It has long been a mystery why HHV-6 is preferentially reactivated in drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug induced hypersensitivity syndrome (DIHS). HHV-6 reactivation occurs in over 60% of severe cases and is part of the definition of DIHS in Japan. Investigators in Japan suspect that the explanation may lie with the CD134 receptor on activated CD4 cells.
Another case of drug induced liver injury accompanied by HHV-6 reactivation has been reported in Japan, the second such case without exanthema to be described. An earlier case was reported last year (Fujita 2015). The authors suggest that drug-induced liver injury cases be investigated for HHV-6 reactivation when liver dysfunction begins several weeks after the initiation of a new drug typically associated with hypersensitivity syndromes.
A group from Baylor College of Medicine reviewed the efficacy of treating viral infections in transplant patients with primary immunodeficiencies using their viral-specific T lymphocytes. A total of 36 patients were treated with these immunotherapy infusions before or after undergoing hematopoietic stem cell transplantation, and a complete or partial antiviral response were seen in 86% of patients with CMV, 76% of patients with EBV and all patients with adenovirus or HHV-6.
A new study suggests that HHV-6 and HHV-7 are important co-factors for the development of CMV infection post-transplant in allogeneic hematopoietic stem cell transplantation patients. Additionally, the presence of HHV-7 and CMV together may result in more severe infections than either virus alone.
In a French study of 366 adult allogenic hematopeietic stem cell transplantation (aHSCT) recipients CD8+ T cell recovery was significantly reduced in patients with HHV-6 reactivation. HHV-6 reactivation was also associated with reduced survival and increased infections of CMV and BKV.
Researchers from Stanford University successfully used circulating cell-free DNA to identify infections in lung transplants that can often be found only with a more invasive transbronchial biopsy. This hypothesis free approach led to find HHV-6 & 7 at high levels in patients with infections, even though these viruses are not generally considered lung pathogens.
A hematology group in Australia reported a case of biopsy-proven HHV-6 myocarditis post-hematopoietic stem cell transplantation (HSCT). he post-mortem exam confirmed dilated cardiomyopathy and focal changes consistent with viral myocarditis and cardiac tissue was positive for HHV-6 DNA by nested and quantitative PCR. Separately, A Japanese group reported a worman who developed pericarditis with over 10,000 copies/ml of HHV-6 DNA in the pericardial fluid, after a cord blood transplant.
A group of researchers from Sao Paulo, Brazil reported the development of HHV-6 infection in the striatum of a 32-year-old man six weeks after allogeneic hematopoietic stem cell transplantation. This is the first reported case of HHV-6 infection affecting the striatum and presenting with Parkinsonism post-HSCT.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four patients (3.8%) were diagnosed with HHV-6 encephalitis. The group used a qualitative multiplex PCR and then used a quantitative PCR to confirm the results.
A prospective study authored by Joshua Hill and Danielle Zerr determined that higher than average HHV-6B DNA levels increased the odds of developing delirium after cord blood transplantation (CBT) by almost three fold. Patients with DNA loads in the top quartile had a 4.5 fold increase in delirium.
HHV-6 may be the cause of “fever of unknown origin” in 30% of stem cell transplant (SCT) patients. By the third week after SCT, 70% of HHV-6 positive patients had a skin rash, compared to 39% of HHV-6 negative patients.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four or 3.8% of the population were diagnosed with HHV-6 encephalitis.
In an article published in the Pediatric Infectious Disease Journal, Tetsushi Yoshikawa’s team from Fujita Health University School of Medicine determined that the severe neutropenia in primary HHV-6B infection is tied to reduced platelet counts, lower RANTES and higher levels of MCP-1, MIG and IP-10.
A large-scale multiplex PCR assay developed by a team in Japan was used to study 13 DNA viruses in 105 allogenic hematopoietic stem cell transplant patients. They found that patients treated with steroids had a significantly higher risk of HHV-6 reactivation (p=0.027), and that HHV-6 was the only virus tied to the onset of acute GVHD (p=0.016).
Intensive care (ICU) patients with co-infections of HHV-6 and CMV are 7.5x more likely to die or have an extended stay in the hospital. On the other hand, single infections with either HHV-6 or CMV did not significantly impact outcome.