigus vegetans is a rare type of pemphigus characterized by vegetative lesions primarily localized to the intertriginous area. Despite its unique clinical presentation, the underlying pathomechanism remains unclear owing to the rarity of the disease. We report a case of pemphigus vegetans with antibodies against desmoglein 1 and desmocollins 1-3. Furthermore, immunohistochemical analyses were performed to address the pathogenesis of this disease. A 73-year-old man presented with multiple vegetative plaques with erythema on the trunk, groins, and extremities. Mucosal lesions were not observed. Laboratory examinations revealed mild leukocytosis with eosinophilia. A histopathological examination of the skin lesion showed epidermal hyperplasia and intraepidermal abscesses with marked infiltration of neutrophils and eosinophils, and infiltration of lymphocytes and eosinophils into the upper derms. Bacterial culture of the skin tissue was positive for Staphylococcus aureus. Direct immunofluorescence showed deposits of IgG and C3 on keratinocyte surfaces in the epidermis. Autoantibodies against desmoglein 1 and autoantibodies against desmocollin 1, desmocollin 2, and desmocollin 3 were detected by enzyme-linked immunosorbent assays. The diagnosis of pemphigus vegetans was made. Initiation of prednisolone (1.0 mg/kg/day) gradually improved his skin symptoms. We performed immunohistochemical analyses of the lesional skin, which revealed infiltration of CD3-positive, CD4-positive, and CD68-positive cells in the upper dermis, but CD20- or CD56-positive cells were negative. In addition, the present case showed more prominent infiltration of IL-17A- and IL-22-positive cells in the upper dermis than in pemphigus foliaceus, a type of pemphigus with autoantibodies against desmoglein 1. Furthermore, these cells co-expressed CD3 and CD68. We hypothesized that IL-22 and IL-17A produced by T cells and macrophages and their dysregulation might be involved in the pathogenesis of pemphigus vegetans. Additionally, skin colonization and/or infection with Staphylococcus aureus could potentially contribute to the pathogenesis of the disease.
Subject(s)
Hypopigmentation , Humans , Hypopigmentation/pathology , Piebaldism/pathology , Piebaldism/complications , Female , MaleSubject(s)
Temporal Arteries , Humans , Temporal Arteries/pathology , Diagnosis, Differential , Arteritis/diagnosis , Arteritis/immunology , Arteritis/pathology , Male , Female , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/complications , Aged , Immunoglobulin G/blood , Giant Cell Arteritis/diagnosis , Middle AgedABSTRACT
Cornulin (CRNN) and repetin (RPTN) belong to the fused-type S100 protein family. Although these proteins have been reported to be expressed in the granular layer of the epidermis and have been suggested to be associated with barrier formation in the epidermis, their exact function remains unclear. This study examined the effects of ultraviolet B (UVB) irradiation on CRNN and RPTN expression in human skin xenotransplantation. The CRNN expression increased in the granular layer of UVB-irradiated skin 2 days after UVB irradiation compared to that in sham-irradiated skin. Interestingly, CRNN signals were observed not only in the cytoplasm, but also in the peripheral regions of granular keratinocytes. In contrast, RPTN was rarely expressed in sham-irradiated skin; however, RPTN signals were markedly increased in the granular layer of the UVB-irradiated skin. In addition, activation of ERK1/2 and STAT3 was observed in UVB-irradiated skin. Accordingly, the present study demonstrated that CRNN and RPTN are novel proteins whose expression can be increased by UVB irradiation. The activation of ERK1/2 and STAT3 may be associated with the regeneration of a UVB-damaged epidermis, and CRNN and RPTN may be induced to repair any dysfunction in the epidermal barrier during this regeneration process.
Subject(s)
STAT3 Transcription Factor , Ultraviolet Rays , Humans , STAT3 Transcription Factor/metabolism , Transplantation, Heterologous , Keratinocytes/metabolism , Keratinocytes/radiation effects , Animals , Skin/metabolism , Skin/radiation effects , Epidermis/metabolism , Epidermis/radiation effects , Skin Transplantation , Cornified Envelope Proline-Rich Proteins/metabolism , Cornified Envelope Proline-Rich Proteins/genetics , Heterografts , S100 Proteins/metabolism , S100 Proteins/genetics , MiceABSTRACT
PTPRD, a well-established tumor suppressor gene, encodes the protein tyrosine phosphatase-type D. This protein consists of three immunoglobulin-like (Ig) domains, four to eight fibronectin type 3 (FN) domains, a single transmembrane segment, and two cytoplasmic tandem tyrosine phosphatase domains. PTPRD is known to harbor various cancer-associated point mutations. While it is assumed that PTPRD regulates cellular functions as a tumor suppressor through the tyrosine phosphatase activity in the intracellular region, the function of its extracellular domain (ECD) in cancer is not well understood. In this study, we systematically examined the impact of 92 cancer-associated point mutations within the ECD. We found that 69.6% (64 out of 92) of these mutations suppressed total protein expression and/or plasma membrane localization. Notably, almost all mutations (20 out of 21) within the region between the last FN domain and transmembrane segment affected protein expression and/or localization, highlighting the importance of this region for protein stability. We further found that some mutations within the Ig domains adjacent to the glycosaminoglycan-binding pocket enhanced PTPRD's binding ability to heparan sulfate proteoglycans (HSPGs). This interaction is proposed to suppress phosphatase activity. Our findings therefore suggest that HSPG-mediated attenuation of phosphatase activity may be involved in tumorigenic processes through PTPRD dysregulation.
