Step 2 CK · Internal Medicine · Infectious Disease

Genital Ulcers, Persistent Urethritis & Less-Common STIs

Name: Genital Ulcers, Persistent Urethritis & Less-Common STIs
Creator: Veli Bakalov, MD

Does it hurt? The question that sorts genital ulcers, plus the STIs that break the usual script

Infectious Disease·HIV & Sexually Transmitted Infections·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Painful genital ulcer = HSV (grouped vesicles, tender nodes; lesion NAAT; valacyclovir) or chancroid (ragged purulent ulcer with suppurative bubo).
Chancroid (Haemophilus ducreyi) → azithromycin 1 g once or ceftriaxone 250 mg IM once; aspirate or incise fluctuant nodes.
Painless indurated clean chancre with firm nontender nodes = primary syphilis → one IM dose of benzathine penicillin G.
LGV (C. trachomatis L1–L3): transient painless papule, then painful buboes with groove sign or hemorrhagic proctocolitis in MSM → doxycycline for 21 days.
Granuloma inguinale: beefy-red friable ulcer, no adenopathy, Donovan bodies → azithromycin for at least 3 weeks.
Test every genital ulcer patient for syphilis and HIV.
Mpox: painful umbilicated anogenital pustules and proctitis → lesion PCR, supportive care, tecovirimat if severe or immunocompromised, JYNNEOS vaccine before or within 4 days of exposure.
DGI: migratory polyarthralgia, tenosynovitis, and sparse hemorrhagic pustules → NAATs from all exposed sites plus blood cultures, IV ceftriaxone; recurrent Neisseria infection suggests C5–C9 deficiency.
Persistent urethritis: confirm it, exclude reinfection, then test for M. genitalium (doxycycline then moxifloxacin) and Trichomonas (metronidazole).

Approach to genital ulcers

Ask about pain. HSV is the most common cause of genital ulcers in the US, followed by syphilis. Painful ulcers point to HSV or chancroid; painless ulcers to primary syphilis, LGV, or granuloma inguinale (donovanosis). The nodes add a second clue, and travel history matters because chancroid, LGV, and donovanosis are uncommon in the US.

Workup. Every ulcer gets syphilis serology plus darkfield microscopy or lesion NAAT for T. pallidum, an HSV lesion NAAT, and an HIV test, because ulcers raise both HIV acquisition and transmission; H. ducreyi testing is added where available. When follow-up is uncertain, treat the likeliest cause presumptively at the first visit.

Genital ulcer diseases

Cause	Ulcer	Nodes	Test	Treatment
HSV	Painful grouped vesicles → shallow ulcers	Tender, bilateral	Lesion NAAT	Valacyclovir
Chancroid (H. ducreyi)	Painful, ragged, purulent	Suppurative bubo	Clinical after excluding syphilis and HSV	Azithromycin or ceftriaxone
Primary syphilis	Painless, indurated, clean	Firm, nontender	Darkfield or NAAT; serology	Benzathine penicillin G
LGV (C. trachomatis L1–L3)	Painless, transient	Painful buboes, groove sign	Chlamydia NAAT	Doxycycline 21 days
Donovanosis (K. granulomatis)	Painless, beefy-red, bleeds	None (pseudobuboes)	Donovan bodies	Azithromycin ≥3 weeks

Painful ulcers: herpes and chancroid

Genital herpes. HSV-2, and increasingly HSV-1, causes painful grouped vesicles on an erythematous base that erode into shallow ulcers. A first episode brings fever, malaise, and dysuria; recurrences are milder and heralded by tingling. Lesion NAAT is the test of choice; type-specific serology cannot prove that a given ulcer is herpes, and the Tzanck smear is obsolete. Treat a first episode with valacyclovir (or acyclovir or famciclovir) for 7–10 days and recurrences with short episodic courses; daily suppression for frequent recurrences also lowers transmission.

Chancroid. Haemophilus ducreyi, a gram-negative coccobacillus that may line up in parallel chains ("school of fish"), causes deep, painful ulcers with ragged undermined edges and a gray purulent base, followed by a tender, often unilateral bubo that can rupture. Culture needs special media, so diagnosis is largely clinical. Treat with azithromycin 1 g orally once or ceftriaxone 250 mg IM once, aspirate or incise fluctuant nodes, and treat recent partners.

