Cytomegalovirus Lymphadenitis



Cytomegalovirus Lymphadenitis


Sa A. Wang, MD










CMV lymphadenitis. This field shows that the sinus is expanded by monocytoid B cells between 2 large, reactive follicles (left and right).






The high-power view of CMV lymphadenitis shows a large cell infected by CMV, which has a prominent intranuclear inclusion surrounded by a halo and multiple, small cytoplasmic inclusions.


TERMINOLOGY


Abbreviations



  • Cytomegalovirus (CMV)


Definitions



  • Lymphadenitis caused by CMV infection


ETIOLOGY/PATHOGENESIS


CMV



  • Member of β-herpes virus family



    • Double-stranded DNA virus with 162 hexagonal protein capsomeres surrounded by lipid membrane


  • Lytic virus that causes cytopathic effect in vitro and in vivo


  • Productive (lytic) infection leads to synthesis of immediate-early, early, and late viral proteins


  • Viral DNA has been detected in monocytes, dendritic cells, megakaryocytes, and myeloid progenitor cells in bone marrow


  • Virus infects T cells but not B cells


  • Monocytes and endothelial cells are also commonly infected by CMV


  • Can be transmitted by a number of means



    • Person-to person via saliva, respiratory secretions, or sexual fluids


    • Blood transfusions


    • Transplacental passage


  • Immunology



    • Body produces neutralizing antibodies upon primary infection


    • Cell-mediated immunity is most important factor in controlling CMV infection


CMV Infection in Immunocompetent Host



  • Mostly primary infection


CMV Infection in Immunocompromised Patients



  • Reactivation of CMV, either iatrogenic or secondary to underlying medical conditions



    • Solid organ or bone marrow transplantation


    • Acquired immunodeficiency syndrome (AIDS)


CMV Infection in Pregnancy



  • Maternal primary CMV infection


  • In utero transmission of CMV, either due to primary CMV infection or reactivation



    • Can be lethal with damage to central nervous system (CNS)


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Infection with CMV is common as determined by presence of serum antibodies



      • In developed countries, 60-80% of population is infected by adulthood


      • In developing countries, most children are infected by 3 years of age


      • > 90% of homosexual men are infected by CMV


    • Age, geography, cultural and socioeconomic status, and child rearing practices affect prevalence


  • Age



    • Congenital



      • 1% of newborns are infected by CMV


    • Perinatal infection due to



      • Maternal cervicovaginal secretions during delivery


      • Breast feeding


    • Daycare toddlers



      • Horizontal transmission of virus to both children and adult daycare center workers


    • Adolescence



      • Sexual transmission



    • Immunocompromised patients, all ages


    • Blood or tissue exposure, all ages


  • Gender



    • No sex preference


  • Ethnicity



    • No preferences


Presentation



  • Immunocompetent patients



    • Asymptomatic or flu-like syndrome


    • Symptoms similar to infectious mononucleosis-type syndrome, but milder



      • Fever of unknown origin


      • Lymphadenopathy, often cervical


      • Pharyngitis


      • Hepatosplenomegaly


      • Blood: Lymphocytosis with atypical lymphocytes


    • CMV reactivation is common in critically ill immunocompetent patients



      • Can be associated with prolonged hospitalization


  • Immunocompromised patients



    • Organ transplant recipients and patients with immunodeficiency syndromes


    • Interstitial pneumonitis



      • Respiratory symptoms, fever, and dyspnea


      • Can be life-threatening


    • Gastrointestinal infection



      • Esophagus: Dysphagia


      • Upper gastrointestinal tract: Ulcer


      • Colon: Bloody diarrhea, fever, and abdominal pain


    • CMV retinitis



      • Frequent in HIV patients with a CD4 count < 50 cells/µL


      • Decreased/impaired visual acuity, floaters, and loss of visual fields on 1 side


      • Can progress to bilateral involvement if untreated


    • Neurologic manifestations



      • CMV encephalitis


      • Guillain-Barré syndrome


      • Other peripheral neuropathies


    • CMV hepatitis



      • Often subclinical


      • Unexplained fever


      • Abnormal liver function tests


      • Portal vein thrombosis (rare)


    • Pericarditis and myocarditis


    • Myeloradiculopathy


    • Disseminated CMV infection is criterion for AIDS


  • Congenital infection



    • At birth



      • Small size for gestational age


      • Hepatosplenomegaly


      • Petechiae and purpura of the skin, jaundice


      • Neurologic involvement: Microcephaly, seizures, and feeding difficulties


    • Sequelae in children



      • Sensorineural hearing loss


      • Chorioretinitis


      • Microcephaly, seizures, or paresis/paralysis


      • Mental retardation


Laboratory Tests



  • Serology



    • Recent and acute CMV infection



      • Detection of CMV-specific IgM antibodies


      • At least 4x increase in CMV-specific IgG titers in specimens obtained at least 2-4 weeks apart


    • To determine past exposure to CMV infection



      • If positive for past infection, monitor those at risk for CMV reactivation syndromes


      • If negative for past infection, monitor for new infection if transplanted with CMV seropositive organ


  • Early antigen detection (shell vial cultures)



    • Methods



      • Centrifugation of clinical samples (e.g., urine, blood) to increase absorption of virus


      • Infected cell monolayers incubated with monoclonal antibodies specific for CMV


    • Results typically available within 2-3 days



      • Accelerates time to diagnosis


  • CMV antigenemia assays



    • Methods




      • Using monoclonal antibodies specific to pp65 lower matrix protein of CMV to detect CMVinfected leukocytes in peripheral blood


      • Results are reported as number of cells with staining per total number of cells counted


    • Advantage



      • Results generally available within 24 hours


      • Antigenemia appears to correlate with viremia


  • Molecular methods for detecting CMV



    • Hybrid Capture System CMV DNA test



      • Signal amplification method using RNA probe that targets CMV


    • COBAS Amplicor test



      • PCR assay that amplifies 365 base pair region of CMV polymerase gene


    • Nucleic acid sequence-based amplification (NASBA)



      • Detects both immediate-early gene UL123 (IE1) and late gene expression (pp67)


    • Utility



      • Sensitive and specific for organ transplant patients


      • Not sensitive in detecting acute CMV infection


  • Other laboratory findings



    • Heterophile antibody is negative


    • Hematologic findings: Absolute lymphocytosis and atypical lymphocytes



      • CD4:CD8 ratio reversed


      • Increased large granular lymphocytes, NK cells


  • Viral cultures



    • CMV grows slowly in cell culture



      • Not a rapid confirmatory test


    • Positive result does not confirm active CMV disease


    • Limited sensitivity


Treatment

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cytomegalovirus Lymphadenitis
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