[Hypogeusia and High Signals in the Nuclei of the Solitary Tract on MRI due to Varicella-Zoster Virus Infection: A Case Report].

A 63-year-old man noticed hypogeusia after presenting hiccups for several days. He was serologically diagnosed with varicella-zoster virus (VZV) infection, but had no skin lesions typical of herpes (zoster sine herpete). Hypogeusia was confirmed by electrogustometry and the filter-paper disk method, which showed damage in the areas innervated by the cord of tympanum, glossopharyngeal nerve, and greater petrosal nerve. High signals in the nuclei of the solitary tract of the medulla oblongata and the enhancement of the bilateral intracranial segments of the cranial nerve IX and X complex were observed by magnetic resonance imaging (MRI). The signal changes in the nuclei of the solitary tract on MRI were seen for more than 2 months, and hypogeusia lasted for more than 7 months. Hypogeusia caused by VZV infection has rarely been reported; however, similar cases could have gone undiagnosed or underdiagnosed in patients with idiopathic hypogeusia. (Received August 18, 2016; Accepted September 29, 2016; Published February 1, 2017).

The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II.

This review on herpes simplex virus type I and type II (HSV­I, HSV­II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV­I infection; HSV-related folliculitis; verrucous HSV­I and HSV­II lesions; the role of recurrent HSV­I infection in burning mouth syndrome; HSV­I and HSV­II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV­I or HSV­II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV­I and anti-HSV­II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV­I and HSV­II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

Varicella-zoster meningoencephaloradiculoneuropathy in an immunocompetent young woman.

The clinical manifestations of varicella-zoster virus infections can be divided into primary infection with chickenpox and reactivated infection with dermatomal shingles, disseminated herpes zoster, zoster sine herpete and varicella-zoster virus encephalitis, meningitis and vasculopathy. We present a case of zoster sine herpete leading to meningitis with cranial and peripheral nerve palsies. A 17-year-old woman was admitted to hospital with intermittent fever, drowsiness, slowness and subsequent frontal headache and horizontal diplopia. Cerebrospinal fluid examination revealed lymphocytic pleocytosis and PCR amplified varicella-zoster virus DNA. Laboratory and clinical findings were suggestive of meningoencephaloradiculoneuropathy, stemming from varicella-zoster virus and affecting cranial and peripheral nerves. Only 5% of patients with zoster develop cranial and peripheral nerve palsies. Diagnosis is imperative in order to initiate prompt antiviral therapy so as to minimize morbidity and the risk of death.

Neurological disease produced by varicella zoster virus reactivation without rash.

Reactivation of varicella zoster virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitis, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy, myelopathy, and various inflammatory disorders of the eye. Importantly, VZV reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions varies from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum.

Association of varicella zoster virus load in the aqueous humor with clinical manifestations of anterior uveitis in herpes zoster ophthalmicus and zoster sine herpete.

AIM: To investigative whether clinical manifestations of anterior uveitis are associated with the viral load of varicella zoster virus (VZV) in the aqueous humor in patients with herpes zoster ophthalmicus (HZO) and zoster sine herpete (ZSH). METHODS: After informed consent was given, an aliquot of aqueous humor was collected from patients with VZV anterior uveitis (n = 8). Genomic DNA of the human herpes viruses was measured in the aqueous humor by two PCR assays: a qualitative multiplex PCR and a quantitative real-time PCR. RESULTS: All patients had unilateral acute anterior uveitis with high intraocular pressure, mutton fat keratic precipitates with some pigmentation, and trabecular meshwork pigmentation. Multiplex PCR demonstrated VZV genomic DNA in all of the samples, but not in other human herpes virus samples (human simplex virus types 1 and 2, Epstein-Barr virus, cytomegalovirus and human herpes virus types 6, 7 and 8). Real-time PCR revealed a high copy number of VZV DNA in the aqueous humor. After the initial onset of anterior uveitis, iris atrophy and distorted pupil with paralytic mydriasis developed. The intensity of iris atrophy and pupil distortion, but not ocular hypertension, correlated with the viral load of VZV in the aqueous humor. CONCLUSION: VZV viral load in the aqueous humor correlated significantly with damage to the iris (iris atrophy and pupil distortion) in patients with HZO and ZSH.

[Case of zoster sine herpete presenting with dysphagia diagnosed by PCR analysis of VZV DNA in auricular skin exudates].

