Association of herpes zoster ophthalmicus with acquired immunodeficiency syndrome and acute retinal necrosis

We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster.     

Chronic varicella-zoster virus skin lesions in patients with human immunodeficiency virus are related to decreased expression of gE and gB

The pathogenesis of chronic, verrucous varicella-zoster virus (VZV) cutaneous lesions in human immunodeficiency virus (HIV)-infected persons is unknown. It has been hypothesized that these lesions are due to an altered pattern of virus gene expression. Immediate early and late (L) gene expression in five chronic verrucous VZV lesions, four full-blown herpes zoster vesicular lesions in HIV-infected persons, and eight vesicular herpes zoster lesions in immunocompetent individuals was semiquantitatively assessed immunohistochemically using specific antibodies to the IE63, gE (L), and gB (L) proteins. All patients had evidence of IE63 expression in keratinocytes; however, gE expression was either weak or absent in keratinocytes of three verrucous lesions, and gB was either weak or absent in two. These results suggest that chronic VZV skin lesions are associated with diminished gE and gB expression. It is inferred that the VZV behavior in keratinocytes may vary from a latency-like state to a fully developed, productive infection.     

Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection

This article describes a prospective longitudinal study of varicella-zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected children, designed to determine their natural history of VZV infection and possible effects of VZV on the progression of HIV infection. Varicella was usually not a serious acute problem, and it did not seem to precede clinical deterioration. The rate of zoster was high: 70% in children with low levels of CD4+ lymphocytes at the time of development of varicella. It is predicted that immunization with live attenuated varicella vaccine is unlikely to be deleterious to HIV-infected children. Moreover, if they are immunized when they still have relatively normal levels of CD4+ lymphocytes, they may have a lower rate of reactivation of VZV than if they were allowed to develop natural varicella when their CD4+ cell counts have fallen to low levels as a result of progressive HIV infection.     

Polymerase chain reaction-based assays of vitreous samples for the diagnosis of viral retinitis. Use in diagnostic dilemmas

OBJECTIVE: This study aimed to review the authors' results using polymerase chain reaction (PCR)-based assays for the diagnosis of viral retinitis. DESIGN: The study design was a retrospective case series. PARTICIPANTS: Thirty-seven patients (38 eyes) with active retinitis from whom vitreous biopsy specimens were received in the authors' laboratory for diagnostic evaluation. INTERVENTION: Vitreous biopsy specimens were evaluated with previously described PCR-based assays for cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV) DNA; clinical histories were reviewed. MAIN OUTCOME MEASURES: Laboratory findings and clinical course were measured. RESULTS: The results of the authors' assays were consistent with the long-term clinical course of each patient. Cytomegalovirus, VZV, or HSV DNA was detected in the vitreous from 24 patients. Cytomegalovirus DNA was detected in vitreous biopsy specimens from 10 patients (11 eyes). Nine patients (ten eyes) with acquired immune deficiency syndrome ultimately were diagnosed with CMV retinitis as they were followed clinically over time. Varicella zoster virus DNA was detected in vitreous biopsy specimens from eight patients; seven adult patients were ultimately diagnosed with acute retinal necrosis or progressive outer retinal necrosis. Herpes simplex virus DNA was detected in vitreous biopsy specimens from six patients; five patients had previous or subsequent herpes encephalitis. No viral DNA was detected in the vitreous from 13 patients; all were ultimately diagnosed with toxoplasmosis, syphilis, Behcet disease, fungal endophthalmitis, or idiopathic inflammation. CONCLUSIONS: These data further support the use of PCR-based assays of vitreous specimens in the diagnostic evaluation of patients with infectious retinitis.     

Varicella-zoster virus is strongly associated with atypical necrotizing herpetic retinopathies

Aqueous humor samples from nine patients with atypical necrotizing retinopathies of suspected viral origin, six with acute retinal necrosis syndrome (ARN), and 17 with active cytomegalovirus (CMV) retinitis underwent amplification for viral DNA of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and human CMV. VZV DNA was detected in seven of the nine aqueous humor samples from patients with atypical necrotizing retinopathies of suspected viral origin and in four of the six samples from individuals with ARN; of the two other samples from patients with ARNS, no viral DNA was found in one, and both CMV DNA and HSV-1 DNA, but not VZV DNA, were detected in one (this patient presented with bilateral ARNS 2 months after being successfully treated for CMV retinitis). Thus, VZV is likely to be the main pathogen of atypical necrotizing herpetic retinopathies. DNA amplification may be used to establish an early, sensitive, and reliable diagnosis of any form of necrotizing retinopathy in 80% of cases, irrespective of viral etiology.     

