What are the differential diagnoses and recommended evaluations for a patient with a history of unprotected sex and concern for sexually transmitted disease (STD) exposure, without signs or symptoms, considering their age, sex, and sexual orientation?

Differential Diagnoses and Screening Approach for Asymptomatic STD Exposure

For an asymptomatic patient with unprotected sexual exposure, you must screen for chlamydia, gonorrhea, syphilis, HIV, and consider hepatitis B and trichomoniasis based on specific risk factors, rather than generating a traditional differential diagnosis list. 1, 2

Core Testing Panel for All Asymptomatic Patients

The following tests should be performed regardless of patient demographics:

• Chlamydia and gonorrhea using nucleic acid amplification tests (NAATs) from appropriate anatomic sites 1, 3, 4
• HIV testing using fourth-generation antigen/antibody testing with reflex confirmatory testing 1, 5
• Syphilis screening using the reverse algorithm (treponemal-specific test first, followed by RPR if positive) 1, 2

Anatomic Site Selection Based on Sexual Practices

For heterosexual women under 25 years or at increased risk:

• Vaginal swab NAAT for chlamydia and gonorrhea (preferred over cervical specimens) 6, 1
• Consider trichomoniasis testing if multiple partners, history of STIs, or high-risk behaviors present 6, 1

For men who have sex with men (MSM):

• Three-site testing is mandatory: urogenital (first-void urine), rectal swab, and oropharyngeal swab for both chlamydia and gonorrhea 2, 3
• Screen every 3-6 months if multiple/anonymous partners, methamphetamine use, or sex during drug use 1, 2

For heterosexual men:

• First-void urine specimen for chlamydia and gonorrhea 1
• Consider more intensive screening based on local prevalence rates and individual risk factors 6, 1

Additional Risk-Stratified Testing

Add hepatitis B surface antigen testing if:

• Patient is from a high-prevalence region 1
• History of injection drug use 1
• Sexual partner with hepatitis B 1
• Never vaccinated for hepatitis B 1

Add hepatitis C testing if:

• Any history of injection drug use, even once 1
• HIV-positive status 1

For HIV-positive patients:

• Screen for all bacterial STIs (chlamydia, gonorrhea, syphilis, trichomoniasis) every 3-6 months due to increased HIV transmission risk when co-infected 6, 1

Critical Timing Considerations

Immediate testing limitations:

• HIV fourth-generation tests detect infection 2-4 weeks post-exposure, but may miss acute infection in the first 2 weeks 1
• Syphilis antibodies may not be detectable for 3-4 weeks after exposure 1
• Consider repeat testing at 4-6 weeks if initial tests are negative and exposure was recent 1

Window period management:

• If high-risk exposure occurred within the past 72 hours, discuss HIV post-exposure prophylaxis (PEP) immediately 7
• Document the date of last unprotected exposure to determine appropriate retesting intervals 6, 1

Common Pitfalls to Avoid

Do not rely on symptoms to guide testing:

• 70% of HSV and trichomoniasis infections are asymptomatic 4
• 53-100% of extragenital gonorrhea and chlamydia infections produce no symptoms 4
• Asymptomatic chlamydial epididymitis can occur without urethral symptoms 8

Do not screen for herpes simplex virus (HSV) in asymptomatic patients:

• No evidence that treating asymptomatic HSV improves outcomes 1, 5
• Testing should only occur if lesions are present 1

Do not omit extragenital sites in MSM:

• Rectal and pharyngeal infections are frequently asymptomatic and will be missed with urogenital-only testing 1, 2

Partner Management Requirements

All sexual partners from the past 60 days must be notified and treated presumptively:

• Partners should receive treatment before test results when indicated 6, 1, 2
• Consider expedited partner therapy where legally permissible 6, 1
• Health department assistance is available for partner notification services 6

Mandatory Follow-Up Testing

Retest at 3 months after any positive result:

• Required for all patients diagnosed with chlamydia or gonorrhea, regardless of whether partners were treated 6, 1, 3
• Reinfection rates reach 25-40% within 3 months of treatment 1, 2

Annual screening thereafter if sexually active:

• All women under 25 years need annual chlamydia and gonorrhea screening 6, 1, 5
• MSM require annual screening at minimum, with 3-6 month intervals if high-risk behaviors continue 1, 2

Reporting Obligations

Notify public health authorities for:

• Syphilis, gonorrhea, chlamydia, and HIV (reportable in all states) 6, 1
• Consult local health department for specific reporting requirements and partner services 6, 1