A 66-year-old woman was admitted to our hospital because of hoarseness and dysphagia after right earache and pharyngalgia. She showed right glossopharyngeal nerve and vagus nerve palsies, but no other neurological deficits. There was no skin rash within the regions of her ear, oral cavity, pharynx and larynx. Slight increase of mononuclear cells was noted in the cerebrospinal fluid. MR brain imaging was normal. We diagnosed her as zoster sine herpete (ZSH) and treated her with acyclovir, after which she almost completely recovered. The examination of antibodies and DNA of varicella zoster virus (VZV) in the serum and cerebrospinal fluid revealed a pattern of previous zoster infection without evidences of reactivation. However, VZV DNA was detected in auricular skin exudates with PCR. We conclude that PCR analysis of VZV DNA in auricular skin exudates can be a useful diagnostic tool for the diagnosis of zoster sine herpete presenting with painful glossopharyngeal nerve and vagus nerve palsies.

Immune deviation and ocular infections with varicella zoster virus.

Since experimental, herpes simplex virus-induced acute retinal necrosis (ARN) develops in mice only if the mice fail to acquire virus-specific delayed hypersensitivity (DH) and despite their production of anti-viral antibodies (i.e. ACAID), I investigated whether a similar situation exists for patients with either varicella zoster virus (VZV)-induced ARN or anterior uveitis caused by VZV. Patients with either acute VZV-induced ARN, anterior uveitis with dermatitis (herpes zoster ophthalmicus, ZO-AU), or anterior uveitis without dermatitis (zoster sine herpete, ZSH-AU) were skin-tested with VZV to evaluate DH. The formal diagnoses of ARN associated with VZV, ZO-AU, and ZSH-AU were established by PCR analysis of the ocular samples and/or by the Goldmann-Witmer coefficient to determine levels of local antibody production. ARN, ZO-AU, and ZSH-AU activity were assessed clinically, and DH skin tests were repeated three months after onset when ocular recovery had taken place. All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV antigen. In contrast, subsets of patients with ARN or ZO-AU displayed loss of VZV-specific DH. Patients with the most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in ARN patients than in normal controls, and the anti-viral titer correlated inversely with the intensity of anti-VZV DH responses. VZV-specific DH responses were restored in patients who recovered from ARN. Patients with ZSH-AU also failed to display VZV-specific DH. The absence of DH reactivity to VZV antigens (i.e. immune deviation) appears to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced ARN or anterior uveitis.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Varicella virus-mononuclear cell interaction.

Varicella zoster virus (VZV) causes varicella (chickenpox), becomes latent in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster (shingles). The main complication of zoster is postherpetic neuralgia (PHN), pain that persists for months and often years after zoster. VZV also causes chronic radicular pain without rash (zoster sine herpete). Viremia is associated with each stage of VZV infection. Viral DNA has been found in peripheral blood mononuclear cells (MNCs) of patients with varicella, zoster, PHN, and zoster sine herpete. In varicella, viremia contributes to the widespread distribution of skin lesions and infection of multiple organs. Although the role of viremia in other VZV-associated diseases is not as clear, the detection of VZV DNA (and sometimes VZV RNA and proteins) helps diagnose neurological diseases produced by VZV, has indicated that PHN may reflect a chronic VZV ganglionitis, and has established that VZV reactivates subclinically, especially in immunocompromised humans. In vitro studies have established that VZV can productively infect MNCs for a short time and have identified the subpopulations of MNCs that are infected. Finally, simian varicella virus (SVV) infection of nonhuman primates shares clinical, pathological, and virologic features with VZV in humans. Like VZV, SV viremia in nonhuman primates during acute infection plays an important role in the pathogenesis of SVV. Infectious virus can be isolated from MNCs, and SVV DNA can be detected in MNCs during varicella. Further, SVV DNA can be detected for months in MNCs of monkeys after experimental infection with SVV. Herein, we review the current literature related to VZV infection of MNCs during naturally occurring varicella, PHN, and zoster sine herpete in humans, including studies of experimental infection of human MNCs with VZV. We also review SVV MNC interaction during naturally occurring simian varicella and after experimental infection of primates with SVV.

Corneal epithelial keratitis in herpes zoster ophthalmicus: "delayed" and "sine herpete". A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To investigate the origin of corneal epithelial keratitis occurring without accompanying herpes zoster ophthalmicus (HZO) cutaneous rash. METHODS: Corneal epithelial lesions in seven patients (four with a history of classical HZO with cutaneous rash, one of herpes zoster oticus, and two with no history of herpes zoster, were examined with the slit lamp and photographed by non-contact in vivo photomicrography. The findings were compared with lesions in classical acute HZO. Polymerase chain reaction (PCR) was done in three patients. RESULTS: Slit lamp appearance, morphology at higher magnification, and kinetics of the lesions were indistinguishable from classical acute HZO. PCR was positive for varicella-zoster virus DNA in all three samples. CONCLUSIONS: The findings strongly suggest that HZO typical corneal epithelial lesions occurring in the absence of cutaneous rash are in fact recurrent episodes of virus shedding.