Human Herpesvirus 6 Infection Research Articles

Is human herpesvirus 8 infection more common in men than in women? an updated meta-analysis

BackgroundClinically, most patients with Kaposi's sarcoma (KS) are male, and several direct and indirect mechanisms may underlie this increased susceptibility in men, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is considered to be the primary etiological agent responsible for KS. Thus, we propose the hypothesis that men are more susceptible to HHV-8 infection, leading to a higher incidence of Kaposi's sarcoma among males. A meta-analysis was conducted to evaluate the association between gender and HHV-8 seropositivity in the general population.MethodsA comprehensive literature search was performed using 6 online databases: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, and Wanfang. Studies published before March 15, 2023, were included.ResultsIn all, 33 articles including 41 studies were included in the meta-analysis. In the included adult population. men had a higher risk of HHV-8 infection than did women in adult populations from all over the world (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.15), but no differences were found in child population from all over the world (OR: 0.90, 95% CI: 0.79–1.01). There was a significant difference in HHV-8 seroprevalence between men and women in sub-Saharan Africa (SSA) adult population (OR: 1.15, 95% CI: 1.05–1.26). However, no significant differences were observed in sub-Saharan Africa (SSA) child population (OR: 0.90, 95%CI 0.78–1.03). As for other continents, the results showed no significant difference, such as the Asian population (OR: 1.03, 95%CI: 0.92–1.16). or the European and American populations (OR 1.01, 95%CI 0.87–1.17).ConclusionThere was a slight gender disparity for HHV-8 infection in the adult population. Among the adult populations from SSA and globally, men were more likely to be infected with HHV-8 than were women. However, no statistical significance was observed in the child populations from SSA and globally. In the future, the inclusion of more standardized studies may strengthen the results of this study.

HHV-8 Linked to Kaposi's Sarcoma and Castleman's Disease in HIV-1-infected patient: Case Report and Review of the Literature

Kaposi’s sarcoma (KS) and multicentric Castleman's disease (MCD) are both linked to human herpesvirus-8 (HHV-8) infection which most commonly affects people living with human immunodeficiency virus (HIV). Herein, we describe the case of a 57-year-old patient who has been admitted for fever, night sweats, weight loss, and diffuse lymphadenopathy with abdominal pain. HIV status was confirmed by a positive Western blot test. His initial CD4 cell count was equal to 270 cells/µL. A histological study of a peripheral lymph node concluded that KS is associated with MCD. These two conditions found in the same patient highlight the malignant potential of HHV-8, particularly in the case of HIV-induced immunodeficiency.

Association between Pityriasis Rosea (PR) and HHV-6/HHV-7 Infection: Importance of Sample Selection and Diagnostic Techniques.

Recent studies have focused on the role of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) in PR etiology with varying results. In our study, with the approach that the discrepancy between the results may be related to the different samples and techniques used, we aimed to clarify the etiology by examining tissue and plasma samples using molecular methods and evaluating the results together with serological parameters. Skin biopsies and plasma samples of twenty-five PR patients were tested to detect HHV-6 and HHV-7 DNA using calibrated quantitative real-time polymerase chain reaction (CQ RT-PCR). IgG and IgM antibodies against HHV-6 and HHV-7 were tested by enzyme-linked immunosorbent assay and indirect immunofluorescence. Of the patient group, 64% were positive for HHV-6 IgG without IgM positivity. HHV-6 DNA was present in seven tissue and ten plasma samples. HHV-7 positivity was 100% and 12% for IgG and IgM antibodies, respectively. HHV-7 DNA was detected in four tissue samples and one plasma sample. Patients with HHV-7 DNA-positive plasma and tissue samples had also HHV-7 IgM antibodies. In conclusion, our results seem to support the role of HHV-6/HHV-7 in the etiology of PR. To clarify the etiology of PR and avoid confusion, the collection of different biological materials simultaneously and the usage of CQ RT-PCR as a diagnostic technique are recommended.

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report

BackgroundHuman herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series.Case PresentationIn this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively.ConclusionThis case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

The role of papillomavirus and herpesvirus infections in the origins and genesis of genital endometriosis. A literature review

Endometriosis is a chronic multifactorial disease that affects one in ten women of reproductive age. Genetic, endocrine and immunological factors play an important role in the pathogenesis of endometriosis. In recent years, an increasing number of studies have been devoted to the role of vaginal microbiota in the pathogenesis of endometriosis. However, the role of viral infections, such as papillomavirus and herpesvirus infections, in the development of the disease has not been sufficiently studied. The review highlights current ideas about the role of human papillomavirus and herpesvirus infections in the genesis of endometriosis. The data obtained have convinced us of the need to further search for new relationships between papillomavirus and herpesvirus infections, microbiota of reproductive organs and pathogenesis of such a complicated disease as endometriosis.

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis.

The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method. The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results. In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis. According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.

Multiple-Factor Analysis of Human Herpes Virus 6 Infection in Complementary Transplantation with Haploidentical Stem Cells and Unrelated Cord Blood

Background: Hematopoietic stem cell transplantation (HSCT) can ultimately cure various hematological disorders. Building upon the basis of post-transplant cyclophosphamide (PT-cy) haploidentical HSCT, we innovatively employed a combination of haploidentical related donors and unrelated cord blood donors for complementary transplantation to treat pediatric leukemia and severe thalassemia. This approach has been successful, and complementary transplantation has become an important option in haploidentical HSCT. However, with the development of haploidentical HSCT and the long-term use of immunosuppressive agents, viral infections have gained increasing attention, and human herpesvirus 6 (HHV-6) is one of the concerning viruses. HHV-6 exists in two variants, HHV-6A and HHV-6B, with HHV-6B being the common infection in HSCT. HHV-6B is characterized by a preference for lymphocytes and neurons and can easily reactivate in patients with compromised immune systems after HSCT, leading to severe and irreversible brain and nerve damage, and in severe cases, death. In this study, we aim to identify the susceptible factors for HHV-6B infection in cases of complementary transplantation, with the goal of improving the safety of complementary transplantation in HSCT. Objective: Through a retrospective analysis, we aim to identify the factors associated with HHV-6 infection after complementary transplantation in HSCT, providing clinical evidence for prevention, diagnosis, and treatment. Methods: We selected cases of HSCT using complementary transplantation from December 2018 to May 2022. Factors such as the primary disease of the patients, gender, age, donor-recipient blood type, haploidentical donor engraftment, different HLA-matched cord blood engraftment, neutrophil and platelet engraftment times, use of ATG and glucocorticoids, fever condition, timing of HHV-6 infection, and the time to seronegativity after treatment were analyzed to identify the characteristics and related risk factors of HHV-6B infection. Results: Among 142 cases (73 with thalassemia, 19 with AML, 37 with JMML, 2 with Fanconi anemia, 8 with SAA, and 8 with ALL) using complementary transplantation, 91 cases were infected with HHV-6, resulting in an infection rate of 64%. In the infection group, 8 patients were under the age of 2 years (8.8%), while 83 patients were 2 years or older (91.2%). In the uninfected group, 17 patients were under 2 years of age (33.3%), and 34 patients were 2 years or older (66.7%). (p<0.001). Regarding the type of graft, 79 patients in the infection group received cord blood transplantation (86.8%), and 12 patients received peripheral blood transplantation (13.2%). In the uninfected group, 19 patients received cord blood transplantation (37.3%), and 32 patients received peripheral blood transplantation (62.7%). (p<0.05). Regarding ATG use, 61 patients in the infection group received ATG (67%), and 12 patients did not (33%). In the uninfected group, 25 patients received ATG (49%), and 26 patients did not (51%). (p=0.035). In terms of glucocorticoid use, 82 patients in the infection group received glucocorticoids (90.1%), and 9 patients did not (9.9%). In the uninfected group, 13 patients did not receive glucocorticoids (25.5%), and 38 patients did (74.5%). (p<0.05). Regarding neutrophil engraftment time, it was 36 days in the infection group and 23 days in the uninfected group. Regarding platelet engraftment time, it was 43.5 days in the infection group and 18.5 days in the uninfected group. In terms of CMV and EB virus infection, only one patient in the infection group had concurrent CMV infection, and there were no cases of concurrent EB virus infection. Conclusion: In complementary transplantation, cord blood transplantation, glucocorticoid use, ATG use, and recipient age are high-risk factors for HHV-6 infection/reactivation. There were no significant differences in HHV-6 infection between different diseases treated with complementary transplantation. Furthermore, HHV-6 infection significantly delays the engraftment of neutrophils and platelets. Keywords: Hematopoietic stem cell transplantation, haploidentical, cord blood, human herpesvirus 6 (HHV-6)

Exploratory Analyses of Lymph Node Tissue, Serum, and Peripheral Blood Mononuclear Cells Do Not Reveal Pathogen Signatures in Idiopathic Multicentric Castleman Disease

Background : Castleman disease (CD) encompasses a group of hematologic disorders that share characteristic histopathological features. Unicentric CD (UCD) involves a solitary enlarged lymph node with typically mild symptoms. Multicentric CD (MCD) involves generalized lymphadenopathy and often severe cytokine-driven multi-organ dysfunction. MCD is further subdivided into cases caused by Human Herpesvirus-8 (HHV-8-associated MCD) infection, POEMS syndrome (POEMS-associated MCD), and those with an idiopathic cause (iMCD). The underlying pathological mechanisms and etiologies of UCD and iMCD are not well understood. Given that a viral pathogen, HHV-8, causes HHV-8-associated MCD, we pursued multiple approaches to identify potential pathogens that may trigger iMCD and UCD. Methods: We used 2 distinct detection methods to identify potential pathogens in CD. PathoChIP is a microarray-based assay that uses ~60,000 DNA/RNA probes to detect 4,000+ pathogens associated with human diseases. Viral Track is a computational method that can be applied to unmapped next-generation sequencing (NGS) reads to search for the presence of viral RNA. Formalin-fixed paraffin-embedded (FFPE) lymph node tissue was analyzed by PathoChIP from iMCD (n=6), UCD (n=8), HHV8-associated MCD (n=1, HHV8-MCD), EBV-driven post-transplant lymphoproliferative disorder (n=1, EBV-PTLD), reactive samples without a clear etiology (n=1), and POEMS-associated MCD (n=2) patients. We also analyzed serum from iMCD patients (n=2) and healthy donors (n=8). A ‘positive’ probe for a given microorganism was defined as exceeding the 95 th percentile on a per-probe basis of the optical signal captured across all probes in the dataset. Data from single-cell RNA sequencing of cryopreserved peripheral blood mononuclear cells (iMCD, n=4; EBV, n=2; HHV8, n=1; healthy donor, n=2) and bulk RNA sequencing of FFPE lymph node tissue (iMCD, n=9; sentinel, n=7; systemic lupus erythematosus (SLE), n=3; Diffuse large B-cell lymphoma (DLBCL), n=3) were used as input into the Viral Track program. To detect a positive viral signal, standard thresholds were required: >50 uniquely mapped reads to a given virus, a read complexity threshold >1.2, and >10% coverage of the length of the respective viral genome. Results: After quality control, 49,657 probes from the PathoCHIP assay were mapped to 4,000+ known pathogens. As expected, the HHV-8 MCD and EBV-PTLD samples identified significantly more positive probes compared to the rest of the cohort for HHV-8 (65/259 vs 1/259) and EBV (38/235 vs 1/235), respectively. Importantly, no other microorganisms were detected in UCD or MCD lymph nodes or serum samples at a significantly increased rate than controls. For Viral Track, human endogenous retrovirus K113 and Escherichia phages were detected at low levels throughout all results. Excluding these viruses, positive controls including HHV-8-MCD, and EBV solely identified their respective predicted virally mapped NGS reads and no viral signature was detected in healthy donors. Importantly, there was no significant viral signature specific to CD in PBMCs or LN tissue. Interestingly, 1 iMCD sample did contain a significant number of NGS sequencing reads mapping to HHV5. These results were confirmed with clinical data reporting a positive IgG, negative PCR, and negative IgM test within 2 weeks of the biopsy date, suggesting that the HHV5 positive result was likely detecting a previous, now latent infection rather than a potential pathological driver of CD. Conclusions: Although there are limitations to this study, including small cohorts and viral mRNA single-cell capture limitations, we were able to use 2 orthogonal pathogen detection methods on multiple tissue types from iMCD patients. Taken together, our results suggest that an active infectious agent is unlikely to be a major contributor or pathological mechanism driving UCD or iMCD. The continued search for potential causative microorganisms in iMCD patients should continue, but our results suggest that alternative hypotheses related to the pathology and etiology of iMCD and UCD should be prioritized.

HHV-6 in Cerebrospinal Fluid in Immunocompetent Children

Background: Human herpes virus-6 (HHV-6) is a ubiquitous virus known as an etiological agent of exanthem subitum. HHV-6-encephalitis in immunocompetent children is a rare complication of the primary infection. There are a lack of data on the prevalence of HHV-6-encephalitis in Russia. The aim of our study was to analyze the prevalence of HHV-6 DNA in the cerebrospinal fluid (CSF) of immunocompetent children with suspected acute meningoencephalitis. Materials and Methods: A total of 712 CSF samples were tested using qualitative PCR over 12 years at N.F. Filatov Children’s City Clinical Hospital No.5, Saint-Petersburg, Russia. Results: HHV-6 DNA was detected in 20 (2.8%) of the samples. Retrospectively, we analyzed the medical records of 15 cases. There were seven boys and eight girls from 1 month to 7 years old; the mean age was 22.3 ± 5.6 months. Most HHV-6 DNA-positive cases were due to the primary form of HHV-6 infection. There were, in total, four cases of HHV-6-meningoencephalitis. All the children had a complete recovery, without neurological deficits or death. Conclusions: HHV-6 encephalitis is a very rare disease in immunocompetent children (four cases among 712 samples over 12 years). Additional studies are needed to develop accurate diagnostic criteria and therapeutic approaches.

Kaposi's Sarcoma in Children After Hematopoietic Stem Cell Transplantation: Two Cases of Rare Primary Tumor Localizations in the Lungs and Lymph Node.

Kaposi's sarcoma (KS) is a vascular / mesenchymal tumor with an indefinite degree of malignancy, caused by complex etiopathogenetic factors including Human Herpes Virus-8 infection of immunocompromised patients. For example, KS is more common in adult men with HIV. We describe 2 very rare cases of iatrogenic KS in children after hematopoietic stem cell transplant with isolated organ damage (case 1: lung; case 2: inguinal lymph node). KS is a potential complication of bone marrow transplant in pediatric patients and can occur in different age groups and at atypical sites.

Prevalence, Risk factors, and Shedding of Human Herpes Virus-8 among Men Having Sex With Men Enrolled in a Pre-exposure Prophylaxis Study.

Seroprevalence and risk factors for Human Herpesvirus-8 (HHV-8) infection among HIV-negative men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) have not been well characterized. Our objectives were to assess the prevalence and incidence of HHV-8 infection in MSM enrolled on PrEP and assess viral shedding in seropositive participants. The ANRS IPERGAY study enrolled 429 participants in France and Canada to evaluate oral PrEP for HIV-1 prevention. Stored sera samples at day 0 (D0) and last visit were tested for the detection of HHV-8 antibodies using an indirect immunofluorescence assay. Baseline characteristics were analyzed to identify risk factors associated with HHV-8 seropositivity. Among seropositive participants, HHV-8 DNA was quantified on available oral and anal swabs, and ORF-K1 typing performed on HHV-8 positive samples. One hundred participants were seropositive at D0 (prevalence of 24%, 95% Confidence Interval (95%CI): 20·0-28·4) and 18/329 seroconverted during the study (incidence rate of 2·66 per 100 person-years, 95%CI: 1·57-4·20). Risk factors independently associated with baseline HHV-8 seropositivity included older age, high number of sexual partners, chemsex use and HSV-2 seropositivity. Among HHV-8 seropositive participants with available swab(s) for virological analysis, 37/115 (32%) displayed HHV-8 oral shedding, and 5/113 (4.4%) anal shedding at least once. Four patients had positive viral load before seroconversion. Prevalence and incidence of HHV-8 infection were high in HIV-negative PrEP users. Among seropositive participants, HHV-8 DNA is mainly detected in saliva, which may play a major role in viral transmission in this population.

