Course Of Acyclovir Research Articles

Anti-N-methyl-D-aspartate Receptor Encephalitis after Herpes Simplex Virus Encephalitis

Abstract Encephalitis due to herpes simplex virus 1 (HSV1) has been described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAR) autoimmune encephalitis within few days to months. Here, we report one such case of anti-NMDAR encephalitis which was triggered by preceding HSV encephalitis. The patient had a history of headache and fever of 1–2-week duration, and cerebrospinal fluid and magnetic resonance imaging picture suggestive of HSV encephalitis. After 2 weeks of completion of 14-day course of acyclovir, he had symptoms of altered behavior, headache, and vomiting. The possibility of anti-N-methyl-D-aspartate (NMDA) encephalitis occurring after HSV encephalitis was considered. Serum for anti-NMDA antibody came positive, and he improved with treatment. A high index of suspicion and awareness of such a possibility can help in making the diagnosis and initiate early therapy.

HSV-1 and HHV-6 Meningoencephalitis in a Child with STAT1 Mutation

Introduction: STAT1 is a critical signal transducer for both the interferon gamma receptor and IFN-alpha/beta receptors and is required for responses to herpesviruses. STAT1 defects vary in severity and clinical presentation. STAT1 loss of function (LOF) mutations with Mendelian Susceptibility to Mycobacterial Disease (MSMD) and STAT1 gain of function (GOF) mutations have been described with a wide clinical spectrum, including nontuberculous mycobacteria, disseminated fungal, bacterial, and viral infections in addition to immune dysregulation. We present a 10-year-old female with HSV-1 and HHV-6 meningoencephalitis that was found to have a variant in STAT1. MethodsRetrospective chart review was conducted. Laboratory investigations included lymphocyte immunophenotyping by flow cytometry, lymphocyte proliferation to mitogens and antigens, NK cell functional assays, quantitative immunoglobulins, toll like receptor function defects, genetic evaluation by next generation sequencing, and assays for further evaluation for MSMD, T helper IL17, STAT GOF. ResultsA previously healthy 10-year-old Caucasian female presented with fever, headache, and new-onset seizure with status epilepticus. She was diagnosed with HSV-1 and HHV-6 meningoencephalitis, as CSF PCR panel was positive for HSV-1 and HHV-6. Brain MRI showed findings compatible with HSV-1 encephalitis. She was treated with a 14-day course of acyclovir with no noted neurological sequelae. Infection history was unremarkable except for one episode of otitis media as a child and a couple upper respiratory viral illnesses. Denied prior history of HSV infection. No family history of immunodeficiency disorders. Both parents reported remote history of herpetic gingivostomatitis. Laboratory immune evaluation was remarkable for decreased lymphocyte proliferative response to Candida antigen. Next generation sequencing revealed a variant of uncertain significance in STAT1 (c.295A>G; p.Ile99Val) and did not detect TLR3 or UNC93B1 mutations. ConclusionThe clinical phenotype caused by STAT1 mutations is highly diverse, and there is overlap between GOF and LOF phenotypes, making it difficult to clinically diagnose. Although HSV gingivostomatitis has been reported in a patient with STAT1 GOF, invasive disease, such as meningoencephalitis, has not been reported in those with variants in STAT1.

S2972 Disseminated Herpes Simplex Virus: A Diagnostic Enigma

Introduction: Disseminated Herpes Simplex Virus (HSV) is rare but is associated with up to 50% mortality, especially in immunocompromised patients and pregnant women in whom the diagnosis is often missed. In pregnant women, it can cause fulminant liver failure and can lead to fetal demise in some cases. We describe a case of disseminated HSV in a pregnant woman with no known active disease prior to pregnancy. Case Description/Methods: A 28-year-old healthy female presented at 26 weeks gestation with fever, chills and back pain. Initial labs were concerning for pyelonephritis and antibiotics were initiated. Despite broad spectrum antibiotics, she had persistent fever and workup for infectious etiology was broadened to include HIV, CMV, EBV, toxoplasma, syphilis, which were all negative. She developed worsening transaminases with AST 384 U/L and ALT 220 U/L. Viral hepatitis serologies and, due to her recent travel to Lyme endemic area, arbovirus serology was tested, which were all negative. She subsequently developed thrombocytopenia and worsening hypertension raising concern for HELLP syndrome and underwent emergent cesarean section. Postpartum course was complicated by persistent fevers and concern for chorioamnionitis; however, she continued to have worsening transaminases (AST 2632, ALT 1000). Computed tomography abdomen found numerous liver lesions concerning for abscesses or metastases. Liver biopsy found microvesicular steatosis consistent with HELLP syndrome. She developed worsening thrombocytopenia, coagulopathy (INR 2) and rising LDH, which was concerning for disseminated intravascular coagulation. She was started on plasma exchange and N-acetylcysteine. HSV PCR serology was tested which returned positive for HSV-2 and she was started on acyclovir. Lumbar puncture returned positive for HSV confirming disseminated HSV. Her course was complicated by encephalopathy that eventually improved and she was able to be discharged on a 21-day course of acyclovir. Transaminases and coagulopathy improved with treatment of disseminated HSV. Discussion: Disseminated HSV has a high mortality in pregnancy but can be missed due to the rarity of the condition. Early diagnosis and administration of acyclovir decreases mortality. A high index of suspicion is necessary, and it should remain in the differential diagnosis in pregnant and postpartum patients with acute hepatitis and even considered in patients with elevated transaminases without any overt history or skin lesions concerning for HSV as in this patient.

