Clinical safety notice: A genital, anal or oral ulcer is a clinical syndrome, not a diagnosis. Examine and test for syphilis, herpes and HIV, consider pregnancy and sexual assault, and treat promptly according to current Uganda guidance. Severe illness, urinary retention, eye/neurologic symptoms, pregnancy complications, necrotic lesions or suspected malignancy require urgent senior/specialist review.
Post focus: Genital-ulcer disease (GUD) — definition, causes, lesion recognition, history, examination, investigations, syndromic management, pathogen-specific doses, complications, counselling and follow-up.
Learning objectives
- Define genital-ulcer disease and classify infectious, inflammatory, traumatic and malignant causes.
- Distinguish the classic patterns of syphilis, herpes, chancroid, LGV and donovanosis while recognising that coinfection and atypical lesions are common.
- Take a complete lesion, sexual, pregnancy, medication, travel and safeguarding history.
- Perform a safe genital, oral, anal, lymph-node, skin, neurologic and eye examination.
- Select lesion swabs, serology, NAAT/PCR, culture and biopsy appropriately.
- Start guideline-based empiric therapy without delaying urgent referral; include doses, contraindications and monitoring.
- Prevent transmission, manage partners, screen for HIV and other STIs, and document healing or treatment failure.
1. Definition and clinical significance
Genital-ulcer disease is loss of continuity of genital, perianal or adjacent mucocutaneous epithelium, producing an erosion, vesicle, pustule, papule or ulcer, with or without inguinal lymphadenopathy. It may be single or multiple, painful or painless, superficial or deep. Lesions can occur on the penis, vulva, vagina, cervix, perineum, anus, buttocks, lips or mouth.
Genital ulcers increase HIV acquisition and transmission risk by disrupting the mucosal barrier and recruiting target immune cells. Clinical appearance alone is unreliable: herpes may be painless in some patients, syphilis may be painful in an HIV-positive person, and mixed infections can alter a classic pattern. A negative test early in disease does not always exclude infection.
2. Causes and classification
| Category | Examples | Clues |
|---|---|---|
| Viral STIs | HSV-1/HSV-2; mpox can cause anogenital or oral lesions. | Grouped vesicles evolving to shallow painful erosions; prodrome; recurrent lesions. Mpox may cause deep, firm, umbilicated lesions with systemic symptoms and lymphadenopathy. |
| Bacterial STIs | Treponema pallidum (syphilis), Haemophilus ducreyi (chancroid), Klebsiella granulomatis (donovanosis), C. trachomatis L1–L3 (LGV). | Indurated painless chancre; painful ragged ulcer and bubo; beefy-red friable ulcer; transient ulcer followed by painful nodes/proctitis. |
| Other infections | Scabies, candidiasis with fissures, bacterial skin infection, tuberculosis or deep fungal disease. | Pruritus, crusting, immunosuppression, chronicity or systemic disease. |
| Inflammatory/immune | Behçet disease, aphthosis, fixed drug eruption, lichen planus, reactive ulcers. | Recurrent oral/genital ulcers, ocular disease, systemic symptoms, medication relationship. |
| Traumatic/irritant | Friction, shaving, sexual injury, caustic substances, instrumentation or genital cutting. | Clear mechanical/chemical history and lesion at contact site; no pathogen on appropriate testing. |
| Neoplastic | Squamous-cell carcinoma, vulval/cervical/penile cancer. | Persistent indurated, bleeding, everted or non-healing ulcer; biopsy required. |
3. Lesion-pattern comparison
| Condition | Incubation/course | Ulcer and nodes | Associated features |
|---|---|---|---|
| Primary syphilis | Usually 10–90 days after exposure. | Single painless, clean-based indurated chancre; non-tender rubbery nodes; may be multiple or atypical. | Heals in 3–6 weeks even untreated, then secondary/latent disease develops. |
| Genital herpes | Usually 2–12 days; primary illness can be extensive. | Clusters of painful vesicles → pustules → shallow erosions; tender nodes; lesions may coalesce. | Prodrome (burning/tingling), dysuria, fever, myalgia; recurrent lesions usually milder and heal faster. |
| Chancroid | Often 3–7 days. | Deep painful ragged ulcer with grey/yellow base, undermined edges; painful unilateral/bilateral suppurative buboes. | Can cause phimosis, scarring and fistula; now uncommon in many regions, so confirm local epidemiology. |
| LGV | Small transient papule/ulcer may occur, often unnoticed; nodes after 2–6 weeks. | Tender unilateral inguinal/femoral nodes (“buboes”) or proctitis in receptive anal exposure. | Rectal pain, tenesmus, bleeding, discharge; chronic strictures/fistula if untreated. |
| Donovanosis | Weeks to months. | Progressive painless beefy-red, friable ulcers that bleed easily; usually no true nodes. | “Pseudobuboes”, autoinoculation and destructive scarring; endemicity/travel matters. |
| Mpox | Usually 3–17 days. | Firm deep-seated umbilicated lesions; may be few and anogenital, with tender nodes. | Fever, headache, myalgia, rectal pain, proctitis; assess exposure and infection-control needs. |
4. History: ask before touching the lesion
4.1 Lesion history
- First noticed date, preceding tingling/blisters, pain/itch, number, progression, discharge, bleeding, odour and healing time.
