Human Herpesvirus 6 DNA Research Articles

Single nucleotide polymorphisms in the open reading frame 26 (ORF26) gene of human herpesvirus 8 (HHV-8) in Kaposi's sarcoma

Objective To study the single nucleotide polymorphisms (SNPs) in the ORF26 gene of HHV-8 in Kaposi's sarcoma (KS),and to assess their correlations with the clinical phenotype and mucosal invasion of KS.Methods HHV-8 DNA was extracted with phenol-chloroform-isoamyl alcohol from paraffin-embedded tissue specimens obtained from 32 cases of KS (including 26 classic and 6 AIDS-related KS).The ORF26 gene of HHV-8 was amplified by nested-PCR followed by bidirectional sequencing.The software DNAStar and program Clustal W were used to assess the SNPs in the ORF26 gene.Statistical analysis was carried out by using the Fisher's exact probability test.Results HHV-8 DNA was detected in 30 of the 32 tissue specimens,and in all of the 6 AIDS-related specimens.The predominant SNPs were 981 T/C (n =12),1086 C/T (n =12) and 1139 A/C (n =12) in the ORF26 gene of the 30 strains of HHV-8.No significant difference was observed in the distribution of SNPs in ORF26 between different phenotypes of KS or between KS with and without mucosal invasion.Conclusion The ORF26 SNPs of HHV-8 seem unrelated to the clinical phenotypes or mucosal invasion of KS.

Identification of human herpesviruses 1 to 8 in Tunisian multiple sclerosis patients and healthy blood donors

Members of the human Herpesviridae family are candidates for representing the macroenvironmental factors associated with multiple sclerosis (MS) pathogenesis. To verify the possible role of human herpesviruses (HHVs) as triggering or aggravating factors in relapsing-remitting multiple sclerosis clinical outcome, we studied the prevalence of all eight human herpesviruses in whole blood samples collected from 51 MS patients and from 51 healthy controls. The presence of DNA of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7) and human herpesvirus 8 (HHV-8) was searched by specific nested polymerase chain reaction. HHVs were significantly more prevalent in the blood of MS patients than in those of the controls (P < 10(-4)). HSV-1, HSV-2, HCMV and HHV-8 were negative in both MS patients and controls samples. In MS patients, EBV, HHV-7, HHV-6 and VZV were detected in 31.3%, 33.3%, 5.8% and 7.8% of samples, respectively, compared with 3.9%, 9.8%, 1.96% and 1.96%, respectively, of samples from controls. We found a statistically significant difference only for EBV DNA and for HHV-7 DNA prevalence (P < 0.001 and P = 0.03). Although these results indicate lack of apparent association in terms of gender, type of diagnosis, symptoms, disease score and β interferon treatment between EBV or HHV-7 to MS among Tunisian patients, heterogeneity related to genetic polymorphism as well as geographical distribution of the disease and of pathogens may be of significance.

Human herpesvirus 6 in biopsies from patients with gastrointestinal symptoms after allogeneic stem cell transplantation

Gastrointestinal complications are frequent after allogeneic stem cell transplantation (allo-SCT). Main differential diagnoses are graft-versus-host disease (GvHD) and viral infections. In this retrospective analysis, we included 50 patients with severe vomiting or diarrhea in the first year after allo-SCT. One hundred two biopsies obtained by colonoscopy or endoscopy of the upper gastrointestinal tract were analysed by conventional histology for signs of GvHD and by qualitative polymerase chain reaction (PCR) for viral DNA of human herpesvirus 6 (HHV-6) and other virus of the herpes family. DNA of HHV-6 was detected in 38 of 75 initial samples (51%) and in 19 of 27 follow-up biopsies (70%). In the initial samples (n = 75), HHV-6 DNA was detected in 20/37 (54%) biopsies in the presence of GvHD compared to 18/38 (47%) biopsies without signs of GvHD. At the time of the first endoscopic investigation, most patients received antiviral prophylaxis with aciclovir. None of the follow-up biopsies was HHV-6 DNA negative after antiviral treatment with aciclovir, foscarnet or ganciclovir. By univariate analysis, no risk factor for HHV-6 detection could be demonstrated. In this cohort of patients with severe gastrointestinal complications, there was no significant difference in the overall survival between patients with or without HHV-6 DNA detection in the gastrointestinal tract. In summary, the detection of HHV-6 DNA had no impact on overall survival. Moreover, antiviral therapy against HHV-6 was without effect. Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT.