Delayed HSV-1 Encephalitis Relapse After Epilepsy Surgery: A Case Report

BACKGROUND AND IMPORTANCE: Herpes simplex virus 1 encephalitis (HSVE) can be a rare postoperative complication after neurosurgery. We present the case of a patient with postoperative, twice recurrent HSVE after 20 years, the longest latency period reported after neurosurgery. CLINICAL PRESENTATION: A 21-year-old man with a history of HSVE at 13 months and intractable epilepsy presented for surgical resection of seizure focus. The patient underwent left temporal craniotomy and resection of left temporal encephalomalacia. Five days after discharge, the patient presented with fever and headache and was found to have herpes simplex virus 1 (HSV-1)–positive cerebral spinal fluid. The infection was treated with acyclovir, with subsequent symptomatic improvement. Six weeks later the patient represented with recurrent symptoms and HSV-1–positive cerebral spinal fluid. This recurrence was treated with a prolonged course of acyclovir, followed by suppressive valacyclovir therapy, resulting in symptomatic improvement. CONCLUSION: HSV-1 encephalitis is a rare but previously reported complication after neurosurgery procedures. In patients with relapse of HSVE, the latency period can range from weeks to years after primary infection, and multiple relapses are rare. We present the case of a patient with twice recurrent, postoperative HSV-1 encephalitis 20 years after initial infection. We aim to emphasize that HSV status should be considered during treatment planning in patients with a history of HSVE being treated for HSV-related illnesses, and HSVE should remain on the differential in these patients when presenting with fever and neurological symptoms after surgery, regardless of time since initial infection.

HSV PNEUMONIA IN AN IMMUNOCOMPETENT PATIENT PROGRESSING TO ORGANIZING PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: HSV pneumonia has been rarely reported in immunocompetent patients. We report a case of a 75-year-old healthy female with intractable pneumonia diagnosed as HSV that progressed to organizing pneumonia CASE PRESENTATION: A 75-year-old female with a past medical history of Barrett's esophagus presented to the ER with a 3-week history of fatigue, fevers, and shortness of breath. She had no family history of autoimmune disorders, she moved from Iran 40 years ago and had no known exposure to TB. She denied smoking and had no pets or any other exposures. Labs showed leukocytosis of 14000 with neutrophilic and monocytic predominance, mild hyponatremia (132 meq/L), and a procalcitonin of 0.25 ng/ml. Chest X-ray revealed infiltrates in the right upper and lower lobes. She was started on ceftriaxone and azithromycin but continued to worsen. Antibiotics were broadened again without clinical response. Urine streptococcus, legionella antigen, B-D-glucan, Tuberculin skin test, HIV, histoplasma were all negative. Bronchoscopy was done on day 10 that revealed copious clear, yellow clear fluid in her proximal and distal airway and with similarly appearing fluid with mucus plugs on the BAL. Cultures from BAL including modified AFB for nocardia were unrevealing. Rheumatological workup including, ANA, ANCA, anti-CCP, Sjogren's antibody, myositis panel, HSP was also negative. Subsequent CT scan revealed worsening infiltrates and a right-sided pleural effusion, patient underwent thoracentesis, and cultures on pleural fluid were positive for HSV. The patient underwent a VATS biopsy (Day 22) that revealed organizing pneumonia with thickened alveoli and fibrinous plugs. HSV 1 IgG antibodies were also positive. She was started on steroids and acyclovir with significant improvement. DISCUSSION: HSV is known to infect the upper airway and can cause gingivostomatitis and pharyngitis. It can progress to pneumonitis or pneumonia in patients who are immunocompromised or mechanically ventilated. Only in rare cases does it manifest as clinically significant lower respiratory tract infections in immunocompetent individuals. Our patient had a biphasic illness, she was diagnosed based on the HSV culture on the pleural fluid, which has a specificity of 99%. Her second episode of respiratory failure with worsening infiltrates represented the development of organizing pneumonia that responded to steroids. The use of acyclovir in such patients is not supported by clinical trials and needs to be studied. Our patient finished a course of acyclovir and was treated with steroids for several weeks. CONCLUSIONS: HSV pneumonia should be considered as an etiology of intractable pneumonia when patients do not show clinical improvement on conventional therapy. This case also suggests that acute herpes infection can have serious complications like organizing pneumonia and further studies are needed to understand this association. REFERENCE #1: Mills B, Ratra A, El-Bakush A, Kambali S, Nugent K. Herpes Simplex Pneumonia in an Immunocompetent Patient With Progression to Organizing Pneumonia. J Investig Med High Impact Case Rep. 2014 Apr 9;2(2):2324709614530560. doi: 10.1177/2324709614530560. PMID: 26425602; PMCID: PMC4528890. REFERENCE #2: Martinez E, de Diego A, Paradis A, Perpiñá M, Hernandez M. Herpes simplex pneumonia in a young immunocompetent man. Eur Respir J. 1994 Jun;7(6):1185-8. PMID: 7925891. DISCLOSURES: No relevant relationships by Chahat Puri, source=Web Response No relevant relationships by Kyunghoon Rhee, source=Web Response No relevant relationships by Donald Slack, source=Web Response No relevant relationships by Jennifer Sullivan, source=Web Response No relevant relationships by Ari Zaiman, source=Web Response

