A young immunocompetent patient with bilateral immune stromal keratitis due to varicella zoster and herpes simplex

This report describes the diagnostic features, clinical management and the issues associated with management of a young immunocompetent male who presented with a presumed left Herpes simplex immune stromal keratitis, and ten months later, a right immune stromal keratitis associated with Herpes zoster ophthalmicus.

Keratitis durch Herpes-simplex- und Varizella-zoster-Virus

Herpes-simplex- und Varizella-zoster-Viren sind die häufigsten Ursachen viraler Keratitiden. Bei chronisch rezidivierendem Verlauf entstehen oft visuslimitierende Komplikationen. Typische Verlaufsformen sind die epitheliale Keratitis (dendritisch/geografisch), stromale Keratitis (infektiös und/oder immunologisch), Endotheliitis (disziform) und neurotrophe Keratopathie (metaherpetische Keratitis). Beim Zoster ophthalmicus kommt die Problematik der postherpetischen Neuralgie hinzu. Mit den verfügbaren Virustatika stehen potente Wirkstoffe zur Verfügung, auch zur Schubprophylaxe. Sobald immunologische Prozesse eine zentrale Rolle spielen, ist der gezielte Einsatz von topischen Kortikosteroiden oder Ciclosporin A notwendig. Der Epithelschluss kann mit Tränenersatzmitteln, Kontaktlinsen oder einer Amnionmembran-Transplantation unterstützt werden. Die Erfolgsrate von elektiven Keratoplastiken kann durch eine Langzeitprophylaxe mit systemischen Virustatika verbessert werden.

Thymoma, immunodeficiency, and herpes simplex virus infections.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

Social stress and the reactivation of latent herpes simplex virus type 1

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpesviruses.

Herpes simplex 2 risk among women in a polygynous setting in rural West Africa

OBJECTIVES: To determine risk factors for herpes simplex 2 (HSV2) infection in women in a polygynous rural Gambian population. METHODS: Data from women who participated in a cross-sectional survey of reproductive health were matched to their own and, for women who had been or were married (ever-married), their spouses' data collected in a cross-sectional survey of fertility interests, including information on marital histories. RESULTS: Data were available on 150 never-married and 525 ever-married women. HSV2 prevalence was 16% amongst never-married women and 36% amongst ever-married women. For ever-married women, their own personal characteristics (age, ethnicity and genital cutting status) and events from their husbands' marriage history were important determinants of HSV2 infection. Women whose husbands married for the first time over age 35 were at greater risk than women whose husbands married by age 24 [odds ratio (OR) 2.72, 95% confidence interval (CI) 1.20-6.10]. Women whose husband reported interest in a new marriage were more likely to be HSV2 positive (OR 1.91, 95% CI 1.18-3.09). Women whose husbands were currently monogamous but had had previous marriages (OR 2.76, 95% CI 1.30-5.88) and women in currently polygynous marriages (OR 2.88, 95% CI 1.66-5.01) were three times as likely to be HSV2 positive as women who were their husband's only wife ever. CONCLUSION: Much transmission of HSV2 in this setting occurs within marriage where opportunity for personal protection is limited. High levels of transmission within marriage may undermine the impact of sexual behaviour change programmes aiming to reduce HSV2 and HIV incidence and complicate their evaluation.