Can plasma HHV8 viral load be used to differentiate multicentric Castleman disease from Kaposi sarcoma?

We measured plasma human herpesvirus 8 (HHV8) DNA load in consecutive patients presenting with HIV-associated multicentric Castleman disease (MCD) and in contemporaneous patients who had Kaposi sarcoma (KS), lymphoma or other diagnoses. All 11 patients with MCD had detectable plasma HHV8 DNA compared with 18 (72%) of 25 patients with KS, none with lymphoma and one of 38 patients with other diagnoses. Detectable plasma HHV8 DNA levels were higher among MCD patients, median (interquartile range [IQR]) = 43,500 (5200-150,000) copies/mL, when compared with those with KS, median (IQR) = 320 (167-822) copies/mL and those with lymphoma and other diagnoses (one-way analysis of variance; P = 0.0303). Using receiver operating characteristic analysis, a cut-off of >1000 copies HHV8 DNA/mL of plasma helped to discriminate between MCD and other diagnoses, with a specificity of 94.7% and a negative predictive value of 97.3%. The level of HHV8 viraemia, while not diagnostic, may aid discrimination between patients with MCD and those with KS and other systemic illnesses.

Dominance of variant A in Human Herpesvirus 6 viraemia after renal transplantation

BackgroundHuman herpesvirus 6 (HHV-6), mostly variant B reactivation in renal transplant patients has been published by other authors, but the pathogenetic role of HHV-6 variant A has not been clarified. Our aims were to examine the prevalence of HHV-6, to determine the variants, and to investigate the interaction between HHV-6 viraemia, human cytomegalovirus (HCMV) infection and clinical symptoms.MethodsVariant-specific HHV-6 nested PCR and quantitative real-time PCR were used to examine blood samples from renal transplant patients and healthy blood donors for the presence and load of HHV-6 DNA and to determine the variants. Active HHV-6 infection was proved by RT-PCR, and active HCMV infection was diagnosed by pp65 antigenaemia test.ResultsHHV-6 viraemia was significantly more frequent in renal transplant patients compared to healthy blood donors (9/200 vs. 0/200; p = 0.004), while prevalence of HHV-6 latency was not significantly different (13/200 vs. 19/200; p > 0.05). Dominance of variant A was revealed in viraemias (8/9), and the frequency of HHV-6A was significantly higher in active infections compared with latency in renal transplant patients (8/9 vs. 2/13; p = 0.0015). Latency was established predominantly by HHV-6B both in renal transplant patients and in healthy blood donors (11/13 and 18/19). There was no statistical significant difference in occurrence of HCMV and HHV-6 viraemia in renal transplant patients (7/200 vs. 9/200). Statistical analysis did not reveal interaction between HHV-6 viraemia and clinical symptoms in our study.ConclusionsContrary to previous publications HHV-6A viraemia was found to be predominant in renal transplant patients. Frequency of variant A was significantly higher in cases of active infection then in latency.

Longitudinal analysis of human herpesvirus-8 DNA and antibodies in an Italian allogeneic stem cell transplant recipient