Acute Kidney Injury During Treatment with Intravenous Acyclovir for Suspected or Confirmed Neonatal Herpes Simplex Virus Infection

To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. We conducted a multicenter (n=4), retrospective cohort study of all hospitalized infants age <60days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P=.002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P=.004), receipt of mechanical ventilation (OR, 5.97; P=.001), and admission to an intensive care unit (OR, 6.02; P=.006) as risk factors for AKI during acyclovir treatment. Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

3165 The Great Masquerade

INTRODUCTION: Syphilis is a sexually transmitted infection caused by T. pallidum. It is often described as “the great imitator,” affecting multiple organ systems, and has a wide variation in its clinical presentation. Syphilitic hepatitis is a rare and occurs in 0.2-3% of cases of secondary syphilis. We present a case of mixed hepatocellular and cholestatic hepatitis that led to the diagnosis of syphilis in a patient who presented with non-specific symptoms. CASE DESCRIPTION/METHODS: A 39-year-old homosexual male was referred for evaluation of worsening jaundice following a course of acyclovir for genital herpes 3 months prior. He reported non-specific symptoms including acute diarrhea, abdominal pain, myalgia, rash and weight loss with no change in mental status. He had no pertinent past medical or family history and denied any exposure to IV drugs or blood transfusions. Clinical exam showed scleral icterus, a soft and non-tender abdomen and macular rash in the extremities. Laboratory evaluation showed AST 209, ALT 617 and ALP 1195 (peaked at 2170). INR was 1.0 and albumin was 3.1. Viral hepatitis A, B, C, EBV and HIV testing were negative. F-actin IgG was positive (36) and ANA negative. MRI abdomen showed hepatomegaly without evidence of biliary obstruction. Liver biopsy showed moderate portal/periportal edema; mixed acute and chronic inflammation and pericholangitis with cholestasis. Syphilis immunostaining and Warthin-Starry staining were negative. Our patient was initially treated as presumed autoimmune hepatitis with prednisone. He had significant clinical and LFT improvement over 3-4 weeks but developed new-onset arthralgia in the midst of treatment. Rheumatological workup revealed positive rapid plasma reagin with T. pallidumreactivity. He completed a course of benzathine penicillin, following which he had complete resolution of his symptoms and normalisation of his LFTs. DISCUSSION: SH presents a diagnostic challenge in view of its infrequency and there are currently no standardised diagnostic criteria. Liver chemistry typically demonstrates a cholestatic picture with a disproportionately elevated ALP, likely secondary to pericholangiolar inflammation. However, in our patient, there was also moderate lobular activity with plasma cells, corresponding to a moderately elevated ALT. It is imperative that clinicians have a high index of suspicion for syphilis in view of the morbidity and mortality associated with a missed or late diagnosis and the availability of an effective treatment.

