0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Study |

High Association of Human Herpesvirus 8 in Large-Plaque Parapsoriasis and Mycosis Fungoides FREE

Alexander Kreuter, MD; Sebastian Bischoff, MD; Marina Skrygan, PhD; Ulrike Wieland, MD; Norbert H. Brockmeyer, MD; Markus Stücker, MD; Peter Altmeyer, MD; Thilo Gambichler, MD
[+] Author Affiliations

Author Affiliations: Department of Dermatology, Ruhr University Bochum, Bochum (Drs Kreuter, Bischoff, Skrygan, Brockmeyer, Stücker, Altmeyer, and Gambichler), and the Institute of Virology, University of Cologne, Cologne (Dr Wieland), Germany.


Arch Dermatol. 2008;144(8):1011-1016. doi:10.1001/archderm.144.8.1011.
Text Size: A A A
Published online

Objective  To investigate the presence of human herpesvirus 8 (HHV-8) in lesional skin of German patients with large-plaque parapsoriasis (LPP) or mycosis fungoides (MF). The pathogenetic relevance of HHV-8 in cutaneous T-cell lymphoma is controversial. Recently, a highly significant association of HHV-8 in LPP was found, which suggests a role in the pathogenesis of this disease.

Design  Retrospective study of the presence of HHV-8 in German patients with lymphoproliferative diseases.

Setting  Dermatologic clinic at a university hospital of the Ruhr University Bochum, Bochum, Germany.

Patients  Fifty-three patients treated for lymphoproliferative skin diseases were included in the study, including 14 patients with LPP, 31 with different stages of MF, and 8 with lymphomatoid papulosis (LyP). Twenty-three patients with Kaposi sarcoma (KS) made up the positive control group, and 10 patients with atopic dermatitis served as negative controls.

Main Outcome Measures  The presence of HHV-8 was analyzed from paraffin-embedded lesional tissue samples using a nested polymerase chain reaction for the open reading frame (ORF) 26 and with immunohistochemical staining for the latency-associated nuclear antigen (LANA) encoded by ORF 73.

Results  A high association of HHV-8 infection in both lymphoproliferative skin diseases was observed: 87% of LPP and 70% of MF tissue samples tested positive for HHV-8 DNA from ORF 26. However, HHV-8 was not detectable in LPP and MF by using the immunohistochemical marker LANA.

Conclusions  A virus unambiguously associated with KS, HHV-8 was frequently detected at low amounts in LPP and MF specimens. However, based on the methods of HHV-8 detection used in this study, no conclusion can be drawn on the etiologic and pathogenetic role of HHV-8 in these diseases.

Figures in this Article

Human herpesvirus 8 (HHV-8), the most recently identified member of the human herpesvirus family, is the etiologic agent of Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease (MCD).13 In addition, HHV-8 DNA sequences have been found in association with other skin diseases such as angiosarcoma and pemphigus vulgaris, but the role of the virus in these diseases is largely unconfirmed and remains controversial.4 Some years ago, several studies provided strong evidence against a role for HHV-8 in the pathogenesis of mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL).5,6

In the October 2005 issue of the Archives, Trento and colleagues7 investigated the prevalence of HHV-8 infection in an Italian population of 22 patients with lymphoproliferative diseases such as large-plaque parapsoriasis (LPP) and MF. Lesional skin samples, plasma, and peripheral blood mononuclear cells were analyzed for the presence of HHV-8. As the predominant result, the authors observed a highly significant association of HHV-8 infection in LPP compared with MF. Consequently, they speculated that HHV-8 could be causally involved in the pathogenesis of LPP and might therefore be a distinct clinical entity separate from MF. The 2 conditions are generally believed to represent different clinical stages of the same disease. This essential observation encouraged us to investigate the presence of HHV-8 in lesional skin of German patients with LPP or MF.

