Continuing medical education
Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management

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Eight of the more than 80 known herpesviruses are human pathogens. Human herpes simplex virus (HSV) is a contagious infection with a large reservoir in the general population. It has a potential for significant complications in the immunocompromised host. In addition, psychological distress caused by the negative stigma associated with genital herpes and visible facial lesions in those experiencing frequent outbreaks renders it a challenging clinical dilemma. This article reviews the epidemiology, pathogenesis, and diagnostic features of HSV infections, providing the clinician with an up-to-date understanding of the available management strategies for mucocutaneous HSV-induced disease.

Learning objectives

At the conclusion of this learning activity, participants should understand the structure and biological properties of human herpesviruses; understand the transmission and epidemiology of human HSV infections; understand the spectrum, pathogenesis, and symptomatology of HSV disease affecting humans; understand the diagnostic features and methodologies employed in clinical practice to diagnose herpes simplex infections; and understand the available management strategies for mucocutaneous HSV-induced disease.

Introduction

More than 80 herpesviruses have been identified, 8 of which are known human pathogens.1, 2, 3 Herpes simplex viruses belong to the ubiquitous Herpesviridae family of viruses, which comprises herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella zoster virus, cytomegalovirus, Epstein-Barr virus as well as human herpesviruses 6 and 7 and Kaposi's sarcoma–associated herpesvirus (type 8).4, 5, 6 HSV-associated diseases are among the most widespread infections, affecting nearly 60% to 95% of human adults.7, 8 They are incurable and persist during the lifetime of the host, often in latent form. Their clinical manifestations are variable and influenced by the portal of viral entry, degree of host immune competence as well as primary or secondary nature of the disease.8 Clinical presentations of HSV infection range from asymptomatic infection to mucocutaneous conditions such as orolabial, ocular, and genital herpes, herpetic whitlow, herpes gladiatorum, and eczema herpeticum as well as central nervous complications such as neonatal herpes and herpetic encephalitis and fatal dissemination, a particular threat in the immunosuppressed host.8, 9, 10

Section snippets

Structure and biological properties

All human herpesviruses measure approximately 200 nm in diameter and contain a linear, double-stranded DNA core of approximately 150 kilo base pair (Kbp) enclosed within a protein capsid, covered by a tegument and a glycoprotein-containing envelope.4, 5, 9, 11, 12, 13 The expressed pattern of alpha, beta, and gamma genes respectively control translation of viral genome, transcription of proteins essential for viral DNA synthesis, and collection/exit of viral particles from the infected cell.4

Primary herpetic gingivostomatitis

Irrespective of the viral type, HSV primarily affects skin and mucous membranes.11 Primary herpetic gingivostomatitis (PHGS) is the most common orofacial manifestation of HSV1 infection and is characterized by oral and/or perioral vesiculoulcerative lesions.8, 73 PHGS typically develops after first-time exposure of seronegative individuals or those who have not produced adequate antibody response during a previous infection with either of the two HSVs.10, 11, 13 A majority of infections are

Diagnosis

The mode of onset, classic constitutional symptoms, appearance and distribution of lesions, absence of prior herpetic episodes on history, and reported exposure to HSV1 often establish the diagnosis of primary herpetic gingivostomatitis.9, 12, 25, 72, 73 The presence of multiple, round, superficial oral ulcerations as well as acute, generalized marginal gingivitis on clinical examination are especially helpful in diagnosis.72 Occasionally, diagnosis of primary HSV infections poses a challenge,

Management

In general, management of HSV infections starts with prevention. Examples of appropriate preventive strategies include education of the public regarding the contagious nature of the disease, its potential for autoinoculation, efficacy of barrier techniques such as condoms in preventing viral transmission, asymptomatic viral shedding, triggers, and prophylactic antiviral therapy.2, 9, 12, 36, 69, 72, 73, 90, 228

An overall evaluation of the clinical signs, symptoms, and general health of the

Conclusion

Mucocutaneous infections caused by HSVs are common in the general population. Although not a major concern in most healthy individuals, frequent outbreaks are often associated with inconvenience, cosmetic concerns, and psychological distress. Such infections may also lead to significant morbidity or mortality in those unable to mount sufficient immune response. Although recent scientific advances have dramatically improved our understanding of the HSV pathogenesis, diagnosis, and treatment, a

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    Conflicts of interest: None declared.

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