- Initial lesion or recurrent episodes; prior diagnosis and treatment, adherence and response.
- Self-treatment: creams, antiseptics, steroids, antibiotics, traditional remedies or attempts to squeeze/drain.
- Urinary retention/dysuria, urethral or vaginal discharge, pelvic pain, rectal pain/tenesmus, fever or rash.
4.2 Sexual and exposure history
- Partners and genders, number/new partner, last contact, practices (vaginal/anal/oral), condom use and partner symptoms.
- Known syphilis, herpes, HIV, mpox or other STI exposure; sexual networks, transactional sex and travel.
- Pregnancy possibility, last menstrual period, contraception and breastfeeding.
- Previous STIs, HIV status, vaccination (HBV/HPV), PrEP/PEP use and drug allergies.
4.3 Safety and safeguarding
- Ask privately about coercion, violence, inability to consent, trafficking or child sexual abuse using local safeguarding pathways.
- Explain confidentiality limits before asking sensitive questions. Do not blame or assume infidelity from a latency-sensitive infection.
5. Examination
- Consent, privacy, chaperone, gloves and adequate light. Offer a self-collected swab if appropriate and acceptable.
- General state: temperature, pulse, blood pressure, hydration, weight, fever, rash, palms/soles lesions, alopecia and lymphadenopathy.
- Inspect penis, glans, foreskin, scrotum, vulva, perineum, anus and buttocks; document site, number, size, edge, base, depth, induration, tenderness, vesicles, crusting and discharge.
- Palpate inguinal/femoral nodes for tenderness, matting, fluctuation and overlying erythema. Do not incise a bubo blindly.
- Speculum/bimanual examination when indicated and consented: vaginal/cervical ulcers, cervicitis, discharge, cervical motion or adnexal tenderness.
- Oral and pharyngeal examination for ulcers; eye examination for conjunctivitis/uveitis; neurologic screen for headache, cranial-nerve deficits, meningism, sensory changes or ataxia.
- Photograph only with explicit consent, institutional policy and secure storage; never identify a patient in teaching material.
6. Urgent red flags
- Sepsis, severe pain, necrosis, rapidly spreading cellulitis, Fournier gangrene or inability to pass urine.
- Sudden severe testicular pain (torsion), severe pelvic pain/bleeding, pregnancy or suspected PID.
- Eye pain/visual loss, neurologic signs, meningism, hearing loss or suspected ocular/oto/neurosyphilis.
- Extensive HSV in an immunocompromised patient, dehydration or HSV urinary retention.
- Fluctuant painful bubo, suspected abscess, fistula, rectal obstruction or severe proctitis.
- Persistent indurated/bleeding ulcer beyond expected healing, or any lesion suspicious for cancer—urgent biopsy/specialist referral.
- Sexual assault, child safeguarding concern or inability to ensure a safe discharge.
7. Investigations
| Investigation | Use | Limitations/notes |
|---|---|---|
| Syphilis serology | RPR/VDRL (quantitative activity) plus treponemal test (TPHA/TPPA/EIA) for confirmation. | Very early primary syphilis can be seronegative; repeat in 2–4 weeks if suspicion remains. Record baseline titre for follow-up. |
| HSV PCR/NAAT or culture from lesion | Best from a fresh vesicle/ulcer; type HSV-1 vs HSV-2 when possible. | Sensitivity falls as lesions heal. A negative test does not fully exclude herpes. |
| Dark-field microscopy/PCR for T. pallidum | Can confirm early chancre where available. | Not widely available; oral contamination can mislead dark-field microscopy. |
| Chancroid culture/PCR | Confirmation where available. | Culture is technically difficult; diagnosis often requires compatible lesion, negative syphilis/HSV tests and local epidemiologic support. |
| NAAT for chlamydia/gonorrhoea | Detects concurrent urethritis/cervicitis and LGV-associated chlamydia. | Site-specific specimens (urine, genital, rectal/pharyngeal) are essential. |
| HIV Ag/Ab test and viral load/CD4 as indicated | Every patient with GUD should be offered HIV testing and prevention linkage. | Consider window period, consent and repeat testing after recent exposure. |
| Mpox PCR | Swab lesions according to national infection-control guidance. | Use appropriate PPE and notify public health when required. |
| Biopsy/histology | Non-healing, indurated, atypical, recurrent or treatment-resistant ulcer. | Include edge/base and request testing for infection and malignancy. |
| Pregnancy, CBC, renal/liver tests | Medication safety and severity assessment. | Do not delay lifesaving treatment while waiting for non-essential results. |
8. Syndromic approach when results are unavailable
- Confirm an ulcer/erosion or vesicular lesion; exclude trauma, dermatitis, candidal fissure and malignancy.
