Diagnostic utility of cytology in a patient with Epstein-Barr virus-positive mucocutaneous ulcer in palatine tonsils: A case report.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU.

Chikungunya associated vulvitis: case report and literature review / Vulvite associada a Chikungunya: relato de caso e revisão de literatura

Introduction: Chikungunya virus is spreading worldwide due to migration and globalization and could be presented with systemic and with unusual symptoms. Objective: To report a case of virus-transmitted infection detected in a woman during the gynecological examination at a vulvar clinic. Case report: A 73-year-old Caucasian woman attended a vulvar clinic because of dyspareunia and vulvar burning. Ulcers were observed on labia minora and perineum. A Chikungunya was diagnosed by seroconversion in paired specimens. She was prescribed prednisolone 40 mg once a day for 10 days. After oral steroid treatment, the woman had no body rashes or lesions on her genitals. Conclusion: This study emphasized that rare signs of unusual vulvitis with ulcers could be associated with Chikungunya infection.

Introdução: O vírus Chikungunya está se espalhando pelo mundo por conta da migração e da globalização, podendo apresentar sintomas sistêmicos e incomuns. Objetivo: Relatar um caso de infecção pelo vírus detectado em uma mulher por ocasião do exame ginecológico em clínica de patologia vulvar. Relato do caso: Uma mulher caucasiana de 73 anos foi a uma clínica vulvar por causa de dispareunia e queimação vulvar. Úlceras foram observadas nos pequenos lábios e no períneo. O diagnóstico de Chikungunya foi realizado por soroconversão em espécimes pareados. Foi prescrita prednisolona 40 mg uma vez ao dia por dez dias. Após o tratamento com esteróides orais, a mulher não apresentou erupções ou lesões nos órgãos genitais. Conclusão: Este estudo enfatizou que quadros raros de vulvite com úlcera podem estar associados à infecção por Chikungunya.

Hypopharyngeal Ulcers in COVID-19: Histopathological and Virological Analyses - A Case Report.

In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.

EBV Positive Mucocutaneous Ulcer (EBVMCU): Single Center Series of Three Cases and Review of Literature.

EBV positive mucocutaneous ulcer (EBVMCU) is a newly recognized clinicopathologic entity in the 2017 World Health Organization (WHO) classification. Patients frequently present with an isolated ulcerative lesion in mucosal and cutaneous sites with immunosuppression as the main risk factor. The disease typically follows an indolent clinical course. Herein we describe a series of three patients diagnosed with EBVMCU. Histopathologic examination of these cases shows ulceration in mucosal or cutaneous surface with a substantial number of large atypical transformed cells in the background of dense polymorphous infiltrates. One patient regressed spontaneously with no treatment, one patient needed Rutiximab, and one patient had persistent EBVMCU process with possible transformation to large B cell lymphoma. The aim of the present case series is to highlight the pathologic, diagnostic and clinical features of patients with EBVMCU.

Refractory pharyngeal ulceration due to cytomegalovirus in a patient with HIV infection: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. CASE PRESENTATION: A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl's eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. CONCLUSIONS: This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

Brief Report: Herpes Simplex Virus Type-2 Shedding and Genital Ulcers During Early HIV in Zimbabwean Women.

BACKGROUND: Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, viral DNA shedding and/or ulcers) preceded HIV acquisition in the hormonal contraception and HIV cohort. METHODS: Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) at each visit. RESULTS: Of 387 HSV-2 seropositive women, most had prevalent as compared with incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, P < 0.01). Shedding occurred around HIV acquisition (t-3months aOR, 2.7; 95% CI, 0.8 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%; P = 0.06) and detection was after HIV acquisition (t+6months aOR, 14.5; 95% CI, 1.6 to 133.9). CONCLUSIONS: HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.

Fatal Herpes Simplex Esophagitis of an Infant Case Report and Review of the Literature.

ABSTRACT: Herpes simplex virus esophagitis is a rare and not readily recognized condition which is often seen in immunocompromised individuals. This case highlights the rare complication of herpes simplex virus in an otherwise healthy male infant who presented with a possible seizure after listlessness, fever, and black stools for 1 day. The decedent died shortly after arrival to the hospital emergency department, and a complete autopsy was performed, which was remarkable for upper gastrointestinal bleeding due to esophageal ulcers secondary to viral infection (herpes simplex virus type 1). To our knowledge, this is the first reported case in which herpes simplex virus esophagitis resulted in ulcerations that extended through the esophagus and involved the adjacent wall of the aorta with subsequent upper gastrointestinal bleeding leading to the death of an infant.

Epigastric pain associated with herpes esophagitis: case report.

BACKGROUND: Herpes esophagitis is uncommon disease caused by Herpes simplex virus (HSV). While the disease most often occurs in immunocompromised patients, including post-chemotherapy, immunosuppression with organ transplants, and in AIDS, Herpes esophagitis can also occur in immunocompetent individuals. CASE PRESENTATION: We report a case of herpes esophagitis in a 72 year- old woman who was presumed to be immunocompromised following prolonged radiotherapy and chemotherapy for lymphoma. Her main symptom was epigastric pain. Upper endoscopy showed multiple rounded ulcers in lower esophagus. The diagnosis was confirmed histologically by multiple biopsies. The patient received Valacyclovir for 2 weeks and started to get better within 3 days of treatment. CONCLUSION: Although there are few published cases of Herpes esophagitis disease in the medical literature, we recommend that this disease should be considered as one of the differential diagnoses when assessing immuno-compromised patients presenting with non-specific abdominal symptoms.

