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

Abstract

BackgroundHerpes 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 presentationA 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.ConclusionDisseminated 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.

The role of active herpesvirus infection in the formation of atopic dermatitis and psoriasis

“…Полученные данные в совокупности с достоверным превышением частоты выявления IgM к ВПГ2 у пациентов с болезнями кожи и подкожной клетчатки по сравнению с донорами крови указывают на активное участие вируса в развитии исследуемой патологии. При этом отсутствие различий в частоте обнаружения IgM к ВПГ2 у больных атопическим дерматитом и псориазом в фазе обострения может быть следствием разных причин, наиболее вероятными из которых являются полиморфизм клинических проявлений активной ВПГ2-инфекции и возможность участия данного возбудителя в патологическом процессе совместно с другими вирусами герпеса [23][24][25]. Отсутствие в Российской Федерации официальной регистрации случаев активной ВПГ1инфекции не позволило осуществить корреляционный анализ динамики заболеваемости относительно болезней кожи и подкожной клетчатки.…”

“…Можно предположить, что вклад вирусов простого герпеса (как ВПГ1, так и ВПГ2) в патологию кожи и подкожной клетчатки осуществляется в двух направлениях: в виде везикулярных высыпаний, появляющихся в разгар клинических проявлений инфекционного процесса [23,24], и в виде иной патологии, обусловленной системным действием возбудителей на организм человека [3,26]. В ходе проведенного исследования впервые показано, что развитие обострения атопического дерматита может быть следствием недавно перенесенного активного инфекционного процесса, вызванного ВПГ1, или его сочетания с ВПГ2 и/или другими представителями семейства Herpesviridae.…”

A Rare Case of Herpes Simplex Virus-2 Hepatitis with Negative Serology

“…Potential mechanisms of herpes induced hepatitis include (i) a large HSV inoculum overwhelming the immune system on initial encounter; (ii) dissemination of mucosal herpetic lesions within a suppressed immune system; (iii) reactivation of a latent HSV reactivation or reinfection with a different new strain of HSV 4 (Hepatovirulent HSV) [4]. Disseminated HSV-2 infection has been defined by presence any of the following criteria, (a) positive HSV-2 IgM antibody test results, (b) HSV-2 DNA detected by polymerase chain reaction (PCR) assay of the peripheral blood mononuclear cells (PBSCs), or (c) involvement of two or more noncontiguous sites concurrently [5].…”

Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System

“…The literature on the genetic causes of HSV HLH is limited. While some clinical case reports of HSV-1 HLH [ 122 , 123 , 124 , 125 , 126 ] and HSV-2 HLH exist [ 127 ], new genetic variants have been discovered in only three studies to date: in a 19-year-old woman suffering from postpartum HSV-1 HLH, a Caspase-8 ( CASP8 ) variant was noted, but a definitive link between the variant and the impaired IFN responses observed in her PBMCs was not established [ 128 ]; a novel variant in EP300 was discovered in a patient with Rubinstein–Taybi syndrome and HSV-1 HLH [ 129 ]; and finally, an 18-year-old female patient was reported in whom a GATA2 variant was identified postmortem, although the disease-causing potential was not functionally validated [ 130 ].…”