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 andcan be divided into HHV-6 A and B. Primary infection is mild and occurs usually in childhood; therefore themajority of healthy adults have serologic evidence of prior infection.  HHV-6 can re-activate in theimmunocompromised transplant recipient leading to asymptomatic viralreplication or less commonly active infection. The highest prevalence by pcr has been shown to occur in bone marrowtransplant recipients (28% to 75%) but viral replication has also been shown tooccur 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 tospecific antiviral treatments.   
How does HHV-6infection present?
HHV-6 infection commonly presents with high fever oftenassociated with leukopenia, and encephalitis between 2-4 weeks posttransplantation.  Other clinicalmanifestations include pneumonitis, hepatitis, colitis and bone marrowsuppression.  Rash typical of a leukocytoclasticvasculitis can also be seen. Encephalitis may be associated with seizure activity andhyponatremia.  Encephalitis is morecommonly seen in BMT patients but has been described in solid organ transplantpatients as well.  HHV-6 infectionscommonly co-exist with other viral infections including CMV. 
HHV-6 reactivation has also been associated with druginduced hypersensitivity syndromes, malignancies, multiple sclerosis, fulminanthepatitis and mycocarditis though causality has not been demonstrated.
What are theassociated laboratory and imaging findings?
CBC: Bone marrow suppression, leucopenia, thrombocytopenia
Chemistry: Transaminitis, hyponatremia
CSF:  High lymphocytecell count with elevated protein.  HHV-6can be detected in CSF by pcr. 
MRI of brain: Symmetric non-enhancing white matter lesions.  MRI may be normal in patients infected withHHV-6.
How can youdiagnose active infection?
Serologic testing: Sensitivity varies and most tests cross react with HHV-7.  A fourfold increase in titers orseroconversion is considered diagnostic.
Virus culture from affected tissue or blood can be done butare difficult to perform.
Viral detection: Virus may be present in PMBC’s of patients with latent infection leadingto a “false” positive pcr.   ThereforeHHV-6 should be identified in affected tissue or acellular plasma orserum. 
What are thetreatment options?
No therapy has been clearly documented to treat HHV-6although several agents with in-vitro activity have been tried.  Ganciclovir is effective against HHV-6B butmay not be active against HHV-6A (minority of infections).  Foscarnet has activity against both A and Bhowever; its use is complicated by nephrotoxicity.  In severe cases both agents can be tried andwhenever possible a reduction in immunosuppression should be considered.


Dr. Vinay Nair

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