Background Changes of HHV-8 antibody reactivity and intermittent detection of HHV-8 DNA have been observed in subjects with Kaposis's Sarcoma and/or HIV infection. Little is known about the longitudinal dynamics of HHV-8 DNA and antibody response in allografted stem cell transplant (SCT) patients without Kaposis's Sarcoma. Objectives To report the natural history of a HHV-8 seropositive patient with chronic lymphocytic leukemia who developed an active HHV-8 infection after SCT. Study design HHV-8 antibodies were measured by IFA and ELISA assays. HHV-8 DNA was detected by real-time PCR quantitative assay in serum and peripheral blood leukocytes (PBL). Results Twenty-two out of 26 (85%) serum samples had detectable HHV-8 antibodies: 21/26 (80%) samples were positive by both IFA and ELISA assays, while 1 sample was ELISA positive-IFA negative. The remaining 4 samples (15%) were negative by both assays. Five out of 6 (83%) serum-PBL samples pairs had detectable HHV-8 DNA: a median of 934 genomes/ml (range 254–6316 genomes/ml) in the serum and a median of 10,000 genomes/10 5 (range 1472–93,460 gen/10 5) in PBL. An active HHV-8 infection occurred early within the first 30 days after the transplant, extended up to day +180 and occurred without evidence of HHV-8-related neoplastic or non neoplastic diseases. Conclusions This study provides evidence that a patient infected with HHV-8 before SCT can be either intermittently HHV-8 DNA-positive and/or seropositive for HHV-8 after SCT. A high and persistent HHV-8 replication may be ongoing even in the absence of overt HHV-8-associated diseases.

Non-Detection of Human Herpesvirus 8 (HHV-8) DNA in HHV-8-Seropositive Blood Donors from Three Brazilian Regions

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiologic agent of all forms of Kaposi's sarcoma, primary effusion lymphoma and the plasmablastic cell variant of multicentric Castleman disease. In endemic areas of sub-Saharan Africa, blood transfusions have been associated with a substantial risk of HHV-8 transmission. By contrast, several studies among healthy blood donors from North America have failed to detect HHV-8 DNA in samples of seropositive individuals. In this study, using a real-time PCR assay, we investigated the presence of HHV-8 DNA in whole-blood samples of 803 HHV-8 blood donors from three Brazilian states (São Paulo, Amazon, Bahia) who tested positive for HHV-8 antibodies, in a previous multicenter study. HHV-8 DNA was not detected in any sample. Our findings do not support the introduction of routine HHV-8 screening among healthy blood donors in Brazil. (WC = 140).

Human herpesvirus-6 entry into the central nervous system through the olfactory pathway

Viruses have been implicated in the development of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and multiple sclerosis. Human herpesvirus-6 (HHV-6) is a neurotropic virus that has been associated with a wide variety of neurologic disorders, including encephalitis, mesial temporal lobe epilepsy, and multiple sclerosis. Currently, the route of HHV-6 entry into the CNS is unknown. Using autopsy specimens, we found that the frequency of HHV-6 DNA in the olfactory bulb/tract region was among the highest in the brain regions examined. Given this finding, we investigated whether HHV-6 may infect the CNS via the olfactory pathway. HHV-6 DNA was detected in a total of 52 of 126 (41.3%) nasal mucous samples, showing the nasal cavity is a reservoir for HHV-6. Furthermore, specialized olfactory-ensheathing glial cells located in the nasal cavity were demonstrated to support HHV-6 replication in vitro. Collectively, these results support HHV-6 utilization of the olfactory pathway as a route of entry into the CNS.

Safety of pre‐engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic stem cell transplantation (SCT). Because our previous trial of preemptive therapy with foscarnet sodium (phosphonoformic acid; PFA) failed to prevent HHV-6 encephalitis, we conducted a prospective study to examine the safety of prophylactic PFA administration and elucidate the changes in the plasma HHV-6 DNA levels in the early post-SCT period. Plasma HHV-6 DNA was measured thrice weekly from day 6. PFA, 90 mg/kg/day, was administered from days 7 to 21 after bone marrow or peripheral blood SCT and to day 25 after umbilical cord blood transplantation. Of the 10 patients enrolled, 2 dropped out of the study, 1 because of early death, and 1 with a low glomerular filtration rate. Grade 3 or greater adverse events occurred in 9 of the 10 prophylactic PFA patients and in 7 of the 10 control patients who had clinical backgrounds similar to the study subjects and underwent SCT during the same period. Neurological disorders developed in none of the study subjects but in 4 of the 10 control patients, including 2 with HHV-6 encephalitis. HHV-6 reactivation occurred in 3 of the 10 study subjects. The prophylactic PFA regimen was thus safe and it may reduce the risk of limbic encephalitis, but is not considered to be potent enough to prevent HHV-6 reactivation.

Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease

AbstractHIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals.

