human herpesvirus

人类疱疹病毒
  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:2022年西方国家报道了儿童急性病因不明肝炎(AHUE)的暴发。先前的研究发现,腺相关病毒2(AAV2)及其辅助病毒,如人腺病毒(HAdV)和人疱疹病毒-6(HHV-6),在AHUE患者中经常检测到。然而,在2022年AHUE暴发之前,尚未调查与AAV2相关的肝炎的存在.我们旨在调查日本儿童AAV2与小儿急性肝炎之间的关联,以及2022年之前AAV2相关肝炎的发病率。
    方法:回顾性分析了2017年至2023年间49例急性肝炎患儿的保存血液样本。来自50名患有急性疾病的儿童和50名患有慢性疾病的儿童的血液样本被用作对照。使用实时PCR定量病毒DNA载量。
    结果:在12%(6/49)的急性肝炎病例中检测到AAV2DNA,但仅在一种急性疾病中检测到,而没有慢性疾病对照病例。6例急性肝炎病例中AAV2DNA的浓度高于急性疾病对照病例。与一种或多种辅助病毒共感染,包括HAdV,HHV-6,巨细胞病毒,和爱泼斯坦-巴尔病毒,在5例AAV2阳性病例中观察到。
    结论:我们的结果表明,在2022年AHUE暴发之前,日本零星发生了与AAV2感染相关的儿童重型肝炎。我们的发现表明,与AAV2和辅助病毒的共感染在发展为严重肝炎中起作用。
    BACKGROUND: Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022.
    METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR.
    RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases.
    CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.
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  • 文章类型: Journal Article
    人疱疹病毒6B(HHV-6B)通过下调I类MHC分子(MHC-I)来阻止宿主免疫反应,阻碍抗原呈递到CD8+T细胞。MHC-I的下调释放自然杀伤(NK)细胞上的抑制性受体,如果NK细胞活化受体如NKG2D已经参与在靶细胞上上调的应激配体,则导致靶细胞的活化和杀伤。以前的工作表明,HHV-6B下调三个MHC样应激配体MICB,ULBP1和ULBP3,由NKG2D识别。相关病毒HHV-6A的U20糖蛋白与ULBP1的下调有关,但确切的机制仍未确定。
    我们着手研究HHV-6BU20在调节NK细胞活性中的作用。我们使用HHV-6BU20表达为重组蛋白或转导到靶细胞中,以及HHV-6B感染,研究与NK细胞配体和受体的结合相互作用,并评估对NK细胞活化的影响。小角度X射线散射用于对齐从机器学习方法导出的分子模型。
    我们证明U20以亚微摩尔亲和力直接结合ULBP1。U20的转导降低了NKG2D在细胞表面与ULBP1的结合,但不降低ULBP1蛋白水平。在细胞表面或在toto中。HHV-6B感染和可溶性U20具有相同的作用。U20的转导阻断响应于细胞表面ULBP1的NK细胞活化。U20-ULBP1复合物的结构模型表明与m152-RAE1γ复合物有一些相似之处。
    UNASSIGNED: Human Herpesvirus 6B (HHV-6B) impedes host immune responses by downregulating class I MHC molecules (MHC-I), hindering antigen presentation to CD8+ T cells. Downregulation of MHC-I disengages inhibitory receptors on natural killer (NK) cells, resulting in activation and killing of the target cell if NK cell activating receptors such as NKG2D have engaged stress ligands upregulated on the target cells. Previous work has shown that HHV-6B downregulates three MHC-like stress ligands MICB, ULBP1, and ULBP3, which are recognized by NKG2D. The U20 glycoprotein of the related virus HHV-6A has been implicated in the downregulation of ULBP1, but the precise mechanism remains undetermined.
    UNASSIGNED: We set out to investigate the role of HHV-6B U20 in modulating NK cell activity. We used HHV-6B U20 expressed as a recombinant protein or transduced into target cells, as well as HHV-6B infection, to investigate binding interactions with NK cell ligands and receptors and to assess effects on NK cell activation. Small-angle X-ray scattering was used to align molecular models derived from machine-learning approaches.
    UNASSIGNED: We demonstrate that U20 binds directly to ULBP1 with sub-micromolar affinity. Transduction of U20 decreases NKG2D binding to ULBP1 at the cell surface but does not decrease ULBP1 protein levels, either at the cell surface or in toto. HHV-6B infection and soluble U20 have the same effect. Transduction of U20 blocks NK cell activation in response to cell-surface ULBP1. Structural modeling of the U20 - ULBP1 complex indicates some similarities to the m152-RAE1γ complex.
