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Dear Editor, Pityriasis rosea is a common, acute, and self-limiting dermatosis, which is associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7 (1). It predominantly affects individuals of both sexes in their second or third decade of life and is clinically characterized by the occurrence of an initial erythematosquamous plaque followed by the appearance of disseminated similar but smaller lesions one or two weeks later. Several patients develop systemic symptoms such as nausea, anorexia, malaise, headache, fever, arthralgia, and lymphadenopathy that may precede or accompany the eruption; the latter follows the cleavage lines of the trunk creating the configuration of a Christmas tree and spontaneously resolves within 4 to 8 weeks. Mainly based on the nature of the underlying viral reactivation, pityriasis rosea is classified into five different forms (2): 1) Classic and 2) Relapsing (characterized by sporadic and relapsing HHV-6/7 systemic reactivation, respectively), 3) Persistent (persistence of HHV-6/7 viremia), 4) Pediatric (longer activity of HHV-6/7 infection; recent primary infection) and 5) Gestational (HHV-6/7 reactivation and possible intrauterine transmission). Clearly, the inevitable impairment of immune response in pregnancy favors viral reactivation and possibly also the intrauterine transmission of HHV-6/7. Indeed, it is well known and documented that pityriasis rosea more frequently occurs in pregnant women (18%) as compared to the general population (6%) (3). However, the literature concerning the possible effect of pityriasis rosea on the outcome of pregnancy is surprisingly sparse. Only an Italian group, Drago et al (4,5), has systematically investigated the impact of this disorder on pregnant women. They found that 22 out of 61 women (36%) who developed pityriasis rosea during pregnancy had unfavorable outcomes, whereas 8 others miscarried (13%). None of the latter had any risk factors, other than pityriasis rosea, for intrauterine fetal death. All miscarrying women reportedly revealed an aggressive course of widespread eruption and severe constitutional symptoms; all of them had HHV-6 DNA in the plasma, placenta, skin lesions, and fetal tissues, whereas HHV-7 DNA was detected in the plasma and skin lesions in 3 out of 8 (37.5%) miscarrying women. HHV-6 DNA was found only in the plasma of 2 out of 31 women (6.45%) with normal pregnancy, whereas HHV-7 DNA was detected in the plasma of 3 (9.45%) and in the skin lesions of 2 women (6.45%) with normal pregnancy. The total abortion rate in women who developed pityriasis rosea during their pregnancy (13%) does not differ from that observed in the general population. Nevertheless, it is markedly higher in cases affected during the first 15 gestational weeks (57%) (4,5). Surprisingly, this devastating impact of pityriasis rosea on the outcome of pregnancy is almost completely unknown not only to the public but also to many members of the medical community. It is also largely unknown that, particularly during the first 15 gestational weeks, all pregnant women should avoid any contact with patients known to have pityriasis rosea. Since we have received a considerable number of requests for consultation with pregnant women with pityriasis rosea over the last few years, our group has compiled suggestions approaching the affected patients: 1. If an eruption suggestive for pityriasis rosea occurs in a pregnant woman, the following factors should be excluded: a. Exposure to drugs prior to the development of the rash (biologic agents, captopril, clonidine, hydrochlorothiazide, atenolol, lamotrigine, nortriptyline, barbiturates, metronidazole, terbinafine, omeprazole, non-steroidal anti-inflammatory drugs, and isotretinoin), which are capable of inducing a pityriasis rosea-like eruption (6) and b. Disorders included in the differential diagnosis (syphilis and infections due to parvovirus, herpes virus, cytomegalovirus, and Epstein-Barr virus). 2. The clinical diagnosis of pityriasis rosea should be made according to the morphological criteria (peripheral collarette scaling with central clearance on at least two lesions) put forth by Chuh (7). 3. Since specific anti-HHV-6 and -7 IgM antibodies are detected only in a low percentage of infected pregnant women (8), HHV-6 and -7 DNA should be assessed in plasma by nested PCR. Especially during the first 15 gestational weeks, pregnant women with positive PCR results deserve, apart from close monitoring, appropriate information about the existing risks in order to be able to make informed decisions. 4. Reliable and definite data from adequate and controlled human studies on the safety of acyclovir or valacyclovir in pregnant women and their efficacy in pityriasis rosea are lacking. Thus, the decision on whether these antiviral compounds will be administered should be tailored to each individual pregnant woman, subsequent to a meticulous assessment of the potential risks and their balancing against the potential benefits.
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PMID:Gestational Pityriasis Rosea: Suggestions for Approaching Affected Pregnant Women. 2812 88

