HHV-6 & Rash/Roseola

Primary Infection:

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 (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).

Immunodeficiency:

Rash associated with HHV-6 reactivation has been reported in additional clinical settings, including acute lymphocytic leukemia (Fujita 1996).