Lichen planus remission is associated with a decrease of human herpes virus type 7 protein expression in plasmacytoid dendritic cells

The cause of lichen planus is still unknown. Previously we showed human herpes virus 7 (HHV-7) DNA and proteins in lesional lichen planus skin, and significantly less in non-lesional lichen planus, psoriasis or healthy skin. Remarkably, lesional lichen planus skin was infiltrated with plasmacytoid dendritic cells. If HHV-7 is associated with lichen planus, then HHV-7 replication would reduce upon lichen planus remission. HHV-7 DNA detection was performed by nested PCR and HHV-7 protein by immunohistochemistry on lesional skin biopsies from lichen planus patients before treatment and after remission. Biopsies were obtained from lichen planus lesions before treatment (n = 18 patients) and after remission (n = 13). Before treatment 61% biopsies contained HHV-7 DNA versus 8% after remission (P = 0.01). HHV-7-protein positive cell numbers diminished significantly after remission in both dermis and epidermis. Expression of HHV-7 was mainly detected in BDCA-2 positive plasmacytoid dendritic cells rather than CD-3 positive lymphocytes. HHV-7 replicates in plasmacytoid dendritic cells in lesional lichen planus skin and diminishes after remission. This study further supports our hypothesis that HHV-7 is associated with lichen planus pathogenesis.     

Lichen planus follicularis tumidus: Immunotyping of the inflammatory infiltrate with focus on plasmacytoid dendritic cells

Lichen planus follicularis tumidus (LPFT) is a rare clinicopathological variant of lichen planus (LP), clinically presenting with red-to-violaceous plaques studded with comedo-like lesions and keratin-filled milia-like cysts. Histopathologically, LPFT is characterized by cystically dilated follicular infundibula in the dermis, surrounded by a dense lichenoid lymphoid infiltrate with an associated interface reaction. We describe the clinicopathological features of an additional case of LPFT, focusing on the number and distribution of CD123(+) TCF4(+) plasmacytoid dendritic cells (pDCs). In our case, pDCs represented approximately 5% of the total inflammatory infiltrate, predominantly exhibiting a lichenoid distribution around the infundibula with no evidence of cluster formation, thus ruling out cutaneous lupus erythematosus. Our report is the first to describe the number and distribution of pDCs in LPFT. The results of our immunohistochemical analysis corroborate the notion that LPFT should be regarded as a rare variant of LP.     

Cutaneous accumulation of plasmacytoid dendritic cells associated with acute myeloid leukemia: a rare condition distinct from blastic plasmacytoid dendritic cell neoplasm

A cutaneous infiltrate composed of plasmacytoid dendritic cells may occasionally occur in a patient suffering from a myeloid neoplasm. To date, the clinical and pathological features associated with this event remains poorly characterized. Herein, we report a patient with acute myeloid leukemia who developed pruritic papules or erythematous plaques scattered on the skin. Microscopic examination showed a dermal infiltrate rich in plasmacytoid dendritic cells expressing CD4, CD43, CD68, granzyme B, CD123, CD303 [blood dendritic cell antigen 2 (BDCA-2)], CD2-associated protein (CD2AP) and T-cell leukemia/lymphoma oncogene 1 (TCL1). Our observation illustrates further that cutaneous lesions associated with some myeloid neoplasms, especially those featuring a monocytic component, may be composed of plasmacytoid dendritic cells. Because of differences in clinical, pathological and genetic features, this rare condition should be distinguished from blastic plasmacytoid dendritic cell neoplasm.     

Tumor‐forming plasmacytoid dendritic cells associated with myeloid neoplasms. Report of a peculiar case with histopathologic features masquerading as lupus erythematosus

Plasmacytoid dendritic cells (PDC) belong to a subtype of dendritic cells that are normally absent in healthy skin. In some inflammatory diseases of the skin, especially lupus erythematosus (LE), these cells are occasionally recruited in great amounts, which can be used as a helpful clue for diagnosis. Rarely, PDC may also accumulate in the skin of patients with myeloid leukemia, a yet poorly known condition currently called ‘tumor‐forming PDC associated with myeloid neoplasms’. In this study, we describe a patient with unsuspected chronic myelomonocytic leukemia who developed cutaneous lesions characterized by a dermal infiltrate rich in PDC. Similarly to LE, such neoplastic PDC were accompanied by interface dermatitis‐like changes, but displayed an aberrant phenotype and shared the same chromosomal abnormality with the leukemic cells identified in the bone marrow, thus revealing the neoplastic nature of the process. This observation illustrates that tumor‐forming PDC associated with myeloid neoplasms may microscopically mimic LE in some patients. Accordingly, a hematologic workup is recommended in any skin lesion featuring excessive numbers of PDC, even if morphological alterations suggestive of interface dermatitis are found.     