Chromosomally integrated human herpesvirus-6 in kidney transplant recipients

During primary infection, human herpesvirus-6 (HHV-6) may become integrated into the chromosome. This entity, termed chromosomally integrated HHV-6 (CIHHV-6), is often mistaken as active infection and treated unnecessarily. The prevalence of CIHHV-6 in kidney transplant recipients is not known. We performed quantitative HHV-6 polymerase chain reaction assay on whole blood samples collected from 47 kidney recipients. CIHHV-6 was defined as HHV-6 DNA levels >1 × 10(6) genomes/mL. One of 47 kidney recipients was found to have CIHHV-6. The prevalence of CIHHV-6 was calculated at 2.1% (95% confidence interval, <0.01-12.1%). Despite an increase in HHV-6 DNA level after transplant, the patient did not develop clinical HHV-6 disease. CIHHV-6 may be observed in kidney transplant recipients. Clinicians should be aware of this entity so as not to provide unnecessary treatment to asymptomatic patients with CIHHV-6.

Prevalence of human herpesvirus 8 infection in systemic lupus erythematosus

BackgroundFor decades, scientists have tried to understand the environmental factors involved in the development of systemic lupus erythematosus (SLE), in which viral infections was included. Previous studies have identified Epstein-Barr virus (EBV) to incite SLE. Human herpesvirus 8 (HHV-8), another member of the gammaherpesvirus family, shares a lot in common with EBV. The characteristics of HHV-8 make it a well-suited candidate to trigger SLE.ResultsIn the present study, serum samples from patients (n = 108) with diagnosed SLE and matched controls (n = 122) were collected, and the prevalence of HHV-8 was compared by a virus-specific nested PCR and a whole virus enzyme-linked immunoassay (EIA). There was significant difference in the prevalence of HHV-8 DNA between SLE patients and healthy controls (11 of 107 vs 1 of 122, p = 0.001); significant difference was also found in the detection of HHV-8 antibodies (19 of 107 vs 2 of 122, p < 0.001).We also detected the antibodies to Epstein-Barr virus viral capsid antigen (EBV-VCA) and Epstein-Barr nuclear antigen-1 (EBNA-1). Both patients and controls showed high seroprevalence with no significant difference (106 of 107 vs 119 of 122, p = 0.625).ConclusionOur finding indicated that there might be an association between HHV-8 and the development of SLE.

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7% of individuals; however, 5.8% of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25% (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica: comparison of lesional T-cell subsets and investigation of viral associations

Pityriasis lichenoides (PL) exhibits a broad clinical spectrum that includes both acute and chronic forms. The precise biologic mechanisms underlying PL remain unclear. To evaluate the immunohistochemical characteristics of PL and to investigate lesional T-cell subsets and the possible role of viral infection in its pathogenesis. Samples from 10 patients with PL et varioliformis acuta (PLEVA) and 13 with PL chronica (PLC) were analyzed immunohistochemically. Epstein-Barr virus early regions were assayed by in situ hybridization and T-cell receptor-γ (TCR-γ) gene rearrangements were assayed by polymerase chain reaction (PCR). We also utilized PCR to assay for human herpesvirus-8 (HHV-8) DNA in 51 patients with PL and in 25 controls. Lymphocytes expressing CD8 and T-cell intracellular antigen-1 were more abundant in patients with PLEVA than with PLC, whereas CD4+ lymphocytes and FOXP3-positive regulatory T-cells were more abundant in PLC. HHV-8 DNA was present in 11 of 51 (21.6%) PL patients and 0 of 25 controls. A clonal TCR-γ gene rearrangement was observed in only one patient with PLEVA. Our data suggests that PL may represent an inflammatory condition induced by various triggering agents, such as HHV-8, rather than a lymphoproliferative disorder. PLEVA, characterized by an acute course with severe symptoms, may indicate a relative lack of regulatory T-cells in comparison with PLC.

Prevalence of human herpesvirus 8 DNA in peripheral blood mononuclear cells of acute and chronic leukemia patients in Taiwan: Table 1

Human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma and several other human malignancies. The prevalence of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) in Taiwanese leukemia populations has not been investigated. In this study, HHV-8 DNA was extracted from PBMCs, and detected in 10.29% of the leukemia cases and 8.94% of the relatives' cases. In addition, the prevalence of HHV-8 DNA in PBMCs was nonsignificantly associated with gender, age and leukemia subtypes. The study examines the prevalence of HHV-8 DNA in PBMCs in Taiwanese leukemia and can be applied in further epidemiological studies.

