Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus.

PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). DESIGN: Retrospective, multicenter case series. METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus. RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU. CONCLUSION: This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.

Octyl substituted butenolides from marine-derived Streptomyces koyangensis.

A new butenolide derivative (1) featuring octyl substitution at γ-position, together with four known analogues (2-5) were isolated from marine-derived Streptomyces koyangensis SCSIO 5802. The structure of 1 was elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configuration of the stereo centre in lactone ring of 1 was determined by comparison of CD spectrum with those of known compounds. Compound 1 exhibited mild antiviral activity against herpes simplex virus with EC50 value of 25.4 µM.

Resolution of herpes simplex virus reactivation in vivo results in neuronal destruction.

A fundamental question in herpes simplex virus (HSV) pathogenesis is the consequence of viral reactivation to the neuron. Evidence supporting both post-reactivation survival and demise is published. The exceedingly rare nature of this event at the neuronal level in the sensory ganglion has limited direct examination of this important question. In this study, an in-depth in vivo analysis of the resolution of reactivation was undertaken. Latently infected C57BL/6 mice were induced to reactivate in vivo by hyperthermic stress. Infectious virus was detected in a high percentage (60-80%) of the trigeminal ganglia from these mice at 20 hours post-reactivation stimulus, but declined by 48 hours post-stimulus (0-13%). With increasing time post-reactivation stimulus, the percentage of reactivating neurons surrounded by a cellular cuff increased, which correlated with a decrease in detectable infectious virus and number of viral protein positive neurons. Importantly, in addition to intact viral protein positive neurons, fragmented viral protein positive neurons morphologically consistent with apoptotic bodies and containing cleaved caspase-3 were detected. The frequency of this phenotype increased through time post-reactivation. These fragmented neurons were surrounded by Iba1+ cells, consistent with phagocytic removal of dead neurons. Evidence of neuronal destruction post-reactivation prompted re-examination of the previously reported non-cytolytic role of T cells in controlling reactivation. Latently infected mice were treated with anti-CD4/CD8 antibodies prior to induced reactivation. Neither infectious virus titers nor neuronal fragmentation were altered. In contrast, when viral DNA replication was blocked during reactivation, fragmentation was not observed even though viral proteins were expressed. Our data demonstrate that at least a portion of reactivating neurons are destroyed. Although no evidence for direct T cell mediated antigen recognition in this process was apparent, inhibition of viral DNA replication blocked neuronal fragmentation. These unexpected findings raise new questions about the resolution of HSV reactivation in the host nervous system.

BILATERAL ACUTE RETINAL NECROSIS: A Case Series.

PURPOSE: To investigate the clinical characteristics and visual outcome of bilateral acute retinal necrosis. METHODS: The study included 30 patients (60 eyes) who were diagnosed with bilateral acute retinal necrosis. The medical records were reviewed. RESULTS: Twenty-five patients developed the disease in the contralateral eye within 5 months and 5 patients at >2 years after the initial onset. At presentation, 14 of 21 eyes suffered from retinal necrosis of more than 180° in the initially affected eye, whereas 3 of 22 eyes suffered it in the later-affected eye. Retinal detachment occurred in 23 of the 27 initially affected eyes and in 5 of the 27 later-affected eyes. The mean logarithm of the minimum angle of resolution best-corrected visual acuity decreased from 2.0 ± 1.1 (Snellen equivalent counting fingers) to 2.2 ± 1.0 (Snellen equivalent counting fingers) in the initially affected eyes after a follow-up of 34.1 ± 48.2 months (P = 0.529), and improved from 0.5 ± 0.4 (Snellen equivalent 20/66) to 0.3 ± 0.4 (Snellen equivalent 20/40) in the later-affected eyes after a follow-up of 21.2 ± 23.3 months (P = 0.005). CONCLUSION: Bilateral acute retinal necrosis usually occurs in the contralateral eye within a few months, but sometimes after several years. Inflammation and retinal necrosis are less severe in the later-affected eye, with less retinal detachment and a better visual outcome.

A literature review of herpes simplex virus hepatitis in pregnancy.