Fibronectin and hyaluronic acid in seminal fluid: relationship with sperm count and percentage of typical forms

OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor.     

The prevalence of herpes family virus DNA in the conjunctiva of patients positive and negative for human immunodeficiency virus using the polymerase chain reaction

OBJECTIVE: To help understand the pathogenesis of herpes family virus ocular infection among patients positive for HIV, the authors compared the rates of detection of herpes family virus DNA from the conjunctiva of patients who are positive and negative for human immunodeficiency virus (HIV) using the polymerase chain reaction (PCR). DESIGN: Cross-sectional study. PARTICIPANTS: The conjunctival scrapings of 30 patients positive for HIV and 30 patients negative for HIV were examined. INTERVENTION: PCR was used to assay for the presence of herpes simplex virus type 1 (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA (n = 240 samples). MAIN OUTCOME MEASURE: The rate of detection of virus DNA in the two groups, controlling for age, gender, and race, was measured. RESULTS: HSV and VZV DNA were not detected in any of the HIV-positive or HIV-negative samples. CMV DNA was detected in 20% (6 of 30) of patients positive for HIV and was undetected in control subjects negative for HIV (P = 0.01). EBV DNA was detected in 40% (12 of 30) of patients positive for HIV and in 47% (14 of 30) of control subjects negative for HIV (P = 0.58). CONCLUSIONS: There was no difference in the frequency of detection of HSV, VZV, or EBV DNA from the conjunctiva of patients positive or negative for HIV. Only CMV DNA was detected at a significantly higher rate in the conjunctiva of patients positive for HIV compared with control subjects negative for HIV. These different rates of peripheral virus shedding may be one possible explanation for the different rates of clinical infection among the herpes family viruses among patients positive for HIV.     

Subcutaneous implantation metastasis of a cholangiocarcinoma of the bile duct after percutaneous transhepatic biliary drainage (PTBD)

The differential diagnosis of herpes simplex and zoster may require virological confirmation, yet virus typing is not regarded as necessary in routine dermatological assessment. In an attempt to evaluate the clinical benefits of the routine detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), we analysed skin swabs from 110 patients who were diagnosed at the first clinical visit as having herpes simplex (n = 45) or zoster (n = 65). Viruses were typed using the polymerase chain reaction (PCR) with the general primer pair GPHV-RU. PCR analysis showed that at the initial clinical presentation, herpes simplex in these patients was not mistaken for zoster but that zoster was incorrectly diagnosed as herpes simplex in nine cases. Thus these results suggest that initial zoster often mimics herpes simplex, hence routine PCR diagnosis of HSV and VZV or alternative rapid diagnostic approaches may be beneficial in these cases.     

Infrequent detection of cytomegalovirus and Epstein-Barr virus DNA in synovial membrane of patients with rheumatoid arthritis

OBJECTIVE: To study the role of the cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus types 1 and 2 (HSV-1 and 2), varicella zoster virus (VZV), and human herpes virus 6 (HHV-6) in the etiology of rheumatoid arthritis (RA). METHODS: Polymerase chain reaction (PCR) was used to detect DNA of the different herpes viruses in synovial membranes from 31 patients with chronic RA and 14 control patients. Specific antibodies were determined by indirect immunofluorescence and ELISA. RESULTS: Out of 31 patients with RA, CMV DNA was detected in synovial membranes from 2 patients and EBV DNA was detected in synovial membranes from 2 other patients. All samples from the patients with RA were negative for DNA from HSV-1 and 2, VZV, and HHV-6. All samples from the 14 control patients were negative in all PCR assays. No statistically significant differences in IgG antibodies were found for CMV, HSV-1, VZV, and HHV-6 in patients with RA compared to controls. Higher titers of IgG antibodies against EBV viral capsid antigen were found in patients with RA, with a significance of p < 0.05. CONCLUSION: Both CMV and EBV DNA were detected in synovial membranes from 6% of the patients with RA. We cannot exclude the possibility that these viruses were associated with disease development in a minority of patients with RA.     

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.     

Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with seizures

Four neonates with convulsions had IgG antibodies in their cerebrospinal fluid (CSF) to varicella zoster virus (VZV). These antibodies were found in the sera of two of these patients after the age of 6 months. Antibodies to 16 different microbes were studied from the serum and CSF of 201 neonates with neurological problems. The presence of DNA specific to HSV-1, HSV-2, and VZV in the CSF was also investigated using the polymerase chain reaction (PCR). Antibodies to VZV were detected in the CSF of four neonates. Antibody indices suggested production of VZV specific antibodies in the central nervous system. These findings suggest that intrathecal production of antibodies to VZV can appear in neonates with neurological problems, which suggests that intrauterine VZV infection can be acquired without cutaneous symptoms in the mother.     

