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STI Differentials

STI Tips

• Asymptomatic patient with recent exposure: HIV antigen/antibody immunoassay, HBV, RPR or VDRL, HSV (perform 1wk after exposure), GC/CT (urethral swab or first void urine)
• Reactive arthritis: arthritis, urethritis, conjunctivitis
• Disseminated gonococcal infection: migratory asymmetric polyarthralgia, rash, fever, tenosynovitis, septic arthritis
• Fitz-Hugh-Curtis syndrome: perihepatic inflammation, pain resolves with antibiotics but adhesions persist

Male Urethritis

• Non-infectious causes: catheterization, reactive arthritis, stricture, stones, lesions
• Diagnosis: urethral discharge, first void urine (10-30mL after waiting 1+ hr after prior void) with leukocyte esterase, centrifuged first void with > 10 WBC, gram stain with > 2 WBC
• Infectious workup: test for GC/CT, often cannot identify causative organism in non-Gonococcal urethritis, usually only consider further workup if no response to empiric treatment
• Non-response to treatment: non-compliance, re-exposure, resistant organism (treat with erythromycin if doxycycline previously used), non-infectious cause or alternative diagnosis
• Follow-up: abstain from sex x1 week, re-test in 3 months (re-infection common)
• Partners: refer for evaluation, treat if sexual contact within 60 days of symptom onset or diagnosis, otherwise treat last sexual partner

Disease	Diagnosis	Treatment	Follow-Up
Gonorrhea	Urine NAAT	Ceftriaxone 250mg IM x1 + Azithromycin 1g PO x1 Substitute gemifloxacin 320mg PO x1 or gentamicin 240mg IM x1 if cephalosporins contraindicated	Abstain from sexual contact x7 days Repeat test in 3-4mo Test prior partners within past 60 days
Chlamydia		Azithromycin 1g PO x1 Doxycycline 100mg PO BID x7 days Erythromycin 500mg PO QID x7 days Levofloxacin 500mg PO daily x7 days Ofloxacin 300mg PO BID x7 days
Mycoplasma	Difficult to diagnosis Suspect if persistent/recurrent urethritis	Azithromycin 1g PO If fails, moxifloxacin 400mg daily x7-14 days	Abstain from sex until symptoms resolve and treatment completed test prior partners within past 60 days

Genital Ulcers

Disease	# Ulcers	Painful?	Lymphadenopathy?	Diagnosis	Treatment
Syphilis Treponema pallidum	Single	No	Regional	Nontreponemal (sensitive): VDRL, RPR Treponemal (specific): FTA-ABS, EIAs	Benzathine penicillin G 2.4 million U IM x1 Doxycycline 100mg PO BID x14 days Tetracycline 500mg PO QID x14 days Other treatments for tertiary syphilis
Herpes HSV	Multiple	Yes	Painful bilateral	Cell culture + PCR (swab ulcer base)	Acyclovir 400mg PO TID x7-10 days Acyclovir 200mg PO x5 x7-10 days Valacyclovir 1g PO BID x7-10 days Famciclovir 250mg PO TID x7-10 days Other regimens for recurrent episodes
Chancroid Haemophilus ducreyi	Multiple, raw	Yes	Unilateral and painful (50%) may become fluctuant and rupture	1+ painful genital ulcers + typical chancroid appearance + negative syphilis and HSV tests	Azithromycin 1g PO x1 Ceftriaxone 250mg IM x1 Ciprofloxacin 500mg PO BID x3 days Erythromycin 500mg PO TID x7 days
Granuloma inguinale Klebsiella granulomatosis	Multiple, friable	No	None	Send-out test	Azithromycin 1g PO qWeek 500mg PO qDay x3 weeks Consider biopsy if no resolution
Lymphgranuloma Venereum C. trachomatis serovars L1-3	Single	No	Painful and unilateral	NAAT available	Doxycycline 100mg PO BID x21 days Erythromycin 500mg PO QID x21 days
Molluscum contagiosum MCV	Multiple	No	No	Based on clinical picture	Observation Avoid auto-inoculation Local therapies

MPox (from Lee 2023)

• Presentation: umbilicated lesion with ulceration and pain
• Genital involvement: seen in 45-60% men, may have another STI (30%) including history of HIV (32%)
• Symptomatic management: tylenol, NSAIDs, topical lidocaine, secondary bacterial infections managed with antibiotics for SSTI (duration 10-14d), can medically debride with collagenase
• Long-term effects: larger lesions may cause skin contraction or discoloration, does not usually require urologic surgical intervention
• Vaccination: JYNNEOS approved for high risk patients (recent exposure, gay/bisexual men with multiple partners)

