Clinical misidentification of patients with first episode genital herpes: a note of caution.

Abstract

IN THIS ISSUE, Diamond and colleagues report that 41 (8%) of 498 persons clinically judged to have first-episode genital herpes at the University of Washington virology clinic had serologic evidence of remotely acquired herpes simplex virus-2 (HSV-2) infection.1 Clinicians have long recognized that overlap in the clinical presentation of first-episode and recurrent disease can make differentiation of first-episode and recurrent disease difficult when based solely on the history and clinical presentation. The issue was clarified somewhat in 1984 when Bernstein and colleagues reported that 75% of persons thought to have first-episode, nonprimary infection (first-episode HSV-2 infection in a person with serologic evidence of prior HSV-1 infection) had preexisting HSV-2 antibodies when tested in the recently introduced, type-specific Western blot assay.2 However, type-specific serologic testing is still unavailable in most clinical settings, and most patients with first-episode genital herpes are managed without determining whether the infection was recently or remotely acquired. In the current report, Diamond and colleagues have confirmed Bernstein's observations in a larger cohort and have carefully contrasted the clinical presentation and course in these patients with the clinical course in persons with serologically-confirmed primary and nonprimary first-episode genital herpes infections. Not unexpectedly, although there were some differences in the clinical presentation and natural history of the first-recognized recurrent episodes, there was enough overlap to prevent reliable differentiation from true primary or nonprimary first episodes based solely on the history or physical examination at presentation. It should be stressed, too, that the 41 patients are undoubtedly not representative of all patients with remote acquisition of HSV-2 who present with a first-recognized episode. The experienced staff at the virology research clinic excluded subjects who presented with a first-recognized episode who were judged on clinical grounds not to have a recently acquired, first-episode infection, but the number of persons excluded for this reason was not reported. These observations have important implications in several areas. The most obvious is in counseling and education of patients with a first episode of genital herpes. Patients and their partners should be counseled that most persons with a first episode have acquired infection from a sex partner within the preceding 2 to 4 weeks and that most persons who transmit infection to a sex partner are not aware that they have genital herpes.3,4 However, they should also be told that a significant proportion of persons who present with a first-recognized episode have acquired infection months or even years earlier. In the Seattle study, approximately 10% had remote acquisition, but the proportion would undoubtedly have been higher if the subjects were seen by less experienced clinicians or if the subjects with clinical findings suggesting recurrent rather than first-episode infection had not been excluded. The knowledge that the current sex partner may not be the source of the infection and that persons who transmit HSV are usually not aware that they have genital herpes may help stabilize a relationship weakened by the unexpected development of genital herpes in one partner. Diamond and colleagues suggest that virus culture and typing and type-specific HSV serology should be part of the routine evaluation of a patient who presents with a first episode of genital herpes. We support routine virus culture and typing, because the former confirms the clinical diagnosis and the latter provides valuable prognostic information about the expected frequency of recurrent episodes.5 The lack of access to reliable, inexpensive type-specific serologic testing in most commercial and public health laboratories may make the authors' recommendation for routine, type-specific serologic testing impractical at this time. However, we do support discussing the availability of type-specific testing with patients with a clinical first episode of genital herpes whenever type-specific serologic testing is available. As suggested by the authors, type-specific antibody testing of an acute serum in conjunction with virus culture and typing will usually allow the clinician to accurately determine whether infection was recent or remote. Furthermore, if the patient is found to have acquired infection recently and has had only one recent sex partner, serologic testing of the sex partner may also be helpful if the partner has no history of genital herpes. Although therapeutic guidelines for first-episode and recurrent genital herpes differ with respect to treatment duration, the recognition of this group of patients with first-episode symptoms and remote acquisition does not merit any change in treatment recommendations. Because antiviral treatment is safe and effective and because this subgroup of patients cannot be accurately identified in the acute setting, it is appropriate to treat them as they present, i.e., as first-episode cases. In summary, approximately 10% of persons with a history and clinical presentation suggesting first-episode genital herpes have serologic evidence of past HSV-2 infection. When available, type-specific serologic testing and virus culture and typing during the first clinical episode can accurately determine whether acquisition of infection was recent or remote.