Serum-Negative, Site Specific HHV-6 Infection Causes Nausea and Vomiting Following Double Umbilical Cord Stem Cell Transplantation

Abstract

Purpose: Current literature describes similar clinical manifestations between human herpes virus 6 (HHV-6) infection and graft versus host disease (GvHD) in post-hematopoietic stem cell transplant (HSCT) recipients. Therefore, it is essential to consider HHV-6 infection in patients with gastrointestinal (GI) symptoms suggestive of GvHD. We present a case that highlights the importance of testing gastroduodenal tissue as an adjunct to serological testing of HHV-6 in this patient population. A 30-year old woman (HHV-6 IgG +) with acute lymphocytic leukemia (ALL) presented for a double umbilical cord stem cell transplant with myeloablative conditioning. Her post-transplant course was complicated by late engraftment, Klebsiella pneumoniae sepsis, BK cystitis, HHV-6 viremia and biopsy-proven stage 4 GvHD of the upper and lower GI tract associated with fever, abdominal pain, diarrhea and vomiting. She was treated with 3 months of high dose steroids for GvHD and one month of a combination of IV foscarnet and oral valganciclovir for HHV-6 reactivation (viral load 66,292 cpy/ml). Her symptoms improved (viral load undectable), but she then returned to the hospital day + 150 post transplant for dehydration secondary to persistent nausea and vomiting. Serum PCR testing for HHV-6 and gastroduodenal biopsies for GvHD were negative. However, PCR of gastroduodenal tissue biopsies for HHV-6 was positive (viral load 5,912 viral copies/1,000 cell equivalent). She was restarted on valgancyclovir for 4 weeks and had total resolution of her symptoms at the end of this time. HHV-6 is a lymphotrophic virus which belongs to the β-herpesviridae family. It typically remains latent in certain host cells but can reactivate in immunocompromised patients. In HSCT recipients, gastrointestinal complications of HHV-6 may include abdominal pain, nausea, vomiting, diarrhea, cholestasis and hepatitis which mimics and can worsen the grade of GvHD. Cord blood transplant recipients and previous episodes of GvHD are found to be predictors of HHV-6 reactivation, as was seen in our patient. This case highlights that HHV-6 viremia need not be synchronous with a site-specific infection in HSCT patients with upper GI symptoms. Given the prevalence and correlation between GI manifestations of HHV-6 and GvHD, isolated local infection should be considered in the differential diagnosis of persistent GI symptoms despite serumnegative HHV-6 testing. The clinical benefit of treating biopsy-proven HHV-6 of the GI tract should be further studied in patients with and without GvHD post-HSCT.