Vaginitis

Workup

• Non-infectious causes: postpartum, postmenopausal, chemical irritation, allergic reaction
• Presentation: vaginal discharge, vulvar irritation, may also have dysuria and odor
• Vaginal pH measure with pH paper, abnormal in BV and Trichomonas
• Saline wet mount: discharge placed on slide, diluted with 1-2 drops normal saline, examine under microscope
• KOH prep: discharge placed on slide, diluted with 1-2 drops 10% KOH, air/flame dried, best for visualizing yeast (KOH lyses cells)
• Whiff test: adding KOH to discharge creates amine odor ("fishy" odor), most common with BV, can be seen with Trichomonas

Diagnoses

Candidal vaginitis risk factors: pregnancy, immunocompromised, DM, contraceptives, recent antibiotic use

Candidiasis management: fluconazole 150mg PO x1 or topical therapies x7-14d, refer to gynecology if recurrent vaginitis or other complicating factors

Bacterial vaginosis: most common cause of discharge, increased risk with new/multiple sexual partners, gold standard diagnosis with Gram stain (but can use Amsel criteria, see below), culture not recommended

Amsel criteria (need 3 of 4): homogenous white discharge covering vaginal walls, clue cells on microscopic examination, pH > 4.5, positive whiff test

Differential

Diagnosis	Discharge	pH	Microscopy	Symptoms	Treatment	Treat partner?
Normal discharge	White, thick, smooth	≤ 4.5	Lactobacilli	-	-	-
Candidiasis (C. albicans)	White, thick, curdlike		Mycelia	Itching, dysuria	Topical therapies Fluconazole 150mg PO x1 Persistent/recurrent infections may require alternate treatments for non-C. albicans	Only if balanitis present
Trichomoniasis	Frothy, purulent	≥ 4.5	Trichomonads, WBC	Vulvar erythema/edema	Metronidazole 2g PO x1 (5% resistance rate) Tinidazole 2g PO x1	Yes
Bacterial vaginosis	Thin, white		Absent lactobacilli, clue cells, amine odor	Increased discharge, odor	Metronidazole 500mg PO BID x7 days Metronidazole gel 0.75% intravaginally daily x5 days Clindamycin 2% cream intravaginally QHS x7 days	No

HPV and HIV

Human papillomavirus(HPV)

• Can cause warts and squamous cell cancer
• Biopsy indications: uncertain diagnosis, no response to standard therapy, worsening during therapy, immunocompromised, pigmented warts, indurated warts, affixed to underlying tissue, persistent ulceration or bleeding
• Patient-applied topical therapies: imiquimod cream 3.75% daily x16 weeks at bedtime, imiquimod cream 5% daily 3x weekly x16 weeks at bedtime, podofilox 0.5% solution/gel 0.5mL/day (max) BID x3 days (rest 4 days) x4 cycles (max), sinecatechins 15% ointment TID x16 weeks
• Physician-applied topical therapies: cryotherapy q1-2 weeks, direct excision, laser therapy, trichloroacetic acid/bichloroaceditc acid 80-90% (neutralize if severe pain with soap/water or NaBicarb)
• Intraurethral therapy: cold-cup biopsy, intraurethral 5-FU instilled after each void for 3-8 days
• Condom use: topical treatments may weaken condoms and condoms may not protect partner from HPV exposure
• HPV vaccine: available for ages 9-45, administered as 2-3 doses

Human immunodeficiency virus

• Initially presents with nonspecific flulike symptoms x2-4 weeks, then may be latent for months-years
• Diagnosis: via screening test should be confirmed with a separate test
• Circumcision: reportedly reduces transmission risk by 50-60% (in high risk populations only)
• Postexposure prophylaxis: should be given for non-occupational exposure within 72hrs
• Preexposure prophylaxis: should be given to individuals at higher risk for transmission
• Urologic complications: increases risk for other STIs, skin infections, HPV, squamous cancer, GU infections, voiding dysfunction, erectile dysfunction
• Urologic manifestations: GU TB, hemorrhagic cystitis (BK, adeno, CMV), Kaposi sarcoma, testis cancer, RCC, nephropathy (HIVAN), retention, hypogonadism, indinavir stones