Varicella zoster virus vaccine--a review

The available published data on the efficacy and safety of a live attenuated varicella vaccine is presented. The data indicate that immunosuppressed leukemic children at high risk for severe varicella can be vaccinated resulting in complete or partial immunity in most children. Vaccination of immunosuppressed children is often associated with fever and rash. There seems to be a decreased risk of herpes zoster in vaccinated leukemic children when compared with a group of naturally infected leukemic children. In order to diminish the risk of varicella zoster virus (VZV) transmission to these high-risk persons family members of these, if susceptible to varicella infection, should be immunized. Although vaccination of healthy children is highly effective and associated with a low frequency of adverse events, vaccination in this group may be questioned due to the benign course of varicella. Due to the more severe VZV-infection seen among non-immune healthy adults, it seems reasonable to offer vaccination to this group. It will, however, require extensive serological testing to identify seronegative individuals. From a theoretical point of view a booster-vaccination to the elderly population, resulting in detectable cell-mediated immunity to VZV, should reduce the risk of herpes zoster. Large placebo-controlled studies are needed to confirm if such an immunization can prevent herpes zoster in this age group.     

Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients

OBJECTIVE: To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients. DESIGN: CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings. METHODS: Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DNA. Histopathological examination of CNS tissue obtained at autopsy or on brain biopsy. RESULTS: DNA of one or more viruses was found in CSF in 181 out of 500 patients (36%; HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%, and JCV 9%). Among the 219 patients with histological CNS examination, HSV-1 or 2 was detected in CSF in all six patients (100%) with HSV infection of the CNS, CMV in 37 out of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36 (97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%) with progressive multifocal leukoencephalopathy. Furthermore, HSV-1 was found in one, VZV in four, CMV in three, EBV in three, HHV-6 in seven, and JCV in one patient without histological evidence of the corresponding CNS disease. CONCLUSIONS: CSF PCR has great relevance for diagnosis of virus-related opportunistic CNS diseases in HIV-infected patients as demonstrated by its high sensitivity, specificity, and the frequency of positive findings.     

Immunomodulatory activity of thunberginol A and related compounds isolated from Hydrangeae Dulcis Folium on splenocyte proliferation activated by mitogens

We have prospectively studied 27 adult patients attending the Department of Infectious Diseases, G?teborg, Sweden, between October 1992 and October 1996 with a diagnosis of acute viral encephalitis. In addition to cerebrospinal fluid (CSF) virus isolations and antibody analyses against herpes simplex virus, cytomegalovirus, varicella zoster virus, Epstein-Barr virus (EBV), enterovirus, adenovirus, tick-borne encephalitis virus, and mycoplasma, polymerase chain reaction test (PCR) to 5 viruses from the family of human herpes viridae, and to adenovirus as well as to enterovirus were analysed in CSF. 10 patients had herpes simplex virus type-1 (HSV-1), 1 had varicella zoster virus, 1 had tick-borne encephalitis, and 2 had Influenza A infections. In 13 patients the aetiology remained unclear. Eight patients with HSV-1 encephalitis and clinical symptoms for 2-11 d before admission were PCR-positive, while 2 patients with a < or = 2 d history of disease were negative for HSV-1 DNA on admission. These 2 patients became positive for HSV-1 DNA in CSF samples taken 4 d later in 1 case and 7 d later in the other. In 4 patients with HSV-1 encephalitis, in 1 patient with Influenza A complicated by encephalitis, and in 1 patient with encephalitis of unknown origin EBV DNA was found in CSF samples during the study. The clinical significance of these findings is unclear. The study shows that HSV-1 was the most common etiological agent in patients with viral encephalitis in the G?teborg area. In spite of improved diagnostic procedures, a large proportion of patients with symptoms and laboratory findings compatible with viral encephalitis still have an unclear aetiology.     

Cord blood leptin reflects fetal fat mass

This case report describes a 15-month-old female who developed diffuse cerebral vasospasm after resection of a cerebellopontine angle primitive neuroectodermal tumor. The patient developed an acute dense left hemiparesis 16 days postoperatively with partial right ptosis. Initial magnetic resonance imaging and diffusion study were unremarkable, though a magnetic resonance angiography 1 day later demonstrated severe intracranial vasospasm of both carotid and vertebral arteries. The vasospasm was confirmed with cerebral angiography. The patient progressed to bihemispheric infarcts with laminar necrosis despite combination therapy with anticoagulation, pharmacological hypertension, hypervolemia, and nimodipine. The clinical course, radiographic, and pathological findings are presented.     