PATIENTS AND CONTROL SUBJECTS

A total of 86 paraffin-embedded lesional skin specimens, including 53 from patients with lymphoproliferative skin diseases, were evaluated in this retrospective study. Patients had LPP (n = 14), MF (n = 31), and lymphomatoid papulosis (LyP) (n = 8). Diagnosis was based on clinical, histopathologic, immunopathologic, and molecular biological characteristics as detailed by the International Society for Cutaneous Lymphoma.8 When available, a detailed review of the clinical characteristics and pretreatment status of all patients with LPP and MF was performed. As positive controls, we used 23 tissue samples of classic and AIDS-associated KS, a tumor that is unambiguously associated with HHV-8. As negative controls, samples from 10 patients with atopic dermatitis (AD) were included. All patients had been diagnosed and treated at the Department of Dermatology, Ruhr University Bochum (observation period, January 1, 1999, through December 31, 2006). The protocol of the study was approved by the ethics review board of Ruhr University Bochum.

PCR ANALYSIS

The presence of HHV-8 DNA was analyzed by amplification of a sequence of open reading frame (ORF) 26 by a nested polymerase chain reaction (PCR) protocol similar to the protocol reported by Trento et al.7 Identical PCR primers were used.7 To prevent possible cross-contamination between samples during the PCR procedure, each paraffin block was cut using a new disposable microtome blade. For DNA extraction, tissue samples were deparaffinized by adding 1 mL of xylene. After 10 minutes, tissue samples were spun, washed twice with 1 mL of 100% ethanol, and kept overnight in 180 μL of lysis buffer containing proteinase K at 56°C. The DNA was isolated using the QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany) following the manufacturer's protocol. The PCR products were checked by 2% agarose gel electrophoresis and ethidium bromide staining. The PCR reaction mixture consisted of 400 ng of DNA, PCR buffer containing 15mM magnesium dichloride, 30 pmol/μL of each primer, 200 μM of each deoxyribonucleoside triphosphate, and 2.5 U of HotStar Taq Plus DNA Polymerase (QIAGEN) in a total volume of 100 μL. Amplification was performed in a thermal cycler (TRIO-Thermoblock; Biometra, Göttingen, Germany). The external PCR product was a single-band fragment of 233 base pairs (bp). The nested PCR analysis was performed using 0.5 μL of the first-round product with the inner primer set. The nested PCR product was a fragment of 138 bp. The HHV-8 DNA PCR was independently performed in 2 different laboratories (Bochum and Cologne).

Epstein-Barr virus (EBV) DNA was determined by real-time PCR in a LightCycler (Roche Applied Science, Mannheim, Germany) using hybridization probes as described previously.9 For sample preparation, the QIAamp DNA Mini Kit was used, and the forward and backward primers described by Stöcher et al9 were slightly elongated 5′ by 2 nucleotides each (forward, 5′-AGGGTGGTTTGGAAAGC-3′; backward, 5′-AACAGACAATGGACTCCCTTAG-3′).

IMMUNOHISTOCHEMICAL ANALYSIS

Sections were deparaffinized in xylol and washed with 100% and 96% ethanol as well as 70% and 50% propanol for 5 minutes each and rinsed with demineralized water. After washing with Target Retrieval Solution (DAKO Cytomation, Hamburg, Germany) at a pH of 6.0 for 20 minutes, sections were stored in a water bath at 96°C. Sections were stained with a rat monoclonal antibody against the latency-associated nuclear antigen (LANA) encoded by ORF 73 of HHV-8 (Advanced Biotechnologies Inc, Columbia, Maryland) at a dilution of 1:3000 for 30 minutes at 25°C in a DAKO Autostainer (DAKO Cytomation). For EBV protein analysis, a mouse monoclonal antibody against the latent membrane protein 1 at a dilution of 1:50 (DAKO Cytomation) was used. After washing with Wash Buffer (DAKO) for 2 minutes, incubation with streptavidin alkaline phosphatase was performed for 30 minutes. Chromogen red (DAKO) was used for visualization before counterstaining with hematoxylin and mounting in Mowiol (Roche Molecular Biochemicals, Mannheim, Germany).

