Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6

Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.     

The detection of human herpesvirus-8 DNA in plasma and peripheral blood mononuclear cells in adult patients with pityriasis rosea by polymerase chain reaction

BACKGROUND: Herpesvirus-like particles have been reported to be detectable by electron microscopy in lesional biopsy of patients with pityriasis rosea (PR). We report a study investigating the association of PR with human herpesvirus-8 (HHV-8) infection. METHODS: Our setting is a teaching clinic affiliated to a university. We recruited eight patients aged 28-47 years (mean: 34.5 years) diagnosed with PR during a one-year period. We collected acute blood specimens at presentation and convalescent blood specimens three to four weeks later. We also collected skin scrapings from the herald patch where present and from truncal secondary lesions. RESULTS: We detected HHV-8 DNA by a nested PCR (polymerase chain reaction) targeting, respectively, a 233-bp and a 160-bp fragment of ORF 26. PCR for HHV-8 DNA was negative in the peripheral blood mononuclear cells and plasma of acute and convalescent specimens of all patients, and negative in all skin scrapings. We detected anti-HHV-8 IgG and IgM antibodies by the indirect immunofluorescence. Four patients had IgG antibodies against HHV-8, but with no significant rise of titre. None were positive for anti-HHV-8 IgM antibody. CONCLUSION: We conclude that PR is not associated with HHV-8 infection.     

玫瑰糠疹与人类疱疹病毒-7型关系的研究

目的探讨玫瑰糠疹(PR)与人类疱疹病毒-7型(HHV-7)的关系。方法采用巢式PCR检测了22例PR急性期患者的血浆、外周血单核细胞(PBMC)、皮损、唾液、尿液,14例恢复期患者的唾液、血浆、外周血单核细胞,14例正常人的唾液、血浆、外周血单核细胞中的HHV-7特异性序列。结果急性期唾液与单核细胞中HHV-7DNA检出率(95.5%,45.4%)明显高于正常人(64.3%,21.4%),唾液中HHV-7DNA检出率亦明显高于恢复期(57.1%),但单核细胞中HHV-7DNA检出率与恢复期(28.6%)无明显差异。8例皮损组织(36.4%)检测到HHV-7DNA。1例血浆中检测到HHV-7DNA(4.54%),其外周血单核细胞、皮损、唾液中亦均检测到HHV-7DNA,其恢复期唾液、单核细胞中HHV-7DNA仍可检测到。恢复期HHV-7DNA在唾液和单核细胞中的检出率与正常人无明显差别。结论有一部分玫瑰糠疹的发生可能与潜伏的HHV-7活化感染有关。     

Pityriasis rosea is not associated with human herpesvirus 7.

OBJECTIVE: To examine the proposed association between pityriasis rosea and human herpesvirus 7 (HHV-7). DESIGN: A retrospective cross-sectional survey. SETTING: University medical center in Switzerland. PATIENTS: Thirteen patients with pityriasis rosea and 14 persons with normal skin (control subjects). MAIN OUTCOME MEASURES: Detection of HHV-7-specific DNA sequences and antigen (85-kd phosphoprotein [pp85]) by nested polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Human herpesvirus 7 DNA sequences and expression of the HHV-7-specific immunodominant pp85 antigen were found in 1 (8%) of 13 lesional skin biopsy specimens of pityriasis rosea. The prevalence of HHV-7 DNA sequences and antigens is even slightly lower in lesional skin of patients with pityriasis rosea than in clinically and morphologically normal skin of 14 control persons, in 2 of whom (14%) HHV-7 DNA sequences and antigens could be detected. CONCLUSION: The low detection rate of HHV-7 DNA sequences and antigens argues strongly against a causative role for HHV-7 in the pathogenesis of pityriasis rosea.     

Pemphigus vulgaris and herpesviruses: is there any relationship?

Background Pemphigus is an autoimmune disorder, which results from interaction of exogenous and endogenous factors. One of these environmental factors is viral infections particularly, herpesviruses. We aimed to detect the presence of HSV 1 and 2 (herpes simplex virus) and HHV8 (human herpesvirus 8) in our patients who were suffering from pemphigus vulgaris. Methods In this cross‐sectional study, 38 patients (19 male and 19 female patients) with pemphigus vulgaris were entered, 32 skins and six peripheral blood cells samples were obtained from the study population. Thereafter, the presence of HHV8 and HSV DNA were evaluated by using polymerase chain reaction (PCR). Results The mean age of patients was 45.05 ± 17.24 years (range: 16–81 years). Twelve patients mentioned history of herpes labial in the past (31.57%). Results of PCR test for detection of HSV and HHV8 DNA in all 32 skin samples and five peripheral blood samples and one case with skin and blood samples were reported negative. Conclusion Inability to detect HHV8 and HSV DNA in this study suggests that herpesviruses may be only occasional factors for development or exacerbation of pemphigus vulgaris.     

