What is the diagnosis and treatment for painless ulcerations on the shaft of the penis?

Painless Penile Ulcerations: Diagnosis and Management

The most likely diagnosis is primary syphilis, and you should immediately obtain serologic testing for syphilis along with darkfield microscopy or direct fluorescent antibody testing for Treponema pallidum, while also testing for HSV and HIV. 1

Critical Diagnostic Principle

The absence of pain is the key clinical feature that narrows your differential diagnosis significantly. While clinical examination alone is unreliable—with classic presentations being only 31-35% sensitive across all genital ulcer diseases—painless ulcers strongly suggest syphilis over other etiologies. 2

Immediate Diagnostic Workup

All patients with genital ulcers require the following tests: 1

• Darkfield examination or direct immunofluorescence test for Treponema pallidum - This is essential for primary syphilis diagnosis 1
• Serologic testing for syphilis - Must be performed in all patients with genital ulcers 1, 3
• HSV culture or PCR testing - HSV is the most common cause of genital ulcers in the U.S., though typically painful 1, 3, 4
• HIV testing - Mandatory given the strong association between genital ulcers (especially syphilis and chancroid) and HIV transmission 1, 5
• Culture for Haemophilus ducreyi - Only if chancroid is prevalent in your geographic area 1

Why Syphilis is Most Likely

Primary syphilis classically presents as a painless, indurated, clean-based ulcer (chancre). 2 While this classic presentation is only 31% sensitive, it is 98% specific when present. 2 The absence of pain and itching in your patient makes syphilis the leading diagnosis, as:

• Genital herpes (most common cause overall) typically presents with painful, multiple, shallow ulcers 1, 2
• Chancroid presents with painful, deep, undermined, purulent ulcers 1, 2
• Primary syphilis is the only common STI that characteristically presents as painless 2

Empiric Treatment Strategy

You must often treat before test results are available. 1 Given the painless presentation:

• Treat for syphilis empirically if the clinical presentation suggests it and you cannot wait for test results 1
• Consider treating for both syphilis and chancroid if you're in a community where chancroid is significant and diagnostic capabilities are limited 1
• Be aware that 25% of genital ulcers have no laboratory-confirmed diagnosis even after complete evaluation 1, 3

Critical Pitfalls to Avoid

Co-infections occur in 10% of patients with genital ulcers—you may find both HSV and T. pallidum in the same lesion. 1, 5 Do not assume a single pathogen. 5

Serologic testing for syphilis must be performed at least 7 days after ulcer onset to avoid false negatives in primary syphilis. 1 If done earlier, repeat testing is necessary. 5

HIV testing is not optional—syphilis and chancroid are cofactors for HIV transmission, and high rates of HIV coinfection are documented. 1, 5 Test at initial diagnosis and repeat at 3 months if initially negative. 5

Follow-Up Requirements

• Reexamine the patient 3-7 days after initiating therapy to assess for clinical improvement 5
• If no improvement occurs, reconsider the diagnosis, check for co-infection, verify HIV status, confirm medication adherence, or consider antibiotic resistance 1, 5
• Large ulcers may require more than 2 weeks to heal even with appropriate therapy 5

Non-Infectious Considerations

If all infectious workup is negative, consider non-infectious causes including: 1, 3, 4

• Aphthous ulcers (can occur on genitalia) 3
• Behçet syndrome 1, 4
• Fixed drug eruption 1, 4
• Sexual trauma 4
• Inflammatory bowel disease (Crohn's disease) 1

Up to 25% of genital ulcers remain undiagnosed despite complete testing, making biopsy necessary if empiric treatment fails. 1, 5