STATISTICAL ANALYSIS

Where appropriate, the 2-sided Fisher exact test for tabulated categorical data was used to analyze the differences between the negative control group (AD specimens) and the other diseases investigated with regard to the frequencies of HHV-8 positivity. A P value of .05 or lower was considered statistically significant.

A total of 53 patients with lymphoproliferative skin diseases were included in this retrospective study. An overview of representative patients with available data on age, stage of MF, duration of disease, and previous topical and systemic therapy is provided in Table 1. In all included patients, the duration of disease was at least 1 year (range, 1-30 years), and all of them had previously been treated with topical and/or systemic agents.

Table Graphic Jump LocationTable 1. Clinical Characteristics of Representative Patients With Large-Plaque Parapsoriasis and Mycosis Fungoides

Lesional skin of patients with LPP and MF as well as control specimens were analyzed for the presence of HHV-8. A significant association of HHV-8 DNA prevalence was found in LPP as well as in MF. Seven of the 8 tissue samples of LPP (87%) (P = .02) and 7 of the 10 skin specimens of MF (70%) (P = .03) tested positive for the presence of HHV-8 DNA. In all specimens of LPP and MF, the viral sequence was already detectable after the first round of PCR and was finally confirmed by nested PCR (Figure 1A). As expected, all KS tissue specimens tested positive for HHV-8 DNA, and compared with LPP and MF, the single band fragment at 233 bp showed a much stronger positive result in KS indicating a larger amount of viral DNA (Figure 1B). All specimens from patients with AD and LyP tested negative in the first PCR round and in the nested PCR reaction. In contrast to the PCR results, all 14 samples of LPP and all 31 samples of MF tested negative for HHV-8 using the immunohistochemical marker for LANA encoded by ORF 73. A strong positive nuclear staining for HHV-8 ORF 73 was detected in lesional skin of all patients with KS, whereas tissue samples of LyP and AD tested negative. All immunohistochemical and PCR results are detailed in Table 2. Representative immunohistochemical images from HHV-8 analysis are provided in Figure 2.

Place holder to copy figure label and caption
Figure 1.

First-round polymerase chain reaction (A) and nested polymerase chain reaction (B) for human herpesvirus 8 (HHV-8) open reading frame 26 in lesional skin specimens of large-plaque parapsoriasis (LPP) (lane 1), mycosis fungoides (MF) (lane 2), and lymphomatoid papulosis (LyP) (lane 4). Lesional skin samples from patients with Kaposi sarcoma (KS) (lane 3) and atopic dermatitis (AD) (lane 5) were used as positive and negative controls, respectively. Lane 6 shows the molecular weight marker; bp indicates base pairs. This agarose gel is representative of the whole study and demonstrates that HHV-8 DNA is commonly detectable in lesional skin of German patients with LPP and MF.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Immunohistochemical analysis for human herpesvirus 8 (HHV-8) in lesional skin specimens of lymphoproliferative diseases and Kaposi sarcoma (KS) (hematoxylin, original magnification ×20). Both large-plaque parapsoriasis (LPP) and mycosis fungoides (MF) samples tested negative for HHV-8 (A and B), whereas the KS specimen shows a strong positive stain for HHV-8 (C). These immunohistochemical pictures are representative of the whole study and demonstrate the absence of HHV-8 in the immunohistochemical findings of German patients with LPP and MF.

Graphic Jump Location
Table Graphic Jump LocationTable 2. Prevalence of Positive HHV-8 DNA Findings and Protein Expression in Patients With Lymphoproliferative Diseasesa

In addition, EBV analysis was performed in patients with LPP and MF. By using real-time PCR, all tissue specimens analyzed (5 samples of LPP and 10 samples of MF) tested negative for EBV DNA. Similarly, 4 paraffin-embedded samples from patients with LPP and 25 samples of MF tested negative for EBV using the immunohistochemical marker latent membrane protein. Samples from a patient with Burkitt lymphoma, which were used as control specimens, showed strongly positive EVB findings. Representative immunohistochemical images for EBV analysis are depicted in Figure 3.