Numerous plasmacytoid dendritic cell infiltration in HIV‐associated psoriasis relieved only with antiretroviral therapy

The onset of psoriasis is often seen in HIV infection, called HIV‐associated psoriasis. Although HIV‐associated psoriasis is usually refractory, there are some cases relieved only by antiretroviral therapy. In those cases, the pathogenesis may be formed differently from psoriasis vulgaris. We present the case of a 42‐year‐old Japanese man with HIV‐associated psoriasis. The patient developed a systemic scaly eruption, especially on the soles. Histopathological examination showed typical psoriatic findings and plasma cell infiltration into the dermis. The eruption dramatically remitted with antiretroviral therapy alone, without systemic treatment for psoriasis. In immunohistological findings, few CD4⁺ cells were seen in the patient's skin. In addition, immunofluorescent staining revealed more BDCA‐2 and CD123 double‐positive plasmacytoid dendritic cell infiltration into the dermis than that of psoriasis vulgaris. We suggest that the immune response to HIV including plasmacytoid dendritic cell infiltration may involve in the development and remission of HIV‐associated psoriasis.     

Lichen planus with involvement of all twenty nails and the oral mucous membrane

A 57-year-old man had had deformities of all ten fingernails for one and a half years before presentation and deformities of all ten toenails for the previous six months. The surfaces of the nails were rough, with excessive longitudinal striations. The bases of the nails were slightly hypertrophic, and the tips were atrophic and itchy. A longitudinal nail biopsy including the nail matrix revealed the typical histology of lichen planus. Reticulated pigmentation, maceration, and erosion on the buccal mucous membrane were also discovered. Histological analysis of the buccal mucous membrane revealed lichen planus intermingled with eosinophils. Immunological blood analysis revealed elevated CD4+ T cells and CD4/CD8 ratio. He worked as a tinsmith and had dental metal. The metal series patch test revealed positive reactions to chromate and tin. Treatment with systemic steroids was quite effective in treating the nail lesions.     

The role of human herpesvirus 6, human herpesvirus 7, Epstein–Barr virus and cytomegalovirus in the aetiology of pityriasis rosea

Aim   To identify the role of human herpesvirus 6 (HHV-6), HHV-7, Epstein–Barr virus (EBV) and cytomegalovirus (CMV) in the pathogenesis of pityriasis rosea (PR).
Material   Polymerase chain reaction with specific primers for HHV-6 and HHV-7 DNA sequences was performed on the blood and tissue samples of 25 patients with PR and on the blood samples of age- and sex-matched healthy controls. HHV-6, EBV, CMV immunoglobulin M (IgM) and IgG were analysed by enzyme-linked immunosorbent assay, HHV-7 IgM and IgG were analysed by indirect immunofluorescence on the serum samples of the study population. In the patient group, the values were studied 2 weeks later again (second control).
Results   There were no differences between the first and second controls of the patients and healthy subjects regarding HHV-6 IgM, HHV-7 IgM, CMV IgM, EBV IgM results. There were significant differences between the first [HHV-6 DNA (2 of 25), HHV-7 DNA (6 of 25)] and second control [HHV-6 DNA (1 of 25), HHV-7 DNA (11 of 25)] of the patients for the blood samples in favour of HHV-7. PR patients showed higher amounts of HHV-6 and HHV-7 DNA positivity when compared with that of healthy subjects. HHV-7 seemed to be more important regarding tissue samples [HHV-6 DNA (7 of 25), HHV-7 DNA (12 of 25) first control, HHV-6 DNA (6 of 25), HHV-7 DNA (12 of 25) second control] as well as blood samples.
Conclusion   Though our results failed to support a causal relationship among EBV, CMV and PR, they indicated a possible role for HHV-6 and especially HHV-7 in a group of Turkish patients but other aetiological factors may exist.     