Synthesis of adenine derivatives and their activities against herpes virus in vitro

A series of 9-(N4-substituted acetaldehyde thiosemicarbazone) adenines were synthesized and evaluated for antiherpes virus activity. Compounds 4a-l were prepared by condensation of 9-(acetaldehyde) adenine(6) and the corresponding N4-substituted thiosemicarbazides (10). The antiviral effects of all compounds 4a-l were tested in vitro in primary rabbit kidney cell cultures infected with herpes simplex virus type 1 (HSV-1) and varicella-herpes zoster virus (VZV), and in primary human embryo cell cultures infected with herpes simplex virus type 2 (HSV-2). The results showed that the minimum inhibitory concentrations (MIC) of 4e and 4f for HSV-1 and VZV were 20, 40, 20 and 20 micrograms.ml-1, respectively, and other compounds were 200 micrograms.ml-1. For HSV-2, the MIC of all tested compounds were 300 micrograms.ml-1. We also evaluated the antiherpetic effect of 4e (and 4f) by combination with acyclovir (ACV) in the ratio of 1:1 in vitro. The MIC of the combined compounds were 2 micrograms.ml-1 for 4e and 6 micrograms.ml-1 for 4f, while their minimum cytotoxicities (MCC) in the cell were markedly reduced compared with the individual compounds.     

三氧化二砷治疗血液病后合并带状疱疹的临床研究

目的 分析三氧化二砷(ATO)治疗血液病后合并带状疱疹感染患者的临床特征及其可能的发生机制.方法 将研究对象分为研究组(应用ATO)和对照组(未应用ATO),观察两组带状疱疹发病率,以及研究组中发生带状疱疹和未发生带状疱疹患者的平均化疗次数.结果 研究组带状疱疹发病率为23.95%(23/96),发生带状疱疹者平均化疗7.60次,未发生带状疱疹者平均化疗7.72次(Z=0.976,P=0.296);对照组带状疱疹发病率7.89%(3/38),两组间带状疱疹发病率差异有统计学意义(χ2=4.492,P=0.034).结论 ATO治疗血液疾病可以增加带状疱疹的发病率,可能与其激活水痘-带状疱疹病毒有关.     

The inverted repeat regions of the simian varicella virus and varicella-zoster virus genomes have a similar genetic organization

Simian varicella virus (SVV) causes a varicella-like disease in nonhuman primates. The DNA sequence and genetic organization of the inverted repeat region (RS) of the SVV genome was determined. The SVV RS is 7559 bp in size with 56% guanine+cytosine (G+C) content and includes 3 open reading frames (ORFs). The SVV RS1 ORF encodes a 1279 amino acid (aa) protein with 58 and 39% identity to the varicella-zoster virus (VZV) gene 62 and herpes simplex virus type 1 (HSV-1) ICP4 homologs, respectively. The predicted 261 aa SVV RS2 polypeptide possesses 52% identity with the VZV gene 63 homolog and 23% identity with the HSV-1 ICP22. The SVV RS3 encodes a 187 aa polypeptide with 56% and 28% identity to the VZV gene 64 and the HSV-1 US10 homologs, respectively, and includes an atypical zinc finger motif. A G+C-rich 16 base-pair (bp) sequence which is repeated 7 times and a putative SVV origin of replication were identified between the RS1 and RS2 ORFs. Comparison with the VZV RS indicates the SVV and VZV RS regions are similar in size and genetic organization.     

Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.     

Herpes simplex virus type 2 induced retinal necrosis in BALB/c mice

We injected herpes simplex virus type 2 of MS- or G-strain into the anterior chamber of BALB/c mice. In the contralateral eye inflammatory cell infiltration began in the ciliary body; focal retinitis, detected by day 8, led to total destruction of the retina by day 10. Contralateral disease was observed in 75% of mice inoculated with 8 x 10(3) pfu herpes simplex virus type 2, but in only 20% of mice receiving 80 pfu herpes simplex virus type 2. Still this low concentration, however, produced a suppressed delayed-type hypersensitivity response. Anti-herpes simplex virus type 2 antibody, first detected on day 8, reached high titers on day 10; by then, most of the mice had died of encephalitis. The G-strain of herpes simplex virus type 2 was more neurotoxic than the MS-strain, but produced the same incidence of contralateral retinitis. Herpes simplex virus type 2 products contralateral necrotizing retinitis comparable to that produced by herpes simplex virus type 1. These findings, like those of other authors, suggest a role for herpes simplex virus type 2 in some cases of acute retinal necrosis in humans.