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What is new on HHV 6,7,8 infections?, Henry J.C. de Vries






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What is new on HHV 6,7,8 infections?, Henry J.C. de Vries What is new on HHV 6,7,8 infections?, Henry J.C. de Vries Presentation Transcript

  • Henry J.C. de Vries Dermatology Academic Medical Centre University of Amsterdam The Netherlands
    • Until 1986, 5 herpes viruses
    • new human herpes viruses (HHV)
    • HHV-6 and -7
      • both members of the Roseolovirus genus of the β-herpesviruses.
      • T-lymphotropic but can infect other cell types
      • primary infections are associated with roseola infantum (a.k.a. exanthem subitum or 6th disease)
    • HHV lifetime infection
    • ubiquitous
    • reactivation
    • HHV-7 and HHV-6 reactivation associated with pityriasis rosea (Drago, 1997 and Yasukawa, 1999)
    • Debated
      • Innocent bystander?
      • Multiple agents?
    • Drug Reaction Eosinophilia and Systemic side effect Syndrome (DRESS)
    • HHV 6 reactivation (Deschamps 2001)
    • exanthema,hepatitis, colitis lymphadenopathy, eosinophilia, fever
    • EBV and amoxicillin associated drug rash in mononucleosis infectiosa
    C Goldberg, UCSD and Ascend Media Healthcare
  • Ascend Media Healthcare
    • Highest prevalence in over 50 year olds
    • Self limiting
    • Normally one episode
    • Association with HCV (Mokni 1991)
      • The epidemiological association is not strong (Imhof, 1997)
  • Electron microscopy of lichen planus lesional skin lichen planus lichen planus lichen planus reference herpes virus
    • Objective :
      • To find candidate herpes viruses associated with lichen planus.
    • Methods :
      • Lichen planus patients (pathologically confirmed, n=18)
      • Intra patient comparison of skin biopsies:
        • lesional vs. non-lesional
        • before vs. after remission
      • Inter patient comparison of skin biopsies:
        • psoriasis patients (lesional, n=11, and non-lesional, n=3)
        • normal skin (redundant after breast reduction, n=4)
      • DNA of HSV1 and 2, VZV, CMV, EBV (commercial PCR )
      • DNA of HHV 6, -7 and -8 (“in house” nested PCR)
  • * p=0,06, # p=0,05 p values calculated with McNemar test
    • All samples were free of HSV-1, HSV-2, VZV, CMV and HHV-8 DNA.
    • EBV DNA was detected in 2/15 lichen planus lesional samples.
    HHV7 HHV6 Lichen planus lesional non-lesional PBMC 11/18 (61%)* ,# 1/11 (9%)* 5/13 (38%) 0/18 (0%) 0/11 (0%) 2/13 (15%) Psoriasis lesional non-lesional 2/11 (18%) # 0/3 (0%) 1/11 (9%) 0/3 (0%) Normal skin 0/4 (0%) 0/4 (0%)
    • Immunohistochemical detection viral protein (HHV-7)
    • tegument protein pp85 (Advanced Biotechnologies)
    • positive cells/mm 2
    • (non) lesional lichen planus, psoriasis, normal skin
    lesional skin non-lesional skin de Vries et al. Br J Dermatol 154: 361, 2006
  • psoriasis lesional lichen planus normal skin non lesional lichen planus de Vries et al. Br J Dermatol 154: 361, 2006 -
  • lesional skin non-lesional skin CD123 positive cells(red), endothelial cells (blue) de Vries et al. Br J Dermatol 154: 361, 2006
  • HHV-7/BDCA-2 double staining HHV-7/CD-3 double staining lesional lichen planus lesional lichen planus de Vries et al. Arch Dermatol Res 299: 213, 2007
  • before treatment after remission de Vries et al. Arch Dermatol Res 299: 213, 2007
    • herpes virus like particles reside in lesional lichen planus skin
    • not HSV1, HSV2, CMV, VZV, HHV6 or HHV8 DNA
    • HHV-7 replicates in lesional lichen planus,
    • not in non-lesional lichen planus, psoriatic or normal skin
    • HHV-7 replicates in plasmacytoid dendritic cells
    • HHV-7 replication in lichen planus stops after remission
    • HHV-7 (subclinical) primo infection during childhood
    • HHV-7 reactivation in adult life
    • replication in basal keratinocytes/dermal lymphocytes
    • presentation (plasmacytoid) dendritic cells
    • inflammatory T lymphocytic response
    • destruction of the basal layer
    Skin Immune System, Bos JD ed. 3rd edition, 2005
    • viral “innocent bystander”
    • Koch’s postulates
    • g eographic variation in viral distribution
    • differences in laboratory protocols
    • virus-virus interactions
    • association with skin diseases?
    • or candidates in search of a disease?
    • Jan van Marle
      • electronmicroscopy
    • Jan Weel
      • virology
    • Fokla Zorgdrager and Marion Cornelissen
      • molecular biology
    • Daisy Picavet and Marcel Teunissen
      • immunohistochemistry