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...
 HHV lifetime infection
 ubiquitous
 reactivation
 HHV-7 and HHV-6
reactivation associated
with pityriasis rosea
(Drag...
 Drug Reaction Eosinophilia
and Systemic side effect
Syndrome (DRESS)
 HHV 6 reactivation
(Deschamps 2001)
 exanthema,h...
Ascend Media Healthcare
 Highest prevalence in over 50 year olds
 Self limiting
 Normally one episode
 Association with HCV (Mokni 1991)
• The...
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 (pathol...
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%)
Pso...
Immunohistochemical detection viral protein (HHV-7)
 tegument protein pp85 (Advanced Biotechnologies)
 positive cells/mm...
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...
HHV-7/BDCA-2 double staining HHV-7/CD-3 double staining
lesional lichen planus lesional lichen planus
de Vries et al. Arch...
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 re...
 HHV-7 (subclinical) primo
infection during childhood
 HHV-7 reactivation in adult
life
 replication in basal
keratinoc...
 viral “innocent bystander”
 Koch’s postulates
 geographic variation in viral distribution
 differences in laboratory ...
 Jan van Marle
• electronmicroscopy
 Jan Weel
• virology
 Fokla Zorgdrager and Marion Cornelissen
• molecular biology
...
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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

  1. 1. Henry J.C. de Vries Dermatology Academic Medical Centre University of Amsterdam The Netherlands
  2. 2.  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)
  3. 3.  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?
  4. 4.  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
  5. 5. Ascend Media Healthcare
  6. 6.  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)
  7. 7. Electron microscopy of lichen planus lesional skin lichen planus lichen planus lichen planus reference herpes virus
  8. 8.  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)
  9. 9. 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%) * 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.
  10. 10. Immunohistochemical detection viral protein (HHV-7)  tegument protein pp85 (Advanced Biotechnologies)  positive cells/mm2  (non) lesional lichen planus, psoriasis, normal skin lesional skin non-lesional skin de Vries et al. Br J Dermatol 154: 361, 2006
  11. 11. psoriasis lesional lichen planus normal skin non lesional lichen planus de Vries et al. Br J Dermatol 154: 361, 2006 -
  12. 12. lesional skin non-lesional skin CD123 positive cells(red), endothelial cells (blue) de Vries et al. Br J Dermatol 154: 361, 2006
  13. 13. 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
  14. 14. before treatment after remission de Vries et al. Arch Dermatol Res 299: 213, 2007
  15. 15.  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
  16. 16.  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
  17. 17.  viral “innocent bystander”  Koch’s postulates  geographic variation in viral distribution  differences in laboratory protocols  virus-virus interactions  association with skin diseases?  or candidates in search of a disease?
  18. 18.  Jan van Marle • electronmicroscopy  Jan Weel • virology  Fokla Zorgdrager and Marion Cornelissen • molecular biology  Daisy Picavet and Marcel Teunissen • immunohistochemistry

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