What does it mean if a genital ulcer caused by herpes simplex virus (HSV) hasn't recurred in three years?

Absence of HSV Recurrence After Three Years

A genital herpes ulcer that has not recurred in three years is highly unusual and should prompt reconsideration of the original diagnosis, as HSV-2 genital herpes is characterized as a recurrent, incurable viral disease with most infected persons experiencing intermittent viral shedding and potential recurrences throughout their lifetime. 1, 2

Understanding the Natural History of Genital Herpes

• Genital herpes simplex virus infection is explicitly described as a "recurrent, incurable viral disease" by the Centers for Disease Control and Prevention, with HSV establishing lifelong latency in sacral ganglia 1, 2
• Most cases of recurrent genital herpes are caused by HSV-2, though HSV-1 can also cause genital infection 1, 3
• Viral reactivation from latency leads to either genital ulceration or asymptomatic viral shedding, which occurs intermittently throughout the infected person's life 2, 3

Why Three Years Without Recurrence Is Atypical

• While the frequency of recurrences varies considerably among infected individuals, the complete absence of any recurrence over three years is not consistent with typical HSV-2 natural history 1, 2
• Some HSV-infected persons have "mild or unrecognized infections," but they still shed virus intermittently in the genital tract even without visible ulcers 1
• A minority of infected persons may have symptoms shortly after initial infection and then experience very infrequent recurrences, but complete absence of recurrence for three years warrants diagnostic reconsideration 1

Alternative Diagnostic Considerations

The original diagnosis should be questioned, as up to 25% of genital ulcers have no laboratory-confirmed diagnosis even after complete evaluation, according to the Centers for Disease Control and Prevention. 1, 4, 5

• If the initial ulcer was not confirmed by HSV culture, PCR/NAAT testing, or type-specific serology, alternative diagnoses should be considered 1, 5
• Other causes of genital ulcers that resolve without recurrence include chancroid (H. ducreyi), primary syphilis (T. pallidum), traumatic ulcers, or fixed drug eruptions 5, 6
• The Centers for Disease Control and Prevention notes that 10% of patients with genital ulcers have co-infections, which could complicate the clinical picture 1, 4

Recommended Approach

• Type-specific HSV serologic testing should be performed now to confirm whether HSV-2 (or HSV-1) infection ever occurred. 1
• HSV-2 serology using enzyme immunoassay or chemiluminescent immunoassay can detect antibodies to HSV glycoprotein G-2, though specificity concerns exist with index values between 1.1-2.9 1
• If HSV-2 serology is negative three years after the initial ulcer, the original diagnosis was likely incorrect, as antibodies develop within weeks to months after primary infection 1
• If HSV-2 serology is positive, the patient represents an unusual case of very infrequent recurrence, and counseling should emphasize that asymptomatic viral shedding can still occur and transmission remains possible 1, 2

Clinical Implications

• Even without visible recurrences, HSV-infected persons can transmit the virus through asymptomatic shedding, and many cases of genital herpes are transmitted by persons who are asymptomatic at the time of sexual contact 1, 3
• Counseling should address the natural history, potential for future recurrences (even after prolonged quiescence), transmission risk, and the role of suppressive antiviral therapy if recurrences do eventually occur 3, 7
• The absence of recurrence does not eliminate the need for partner notification and counseling about transmission prevention strategies 3