寻常型银屑病与单纯疱疹病毒1型相关性的研究

目的 探讨寻常型银屑病与单纯疱疹病毒1型(HSV-1)的可能相关性。方法 应用PCR法检测患者皮损、外周血单一核细胞(PBMCs)和咽拭子中HSV-1DNA,ELISA法检测患者血清中抗HSV-1的IgM、IgG抗体,并与正常人对照做比较。结果 患者皮损、PBMCs和咽拭子中HSV-1DNA检出率分别为37.5%、18.6%和18.8%,血清中抗HSV-1的IgM、IgG抗体检出率分别为37.2%和53.5%.经χ²检验,患者皮损、PBMCs中HSV-1DNA和血清中IgM抗体检出率显着高于正常人对照,点滴状患者的皮损、PBMCs和咽拭子中HSV-1DNA以及血清中抗HSV-1IgM抗体检出率显着高于斑块状患者。结论 寻常型银屑病尤其是皮损呈点滴状者与HSV-1显着相关,患者可能存在HSV-1的近期感染。     

Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disorder that is suspected to have an infectious aetiology. OBJECTIVES: We aimed to study the role of human herpesvirus (HHV)-7 and HHV-6 in the pathogenesis of PR. METHODS: We performed seroepidemiological studies (indirect immunofluorescence test) and polymerase chain reaction (PCR) analysis for HHV-6 and HHV-7 in patients with PR. Seventy-two serum samples and 37 samples of peripheral blood mononuclear cells (PBMC) from 44 patients with PR were obtained. Twenty-five patients with other skin disorders such as drug eruption, urticaria or herpes zoster were studied as controls in the PCR analysis. RESULTS: HHV-7 DNA was detected in 13 of 30 (43%) samples of PBMC of the patients with PR and 14 of 25 (56%) samples of PBMC of controls. HHV-6 DNA was detected in six of 29 (21%) patients with PR and nine of 23 (39%) controls. Thus there was no difference in the prevalence of HHV-6 or HHV-7 in PBMC between patients with PR and those with other skin disorders. In the seroepidemiological study, two cases of at least a fourfold rise in titre and five cases of a fourfold decrease in titre to HHV-7 antibody, and two cases of a fourfold rise in titre and two cases of a fourfold decrease in titre to HHV-6 antibody, were observed in 24 patients with PR. This seroepidemiological study revealed antibody responses consistent with active infection in several PR patients, but the greater proportion of the patients had no definite increase in the antibody titres. CONCLUSIONS: We conclude that HHV-7 and HHV-6 may play a part in some patients with PR, but that other causative agents may exist. Further analyses are needed to determine the causative agents of PR.     

CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM)

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.     

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): a viral disease with an autoimmune component

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.     

Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme

The association between infection with HSV and the subsequent, development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes-associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus-specific. In the current, prospective study, we examined biopsies of lesional, non-involved, and previously involved but healed skin, in addition lo specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non-involved skin biopsies obtained at the same time. I ISV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of pal inns with HAEM appears lo be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hemalogenous spread of viral DNA may bean important factor in the development of HAEM.     

蕈样肉芽肿皮损及外周血人类疱疹病毒1、2、4、5型DNA的检测

目的　探讨蕈样肉芽肿与人类疱疹病毒 1型 (单纯疱疹病毒 1型 )、2型 (单纯疱疹病毒 2型 )、4型 (ep stein barr病毒 )、5型 (人类巨细胞病毒 )间有无相关性。方法　酚 氯仿法提取皮肤组织 (蕈样肉芽肿 3 2份、正常皮肤 2 9份、慢性湿疹与慢性单纯性苔藓 2 4份 )及外周血白细胞 (蕈样肉芽肿 15份、健康献血员 40份、慢性湿疹与慢性单纯性苔藓 11份 )中基因组DNA。采用聚合酶链反应技术检测病毒DNA ,扩增产物回收后以限制性内切酶BamHⅠ、SmaⅠ酶切鉴定。结果　蕈样肉芽肿皮损及外周血中 ,各有 2份检测到人类疱疹病毒 1型DNA ;蕈样肉芽肿皮损中有 5份存在人类疱疹病毒 4型DNA ;健康献血员外周血以及正常皮肤、慢性湿疹与慢性单纯性苔藓患者皮损组织及外周血中未检测到此4种病毒DNA。结论　蕈样肉芽肿与人类疱疹病毒 1、2、4、5型间可能不具有相关性。     