Type 1 IFN-induced protein MxA and plasmacytoid dendritic cells in lesions of morphea

Morphea is an autoimmune sclerotic skin disease of unknown pathogenesis. As type 1 interferons (IFN) have been implicated in the pathogenesis of systemic sclerosis, we proposed that type 1 IFN promote localized inflammation and fibrosis in morphea. To investigate the expression of the type 1 IFN-inducible protein myxovirus A (MxA) and the presence of plasmacytoid dendritic cells (pDC) in lesions of morphea, lesional skin of 10 patients with morphea was examined by immunohistochemistry for the presence of the type 1 IFN-inducible protein, myxovirus A (MxA), and the pDC markers, CD123 and BDCA-2, and was compared with lesional skin of cutaneous lupus erythematosus, lichen planus and keloid. Lesional and non-lesional morphea skin was compared. MxA was expressed in the epidermis as well as the reticular dermis and subcutis in morphea. pDCs were abundant around vessels and between fibrous bundles. Non-lesional biopsies demonstrated little or no expression of MxA and pDC markers. Keloid showed minimal expression of MxA and pDC markers. We demonstrate the expression of type 1 IFN-related protein MxA and plasmacytoid DCs in lesional but not in non-lesional biopsies of morphea. These findings suggest a potential role for type 1 interferons in the pathogenesis of morphea.     

Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas

BACKGROUND: Several studies have investigated the possible involvement of viral agents, particularly herpesviruses, in primary cutaneous lymphoma (PCL). OBJECTIVES: Our aim was to screen for the presence of human herpesvirus 7 (HHV-7) and 8 (HHV-8) genomes in samples of PCL, and to determine if their presence was independent of Epstein-Barr virus (EBV). METHODS: Screening was performed using polymerase chain reaction assay in 64 skin samples from historical lesional tissues with PCL. RESULTS: Only nine cases showed positivity for HHV-7: four of 29 mycosis fungoides (MF), two of four CD30-positive large-cell cutaneous T-cell lymphoma (CTCL), two of 12 follicle centre cutaneous B-cell lymphoma (CBCL) and one of nine marginal zone CBCL. Fifteen cases tested positive for EBV: seven of 29 MF, two of four pleomorphic small/medium sized CTCL, three of three angiocentric CTCL, one of 12 follicle centre CBCL and two of nine marginal zone CBCL. All cases were uniformly negative for HHV-8. No simultaneous positivity was found for EBV and HHV-7. Controls tested negative for all viruses. CONCLUSIONS: The findings indicate that EBV, HHV-7 and HHV-8 seem not to be involved in the pathogenesis of PCL.     

药疹患者人类疱疹病毒7型感染的检测

目的 探讨人类疱疹病毒7型（HHV-7）感染在药疹发病中的作用。 方法 收集50例药疹患者（其中重型药疹15例）及50例健康人外周血,采用PCR检测外周血单一核细胞中HHV-7 DNA特异性片段;酶联免疫吸附试验（ELISA）检测血清HHV-7 IgM水平。 结果 50例药疹患者HHV-7 DNA阳性率（82.00%,41例）高于健康对照组（62.00%,31例）,两组差异有统计学意义（χ2 = 4.96,P < 0.05）;重型药疹患者（93.33%,14/15）、轻型药疹患者（77.14%,27/35）及健康对照组HHV-7 DNA阳性率差异有统计学意义（χ2 = 6.32,P < 0.05）,其中重型组高于对照组（q = 3.50,P < 0.05）;重型药疹患者急性期与恢复期HHV-7 DNA阳性率差异无统计学意义（P > 0.05）。药疹患者HHV-7 IgM水平（69.3190 ± 25.2897 ng/L）高于健康对照组（59.7853 ± 22.4382 ng/L,t = 1.99,P < 0.05）;轻型药疹（65.4791 ± 21.3261 ng/L）、重型药疹（74.3407 ± 31.4112 ng/L）及健康对照组间差异均无统计学意义（均P > 0.05）。HHV-7 DNA阳性与阴性药疹患者HHV-7特异性IgM水平（分别为63.7481 ± 27.2391 ng/L、65.5802 ± 36.2584 ng/L）差异无统计学意义（P > 0.05）。 结论 药疹患者中存在HHV-7活动性感染,HHV-7感染可能是药疹发病或加重的因素。     

Lichen planus with lesions on the palms and/or soles: prevalence and clinicopathological study of 36 patients

According to the literature, palmoplantar lesions in lichen planus (LP) are uncommon, and do not usually have the classically described clinical morphology. The aim of this study was to evaluate the prevalence of palmoplantar lesions in LP and to describe the characteristic clinicopathological appearances of LP affecting palms and soles. Palmoplantar LP with accompanying skin involvement accounted for 26% of our cases. The presence of very pruriginous erythematous scaly and/or hyperkeratotic plaques, with well-defined edges, located on the internal plantar arch, without involvement of the fingertips, and which usually disappear in a few months, is characteristic of palmoplantar LP. Histopathological examination shows the characteristic features of LP.     

