Clinical and Histopathologic Features Can Help Target Immunohistochemical Stain Use in the Diagnosis of Viral Esophagitis.

OBJECTIVES: Herpes simplex virus (HSV) and cytomegalovirus (CMV) immunohistochemical stains (IHC) are frequently applied on esophageal biopsies. Our aims were to identify IHC use patterns in viral esophagitis (VE), and clinicopathologic features of VE that could guide IHC use. METHODS: We included 58 VE cases and 60 controls, defined as patients with negative HSV/CMV IHC between January 2006 and July 2017. Biopsies were reviewed and histologic features and clinical data recorded. RESULTS: Thirteen cases required IHC for diagnosis. IHC was performed in 13 HSV and 5 CMV cases where diagnostic viral inclusions were present. VE patients were more likely to have endoscopic ulcer (P=0.002) and be immunocompromised (P<0.001). Pretest clinical concern for VE was common (P=0.006). Histologically, VE patients were more likely to have ulcer (P=0.004), ulcer exudate rich in neutrophils and histiocytes (P=0.001), neutrophils in squamous mucosa (P<0.001), histiocyte aggregates >15 (P<0.001) and spongiosis (P<0.001). Controls had frequent eosinophils, alone (P=0.008) or admixed with other inflammatory cells (P<0.0001). CONCLUSIONS: IHC is used in VE biopsies despite definite viral inclusions on hematoxylin and eosin and in patients without concerning histology or clinical concern for VE. History, endoscopic findings, and histology can be used to better target IHC use in VE.

Machine learning approach for differentiating cytomegalovirus esophagitis from herpes simplex virus esophagitis.

The endoscopic features between herpes simplex virus (HSV) and cytomegalovirus (CMV) esophagitis overlap significantly, and hence the differential diagnosis between HSV and CMV esophagitis is sometimes difficult. Therefore, we developed a machine-learning-based classifier to discriminate between CMV and HSV esophagitis. We analyzed 87 patients with HSV esophagitis and 63 patients with CMV esophagitis and developed a machine-learning-based artificial intelligence (AI) system using a total of 666 endoscopic images with HSV esophagitis and 416 endoscopic images with CMV esophagitis. In the five repeated five-fold cross-validations based on the hue-saturation-brightness color model, logistic regression with a least absolute shrinkage and selection operation showed the best performance (sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve: 100%, 100%, 100%, 100%, 100%, and 1.0, respectively). Previous history of transplantation was included in classifiers as a clinical factor; the lower the performance of these classifiers, the greater the effect of including this clinical factor. Our machine-learning-based AI system for differential diagnosis between HSV and CMV esophagitis showed high accuracy, which could help clinicians with diagnoses.

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.

Toll-like receptor 3 (TLR3) variant and NLRP12 mutation confer susceptibility to a complex clinical presentation.

Genetic aberrations in the toll-like receptor (TLR)3 pathway are associated with increased susceptibility to herpes simplex virus (HSV) infections. Leucine-rich repeat and PYD-containing protein (NLRP)12 is a component of the inflammasome apparatus, which is critical to an immediate innate inflammatory response. Aberrations in NLRP12 have been shown to mediate auto-inflammation. In this study, we present a 44-year old patient with severe HSV esophagitis and Crohn's disease. An immune and genetic investigation confirmed two coinciding genetic mutations in TLR3 and NLRP12. Our findings support conducting laboratory workup that targets TLR3 pathway in the immunocompetent host developing recurrent HSV infections.

Herpes Simplex Esophagitis in Immunocompetent Patients: A Rare But Easily Managed Condition.

Herpes simplex (HS) is an opportunistic infection, primarily in immunocompromised patients, caused by herpes simplex virus. Oral and genital mucosa are the most commonly involved sites; it is rare for HSV to invade the esophagus and cause esophagitis, especially in immunocompetent patients. Here, we present a case where an immunocompetent patient presented with HS esophagitis, which had evolved into esophageal ulcers. He was successfully treated with acyclovir. Subsequently, we did a comprehensive literature search and tabulated all the possible complications and management plans of previously reported cases of HS in immunocompetent patients.

Severe Bleeding due to Cytomegalovirus Esophagitis in a Patient with Diabetes after Interbody Fusion Surgery.