- Test for syphilis and HIV at the first visit and obtain an HSV swab where possible.
- Use local surveillance to decide whether chancroid treatment is justified. In many settings herpes and syphilis predominate; empiric treatment should cover the most likely causes without indiscriminate polypharmacy.
- Start treatment the same day because early therapy reduces transmission and complications. Arrange review in 3–7 days (earlier if severe).
- If the ulcer has not clearly improved, reassess diagnosis, adherence, re-exposure, HIV/immunosuppression, resistant infection and malignancy; biopsy/refer.
9. Pathogen-specific treatment and doses
Dose and protocol notice: The examples below reflect widely used WHO/CDC-style regimens. Use the latest Uganda Clinical Guidelines, local resistance information, pregnancy guidance and available formulations. Confirm allergy, weight, renal/hepatic function and drug interactions before prescribing.
9.1 Syphilis
- Primary, secondary or early latent (<1 year): benzathine penicillin G 2.4 million units IM once, divided into two injection sites. Observe after injection for anaphylaxis and counsel about the Jarisch–Herxheimer reaction (fever, chills, myalgia within 24 hours).
- Late latent or unknown duration: benzathine penicillin G 2.4 million units IM weekly for 3 doses (total 7.2 million units). If a dose is delayed beyond the protocol window, restart according to national guidance.
- Neurosyphilis/ocular/otosyphilis: hospital/specialist care; aqueous crystalline penicillin G 18–24 million units/day IV (3–4 million units every 4 hours or continuous infusion) for 10–14 days is a common international regimen. Do not use benzathine penicillin alone.
- Pregnancy: penicillin is the only proven treatment that prevents congenital syphilis. Desensitise and treat urgently if allergic; do not substitute doxycycline.
- Test and treat partners according to exposure stage; screen for HIV and other STIs; perform quantitative RPR/VDRL follow-up at recommended intervals.
9.2 Genital herpes
- First clinical episode: acyclovir 400 mg orally three times daily for 7–10 days (or valacyclovir 1 g twice daily for 7–10 days). Extend if not healed; adjust for renal impairment.
- Episodic recurrent disease: acyclovir 800 mg orally twice daily for 5 days or 800 mg three times daily for 2 days (follow local protocol and start during prodrome).
- Suppressive therapy: acyclovir 400 mg twice daily for up to 12 months in frequent/distressing recurrences; review annually. Suppression reduces recurrences and transmission but does not replace condoms or disclosure.
- Severe, disseminated, CNS disease, urinary retention, pregnancy near delivery or immunocompromise requires specialist/IV treatment. Provide saline cleansing, analgesia, hydration and urinary support.
9.3 Chancroid
Use only when supported by local epidemiology/clinical-laboratory assessment. Common international options include azithromycin 1 g orally once or ceftriaxone 250 mg IM once; alternatives include ciprofloxacin 500 mg orally twice daily for 3 days or erythromycin base 500 mg orally three times daily for 7 days. Current local guidance may differ. Re-examine in 3–7 days; large buboes may require aspiration through intact skin, not incision and drainage.
9.4 Lymphogranuloma venereum
Typical regimen: doxycycline 100 mg orally twice daily for 21 days. Alternatives in specialist/local guidance include azithromycin 1 g orally weekly for 3 weeks or erythromycin 500 mg orally four times daily for 21 days. Test for rectal involvement and HIV; review until proctitis and nodes resolve.
9.5 Donovanosis
Specialist/public-health confirmation is desirable. A common regimen is azithromycin 1 g orally once weekly or 500 mg orally daily until lesions have healed (at least 3 weeks). Continue until complete epithelialisation and investigate for malignancy if healing is atypical.
9.6 Mpox or other ulcerative infections
Isolate/precaution according to national policy, swab lesions for PCR, provide analgesia and hydration, assess immunocompromise and refer severe disease. Do not assume every anogenital ulcer is an STI or prescribe antibiotics without evidence of bacterial infection.
