[Current vaccination and immunization strategies in dermatology]. / Aktuelles zu Impfungen und Immunisierungsstrategien in der Dermatologie.

Vaccinations are an important pillar of public health. They have high benefits for individuals and society as a whole by specifically preventing or mitigating infectious diseases. In many cases, they offer benefits that go beyond protection against the disease in question, e.g., protective cardiovascular effects. Vaccination recommendations in Germany are drawn up by the Standing Committee on Vaccination (STIKO), while the European Medicines Agency (EMA) is responsible for the approval of vaccines in the EU. Vaccinations may be carried out by physicians regardless of their specialty. In dermatology, vaccinations against varicella (chickenpox), herpes zoster, and human papillomavirus are established. The development of vaccines against other dermatologically relevant diseases and cancer vaccines is the subject of intensive research. Particularly in the case of immunosuppression, the physician must also take into consideration which vaccinations are possible and useful or contraindicated. Type I or type IV allergies to components of vaccinations are very rare, but reactions at the injection site often occur as a dermatological side effect. Urticarial reactions are also possible, as does the worsening of underlying dermatological conditions such as psoriasis vulgaris.

Herpes zoster ophthalmicus uveitis: onset and complications: Herpes Zoster Uveitis.

PURPOSE: To describe the timing of uveitis onset and frequency of associated complications in individuals with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective, cohort study METHODS: Individuals with acute HZO seen at the Auckland District Health Board from 2006 to 2016 were studied. The primary outcome measures were the proportion who developed uveitis and time to diagnosis of uveitis following the onset of HZO. Secondary outcome measures included complications of HZO uveitis and effects of prompt antiviral (within 72 hours) on outcomes. RESULTS: 869 patients with HZO were included for analysis, of whom 413 (47.6%) developed uveitis. Median time from onset of rash to diagnosis of uveitis was 10 days (IQR 6 - 14). Of the 658 individuals examined within the first week following rash onset (days 0 through 7), 17.6% (116/658) were diagnosed with uveitis at that initial presenting examination, with an additional 24.9% (164/658) diagnosed with uveitis at a subsequent visit. Complications were higher in eyes with uveitis, including: moderate or severe vision loss, corneal scarring, neurotrophic keratitis, band keratopathy, corneal melt, elevated intraocular pressure, glaucoma, and cataract (all p<0.01). Prompt antiviral was associated with a lower rate of moderate vision loss among eyes with uveitis (p=0.02). CONCLUSIONS: Uveitis occurred in approximately half of individuals with HZO and was most frequently diagnosed during the second week following rash onset. Eyes with uveitis were more likely to have other ocular complications and loss of vision.

Israeli neonatal herpes simplex infection: Unique epidemiology and clinical profile.

To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, p-value < 0.01) and seizures (0% vs. 6%, p-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, p-value < 0.01; 37% vs. 1%, p-value < 0.01; 25% vs. 1%, p-value < 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation.

Natural Language Processing Versus Diagnosis Code-Based Methods for Postherpetic Neuralgia Identification: Algorithm Development and Validation.

Background: Diagnosis codes and prescription data are used in algorithms to identify postherpetic neuralgia (PHN), a debilitating complication of herpes zoster (HZ). Because of the questionable accuracy of codes and prescription data, manual chart review is sometimes used to identify PHN in electronic health records (EHRs), which can be costly and time-consuming. Objective: This study aims to develop and validate a natural language processing (NLP) algorithm for automatically identifying PHN from unstructured EHR data and to compare its performance with that of code-based methods. Methods: This retrospective study used EHR data from Kaiser Permanente Southern California, a large integrated health care system that serves over 4.8 million members. The source population included members aged ≥50 years who received an incident HZ diagnosis and accompanying antiviral prescription between 2018 and 2020 and had ≥1 encounter within 90-180 days of the incident HZ diagnosis. The study team manually reviewed the EHR and identified PHN cases. For NLP development and validation, 500 and 800 random samples from the source population were selected, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F-score, and Matthews correlation coefficient (MCC) of NLP and the code-based methods were evaluated using chart-reviewed results as the reference standard. Results: The NLP algorithm identified PHN cases with a 90.9% sensitivity, 98.5% specificity, 82% PPV, and 99.3% NPV. The composite scores of the NLP algorithm were 0.89 (F-score) and 0.85 (MCC). The prevalences of PHN in the validation data were 6.9% (reference standard), 7.6% (NLP), and 5.4%-13.1% (code-based). The code-based methods achieved a 52.7%-61.8% sensitivity, 89.8%-98.4% specificity, 27.6%-72.1% PPV, and 96.3%-97.1% NPV. The F-scores and MCCs ranged between 0.45 and 0.59 and between 0.32 and 0.61, respectively. Conclusions: The automated NLP-based approach identified PHN cases from the EHR with good accuracy. This method could be useful in population-based PHN research.

