Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

Abstract

In contrast to other causes of herpetic lymphadenitis, the histological features associated with human herpesvirus-6 (HHV-6) infection have remained elusive since its discovery in 1986. We describe the histologic and phenotypic changes associated with acute HHV-6 lymphadenitis in two immunocompetent adults who presented with fever, fatigue, generalized lymphadenopathy, and elevated liver enzymes. Serologic tests for human immunodeficiency virus, acute Epstein-Barr virus, and cytomegalovirus infection were negative. Lymph node biopsies were consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were identified in CD4-positive T lymphocytes in expanded paracortical areas. Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa envelope glycoprotein showed that the inclusions were positive for viral antigen. Electron microscopy demonstrated numerous viral particles in the cytoplasm and nucleus, characteristic of Herpesviridae family. Clustering of viral particles was observed, which has previously been reported only in infected tissue culture cells. PCR followed by sequencing of DNA extracted from the lymph nodes identified the virus as HHV-6, type B. This is the first report that documents distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the cells harboring the virus in vivo are CD4-positive T lymphocytes.

Anatomical mapping of human herpesvirus reservoirs of infection

“…[38][39][40] In adults, HHV-6 infection may present with a mononucleosislike syndrome with acute lymphadenitis. 41 Disseminated infection may be associated with hepatitis, pneumonia, marrow suppression, and encephalitis. HHV-6 has also been detected, albeit at low levels, in Hodgkin's lymphoma and angioimmunoblastic lymphadenopathy, 42 and has been implicated in multiple sclerosis.…”

U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis

“…Virus infection has a significant effect on EC physiology, upregulating the production of specific chemokines, such as MCP-1, IL-8, and RANTES (14,15). The observations that lymph nodes are a site of viral persistence and viral infection has been associated to lymphadenitis (16) suggest that lymphatic ECs (LECs) from lymphatic tissue might be even more relevant for HHV-6 biology than vascular ECs. However, no information is available on the ability of HHV-6 to infect LECs, due to the lack of suitable in vitro systems.…”

Evidence for human herpesvirus-6B infection of regulatory T-cells in acute systemic lymphadenitis in an immunocompetent adult with the drug reaction with eosinophilia and systemic symptoms syndrome: A case report

“…A previous study demonstrated the presence of HHV-6-infected cells in the lymph node in a case of DRESS syndrome [14]. Another group also reported a patient with HHV-6-associated lymphadenopathy who had taken medication including sulfasalazine before admission and had died because of multiple organ failure (Case 2 of the reference [13]). These two cases are similar to the present case of a DRESS syndrome with HHV-6-associated lymphadenitis.…”

“…Although lymphadenopathy is very common among the patients with DRESS syndrome, so far there have been a few immunohistochemical studies of the lymphadenopathy [13,14]. A previous study demonstrated the presence of HHV-6-infected cells in the lymph node in a case of DRESS syndrome [14].…”

“…A few cases of HHV-6-associated acute lymphadenitis have been reported in pathological studies, including one in a patient with DRESS syndrome [13,14]. The expression of CD25 and FoxP3 is known to be induced by infections with viruses including the human T-lymphotropic virus 1 [15], and HHV-6 [16,17], but there have been no reports so far describing HHV-6 activation in Tregs or CD25(+)/FoxP3(+) cells.…”