A 49-year-old man with diabetes taking clopidogrel and celecoxib underwent interbody fusion surgery for spinal spondylolysis. Ten days after the surgery, he vomited a large amount of fresh blood. A blood examination revealed hemodynamic failure. Esophagogastroduodenoscopy showed an adherent blood clot and multiple superficial ulcers in the esophagus. Endoscopic hemostasis was successfully achieved. Biopsy specimens from the esophageal ulcer showed positive immunohistochemical staining results for anti-CMV antibodies. The esophageal ulcer improved after the oral administration of ganciclovir. This case emphasizes that CMV esophagitis with bleeding can occur in a diabetic patient with a poor nutritional status due to relative immune dysfunction.

Can endoscopists differentiate cytomegalovirus esophagitis from herpes simplex virus esophagitis based on gross endoscopic findings?

Differential diagnosis between herpes simplex virus (HSV) esophagitis and cytomegalovirus (CMV) esophagitis is challenging because there are many similarities and overlaps between their endoscopic features. The aims of this study were to investigate the implications of the endoscopic findings for the diagnosis of HSV and CMV esophagitis, and to develop a predictive model for differentiating CMV esophagitis from HSV esophagitis.Patients who underwent endoscopic examination and had pathologically-confirmed HSV or CMV esophagitis were eligible. Clinical characteristics and endoscopic features were retrospectively reviewed and categorized. A predictive model was developed based on parameters identified by logistic regression analysis.During the 8-year study period, HSV and CMV esophagitis were diagnosed in 85 and 63 patients, respectively. The endoscopic features of esophagitis were categorized and scored as follows: category 1 (-3 points): discrete ulcers or ulcers with vesicles, bullae, or pseudomembranes, category 2 (-2 points): coalescent or geographic ulcers, category 3 (1 points): ulcers with an uneven base, friability, or with a circumferential distribution, category 4 (2 points): punched-out, serpiginous, or healing ulcers with yellowish exudates. And previous history of transplantation (2 point) was included in the model as a discriminating clinical feature. The optimal cutoff point of the prediction model was 0 (area under receiver operating characteristic curve: 0.967), with positive scores favoring CMV esophagitis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 89.4%, 92.6%, 87.3%, and 97.5%, respectively.The predictive model based on endoscopic and clinical findings appears to be accurate and useful in differentiating CMV esophagitis from HSV esophagitis.

An uncommon case of herpetic esophagitis in a small child with allergic rhinitis: A case report and literature review (CARE compliant).

RATIONALE: Herpetic esophagitis (HE) is a common condition in immunosuppressed patients, but a rare entity in immunocompetent patients affecting especially male teenagers and young adults. PATIENT CONCERNS: We report the case of a 5-year-old male patient, with a history of allergic rhinitis admitted in our clinic for acute onset fever refractory to antipyretics, chest pain, anorexia, refusal of solid food, accepting only small amounts of fluids, odynophagia, and epigastric pain. The clinical exam revealed severe malaise, pallor, decreased skin turgor, abdominal epigastric tenderness, heartburn at palpation within the epigastric area. The laboratory tests showed leukocytosis, monocytosis, hypoglycaemia, and elevated inflammatory biomarkers. DIAGNOSES: The serology tests for human immunodeficiency virus (HIV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV) were negative, except for immunoglobulin G (IgG) anti-EBV which was positive. The chest radiography was normal, and the abdominal ultrasound showed abdominal bloating. The upper digestive endoscopy revealed friable esophageal mucosa, with multiple ulceration on the entire esophagus, and whitish exudates especially on the middle and lower part of the esophagus suggesting a possible eosinophilic esophagitis or caused by Candida. Despite the empirical initiated treatment, the patient's evolution was only slowly favorable. The histological exam established the diagnosis of HE. INTERVENTIONS: We initiated acyclovir therapy with an outstandingly favorable evolution. OUTCOMES: After 1 month, we detected the seroconversion of IgG anti-HSV. The patient's follow-up revealed no additional complaints. LESSONS: Despite its rarity in immunocompetent individuals, HE must be taken into account even in otherwise healthy small children. Allergic conditions might represent a predisposing factor for HE.

Eosinophilic esophagitis after an episode of herpetic esophagitis.