Purpose: Hepatitis due to herpes simplex virus (HSV) during pregnancy is rare, it is often not included in the differential disease. However, hepatitis leads to maternal death; hence, early diagnosis is necessary. Hepatic enzyme elevation in late pregnancy is often associated with obstetric-related diseases, such as acute gestational fatty liver and HELLP syndrome (hemolytic anemia, elevated liver enzymes, low platelet count). These pregnancy-related diseases often improve maternal condition after completion of pregnancy, but in patients with HSV hepatitis, invasive treatment, such as cesarean section, may lead to deterioration of maternal condition after completion of pregnancy. A systematic review was conducted to extract necessary factors to avoid maternal death caused by herpetic hepatitis.Methods: In 24 cases reported since 1991, age, onset gestational weeks, initial symptoms, days from onset of symptoms to consultation, diagnosis method, treatment method, maximum liver escape enzyme value during hospitalization, bilirubin value, international normalized ratio value, and fetal/neonatal prognosis were extracted, and the relationship between maternal death group (n = 6) and maternal alive group (n = 18) was statistically analyzed.Results: Fever as an initial symptom was observed in all cases. Maternal death did not occur in patients administered with acyclovir (ACV) as empiric therapy. No difference was found between the two groups in other factors.Conclusion: Early diagnosis and treatment of herpetic hepatitis during pregnancy are important, as well as administration of empiric ACV concurrently with noninvasive diagnosis when a pregnant woman has elevated liver enzyme accompanied by fever in late pregnancy.

Neonatal Herpes Simplex Virus-1 Recurrence with Central Nervous System Disease in Twins after Completion of a Six-Month Course of Suppressive Therapy: Case Report.

Seventeen-day-old twins were hospitalized for neonatal herpes simplex virus 1 (HSV-1) with central nervous system disease and internal capsule and thalamic lesions on magnetic resonance imaging (MRI). They were treated with the usual intravenous (IV) treatment and oral therapy for 6 months. The clinical course was good in both children with negative HSV polymerase chain reaction on completion of IV therapy. The neurological condition recurred in one child with new radiological lesions at 7 months of age, 2 weeks after discontinuation of oral treatment. Cerebral lesions highlighted on the MRI scan are specific to the neonatal period and impact long-term prognosis. The likely genetic predisposition in this case is interesting and requires further investigation. In addition, this case raises questions about the duration of oral acyclovir suppressive therapy.

Hyperammonemia in a case of herpes simplex and anti-N-methyl-d-aspartate receptor encephalitis.

Herpes simplex encephalitis (HSE) is a widely accepted risk factor for anti N-methyl-d-aspartate receptor (NMDAR) encephalitis. Association of inherited metabolic disease has never been reported in a patient with HSE and anti-NMDAR encephalitis. Herein, we report a case of pediatric HSE complicated by development of anti-NMDAR encephalitis; this patient showed subsequent recurrent, unexplained episodes of encephalopathy associated with hyperammonemia. The patient was diagnosed with lysinuric protein intolerance (LPI), a rare inborn metabolic disorder. Although it would be difficult to make conclusions regarding the casual link of HSE and anti-NMDAR encephalitis with LPI from a single case, there have been many reports that autoimmune diseases and immunologic abnormalities are frequently associated with LPI. Thus, we speculate that LPI may contribute to the development of anti-NMDAR encephalitis following HSE.

Variations in the Clinical Course of Patients with Herpes Simplex Virus Esophagitis Based on Immunocompetence and Presence of Underlying Esophageal Disease.

BACKGROUND AND AIMS: Herpes simplex esophagitis (HSE) is the second most common cause of infectious esophagitis and occurs in both immunocompetent and immunocompromised patients. The aim of this study was to reappraise the clinical course of HSE in different patient populations based on degree of immunocompetence and the presence or absence of underlying esophageal disease. METHODS: Patients with histopathologically confirmed HSE identified from the Mayo Clinic pathology database from 2006 to 2016 were included in this study. Relevant demographic, clinical, and endoscopic data were retrospectively reviewed and compared between two cohorts: (a) immunocompromised and immunocompetent patients and (b) patients with and without underlying esophageal disorders. RESULTS: Forty-six patients were included in the study. The most common presenting symptoms were odynophagia (34.8%) and dysphagia (30.4%). Thirty-three (71.7%) patients were immunocompromised, and these patients who experienced longer duration of symptoms (25.5 ± 23.4 days vs. 7.0 ± 5.5 days, p = 0.04) were more likely to require an extension of treatment course (38.1% vs. 8.3%, p = 0.05) compared to their immunocompetent counterparts. Seventeen (37%) patients had underlying esophageal disease, and these patients were more likely to have concomitant esophageal candidiasis (41.2% vs. 10.3%, respectively; p = 0.01). CONCLUSION: Herpes simplex virus causes esophagitis in both immunocompetent and immunocompromised patients. While the disease course appears to be self-limited for all patient populations, clinical and endoscopic differences in the disease presentation and clinical course based on immune status and the presence or absence of underlying esophageal disease exist.