Different characteristics of human herpesvirus 6 encephalitis between primary infection and viral reactivation

Background Pathogenesis of human herpesvirus 6 (HHV-6) encephalitis, in particular difference between HHV-6 encephalitis at the time of primary infection and reactivation remains unclear. Objectives To elucidate the mechanism of HHV-6 encephalitis at the time of primary infection and reactivation. Study design Twenty-two HHV-6 encephalitis patients at the time of primary infection, 6 febrile convulsion (FC) patients caused by HHV-6 infection, and 14 FC patients without HHV-6 infection (non HHV-6 FC) were enrolled. Additionally, 7 stem cell transplant recipients with HHV-6 encephalitis and eight adult controls were also enrolled in this study. Cerebrospinal fluid (CSF) HHV-6 DNA copy numbers and biomarkers levels were compared. Results Low copy number of CSF HHV-6 DNA was detected in 7 of the 22 patients with HHV-6 encephalitis in primary infection, whereas all seven CSF samples collected from post-transplant HHV-6 encephalitis patients contained high viral DNA copy numbers ( P < 0.001). CSF concentrations of IL-6 ( P = 0.032), IL-8 ( P = 0.014), MMP-9 ( P = 0.004), and TIMP-1 ( P = 0.002) were significantly higher in patients with HHV-6 encephalitis in primary infection than non-HHV-6 FC. CSF IL-6 ( P = 0.008), IL-8 ( P = 0.015), and IL-10 ( P = 0.019) concentrations were significantly higher in patients with post-transplant HHV-6 encephalitis than adult controls. Conclusion The present study suggests that the characteristics of HHV-6 encephalitis are different between HHV-6 encephalitis at the time of primary infection and reactivation in transplant recipients.

Role of Human Herpes Virus 6 in Corneal Inflammation Alone or With Human Herpesviruses

: The purpose of this study was to determine the association of human herpes virus 6 (HHV-6) and/or other human herpesviruses in corneal inflammation using polymerase chain reaction (PCR). : We collected tear films, conjunctival smears, and a corneal button of inflamed cornea, and the presence of HHV-6 and other herpesviruses in these samples were assessed by a nested PCR. : In tear films collected from 3 of 9 patients with dendritic keratitis, HHV-6 DNA was positive twice, together with herpes simplex virus (HSV) or varicella zoster virus DNA most often, during the acute phase of the disease. Two other patients in this group were either positive for HSV-1 and varicella zoster virus or for HSV-1 and Epstein-Barr virus DNA but negative for HHV-6. When another 12 patients' smear samples from corneal ulcer or keratouveitis were examined, 9 were positive for HHV-6 DNA. Of these, 4 were positive for HSV-1 simultaneously, whereas the remaining 5 patients were negative for HSV-1. One patient's smear was positive for HSV-1 but not for HHV-6. In the corneal button, both HSV and HHV-6 DNAs were positive by nested PCR. HHV-6 was also positive by nested PCR in the conjunctival swab obtained from the contralateral inflamed eye of the patient. : In 22 patients with corneal inflammation, HHV-6 was positive in 14 of 22 patients and HSV-1 was found in 9 of those patients. These data indicated that the association of HHV-6 with disease was more frequent than with other herpesviruses and that HHV-6 may be another sole causative agent for corneal inflammation.