We want to present a case of eosinophilic esophagitis (EoE) after a herpetic esophagitis (HE) to increase the available evidence on the association suggested between both entities recently published by Iriarte Rodríguez et al.

Variations in the Clinical Course of Patients with Herpes Simplex Virus Esophagitis Based on Immunocompetence and Presence of Underlying Esophageal Disease.

BACKGROUND AND AIMS: Herpes simplex esophagitis (HSE) is the second most common cause of infectious esophagitis and occurs in both immunocompetent and immunocompromised patients. The aim of this study was to reappraise the clinical course of HSE in different patient populations based on degree of immunocompetence and the presence or absence of underlying esophageal disease. METHODS: Patients with histopathologically confirmed HSE identified from the Mayo Clinic pathology database from 2006 to 2016 were included in this study. Relevant demographic, clinical, and endoscopic data were retrospectively reviewed and compared between two cohorts: (a) immunocompromised and immunocompetent patients and (b) patients with and without underlying esophageal disorders. RESULTS: Forty-six patients were included in the study. The most common presenting symptoms were odynophagia (34.8%) and dysphagia (30.4%). Thirty-three (71.7%) patients were immunocompromised, and these patients who experienced longer duration of symptoms (25.5 ± 23.4 days vs. 7.0 ± 5.5 days, p = 0.04) were more likely to require an extension of treatment course (38.1% vs. 8.3%, p = 0.05) compared to their immunocompetent counterparts. Seventeen (37%) patients had underlying esophageal disease, and these patients were more likely to have concomitant esophageal candidiasis (41.2% vs. 10.3%, respectively; p = 0.01). CONCLUSION: Herpes simplex virus causes esophagitis in both immunocompetent and immunocompromised patients. While the disease course appears to be self-limited for all patient populations, clinical and endoscopic differences in the disease presentation and clinical course based on immune status and the presence or absence of underlying esophageal disease exist.

Unusual manifestation of disseminated herpes simplex virus type 2 infection associated with pharyngotonsilitis, esophagitis, and hemophagocytic lymphohisitocytosis without genital involvement.

BACKGROUND: Herpes simplex virus (HSV) has various presentations, depending on the patient's immune status, age, and the route of transmission. In adults, HSV type 1 is found predominantly in the oral area, and HSV type 2 (HSV-2) is commonly found in the genital area. HSV-2 infection without genital lesions is uncommon. Herein we report a unique case of pharyngotonsillitis as an initial manifestation of disseminated HSV-2 infection without genital involvement. CASE PRESENTATION: A 46-year-old male was admitted to our hospital with a 1-week history of fever and sore throat. His past medical history included hypereosinophilic syndrome diagnosed at age 45 years. Physical examination revealed throat congestion, bilaterally enlarged tonsils with exudates, tender cervical lymphadenopathy in the left posterior triangle, and mild epigastric tenderness. The laboratory data demonstrated bicytopenia, elevated liver enzyme levels, and hyperferritinemia. A bone marrow smear showed hypocellular marrow with histiocytes and hemophagocytosis. The diagnosis of HLH was confirmed, and the patient was treated with methylprednisolone pulse therapy on days 1-3. On day 5, despite initial improvement of the fever and sore throat, multiple, new, small bullae developed on the patient's face, trunk, and extremities. Additional testing showed that he was positive for HSV-specific immunoglobulin M and immunoglobulin G. Disseminated HSV infection was suspected, and intravenous acyclovir (10 mg/kg every 8 h) was begun. A subsequent direct antigen test of a bulla sample was positive for HSV-2. Moreover, tonsillar and esophageal biopsies revealed viral inclusion bodies. Immunohistochemical staining and a quantitative real-time polymerase chain reaction (PCR) assay confirmed the presence of HSV-2. Disseminated HSV-2 infection with multiple bullae, tonsillitis, esophagitis, and suspected hepatic involvement was diagnosed. After a 2-week course of intravenous acyclovir, his hematological status and liver function normalized, and his cutaneous skin lesions resolved. He was discharged on day 22 in good general health and continued taking oral valacyclovir for viral suppression due to his immunosuppressed status. CONCLUSION: Disseminated HSV-2 infection should be considered as one of the differential diagnoses in patients with pharyngotonsillitis and impaired liver function of unknown etiology even if there are no genital lesions.