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  • 文章类型: Journal Article
    这项研究的目的是为完善药物方案提供指导,制定替代战略,并在个性化的临床环境中增强对疱疹病毒感染的保护。
    2004年第一季度至2022年第四季度的抗疱疹病毒不良药物事件(ADE)数据是从FDA不良事件报告系统(FAERS)收集的。不相称性分析使用报告赔率比(ROR),比例报告比率(PRR),和贝叶斯置信传播神经网络(BCPNN)数据挖掘方法。
    共有18,591,24206,6,150和419份与阿昔洛韦(ACV)相关的ADE报告,伐昔洛韦(VACV),更昔洛韦(GCV),从FAERS中筛选并提取泛昔洛韦(FCV)。在这项研究中,该报告总结了4种药物在首选术语(PT)水平的ADE的高频率和强相关性.此外,分析还确定了ADE与年龄等因素之间的关系,性别,和系统器官等级(SOC)水平的结果严重程度。
    四核苷类似物抗疱疹病毒药物的安全性报告多种多样且相互关联。疱疹病毒感染患者的剂量应根据他们的具体情况和潜在的疾病风险进行调整。
    UNASSIGNED: The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings.
    UNASSIGNED: Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining.
    UNASSIGNED: A total of 18,591, 24,206, 6,150, and 419 reports of ADEs associated with acyclovir (ACV), valacyclovir (VACV), ganciclovir (GCV), and famciclovir (FCV) were screened and extracted from the FAERS. In this study, the report summarized the high frequency and strong correlation of ADEs for the four drugs at the Preferred Term (PT) level. Additionally, the analysis also identified the relationship between ADEs and factors such as age, gender, and severity of outcome at the System Organ Class (SOC) level.
    UNASSIGNED: The safety reports for the four-nucleoside analogue anti-herpesvirus drugs are diverse and interconnected. Dosing for patients with herpesvirus infections should be tailored to their specific conditions and the potential risk of disease.
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  • 文章类型: Journal Article
    目的:探讨人类疱疹病毒(HHV)携带对肺部微生物群的影响,及其与患者临床特征和实验室指标的相关性。方法:对30例门诊肺部感染病例进行回顾性分析,分为HHV组(n=15)和非HHV组(n=15)。mNGS检测到微生物组成。使用Shannon和Chao1指数测试了微生物的多样性和丰度。探讨了它们与实验室指标的关系。结果:两组微生物丰度和分布差异有统计学意义(p<0.05)。此外,HHV组与Prevotella之间呈负相关(p<0.05),卟啉单胞菌,链球菌和嗜碱性粒细胞/嗜酸性粒细胞百分比。结论:HHV携带会影响肺部菌群,强调临床医生需要重视门诊肺部感染患者的HHV再激活。
    这项研究研究了一种称为人类疱疹病毒(HHV)的常见病毒如何影响我们肺部的细菌。我们想看看HHV是否与我们的病态和测试表明有关。我们将30名肺部感染的人分成两组,15名患有HHV的人和15名没有HHV的人,并检查了他们的病情,做了一些测试,观察他们肺部的细菌类型。两组都感到同样的不适,药物治疗好转,但是患有HHV的人有较少的某种类型的血细胞。有和没有HHV的人在他们的肺部也有不同类型的细菌。这项研究帮助我们理解为什么人们会因肺部感染而生病,以及如何使他们变得更好。它还可以帮助医生决定如何治疗肺部感染患者。
    Aim: To investigate the impact of human herpes virus (HHV) carriage on lung microbiota, and its correlation with clinical features and laboratory indicators in patients.Methods: Retrospective analysis was conducted on 30 outpatient lung infection cases, which were divided into HHV (n = 15) and non-HHV (n = 15) groups. mNGS detected microbial composition. Microbial diversity and abundance were tested using Shannon and Chao1 indices. Their relationship with laboratory indicators were explored.Results: Significant differences in microbial abundance and distribution were found between two groups (p < 0.05). Moreover, HHV group showed negative correlations (p < 0.05) between Prevotella, Porphyromonas, Streptococcus and basophil/eosinophil percentages.Conclusion: HHV carriage impacts lung microbiota, emphasizing the need for clinicians to pay attention to HHV reactivation in outpatient lung infection patients.
