What is the appropriate workup for a patient presenting with an open penile ulcer, considering potential sexually transmitted infections (STIs) and underlying conditions?

Workup for Open Penile Ulcer

All patients presenting with an open penile ulcer require serologic testing for syphilis, HSV culture or PCR from the ulcer base, and HIV testing at initial presentation, as these represent the three most common causes of genital ulceration in the United States. 1

Essential Laboratory Testing

Mandatory Initial Tests

• Serologic test for syphilis (RPR or VDRL) must be performed in all cases, as syphilis accounts for a significant proportion of genital ulcers and 90% of primary syphilis cases show positive titers 2, 1
• HSV culture or PCR from the ulcer base is the gold standard, as genital herpes is the most common cause of genital ulcers in the United States, accounting for approximately 49% of cases 2, 3
• HIV testing is mandatory at initial presentation and should be repeated at 3 months if initially negative, as genital ulcers facilitate HIV transmission and are established co-factors for HIV acquisition 1, 2

Additional Diagnostic Tests Based on Clinical Presentation

• Darkfield examination or direct immunofluorescence for Treponema pallidum provides immediate diagnosis of syphilis when available 1
• Culture for Haemophilus ducreyi should be obtained if chancroid is suspected (painful ulcer with ragged, undermined edges and purulent base, especially with tender inguinal adenopathy), though sensitivity is only 80% even with special media 1, 2
• PCR testing for T. pallidum, HSV, and H. ducreyi may be available and offers improved sensitivity over traditional methods 1, 3

Critical Clinical Assessment Points

Key Historical Features to Elicit

• Sexual history including number of partners, partners with known STIs, men who have sex with men status, and sex work involvement increases likelihood of co-infections 2
• Pain characteristics: Painful ulcers suggest HSV or chancroid, while painless indurated ulcers suggest syphilis (though classic presentation occurs in only 31% of syphilis cases) 2
• Timing and progression: HSV typically presents with multiple shallow ulcers that may be preceded by vesicles lasting less than 10 days 1
• Immunocompromised status (HIV, diabetes) as these patients have atypical presentations, slower healing, and increased treatment failure rates 2, 4

Physical Examination Specifics

• Ulcer characteristics: Number, size, depth, edge appearance (undermined suggests chancroid, indurated suggests syphilis), and presence of vesicles 2
• Lymphadenopathy assessment: Tender inguinal adenopathy occurs in one-third of chancroid patients; when suppurative, it is almost pathognomonic 1, 2
• Examine for co-existing lesions as 3-10% of patients have co-infections with multiple pathogens 2, 4

Critical Management Pitfalls

Co-infection Considerations

• 10% of chancroid patients are co-infected with T. pallidum or HSV, and occasionally both HSV and T. pallidum can be recovered from the same lesion 1, 2
• Do not assume a single pathogen as 3-10% of all genital ulcer patients have more than one disease present 1, 2

Diagnostic Limitations

• 25% of patients have no laboratory-confirmed diagnosis even after complete evaluation, so empiric treatment is often necessary 1, 4
• Syphilis serology may be negative if performed less than 7 days after ulcer onset, requiring repeat testing 1
• HSV culture sensitivity decreases as lesions age and crust over, so sample early from ulcer base or vesicular fluid 1

Special Population Considerations

• HIV-positive patients require modified approaches with slower healing, higher treatment failure rates, and may require prolonged therapy courses beyond standard regimens 2, 4
• Uncircumcised patients may not respond as well to treatment as circumcised patients 1

Non-infectious Differential Diagnoses to Consider

When infectious workup is negative, consider:

• Traumatic ulceration from sexual activity or masturbation 5
• Behçet syndrome presenting with mucosal ulcerations 1, 3
• Fixed drug eruption 1
• Inflammatory bowel disease (Crohn disease) 1
• Psoriasis 3

These require tissue biopsy for definitive diagnosis if infectious causes are excluded 4, 3