Subject(s)
Heparan Sulfate Proteoglycans , Neoplasms , Humans , Heparan Sulfate Proteoglycans/metabolism , Point Mutation , Extracellular Matrix Proteins/genetics , Immunoglobulins , Protein Stability , Tyrosine/genetics , Phosphoric Monoester Hydrolases/genetics , Heparitin Sulfate , Receptor-Like Protein Tyrosine Phosphatases, Class 2/genetics , Receptor-Like Protein Tyrosine Phosphatases, Class 2/metabolismSubject(s)
Breast Neoplasms , Skin Neoplasms , Humans , Female , Retrospective Studies , Skin Neoplasms/pathology , Skin Neoplasms/secondary , Skin Neoplasms/diagnosis , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Japan/epidemiology , Middle Aged , Aged , Adult , Aged, 80 and over , Skin/pathologyABSTRACT
BACKGROUND: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched. OBJECTIVES: Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis. METHODS: We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects. RESULTS: Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of Enterococcus was inversely correlated with the degree of vitiligo progression. Gammaproteobacteria, Staphylococcus spp., and Corynebacterium spp. were more abundant in vitiligo patients, with notable Staphylococcus spp. prevalence during the stable phase on the forehead. Conversely, the proportion of Malassezia sympodialis was lower and that of Malassezia globosa was higher in the progressive phase on the back of vitiligo patients. CONCLUSION: Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches.
Subject(s)
Microbiota , Mycobiome , RNA, Ribosomal, 16S , Skin , Vitiligo , Adult , Female , Humans , Male , Middle Aged , Young Adult , Back/microbiology , Case-Control Studies , Corynebacterium/isolation & purification , East Asian People , Forehead/microbiology , Japan , Malassezia/isolation & purification , RNA, Ribosomal, 16S/genetics , Skin/microbiology , Skin/pathology , Staphylococcus/isolation & purification , Vitiligo/microbiologyABSTRACT
We have previously identified the filaggrin (FLG)-like protein, hornerin (HRNR). Recently, there have been several reports regarding the relationship between HRNR and atopic dermatitis (AD). In the present study, we examined HRNR expression in the skin lesions of seven unrelated patients with AD to clarify the role of HRNR in the pathogenesis of AD. HRNR was detected in chronic AD lesions (n = 4), whereas no HRNR signals were observed in acute AD lesions (n = 3). HRNR was detected in the cytokeratin 6-expressing epidermis, and Ki67-positive keratinocytes were more abundant in the HRNR-positive epidermis. These findings suggest that HRNR may be associated with epidermal hyperproliferation in AD lesions. Next, we examined HRNR expression in skin diseases associated with hyperkeratosis. HRNR signals were irregularly observed in different cells from those expressing FLG in epidermolytic ichthyosis and actinic keratosis. Therefore, HRNR may play a unique role in the molecular process of cornification.
Subject(s)
Dermatitis, Atopic , Skin Diseases , Humans , Calcium-Binding Proteins/metabolism , Dermatitis, Atopic/pathology , Epidermis/pathology , Intermediate Filament Proteins/metabolism , Keratinocytes/metabolism , Skin/pathology , Skin Diseases/metabolismABSTRACT
We herein report a typical case of alopecia neoplastica secondary to breast cancer. Alopecia neoplastica is a rare form of alopecia resulting from metastasis of a primary tumour to the scalp and is often misdiagnosed as alopecia areata.
ABSTRACT
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse reaction involving multiorgan failure, with a complex interaction of various drugs, human herpesvirus reactivation and immune abnormalities suggested as the aetiology. We herein present the case of a 70-year-old man with a one-week history of fever, facial oedema, erythematous macules and purpura on his trunk and extremities. He had anti-TIF1γ antibody-positive dermatomyositis and was treated with prednisolone sodium succinate (20 mg/day). Three weeks earlier, he was treated with ganciclovir (250 mg/day) for 7 days to treat asymptomatic cytomegalovirus viraemia. Laboratory investigations revealed eosinophilia with atypical lymphocytes and elevated liver enzyme levels. A histological examination showed interface dermatitis with necrotic keratinocytes, perivascular infiltration of lymphocytes and eosinophils in the upper dermis and erythrocyte extravasation without vasculitis. A lymphocyte transformation test (LTT) was positive for ganciclovir (stimulation index: 260%; normal: <180%). We diagnosed DRESS caused by ganciclovir on the basis of clinical findings and course (Definite; RegiSCAR score: 7). He was treated with prednisolone sodium succinate (40 mg/day) and topical clobetasol propionate (0.05%) ointment twice daily. After the initiation of treatment, the skin lesions and laboratory abnormalities gradually improved. To our knowledge, this is the first case of DRESS caused by ganciclovir. The patients in whom ganciclovir is used are often immunosuppressed and may be overlooked as the causative drug for DRESS by conventional skin tests. We considered that LTT is useful for identifying causative drugs of DRESS, especially in immunosuppressed patients, such as the present case.