HSV-1 immune escapes in microglia by down-regulating GM130 to inhibit TLR3-mediated innate immune responses.

BACKGROUND: To investigate the mechanism of Golgi matrix protein 130(GM130) regulating the antiviral immune response of TLR3 after herpes simplex virus type 1(HSV-1) infection of microglia cells. We explored the regulatory effects of berberine on the immune response mediated by GM130 and TLR3. METHODS: An in vitro model of HSV-1 infection was established by infecting BV2 cells with HSV-1. RESULTS: Compared to the uninfected group, the Golgi apparatus (GA) fragmentation and GM130 decreased after HSV-1 infection; TLR3 increased at 6 h and began to decrease at 12 h after HSV-1 infection; the secretion of interferon-beta(IFN-ß), tumour necrosis factor alpha(TNF-α), and interleukin-6(IL-6) increased after infection. Knockdown of GM130 aggravated fragmentation of the GA and caused TLR3 to further decrease, and the virus titer also increased significantly. GM130 knockdown inhibits the increase in TLR3 and inflammatory factors induced by TLR3 agonists and increases the viral titer. Overexpression of GM130 alleviated fragmentation of the GA induced by HSV-1, partially restored the levels of TLR3, and reduced viral titers. GM130 overexpression reversed the reduction in TLR3 and inflammatory cytokine levels induced by TLR3 inhibitors. Therefore, the decrease in GM130 levels caused by HSV-1 infection leads to increased viral replication by inhibiting TLR3-mediated innate immunity. Berberine can protect the GA and reverse the downregulation of GM130, as well as the downregulation of TLR3 and its downstream factors after HSV-1 infection, reducing the virus titer. CONCLUSIONS: In microglia, one mechanism of HSV-1 immune escape is disruption of the GM130/TLR3 pathway. Berberine protects the GA and enhances TLR3-mediated antiviral immune responses.

Assessment of the humoral immune status of varicella-zoster virus in patients with diffuse connective tissue diseases.

Background: Diffuse connective tissue diseases (DCTDs) require long-term immunosuppressive treatment, increasing the risk of varicella-zoster virus (VZV) infection. This study aims to evaluate the humoral immune status against VZV in DCTD patients and explore factors that may influence their immune levels. Methods: This is a retrospective cohort study that collected data from adult DCTD patients (≥18 years) attending our outpatient clinic. The geometric mean concentration (GMC) of VZV-specific IgG antibodies in the patients' sera was measured using the enzyme-linked immunosorbent assay (ELISA). Results: A total of 280 RA patients, 272 SLE + MCTD patients and 280 healthy controls were included. SLE + MCTD patients had significantly higher VZV IgG antibody levels than RA patients (p < 0.05) but showed no significant difference compared to healthy controls (p > 0.05). Notable differences were observed particularly among female patients and those aged 30-49 years, (p < 0.05). SLE + MCTD patients in an active disease state had significantly higher VZV IgG antibody titers than RA patients (p < 0.05). Additionally, patients with a history of herpes zoster, regardless of being in the SLE + MCTD, RA, or control group, exhibited higher VZV IgG titers (p < 0.05). Conclusion: Although DCTD patients, particularly those with SLE and MCTD, exhibit higher VZV IgG antibody levels, they still face a higher risk of developing herpes zoster (HZ), which may be related to their underlying disease and immunosuppressive treatment. The presence of antibodies alone may not provide complete protection, necessitating consideration of cellular immune mechanisms. It is recommended to enhance monitoring of VZV antibody levels in high-risk patients and consider herpes zoster vaccination to reduce HZ-related complications.

