A 61-year-old man presents 2 weeks after onset of pruritic genital lesions that progressed to painful vesiculoulcerative lesions on the penile shaft and glans with swelling of the penis and scrotum, without urinary symptoms. What is the most likely diagnosis and appropriate management?

Diagnosis and Management of Genital Ulcerative Disease in a 61-Year-Old Male

Most Likely Diagnosis

This presentation is most consistent with primary genital herpes simplex virus (HSV) infection, which is the most common cause of genital ulcers accounting for approximately 49% of cases. 1 The progression from pruritic lesions to painful vesiculoulcerative lesions with penile and scrotal swelling over 2 weeks, without urinary symptoms, strongly suggests HSV rather than other causes of genital ulceration. 2, 1

Diagnostic Approach

Laboratory confirmation must always be sought because clinical diagnosis alone is often inaccurate. 1, 3

Essential Testing

• HSV culture or PCR from the ulcer base is the gold standard for diagnosis and should be performed immediately 1, 3
• Serologic testing for syphilis is mandatory in all cases, as 90% of primary syphilis cases show positive titers and up to 10% of genital ulcer patients have HSV co-infected with Treponema pallidum 1, 4, 3
• HIV testing is strongly recommended at initial presentation and should be repeated at 3 months if initially negative, as genital ulcers facilitate HIV transmission 1, 4, 3
• Darkfield examination or direct immunofluorescence for T. pallidum provides immediate diagnosis of syphilis when available 2
• Culture for Haemophilus ducreyi should be considered if chancroid is endemic in your area, though sensitivity is only 80% 2, 1

Key Clinical Discriminators

The painful nature of the ulcers strongly favors HSV over syphilis, which typically causes painless chancres 3. The absence of tender inguinal lymphadenopathy argues against chancroid, where this finding occurs in one-third of patients and is almost pathognomonic when suppurative 1, 3. The progression from vesicles to ulcers is characteristic of HSV, as vesicles burst forming shallow ulcers that eventually crust and heal spontaneously 2.

Empiric Treatment Strategy

When the diagnosis is uncertain, treat for the most likely diagnosis based on clinical presentation. 3 Given this patient's presentation strongly suggests HSV, empiric antiviral therapy should be initiated immediately.

Recommended Treatment for Primary Genital Herpes

• Acyclovir 400 mg orally 5 times daily for 10 days 4
• Antiviral therapy should be initiated within 72 hours of primary infection for maximum effectiveness 5
• Alternative regimens include acyclovir 200 mg orally 5 times daily or valacyclovir 1 g twice daily for 7-10 days 2

Coverage for Co-infections

Many experts recommend empiric treatment for both chancroid and syphilis if the diagnosis is unclear and the patient resides in a community with notable chancroid morbidity. 3 In this case:

• For syphilis coverage: Benzathine penicillin G 2.4 million units IM in a single dose 4
• For chancroid coverage: Azithromycin 1 g orally in a single dose OR ceftriaxone 250 mg IM in a single dose 2, 4

Critical Management Considerations

Co-infection Risk

Co-infection is common, with 3-10% of patients with genital ulcers having more than one pathogen present, and up to 10% of chancroid patients co-infected with T. pallidum or HSV. 1, 4, 3 This mandates comprehensive testing even when one diagnosis seems clinically obvious.

Special Populations

HIV-positive patients with genital ulcers have slower healing, higher treatment failure rates, and may require prolonged therapy courses beyond standard regimens. 4 If HIV testing is positive, consider erythromycin 500 mg orally 4 times daily for 7 days for chancroid coverage with close follow-up 4.

Severe Disease Management

Debridement is only necessary when herpetic ulceration is not healing on its own and necrotic tissue forms that can harbor bacteria. 5 This patient's extensive disease with significant swelling may require hospitalization if systemic symptoms develop 2.

Follow-up Protocol

• Re-examine at 3-7 days after initiating therapy to assess for symptomatic and objective improvement 4
• Ulcers should improve symptomatically within 3 days and objectively within 7 days after appropriate therapy 2, 4
• Large ulcers may require more than 2 weeks for complete healing, even with appropriate therapy 4
• Repeat HIV and syphilis testing at 3 months if initial results are negative 2, 4

Failure to Improve

If no clinical improvement is evident by 3-7 days, consider: 2

• Incorrect diagnosis
• Co-infection with another STD
• HIV infection
• Non-adherence to treatment
• Resistant organism

Partner Management

All sexual contacts within 10 days before symptom onset should be treated empirically, regardless of whether symptoms are present, to prevent further transmission 4. The patient should avoid sexual contact until ulcers are completely healed and treatment is completed 4.

Common Pitfalls to Avoid

• Do not rely on clinical diagnosis alone - at least 25% of patients with genital ulcers have no laboratory-confirmed diagnosis even after complete evaluation 2
• Do not assume a single pathogen - test for all common causes as co-infection rates are significant 1, 3
• Do not delay antiviral therapy - initiate within 72 hours for primary HSV infection 5
• Do not forget HIV testing - genital ulcers are established co-factors for HIV acquisition 1, 4