Introduction 4 14 13 5 16 18 1 Materials and methods 5 17 5 12 5 11 2 P Results 1 Table 1 Treatment characteristics and HHV-7 data before treatment and after remission Patient Disease duration (months) Treatment modality Treatment duration (days) Biopsy site Relapse interval (months) Before treatment After remission HHV-7 positive epidermal cells HHV-7 positive dermal cells  BDCA2 positive cells HHV-7/BDCA2 double positive cells HHV-7 PCR HHV-7 positive epidermal cells HHV-7 positive dermal cells BDCA2 positive cells HHV-7/BDCA2 double positive cells HHV7 PCR Pathology 1 12 Prednisone 66 Lower leg 5 5,1 24,7   Positive 8,8 8,8   Negative Normal 2 2 Prednisone 169 Lower leg 13 5,7 89,2   Positive 6,2 11,1   Negative Normal 3 12 Prednisone 139 Lower leg None 4,7 11,7 118,7 38,7 Positive 3,3 45,3 65 11 Negative Normal 4 5 Prednisone 72 Lower leg 1 6,7 53   Positive NA NA   NA NA 5 6 Prednisone 64 Foot 6 2,4 29,4   Negative 4,7 20,5   Negative Inflam 6 1 Topical NA Foot NA 53,8 82,9 28 13,3 Positive NA NA NA NA NA NA 7 6 PUVA 96 Lower leg None 22,3 39   Negative 2,3 5,9   Negative Inflam 8 1 Prednisone 75 Foot 43 16,9 67   Positive 1,8 5,3   Negative Normal 9 4 Topical 200 Lower leg None 9,6 23 69,7 35,3 Positive 2,9 6 38 12,3 Negative Normal 10 2 Prednisone 205 Wrist 7 16 115,9   Negative 3,2 26,9   Negative Inflam 11 2 Prednisone NA Lower leg NA 12 34,9   Positive NA NA   NA NA 12 2 Acitretin NA Flank None 7,4 38,6   Positive NA NA   NA NA 13 7 Prednisone 95 Back 5 13,4 66,1 187 48 Positive 4 17,7 42 6,7 Negative Normal 14 7 Prednisone 247 Lower leg 44 9 42,8   Negative 2,4 15,5   Negative Normal 15 6 Prednisone 131 Foot 1 4,19 79,5   Negative 2 4,7   Positive Normal 16 2 Prednisone NA Back None 7,4 35,6   Negative NA NA   NA NA 17 3 Prednisone 154 Foot None 19,3 119,3   Positive 0,8 2,5   Negative Inflam 18 4 Prednisone 187 Foot None 13,1 106,8 32,7 5,7 Negative 0,8 3,2 22 4,3 Negative Normal 2 NA  During follow up (with a minimum period of 30 months) 9 out of 16 patients experienced a relapse of lichen planus symptoms, 6 patients within 1 year, 3 within 4 years. All relapses occurred in patients treated with oral prednisone. In 2 patients with relapses, remnant inflammation after remission had been noticed. P 2 1 P t  Fig. 1 2 white bars black bars P  2 1 3 Fig. 2 blue stain red stain a b  Fig. 3 red stain blue stain  Discussion Lichen planus is characterized by a band-like lymphocytic infiltrate, which seems to be involved in an attack of the basal epidermal layer. It is suggested that these T lymphocytes are directed towards infected skin cells expressing viral antigens. Molecular mimicry is a second conceivable inflammatory mechanism initiated by microbial antigens or microbial-reactive T lymphocytes that cross react with self antigens sharing homology (i.e., basal layer structures). 5 10 15 21 Here we investigated the effect of therapy-induced remission of lichen planus on HHV-7 replication. Both the number of HHV-7 DNA containing skin samples and the absolute number of HHV-7 antigen containing skin cells (in dermis and epidermis) diminished significantly after treatment-induced remission. Since we included a 2-week washout period between treatment termination and obtaining the post remission biopsies, a direct medication effect on viral replication is unlikely. In contrast to a fourfold diminution in HHV-7 positive cells after treatment, there was only a twofold reduction in the number of BDCA2 positive plasmacytoid dendritic cells. This makes it unlikely that the diminished HHV-7 expression only depends on a reduced number of plasmacytoid dendritic cells after treatment. Whether plasmacytoid dendritic cells are carriers of HHV-7 driving the disease activity or that these cells are infected as innocent bystanders, or actively induce the inflammatory process is not yet clear and needs further study. 10 1 3 7 2 19 6 It is unlikely that HHV-7 primary infections cause lichen planus, since first transmission mostly occurs during childhood, whereas lichen planus affects mainly patients during midlife. Yet, it is conceivable that HHV-7 reactivation triggers lichen planus, in the same fashion as Epstein-Barr virus reactivation is associated with Burkitt lymphoma. The apparent paradoxical efficacy of steroid therapy in lichen planus and a considered viral cause can be explained by a “hit and run” model where the actual viral reactivation would be short lived but subsequently responsible for an independently propagated inflammatory skin reaction. This could also explain why not in all patients HHV-7 was detected at the time of inclusion. Moreover, in one patient (no. 15) HHV-7 DNA was detected after remission. It is this patient that experienced a relapse 1 month later and returned to the clinic for additional treatment. Possibly HHV-7 can trigger lichen planus episodes, including relapses, but resolve before clinical lichen planus symptoms appear. The other patient (no. 4) with a relapse within 1 month unfortunately refused us a post remission skin sample. On the other hand, the absence of HHV-7 replication in some of our patients could also be explained assuming a multi causal pathogenesis for lichen planus. 8 20 9 5