acyclovir and Lymphohistiocytosis--Hemophagocytic

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that can be triggered by infections, malignancies, or auto-immune diseases. Here, we present a patient with rapidly progressive HLH triggered by a herpes simplex virus type 2 (HSV-2) primary infection. The patient was successfully treated with intravenous high-dose acyclovir, immunoglobulins, and dexamethasone. This is the first report of HSV-2-associated HLH in an immunocompetent adult patient.

Topics: Acyclovir; Adult; Herpes Simplex; Herpesvirus 2, Human; Humans; Lymphohistiocytosis, Hemophagocytic

We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic syndrome (HPS) in a 37-year-old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi-organ failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases).

Topics: Acyclovir; Antiviral Agents; Diarrhea; Drug Therapy, Combination; Epstein-Barr Virus Infections; Fatal Outcome; Female; Fever; Ganciclovir; Glomerulonephritis, IGA; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lymphohistiocytosis, Hemophagocytic; Multiple Organ Failure; Oliguria

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.. 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.. 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.

Topics: Acyclovir; Esophagitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompromised Host; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Pharyngitis; Tonsillitis; Urogenital System

Hemophagocytic lymphohistiocytosis (HLH) associated with herpes simplex virus (HSV)-1 infection (HSV-1-HLH) is uncommon and is potentially fatal without appropriate treatment. We herein report the case of an adult patient with HSV-1-HLH who was successfully treated with acyclovir. A 69-year-old man developed fever, pancytopenia and liver enzyme elevation after the resolution of pneumonia. These findings and the presence of hemophagocytosis in the patient's bone marrow were consistent with a diagnosis of HLH. The patient was diagnosed with HSV-1-HLH based on the results of a polymerase chain reaction (PCR) for HSV-1. The early administration of acyclovir improved his clinical symptoms and laboratory results within two weeks. In the present case, the rapid and precise diagnosis facilitated the successful treatment of HSV-1-HLH.

Topics: Acyclovir; Aged; Herpes Simplex; Herpesvirus 1, Human; Humans; Lymphohistiocytosis, Hemophagocytic; Male

We here report the case of a 52-year old man who presented hepatitis with hemophagocytic syndrome triggered by herpes simplex 1 (HSV-1) primary infection. A high-level viremia was observed, and HSV-1 DNA remained detectable in blood for a long time after patient's recovery.

Topics: Acyclovir; DNA, Viral; Etoposide; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulins, Intravenous; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Treatment Outcome; Viral Load

