Alteration of microbial composition in the skin and blood in vasculitis.

Vasculitis is a systemic autoimmune disease characterized by leukocyte infiltration into blood vessels. Various microorganisms have been associated with the pathogenesis of vasculitis; however, the causal microbial agents and underlying mechanisms are not fully understood, possibly because of the technical limitations of pathogen detection. In the present study, we characterized the microbiome profile of patients with cutaneous vasculitis using comprehensive metagenome shotgun sequencing. We found that the abundance of the SEN virus was increased in the affected skin and serum of patients with vasculitis compared to healthy donors. In particular, the abundance of SEN virus reads was increased in the sera of patients with cutaneous arteritis. Among the bacteria identified, Corynebacteriales was the most differentially associated with vasculitis. Linear discriminant analysis effect size also indicated differences in the microbial taxa between patients with vasculitis and healthy donors. These findings demonstrate that vasculitis is associated with considerable alteration of the microbiome in the blood and skin and suggest a role for the infectious trigger in vasculitis.

Near-infrared radiation causes sebaceous gland enlargement along with an ROS-dependent augmentation of epidermal growth factor receptor expression in hamsters.

As near-infrared radiation (NIR), which is a composition of sunlight with an 780-1400 nm wavelength, is associated with skin aging such as wrinkles and slacks, the biological actions of NIR with high dermal penetration remains unclear. In the present study, we found that NIR irradiation (40 J/cm2 ) at different levels of irradiance (95-190 mW/cm2 ) using a laboratory device with a xenon flash lamp (780-1700 nm) caused sebaceous gland enlargement concomitantly with skin thickening in the auricle skin of hamsters. The sebaceous gland enlargement resulted from the proliferation of sebocytes due to an increase in the number of proliferating cell nuclear antigen (PCNA)- and lamin B1-positive cells in vivo. In addition, NIR irradiation transcriptionally augmented the production of epidermal growth factor receptor (EGFR) accompanied with an increase in the reactive oxygen species (ROS) level in hamster sebocytes in vitro. Furthermore, the administration of hydrogen peroxide increased the level of EGFR mRNA in the sebocytes. Therefore, these results provide novel evidence that NIR irradiation causes the hyperplasia of sebaceous glands in hamsters by mechanisms in which EGFR production is transcriptionally augmented through ROS-dependent pathways in sebocytes.

Correlation between higher-order aberration and photophobia after cataract surgery.

Cataract surgery impinges on the spatial properties and wavelength distribution of retinal images, which changes the degree of light-induced visual discomfort/photophobia. However, no study has analyzed the alteration in photophobia before and after cataract surgery or the association between retinal spatial property and photophobia. Here, we measured the higher-order aberrations (HOAs) of the entire eye and the subjective photophobia score. This study investigated 71 eyes in 71 patients who received conventional cataract surgery. Scaling of photophobia was based on the following grading system: when the patient is outdoor on a sunny day, score of 0 and 10 points were assigned to the absence of photophobia and the presence of severe photophobia prevents eye-opening, respectively. We decomposed wavefront errors using Zernike polynomials for a 3-mm pupil diameter and analyzed the association between photophobia scores and HOAs with Spearman's rank sum correlation (rs). We classified patients into two groups: photophobia (PP) unconcerned included patients who selected 0 both preoperatively or postoperatively and PP concerned included the remaining patients. After cataract surgery, photophobia scores increased, remained unchanged (stable), and decreased in 3, 41, and 27 cases, respectively. In the stable group, 35 of 41 cases belonged to PP unconcerned. In PP concerned, there were significant correlations between photophobia score and postoperative root-mean-square values of total HOAs (rs = 0.52, p = 0.002), total coma (rs = 0.52, p = 0.002), total trefoil (rs = 0.47, p = 0.006), and third-order group (rs = 0.53, p = 0.002). In contrast, there was no significant correlation between photophobia scores and preoperative HOAs. Our results suggest that the spatial properties of retinal image modified by HOAs may affect the degree of photophobia. Scattering light due to cataracts could contribute to photophobia more than HOAs, which may mask the effect of HOAs for photophobia preoperatively.

Multimodal Imaging of Subfoveal Pachydrusen Containing a Blood Flow Signal.

