Elsevier

Mayo Clinic Proceedings

Volume 87, Issue 10, October 2012, Pages 1004-1014
Mayo Clinic Proceedings

Review
Human Herpesviruses 6, 7, and 8 From a Dermatologic Perspective

https://doi.org/10.1016/j.mayocp.2012.04.010Get rights and content

Abstract

Human herpesviruses (HHVs) have frequently been suspected as etiologic agents or cofactors in cutaneous disease. However, clearly established associations are rare. Investigations into an etiologic association between HHVs and cutaneous disease are complicated by the ubiquity and nearly universal prevalence of some herpesviruses. This article summarizes the associations between cutaneous disease and HHV-6, HHV-7, and HHV-8. In addition to a personal library of references, the PubMed database of biomedical literature was searched using the following Medical Subject Heading terms: HHV-6, HHV-7, and HHV-8, each in conjunction with cutaneous manifestations, virology, epidemiology, dermatopathology, and therapeutics, between 1998 and March 2011. Free-text searches with known or suspected disease associations were added for broader coverage. The results have been summarized to provide a practical review for the physician likely to encounter cutaneous diseases.

Section snippets

HHV-6 and HHV-7 and Their Epidemiologic Features

Classification of the herpesviruses includes alpha herpesviruses (HHV-1 and HHV-2), which are fast growers; beta herpesviruses, which are slow growers and include the genus Roseolovirus (HHV-6 and HHV-7) and the genus Cytomegalovirus (CMV); and gamma herpesviruses, which include Epstein-Barr virus in the genus Lymphocryptovirus. This discussion is restricted to HHV-6, HHV-7, and HHV-8. Human herpesvirus 6 has 2 variants, A and B, although new evidence suggests that these subtypes are distinct

Cutaneous Disease Caused by HHV-6 and HHV-7

The identified disease association of HHV-6 and HHV-7 is roseola infantum, also known as exanthem subitum,20 which develops in only a few infected children. On the basis of isolation of the virus and seroconversion in blood samples from 4 patients in the febrile phase of the illness, Yamanishi et al21 proposed a causal association in 1988. One year later, a report from a prospective study of 38 children confirmed HHV-6 viremia in 100% of patients with roseola infantum in the early stages of the

Clinical Features of Cutaneous Diseases Associated With HHV-6 and HHV-7

Diagnosis of viral exanthems is often easier said than done. In a Brazilian study of 223 children, 43.5% had evidence of primary HHV-6 infection.60 However, only 21% with HHV-6 had a typical roseola-like illness, whereas 73% and 46% met the clinical criteria for measles and rubella, respectively. The diagnosis assigned most commonly to children with serologically proven primary HHV-6 infection was “unknown.” Future proposed clinical criteria for such diagnoses would be important not only for

Viral Diagnostic Testing

In clinical practice, the diagnosis and management of HHV-6 and HHV-7 by cutaneous manifestations usually depend on clinical acumen rather than viral detection. Each disease might also have unique nonviral features. However, discerning the presence of HHV-6 and HHV-7, if not necessarily their contribution to skin abnormalities, has become increasingly sophisticated and may play an increasing role in the future, as evidenced by the Japanese consensus group diagnostic criteria for DIHS.46

Antiviral Treatments

Better understanding of their pathogenesis may lead to better targeting of HHV and HHV-associated diseases. Tailored therapies for HHV-6, HHV-7, and HHV-8 are still in their infancy. There are currently no approved treatments for HHV-6 and HHV-7 infections. From a practical perspective, immunocompetent persons with uncomplicated skin manifestations associated with HHV-6 and HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic and supportive management. In addition,

Conclusion

Investigation of the 3 most recently identified HHV viruses is fascinating for several reasons. First, although the currently available data mostly allow disease association rather than causation analyses, it is likely that these 3 viral siblings serve as provoking, contributing, or complicating factors in multiple cutaneous disease presentations. Second, HHV-6, HHV-7, and HHV-8 have ingeniously incorporated key host DNA fragments that allow them to adapt more easily, to escape immunodetection,

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