Longitudinal study of a patient with herpes-simplex-virus-associated erythema multiforme: viral gene expression and T cell repertoire usage.

BACKGROUND: Erythema multiforme is a polymorphous self-limited, often recurrent eruption that can follow herpes simplex virus (HSV) infection, hereby designated HAEM. Studies of relatively large groups of patients during one recurrent episode indicated that HAEM pathogenesis is associated with HSV gene expression, Vbeta2 T cell infiltration of lesional skin and altered T cell receptor (TCR) repertoire usage by HSV-stimulated peripheral blood mononuclear cells (PBMC). However, HAEM recurrences are not always preceded by overt HSV eruptions and virus cannot be isolated from HAEM lesional skin. Therefore, it is unknown whether all HAEM recurrences experienced by a given patient are HSV related. OBJECTIVE: The studies described in this report were designed to examine whether all HAEM recurrences experienced by a given patient are HSV related. METHODS: We describe one patient who was studied longitudinally during 6 HAEM recurrences and in the intervening lesion-free periods. Lesional skin from all HAEM episodes was studied for HSV gene expression and infiltration by Vbeta2 and Vbeta3 T cells. PBMC obtained at these times were assayed for TCR repertoire usage upon HSV stimulation. RESULTS: Lesional skin from all HAEM episodes was positive for HSV gene expression (RNA and protein) as well as Vbeta2 T cell infiltration. HSV-stimulated PBMC obtained at these times had an altered TCR repertoire characterized by a predominance of Vbeta2 cells. The duration of viral gene expression, Vbeta2 cell infiltration and altered TCR repertoire usage correlated with the duration of clinical symptoms. CONCLUSION: The data suggest that HSV and a virus-specific immunopathology component are involved in the causation of all HAEM episodes experienced by the patient.     

Erythema multiforme lesions are associated with expression of a herpes simplex virus (HSV) gene and qualitative alterations in the HSV-specific T-cell response

A common form of erythema multiforme, herpes-associated erythema multiforme (HAEM), occurs following infection with herpes simplex virus (HSV). Here we report that HSV gene expression and the qualitative nature of the virus-specific T-cell responses are related to HAEM lesion development. Skin from HAEM lesions and 1–3 months healed HAEM lesional skin were positive for the viral DNA polymerase gene (Pol) by polymerase chain reaction. However, gene expression as determined by immunohistochemistry with Pol-specific antibody was seen only in HAEM lesions, suggesting that lesion development is associated with Pol gene expression. Similar HSV-specific T-cell lymphoproliferative responses were seen in peripheral blood mononuclear cells (PBMCs) from patients with acute or healed HAEM lesions or HSV lesions and from HSV-seropositive patients with unrelated inflammatory diseases. However, the T-cell receptor variable (Vβ ) chain repertoire of HSV-stimulated PBMCs obtained from HAEM lesions was altered; the prevalence of some families of variable chain (namely Vβ16 and Vβ19) was reduced, whereas the prevalence of others was increased (namely Vβ2 and Vβ7). Vβ2 cells were found in HAEM lesional skin positive for Pol antigen, suggesting that these cells home to viral antigen-positive skin.     