    This study looked at how a common virus called human herpesvirus (HHV) affects the bacteria in our lungs. We wanted to see if HHV is linked to how sick we feel and what tests show. We split 30 people who had lung infections into two groups – 15 with HHV and 15 without – and checked how sick they felt, did some tests, and looked at the types of bacteria in their lungs. Both groups felt similarly sick and got better with medicine, but people with HHV had fewer of a certain type of blood cell. People with and without HHV also had different types of bacteria in their lungs. This study helps us understand why people get sick with lung infections and how to make them better. It might also help doctors decide how to treat people with lung infections.
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  • 文章类型: Case Reports
    病毒性肺炎引起的成人呼吸窘迫综合征主要发生在免疫缺陷人群中;继发于人类疱疹病毒HHV-6和HHV-7肺炎的成人呼吸窘迫综合征极为罕见。Whipple病,由Tropherymawhipplei引起,革兰氏阳性杆菌和专性细胞内病原体,临床诊断具有挑战性。Whipple病是由WhippleiT.引起的慢性多系统传染病,最常影响胃肠道和关节,很少有肺。两种病原体都是机会主义的。我们报告了一例2型糖尿病患者的混合感染性肺炎。患者出现呼吸困难和间歇性发热。影像学显示左肺有多个大的斑片状巩固。常规抗感染治疗无效。支气管肺泡灌洗液的宏基因组下一代测序表明,HHV-6和HHV-7肺炎同时伴有T.whipplei和链球菌共感染。给予美罗培南以改善治疗。此病例代表由多种罕见病原体引起的罕见混合肺部感染,具有特殊的临床意义。
    Adult respiratory distress syndrome due to viral pneumonia occurs predominantly in immunodeficient populations; adult respiratory distress syndrome secondary to human herpesvirus HHV-6 and HHV-7 pneumonia is extremely rare. Whipple\'s disease, caused by Tropheryma whipplei, a Gram-positive bacillus and obligate intracellular pathogen, is clinically challenging to diagnose. Whipple\'s disease is a chronic multisystem infectious disease caused by T. whipplei, most often affecting the gastrointestinal tract and joints, seldom the lungs. Both pathogens are opportunistic. We report a case of mixed infectious pneumonia in a patient with type 2 diabetes mellitus. The patient presented with dyspnea and intermittent fever. Imaging revealed multiple large patchy consolidations in the left lung. Routine anti-infective therapy was ineffective. Metagenomic next generation sequencing of bronchoalveolar lavage fluid indicated HHV-6 and HHV-7 pneumonia concurrent with T. whipplei and Streptococcus co-infections. Meropenem was administered to improve treatment. This case represents a rare mixed lung infection by multiple uncommon pathogens, and is of particular clinical significance.
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  • 文章类型: Journal Article
    目的:本研究的目的是确定肝硬化患者血浆和唾液中是否存在人类疱疹病毒(HHV),并将其与临床数据和实验室检查相关联。这是一个飞行员,观察,和横断面研究。
    结果:通过聚合酶链反应分析了72例肝硬化患者的血浆和唾液样本。患者群体的平均年龄为54.84岁(SD±10),70%为男性(51/72)。大约47%(n=34)的患者患有白细胞减少症,血浆标本中未发现HHV。唾液中确定的HHV的主要物种是HHV-7(n=42,62%)和EB病毒(EBV)(n=30,41%)。此外,含有EBV的唾液中白细胞和淋巴细胞的总数显着减少(分别为P=.038和P=.047)。
    结论:结果显示,肝硬化患者唾液中EBV的存在与其循环免疫状态相关。肝硬化患者表现出的免疫功能障碍可能在EBV脱落到唾液中起作用。
    OBJECTIVE: The objective of this study was to identify the presence of human herpesvirus (HHV) in the plasma and saliva of hepatic-cirrhosis patients and correlate it with clinical data and laboratory tests. This is a pilot, observational, and cross-sectional study.
    RESULTS: Specimens of plasma and saliva from 72 cirrhotic individuals were analyzed by means of polymerase chain reaction. The patient population had a mean age of 54.84 years old (SD ± 10) and was 70% males (51/72). Approximately 47% (n = 34) of the patients had leukopenia and HHV was not identified in the plasma specimens. The main species of HHV identified in the saliva were HHV-7 (n = 42, 62%) and Epstein-Barr virus (EBV) (n = 30, 41%). Moreover, there was a significant decrease in the total number of leukocytes and lymphocytes in saliva containing EBV (P = .038 and P = .047, respectively).
