What test should be ordered for a patient with a painless penile ulceration and lymph node swelling, suggestive of a sexually transmitted infection?

Diagnostic Testing for Painless Penile Ulceration with Lymphadenopathy

The provider should order a PCR test for Treponema pallidum (Option C) as the most specific and sensitive diagnostic test for this clinical presentation highly suggestive of primary syphilis. 1

Clinical Reasoning

The clinical presentation—painless genital ulceration with bilateral inguinal lymphadenopathy persisting for 7 days—is pathognomonic for primary syphilis (chancre). 1 While multiple diagnostic approaches exist, the testing strategy must prioritize both sensitivity and specificity for optimal patient outcomes.

Why PCR Testing is Preferred

• PCR/NAAT testing for T. pallidum directly detects the organism from the ulcer, providing definitive diagnosis without waiting for antibody development. 1
• Darkfield microscopy is rarely available in most clinical laboratories, making molecular testing the practical gold standard. 1
• Early primary syphilis may present before serologic conversion, meaning RPR/VDRL tests can be falsely negative in the first 1-2 weeks after chancre appearance. 1
• PCR does not require viable organisms and can be performed on genital ulcer specimens with high sensitivity. 1

Why RPR Alone is Insufficient (Option A)

• Nontreponemal tests like RPR are less sensitive in early primary syphilis and may be nonreactive during the initial presentation. 1
• The prozone phenomenon can cause false-negative RPR results in patients with high antibody titers, particularly in secondary syphilis or HIV co-infection. 2
• RPR should be used for confirmation and monitoring treatment response, not as the sole initial diagnostic test when direct organism detection is available. 1

Why NAAT for Other STIs is Not the Answer (Option D)

• While NAAT for Chlamydia trachomatis and Neisseria gonorrhoeae is excellent for urethritis and cervicitis, these organisms do not typically cause painless ulcerations with lymphadenopathy. 1
• The clinical presentation does not suggest urethritis (no dysuria or discharge mentioned), making routine STI screening less relevant to the immediate diagnostic question. 1
• However, co-testing for other STIs should still be performed given the high rate of co-infection in patients with any STI. 1

Optimal Testing Algorithm

Immediate testing from the ulcer:

• PCR/NAAT for T. pallidum from ulcer swab (most specific). 1
• If PCR unavailable, darkfield microscopy if expertise exists. 1

Concurrent serologic testing:

• Both treponemal (EIA/CIA) and nontreponemal (RPR/VDRL) tests should be ordered simultaneously. 1
• Many laboratories now use reverse sequence screening (treponemal test first), which may identify early infection before RPR becomes positive. 1, 3
• If initial RPR is negative but clinical suspicion remains high, repeat RPR in 1-4 weeks to capture seroconversion. 1

Additional recommended testing:

• HIV testing is mandatory in all patients with genital ulcers. 1
• Consider HSV PCR from the ulcer to exclude herpes simplex, though the painless nature makes this less likely. 1

Critical Pitfalls to Avoid

• Do not rely solely on RPR in early primary syphilis—up to 30% may be seronegative at initial presentation. 1
• Do not delay treatment while awaiting confirmatory testing if clinical suspicion is high; empiric treatment with benzathine penicillin G 2.4 million units IM should be initiated. 1
• Do not forget partner notification and testing—all sexual contacts within the preceding 90 days require evaluation and presumptive treatment. 1
• Request diluted RPR testing if the undiluted test is negative to avoid missing the prozone phenomenon. 2

Why Urinalysis is Irrelevant (Option B)

• Urinalysis has no role in diagnosing genital ulcerative disease. 1
• This test would be appropriate for suspected urinary tract infection or urethritis, neither of which match this clinical presentation. 1