HHV-6B infection commonly presents with a skin rash. This exanthemous rash is associated with the following clinical manifestations:
Over 90% of all children undergo HHV-6B primary infection by the age of three. Although normally an asymptomatic event, approximately 20% of these infections manifest as exanthema subitum (commonly known as roseola), a condition characterized by fever and febrile illness followed by an erythematous maculopapular rash. HHV-6 encephalopathy/encephalitis can also occur with rash during this initial infection (Yoshikawa 2009), and is the leading cause of hospitalization for infants with febrile illness (Zerr 2005).
Post-transplant HHV-6 reactivation and acute GVHD:
The most frequent manifestation of HHV-6 reactivation following hematopoietic stem cell transplantation (HSCT) is febrile rash, which normally presents in the first month following transplantation (Gotoh 2014, Roux 2012, Yoshikawa 2001). Furthermore, HHV-6—related rash is considered a differential diagnosis of acute graft-versus-host disease in the post-transplant setting (Pichereau 2011).
Hypersensitivity (DIHS/DRESS and SJS/TEN):
Numerous studies have linked the reactivation of HHV-6 to Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), an uncommon but severe cutaneous adverse drug reaction characterized by acute widespread erythematous maculopapular rash likely caused by the recruitment of HHV-6 to the skin following adverse drug reaction (Tohyama 2011). This rash associated with HHV-6 reactivation also occurs in SJS/TEN (Teraki 2010).
Rash associated with HHV-6 reactivation has been reported in additional clinical settings, including acute lymphocytic leukemia (Fujita 1996).