Associations of head and neck cancers with herpes zoster in the preceding five years.

This population-based study investigated the risk of having had prior herpes zoster within five years preceding a diagnosis of head and neck cancer. We conducted a case-control study that included 9,191 patients with a diagnosis of head and neck cancer in Taiwan's Longitudinal Health Insurance Database 2010 and 36,764 matched controls. We assessed the odds of patients with head and neck cancer having had a diagnosis of herpes zoster during the five years preceding head and neck cancer using multiple logistic regression analysis. The prevalence of prior herpes zoster among the total sample was 4.6%, 7.9% and 3.8% among patients with and without head and neck cancer, respectively (p < 0.001). The odds ratio of herpes zoster among the head and neck cancer- versus control group was 2.198 (95% CI = 2.001 ~ 2.415) after adjusting for sociodemographic characteristics and hypertension, diabetes, hyperlipidemia, tobacco use disorder, HPV infection, and alcohol dependence syndrome. Statistically significant excess odds were observed for all specific subtypes of head and neck cancer except for sinonasal cancer. Herpes zoster infection within the 5 years preceding a diagnosis of head and neck cancer may be a harbinger of developing head and neck cancer.

Eczema Herpeticum: Clinical Insights and Pathogenesis Hypotheses on Basolateral Adhesion Proteins.

Eczema herpeticum (EH) is a severe viral complication caused by the herpes simplex virus (HSV) that occurs in individuals with compromised skin barriers, such as those with atopic dermatitis (AD). EH is characterized by the rapid spread of HSV across skin lesions, potentially leading to systemic involvement. Although commonly observed in the context of AD, EH can also arise in various dermatological conditions, necessitating prompt recognition and management by healthcare providers. This case report details the diagnosis and treatment of EH in a five-year-old girl with a history of AD who presents with fever and painful skin lesions. Despite the absence of confirmatory tests initially, a positive IgM anti-HSV-1 serology, combined with clinical presentation, supported the diagnosis of EH. The patient received intravenous aciclovir, resulting in significant improvement within 48 hours. This case highlights the importance of early diagnosis and treatment, particularly when confirmatory tests are not available. The report discusses the clinical presentation of EH, which includes vesicular lesions, fever, and rapid progression. The differential diagnosis includes chickenpox, impetigo, eczema vaccinatum, and contact dermatitis. Understanding the epidemiology and pathogenesis of EH, especially in relation to AD, is crucial for effective management. The case also introduces a novel hypothesis linking structural protein alterations to immune dysfunction in EH, suggesting a need for further research. Acyclovir remains the gold standard for treating EH, and timely intervention is essential. This case underscores the necessity of a diagnostic algorithm in the absence of guidelines and highlights the role of IgM serology and clinical judgment in managing suspected EH cases.

Factors Influencing Herpes Zoster Vaccine Utilization Among Adults Aged 50 and Above Attending Primary Healthcare Center in Saudi Arabia: A Cross-Sectional Study.

INTRODUCTION: Herpes zoster, or shingles, is a significant health concern for older adults caused by the varicella-zoster virus (VZV) reactivation. The availability of effective herpes zoster vaccines offers a crucial preventive measure to reduce the incidence and severity of this condition. However, the uptake of the available vaccine remains suboptimal, especially among adults aged 50 and above. Understanding the factors that influence vaccine utilization is not only essential for developing strategies to improve vaccination rates but also has the potential to significantly reduce the disease burden. METHODS: This cross-sectional study aimed to identify factors influencing herpes zoster vaccine utilization among adults aged 50 and above attending primary healthcare center in Saudi Arabia. Data were collected using a validated questionnaire administered to visitors attending Al-Wazarat Primary Healthcare Center in Riyadh. Descriptive and inferential statistics were employed to analyze the data. RESULTS: A total of 403 participants were included in the study, with 73.7% of participants having heard of the disease, yet only 34.2% had received the vaccine. Vaccine uptake was significantly associated with gender, educational level, and healthcare provider recommendations. Common barriers to vaccination included fear of side effects, lack of perceived susceptibility, concerns about vaccine effectiveness, and access to healthcare facilities. CONCLUSION: Herpes zoster vaccine utilization among older adults in Saudi Arabia is relatively low despite moderate awareness. Enhancing public education through targeted campaigns and strengthening healthcare provider recommendations are crucial to improving vaccine uptake. Addressing specific barriers and misconceptions is essential to reduce the burden of herpes zoster in this population. The need for future research to explore strategies to overcome these challenges and promote higher vaccination rates is urgent and important.