The lack of association between herpes simplex virus 1 or Toxoplasma gondii infection and cognitive decline in the general population: An 11-year follow-up study.

BACKGROUND: Inflammation has been suggested to be one, possibly treatable, cause of cognitive decline and dementia. The purpose of the present article was to investigate whether the herpes simplex virus 1 (HSV-1) or Toxoplasma gondii (T. gondii) infections are related to cognitive decline or dementia. METHOD: The Health 2000 survey, conducted 2000-2001, is a population-representative sample of people over 30 years old that involved 7112 participants. The sample was followed up in the year 2011, in the Health 2011 study. At both time points, cognitive performance was assessed with two tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessing verbal fluency and verbal learning. In addition, the abbreviated Mini-Mental State Examination was administered to people aged over 55. In addition, tests assessing reaction and movement time were performed at baseline. Dementia diagnoses from nationwide health care registers were followed up until the end of year 2013. The presence of HSV-1 and T. gondii immunoglobulin G (IgG) was determined by solid-phase immunoassay at baseline. RESULTS: HSV-1 or T. gondii seropositivity, or IgG antibody levels, were not associated with cognitive decline when investigated as infection × time interactions. In addition, the infections were not associated with the risk of dementia. CONCLUSIONS: In a large sample of participants that is representative of the whole country and with a long follow-up, the results suggest that latent HSV-1 or T. gondii infections are not related to either decline in cognitive performance or dementia risk.

Clinical Correlations of Positive Herpes Simplex PCR in Cerebrospinal Fluid.

OBJECTIVES: Herpes simplex viruses (HSV) can produce encephalitis (HSE), which requires early detection, typically using polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). However, other neurological conditions not directly caused by HSV may also present with a positive HSV PCR in the CSF (NCNHPCR+). We aimed to analyze the clinical features of both groups of patients (HSE vs. NCNHPCR+) and to consider the potential relevance of this finding in the latter. METHODS: A retrospective analysis of clinical presentation, workup (CSF, EEG, and MRI) and outcome of patients with an HSV+ result in CSF was conducted from Jan-2007 to Sep-2015 in our institution. Patients under 18 years and those with nonencephalitic HSV associated disorders were excluded. Group comparison between HSE and NCNHPCR+ patients was conducted using parametric and nonparametric tests accordingly. RESULTS: Sixteen HSE and 23 NCNHPCR+ patients were included. Patients with HSE presented a higher incidence of headache (87.5% vs. 43.5%; P=0.008), meningeal symptoms (50% vs. 17.4%; P=0.04), pleocytosis (75% vs. 18%; P=0.001), EEG abnormalities (46.67% vs. 22%; P=0.02) and typical MRI findings (50% vs. 0%; P<0.001), whereas 35% of patients with NCNHPCR+ had an underlying immunologic disorder (35% vs. 0%; P=0.012). CONCLUSIONS: The pathogenic role of HSV in NCNHPCR+ is uncertain. This finding must be interpreted in the appropriate clinical, EEG, and neuroimaging context. Immunocompromise and neuroinflammation states could be related to a higher presence of HSV in CSF.

Activation of Herpes Simplex Infection after Tattoo.

