What is the treatment for genital ulcers caused by sexually transmitted infections (STIs)?

Treatment for Genital Ulcers

When treating genital ulcers caused by STIs, initiate empiric therapy based on the most likely diagnosis while awaiting test results, prioritizing treatment for syphilis in unclear cases, or both syphilis and chancroid in high-prevalence areas. 1

Diagnostic Testing Before Treatment

All patients with genital ulcers require the following baseline tests:

• Serologic test for syphilis (mandatory in all cases) 1, 2
• HSV culture or PCR from the ulcer base (HSV is the most common cause of genital ulcers in the United States) 1, 2
• Culture for Haemophilus ducreyi if chancroid is endemic in your area 1
• HIV testing should be performed at diagnosis and repeated at 3 months if initially negative, as genital ulcers facilitate HIV transmission 1, 3

Critical caveat: Even with complete diagnostic evaluation, 25% of genital ulcers remain undiagnosed, so empiric treatment is often necessary before results return 1, 3

Empiric Treatment Strategy

When Diagnosis is Clear:

For Genital Herpes (most common in US):

• Acyclovir 400 mg orally 5 times daily for 10 days for initial episodes 3, 4
• Valacyclovir and famciclovir are alternative options 5, 6
• Treatment should ideally begin within 72 hours of symptom onset for initial episodes and within 24 hours for recurrent episodes 5

For Chancroid:

• Azithromycin 1 g orally as a single dose (preferred for adherence) 1, 7
• OR Ceftriaxone 250 mg IM as a single dose 1
• OR Ciprofloxacin 500 mg orally twice daily for 3 days (contraindicated in pregnancy, lactation, and patients <18 years) 1
• OR Erythromycin base 500 mg orally 4 times daily for 7 days 1

For Primary Syphilis:

• Benzathine penicillin G 2.4 million units IM as a single dose 4, 6

When Diagnosis is Unclear:

If you cannot wait for test results and the diagnosis is uncertain:

• Treat for syphilis as the default 1
• Add chancroid treatment if the patient lives in an area where H. ducreyi is prevalent, especially when diagnostic capabilities are limited 1
• Consider treating for both HSV and syphilis if clinical features suggest possible co-infection (occurs in 10% of cases) 1, 4

Special Populations

HIV-Positive Patients:

• Experience slower healing and higher treatment failure rates 3, 4
• For chancroid, use erythromycin 500 mg orally 4 times daily for 7 days with close follow-up rather than single-dose regimens 3, 4
• All four chancroid regimens remain effective in HIV-infected patients, but longer courses may be needed 1

Uncircumcised Men:

• May not respond as well to standard chancroid treatment 1
• Require closer monitoring at 3-7 day follow-up 1

Follow-Up Protocol

Re-examine patients 3-7 days after starting treatment:

• Ulcers should show symptomatic improvement within 3 days and objective improvement within 7 days 1, 3
• Large ulcers may require >2 weeks for complete healing even with appropriate therapy 3, 4
• Fluctuant lymphadenopathy resolves more slowly and may require needle aspiration through intact skin 3

If no improvement at 3-7 days, consider:

• Incorrect diagnosis 1, 3
• Co-infection with another STD (occurs in 10% of cases) 1, 4
• HIV co-infection 1, 3
• Non-adherence to treatment 1
• Antibiotic resistance 1
• Non-infectious causes (trauma, Behçet syndrome, fixed drug eruption, malignancy) 6, 2

Obtain tissue biopsy if no response after 7 days of appropriate therapy rather than continuing empiric antibiotics indefinitely 3

Partner Management

Treat all sexual contacts within 10 days before symptom onset empirically, regardless of whether they have symptoms, to prevent ongoing transmission 3, 4

Critical Pitfalls to Avoid

• Do not assume a single pathogen: Co-infections occur in 10-17% of cases, particularly HSV with syphilis or chancroid with T. pallidum 1, 3, 4
• Do not skip HIV testing: Genital ulcers dramatically increase HIV transmission risk, and HIV status affects treatment response 1, 3
• Do not continue empiric antibiotics indefinitely: If ulcers fail to improve after 7 days, obtain tissue diagnosis before continuing treatment 3
• Do not rely on clinical diagnosis alone: Clinical examination is neither sensitive nor specific for determining etiology 8, 2
• Do not forget syphilis serology timing: If performed <7 days after ulcer onset, repeat testing is necessary as early primary syphilis may be seronegative 1