A study on the causal relationship between the gut microbiome and herpes zoster using Mendelian randomization.

Introduction: The relationship between herpes zoster recurrence and the gut microbiome was not studied. We analyzed data on the gut microbiome and herpes zoster from the Large-Scale Genome-Wide Association Study (GWAS) database using bidirectional Mendelian randomization. For the first time, we identified a potentially bidirectional causal relationship between the gut microbiome and herpes zoster (HZ). These findings are groundbreaking and hold promise for new directions in the treatment of HZ, a global disease. Background and aims: HZ had a high global incidence, characterized by shingled blisters, blood blisters, and neuropathic pain, and could develop in various parts of the body, including the ear and throat. It was believed its onset was closely related to old age and infirmity. Some studies reported that the incidence of herpes zoster in patients with inflammatory intestinal diseases (such as Crohn's disease and ulcerative colitis) was higher than in the general population. Existing studies attributed this to the reactivation of varicella-zoster virus (VZV) due to autoinflammatory attacks and immunosuppressive drugs. This provided a basis for exploring the new pathogenesis of HZ and investigating whether there was a relationship between intestinal auto-flora and the development of HZ. This study aimed to examine this potential relationship using bidirectional Mendelian analyses. Methods: GWAS data on HZ and gut microbiota were obtained from FinnGen, the Mibiogen consortium, and HZ meta-analysis data from the IEU Open GWAS Project. These data were subjected to two-sample Mendelian randomization (MR) analysis to determine if there is a causal relationship between gut microbiota and HZ. Additionally, bidirectional Mendelian analyses were conducted to identify the direction of causality and to clarify any potential interactions. Results: In our Mendelian Randomization (MR) analysis, we identified, for the first time, two gut microbes that might be associated with HZ reactivation. In the reverse MR analysis, four gut microbiota showed a potential association between the genetic susceptibility of gut microbiota and HZ reactivation. We found that genus Tyzzerella3 (OR: 1.42, 95% CI: 1.17-1.72, FDR < 0.1) may be strongly correlated with an increased probability of HZ (ICD-10: B02.901) reactivation. Additionally, phylum Cyanobacteria was identified as a potential risk factor for the onset of HZ rekindling (OR: 1.42, 95% CI: 1.09-1.87). Analyzing the results of the reverse MR, we also identified a potential inhibitory effect (OR: 0.91, 95% CI: 0.84-0.99) of HZ onset on the genus Eubacteriumhallii group in the gut, suggesting that HZ might reduce its abundance. However, genus Escherichia/Shigella (OR: 1.11, 95% CI: 1.01-1.22), genus Veillonella (OR: 1.16, 95% CI: 1.04-1.30), and phylum Proteobacteria (OR: 1.09, 95% CI: 1.01-1.18) appeared to act as potential protective factors, indicating that the relative abundance and viability of these three bacteria increased in the HZ state. Conclusion: We identified the influence of gut flora as a new causative factor for HZ reactivation. Additionally, we found that individuals suffering from HZ might potentially impact their gut flora. Specific bacterial taxa that could influence the onset and progression of HZ were identified, potentially providing new directions for HZ treatment.

Efficacy and Safety of Pulsed Radiofrequency of Dorsal Root Ganglion in Elderly Patient Population With Acute and Subacute Zoster-Related Pain.

