To acknowledge the place of inherited chromosomally integrated HHV-6 in an allogeneic HSCT recipient and discuss its pathogenicity.

Viral infections are a major cause of morbidity and mortality in HSCT patients. HHV-6 reactivation occurs in approximately 50% of HSCT recipients, typically early after engraftment and is linked to an increased risk of acute graft versus host disease (GVHD) and cytomegalovirus (CMV) reactivation. The incidence of HHV-6 encephalitis is around 1.4% and is associated with a high mortality rate and long-term cognitive sequelae in survivors. Chromosomally integrated HHV-6 occurs when the virus integrates into germline chromosomal telomeres, resulting in high levels of viral DNA in blood and tissues, without necessarily representing reactivation and need for treatment.

Case report

A 54-year-old woman with myelodysplastic syndrome presented with nausea, vomiting, headache, visual hallucinations, confusion, and progressive weakness one month after an allogeneic HSCT. The HHV-6 viral load (VL) in the cerebrospinal fluid was 8,600 copies/mL and 2,400,000 copies/mL in whole blood, with associated Epstein Barr Virus viremia. The tacrolimus level was elevated. She improved rapidly with adjustment of tacrolimus dose, foscarnet and rituximab. She was readmitted 3 weeks later with a new pruritic rash on her extremities, diarrhea, headache, and a persistently high HHV-6 VL in whole blood despite continuous antiviral treatment. The skin biopsy was diagnostic for GVHD, and colon biopsy was negative for inflammation or CMV. Of interest, the HHV-6 viral load on the donor’s whole blood was 2,700,000 copies/ml, favoring chromosomally integrated HHV-6 over reactivation. The patient was treated for GVHD with good outcome and the treatment for HHV-6 was discontinued. Retrospectively, HHV-6 was unlikely the reason that led to her first hospitalization.

Chromosomally integrated HHV-6 needs to be considered in patients with a persistent and elevated viral load in whole blood despite appropriate treatment.