Epstein-Barr virus-associated enteritis with multiple ulcers: The first autopsy case.

Epstein-Barr virus (EBV)-associated enteritis is extremely rare and has not been well characterized. Herein, we present the first autopsy case of EBV-associated enteritis with multiple ulcers in a 73-year-old Japanese male. The patient had abdominal pain and was clinically diagnosed with enteritis. An endoscopic examination revealed multiple ulcers at the terminal ileum. His condition worsened due to serosanguinous bowel discharge and the patient was then admitted to the hospital. Ileocecal and subtotal small intestinal resection was performed for repetitive hemorrhage from ulcers. However, the patient died due to uncontrolled hemorrhage. An autopsy was then performed in order to explore the cause of ulcers in the small intestine. Macroscopic findings revealed multiple ulcers with occasional cobblestone-like appearance of the ileum. Histological analysis revealed marked infiltration of lymphocytes and plasma cells around the ulcer. EBV-encoded RNA in situ hybridization (EBER-ISH) revealed positive inflammatory cells. Cytomegalovirus was immunohistochemically negative. Macroscopic and microscopic findings obtained from autopsy specimens showed no foci of inflammation and EBER-ISH-positive stromal cells in the esophagus, stomach, and colorectum. EBV-associated enteritis can cause uncontrolled repetitive hemorrhage from ulcers and result in critical condition of the patient, which can be used for differential diagnosis.

Chronic Active Epstein-Barr Virus-Associated Enteritis: CT Findings and Clinical Manifestation.

AIM: To improve the identification and computed tomography (CT) diagnostic accuracy of chronic active Epstein-Barr virus (EBV)-associated enteritis (CAEAE) by evaluating its CT findings and clinical manifestation. METHODS: The data of three patients with pathologically and clinically confirmed CAEAE who underwent CT enterography (CTE) were retrospectively reviewed from January 2018 to October 2019. The following data were evaluated: imaging characteristics (length of involvement, pattern of mural thickening, pattern of attenuation, perienteric abnormalities), clinical symptoms, endoscopic records, laboratory examinations, and pathologic findings. RESULTS: Based on CT findings, two patients demonstrated segmental bowel wall thickening (involvement length >6 cm), asymmetric thickening, layered attenuation, fat stranding, and adenopathy, whereas the remaining one had no positive finding. The endoscopic results of all patients showed numerous irregular ulcers in the colon, and one patient had a focal esophageal ulcer. The major clinical symptoms were abdominal pain (n = 3), retrosternal pain (n = 1), fever (n = 3), diarrhea (n = 2), hematochezia (n = 1), and adenopathy (n = 3). The main laboratory examination indicators were increased serum EBV DNA load (n = 1) and increased inflammatory markers (n = 3). With regard to the main pathologic findings, all patients showed positive EBV-encoded RNA (EBER) situ hybridization in the colonic biopsy specimen, with one patient being positive in the esophagus. CONCLUSION: CAEAE is rare and is usually misdiagnosed as inflammatory bowel disease (IBD). The imaging features of CAEAE overlap with those of Crohn's disease and ulcerative colitis. The presence of segmental and asymmetric bowel wall thickening, layered attenuation, and fat stranding in the CTE image may be helpful in differentiating CAEAE from IBD.

The global and regional burden of genital ulcer disease due to herpes simplex virus: a natural history modelling study.

Introduction: Herpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due to HSV type 2 (HSV-2), but may also be due to genital HSV type 1 (HSV-1), which has less frequent recurrent episodes than HSV-2. The global burden of GUD has never been quantified. Here we present the first global and regional estimates of GUD due to HSV-1 and HSV-2 among women and men aged 15-49 years old. Methods: We developed a natural history model reflecting the clinical course of GUD following HSV-2 and genital HSV-1 infection, informed by a literature search for data on model parameters. We considered both diagnosed and undiagnosed symptomatic infection. This model was then applied to existing infection estimates and population sizes for 2016. A sensitivity analysis was carried out varying the assumptions made. Results: We estimated that 187 million people aged 15-49 years had at least one episode of HSV-related GUD globally in 2016: 5.0% of the world's population. Of these, 178 million (95% of those with HSV-related GUD) had HSV-2 compared with 9 million (5%) with HSV-1. GUD burden was highest in Africa, and approximately double in women compared with men. Altogether there were an estimated 8 billion person-days spent with HSV-related GUD globally in 2016, with 99% of days due to HSV-2. Taking into account parameter uncertainty, the percentage with at least one episode of HSV-related GUD ranged from 3.2% to 7.9% (120-296 million). However, the estimates were sensitive to the model assumptions. Conclusion: Our study represents a first attempt to quantify the global burden of HSV-related GUD, which is large. New interventions such as HSV vaccines, antivirals or microbicides have the potential to improve the quality of life of millions of people worldwide.