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that essentially affects the white matter of the central nervous system. The diagnosis is based on clinical-imaging and developmental findings. Magnetic resonance imaging of the brain is the most useful diagnostic tool. The disease course is usually monophasic and the preferred initial treatment is with corticoids.. We conducted a retrospective study of 18 patients with a presumptive diagnosis of ADEM. Symptoms, imaging findings, progress and treatment were analysed. The definitive diagnosis was established in 12 patients, excluding one patient with positive polymerase chain reaction for herpes simplex virus in cerebrospinal fluid, one with a clinical picture that was consistent but normal magnetic resonance imaging of the brain, and four with an onset that was similar to ADEM whose definitive diagnoses were: Rassmusen's syndrome, haemophagocytic syndrome, brain tumour, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes).. The median age was 31 months with no predominance of either sex. Infection of the upper respiratory tract was the most frequent cause in children over 2 years of age and of the gastrointestinal tract in those under the age of 2. All of them presented altered levels of consciousness and multifocal neurological deficits. The most frequent imaging finding was multifocal alteration of the white matter in both hemispheres. Corticoids were the preferred treatment in most cases. Progression was favourable in nearly all patients except for two, who were left with important sequelae.. ADEM may present at any age, including in infants. There are a number of conditions that can mimic ADEM in the early stages.. Analisis de una serie de casos con diagnostico inicial de encefalomielitis aguda diseminada en el periodo 2000-2010.. Introduccion. La encefalomielitis aguda diseminada (EMAD) es una enfermedad desmielinizante que afecta fundamentalmente a la sustancia blanca del sistema nervioso central. El diagnostico se basa en hallazgos clinicorradiologicos y evolutivos. La resonancia magnetica cerebral es la herramienta diagnostica mas util. El curso suele ser monofasico y el tratamiento inicial de eleccion, los corticoides. Pacientes y metodos. Estudio retrospectivo de 18 pacientes con diagnostico de sospecha inicial de EMAD. Se analizo la sintomatologia, los hallazgos radiologicos, la evolucion y el tratamiento. El diagnostico definitivo se establecio en 12 pacientes, excluyendo un paciente con reaccion en cadena de la polimerasa positiva para el virus herpes simple en el liquido cefalorraquideo, uno con clinica compatible pero resonancia magnetica cerebral normal, y cuatro con inicio similar a EMAD cuyos diagnosticos definitivos fueron: sindrome de Rassmusen, sindrome hemofagocitico, tumor cerebral y MELAS (encefalomiopatia mitocondrial con acidosis lactica y accidentes cerebrovasculares). Resultados. La mediana de edad fue de 31 meses, sin predominio de sexo. La infeccion de la via respiratoria superior fue la causa mas frecuente en niños mayores y la gastrointestinal, en menores de 2 años. Todos presentaron alteracion en el nivel de conciencia y deficits neurologicos multifocales. El hallazgo radiologico mas frecuente fue la alteracion multifocal bihemisferica de la sustancia blanca. Los corticoides fueron el tratamiento de eleccion en la mayoria. La evolucion fue favorable en casi todos los pacientes excepto en dos, que tuvieron secuelas importantes. Conclusiones. La EMAD puede presentarse a cualquier edad, incluyendo lactantes. Hay multiples entidades que pueden simular una EMAD en un inicio.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Antiviral Agents; Child; Child, Preschool; Diagnosis, Differential; Disease Progression; Encephalitis, Herpes Simplex; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Female; Humans; Immunoglobulins, Intravenous; Infant; Lymphohistiocytosis, Hemophagocytic; Magnetic Resonance Imaging; Male; Plasmapheresis; Recovery of Function; Respiratory Tract Infections; Retrospective Studies; Spain; Symptom Assessment

Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus.. We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome. Positive plasma polymerase chain reaction (PCR) with negative serology revealed a primary, disseminated infection with herpes simplex virus-1 as the triggering pathogen. After treatment with acyclovir, high-dose steroids, immunoglobulins, and etoposide, the patient recovered.. Early diagnosis of potentially underlying infections of hemophagocytic syndrome influences the therapeutic approach. It is important to consider a variety of infectious agents, particularly in immunosuppressed individuals. The reported case emphasizes the importance of screening for herpes simplex virus 1.

Topics: Acyclovir; Etoposide; Herpes Simplex; Herpesvirus 1, Human; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Steroids

Two adolescents, on immunosuppressive therapy for graft-versus-host disease, developed hemophagocytic lymphohistiocytosis (HLH) after varicella zoster virus (VZV) reactivation. In the absence of dermatome restricted characteristic skin lesions, VZV reactivation was not immediately recognized and treatment with acyclovir was delayed. The first patient developed optical neuritis and died 2 months after the VZV episode due to massive intracranial hemorrhage. The second patient presented with severe abdominal pain and pancreatitis, followed by atypical skin eruptions, which prompted a faster diagnosis. Both patients recovered from their HLH, the first patient being successfully treated with immunosuppressive agents and the second with VZV treatment only. These two cases demonstrate the difficulties in recognizing VZV reactivation, and in order to start adequate and timely treatment, the need to consider VZV as a possible cause of HLH in severely immunocompromised patients.