Individuals with pachydrusen, larger than 125 µm, have a significantly thicker choroid than do those with soft drusen or reticular pseudodrusen. Little is known about cases of abnormal blood flow within pachydrusen. The purpose of this report was to demonstrate a blood flow signal within pachydrusen using optical coherence tomography (OCT) angiography. A 76-year-old Japanese woman presented with innumerable drusen/pachydrusen in both posterior poles. Her visual acuity was good. OCT showed subfoveal pachydrusen in the left eye, but no exudative changes. The subfoveal choroidal thickness was increased to 274 µm in the left eye. OCT angiography revealed a blood flow signal within the pachydrusen. However, fluorescein and indocyanine green angiographies indicated no abnormal hyperfluorescent lesion in the macula of the left eye. During the 13-month follow-up, the blood flow signal in OCT angiography did not change in diameter, and no exudative change was observed. The blood flow signal may have properties of capillary blood vessels derived from the choriocapillaris, rather than angiogenic vessels from choroidal neovascularization or polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization.

TERT/BMI1-transgenic human dermal papilla cells enhance murine hair follicle formation in vivo.

BACKGROUND: Dermal papilla cells (DPCs) are one type of mesenchymal cells; they play a key role on hair follicle induction. Their hair inductivity and proliferation abilities are rapidly lost during the 2-dimensional culture. Cell senescence is induced by inadequate culture conditions and telomere shortening. We previously reported that overexpression of TERT coding telomerase reverse transcriptase and BMI1 coding human B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) avoided senescence of murine DPC and restored hair inductive activity. OBJECTIVE: To evaluate the function of TERT and BMI1 in the human DPCs (hDPCs). METHODS: Cultured hDPCs obtained from human scalp hair were transduced with TERT alone (hDP-T), BMI1 alone (hDP-B), both TERT and BMI1 (hDP-TB) and empty vector (hDP-E). The hair inductive activity of those cells was assessed by chamber assay in vivo. Gene expressions were analyzed by quantitative PCR (q-PCR). RESULTS: hDP-TB proliferated more than hDP-T and hDP-B in vitro and only hDP-TB showed hair inductivity in vivo. Moreover, the expressions of VCAN, CTNNB1, LEF1, FGF7 and VEGFA in hDP-TB were elevated compared to those in hDP-E. CONCLUSION: Overexpression of both TERT and BMI1 extends the life span of cultured hDPCs and ameliorates their hair inducing ability on mouse hair follicles.

Pathogens in Vasculitis: Is It Really Idiopathic?

Vasculitis is an autoimmune disease characterized by the infiltration of leukocytes in blood vessels. An increasing number of studies on human and animal models have implicated various microorganisms in the pathogenesis of vasculitis. Previous studies have shown the presence of infectious agents, including viruses, bacteria, and fungi, in diseased vessels. However, despite continued research, the link between infection and vasculitis is not fully understood, possibly owing to the lack of appropriate animal models that mirror human disease and the technical limitations of pathogen detection in blood vessels. Among the pathogen-induced animal models, Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis is currently considered one of the representative models of Kawasaki (KD) disease. Advances in metagenomic next-generation sequencing have enabled the detection of all nucleic acids in tissue, which can help identify candidate pathogens, including previously unidentified viruses. In this review, we discuss the findings from reports on pathogen-associated vasculitis in animal models and humans, with a specific focus on the investigation of the pathogenesis of vasculitis. Further studies on animal models and microbes in diseased vessels may provide important insights into the pathogenesis of vasculitis, which is often considered an idiopathic disease.

Survey of Japanese dermatological vasculitis specialists on cases of cutaneous arteritis (cutaneous polyarteritis nodosa).

We developed a questionnaire to examine the findings of cutaneous arteritis among dermatological specialists experienced in vasculitis as certified by the Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. We sent a questionnaire to 12 dermatological facilities identified through the revised Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. Retrospective data obtained from 84 patients at the 12 dermatological facilities between 2012 January 2016 December were evaluated. The 84 patients were categorized into two groups, a systemic steroid treatment group (group 1, n = 52) and a no systemic steroid treatment group (group 2, n = 32). C-reactive protein in group 1 patients was significantly higher than that in group 2 patients. Frequency of fever, arthritis, myalgia- and peripheral neuropathy in group 1 was significantly higher than that in group 2. We propose that these symptoms could serve as early markers for the transfer from cutaneous arteritis to systemic polyarteritis nodosa. We further suggest that patients who are subsequently associated with cerebral hemorrhage and infarction, who are originally diagnosed as having cutaneous arteritis, could progress to systemic polyarteritis nodosa. The study demonstrated that it is important for dermatologists to detect these findings early in order to establish an accurate diagnosis and a timely treatment.

