Wednesday, June 15, 2011

Human Herpes Virus – 6: An uncommon but potentially treatable infectious agent in transplant recipients

HHV-6 is a DNA virus part of the beta-herpesvirus family and can be divided into HHV-6 A and B.  Primary infection is mild and occurs usually in childhood; therefore the majority of healthy adults have serologic evidence of prior infection.  HHV-6 can re-activate in the immunocompromised transplant recipient leading to asymptomatic viral replication or less commonly active infection.  The highest prevalence by pcr has been shown to occur in bone marrow transplant recipients (28% to 75%) but viral replication has also been shown to occur in liver (28% to 32%) and renal transplant recipients (23% to 36%).  Although asymptomatic viremia is common, clinically active infection carries a high mortality and may be susceptible to specific antiviral treatments.   
How does HHV-6 infection present?
HHV-6 infection commonly presents with high fever often associated with leukopenia, and encephalitis between 2-4 weeks post transplantation.  Other clinical manifestations include pneumonitis, hepatitis, colitis and bone marrow suppression.  Rash typical of a leukocytoclastic vasculitis can also be seen.  Encephalitis may be associated with seizure activity and hyponatremia.  Encephalitis is more commonly seen in BMT patients but has been described in solid organ transplant patients as well.  HHV-6 infections commonly co-exist with other viral infections including CMV. 
HHV-6 reactivation has also been associated with drug induced hypersensitivity syndromes, malignancies, multiple sclerosis, fulminant hepatitis and mycocarditis though causality has not been demonstrated.
What are the associated laboratory and imaging findings?
CBC: Bone marrow suppression, leucopenia, thrombocytopenia
Chemistry: Transaminitis, hyponatremia
CSF:  High lymphocyte cell count with elevated protein.  HHV-6 can be detected in CSF by pcr. 
MRI of brain:  Symmetric non-enhancing white matter lesions.  MRI may be normal in patients infected with HHV-6.
How can you diagnose active infection?
Serologic testing:  Sensitivity varies and most tests cross react with HHV-7.  A fourfold increase in titers or seroconversion is considered diagnostic.
Virus culture from affected tissue or blood can be done but are difficult to perform.
Viral detection:  Virus may be present in PMBC’s of patients with latent infection leading to a “false” positive pcr.   Therefore HHV-6 should be identified in affected tissue or acellular plasma or serum. 
What are the treatment options?
No therapy has been clearly documented to treat HHV-6 although several agents with in-vitro activity have been tried.  Ganciclovir is effective against HHV-6B but may not be active against HHV-6A (minority of infections).  Foscarnet has activity against both A and B however; its use is complicated by nephrotoxicity.  In severe cases both agents can be tried and whenever possible a reduction in immunosuppression should be considered.


Dr. Vinay Nair

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