Tattooing is a procedure where ink is applied to an area of the skin, mostly intraepidermally (1). This procedure is carried out mainly for aesthetic purposes. Lately, it has been used as a corrective medical procedure following amputation of mammilla. The procedure is aggressive (2), and the fact that skin is punctured many times with the same needle which cannot be fully sterilized may cause infection of the treated area with bacterial, fungal, or viral agents that may lead to health consequences manifesting in the form of verrucae vulgaris, molluscum contagiosum, and herpes simplex. On the other hand, complications such as granulomas, allergic reactions, Koebner phenomenon, lupus erythematosus, psoriasis, lichen ruber planus, hepatitis C, and HIV infections should also be considered as potential consequences of tattooing (3-7). Even systemic reactions have been reported. Herein we describe a case of herpes infection activation after tattooing. Herein we present the case of a 46-year-old woman, employed in the medical sector, with a two-day history of herpes simplex in the labial area that manifested following application of a cosmetic tattoo meant to outline the lips (Figure 1). Two days after tattoo application, the vesicular lesions appeared along the area that was filled with ink, followed by sub-febrile temperature and fever and a subjective feeling of itching initially, followed by burning sensation and pain. The skin signs located on erythematous base were mainly grouped vesicles with sharply demarcated borders. Regional lymphatic nodes, mainly retro auricular, were enlarged. Within 48 hours, the patient was treated with acyclovir tablets in a dose of 800 mg three times a day and an antipyretic. Acyclovir ointment was administered during the first two days, as well as tetracycline ointment after the second day of the eruption. On the fifth day, we observed regression of the skin changes (Figure 2), and complete healing was achieved after one week. We assessed the medical history of the patient, which revealed the following: hypothyreosis due to lobectomy performed for the treatment of toxic adenoma. The patient was under substitutional therapy with 75 mg levothyroxine. The patient had herpes simplex before, and this was the second herpetic eruption. Herpes simplex is caused by a herpes simplex virus (HSV) type-1 infection that is transmitted through droplets of saliva or direct contact with the affected area, for example during kissing (8-10). Histology reveals intraepidermal blisters, degeneration in epidermal cells at the base of the vesicle, and multilocular eosinophilic inclusional bodies inside cells. Infection is usually more pronounced in the initial phase of disease, where the symptoms are also more intense. Activation of the infection occurs when the body undergoes a decrease in immunity (1), in situations of extensive exposure to the sun, and also in some other circumstances, such as the application of a tattoo as described herein. Tattooing can inoculate the virus or trigger the activation of the herpes virus and other viruses (1,8-10). Tattooing, apart from bringing social stigma in some cases, which is one of the major issues for persons who undergo the procedure, may also cause injuries, contact dermatitis, foreign body granuloma, infections, and allergic reactions including anaphylaxis. Herpes simplex infections are also possible, either by inoculation or reactivation of the HSV. Except in situations where the tattoo is performed for medicinal purposes, tattooing is not a procedure that is supported by dermatologists. Furthermore, tattooing also causes a number of side effects. Allergic reactions (3,4), anaphylactic shock, foreign body granuloma, lichen ruber planus (5), granuloma pyogenes (5), verruca vulgaris, molluscum contagiosum, herpes simplex, and some other bacterial and viral infections.

The study of leukocyte phagocytic activity in the presence of herpetic infection and stroke.

OBJECTIVE: Inrtoduction: Post-stroke complications are one of the urgent and insufficiently resolved problems. According to different literature data 23% to 65% of patients suffer from the post-stroke development of an infectious process. Herpes simplex virus type 1 and 2 can also be etiological factors of stroke development, however their reactivation is seldom mentioned in clinical observations. The development of immune suppression is considered to be the cause of these complications. The aim: The current study aims at determining post-stroke changes in leukocyte component of the immunity and in the presence of concomitant herpetic infection as well as at finding changes in phagocytosis parameters during antiviral treatment. PATIENTS AND METHODS: Materials and methods: The experiments were carried out on mice of the Balb/с line. The animals were infected with the herpes simplex virus type I, and 30 days later hemorrhagic stroke was simulated by administering 0.1 ml of autoblood into the right hemisphere. Following the acute stroke some animals were given acyclovir, proteflazid or altabor. From the animals' blood leukocytes were obtained and phagocytic activity and production of reactive oxygen species of granulocytes and agranulocytes in relation to fluorescent E.coli bacteria were studied by flow cytometry. RESULTS: Results: The experiment revealed significant changes in the redistribution between two major types of leukocytes in mice with stroke (an increased number of agranulocytes by 19.9%) and decreased phagocytosis activity, in the animals infected with herpes simplex virus type І in particular. Ischemic brain damage had an immunosuppressive effect on blood leukocytes. For comparison a significant increase in phagocyte count in leukocytes was found in the case of viral infection. The use of drugs with antiviral effects did not affect the activity of granulocytes / agranulocytes. CONCLUSION: Conclusion: Stroke can be the cause of latent herpes virus infection reactivation and has essential negative effect on immune characteristics of leukocytes that remain unchanged with the use of antiviral agents.

Strange case of dimorphic skin rash in a patient with cirrhosis: atypical herpes simplex and sweet's syndrome.

A middle-aged man with decompensated cirrhosis and a dimorphic multisite skin rash is diagnosed with rare atypical herpes simplex infection, manifesting Sweet's syndrome (SS) in the absence of other described associations. SS, an acute febrile neutrophilic dermatosis, has three common forms-classical or idiopathic, malignancy associated and drug induced. Systemic autoimmune, connective tissue diseases and infections are also strong associations. The latter is commonly described in Gram-positive bacteria, salmonellosis and Yersinia Herpes infections are a rare cause of SS, reported only thrice in literature, one with concomitant lupus, the second with associated mycobacterial infection and third, in metastatic breast disease in contrast to our patient. Atypical rash, especially if dimorphic, warrants histopathological evaluation to confirm underlying disease.