Less-Common STIs and Exposure Management: Recognition and Referral
Core concept: Less-common sexually transmitted infections and high-risk sexual exposures require anatomy-based evaluation, appropriate organism testing, timely treatment or prevention, and public-health coordination.
Key clinical distinction: Genital ulcer disease, proctitis, lymphadenopathy, and exposure after sexual assault are not interchangeable with uncomplicated cervicitis treatment.
Prescribing priority: Recognize when the presentation requires organism-specific treatment or urgent specialist/public-health services, rather than extrapolating the chlamydia or gonorrhea regimen (Sexually Transmitted Infections and Vaginitis, n.d.).
Genital ulcer syndromes
Painful genital ulcers can be caused by genital HSV and, in appropriate epidemiologic circumstances, chancroid; painless ulcers may suggest early syphilis, although presentations overlap. Test for syphilis and HSV using the relevant clinical approach, review HIV status and exposure, and consider other noninfectious causes. Chancroid has become uncommon in many U.S. settings, so pretest probability matters; the older instructional slides mention several oral and injectable regimens, but their specific dosing should not be republished without modern verification (Sexually Transmitted Infections and Vaginitis, n.d.).
Lymphogranuloma venereum and granuloma inguinale
Lymphogranuloma venereum (LGV) can cause inflammatory proctocolitis and/or inguinal lymphadenopathy. CDC recommends doxycycline 100 mg orally twice daily for 21 days for typical LGV, rather than the seven-day regimen used for uncomplicated chlamydia. Granuloma inguinale (donovanosis) warrants prolonged treatment; CDC lists azithromycin 1 g orally weekly or 500 mg daily for more than three weeks AND until all lesions have healed. Chancroid requires exclusion of syphilis and HSV and has a CDC-listed azithromycin 1 g orally once regimen; its rarity and limited resistance data argue for public-health or specialist consultation. Pregnancy, allergy, local epidemiology, severe infection, and coinfections change the plan. Retesting and partner management are infection-specific (CDC, 2021a, 2021b, 2021c).
Sexual assault and postexposure services
After sexual assault, prioritize consent and trauma-informed care, forensic options as desired, emergency contraception, STI testing, hepatitis B and HPV vaccination assessment, HIV risk evaluation, and continuity of care. CDC 2021 empiric STI prophylaxis for eligible adolescent/adult female survivors includes ceftriaxone 500 mg IM once (1 g if at least 150 kg), doxycycline 100 mg orally twice daily for seven days, and metronidazole 500 mg orally twice daily for seven days. For eligible male survivors, the CDC example is ceftriaxone plus doxycycline without routine metronidazole. These are not universal prescriptions; allergies, pregnancy, site, consent, and local resources change treatment. For substantial HIV-risk exposure, initiate nPEP as soon as possible, ideally within 24 hours and no later than 72 hours, without waiting for all baseline laboratory results, and arrange a full 28-day course when indicated (CDC, 2021d, 2025).
Patient population and exposure-site decisions
Offer respectful, anatomy- and practice-based history taking and testing for all relevant anatomic sites. Consider pregnancy, adolescents, immune status, PrEP/PEP eligibility, and barriers to follow-up. Partner notification, reporting, and expedited partner therapy have infection-specific rules. Pubic lice and scabies belong to a separate parasitic-infection treatment reference and can be linked rather than duplicated (Sexually Transmitted Infections and Vaginitis, n.d.).
Specimen and disposition before an unverified regimen
A genital ulcer or inflammatory proctitis is a diagnostic syndrome, not one organism. Obtain site-specific testing for common infections as indicated, syphilis serology, lesion HSV testing, and HIV assessment. CDC provides directly verified treatment regimens for LGV (doxycycline 100 mg twice daily for 21 days), chancroid (including azithromycin 1 g once), and donovanosis (azithromycin for at least three weeks and until lesions heal); these must not be interchanged with uncomplicated chlamydia management. Severe proctitis or regional nodes may warrant presumptive LGV therapy when the syndrome fits, along with specialist/public-health follow-up. Pregnancy, immunocompromise, and drug allergies may alter treatment (CDC, 2021a, 2021b, 2021c).
Time-sensitive postexposure care
After a substantial sexual or other nonoccupational HIV exposure, CDC 2025 guidance recommends starting HIV nPEP ideally within 24 hours, no later than 72 hours, for 28 days. Preferred adult/adolescent regimens without relevant contraindications include bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus TAF or TDF plus FTC or lamivudine. Assess renal/hepatic function, pregnancy, co-medications and interactions, and HIV status, but do not delay the first indicated dose for pending laboratory results. Survivors also need trauma-informed consent, access to STI prophylaxis, emergency contraception, hepatitis B/HPV prevention where indicated, coordinated test-result review, and follow-up HIV testing; no intervention is contingent on agreeing to forensic examination (CDC, 2021d, 2025).
Clinical application
A patient presents 36 hours after sexual assault with concern for pregnancy, HIV exposure, and anogenital discomfort. Do not focus solely on whether an STI test is positive at presentation. Offer trauma-informed care and consent-based forensic options, assess time-sensitive HIV nPEP eligibility and emergency contraception, collect exposure-site testing as appropriate, discuss presumptive STI prophylaxis under current guidance, and arrange follow-up for results and support. In a different patient with severe proctitis and inguinal nodes, investigate invasive STI rather than defaulting to uncomplicated rectal-chlamydia treatment (CDC, 2021d, 2025; Smith & Honeywell, 2026).
High-yield distinctions
Ulcer diagnosis requires a differential rather than visual certainty. LGV is not routine chlamydia. Time-sensitive HIV prophylaxis and patient-directed forensic decisions require a dedicated care pathway.
Related YourDNP Resources
Pharmacology learning hub · Gonorrhea · Syphilis · Chlamydia and genital warts · Genital herpes · Pelvic inflammatory disease · Lice and scabies
Content last reviewed:
References
Centers for Disease Control and Prevention. (2021a). Chancroid. https://www.cdc.gov/std/treatment-guidelines/chancroid.htm
Centers for Disease Control and Prevention. (2021b). Granuloma inguinale (donovanosis). https://www.cdc.gov/std/treatment-guidelines/donovanosis.htm
Centers for Disease Control and Prevention. (2021c). Lymphogranuloma venereum. https://www.cdc.gov/std/treatment-guidelines/lgv.htm
Centers for Disease Control and Prevention. (2021d). Sexual assault and abuse and STIs. https://www.cdc.gov/std/treatment-guidelines/sexual-assault-adults.htm
Centers for Disease Control and Prevention. (2025). Antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV. MMWR, 74(RR-1), 1–56. https://www.cdc.gov/mmwr/volumes/74/rr/rr7401a1.htm
Sexually transmitted infections and vaginitis [PowerPoint slides, Chapter 47]. (n.d.). Pharmacotherapeutics for advanced practice nurse prescribers (5th ed.). User-supplied instructional resource.
Smith, U. D., & Honeywell, M. S. (2026). Sexually transmitted infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed., Chapter 83). McGraw Hill.