Vesicular Lesion on the Penis After Sexual Intercourse
The most likely diagnosis is genital herpes simplex virus (HSV) infection, and you should initiate empiric antiviral therapy with acyclovir while obtaining laboratory confirmation through PCR or viral culture from the vesicular fluid. 1, 2
Diagnostic Approach
Primary Differential Diagnosis
The vesicular presentation strongly suggests HSV infection, which classically progresses from papules to vesicles containing clear fluid with thousands of infectious viral particles, then bursts to form shallow ulcers that crust and heal without scarring within 10 days. 3, 1
Laboratory confirmation is mandatory because clinical diagnosis alone is unreliable and can lead to both false-positive and false-negative diagnoses. 3
Essential Diagnostic Testing
You must obtain the following tests:
- HSV testing via PCR or viral culture from the vesicle base or vesicular fluid (PCR is preferred as it provides typing and has highest sensitivity, especially for suboptimal specimens). 3, 1
- Syphilis serology is mandatory because up to 10% of patients with genital ulcers have HSV co-infected with Treponema pallidum, and occasionally both organisms can be recovered from the same lesion. 3, 2
- HIV testing is strongly recommended as genital ulcers increase HIV transmission risk. 3, 2
- Testing for Chlamydia trachomatis and Neisseria gonorrhoeae should be performed as part of comprehensive STI screening. 1
Specimen Collection Technique
For vesicular lesions specifically:
- Open vesicles with a sterile needle
- Collect vesicular fluid content with a swab
- Apply to microscope slide for immunofluorescence or introduce into transport media for viral culture/PCR 3
Critical Clinical Distinctions
Features Supporting HSV Diagnosis
Painful ulcers strongly favor HSV over syphilis, which typically causes painless chancres. 2 However, be aware that primary syphilis lesions are frequently painful (49.2%) and/or multiple (37.7%) even without HSV co-infection, contrary to classic teaching. 4
Important Pitfalls to Avoid
- Do not rely on the "painless chancre" rule to exclude syphilis—recent evidence shows nearly half of primary syphilis lesions are painful. 4
- Do not assume a single pathogen—3-10% of genital ulcer patients have more than one pathogen present. 2
- Even after complete diagnostic evaluation, 25% of genital ulcers have no laboratory-confirmed diagnosis, emphasizing the importance of empiric treatment. 1
Non-Infectious Mimics to Consider
The differential diagnosis must include:
Treatment Recommendations
Empiric Antiviral Therapy
Initiate acyclovir immediately while awaiting laboratory confirmation, as early treatment significantly reduces duration of acute infection, lesion healing time, pain duration, and new lesion formation. 5
Dosing for initial genital herpes:
- Acyclovir 400 mg orally three times daily for 7-10 days, OR
- Acyclovir 200 mg orally five times daily for 7-10 days 5
The incubation period for HSV is typically 2-10 days (up to 4 weeks), which fits the post-coital timing. 3
When Diagnosis is Uncertain
If the diagnosis remains unclear after initial evaluation, treat for the most likely diagnosis based on clinical presentation. 2 Many experts recommend empiric treatment for both chancroid and syphilis if the diagnosis is uncertain and the patient resides in a community with notable chancroid morbidity. 2
Partner Management and Follow-Up
- Instruct the patient to refer sex partners for evaluation and treatment if their last sexual contact was within 30 days of symptom onset (for symptomatic patients) or within 60 days of diagnosis (for asymptomatic patients). 3
- Patients must abstain from sexual intercourse until both patient and partners complete therapy and are without symptoms. 3
- Failure to improve within 3 days requires re-evaluation of both diagnosis and therapy. 3
Special Considerations
HIV-Positive Patients
HIV-infected persons with genital HSV should receive the same treatment regimen as HIV-negative patients, though they may require more aggressive monitoring. 3