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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Chlamydia: NAAT; doxycycline 7 days preferred, azithromycin in pregnancy or adherence concerns
- Gonorrhea: ceftriaxone IM; add doxycycline if chlamydia not excluded
- Syphilis: diagnose with nontreponemal plus treponemal tests; benzathine penicillin G for primary/secondary/early latent; IV penicillin G for neurosyphilis
- Genital herpes: painful grouped vesicles/ulcers; treat episodic or suppressive disease with acyclovir, valacyclovir, or famciclovir
- Trichomoniasis: frothy discharge, strawberry cervix; metronidazole and partner treatment
- HPV prevention is vaccination; genital warts are treated clinically, while cervical dysplasia is managed by screening algorithms
- Always test for HIV, syphilis, gonorrhea, and chlamydia when one STI is diagnosed; treat partners when indicated
Overview
Sexually transmitted infections are a major Step 2 CK topic because syndromic presentations overlap: urethritis, cervicitis, pelvic inflammatory disease, genital ulcers, vaginal discharge, proctitis, epididymitis, neonatal infection, and infertility. US practice follows CDC STI Treatment Guidelines, which emphasize NAAT-based testing, site-specific screening based on exposure, partner notification and treatment, pregnancy-specific regimens, HIV testing, and prevention including vaccination and PrEP.
Epidemiology
Chlamydia is the most commonly reported bacterial STI in the United States. Gonorrhea has increasing antimicrobial resistance and requires ceftriaxone-based therapy. Syphilis rates have risen substantially, including congenital syphilis. HSV-2 causes recurrent genital ulcers, HPV causes genital warts and anogenital/oropharyngeal cancers, and trichomoniasis is a common nonviral STI associated with adverse pregnancy outcomes and increased HIV acquisition risk.
Clinical Features
Symptoms
Chlamydia/gonorrhea: dysuria, urethral discharge, cervicitis, postcoital bleeding, pelvic pain, or asymptomatic infection
PID: lower abdominal pain, fever, cervical motion tenderness, adnexal tenderness, mucopurulent discharge
Primary syphilis: painless chancre with non-tender lymphadenopathy
Secondary syphilis: diffuse rash including palms/soles, mucous patches, condyloma lata, fever, lymphadenopathy
HSV: painful grouped vesicles that ulcerate; dysuria and tender lymphadenopathy during primary infection
Trichomoniasis: malodorous frothy yellow-green discharge, pruritus, dysuria, strawberry cervix
Signs
Mucopurulent cervical or urethral discharge
Cervical motion tenderness or adnexal tenderness suggests PID and warrants empiric treatment
Painless indurated chancre or broad moist condyloma lata in syphilis
Painful vesicles/ulcers in HSV; tender inguinal nodes
Exophytic cauliflower-like genital warts from HPV
Fever, RUQ pain, or peritonitis may indicate Fitz-Hugh-Curtis syndrome or complicated PID
Investigations
First-line
NAAT for chlamydia and gonorrheaUse urine, vaginal/cervical, rectal, or pharyngeal samples based on exposure site
Syphilis serologyNontreponemal RPR/VDRL for activity and titers plus treponemal confirmatory testing
HIV test and pregnancy testEssential when STI diagnosed or suspected; pregnancy changes therapy
Wet mount / NAAT for trichomonasNAAT is more sensitive; wet mount may show motile trichomonads and elevated pH
Second-line
HSV PCR from lesionPreferred test for active genital ulcer; serology can support diagnosis when lesions absent
Hepatitis B/C testingBased on risk, STI diagnosis, HIV status, or injection drug use
Microscopy for urethritis/vaginitisWBCs, clue cells, yeast, trichomonads; useful but less sensitive than NAAT for several STIs
Specialist
Lumbar punctureIf neurologic, ocular, or otic syphilis symptoms; ocular disease needs urgent ophthalmology and treatment even if CSF normal
Pelvic ultrasoundIf PID with concern for tubo-ovarian abscess, pregnancy, severe illness, or no improvement after 72 hours
1
Chlamydia and gonorrhea
- Chlamydia: doxycycline 100 mg BID for 7 days; pregnancy: azithromycin 1 g once
- Gonorrhea: ceftriaxone IM single dose; add doxycycline 7 days if chlamydia not excluded
- Treat sexual partners; abstain from sex until patient and partners complete therapy and symptoms resolve
- Retest for reinfection in about 3 months for chlamydia, gonorrhea, and trichomoniasis
2
Syphilis
- Primary, secondary, early latent: benzathine penicillin G IM single dose
- Late latent or unknown duration: benzathine penicillin G weekly for 3 doses
- Neurosyphilis/ocular/otosyphilis: aqueous crystalline penicillin G IV for 10-14 days
- Pregnancy: penicillin is the only proven therapy; desensitize if allergic
- Jarisch-Herxheimer reaction: fever, chills, myalgias after treatment; supportive care, not allergy
3
HSV, HPV, trichomoniasis
- HSV first episode: acyclovir, valacyclovir, or famciclovir; offer suppressive therapy for frequent recurrences or transmission reduction
- HPV warts: patient-applied imiquimod/podofilox or clinician cryotherapy/TCA; vaccination prevents disease but does not treat existing infection
- Trichomoniasis: metronidazole; treat partners and avoid alcohol if counseling for intolerance is relevant
4
Syndromic emergencies
- PID: ceftriaxone plus doxycycline plus metronidazole; do not wait for NAAT results
- Epididymitis in sexually active men: ceftriaxone plus doxycycline; enteric-risk cases may need fluoroquinolone-based therapy
- Sexual assault: empiric STI prophylaxis, emergency contraception, hepatitis B vaccination, HIV PEP assessment
Complications
- PID and infertility: Chlamydia and gonorrhea can cause tubal scarring, ectopic pregnancy, chronic pelvic pain
- Disseminated gonococcal infection: Dermatitis, tenosynovitis, migratory polyarthralgia, septic arthritis
- Congenital infection: Syphilis, HSV, HIV, hepatitis B, chlamydial conjunctivitis/pneumonia, gonococcal ophthalmia
- Neurosyphilis and ocular syphilis: Can occur at any stage
- Cancer: HPV causes cervical, anal, penile, vulvar, vaginal, and oropharyngeal cancers
USMLE Step 2 CK Exam Tips
- 1Painless chancre = primary syphilis; painful vesicles = HSV; painful ragged ulcer + tender suppurative nodes = chancroid
- 2Rash on palms and soles = secondary syphilis until proven otherwise
- 3Pregnant patient with syphilis and penicillin allergy = desensitize and give penicillin
- 4Cervical motion tenderness is enough to treat PID empirically; do not wait for imaging
- 5Gonorrhea is treated with ceftriaxone; add doxycycline if chlamydia has not been excluded
- 6Disseminated gonorrhea = dermatitis-tenosynovitis-polyarthralgia syndrome
- 7Trichomonas = motile organisms, frothy discharge, strawberry cervix; treat partners
- 8HPV vaccine prevents future HPV disease but does not treat existing warts or dysplasia
practicetest your knowledge on sexually transmitted infections (chlamydia, gonorrhea, syphilis, hsv, hpv, trichomoniasis)Apply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — infectious diseases and beyond.
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