Topics: Acyclovir; Adolescent; Antiviral Agents; Graft vs Host Disease; Herpes Zoster; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lymphohistiocytosis, Hemophagocytic; Male

To assess the etiology, prognosis, and appropriate treatment of hemophagocytic lymphohistiocytosis (HLH) in neonates.. We collected information on neonates in whom HLH was diagnosed between 1997 and 2007 from participating members of the Japanese Society of Pediatric Hematology.. HLH was diagnosed in 20 patients within 4 weeks after birth. Of the diagnostic criteria for HLH-2004, the incidence of fever was quite low in preterm infants, and hypertriglyceridemia and neutropenia were uncommon. Familial HLH (n = 6) or severe combined immunodeficiency-associated HLH (n = 1) was diagnosed in 7 patients, and 2 of them have survived. Herpes simplex virus-associated HLH was diagnosed in 6 patients, and 2 of them have survived. The overall survival rate for the 20 patients was 40%.. HLH is rare in neonates and has a poor prognosis. Early diagnosis and immediate treatment are required when considering the possibility of herpes simplex virus-associated or familial HLH.

Topics: Acyclovir; Adrenal Cortex Hormones; Antineoplastic Agents, Phytogenic; Antiviral Agents; beta 2-Microglobulin; Consciousness Disorders; Cyclosporine; Erythema; Etoposide; Exanthema; Female; Fetal Distress; Fever; gamma-Globulins; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunologic Factors; Immunosuppressive Agents; Infant, Newborn; Infant, Premature; Japan; L-Lactate Dehydrogenase; Leukocytosis; Lymphohistiocytosis, Hemophagocytic; Male; Ocular Motility Disorders; Plasma Exchange; Prognosis; Respiratory Distress Syndrome, Newborn; Seizures; Severe Combined Immunodeficiency

Neonatal disseminated herpes simplex virus (HSV) infection with acute liver failure (ALF) and neonatal hemophagocytic lymphohistiocytosis (HLH) are severe diseases. We recently experienced a male infant with HLH and ALF induced by HSV type 1 (HSV-1). The infant, born at 39 weeks of gestation by normal delivery, developed a fever on day 4. On day 9, laboratory investigations showed progressive liver dysfunction and coagulopathy, and the serum ferritin was excessively elevated. Furthermore, the blood levels of interleukin (IL)-6, IL-10, and interferon-gamma were also elevated. HSV-1 DNA was detected in the serum and cerebrospinal fluid by the real-time PCR method. A diagnosis of HLH was established based upon the following criteria: fever, splenomegaly, cytopenia (two cell lines), serum ferritin (> 500 mug/l) and hypofibrinogenemia (< 150 mg/dl). High-dose acyclovir therapy, steroid pulse therapy using methylprednisolone, high-dose gamma globulin therapy and a blood transfusion were given. The patient recovered without neurological deficit. Neonatal disseminated HSV infections may be complicated by the development of HLH and hypercyokinemia. If HLH is suspected, not only high-dose acyclovir therapy but also anti-cytokine therapy should be considered.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Blood Transfusion; Coma; Cytokines; DNA, Viral; gamma-Globulins; Glasgow Coma Scale; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Liver Failure, Acute; Liver Function Tests; Lymphohistiocytosis, Hemophagocytic; Male; Methylprednisolone

Topics: Acyclovir; Adolescent; Antiviral Agents; Aspergillosis; Azathioprine; Brain; Chickenpox; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Lung; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Meninges; Multiple Organ Failure; Myocardium; Opportunistic Infections; Prednisolone

A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT) during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23). Tacrolimus was given for prophylaxis of graft-versus-host disease. The posttransplantation clinical course was mostly uneventful, and the leukemia remained in remission. Fourteen months after CBT, the patient developed pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone marrow was hypocellular with increased numbers of macrophages and hemophagocytes. The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were remarkably high. Although the patient showed complete donor-type hematopoiesis, the titer of viral capsid antigen immunoglobulin G was low, and the results of a test for EBV nuclear antigen were negative. There was no clinical response to the reduction of immunosuppressive therapy or to the administration of high-dose methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic failures. This case demonstrates that fatal EBV-associated hemophagocytic syndrome (HPS) can occur more than 1 year after CBT. This report is the first of a case of late-onset EBV-associated HPS following CBT.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antibodies, Viral; Antiviral Agents; Bone Marrow Diseases; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Hematopoiesis; Hemorrhage; Herpesvirus 4, Human; Humans; Immunoglobulin G; Liver Failure; Lymphohistiocytosis, Hemophagocytic; Methylprednisolone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Transplantation Chimera