HHV-6 acute lymphadenitis in immunocompetent patients

In All, Lymphadenitis, News by hhv6foundation

HHV-6 acute lymphadenitis in immunocompetent patients

A new case report describes a case of HHV-6 acute lymphadenitis in an immunocompetent patient, and reviews several other case reports of this condition. Although most viral lymphadenopathy is caused by EBV infection, CMV and HHV-6 are rare causes of mononucleosis in approximately 5% of cases (Naito 2006, Ablashi 1996). HHV-6 lymphadenitis is typically accompanied by fever, fatigue and generalized lymphadenopathy and elevated liver enzymes, and HHV-6 is usually only investigated when laboratory tests for EBV and CMV are negative. Plasma DNA testing for this highly cell associated virus may not be the best way to determine presence of HHV-6 infection in lymph nodes. For example, one group from Brazil reported that 25% of lymphadenopathy cases were positive for HHV-6 IgM antibodies (Freitas 2003). No study of  HHV-6 in lymph node biopsies has been conducted.

The report describes a 60-year-old man with 10-day history of fever, generalized lymphadenopathy and sore throat. Upon biopsy, the cervical lymph node showed diffuse paracortical expansion and scattered large atypical lymphoid cells with large nucleus and eosinophilic nucleoli, resembling immunoblasts. Furthermore, intranuclear eosinophilic viral inclusions were identified. Immunohistochemical analysis demonstrated that the large atypical lymphoid cells were positive for CD3 and CD4, consistent with a previous case report identifying the HHV-6 virus predominantly in CD4 positive T lymphocytes by electron microscopy (Maric 2004).

Other case reports include a 43-year-old man with fever, cervical lymphadenopathy, splenomegaly and pharyngitis, as well as 6-year-old girl with a rash on her trunk and face. The authors note that  the biopsies of immunocompetent patients with HHV-6 acute lymphadenitis contain atypical cells with large nucle­us containing large, eosinophilic inclusions that can easily be mistaken for Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). They suggest that a predominantly sinusal and paracortical distribution of the large lym­phoid cells with reactive lymphoid follicles should raise suspicion of HHV-6 associated lymphadenitis.

While most patients recover without antiviral treatment, one previous case describes a patient who died with worsening liver failure and encephalopathy 17 days after admission (Maric 2004). In the present case, the patient’s clinical symptoms eventually resolved over 24 months of periodic follow-up.

The review and report came from Zhejiang University College of Medicine in Hangzhou, China.

For more information, read the full paper, and visit the HHV-6 Foundation’s webpage on HHV-6 & mononucleosis/lymphadenopathy