Evaluation of a Cytomegalovirus Prophylaxis Protocol in Cytomegalovirus-IgG Positive Renal Transplant Recipients (R+)

BackgroundThe aim of the study was to evaluate the efficacy of a unique cytomegalovirus- (CMV) prophylaxis protocol in terms of CMV infection and disease progression in CMV IgG positive kidney transplant recipients. MethodsAchievement of negative CMV load, using concurrent prophylactic intravenous ganciclovir therapy during induction immunosuppression, combined with a 6-month prophylactic course of acyclovir, would yield a reduced incidence of early CMV infection and disease. CMV DNA was tested for at discharge, at the third, and sixth post-op months, and at the occurrence of any event that could be associated with CMV infection. CMV DNA positive patients received ganciclovir treatment until the viral load became negative. CMV replication was monitored using a quantitative PCR method capable of detecting as few as 42.5 copies/mL. All patients were given a maintenance dose of acyclovir. ResultThe file data of 267 patients who had undergone kidney transplantation between 2007 to 2016 were examined. Thirty-four patients were excluded from the study for various reasons, unrelated to the protocol. Of the remaining 233 patients, 42 (18%) had CMV DNA infection. Three patients had CMV disease (1.3%), 1of whom died of pneumonia. Diabetes mellitus (DM) was a risk factor for CMV DNA positivity (P < .004). ConclusionThe incidence of CMV infection and disease is low in renal transplant recipients whose CMV viral load is eliminated after concurrent ganciclovir administration with induction immunosuppression.

HAIRY LEUKOPLAKIA IN A PATIENT UNDERGOING ANTI-RETROVIRAL THERAPY

We report a case of hairy leukoplakia that developed in a patient undergoing anti-retroviral therapy. A 53-year old white male presented with mild erythema in the anterior maxillary gingiva and was managed with clobetasol gel, after excluding the possibility of candidiasis. Patient's medical history was significant for HIV, bipolar disorder, high blood pressure, high cholesterol, chronic bronchitis, smoking, and alcohol. His medications included Androgel, Axiron, atorvastatin, bupropion, clonazepam, finasteride, hydrochlorothiazide, lamotrigine, lisinopril, pantoprazole, Prezcobix, Trazadone, Truvada (200 mg emticitabine, 300 mg tenofovir), Ziprasidone, zolpidem, and baby aspirin. During one of multiple follow-up appointments, an asymptomatic white plaque was identified on right lateral tongue. Clinical differential diagnoses included hairy leukoplakia and hyperkeratosis secondary to trauma. Patient reported that his physician changed Truvada to Descovy (200 mg emticitabine, 25 mg tenofovir) since his last appointment. At the appointment six weeks later, the white plaque increased in size, and additional white plaques were found on the left dorso-lateral surface and dorsal tongue. Two biopsies were taken, one from the right lateral and the other from left dorso-lateral tongue. The biopsies showed similar histological features including hyperparakeratosis with shaggy surface and bacterial colonization. Intracellular edema and pyknotic nuclei were noted in the spinous cell layer. Upper spinous cell nuclei were enlarged and glassy appearing, without obvious nucleoli or nuclear beading. An Epstein-Barr encoding region (EBER) in-situ hybridization was performed, which demonstrated presence of EBV. Blood testing, taken five days after the biopsy, showed a CD4 count and viral load within normal limits. The patient's physician prescribed a course of acyclovir 800mg for treating oral hairy leukoplakia. The oral lesions reduced in size at the follow-up appointment three weeks after completion of acyclovir therapy. Further follow-up information also will be presented.

Primary Herpes Simplex Virus-1 Infection Manifesting as Severe Esophagitis in an Adult Immunocompetent Host With Eosinophilic Esophagitis