Place holder to copy figure label and caption
Figure 3.

Immunohistochemical analysis for Epstein-Barr virus (EBV) in lesional skin specimens of patients with large-plaque parapsoriasis (LPP) and mycosis fungoides (MF) (hematoxylin-eosin, original magnification ×20). All specimens from patients with LPP and MF tested negative for EBV (A and B), whereas those samples obtained from a patient with Burkitt lymphoma (positive control) showed strongly positive EBV findings in numerous blasts (C). These immunohistochemical pictures are representative for the whole study and demonstrate the absence of EBV in the immunohistochemical analysis of German patients with LPP and MF.

Graphic Jump Location

Human herpesvirus type 8 is a gamma herpesvirus isolated from KS lesions for the first time in 1994.1 The 140-kilobase genome of HHV-8 can be divided into 4 major subtypes (A-D), and these can be further differentiated into 14 distinctive variants. Human herpesvirus type 8 carries at least 11 ORFs that encode homologues to cellular proteins involved in signal transduction, cell cycle regulation, inhibition of apoptosis, and immune modulation.10 Thus, HHV-8 has the genetic armamentarium of an oncogenic virus. A sexual mode of transmission has been confirmed for HHV-8, although an obvious nonsexual horizontal mode of transmission exists in endemic regions.11 Seroprevalence of HHV-8 ranges from 100% in some African countries to 15% or 20% in the Mediterranean area and decreases to approximately 2% to 5% in northern Europe and in the United States.12

Besides KS, primary effusion lymphoma, and multicentric Castleman disease, several diseases have been reported to be associated with HHV-8 (eg, angiosarcoma and pemphigus vulgaris), but subsequent studies failed to demonstrate the presence of HHV-8 in these conditions.1317 The detection of HHV-8 in a lymphomalike germinotropic disorder18 and in primary effusion lymphoma with T-cell phenotype19 led to the assumption that HHV-8 might also be present in CTCL. However, initial investigations failed to demonstrate an association.5,6,20 Moreover, HHV-8 was undetectable in MF lesions of 2 patients with concomitant KS, whereas viral DNA was found in the KS tissue of these patients.21

In contrast, Trento et al7 recently reported the detection of HHV-8 infection in skin lesions and peripheral blood of 100% of patients with LPP and in skin lesions and peripheral blood of 25% of patients with MF. Based on these findings, the authors speculated that LPP might be an entity separate from MF. In the present study, we confirmed the high association of HHV-8 with LPP. However, in contrast to the findings of Trento et al,7 most MF tissue samples in our study also harbored low amounts of HHV-8 DNA. The observation of a high association of HHV-8 with LPP might be explained by geographic regions of high seroprevalence of HHV-8, such as Italy or East Africa.10 However, all included subjects in the present study were of German descent and living in Germany, where the HHV-8 prevalence is considered to be low (<5%).12 Moreover, although not documented in the patient's files, high-risk sexual behavior and preferences that could explain the high association of HHV-8 seem to be rather unlikely in the investigated cohort. Thus, further epidemiologic studies are required to define the mode of transmission of HHV-8 infection in patients with CTCL.