    CONCLUSIONS: The results show that the presence of EBV in the saliva of cirrhotic patients was correlated with their circulating immune status. It may be possible that the immune dysfunction displayed by the cirrhotic patients plays a role in the shedding of EBV into saliva.
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  • 文章类型: Journal Article
    背景:体液记忆和特异性抗体水平取决于抗原的种类和个体免疫因子。IgM抗体的存在或特异性IgG水平升高四倍通常被认为是急性病毒感染血清学中的诊断因素。这个基本模型对疱疹病毒来说是不够的,尤其是造血干细胞移植(HSCT)后,由于连续,通常是多灶性抗原刺激,各种供体血清,免疫抑制,和个体免疫重建。
    方法:进行了一项病例对照研究,以确定人类疱疹病毒(HHV)的活动性感染病例(来自300例确诊的免疫功能低下患者),并评估历史相关的体液因素以观察结果。我们仅考虑经过细致鉴别诊断的患者数据,以排除其他原因,从而观察路径和时间关系,不是通常在队列中收集的统计信息。尽管数量少,这种数据收集和分析方法避免了一些偏见,并指出了因果关系。
    结果:在这项观察性研究中,对临床诊断为单纯疱疹病毒(HSV)和水痘带状疱疹病毒(VZV)再激活的300例患者的数据进行的回顾性分析显示存在许多偏差.具有各种疾病和免疫参数的条件演变的两个分化良好的病例(通过Tzanck测试证实)显示出有趣的途径。观察到HSCT在病毒复制之前特异性IgG的指数减少,具有细胞病变效应(带状疱疹,VZV脑炎和HSV引起的粘膜炎)。对于VZV和HSV,疱疹病毒再激活前的最小值(最低IgG水平)为234.23mIU/mL和94RU/mL,分别。这与低CD4滴度相吻合,但没有其他感染过程。其他免疫应答参数如Treg、细胞毒性T细胞,补体和总IgG水平与移植前相同。有趣的是,并不总是观察到第二波免疫重建与记忆抗体反应。它与长期的疱疹病毒感染相吻合。在调理中淋巴细胞耗竭的患者显示出更早的第二波免疫重建(第6与14个月)。
    结论:对于婴儿期,HSCT后IgG水平的动力学是独特的(下降阶段是第一)。宿主微生物组因子(例如,应考虑HHV1-3-血清状态)以预测HSCT后非复发死亡率和生存率的风险。特异性抗体的水平有助于预测预后和改善疾病管理。缺乏差异化和评估者令人困惑的偏见(即,观察者选择偏差)是统计HHV1-3研究的主要障碍。这种延时案例研究可能是第一个建立途径和免疫参数与HHV疾病之间关联的证据。
    BACKGROUND: Humoral memory and specific antibody levels depend on the kind of antigen and individual immunofactors. The presence of IgM antibodies or a fourfold rise in specific IgG levels are generally accepted as diagnostic factors in the serology of acute viral infections. This basic model is not adequate for the herpes virome, especially after hematopoietic stem cell transplantation (HSCT), due to continuous, usually multifocal antigenic stimulation, various donor serostatuses, immunosuppression, and individual immunoreconstitution.
    METHODS: A case-control study was conducted to identify active infection cases of human herpesvirus (HHV) (from 300 diagnosed immunocompromised patients) and to evaluate historically associated humoral factors to look at outcomes. We considered only the data of patients with meticulous differential diagnosis to exclude other causes, and thereby to observe pathways and temporal relationships, not the statistical ones usually collected in cohorts. Despite the small number, such data collection and analysis methods avoid a number of biases and indicate cause and effect.
    RESULTS: In this observational study, a retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation showed a number of biases. Two well-differentiated cases (confirmed by a Tzanck test) with various diseases and conditioning evolutions of immune parameters showed an interesting pathway. Exponential decreases in specific IgGs after HSCT preceded virus replication were observed, with a cytopathic effect (shingles, VZV encephalitis and HSV-induced mucositis). The minima (lowest IgG levels) before herpesvirus reactivation were 234.23 mIU/mL and 94 RU/mL for VZV and HSV, respectively. This coincided with a low CD4 titer, but without other infectious processes. Other immune response parameters such as Treg, cytotoxic T cells, and complement and total IgG level were the same as they were before the transplant procedure. Interestingly, a second wave of immunoreconstitution with an anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. A patient with lymphocyte depletion in conditioning showed an earlier second wave of immunoreconstitution (6th vs. 14th month).