Herpes simplex virus (HSV) is the most common cause of non-epidemic, sporadic, acute focal encephalitis in the United States. Inflammation of the vasculature makes them friable and susceptible to hemorrhage. Massive hemorrhage, though rare, can present in a delayed fashion after initiation of acyclovir and often requires surgical intervention. We report a unique case of delayed temporal lobe hemorrhage after initiation of acyclovir in an immunocompetent patient, specifically for its presentation, virology, and surgical management. A 40-year-old left-handed Caucasian female with chronic headaches, along with a 20-pack-year smoking history, presented to an outside facility with one week of diffuse, generalized headache, fever, nausea, and vomiting. Initial cranial imaging was negative for hemorrhage. Cerebrospinal fluid (CSF) studies showed a lymphocytic pleocytosis with elevated protein, along with polymerase chain reaction (PCR) positive staining for HSV, establishing the diagnosis of HSV-2 encephalitis, which is less common in adults. Acyclovir was initiated and one week later while still hospitalized, the patient developed acute altered mental status with cranial imaging showing a large right temporal lobe hemorrhage with significant midline shift. She was transferred to our facility for surgical intervention. Computed tomography angiography (CTA) was negative for any underlying vascular lesion. She was taken to the operating room for a decompressive unilateral (right) hemicraniectomy and temporal lobectomy. She had no postoperative complications and completed a three-week course of acyclovir. She was discharged to acute rehab with plans to return at a later date for cranioplasty. Intracerebral hemorrhage is an uncommon, although possible sequela, of herpes encephalitis. Despite initiation of early antiviral therapy, close monitoring is warranted, given the pathophysiology of the vasculature. Any decline in the neurological exam and/or increasing symptomatology of increased intracranial pressure mandates immediate cranial imaging to evaluate for possible hemorrhage. Emergent surgical intervention is warranted with large temporal lobe hemorrhages.
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PMID:Delayed Temporal Lobe Hemorrhage After Initiation of Acyclovir in an Immunocompetent Patient with Herpes Simplex Virus-2 Encephalitis: A Case Report. 2819 84

Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.
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PMID:Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia. 2845 63

Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. Methods RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia. The samples were also characterized for transcripts derived from viral and microbial genomes. Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the luciferase immunoprecipitation assay. Results Observed molecular heterogeneity could be explained by sampling of anatomically distinct sub-regions of the excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann cell, enriched subregions. The levels of HSV-1 transcripts detected in trigeminal ganglia correlated with blood levels of HSV-1 antibodies. Multiple migraine susceptibility genes were strongly expressed in neurally-enriched trigeminal samples, while others were expressed in blood vessels. Conclusions These data provide a comprehensive human trigeminal transcriptome and a framework for evaluation of inhomogeneous post-mortem tissues through extensive quality control and refined downstream analyses for RNA-Seq methodologies. Expression profiling of migraine susceptibility genes identified by genetic association appears to emphasize the blood vessel component of the trigeminovascular system. Other genes displayed enriched expression in the trigeminal compared to dorsal root ganglion, and in-depth transcriptomic analysis of the KCNK18 gene underlying familial migraine shows selective neural expression within two specific populations of ganglionic neurons. These data suggest that expression profiling of migraine-associated genes can extend and amplify the underlying neurobiological insights obtained from genetic association studies.
Cephalalgia 2018 04
PMID:RNA-Seq investigations of human post-mortem trigeminal ganglia. 2869 3

We report the case of a 9-year-old girl admitted with fever, headache, and a cerebrospinal fluid lymphocytic pleocytosis. Polymerase chain reaction was positive for human herpes virus 6. She subsequently developed ataxia and bilateral loss of vision. Magnetic resonance imaging (MRI) showed bilateral optic nerve lesions with extension to optic chiasm and a short-segment myelitis. Serologic studies were positive for Borrelia burgdorferi IgM. Anti-aquaporin 4 antibody was negative and anti-myelin oligodendrocyte glycoprotein antibody (MOG) positive. After intravenous methylprednisolone, ceftriaxone, and intravenous immunoglobulin, her vision slowly recovered. The patient was discharged with only mild visual acuity loss, 1 month after admission. Brain MRI was repeated later and was normal and MOG assay became negative. In our view, this patient suffered from a postinfectious, anti-MOG-mediated, spinal cord and optic nerve demyelination.
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PMID:Postinfectious Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis and Myelitis. 2882 14

A great variety of viruses which cause exanthema share other clinical manifestations, making the etiologic identification a very difficult task, relying exclusively on the clinical examination. Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). In the present report, we described the presence of Zika virus (ZIKV) particles in urine samples and also ZIKV isolation in SIRC cells from the urine of a patient in acute phase of suspected rubella disease. The 50-year-old unvaccinated woman living in Sao Paulo, Brazil, was admitted to the emergency room with fever, headache, rash, arthralgia and prostration. Urine samples were collected for virus isolation and RT-qPCR. SIRC and Vero cells were inoculated with urine samples during 7 days. RT-qPCR was performed using measles virus (MV) and RV primers and both were found to be negative. After this result, RT-qPCR was performed for parvovirus B19, herpes virus 6 and ZIKV. The urine sample and the isolate were positive by Real Time PCR for ZIKV and negative for all other viruses tested. The sequences isolated are from the Asiatic lineage.
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PMID:Isolation of infectious Zika virus from a urine sample cultured in SIRC cells from a patient suspected of having rubella virus. 2955 85

We report the case of an MS patient with aseptic temporal lobe encephalitis while on treatment with fingolimod. This 49-year-old woman developed headache and decreasing level of consciousness after 3.5 years of fingolimod therapy. Imaging, CSF studies, and rapid clinical response to acyclovir suggested a viral etiology, although CSF cultures and viral PCR were negative. This case illustrates the potential for severe manifestations of infectious illnesses on fingolimod, which may have a predilection for the CNS and also include herpes virus infections, cryptococcus, and PML. Efforts to prevent these secondary infections are limited by a lack of established risk factors.
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PMID:Severe aseptic temporal lobe encephalitis on fingolimod. 2968 73

A man, 26years-old, presented fever, mental confusion and a progressively worsening headache 6days prior to admission. The CSF study was suggestive of meningoencephalitis, the PCR study revealed presence of HSV-1 and ZIKV, while other immunology tests were negative. ZIKV was also identified in serum. The MRI showed temporal lobe hyper-intensity in FLAIR-weight sequence with areas of contrast enhancement and the electroencephalogram showed slow wave activity in such region. Patient was treated with acyclovir and supportive measures and had good clinical outcome at evaluation after 6 months. Neurological spectrum of ZIKV manifestations is wide, but meningoencephalitis is not frequent. Co-infection HSV-1 plus ZIKV was not yet related in humans, but there is increased cellular damage caused by association of ZIKV and herpes virus family infection. ZIKV may facilitate infection or recrudescence by other viruses or cause concurrently neuronal injury by direct or indirect mechanisms. We suggest that clinicians attempt new manifestations related to ZIKV and include this agent in differential diagnosis of neurological diseases even when other agents were identified.
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PMID:Co-infection ZIKV and HSV-1 associated with meningoencephalitis: Case report and literature review. 2970 10

Primary amoebic meningoencephalitis (PAM) is a rare, fulminating, hemorrhagic infection of the brain caused by Naegleria fowleri, a thermophilic, free-living amoeba. A 74-year male presented with sudden severe global headache and fever with features of anomic aphasia. Magnetic resonance imaging (MRI) suggested herpes encephalitis and acyclovir (IV) was started but the patient developed altered sensorium, agitation and progressive weakness of lower limbs with gradual truncal weakness. Repeat MRI showed increase in lesion size and edema with confluent blood areas. Dexamethasone showed significant improvement. Ten days after completion of acyclovir, there was recurrence of altered sensorium with seizures. Repeat MRI showed new lesions appearing. Excisional biopsy of brain confirmed N. fowleri. Amphotericin B and miltefosin was started but patient succumbed to his illness after 10 days. This is a first case of PAM in Nepal, involving elderly immune-competent male without environmental exposure to freshwater, mimicking as herpes encephalitis.
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PMID:Fatal case of amoebic encephalitis masquerading as herpes. 2974 28

Acyclovir has been used in the treatment of herpes simplex and varicella zoster viral infections for over 30 years. The side effects of oral treatment at standard doses are rare and include headache, diarrhoea, dizziness and malaise. We report a patient with a new diagnosis of systemic lupus erythematosus (SLE) who developed thrombocytopaenia within days on a therapeutic dose with acyclovir. Prompt discontinuation of acyclovir and treatment with intravenous immunoglobulin resulted in reversal of the above potentially serious complication. Therefore a high index of suspicion should be exercised in patients with SLE who require treatment with acyclovir for herpes viral infections. In these patients regular platelet count measurement should be considered while on treatment with the above antiviral agent.
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PMID:Acyclovir-induced thrombocytopaenia in a patient with SLE. 2988 20


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