Importantly, all previous studies that failed to detect HHV-8 in MF specimens used skin samples from patients naïve to any kind of therapy.5,6 In the present study, however, all individuals had been previously treated with topical and/or systemic immunosuppressive agents. The high prevalence of positive findings for HHV-8 DNA in our study population might be explained by a new or recent infection or reactivation of HHV-8 in individuals who had undergone extensive treatment and/or who had an advanced stage of the disease, which is associated with altered immunocompetence. Similar observations have been made in patients with common variable immunodeficiency, in which an overproduction of inflammatory cytokines enhances the replication of HHV-8 and promotes tumor progression.22 None of the analyzed specimens in the present study harbored EBV, a B-lymphotropic gamma herpesvirus that is widespread in all human populations and that presents together with HHV-8 as a dual infection in some body cavity lymphomas or AIDS-related, non-Hodgkin lymphomas.23 The lack of EBV and the high prevalence of HHV-8 DNA in LPP and MF might rather reflect a causal relation than a reactivation or secondary colonization of HHV-8 in CTCL. None of the tissue samples of LyP included in the present study carried HHV-8 DNA, thus confirming the results of previous investigations.24

Interestingly, while our PCR analysis revealed HHV-8 at a high rate in LPP and MF specimens, immunohistochemical findings were negative. Similar discrepancies between DNA detection and protein expression have also been reported by Hammock et al25 and Wheat et al,22 who investigated HHV-8 in benign vascular tumors and in lymphoproliferative disorders such as B-cell lymphomas, respectively. For example, liver specimens from patients with common variable immunodeficiency and granulomatous lymphocytic interstitial lung disease tested positive by nested PCR for HHV-8 DNA but negative for LANA by immunohistochemical staining, possibly reflecting the relative insensitivity of immunohistochemical analysis to detect very low amounts of HHV-8.22 Molecular genetic techniques such as PCR are more sensitive than LANA immunohistochemical analysis.25 By contrast, highly sensitive PCR techniques have also led to a recent controversy. For example, initial studies using these methods suggested a biological association between HHV-8 and multiple myeloma. However, most experts now believe these to be false-positive reactions.26 Nevertheless, the high occurrence of HHV-8 DNA in patients with LPP and MF and the absence of HHV-8 in patients with LyP and AD would not indicate false-positive findings in the present study.

In conclusion, this retrospective study demonstrated the presence of HHV-8 DNA in 2 clinical variants of CTCL (LPP and MF) in patients living in Germany, where the general HHV-8 seroprevalence is considered to be low. Possibly, in the context of systemic or local impairment of immunocompetence secondary to advanced disease or to aggressive and/or long-term disease treatment, HHV-8 acts as a cofactor in the progression of CTCL. Based on the methods of detection used in this study, no conclusion can be drawn on the etiologic and pathogenetic role of HHV-8 in these diseases. Because the virus was detected only by PCR and not by immunohistochemical analysis, we were unable to show whether HHV-8 is located in endothelial cells, keratinocytes, or neoplastic T cells. Given the limitations of this study and the discrepancies in other investigations, the etiologic and pathogenetic role of HHV-8 in CTCL and its precursors requires further research.

Correspondence: Alexander Kreuter, MD, Department of Dermatology, Ruhr University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany (a.kreuter@derma.de).

Accepted for Publication: August 21, 2007.

Author Contributions:Study concept and design: Kreuter and Gambichler. Acquisition of data: Kreuter, Bischoff, Skrygan, Wieland, and Stücker. Analysis and interpretation of data: Kreuter, Wieland, Brockmeyer, and Altmeyer. Drafting of the manuscript: Kreuter and Gambichler. Critical revision of the manuscript for important intellectual content: Kreuter, Bischoff, Skrygan, Wieland, Brockmeyer, Stücker, and Altmeyer. Statistical analysis: Gambichler. Administrative, technical, and material support: Bischoff, Skrygan, Wieland, and Stücker. Study supervision: Kreuter, Brockmeyer, and Altmeyer.

Financial Disclosure: None reported.