Clinical utility of loop‐mediated isothermal amplification assay for the diagnosis of common alpha herpesvirus skin infections

Loop‐mediated isothermal amplification (LAMP) is a nucleic acid amplification method with a high specificity, efficiency and speed. No reports exist regarding the usefulness of LAMP for clinically suspected skin infections caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The aim of this study was to evaluate the clinical usefulness of LAMP in the diagnosis of common cutaneous alpha herpesvirus (HSV type 1 and 2, and VZV) infections. LAMP and real‐time polymerase chain reaction (PCR) were performed using swab samples collected from 106 patients with clinically suspected alpha herpesvirus skin infections. The results of LAMP performed with DNA extraction did not differ from those performed without DNA extraction. The sensitivity of LAMP tested against real‐time PCR was 96% in herpes simplex, 78% in eczema herpeticum, 93% in herpes zoster and 100% in varicella. No viral DNA was detected by LAMP in all negative real‐time PCR samples. Viral DNA load was significantly lower in samples with false‐negative LAMP results than in the LAMP‐positive samples. LAMP enables confirmation of clinically suspected cutaneous HSV and VZV infections. However, the sensitivity of LAMP is lower than real‐time PCR. The accuracy of LAMP may increase if sufficient viral DNA is obtained from lesions. LAMP performed without DNA extraction remains sensitive; thus, LAMP represents a quick and economical method for the diagnosis of common alpha herpesvirus skin infections.     

Detection of cutaneous herpes simplex virus infections by immunofluorescence vs. PCR

BACKGROUND: Detection of cutaneous infections with herpes simplex virus (HSV) has proven difficult, as serum antibody tests sometimes are not sensitive and specific enough for that purpose. OBJECTIVE: This study was conducted to compare the sensitivity for detection of HSV of an immunofluorescence method (Syva Microtrak) and an internally controlled PCR. METHODS: Cutaneous swabs from skin lesions were analysed by immunofluorescence separately for HSV types 1 and 2 and by competitive PCR. Detection of PCR products was done by ELISA, if positive additionally by agarose gel electrophoresis. RESULTS: Of 79 samples 34 were PCR-positive by ELISA (34 = 100%), of which 23 (68%) were also positive on the agarose gel. Eleven samples (32%) were positive by immunofluorescence. No sample was positive by immunofluorescence and negative by PCR. CONCLUSIONS: These results demonstrate that immunofluorescence using Syva Microtrak is not suitable for exclusion of herpes simplex virus infection as sensitivity was only 32%. However, as immunofluorescence is cheaper and faster than PCR, first screening can be done with immunofluorescence, and negative samples can be investigated by PCR to finally prove or exclude the presence of HSV DNA.     

Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7

To elucidate the role of human herpesvirus (HHV)-6 and -7 (HHV-7) in pityriasis rosea (PR), we measured their DNA load in plasma, peripheral blood mononuclear cells (PBMC), and tissues using a calibrated quantitative real-time PCR assay. We also studied HHV-6- and HHV-7-specific antigens in skin by immunohistochemistry and anti-HHV-7 neutralizing activity using a syncytia-inhibition test. Plasma and PBMC were obtained from 31 PR patients (14 children, 17 adults), 12 patients with other dermatites, and 36 blood donors. Skin biopsies were obtained from 15 adults with PR and 12 with other dermatites. HHV-6 and HHV-7 DNA were detected in 17% and in 39% of PR plasmas, respectively, but in no controls. HHV-7 viremia was associated with a higher PBMC load and, in adults, with systemic symptoms. HHV-7, but not HHV-6, levels in PBMC were higher in PR patients than in controls. HHV-6 and HHV-7 antigens were found only in PR skin (17% and 67% of patients analyzed, respectively), indicating a productive infection. Syncytia-neutralizing antibodies were found in PR patients and controls, but their titers were lower in patients with HHV-7 viremia. These data confirm the causal association between PR and active HHV-7 or, to a lesser extent, HHV-6 infection.     

Detection of herpes simplex virus genomic DNA in various subsets of Erythema multiforme by polymerase chain reaction

BACKGROUND: The wide variation in the detection of herpes simplex virus (HSV) DNA (36-75%) by polymerase chain reaction (PCR) in erythema multiforme (EM) may be partly attributed to differences in case selection in terms of subsets of EM studied. OBJECTIVE: To determine the frequencies of detection of HSV DNA in specific subsets of EM. METHODS: Nested PCR was used to detect HSV DNA in skin biopsies with histologically proven EM. RESULTS: PCR was performed on skin biopsies from 63 patients with EM. HSV DNA was detected in 3/11 (27.2%) of single-episode HSV-associated EM (HAEM), 6/10 (60%) of recurrent HAEM, 1/4 (25%) of single-episode idiopathic EM and 6/12 (50%) of recurrent idiopathic EM. HSV DNA was not detected in atypical EM (0/11), suspected drug-induced EM (0/9) or Stevens-Johnson syndrome (0/6). CONCLUSION: The overall PCR positive rates of HAEM (42.9%) and idiopathic EM (43.8%) were comparable suggesting that idiopathic EM is likely to be related to a subclinical HSV infection.     