Subject(s)
Melanoma , Purpura, Thrombocytopenic, Idiopathic , Uveal Neoplasms , Humans , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Melanoma/drug therapy , Melanoma/pathology , Uveal Neoplasms/drug therapyABSTRACT
Anti-p200 pemphigoid is a rare subepidermal blistering disease showing immunoglobulin G (IgG) autoantibodies reactive with a 200-kDa protein. In most patients, serum IgG antibodies react with laminin γ1. The diagnosis of anti-p200 pemphigoid is occasionally difficult, mainly due to the lack of standardized tests. We performed fluorescence overlay antigen mapping by laser scanning confocal microscopy (FOAM-LSCM) to identify autoantigens in an anti-p200 pemphigoid patient and assessed its usefulness for the diagnosis. A 71-year-old man presented with blisters and erosions on the bilateral forearms. No mucosal lesions were observed. Laboratory examinations revealed mild leukocytosis and antinuclear antibody negativity. A histopathological examination showed subepidermal blisters with neutrophil infiltration. Direct immunofluorescence showed linear IgG staining along the basement membrane zone. Indirect immunofluorescence using 1 M NaCl-split skin sections revealed IgG reactivity on the dermal side. Immunoblotting detected circulating IgG autoantibodies that reacted with a 200-kDa protein. Accordingly, anti-p200 pemphigoid was diagnosed. FOAM-LSCM revealed that the patient's IgG signals were co-localized with laminin γ1 but were observed above type VII collagens. A direct immunofluorescent analysis for IgG deposition patterns showed an n-serrated pattern. Thus, FOAM-LSCM may be useful for diagnosing anti-p200 pemphigoid.
Subject(s)
Autoantigens , Pemphigoid, Bullous , Male , Humans , Aged , Blister/pathology , Autoantibodies , Fluorescent Antibody Technique, Indirect , Immunoglobulin GABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with elevated interleukin (IL)-4 and IL-13 signatures and extensive barrier dysfunction, which is correlated with the downregulation of filaggrin (FLG). FLG is a member of the S100 fused-type protein family and this family also includes cornulin (CRNN), filaggrin-2 (FLG2), hornerin (HRNR) repetin (RPTN), trichohyalin (TCHH) and trichohyalin-like 1 (TCHHL1). The present study aimed to examine the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins using a three-dimensional (3D) AD skin model by immunohistochemical study and quantitative polymerase chain reaction. In the 3D AD skin model, which was generated by a stimulation of recombinant IL-4 and IL-13, the expression of FLG, FLG2, HRNR and TCHH was decreased, while that of RPTN was increased in comparison to the 3D control skin. In the FLG knockdown (KD) 3D skin model, which was generated using FLG siRNA, the expression of HRNR was increased. The expression of the other proteins did not differ to a statistically significant extent. The expression of fused-S100 type protein family members may differ in AD skin. This suggests that these proteins play different roles in the pathogenesis of AD.
Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/metabolism , Filaggrin Proteins , Interleukin-4/metabolism , Interleukin-13/metabolism , Skin/metabolism , S100 Proteins/genetics , S100 Proteins/metabolism , Intermediate Filament Proteins/genetics , Intermediate Filament Proteins/metabolismABSTRACT
Hypereosinophilic syndrome (HES) is a heterogeneous group of diseases, characterized by persistent hypereosinophilia and end-organ damage. The FIP1L1-PDGFRA (F/P) fusion gene is found in 3-25% of patients with HES and is an oncogenic driver of myeloid neoplasms with clonal eosinophilia. Although cutaneous symptoms are the most common type of symptom in patients who have F/P fusion gene-positive HES (F/P HES), histological reports are limited. We herein present the case of a 78-year-old man with erythematous macules and severe pruritus on his trunk and extremities. Laboratory investigations revealed marked eosinophilia and elevated serum vitamin B12. A histological examination showed massive infiltration of eosinophils and mast cells around the vessels in the upper dermis. Fluorescence in situ hybridization revealed F/P fusion genes in nuclei in the peripheral blood and the skin lesion. The patient was diagnosed with F/P HES, and showed an excellent clinical and haematological response to imatinib.
Subject(s)
Hypereosinophilic Syndrome , Male , Humans , Aged , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/genetics , Hypereosinophilic Syndrome/pathology , In Situ Hybridization, Fluorescence , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Imatinib Mesylate/therapeutic use , Eosinophils/pathology , Oncogene Proteins, Fusion/genetics , mRNA Cleavage and Polyadenylation Factors/geneticsABSTRACT
The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.