[Skin Manifestations of Vasculitis].

Skin symptoms that might indicate vasculitis include palpable purpura, blisters, skin ulcers, livedo, and subcutaneous nodules. Palpable purpura, livedo, and subcutaneous nodules are particularly important; the first correlates with small vessel vasculitis, and the latter two with medium vessel vasculitis on histopathology. If the presence of deep lesions, as seen in cases of livedo and subcutaneous nodules are suspected, the skin biopsy must include fat tissue from the active skin lesions to arrive at the accurate histological diagnosis. Differential diagnoses should be considered based on the size of the most heavily impacted vessels, to determine the type of vasculitis. The diagnosis and treatment of vasculitis requires cooperation between the Nephrology, Neurology, Respiratory Medicine, Rheumatology, Dermatology, and Pathology Departments.

Outline of guidelines for the management of vasculitis and vascular disorders in Japan, 2016 revised edition.

The proposal by the 1994 International Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides (CHCC1994) and by the CHCC2012 markedly influenced the classification and way of considering cutaneous vasculitis. In the proposal by the CHCC1994, hypersensitivity angiitis was defined as an equivalent pathological condition to microscopic polyangiitis or cutaneous leukocytoclastic angiitis (CLA), and it was not adopted as a disease name. However, CLA which was positioned as a type of small-vessel vasculitis is only a pathological name. In the proposal by the CHCC2012, a new category of single-organ vasculitis included CLA and cutaneous arteritis. Vasculitis allergica cutis (Ruiter) corresponded to CLA and cutaneous polyarteritis nodosa corresponded to cutaneous arteritis. The Japanese Dermatological Association (JDA) prepared guidelines for the management of vasculitis and vascular disorders in 2008 based on the proposal by the CHCC1994 and their original viewpoint of dermatology. The JDA subsequently revised the 2008 edition guidelines in 2016 following publication of the proposal of the CHCC2012 in Japanese. We presented the outline of the 2016 edition guidelines and propose a treatment algorithm for primary vasculitides based on the evaluation of the cutaneous symptoms for cases suspected as primary cutaneous vasculitides, which integrates the 2008 JDA guideline and CHCC2012 classification. This is the secondary English version of the original Japanese manuscript for the guideline for management of vasculitis and vascular disorders published in the Japanese Journal of Dermatology 127(3); 299-415, 2017.

Detailed analysis of a superficial CD34-positive fibroblastic tumor: A case report and review of the literature.

Superficial cluster of differentiation (CD)34-positive fibroblastic tumor (SCPFT) is a rare mesenchymal neoplasm of borderline malignancy. It is characterized by a superficial location, marked cellular pleomorphism, an extremely low incidence of mitotic figures, and strong CD34 immunohistochemical positivity. As SCPFT is a recently described neoplasm, its characteristics are yet to be fully elucidated. To the best of our knowledge, no detailed studies regarding the imaging findings and cytogenetic analyses of SCPFTs exist. The present study describes a typical case of an 18-year-old man who developed an SCPFT measuring 87×70×80 mm in the subcutaneous adipose tissue of his right thigh. Computed tomography (CT) revealed a well-marginated tumor without calcification, and the enhancement on CT was weak. The tumor demonstrated abnormal uptake on 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography (PET), with a maximum standardized uptake value of 2.57. Magnetic resonance imaging (MRI) revealed a clearly defined tumor that exhibited homogeneous low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging, with small lobulated structures. Histopathologically, the tumor was composed of irregular spindle-to-oval-shaped cells with eosinophilic glassy cytoplasm and hyperchromatic, bizarre and pleomorphic nuclei that frequently exhibited intranuclear pseudoinclusions. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34. The Mindbomb E3 ubiquitin protein ligase 1 labeling index was 8.6%. Ultrastructurally, the tumor cells exhibited irregular or convoluted nuclei with abundant euchromatin-prominent nucleoli. The cytoplasmic organelles consisted of scattered, abundant rough endoplasmic reticulum, mitochondria, lysosomes, ribosomal rosettes and aggregated lipid globules. Of 18 metaphase cells identified, 2 demonstrated translocation between chromosomes 2 and 5 in cytogenetic studies. To the best of our knowledge, this is the first study describing imaging data (CT, MRI and PET-CT) and chromosomal aberrations for SCPFT.