Chang  YCesarman  EPessin  MS  et al.  Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266 (5192) 1865- 1869
PubMed Link to Article
Cesarman  EChang  YMoore  PSSaid  JWKnowles  DM Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332 (18) 1186- 1191
PubMed Link to Article
Nador  RGCesarman  EChadburn  A  et al.  Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996;88 (2) 645- 656
PubMed
Geraminejad  PMemar  OAronson  IRady  PLHengge  UTyring  SK Kaposi's sarcoma and other manifestations of human herpesvirus 8. J Am Acad Dermatol 2002;47 (5) 641- 655
PubMed Link to Article
Henghold  WB  IIPurvis  SFSchaffer  JGiam  CZWood  GS No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders. J Invest Dermatol 1997;108 (6) 920- 922
PubMed Link to Article
Nagore  ELedesma  ECollado  COliver  VPerez-Perez  AAliaga  A Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas. Br J Dermatol 2000;143 (2) 320- 323
PubMed Link to Article
Trento  ECastilletti  CFerraro  C  et al.  Human herpesvirus 8 infection in patients with cutaneous lymphoproliferative diseases. Arch Dermatol 2005;141 (10) 1235- 1242
PubMed
Pimpinelli  NOlsen  EASantucci  M  et al.  Defining early mycosis fungoides. J Am Acad Dermatol 2005;53 (6) 1053- 1063
PubMed Link to Article
Stöcher  MLeb  VBozic  M  et al.  Parallel detection of five human herpes virus DNAs by a set of real-time polymerase chain reactions in a single run. J Clin Virol 2003;26 (1) 85- 93
PubMed Link to Article
Lazzi  SBellan  CAmato  T  et al.  Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8-related lymphomas? Hum Pathol 2006;37 (1) 23- 31
PubMed Link to Article
Martin  JNGanem  DEOsmond  DHPage-Shafer  KAMacrae  DKedes  DH Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 1998;338 (14) 948- 954
PubMed Link to Article
Chatlynne  LGAblashi  DV Seroepidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV). Semin Cancer Biol 1999;9 (3) 175- 185
PubMed Link to Article
Gyulai  RKemeny  LKiss  M  et al.  Human herpesvirus 8 DNA sequences in angiosarcoma of the face. Br J Dermatol 1997;137 (3) 467
PubMed Link to Article
Fink-Puches  RZochling  NWolf  PBack  BKerl  HSoyer  HP No detection of human herpesvirus 8 in different types of cutaneous angiosarcoma. Arch Dermatol 2002;138 (1) 131- 132
PubMed Link to Article
Memar  OMRady  PLGoldblum  RMYen  ATyring  SK Human herpesvirus 8 DNA sequences in blistering skin from patients with pemphigus. Arch Dermatol 1997;133 (10) 1247- 1251
PubMed Link to Article
Wang  GQXu  HWang  YK  et al.  Higher prevalence of human herpesvirus 8 DNA sequence and specific IgG antibodies in patients with pemphigus in China. J Am Acad Dermatol 2005;52 (3, pt 1) 460- 467
PubMed Link to Article
Cohen  SSWeinstein  MDHerndier  BGAnhalt  GJBlauvelt  A No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus. J Invest Dermatol 1998;111 (5) 781- 783
PubMed Link to Article
Du  MQDiss  TCLiu  H  et al.  KSHV- and EBV-associated germinotropic lymphoproliferative disorder. Blood 2002;100 (9) 3415- 3418
PubMed Link to Article
Said  JWShintaku  IPAsou  H  et al.  Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype. Arch Pathol Lab Med 1999;123 (3) 257- 260
PubMed
Erkek  ESenturk  NDincer  I  et al.  Identification of herpes simplex virus DNA and lack of human herpesvirus-8 DNA in mycosis fungoides. Acta Derm Venereol 2002;82 (3) 214- 216
PubMed Link to Article
Guttman-Yassky  EBergman  RCohen  ASarid  R Absence of Kaposi's sarcoma-associated herpesvirus in lesions of mycosis fungoides in patients with concomitant Kaposi's sarcoma. J Am Acad Dermatol 2004;51 ((2 suppl)) S133- S134
PubMed Link to Article
Wheat  WHCool  CDMorimoto  Y  et al.  Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005;202 (4) 479- 484
PubMed Link to Article
Miller  GHeston  LGrogan  E  et al.  Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells. J Virol 1997;71 (1) 314- 324
PubMed
Kempf  WKadin  MEKutzner  H  et al.  Lymphomatoid papulosis and human herpesviruses-A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 related herpesviruses. J Cutan Pathol 2001;28 (1) 29- 33
PubMed Link to Article
Hammock  LReisenauer  AWang  WCohen  CBirdsong  GFolpe  AL Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients. Mod Pathol 2005;18 (4) 463- 468
PubMed Link to Article
Brander  CRaje  NO'Connor  PG  et al.  Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma. Blood 2002;100 (2) 698- 700
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