Background: Herpes zoster (HZ) is typically characterized by a burning, stabbing pain, hyperalgesia, and allodynia. In some patients, despite the lesions resolving, the pain persists and becomes chronic. If the pain continues for more than 6 months after the onset of the pain phase, this condition is called postherpetic neuralgia (PHN). The frequency and severity of PHN increase with advancing age. The pain in PHN can be severe, sometimes resistant to medications, significantly impacting the patients' quality of life. The elderly patient population cannot tolerate the medications due to their side effects. In this situation, interventional pain treatment should be applied in the elderly patient group who have a high risk of developing PHN compared to other age groups. Method: We included patients over 65 years of age with HZ-related pain who underwent dorsal root ganglion (DRG) pulsed radiofrequency (PRF) within the first 6 months from the onset of pain. We divided these patients into 2 groups: patients who underwent intervention within the first 1 month from the onset of pain and patients who underwent intervention between 1 and 6 months. We recorded medication doses and Numeric Rating Scale (NRS) scores before the procedure and at 1 week, 1 month, 3 months, and 6 months after the procedure. Results: After the DRG PRF treatment, NRS scores improved significantly in both groups (p < 0.05). The mean NRS score in the early DRG PRF group was significantly lower than that in the late DRG PRF group (p < 0.05). The medication doses in the early DRG PRF group were significantly lower than those in the other group (p < 0.05). Conclusions: Interventional pain treatment should be applied as soon as possible in the elderly patient group who do not respond to first-line medical treatment or cannot tolerate medical treatment due to its side effects and who have a high risk of developing PHN compared to other age groups. DRG PRF, applied in the early period of medical treatment-resistant acute HZ, is safe and effective, preventing the progression to PHN.

Understanding herpes zoster vaccine hesitancy and information asymmetry: a qualitative study in China.

Background: Herpes zoster is more prevalent among the older adult due to the age-related immune decline, leading to significant pain and complications. Although vaccination effectively prevents viral infections, vaccine hesitancy remains a major barrier to achieving high vaccination rates.To address this, we conducted a qualitative survey using Vaccine Hesitancy Determinants Matrix and 5C model to understand and improve vaccination rates in this group. Methods: Descriptive qualitative research design based on the philosophical underpinnings of naturalistic inquiry and purposive sampling methodology was conducted on adults aged 50 and above, as well as community health workers. Data were collected through semi-structured, in-depth personal interviews. The interview outline was constructed following a comprehensive review of the literature and consideration of the theoretical framework. Results: Seventeen adults over 50 years and four community healthcare workers were included in this study. The study found that information asymmetry in immunization planning was evident at all stages of vaccine supply, dissemination and demand. The main manifestations included limited access to authoritative information, insufficient community awareness of herpes zoster as a route of vaccination, insufficient vocational training, significant gaps in vaccine knowledge, and high levels of complacency among individual residents. Conclusion: Herpes zoster vaccine hesitancy is prevalent among middle-aged and older adults in China due to information asymmetry, vaccine complacency, inadequate community services, and other multiple layers of factors. Public health strategies should aim to reduce cognitive biases and information gaps by disseminating diverse and credible vaccine information through social media, medical institutions, and offline channels to promote higher vaccination rates.

A drug repurposing screen identifies decitabine as an HSV-1 antiviral.

Herpes simplex virus type 1 (HSV-1) is a highly prevalent human pathogen that causes a range of clinical manifestations, including oral and genital herpes, keratitis, encephalitis, and disseminated neonatal disease. Despite its significant health and economic burden, there is currently only a handful of approved antiviral drugs to treat HSV-1 infection. Acyclovir and its analogs are the first-line treatment, but resistance often arises during prolonged treatment periods, such as in immunocompromised patients. Therefore, there is a critical need to identify novel antiviral agents against HSV-1. Here, we performed a drug repurposing screen, testing the ability of 1,900 safe-in-human drugs to inhibit HSV-1 infection in vitro. The screen identified decitabine, a cytidine analog that is used to treat myelodysplastic syndromes and acute myeloid leukemia, as a potent anti-HSV-1 agent. We show that decitabine is effective in inhibiting HSV-1 infection in multiple cell types, including human keratinocytes, that it synergizes with acyclovir, and acyclovir-resistant HSV-1 is still sensitive to decitabine. We further show that decitabine causes G > C and C > G transversions across the viral genome, suggesting it exerts its antiviral activity by lethal mutagenesis, although a role for decitabine's known targets, DNA methyl-transferases, has not been ruled out. IMPORTANCE: Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen with a limited arsenal of antiviral agents, resistance to which can often develop during prolonged treatment, such as in the case of immunocompromised individuals. Development of novel antiviral agents is a costly and prolonged process, making new antivirals few and far between. Here, we employed an approach called drug repurposing to investigate the potential anti-HSV-1 activity of drugs that are known to be safe in humans, shortening the process of drug development considerably. We identified a nucleoside analog named decitabine as a potent anti-HSV-1 agent in cell culture and investigated its mechanism of action. Decitabine synergizes with the current anti herpetic acyclovir and increases the rate of mutations in the viral genome. Thus, decitabine is an attractive candidate for future studies in animal models to inform its possible application as a novel HSV-1 therapy.