While a common cause for infectious esophagitis in the immunocompromised, primary herpes esophagitis rarely affects immunocompetent hosts. Meanwhile, incidence of eosinophilic esophagitis (EoE) has increased over the past several decades, with a majority of those affected being young males. Several cases have been reported in the pediatric population, but we describe a case of an immunocompetent adult with known EoE who presented with a primary herpes simplex virus 1 (HSV1) infection manifesting as severe esophagitis. A 20-year-old male with known EoE complicated by prior esophageal food impactions presented to the emergency department with severe odynophagia and solid food dysphagia. The diagnosis of EoE was based on esophageal biopsies showing greater than 50 eosinophils per high powered field. He had been prescribed courses of swallowed aerosolized fluticasone in the past for symptomatic EoE, but had not required treatment in several years. The preceding week, he experienced fevers, chills, ear pain, pharyngitis, and a pustular lesion on his genitalia. He reported difficulty maintaining oral intake, and was found to have a mild leukocytosis. EGD was performed which showed multiple nonbleeding medium sized punched-out ulcers in the mid and distal esophagus. Biopsies of ulcer periphery demonstrated viral cytopathic effect and confirmed HSV by immunohistochemical staining. Histology also confirmed presence of eosinophils, up to 6 per high powered field. The patient was treated with a course of acyclovir with subsequent resolution of his symptoms. Initial HSV serologies were negative, but repeat testing several weeks later showed HSV seroconversion (HSV-1 IgG: 9.08). The patient tested negative for HIV and other sexually transmitted infections. This case adds to the few, but growing number of young immunocompetent hosts with EoE who present with primary HSV esophagitis. One potential reason why such patients are at risk for infectious esophagitis is the need for topical steroid therapy, but as illustrated above, our patient had not been on this treatment for many years. Rather, perhaps the impaired esophageal mucosal integrity present in EoE allows for increased susceptibility to HSV infection at this location. Recognition of this association allows for earlier detection and more targeted treatment.1773_A Figure 1. Severe HSV esophagitis, distal esophagus.1773_B Figure 2. HSV ulcers, mid esophagus.

T69. Continuous Electroencephalogram (CEEG) as a biomarker for progression of Herpes Simplex Virus Encephalitis (HSE)

Introduction HSE is the most common cause of sporadic fatal encephalitis worldwide and remains a devastating disease despite antiviral therapy. Clinically, it is often characterized by fever, headache, seizures and focal neurologic signs. EEG can be an important tool in the diagnosis of HSV. In the acute stage, EEG can show different EEG patterns, commonly including lateralized periodic discharges (LPDs), sharp waves, focal or generalized slowing. As such, EEG can be used to monitor the progression of the disease in patients with treatment refractory HSE. Methods Case report of a patient with HSE who was monitored on CEEG throughout course of her disease. Results A 62-year old female with no history of neurologic disease, who presented with generalized weakness and lethargy for 2 weeks and rapidly deteriorated with encephalopathy, fever, and seizures. Lumbar puncture demonstrated elevated protein and WBC with positive HSV DNA. CEEG initially showed right prefrontal 2-Hz LPD’s. Over the next 48 h, these evolved into focal right prefrontal status epilepticus. After a period of iatrogenic burst suppression, the CEEG showed right frontotemporal LPD’s which evolved into right frontotemporal electrographic seizures. As the CEEG progressed, the right sided seizures appeared to have a more posterior temporal focus. Later, there was additional independent semi-rhythmic 2–4 Hz delta over the left frontotemporal region which was on the ictal-interictal continuum but did not clearly evolve into seizures. As the recording continued, there were left frontal LPD’s more than right-sided ones. The final CEEG demonstrated bilateral independent sharp waves and generalized periodic discharges (GPD’s) with triphasic morphology with resolution of electrographic seizures. As the CEEG revealed evolution of the underlying disease, treatment was escalated with a 21 day course of acyclovir, multiple anti-epileptic agents, including suppressing medications (i.e., midazolam and ketamine), as well as use of plasma exchange and steroids given the refractory seizures. MRI was obtained at three points during hospital stay and confirmed what CEEG heralded. Initially, there was diffusion restriction of the bilateral (right > left) insular cortices and right hippocampus/amygdala. Repeat MRI showed diffusion normalization with T2-weighted and FLAIR hyperintensity in the right > left insula and new involvement of the right temporal lobe. The final MRI demonstrated involvement of the bilateral inferior frontal regions and left temporal lobe, consistent with evolution from the prior studies and with new findings seen on CEEG, suggesting spread of HSE to these regions. Conclusion We report the case of a patient with HSE who was monitored on CEEG and propose that CEEG can be used as a marker for progression of disease and thus may prompt escalation in therapy. While imaging studies may confirm spread of disease, using CEEG may prevent the delay of treatment and lead to more rapid therapy in cases of refractory HSE.

