Understanding the role of HHV-6 in D.R.E.S.S.

It's difficult to discuss DRESS without recognizing the important role that the Human Herpes Virus 6 HHV-6 plays in this condition. In the world of severe cutaneous adverse drug reactions, the virus, HHV-6 preferentially reactivates in DRESS patients, occurring in over 50% of cases.

 

While it has long been controversial as to the exact development of this virus in DRESS, it is well known amongst the medical experts that those who develop HHV-6 tend to have a more severe course of illness including late flare in symptoms and organ failure. Identifying reactivation of HHV-6 can help aid in diagnosis of DRESS. In fact, it is part of the definition of this condition DIHS (drug induced hypersensitivity syndrome) in Japan. While there currently are no internationally approved guidelines for the treatment of HHV-6, the use of antivirals has proven effective in some clinical cases and may be indicated in severe DRESS.

What is HHV-6?

HHV-6 stands for Human Herpes Virus 6. The majority of humans have been infected with it by the early age of three. Symptoms are often mild consisting of fever, diarrhea and the rash known as roseola. Like other herpesviruses, such as Epstein Barr and chicken pox, this virus lives dormant in most of us, sleeping quietly and causes no trouble. However, in certain conditions of immunocompromisation, such as drug hypersensitivity like DRESS, HHV-6 reactivation can occur and may wreak havoc in the body.

What is reactivation of a virus? 

It’s when a virus switches from a latent or “quiet” stage where it’s laying dormant and not replicating,  to a lytic or “active” phase where it is once again replicating. Reactivation can be provoked by external or internal cell stimuli. 

Why does HHV-6 reactivate in DRESS patients?

We don’t know, exactly. While there are some theories, it remains a bit of a mystery. Scientist have been trying to figure this out for some time now. More studies are need to truly understand the DRESS/HV-6 connection.

Why is it important? 

DRESS patients who have an HHV-6 reactivation typically become more ill and, in severe cases, may require additional treatment with antivirals. It’s necessary to monitor these patients for a long time after the acute infection for signs of organ injury and autoimmune conditions like thyroiditis and diabetes.

Also, HHV-6 tends to preferentially reactivate in DRESS patients as opposed to other severe adverse drug conditions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) --making it an important diagnostic tool.

How will I know if I have an HHV-6 reactivation?

Your medical team should do blood tests to check for this as part of your diagnostic workup. There are only a few labs in the US that can properly test for active infection versus a prior infection of HHV-6. Detection of HHV-6 DNA in plasma generally means the patient has an active infection. Specific testing information can be found here: Overview on Testing for HHV-6 infection.

What else do I need to know about testing for HHV-6 specifically with DRESS?

HHV-6 reactivation can usually be detected two weeks after first symptoms (fever/rash) of DRESS occur. Thus, testing negative earlier than this does not mean that the patient is clear. It is important to retest when the virus may be detectable —a couple of weeks into the course of illness. 

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The HHV-6 Foundation is a non-profit organization with a wealth of information and scientific articles regarding the role of HHV-6 in drug hypersensitivity.