First-round polymerase chain reaction (A) and nested polymerase chain reaction (B) for human herpesvirus 8 (HHV-8) open reading frame 26 in lesional skin specimens of large-plaque parapsoriasis (LPP) (lane 1), mycosis fungoides (MF) (lane 2), and lymphomatoid papulosis (LyP) (lane 4). Lesional skin samples from patients with Kaposi sarcoma (KS) (lane 3) and atopic dermatitis (AD) (lane 5) were used as positive and negative controls, respectively. Lane 6 shows the molecular weight marker; bp indicates base pairs. This agarose gel is representative of the whole study and demonstrates that HHV-8 DNA is commonly detectable in lesional skin of German patients with LPP and MF.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Immunohistochemical analysis for human herpesvirus 8 (HHV-8) in lesional skin specimens of lymphoproliferative diseases and Kaposi sarcoma (KS) (hematoxylin, original magnification ×20). Both large-plaque parapsoriasis (LPP) and mycosis fungoides (MF) samples tested negative for HHV-8 (A and B), whereas the KS specimen shows a strong positive stain for HHV-8 (C). These immunohistochemical pictures are representative of the whole study and demonstrate the absence of HHV-8 in the immunohistochemical findings of German patients with LPP and MF.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Immunohistochemical analysis for Epstein-Barr virus (EBV) in lesional skin specimens of patients with large-plaque parapsoriasis (LPP) and mycosis fungoides (MF) (hematoxylin-eosin, original magnification ×20). All specimens from patients with LPP and MF tested negative for EBV (A and B), whereas those samples obtained from a patient with Burkitt lymphoma (positive control) showed strongly positive EBV findings in numerous blasts (C). These immunohistochemical pictures are representative for the whole study and demonstrate the absence of EBV in the immunohistochemical analysis of German patients with LPP and MF.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Clinical Characteristics of Representative Patients With Large-Plaque Parapsoriasis and Mycosis Fungoides
Table Graphic Jump LocationTable 2. Prevalence of Positive HHV-8 DNA Findings and Protein Expression in Patients With Lymphoproliferative Diseasesa

