A new case study suggests that HHV-6 might play a role in the multi-organ failure that often follows extreme cases of drug hypersensitivity. Although there have been many studies documenting HHV-6 viremia in drug hypersensitivity (DIHS/DRESS) cases, this is the first to examine an affected organ for signs of HHV-6 DNA and proteins.
The mortality rate from severe drug hypersensitivity is approximately 10%, and death usually results from a late flare in symptoms and failure of one or more organ, typically the liver, kidney, lungs or heart. HHV-6 viremia occurs in the majority of extreme drug hypersensitivity cases (Pritchett 2012) but the reason for the disproportionate reactivation of HHV-6 is not understood.
The case, which is presented by a Japanese group at Nara Medical School, described a man who developed renal failure of a man after a reaction to trimethoprim/sulphamethoxazole (TMP/SMX). The patient developed a rash, responded to corticosteroids, but then suffered a flare and sudden renal failure after 79 days. At autopsy, the kidney was strongly positive for HHV-6 DNA (800 copies per mg) compared to barely detectable levels (8 copies/mg) in other organs. Immunohistochemistry revealed that the tubular epithelial cells stained positive for HHV-6B. The patient’s skin was not positive for viral antigen. The authors conclude that HHV-6 infection of the kidney contributed to renal failure in this case.
Relatively few studies have been performed on the role of HHV-6 in renal allograft rejection. Two groups have shown that HHV-6 antigen is expressed in the tubular cells of transplant recipients (Hoshino 1995, Helantera 2008). Okuna et al reported that 8 of 21 kidney recipients had an increase in HHV-6 antibody titer and, in all 8 instances, the recipients suffered severe kidney damage. Virus was isolated from 2 of the recipients tested. The authors concluded that HHV-6 could induce rejection of renal transplants (Okuno 1990). A more recent study reported an association of both HHV-6 and HHV-7 reactivation in chronic allograft nephropathy (Chapenko 2009).
The liver is the most common organ to fail in extreme drug hypersensitivity (DIHS/DRESS) cases. HHV-6 can also cause acute liver disease, although in persistent liver disease there is often no sign of HHV-6 viremia (Buyse 2013). Similarly, one can die of persistent HHV-6 myocarditis with no sign in the peripheral blood (Leveque 2011). And in lung disease, the HHV-6 is often detectable in bronchial samples, but not the plasma (Seo 2015).
For more information, read the full case report.