What is the diagnosis and treatment for a 25-year-old male with a painless genital ulcer, no past medical history, and multiple recent sexual partners?

Primary Syphilis: Case Presentation

Clinical Scenario

A 25-year-old male presents with a painless genital ulcer and reports multiple recent sexual partners, with no significant past medical history.

Most Likely Diagnosis

This presentation is classic for primary syphilis caused by Treponema pallidum, characterized by a painless chancre at the site of inoculation. 1

Key Diagnostic Features Supporting Primary Syphilis

• Painless ulcer: The absence of pain strongly favors syphilis over HSV, which typically causes painful ulcers 2
• Sexual risk factors: Multiple recent sexual partners increases likelihood of sexually transmitted infection 1
• Classic chancre characteristics: The ulcer is typically indurated with a clean base, though this classic presentation occurs in only 31% of cases 1
• Regional lymphadenopathy: Non-tender, firm inguinal lymph nodes are often present (though not mentioned in this case) 3

Differential Diagnosis to Consider

Primary Alternatives

• Genital Herpes (HSV): Most common cause of genital ulcers in the United States (49% of cases), but typically presents with multiple shallow, tender ulcers that may be preceded by vesicles 1, 4
• Chancroid (H. ducreyi): Presents with painful ulcers with ragged, undermined edges and purulent bases; tender inguinal adenopathy occurs in one-third of patients 1
• Lymphogranuloma venereum (LGV): May present with self-limited genital ulcer, though most patients present after ulcer resolution with inguinal/femoral lymphadenopathy 5, 1

Critical Consideration

Co-infection occurs in 3-10% of patients with genital ulcers, with up to 10% of chancroid patients co-infected with T. pallidum or HSV. 2, 1, 6 This mandates comprehensive testing rather than relying on clinical diagnosis alone.

Mandatory Diagnostic Workup

Essential Laboratory Tests

• Syphilis serology: Mandatory in all cases of genital ulcers; 90% of primary syphilis cases show positive titers 1, 6
• Darkfield microscopy or direct fluorescent antibody (DFA) test: Provides immediate diagnosis of T. pallidum when available 5, 4
• HSV testing: PCR or culture from ulcer base (gold standard) to exclude the most common cause of genital ulcers 2, 1
• HIV testing: Strongly recommended at initial presentation and repeated at 3 months if initially negative, as genital ulcers facilitate HIV transmission 2, 1, 6

Additional Testing if Diagnosis Unclear

• Culture for H. ducreyi: If chancroid is suspected, though sensitivity is only 80% even with special media 1
• Chlamydia trachomatis testing: From rectal and oropharyngeal sites in high-risk individuals 6

Critical Diagnostic Pitfall

Clinical diagnosis alone is neither sensitive nor specific, and even after complete diagnostic evaluation, 25% of genital ulcers remain undiagnosed. 6, 4 Laboratory confirmation is mandatory before initiating treatment when possible.

Treatment Approach

Recommended Treatment for Primary Syphilis

One dose of intramuscular penicillin G benzathine is the recommended treatment for genital ulcers caused by primary syphilis. 4

Empiric Treatment Strategy When Diagnosis Uncertain

When the diagnosis is unclear and test results are not immediately available, many experts recommend empiric treatment for both syphilis and chancroid if the patient resides in a community with notable chancroid morbidity. 2, 1 This approach prevents devastating neurologic and cardiovascular complications of untreated syphilis while awaiting confirmatory testing. 6

Treatment Timing

Treatment should be initiated as soon as possible after diagnosis to prevent complications and reduce transmission. 5 However, if diagnostic testing is available, it should be performed before treatment when feasible to ensure accurate diagnosis and appropriate partner notification.

Partner Management

Contact Tracing Requirements

• All sex partners within the preceding 60-90 days should be referred for evaluation, testing, and empiric treatment. 5
• Syphilis is a mandatory reportable disease to the local health department. 7
• Partners should be treated presumptively even before test results are available if they had sexual contact during the infectious period. 5

Follow-Up and Monitoring

Clinical Follow-Up

• Patients should be followed clinically until signs and symptoms have resolved. 5
• Repeat HIV testing at 3 months if initially negative, given the increased risk of HIV acquisition through genital ulcers. 1
• Serologic follow-up for syphilis to document treatment response and rule out treatment failure. 6

Patient Education

• Instruct patient to abstain from sexual intercourse until ulcer is completely healed and treatment is completed. 5
• Counsel on HIV risk and the importance of partner notification and treatment. 2, 8
• Discuss safer sex practices and risk reduction strategies for future prevention. 3

Special Considerations

High-Risk Populations

HIV-positive patients may have atypical presentations, slower healing, higher treatment failure rates, and may require prolonged therapy courses beyond standard regimens. 1 These patients require modified treatment approaches and closer monitoring.

Co-Infection Risk

Because 3-10% of patients have more than one pathogen present, comprehensive testing for all common causes of genital ulcers is essential rather than stopping at the first positive test. 1, 6