References

Chang  YCesarman  EPessin  MS  et al.  Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266 (5192) 1865- 1869
PubMed Link to Article
Cesarman  EChang  YMoore  PSSaid  JWKnowles  DM Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332 (18) 1186- 1191
PubMed Link to Article
Nador  RGCesarman  EChadburn  A  et al.  Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996;88 (2) 645- 656
PubMed
Geraminejad  PMemar  OAronson  IRady  PLHengge  UTyring  SK Kaposi's sarcoma and other manifestations of human herpesvirus 8. J Am Acad Dermatol 2002;47 (5) 641- 655
PubMed Link to Article
Henghold  WB  IIPurvis  SFSchaffer  JGiam  CZWood  GS No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders. J Invest Dermatol 1997;108 (6) 920- 922
PubMed Link to Article
Nagore  ELedesma  ECollado  COliver  VPerez-Perez  AAliaga  A Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas. Br J Dermatol 2000;143 (2) 320- 323
PubMed Link to Article
Trento  ECastilletti  CFerraro  C  et al.  Human herpesvirus 8 infection in patients with cutaneous lymphoproliferative diseases. Arch Dermatol 2005;141 (10) 1235- 1242
PubMed
Pimpinelli  NOlsen  EASantucci  M  et al.  Defining early mycosis fungoides. J Am Acad Dermatol 2005;53 (6) 1053- 1063
PubMed Link to Article
Stöcher  MLeb  VBozic  M  et al.  Parallel detection of five human herpes virus DNAs by a set of real-time polymerase chain reactions in a single run. J Clin Virol 2003;26 (1) 85- 93
PubMed Link to Article
Lazzi  SBellan  CAmato  T  et al.  Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8-related lymphomas? Hum Pathol 2006;37 (1) 23- 31
PubMed Link to Article
Martin  JNGanem  DEOsmond  DHPage-Shafer  KAMacrae  DKedes  DH Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 1998;338 (14) 948- 954
PubMed Link to Article
Chatlynne  LGAblashi  DV Seroepidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV). Semin Cancer Biol 1999;9 (3) 175- 185
PubMed Link to Article
Gyulai  RKemeny  LKiss  M  et al.  Human herpesvirus 8 DNA sequences in angiosarcoma of the face. Br J Dermatol 1997;137 (3) 467
PubMed Link to Article
Fink-Puches  RZochling  NWolf  PBack  BKerl  HSoyer  HP No detection of human herpesvirus 8 in different types of cutaneous angiosarcoma. Arch Dermatol 2002;138 (1) 131- 132
PubMed Link to Article
Memar  OMRady  PLGoldblum  RMYen  ATyring  SK Human herpesvirus 8 DNA sequences in blistering skin from patients with pemphigus. Arch Dermatol 1997;133 (10) 1247- 1251
PubMed Link to Article
Wang  GQXu  HWang  YK  et al.  Higher prevalence of human herpesvirus 8 DNA sequence and specific IgG antibodies in patients with pemphigus in China. J Am Acad Dermatol 2005;52 (3, pt 1) 460- 467
PubMed Link to Article
Cohen  SSWeinstein  MDHerndier  BGAnhalt  GJBlauvelt  A No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus. J Invest Dermatol 1998;111 (5) 781- 783
PubMed Link to Article
Du  MQDiss  TCLiu  H  et al.  KSHV- and EBV-associated germinotropic lymphoproliferative disorder. Blood 2002;100 (9) 3415- 3418
PubMed Link to Article
Said  JWShintaku  IPAsou  H  et al.  Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype. Arch Pathol Lab Med 1999;123 (3) 257- 260
PubMed
Erkek  ESenturk  NDincer  I  et al.  Identification of herpes simplex virus DNA and lack of human herpesvirus-8 DNA in mycosis fungoides. Acta Derm Venereol 2002;82 (3) 214- 216
PubMed Link to Article
Guttman-Yassky  EBergman  RCohen  ASarid  R Absence of Kaposi's sarcoma-associated herpesvirus in lesions of mycosis fungoides in patients with concomitant Kaposi's sarcoma. J Am Acad Dermatol 2004;51 ((2 suppl)) S133- S134
PubMed Link to Article
Wheat  WHCool  CDMorimoto  Y  et al.  Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005;202 (4) 479- 484
PubMed Link to Article
Miller  GHeston  LGrogan  E  et al.  Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells. J Virol 1997;71 (1) 314- 324
PubMed
Kempf  WKadin  MEKutzner  H  et al.  Lymphomatoid papulosis and human herpesviruses-A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 related herpesviruses. J Cutan Pathol 2001;28 (1) 29- 33
PubMed Link to Article
Hammock  LReisenauer  AWang  WCohen  CBirdsong  GFolpe  AL Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients. Mod Pathol 2005;18 (4) 463- 468
PubMed Link to Article
Brander  CRaje  NO'Connor  PG  et al.  Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma. Blood 2002;100 (2) 698- 700
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 4

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles