Multicentric Castleman's disease and Kaposi's sarcoma in a cyclosporin treated, HIV-1 negative patient: case report

BACKGROUND: Multicentric Castleman's disease (MCD) is a rare disease, but is more frequent in AIDS patients. MCD has only been reported twice before in patients receiving immunosuppressive therapy after renal transplantation, and never in patients receiving immunosuppressive therapy without transplantation. About half of the cases of MCD are human herpesvirus 8 (HHV8) - related, in contrast to Kaposi's sarcoma, a more common complication arising after immunosuppression, where the virus is found in virtually all cases. CASE PRESENTATION: We report a HIV-1 negative, non-transplant patient who developed HHV8-associated multicentric Castleman's disease and Kaposi's sarcoma after 17 years of immunosuppressive treatment with cyclosporin A for a minimal change nephropathy. Chemotherapy with liposomal doxorubicin resolved both symptoms of multicentric Castleman's disease and Kaposi's sarcoma in this patient. A concomitant decline in the HHV8 viral load in serum/plasma, as determined by a quantitative real-time PCR assay, was observed. CONCLUSIONS: Multicentric Castleman's disease can be a complication of cyclosporin A treatment. Both multicentric Castleman's disease and Kaposi's sarcoma in this patient were responsive to liposomal doxorubicin, the treatment of choice for Kaposi's sarcoma at the moment, again suggesting a common mechanism linking both disorders, at least for HHV8-positive multicentric Castleman's disease and Kaposi's sarcoma.HHV8 viral load measurements can be used to monitor effectiveness of therap

Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy

This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART). Grade 4 LEE was defined as aminotransferase levels 1 10 times the upper limit of normal and 1 200 U above baseline levels. A multivariate Cox model was used to identify risk factors. The incidence of LEE was 6.3%. No patients died of LEE consequences. Risk factors were higher baseline alanine aminotransferase levels, chronic hepatitis B or C virus infection, antiretroviral therapy-naive patients undergoing their first HAART regimen, recent start of a regimen of nevirapine or high-dose ritonavir, and female sex. In hepatitis B virus (HBV)-coinfected patients, discontinuing lamivudine (3TC) use was a risk factor. In 97% of cases, greater than or equal to1 risk factor was present. In HBV-coinfected patients using 3TC, continued use of 3TC should be considered, even if 3TC-resistant HIV strains develo

Development of virus-specific CD4(+) T cells on reexposure to varicella-zoster virus

Immunity to childhood diseases is maintained for decades by mechanisms that, at present, are still unclear. We longitudinally studied immune responses in 16 adults exposed to children experiencing varicella (chicken pox). None of the individuals showed clinical signs of infection, and varicella-zoster virus (VZV) DNA could not be detected in peripheral blood or cultured from nasopharyngeal swabs. Exposure to VZV, however, induced expansion of antigen-specific CD4(+) T cells in peripheral blood, with concomitant changes in cytotoxic CD8(+) T cells and natural killer cells. VZV-specific memory CD4(+) T cells were uniformly CD45RA(-) and enriched for CD27(-) cells. The virus-specific cells produced interferon- gamma, tumor necrosis factor- alpha, and interleukin-2. These memory responses to VZV were compared with the primary immune responses of children experiencing varicella. VZV-specific memory CD4(+) T cell responses largely resemble the primary immune response to VZ

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

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

Differentiation of cytomegalovirus-specific CD8(+) T cells in healthy and immunosuppressed virus carriers

During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD8(+) T cells and persisting viruses, frequencies and phenotypes of CMV-specific CD8(+) T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating virus-specific CD8(+) T cells, as measured by peptide-induced interferon gamma (IFN-gamma) production, but not the number of virus-specific T cells enumerated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-gamma-secreting CD4(+) helper T cells. Circulating CMV- specific CD8(+) T cells did not express CCR7 and may therefore not be able to recirculate through peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV-specific T cells in healthy donors appeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD8(+) T cells were significantly higher in immunosuppressed individuals than in healthy donors. In these patients CMV-specific cells predominantly had an effector phenotype, that is, CD45R0(+)CD27(-)CCR7(-) or CD45RA(+)CD27(-)CCR7(-) and contained both granzyme B and perforin. Our data show that in response to immunosuppressive medication quantitative and qualitative changes occur in the CD8(+) T-cell compartment. These adaptations may be instrumental to maintain CMV latency. (Blood. 2001;98:754-761