副银屑病皮损及外周血TCRγ基因重排的检测及其临床意义探讨

目的：检测副银屑病患者皮损及外周血TCRγ基因重排并探讨其临床意义。方法20例副银屑病患者,采用BIOMED?2多重PCR扩增体系检测其皮肤及外周血TCRγ链基因重排,分析TCRγ基因重排与患者一般资料、临床类型、组织病理表现（非特异表现和非典型表现）的相关性。结果20例副银屑病患者皮损中,7例TCRγ基因重排阳性。11例外周血TCRγ基因重排检测中3例阳性,其中2例皮损检测亦阳性。皮损及外周血TCRγ基因重排与患者性别、年龄、病程、临床类型均无关（P>0.05）,而皮损TCRγ基因重排阳性与蕈样肉芽肿相关不典型表现有关（P<0.05）。20例患者平均随访（44.85±18.48）个月,1例进展为蕈样肉芽肿,2例痊愈。结论副银屑病患者皮损TCRγ基因重排阳性可能与蕈样肉芽肿相关不典型表现有关,结合组织病理不典型表现,提示有进展为蕈样肉芽肿的可能。     

Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases

Summary Background A novel polyomavirus, the Merkel cell polyomavirus (MCPyV), has recently been identified in Merkel cell carcinoma (MCC). Objectives To investigate the specificity of this association through the detection, quantification and analysis of MCPyV DNA in lesional and nonlesional skin biopsies from patients with MCC or with other cutaneous diseases, as well as in normal skin from clinically healthy individuals. Methods DNA was extracted from lesional and nonlesional skin samples of patients with MCC or with other cutaneous diseases and from normal‐appearing skin of clinically healthy subjects. MCPyV DNA was detected by polymerase chain reaction (PCR) and quantified by real‐time PCR. Additionally, the T antigen coding region was sequenced in eight samples from seven patients. Results MCPyV DNA was detected in 14 of 18 (78%) patients with MCC, five of 18 (28%) patients with other skin diseases (P = 0·007) and one of six (17%) clinically healthy subjects. In patients with MCC, viral DNA was detected in nine of 11 (82%) tumours and in 10 of 14 (71%) nontumoral skin samples (P = 0·66). MCPyV DNA levels were higher in MCC tumours than in nontumoral skin from patients with MCC, and than in lesional or nonlesional skin from patients with other cutaneous disorders. Signature mutations in the T antigen gene were not identified in the two MCC tumour specimens analysed. Conclusions High prevalence and higher levels of MCPyV DNA in MCC supports a role for MCPyV in tumorigenesis. However, the high prevalence of MCPyV in the nontumoral skin and in subjects without MCC suggests that MCPyV is a ubiquitous virus.     

Lichen planus is associated with human herpesvirus type 7 replication and infiltration of plasmacytoid dendritic cells

BACKGROUND: Lichen planus (LP) is a common inflammatory skin disease of unknown aetiology. Viral causes have been suggested. OBJECTIVES: To find candidate viruses associated with LP. METHODS: Lesional and nonlesional skin samples, peripheral blood mononuclear cells and serum were obtained from patients with LP. Ultrastructural, viral DNA, immunohistochemical and serological analyses were performed, and comparisons were made with psoriatic and normal skin. RESULTS: Electron microscopy revealed typical 120-200-nm enveloped particles with a 100-nm nucleus resembling human herpesvirus (HHV) virions both in dermis and in epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP samples, as opposed to only one of 11 nonlesional LP samples (P =0.06), two of 11 lesional psoriasis samples (P = 0.05) and none of four normal skin samples. No relation was found between LP skin and DNA of other known HHVs (HHV-1-6 and 8). With immunohistochemistry, significantly more HHV-7+ cells were found in lesional LP epidermis than in normal epidermis. Lesional LP dermis contained significantly more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP skin contained overwhelmingly and consistently more plasmacytoid dendritic cells (upregulated in virally induced conditions) than nonlesional LP samples. CONCLUSIONS: We conclude that HHV-7 replicates in LP lesions, but not in psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the pathogenesis of LP. These preliminary data make further research on this topic of interest.