Detection of human herpes virus 6B in patients with mesial temporal lobe epilepsy in West China and the possible association with elevated NF-κB expression

There has been a long-standing suspicion that an association exists between mesial temporal lobe epilepsy (MTLE) and the herpes virus. Evidence for HHV-6B involvement has been reported. However, no investigation has been performed in China. We used nested PCR and immunohistochemistry to detect viral DNA of human herpes virus (HHV)-6B, HHV-6A, herpes simplex virus (HSV)-1 and HSV-2 in resected brain tissues from patients with MTLE and control. A principal transcription factor, NF-κB, that is associated with the inflammatory response was also investigated by real-time PCR, western blotting and immunohistochemistry. HHV-6B DNA was detected in hippocampal samples from 9 out of 32 (28.1%) patients with MTLE and in 1 of 12 (8.3%) control samples. Immunoreactivity for HHV-6B was consistently present in MTLE patients positive for HHV-6 detected by PCR. Significant staining for HHV-6B antigen was distributed mainly around or in the nucleus of cells that morphologically resembled astrocytes and microglia. HHV-6B positivity was related to febrile convulsion history of patients with MTLE. The expression of NF-κB was up-regulated and distributed in the nucleus of glial cells in MTLE patients positive for HHV-6B. This study was first to find HHV-6B in MTLE patients from West China and demonstrate a possible association between HHV-6B positivity and activation of NF-κB. The detailed role of HHV-6B and its association with NF-κB in the development of chronic MTLE requires further investigation.

Human herpesvirus-6 viral load and antibody titer in serum samples of patients with multiple sclerosis

Despite the number of cases with definite diagnosis of multiple sclerosis (MS) being on increase, the role of human herpesvirus-6 (HHV-6) infection as a trigger for MS disease still is deliberated. Based on antibody detection and quantitative HHV-6 polymerase chain reaction assay, this study was achieved to find out the possible association between infection with HHV-6 and clinical progression of MS disease. A total of 108 serum samples were obtained from 30 MS patients followed prospectively for a 6-month period. These samples were analyzed for the presence of HHV-6 DNA by nested polymerase chain reaction enzyme-linked immunosorbent assay and for anti-HHV-6 IgG titer. Activation of the disease was determined by either magnetic resonance imaging or by clinical status of the patients. Control groups were also included. The average antibody index for the MS patients in the first sample collection was higher than both control groups (p=0.001). HHV-6 DNA was detected in the serum samples of 10 of 30 MS patients. The mean HHV-6 viral load in patients with relapsing-remitting multiple sclerosis (RRMS) with and without relapse was 973 and 714, respectively. Seven patients showed an exacerbation during the study period. Of those, four patients had HHV-6 DNA in their collected samples. The prevalence of HHV-6 DNA was significantly higher in patients with MS as compared with control groups (p=0.001). The results indicate that HHV-6 is implicated somehow in MS disease. Over time, rising HHV-6 IgG antibody titers together with an exacerbation and detection of HHV-6 DNA in serum samples of some MS patients suggests possible association between the reactivation of the virus and disease progression.

Prurigo pigmentosa: a clinicopathological study and analysis of associated factors

Prurigo pigmentosa (PP), a rare inflammatory disease of the skin, is mostly reported in the ethnic Japanese population. Its pathogenesis remains unclear. The chronic and recurrent nature of PP implies a possible role of viral infection in the pathogenesis. The anti-inflammatory mechanism of doxycycline, which is well documented as a good treatment for PP, is related to the suppression of interleukin expression. We identified and retrospectively analyzed 16 biopsy-proven and criteria-matched patients over a seven year period at a single medical center. DNA extracted from formalin-fixed, paraffin-embedded specimens was analyzed for herpes simplex virus-1 (HSV-1), HSV-2, and human herpes virus-6 (HHV-6) DNA by polymerase chain reaction. Immunohistochemistry was performed to determine the interleukin-6 (IL-6) and interleukin-8 (IL-8) expression in PP skin lesions. Clinicopathological findings in the ethnic Chinese population are similar to those reported in Japanese studies. All patients had a good response to doxycycline treatment, with a mean duration of use of 2.4 weeks. However, recurrence was noted in six patients. HSV-1, HSV-2, and HHV-6 DNA in PP skin lesions were negative. Immunohistochemistry showed IL-6 (P = 0.035) to be more strongly expressed in PP skin lesions. There was no statistical significance of elevated IL-8 expression in PP (P = 0.123). Prurigo pigmentosa is not uncommon in the ethnic Chinese population. There was no evidence of herpes virus DNA in PP skin lesions. Increased expression of IL-6 in PP skin lesions may explain the effects of doxycycline in terms of its anti-inflammatory properties.