Varicella meningitis : An atypical presentation in an immunocompetent individual with seizures managed with acyclovir

Viral meningitis, also known as aseptic meningitis, is the most common cause of meningitis and is responsible for between 26,000 and 42,000 hospitalizations yearly in the United States. Bacterial meningitis affects about 4,000 people each year, while viral meningitis affects about 10 people in every 100,000. The most commonly identified pathogens are enterovirus, herpes simplex virus and human immunodeficiency virus. Varicella, rabies and influenza are other viruses that are rarely responsible for viral meningitis. Varicella Zoster is a relatively common disorder in immunocompromised patients characterized by radicular pain and grouped vesicular eruptions. The typical findings in reported cases of VZV meningitis involve skin manifestations and classical signs of meningitis such as neck stiffness. However, only a few cases of meningitis caused by Varicella Zoster Virus (VZV) have been reported. The incidence of VZV meningitis in immunocompetent patients has been reported to be as low as 0.5%. We report an atypical presentation of VZV meningitis in an immunocompetent patient with headache, dizziness, sequalae of seizures without fever and skin manifestations.Our patient is a 59‐year‐ old African American male who presented with worsening dizziness, confusion, ataxia, lethargy and left‐sided frontal headache. Magnetic resonance imaging revealed mild to moderate burden of white matter abnormality, nonspecific but most likely due to chronic microvascular ischemic disease. No acute stroke. The next day sedation was weaned off and patient remained seizure free on continuous EEG and was extubated 3 days later the CSF came back positive for an elevated Varicella PCR of 42016. Patient was seen by infectious diseases consultant and was advised a course of acyclovir 10mg/kg intravenous every 8 hours for 14 days. All other antibiotics were stopped. Upon discharge, the patient had fully recovered from his symptoms with no neurologic sequalae.This unique case illustrates an atypical presentation of VZV meningoencephalitis in an immunocompetent patient that lacks many of the obvious features that usually distinguish the disease. Our patient lacked the vesicular rash, as well as other typical features of aseptic meningitis including nuchal rigidity, headache, photophobia, etc. Additionally, the patient's course was complicated by seizure, another relatively uncommon feature of VZV meningoencephalitis. VZV infection or reactivation is, rightfully, most commonly associated with the vesicular rash and prodromal pain that usually accompanies it.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Herpes Esophagitis in an Immunocompetent Patient

HSV esophagitis is well recognized in the immunocompromised host, but can infrequently be seen in the immunocompetent. It rarely causes significant complications such as GI bleed and esophageal perforation. We report a case of an immunocompetent patient who presented with upper GI bleed and was noted to have HSV esophagitis on EGD. This is a 58 year old female with a history May-Thurner syndrome and multiple DVTs admitted for IR thrombolysis of extensive DVT. During her admission she was on aspirin, clopidogrel, and therapeutic enoxaparin. While in the hospital, she developed melena, so she was started on pantoprazole drip and GI was consulted. EGD was done and noted patches of white esophageal exudates with underlying ulcers. Biopsy results showed squamous cells with intranuclear viral type inclusions that were positive for HSV on immunochemical stain. The patient had no previous history of immunodeficiency and has not been on any steroids or other immunosuppressants. HIV screening came back negative. She was treated with acyclovir, pantoprazole and sucralfate and completed a seven day course of acyclovir as an outpatient. Herpes esophagitis in immunocompetent hosts is thought to be exceedingly rare, but may be significantly underestimated. Although typical symptoms include acute dysphagia, odynophagia, chest pain, and fever, an atypical or milder presentation is not uncommon. These patients may be treated empirically with acid suppression for GERD. Resolution of symptoms in these individuals would be expected, despite absence of antivirals, because HSV esophagitis is largely self limited in immunocompetent individuals. Therefore HSV esophagitis in the immunocompetent may be more common than we think and patients are likely going undiagnosed due to atypical presentation and self limiting disease.

A Case Report of Herpes Esophagitis in an Immunocompetent Patient with Cyclic Vomiting Syndrome