扁平苔藓皮损中肥大细胞数和P物质的表达及其意义

目的:探讨肥大细胞和P物质在扁平苔藓发病中的作用。方法:采用组织化学和免疫组化的染色方法,检测扁平苔藓皮损中未脱颗粒的肥大细胞数和P物质的表达情况。结果:甲苯胺蓝特殊染色发现,扁平苔藓皮损中未脱颗粒的肥大细胞数(3.56±1.52)明显低于正常对照组(5.22±1.28),其差异具有统计学意义(P<0.01);免疫组化染色发现,扁平苔藓皮损中P物质的表达强度明显高于正常对照组,其差异具有统计学意义(P<0.01);采用Spearman等级相关分析,二者呈一定的负相关(rs=-0.397,P<0.05)。结论:肥大细胞和P物质在扁平苔藓的发病中可能起一定的作用。     

T cells reactive with the NC16A domain of BP180 are present in vulval lichen sclerosus and lichen planus

Background Lichen sclerosus (LS) is a chronic inflammatory skin condition. The recent demonstration of circulating autoantibodies to extracellular matrix protein 1 and to basement membrane zone (BMZ) components, chiefly BP180, suggests that autoimmunity to these components might contribute to pathogenesis. However, there is no binding of autoantibodies in vivo and as LS is characterized by a lymphocytic infiltrate, it seems likely that LS is mediated, in part, by antigen‐specific lymphocytes. Similar mechanisms may apply to vulval lichen planus (LP), an interface dermatitis, with clinical and immunological overlap with LS. Objectives This study aims to test the hypothesis that T cells reactive with the NC16A domain of BP180 are present in the peripheral blood of patients with vulval LS and LP. Methods Isolated peripheral blood mononuclear cells from 14 patients with vulval LS, 5 with vulval LP and 4 healthy controls were grown in vitro. We examined for immunogenicity of overlapping peptides spanning the NC16A domain of BP180 using interferon‐γ enzyme‐linked immunospot assay (ELIspot) on the cultured T‐cell lines. BMZ antibodies were assayed, HLA type determined and clinical parameters noted. Results Significant interferon‐γ production was observed in response to the NC16A peptides in 6 of the 14 vulval LS and 2 of the 5 LP patients, but not in the control subjects. There was an associated autoantibody response to BP180 in 3 LS and 1 LP patient with T‐cell responses. These data suggest that in some vulval LS and LP patients, NC16A domain‐specific T cells circulate at sufficiently high frequency to be detectable in vitro and show rapid effector function. There was no association with HLA type or clinical parameters. Conclusion We have demonstrated that in > 40% of our vulval LS and LP patients, the NC16A domain of BP180 is a target for circulating T cells, and in vulval LS and LP there are associated autoantibodies to BP180.     

Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planus

BACKGROUND: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. OBJECTIVES: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes (PBL) in exacerbation and remission phases of the disease as well as in skin lesions. METHODS: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. RESULTS: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+ perforin+ cells) in the exacerbation phase of disease (P < 0.05), which was mostly located in the CD8+ subpopulation (CD8+ perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+ and CD8+ phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). CONCLUSIONS: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.     

Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Toxic epidermal necrolysis induced by human herpesvirus 7 treated with a tumor necrosis factor-α inhibitor

Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a life-threatening hypersensitivity reaction. Long-term sequelae include dry eyes, visual impairment and psychological complications. TEN is mostly induced by medication; however, viral infections, such as coxsackievirus A6, are known triggers of this disease. However, how to define the role of infection in SJS/TEN is still a problem. Most patients develop SJS/TEN over the course of symptoms of the infection first, and then take medication. Therefore, virus culture and nucleic acid detection at the acute stage cannot predict that the virus itself will indeed produce such a serious reaction. Furthermore, many SJS/TEN patients who are diagnosed with an infection are afraid of receiving the drug rechallenge test. Thus, we report the first case worldwide of a patient who suffered from TEN caused by herpesvirus 7 infection, which was confirmed by both real-time polymerase chain reaction and lymphocyte transformation test.