Constrictive Pericarditis induced by Human Herpes Virus Infection: A Case Report

Constrictive pericarditis represents a severe diastolic heart failure secondary to an inelastic and poorly compliant pericardium mediated by inflammation and fibrosis. It shows relative regional and temporal differences with respect to the etiologies.

The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection.

The incidence of human herpesvirus (HHVs) is gradually increasing and has affected a wide range of population. HHVs can result in serious consequences such as tumors, neonatal malformations, sexually transmitted diseases, as well as pose an immense threat to the human health. The cGAS-STING pathway is one of the innate immune pattern-recognition receptors discovered recently. This article discusses the role of the cGAS-STING pathway in human diseases, especially in human herpesvirus infections, as well as highlights how these viruses act on this pathway to evade the host immunity. Moreover, the author provides a comprehensive overview of modulators of the cGAS-STING pathway. By focusing on the small molecule compounds based on the cGAS-STING pathway, novel targets and concepts have been proposed for the development of antiviral drugs and vaccines, while also providing a reference for the investigation of disease models related to the cGAS-STING pathway. HHV is a double-stranded DNA virus that can trigger the activation of intracellular DNA sensor cGAS, after which the host cells initiate a cascade of reactions that culminate in the secretion of type I interferon to restrict the viral replication. Meanwhile, the viral protein can interact with various molecules in the cGAS-STING pathway. Viruses can evade immune surveillance and maintain their replication by inhibiting the enzyme activity of cGAS and reducing the phosphorylation levels of STING, TBK1 and IRF3 and suppressing the interferon gene activation. Activators and inhibitors of the cGAS-STING pathway have yielded numerous promising research findings in vitro and in vivo pertaining to cGAS/STING-related disease models. However, there remains a dearth of small molecule modulators that have been successfully translated into clinical applications, which serves as a hurdle to be overcome in the future.

Detection of Human Herpesviruses in Sera and Saliva of Asymptomatic HIV-Infected Individuals Using Multiplex RT-PCR DNA Microarray.

Human herpesviruses (HHVs) are frequently linked to an increased risk of acquiring human immunodeficiency virus (HIV), and vice versa. This study aimed to detect human herpesvirus (HHV) members in the sera and saliva of asymptomatic HIV-infected individuals. Paired saliva and serum samples were obtained from 30 asymptomatic HIV-infected individuals. HHVs were detected with a multiplex reverse transcription-polymerase chain reaction (RT-PCR) DNA microarray Clart®Entherpex kit. A total of 30 subjects were enrolled: 23 (76.67%) men and 7 (23.33%) women. The present study showed that at least one or more HHV members were detected in the saliva and sera of all (100%) of the subjects. In the saliva, we detected herpes simplex virus 1 (HSV-1) 6.67%, herpes simplex virus 2 (HSV-2) 6.67%, Epstein-Barr virus (EBV) 86.67%, cytomegalovirus (CMV) 63.33%, HHV-6 (40%), and HHV-7 (83.33%). In the sera, HSV-2 (20%), EBV (30%), CMV (40%), HHV-6 (0%), and HHV-7 (76.67%) were found, but not HSV-1. VZV and HHV-8 were not detected in either the saliva or sera. EBV and HHV6 were significantly more prevalent in the saliva than they were in the sera of asymptomatic HIV-infected individuals (p < 0.05). However, no significant differences were found in the prevalence of HSV-1, EBV, CMV, HHV-6, and HHV-7 in the saliva and sera of asymptomatic HIV-infected individuals (p > 0.05). In conclusion, the multiplex RT-PCR DNA microarray can serve as a valuable diagnostic tool that can be used as a screening tool or a first-line test for HHVs infections.