Herpes Zoster Risk After Total Knee Replacement: a multicenter, propensity-score-matched cohort study in the United States.

Background: Total knee replacement (TKR) is a common surgical procedure for osteoarthritis (OA) patients. TKR may increase susceptibility to herpes zoster (HZ) by inducing immunosuppression, surgical stress, and nerve injury. However, limited data exist on the relationship between TKR and HZ. This study examined the risk of HZ over time among OA patients who underwent TKR and those who did not, using a large population-based cohort. Method: Utilizing the TriNetX research network, people with OA and underwent TKR were recruited as case group. After 1:1 propensity score matching, OA patients who never experienced TKR were included as control group. Covariates, including demographics, comorbidities, and laboratory data, were balanced using propensity score matching. A 5-year follow-up assessed the hazard ratio of incident HZ and related complications. Results: Compared to the control group, a significantly elevated risk of HZ was observed in the TKR cohort across 5-year follow-up period, with the hazard ratio of 1.223 (95% CI: 1.089-1.373). Zoster without complications presented 1.173-fold risk in TKR patients while comparing with non-TKR controls. However, most other secondary outcomes related to HZ complications-such as encephalitis, neurological involvement, ocular disease, and disseminated zoster-did not show a significant increase in risk. The risk of HZ was statistically significant for females and older adults in the TKR cohort than in the control cohort. Conclusions: OA patients who underwent TKR had an increased risk of HZ compared to those who did not receive the procedure, especially females and older adults. These findings highlight the need for HZ monitoring/prevention protocols and further research on mitigating viral reactivation after major joint surgery.

Concurrent Varicella-Zoster Virus Reactivation and Recurrent Herpes Simplex Virus Infection in the C2 Dermatome With Varicella-Zoster Virus Encephalitis: A Case Report and Review of the Literature.

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are common viruses that are present in the general population. However, it is uncommon for both viruses to coincide at the same time and location. These viruses infect the nervous system to establish latency and have been associated with neurological disorders. We discuss a case of co-occurring VZV reactivation and recurrent HSV infection with subsequent VZV encephalitis following an insult to the neurologic system.

A Diagnostically Challenging Case of Recurrent Encephalitis With Impending Herniation.

Encephalitis is characterized by inflammation of the brain parenchyma with typical presenting symptoms of altered mental status and seizures. However, diagnostic workup is complex given the multitude of possible etiologies for encephalitis. Further, recurrence of encephalitis is rare, and understanding its risk factors, mechanisms, prognosis, and optimal treatment remains incomplete. Here, we present the case of a 69-year-old woman admitted to our hospital with altered mental status who was diagnosed with encephalitis based on clinical and imaging findings. This case highlights the diagnostic approaches required to obtain the final diagnosis and the treatment plan that resulted in the patient's eventual return to baseline and functional independence.

Herpes Vegetans in a Patient With Acquired Immunodeficiency Syndrome (AIDS) in the Setting of Immune Reconstitution Inflammatory Syndrome.

Herpes simplex virus (HSV) infections classically present as a vesicular eruption on an erythematous base; however, viral infections may present much differently in the setting of immune deficiency. Herpes vegetans is an atypical presentation of HSV that occurs in immunocompromised patients, typically those with human immunodeficiency virus infection and acquired immunodeficiency syndrome (AIDS). Herpes vegetans is characterized by hyperkeratotic, exophytic, and, sometimes, ulcerated nodules, often with a chronic and persistent course. Herein, we present an interesting example of biopsy-confirmed anogenital herpes vegetans in a 61-year-old male with AIDS in the setting of immune reconstitution inflammatory syndrome, an association that is less frequently described. This case serves as an important reminder to consider atypical presentations of infectious disease when examining immunocompromised patients, as prompt diagnosis and treatment are essential in this population.

Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.

Purpose: Immunizations have long been pivotal in preventing diseases like HZ (herpes zoster), caused by VZV (varicella zoster virus). This study aims to evaluate the efficacy and safety of the RZV (recombinant zoster vaccine) compared to the ZVL (zoster vaccine live) and to report rare adverse events following RZV administration. Observation: Herein, we report an unusual case of a 59-year-old man who developed a V1-limited rash with a positive HZ PCR (polymerase chain reaction) test following administration of RZV in the United States. Conclusion: The development of RZV has significantly improved the prevention of HZ compared to ZVL. Nevertheless, rare adverse events, such as dermatomal reactions, underscore the importance of ongoing monitoring and research into the immunomodulatory effects of RZV. Physicians should continue to administer the RZV to patients but be cognizant that reactivation may rarely subsequently occur. Case Presentation: The patient with a history of benign prostatic hyperplasia was treated at an outside hospital two days after receiving the RZV complaining of paresthesia and a rash on his nasolacrimal area and forehead. The patient presented to the ED (emergency department), 9 days post-vaccination due to persistence of his symptoms despite use of amoxicillin, valacyclovir, and an unidentified eye drop. The dose of valacyclovir was increased, and he completed 1 g TID (three times a day) PO (per orally) for 10 days with subsequent resolution of symptoms. A positive PCR test confirmed the diagnosis of HZ. Topical mupirocin ointment was initiated and the patient was referred for ophthalmologic evaluation.

Herpes simplex virus 1 inhibits phosphorylation of RNA polymerase II CTD serine-7.

Transcriptional activity of RNA polymerase II (Pol II) is influenced by post-translational modifications of the C-terminal domain (CTD) of the largest Pol II subunit, RPB1. Herpes simplex virus type 1 (HSV-1) usurps the cellular transcriptional machinery during lytic infection to efficiently express viral mRNA and shut down host gene expression. The viral immediate-early protein ICP22 interferes with serine 2 phosphorylation (pS2) by targeting CDK9 and other CDKs, but the full functional implications of this are not well understood. Using Western blotting, we report that HSV-1 also induces a loss of serine 7 phosphorylation (pS7) of the CTD during lytic infection, requiring expression of the two immediate-early proteins ICP22 and ICP27. ICP27 has also been proposed to target RPB1 for degradation, but we show that pS2/S7 loss precedes the drop in total protein levels. Cells with the RPB1 polyubiquitination site mutation K1268R, preventing proteasomal degradation during transcription-coupled DNA repair, displayed loss of pS2/S7 but retained higher overall RPB1 protein levels later in infection, indicating this pathway is not involved in early CTD dysregulation but may mediate bulk protein loss later. Using α-amanitin-resistant CTD mutants, we observed differential requirements for Ser2 and Ser7 for the production of viral proteins, with Ser2 facilitating viral immediate-early genes and Ser7 appearing dispensable. Despite dysregulation of CTD phosphorylation and different requirements for Ser2/7, all CTD modifications tested could be visualized in viral replication compartments with immunofluorescence. These data expand the known means that HSV employs to create pro-viral transcriptional environments at the expense of host responses.IMPORTANCECells rapidly induce changes in the transcription of RNA in response to stress and pathogens. Herpes simplex virus (HSV) disrupts many processes of host mRNA transcription, and it is necessary to separate the actions of viral proteins from cellular responses. Here, we demonstrate that viral proteins inhibit two key phosphorylation patterns on the C-terminal domain (CTD) of cellular RNA polymerase II and that this is separate from the degradation of polymerases later in infection. Furthermore, we show that viral genes do not require the full "CTD code." Together, these data distinguish multiple steps in the remodeling of RNA polymerase during infection and suggest that shared transcriptional phenotypes during stress responses do not revolve around a core disruption of CTD modifications.