Herpes esophagitis (HE) is common in the immunosuppressed but has rarely been reported in the immunocompetent. A recent case series identified 56 cases of confirmed HE in immunocompetent hosts since 1950. Cyclic Vomiting Syndrome (CVS) is an idiopathic disorder characterized by chronically recurring, self-limited episodes of intense nausea and vomiting with a 2% prevalence in the pediatric population. Complications of acute episodes of CVS include dehydration, electrolyte imbalance, Mallory-Weiss tear, weight loss, and esophagitis. To our knowledge, there have been no reported cases of HE in an immunocompetent patient with a history of CVS until now. 19-year-old male with past medical history of depression and 5 year history of nausea and vomiting, which had recently been diagnosed as CVS after extensive workup. He had been released from the hospital 3 days ago for intractable nausea and vomiting, but presented again to the ED with multiple episodes of vomiting. In the ED he complained of new pleuritic chest pain and tightness. Examination revealed pleural rub. Labs revealed a WBC count of 22.4, a creatinine of 1.4, and a UDS positive for THC. Chest x-ray showed pneumopericardium and pneumomediastinum. Follow-up CT chest confirmed esophageal perforation. He was immediately taken for an EGD, which showed no tear or perforation suggesting that occult perforation had sealed spontaneously. EGD did reveal new ulcerations in the distal third of the esophagus, which had not been seen on EGD in the previous workup of CVS. Biopsies obtained from the ulcers were positive for Herpes Simplex Virus. Subsequent testing for HIV and other sources of immunodeficiency were negative. He was then prescribed course of acyclovir, stabilized, and was discharged. HE is rarely reported in immunocompetent hosts, and has not been previously reported in patients with CVS. Young males are most often affected (male:female ratio 2.3:1) (mean age 35 +/- 18.8 years). HE most often presents with odynophagia, fever, chest pain, and dysphagia. Rarely, HE presents with nausea and vomiting. The disease is often self-limited. While esophagitis has been noted as a complication of CVS, we know of no prior reports of immunocompetent HE associated with CVS. This finding raises questions about the possible relationship between CVS and HE. CVS may predispose patients to infection. Alternatively, some presumed cases of CVS may in fact be rare presentations of HE.

Herpes Simplex Hepatitis: Is Mickie Mouse Infectious?

Background: Herpes simplex virus (HSV) hepatitis is a rare complication of HSV infection, but it can often lead to acute liver failure (ALF). It is predominantly seen in immunocompromised patients and pregnant women. However, up to 25% of reported cases occurred in immunocompetent patients. It is unclear why immunocompetent patients are at risk. One theory is that a high inoculation of HSV viremia at initial infection may overcome a competent immune system. Case Report: A 23 year old male with no medical history was admitted with fevers, diffuse abdominal pain, diarrhea, non-bloody emesis, and a centripetal malar rash on his lower extremities. One week prior to admission, he traveled to an amusement park in Florida on a family vacation. Shortly afterwards, he became symptomatic and arrived to our hospital 4 days after presentation. Upon initial evaluation he was found to be pancytopenic (WBC 2.9, Hgb 10.9, Plt 55,000) with hepatocellular LFT abnormalities (AST 273, ALT 236, ALP 71, INR 1.1). He was treated empirically with doxycycline for tick borne illnesses and piperacillin/tazobactam for possible aspiration pneumonia seen on CT. His clinical status deteriorated with persistent fevers, lethargy, and increasing hepatocellular liver tests (AST peaked at 3733, ALT peaked at 2564, INR peaked at 1.4). He was empirically started on acyclovir with hepatitis serology, EBV, CMV, HSV, and HIV PCR pending. A liver biopsy was performed and serum PCR was positive for HSV 1. Over the next few days, the patient improved clinically with normalization of his laboratory values. Patient was discharged on a 3-week course of acyclovir. Discussion: Common features of HSV hepatitis on presentation include fever, leukopenia, thrombocytopenia, encephalopathy, elevated aminotransferases, and coagulopathy. Interestingly, oral and/or genital lesions are seen in only 44 % of patients. Unfortunately, HSV hepatitis is frequently diagnosed post mortem due to its non-specific clinical presentation with high morbidity and mortality. HSV patients who were promptly treated with acyclovir had a much lower progression to death or liver transplantation than untreated patients; 55.1% to 81%. Therefore empiric treatment with acyclovir should be initiated early in a toxic patient prior to confirmation of HSV.Figure 1Figure 2

Disseminated Herpes Simplex Virus with Fulminant Hepatitis.

Disseminated herpes simplex virus (HSV) is a rare cause of acute fulminant liver failure. We hereby present a case series of three patients with acute disseminated HSV with necrotizing hepatitis successfully treated with a week course of acyclovir. Early empiric administration of acyclovir therapy while awaiting confirmatory tests is critical in this potentially lethal disease.

Chronic ulcerating genital herpes simplex virus infection: A diagnosis mislead by HIV infection

We report a case of chronic herpes simplex in a 27 year old lady presenting with a history of persistent verrucous ulcer in the natal cleft of nine months duration. The patient was diagnosed and treated initially as a case of Tuberculosis Verrucosa Cutis (TVC) based on the chronicity of the ulcer, negative HIV serological tests and histopathological findings. The diagnosis had to be revised as the lesion was increasing in size and the patient was not responding to treatment even after completing antituberculous treatment for six months. Repeat histopathological examination and immunohistochemistry showed DNA of herpes simplex. Based on this finding a repeat HIV serology was sent which was positive. The ulcer healed after a course of acyclovir. The case is being reported to highlight the importance of considering chronic herpes simplex infection in a case of chronic genital ulcer. In addition this case reminds us the nature of HIV infection to mislead the diagnosis by altering the natural course of the disease process.