HHV-6 infections in hospitalized young children of Gabon

PurposeFever is a common cause for hospitalization among the pediatric population. The spectrum of causative agents is diverse. Human herpesvirus 6 (HHV-6) is a ubiquitous virus that often causes hospitalization of children in western countries. Previously, we investigated the cause of fever of 600 febrile hospitalized children in Gabon, and in 91 cases the causative pathogen was not determined. In this study, we assessed HHV-6 infection as potential cause of hospitalization in this group.MethodsBlood samples were assessed for HHV-6 using real-time quantitative PCR. Three groups were investigated: (1) group of interest: 91 hospitalized children with febrile illness without a diagnosed causing pathogen; (2) hospitalized control: 91 age-matched children hospitalized with febrile illness with a potentially disease-causing pathogen identified; both groups were recruited at the Albert Schweitzer Hospital in Lambaréné, Gabon and (3) healthy control: 91 healthy children from the same area.ResultsSamples from 273 children were assessed. Age range was two months to 14 years, median (IQR) age was 36 (12–71) months; 52% were female. HHV-6 was detected in 64% (58/91), 41% (37/91), and 26% (24/91) of the samples from groups 1, 2, and 3, respectively; with statistically significant odds of being infected with HHV-6 in group 1 (OR = 4.62, 95% CI [2.46, 8.90]). Only HHV-6B was detected.ConclusionsAlthough tropical diseases account for a large proportion of children's hospitalizations, considering common childhood diseases such as HHV-6 when diagnosing febrile illnesses in pediatric populations in tropical countries is of importance.

Human Herpesvirus-8 Positive Multicentric Castleman’s Disease with Complete Response after Rituximab Monotherapy: A Case Report

Castleman’s disease is a rare non-neoplastic lymphoproliferative disorder of unknown origin. It is classified into unicentric or multicentric based on its anatomical distribution. Multicentric Castleman’s disease can be subdivided according to the presence of human herpesvirus-8 (HHV-8) infection. Castleman’s disease has a rare incidence, and HHV-8-positive multicentric Castleman’s disease is even rarer. There are several types of natural course for this disease, and the rapidly progressing type can lead to death within a few weeks, emphasizing the need for prompt diagnosis and treatment. We report a recent case from Korea, presenting with multiple lymphadenopathies, confirmed as HHV-8-positive multicentric Castleman’s disease through biopsy, and achieving complete response with rituximab monotherapy.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.

Investigation on colorectal cancer and human herpesvirus infection among Algerian patients.

Herpesviruses are a widespread family of double-stranded DNA viruses that establish life-long persistent infection in their hosts. Cumulative evidence tends to argue for the association of human herpesviruses, such as Kaposi's sarcoma herpesvirus (KHSV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) with various human disorders and diseases. The present study aims to investigate the presence of herpesviruses in colorectal cancer (CRC). We investigated the presence of herpesviruses in 69 formalin-fixed paraffin embedded tissue (FFPE) biopsies, using a pan-herpesvirus nested polymerase chain reaction (PCR) with degenerate primers and HCMV specific primers to identify the presence of herpesviruses in CRC tissue. None of the samples we examined were positive for herpesviruses. Our results suggest that there is no (or very low) prevalence of lifelong herpesvirus infection in Algerian CRC patients. Larger cohorts may provide more insight into the prevalence of herpesviruses in Algerian CRC biopsies.

Association between atopic dermatitis, autoimmune illnesses, Epstein-Barr virus, and cytomegalovirus.

Atopic dermatitis (AD) is a Th2-driven inflammatory skin disease that has been associated with other autoimmune illnesses (AI) and has a well-known predisposition to infection with herpes simplex virus infection. Yet, few studies have evaluated the association between atopic dermatitis, autoimmune illness, and other human herpes virus (HHV) infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). We aimed to evaluate the association between AD, specific AIs, CMV, and EBV in a random sample of the Optum Clinformatics Data Mart database, a US administrative claims database. AD was defined based on ICD diagnostic codes. Patients with AD were exact matched to those without AD on sex, age at enrollment, time observed in the dataset and census division. Our outcomes of interest were rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), CMV, and EBV infection as defined by specific ICD codes. Logistic regression models were used to examine the association between AD and our outcomes of interest [odds ratio (95% confidence intervals)]. Our full cohort included 40,141,017 patients. In total, 601,783 patients with AD were included. As expected, patients with AD had a higher prevalence of asthma and seasonal allergies versus controls. Individuals with AD have an increased risk of EBV, CMV, RA, CD, UC, and MS. While we cannot demonstrate a causal association, the observed associations between AD and AI may be in part mediated by these types of HHV (i.e., CMV and EBV), a finding that merits further study.