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)

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.

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 skinde Vries et al. Br J Dermatol 154: 361, 2006

psoriasis lesional lichen planusnormal 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 geographic 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