Gliomatosis cerebri mimicking acute viral encephalitis and with malignant transformation of partial lesions: A case report.

Gliomatosis cerebri (GC) is a rare glial neoplasm, characterized by extensive diffuse brain infiltration and relative preservation of the underlying architecture. In the present case report, a patient with type 2 GC, which mimicked the clinicoradiological course of acute viral encephalitis, is presented. A 56-year-old male presented with fever, dizziness, headache and numbness in the right extremities three days prior to admission to hospital. The cerebrospinal fluid (CSF) showed mild pleocytosis. Brain magnetic resonance imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery images in the left frontal, temporal, insular lobes and in the left thalamus. No signal enhancement was observed following gadolinium administration. The patient was diagnosed with acute viral encephalitis of unknown cause and received a 10-day course of acyclovir, intravenously. At the follow-up three months later, the patient had personality changes and memory deterioration. The results from the follow-up MRI revealed no remarkable changes. At the follow-up six months after presentation, the patient had expressive aphasia and severe headaches. Subsequently, the patient had two tonic-clonic seizure onsets. The results from the MRI showed an increase in lesion size, more edema around the lesion and irregular enhancement in the left frontal lobe. However, the lesions in the left temporal and insular lobes and in the left thalamus were nearly unchanged. Magnetic resonance spectroscopy (MRS) showed elevated choline (Cho)/creatine (Cr) and Cho/N-acetylaspartate (NAA) ratios, as well as decreased NAA/Cr ratios. Surgery was performed and the neuropathological diagnosis of WHO grade III astrocytoma was confirmed. Thus, it is important to pay attention to the differential diagnoses of GC and acute viral encephalitis in patients who have widespread MRI lesions. A brain biopsy is recommended for a diagnosis in this case.

Synchronous HSV Esophagitis and CMV Colitis in Multiple Myeloma Presenting with Massive GI Bleed

Purpose: Opportunistic viral infections like cytomegalovirus and herpes simplex virus constitute a signifi cant component of morbidity in immunocompromised patients. CMV reactivation has a high incidence in patients who undergo autologous bone marrow transplantation for multiple myeloma. Likewise, HSV manifestations including disseminated HSV are observed in HIV and other immunocompromised patients. Here, we report a case of newly diagnosed multiple myeloma presenting with GI bleeding, who was found to have HSV ulcerative esophagitis and CMV ulcerative colitis. An 84-year-old female presented to our facility with a complaint of increasing thoracic spine pain. MRI of spine revealed that she had multiple levels of signal change. Serum electrophoresis showed a spike in IgG, consistent with multiple myeloma. On the following day, she developed acute cord compression at T5, leading to lower extremity weakness and urinary incontinence. Methylprednisone was started, and a ten-day course of radiation was initiated. During the course of hospitalization, she developed odynophagia and massive hematochezia, requiring four packed RBC transfusion to maintain hemoglobin above 10 mg/dl. Esophagogastroduodenoscopy revealed three mid esophageal ulcers and one ulcer at the gastroesophageal junction. Biopsies were obtained from both sites. Distal esophageal biopsy revealed erosive esophagitis with characteristic multinucleated giant cells and immunostains positive for HSV, while mid esophageal ulcers demonstrated inflamed muscularis mucosa with immune stains positive for CMV. Subsequently, colonoscopy was performed and severe ulceration was noted at the splenic flexure, which was suspicious for ischemic colitis. However, biopsies showed acute colitis with fibrinopurulent exudates and viral cytopathic changes consistent with cytomegalovirus, which were confirmed by immunostains. The patient was started on a 14-day course of acyclovir and ganciclovir for HSV and CMV, respectively. Her hematochezia and odynophagia got completely resolved. To the best of our knowledge, this is the first reported case of multiple myeloma having coexistence of HSV and CMV viruses in esophageal ulcers with massive hematochezia due to CMV colitis. Biopsies from multiple sites of ulceration proved to be a pivotal factor in the diagnosis and treatment of our patient.

Disease Remission in a Horse with EHV‐5‐Associated Lymphoma

Disease Remission in a Horse with <scp>EHV</scp>‐5‐Associated Lymphoma