    CONCLUSIONS: As is typical for infancy, the kinetics of the IgG level is unique after HSCT (the decline phase is first). Host microbiome factors (e.g., HHV1-3-serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help in predicting prognoses and improve disease management. A lack of differentiation and the confusing bias of the assessor (i.e., observer selection bias) are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be the first to build evidence of a pathway and an association between immune parameters and HHV disease.
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  • 文章类型: Meta-Analysis
    背景:关于巨细胞病毒(CMV)感染与阿尔茨海默病(AD)相关的证据很少,结果不一致。
    目的:探讨CMV感染与AD发病风险的关系。
    方法:关于CMV感染与AD之间关系的观察性研究来自PubMed,Embase,WebofScience,和Cochrane图书馆,直到2022年9月30日。使用纽卡斯尔-渥太华量表评估纳入研究的质量。随机效应荟萃分析使用通用逆方差方法进行,其次是基于研究设计的敏感性分析和亚组分析,regions,调整,和人口类型。
    结果:我们的搜索产生了870篇文章,其中200个是重复的,663个不符合纳入标准,最终有6,772名参与者进行了7项研究。在总结分析中没有观察到关于CMV感染和AD风险关联的有力证据(比值比[OR]=1.33;95%置信区间[CI]:0.88,2.03,I2=69.9%)。然而,亚组分析显示,东亚人的AD风险增加(OR=2.39;95%CI:1.63,3.50,I2=0.00%),队列研究(OR=1.99;95%CI:1.35,2.94,I2=28.20%),和具有混杂校正的研究(OR=2.05;95%CI:1.52,2.77,I2=0.00%)。
    结论:这项荟萃分析提供了证据支持CMV感染与AD之间相关性的异质性。未来有必要进行更大样本量和多种族人群的研究。
    BACKGROUND: Evidence on the association of cytomegalovirus (CMV) infection with Alzheimer\'s disease (AD) is scarce and the results are inconsistent.
    OBJECTIVE: To investigate the association of CMV infection with the risk of AD.
    METHODS: Observational studies on the relationship between CMV infection and AD were identified from PubMed, Embase, Web of Science, and the Cochrane Library until September 30, 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effect meta-analysis was performed using a generic inverse-variance method, followed by sensitivity analyses and subgroup analyses based on study designs, regions, adjustments, and population types.
    RESULTS: Our search yielded 870 articles, of which 200 were duplicates and 663 did not meet the inclusion criteria, and finally yielded seven studies with 6,772 participants. No strong evidence was observed in the summary analysis for the association of CMV infection and risk of AD (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 0.88, 2.03, I2 =69.9%). However, subgroup analysis showed that an increased risk of AD was detected in East Asians (OR = 2.39; 95% CI: 1.63, 3.50, I2 = 0.00%), cohort studies (OR = 1.99; 95% CI: 1.35, 2.94, I2 = 28.20%), and studies with confounder adjustment (OR = 2.05; 95% CI: 1.52, 2.77, I2 = 0.00%).
    CONCLUSIONS: This meta-analysis provides evidence to support the heterogeneity of the associations between CMV infection and AD. Future studies with larger sample sizes and multi-ethnic populations are necessary.
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  • 文章类型: Case Reports
    玫瑰糠疹(PR),良性和自限性皮肤病,通常表现为称为先驱片的单个初始病变。先兆斑块通常伴随着继发性红斑丘疹和斑块的发展,与兰格的线条对齐,形成特定的分布模式,背面像圣诞树,上胸部有V形图案。因此,根据其典型的临床表现诊断PR可能并不困难。相比之下,已经报道了非典型PR表现的病例,包括几种鉴别诊断。这里,我们提出了一个需要与癣区分的多个先驱补丁的案例,梅毒,和红斑环状离心机。随后,我们的病例被诊断为PR,因为补丁形成了V形图案和圣诞树分布。
    Pityriasis rosea (PR), a benign and self-limiting skin disorder, typically manifests as a single initial lesion known as the herald patch. The herald patch is commonly followed by the development of secondary erythematous papules and plaques, aligning with Langer\'s lines to form a specific distribution pattern, resembling a Christmas tree on the back and a V-shaped pattern on the upper chest. Therefore, diagnosing PR may not be difficult based on its typical clinical presentation. In contrast, cases of atypical PR presentation have been reported, encompassing several differential diagnoses. Here, we present a case with multiple herald patches that needed differentiation from ringworm, syphilis, and erythema annular centrifugum. Subsequently, our case was diagnosed with PR, as the patches formed a V-shaped pattern and a Christmas-tree distribution.
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