With H. ducreyi you "do cry": ulcer and node both hurt.

Painless ulcers: syphilis, LGV, and donovanosis

Primary syphilis. About 3 weeks (10–90 days) after exposure a usually single, painless, indurated, clean-based chancre appears and heals in 3–6 weeks even untreated. Darkfield microscopy or lesion NAAT confirms it. Nontreponemal tests (RPR, VDRL) may still be negative early, so repeat serology when suspicion is high. One IM dose of benzathine penicillin G 2.4 million units cures it.

Lymphogranuloma venereum. The L1–L3 serovars invade lymphatics. The primary papule is small, painless, and often unnoticed; 2–6 weeks later painful, fluctuant inguinal and femoral buboes appear, sometimes on both sides of the inguinal ligament (groove sign). After receptive anal sex, LGV instead causes hemorrhagic proctocolitis that mimics inflammatory bowel disease, now seen mainly in MSM. Untreated disease leaves fistulas, rectal strictures, and genital lymphedema. Chlamydia NAAT of the lesion, node aspirate, or rectum supports the diagnosis; treat with doxycycline 100 mg twice daily for 21 days.

Donovanosis. Klebsiella granulomatis, acquired mainly in tropical regions, causes slowly enlarging, highly vascular ulcers that bleed on contact. Subcutaneous granulomas can mimic nodes. Crush preparation or biopsy shows Donovan bodies, bipolar-staining bacteria inside macrophages that resemble closed safety pins; treat with azithromycin for at least 3 weeks and until all lesions heal.

Mpox

Presentation. Mpox is an orthopoxvirus; the 2022 clade II outbreak spread mainly among MSM through close skin and sexual contact. Fever and lymphadenopathy may precede firm, deep-seated, umbilicated vesicles or pustules that crust over. Lesions are often few, anogenital or perioral, and painful, and proctitis with rectal pain and bleeding is common. Prominent lymphadenopathy helps separate mpox from varicella and smallpox. Swab lesions for mpox PCR, and test for HIV and other STIs.

Management. Most infections need only analgesia, sitz baths, stool softeners for proctitis, and isolation until lesions crust and new skin forms. Tecovirimat, obtained through CDC, is reserved for severe disease, eye involvement, or immunocompromise such as advanced HIV. JYNNEOS, a nonreplicating 2-dose vaccine, is given before exposure to people at risk and as post-exposure prophylaxis, ideally within 4 days.

Disseminated gonococcal infection

Presentation. Bloodstream spread of Neisseria gonorrhoeae is favored by menses, pregnancy, and terminal complement (C5–C9) deficiency, including eculizumab therapy. The arthritis-dermatitis syndrome combines fever, migratory polyarthralgia, tenosynovitis of the wrists and hands, and a few painful pustules on a hemorrhagic base; the other pattern is a purulent monoarthritis, often of the knee.

Diagnosis and treatment. Send NAATs from urogenital, rectal, and pharyngeal sites plus blood and joint cultures, which provide susceptibility data. Admit for ceftriaxone 1 g IV daily, switching after 24–48 hours of improvement to susceptibility-guided oral therapy to complete at least 7 days; add doxycycline if chlamydia has not been excluded. Fluoroquinolone resistance rules out ciprofloxacin.

Persistent urethritis

Confirm first. Document discharge, ≥2 WBC per oil-immersion field on Gram stain, or positive leukocyte esterase or ≥10 WBC/hpf in first-void urine. Reinfection from an untreated partner and nonadherence explain most persistence; after that, test for Mycoplasma genitalium and Trichomonas vaginalis, which is treated with metronidazole.

Mycoplasma genitalium. It lacks a cell wall, so β-lactams are useless, and macrolide resistance is common. It causes persistent urethritis, cervicitis, and PID. Without resistance testing, give doxycycline 100 mg twice daily for 7 days followed by moxifloxacin 400 mg daily for 7 days; if the strain is macrolide-susceptible, doxycycline is followed by high-dose azithromycin.