Late reactivation of herpes zoster keratitis results in band keratopathy

Purpose To report an unusual case of a late-stage reactivation of immune stromal keratitis associated with herpes zoster ophthalmicus (HZO), occurring without any apparent predisposing factors, more than 4 years after an acute zoster dermatomal rash. Significant corneal hypoesthesia and a central band keratopathy developed within 6 months of the late-stage reactivation. The clinical case management, issues associated with management, and management options are discussed, including the use of standardized, regulatory approved, antibacterial medical honey. Case Report An 83-year-old woman presented for routine review with a reactivation of right anterior stromal keratitis and mild anterior uveitis, occurring more than 4 years after an acute HZO dermatomal rash and an associated initial episode of anterior stromal keratitis. Corneal sensation became markedly impaired, and over the subsequent 6 months, a right central band keratopathy developed despite oral antiviral and topical steroid therapy. Visual acuity with pinhole was reduced to 20/100 in the affected eye and moderate irritation and epiphora were experienced. The patient declined the surgical intervention options of chelation, lamellar keratectomy, and phototherapeutic keratectomy to treat the band keratopathy. Longer-term management has involved preservative-free artificial tears, eyelid hygiene, standardized antibacterial medical honey, topical nonpreserved steroid, and UV-protective wraparound sunglasses. The clinical condition has improved over 14 months with this ocular surface management regimen, and visual acuity of 20/30 is currently achieved in a comfortable eye. Conclusions The chronic and recurrent nature of HZO can be associated with significant corneal morbidity, even many years after the initial zoster episode. Long-term review and management of patients with a history of herpes zoster stromal keratitis are indicated following the initial corneal involvement. Standardized antibacterial medical honey can be considered in the management of the chronic ocular surface disease associated with HZO and warrants further evaluation in clinical trials.

Herpes Simplex Virus Infection, Pathological Pain and Recurrent Lymphocytic Meningitis

Background: Aims of the study were: (i) to characterise the clinical picture, immunological features and changes in brain morphology and function in patients with widespread unilateral pain and HSV-infections, and (ii) to analyse the prevalence, clinical symptoms and immunological predisposing factors of HSV-2 induced recurrent lymphocytic meningitis (RLM) in Southern Finland. Patients and methods: Patients for the studies were recruited from the Pain Clinic, and from the Department of Neurology, at Helsinki University Central Hospital. Plasma concentrations of IgM, IgA, IgG, and IgG1-4, and serum concentrations of C3, C4 were measured. Serological anti-HSV-1 and -2 antibody status was tested. C4 genotyping, HLA-A, HLA-B and HLA-DRB1 typing, MBL2 genotyping, and IgG1 and IgG3 allotyping (Gm) were performed. Clinical neurological examination, quantitative sensory testing, skin biopsy, and functional magnetic resonance imaging were also performed. Results: HSV probably has a role in the generation of a pathological pain state. Low serum IgG1 and IgG3 levels, made the patients vulnerable for recurring HSV infections. Both functional and structural changes were observed in the brain pain-processing areas in the patients: they had less pain-related activity in the insular cortices bilaterally, in the anterior cingular cortex (ACC), and in the thalamus, and the gray matter density was lower in the ACC, in the frontal and prefrontal cortices. In the meningitis studies it was shown that RLM is more common and less benign than previously reported, and that neuropathic pain is frequently present both during and after meningitis episodes. HLA-DRB1*01, HLA-B*27, and low IgG1 levels are predisposing factors for RLM. Conclusions: Patients are vulnerable to recurrent HSV infections because of subtle immunological abnormalities. HSV causes diverse clinical manifestations. First, the herpes simplex virus, or the inflammatory process triggered by it, may cause pathological widespread pain probably by activating glial cells in the CNS. In these patients, signs of alterations in the brain pain-processing areas can be demonstrated by functional brain imaging methods. Secondly, HSV-2 induced RLM is a rare complication of HSV-2 virus. The predisposing factors include low IgG1 subclass levels, HLA-DRB1*01 and HLA –B*27 genotypes. Neuropathic pain is frequently associated with RLM.

Plasmid DNA mediated transfer of the herpes simplex virus thymidine kinase gene to a new bromodeoxyuridine resistant variant of human primary lung carcinoma cells

A human primary lung carcinoma cell line (HPL-R1) established from the tumor biopsy of a lung cancer patient, lacking in cytochrome P1-450 [aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH)], was cloned and used to obtain variants deficient in the expression of thymidine-kinase via treatment with 5-bromo-2'-deoxyuridine, and selection for drug resistance phenotype. The variant cell line, precharacterized for thymidine kinase negative phenotype, was transfected with the thymidine kinase gene bearing p R-tk and px1-tk plasmids. Transfections from both the plasmids, demonstrated a frequency of 5.5 X 10(-5). The transfectants showed a 76-100% retention of the transferred phenotype. These data suggest that transfection in variant human cells can approach significant levels of stability observed with rodent cell recipients.

Gene therapy for glioblastoma [correction of gliobestome] multiform: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

Clinical Trial