10. Medication safety
| Medicine | Key cautions | Adverse effects/interactions |
|---|---|---|
| Benzathine penicillin | Confirm allergy; never give IV. Use specialist desensitisation in pregnancy allergy. | Anaphylaxis, injection pain, Jarisch–Herxheimer reaction; monitor and document dose. |
| Acyclovir/valacyclovir | Renal-dose adjustment; maintain hydration. | Headache, nausea, renal toxicity/neurotoxicity in renal failure. |
| Doxycycline | Avoid in pregnancy unless specialist; caution in young children. | Oesophagitis, photosensitivity; separate iron/calcium/antacids. |
| Azithromycin | QT prolongation, hepatic disease, macrolide allergy. | GI effects, QT prolongation, hepatotoxicity; review other QT-prolonging drugs. |
| Ciprofloxacin | Do not use empirically where resistance is likely; avoid pregnancy unless specialist. | Tendon injury, neuropathy, dysglycaemia, QT/CNS effects; interactions with cations/warfarin. |
11. Partner care, counselling and prevention
- Explain that some infections are latent or asymptomatic; a new diagnosis does not prove when or from whom infection was acquired.
- Notify and evaluate partners according to the specific infection and exposure window. Provide confidential partner-notification options.
- Avoid vaginal, anal and oral sex while ulcers are present and until treatment is complete; condoms/dental dams reduce but do not eliminate transmission because uncovered skin can shed HSV/syphilis.
- Offer HIV testing, condoms, HIV PrEP/PEP assessment, hepatitis B and HPV vaccination, and screening for gonorrhoea/chlamydia/trichomonas.
- Give written wound-care and analgesia advice; avoid caustic antiseptics, steroid creams or unprescribed antibiotics.
- Discuss pregnancy planning, neonatal risk and immediate obstetric review for pregnancy or delivery near active herpes lesions.
12. Follow-up and documentation
- Review at 3–7 days to assess pain, ulcer size, new lesions, fever, node fluctuation, adherence and test results; schedule further review until healed.
- Syphilis: record baseline RPR/VDRL titre and follow national serologic schedule; evaluate a fourfold titre failure or new symptoms for reinfection/treatment failure.
- Herpes: review recurrent episodes, psychosocial effect, suppressive-therapy need and pregnancy plans.
- Failure to improve: confirm adherence/re-exposure, repeat syphilis/HSV/HIV testing if early window, culture/NAAT, biopsy and specialist referral.
- Document lesion morphology and measurements, sites sampled, results, dose/route/time of treatment, allergies, partner plan, counselling and follow-up date.
13. Nursing and emergency-care interventions
- Use a trauma-informed, confidential approach; offer a chaperone, interpreter and patient-controlled pauses.
- Assess pain, fever, hydration, urine output, pregnancy, immune status and medication allergies.
- Provide prescribed analgesia, wound hygiene, hydration and local comfort measures; monitor for anaphylaxis after injectable penicillin.
- Use standard precautions and lesion-specific infection control; safely package swabs and label all anatomical sites.
- Teach medication adherence, Jarisch–Herxheimer expectations, genital-care precautions, abstinence and danger signs.
- Coordinate HIV/STI testing, partner notification, vaccination, safeguarding and referral before discharge.
14. Worked cases
Case 1: painless indurated ulcer
A patient has a single painless indurated chancre and rubbery nodes. Obtain syphilis serology and HIV test, treat promptly for early syphilis according to current guideline, counsel about Jarisch–Herxheimer reaction, notify partners and arrange titre follow-up. If neurologic/ocular symptoms exist, refer for CSF/ocular evaluation rather than routine benzathine alone.
Case 2: painful grouped lesions
Grouped painful vesicles, dysuria and tender nodes suggest first-episode HSV. Swab a fresh lesion for PCR, start acyclovir promptly, provide analgesia and hydration, test for HIV/syphilis and review for urinary retention or disseminated disease.
Case 3: non-healing ulcer
An indurated ulcer that bleeds after four weeks despite empiric STI treatment requires biopsy and specialist referral. Do not keep repeating antibiotics while cancer, inflammatory disease and atypical infection remain possible.
15. Quick self-test
- Why can ulcer appearance not reliably identify the pathogen?
- What are the classic differences between a syphilitic chancre, HSV and chancroid?
- What is the standard benzathine penicillin G dose for early syphilis?
- When must a genital ulcer be biopsied or urgently referred?
- Why are HIV testing and partner services integral to GUD care?
Answers
- Coinfection, HIV/immunosuppression and atypical lesions alter classic appearances; clinical diagnosis alone is insensitive.
- Syphilis: usually painless indurated clean ulcer; HSV: painful grouped vesicles/erosions; chancroid: painful ragged deep ulcer with tender suppurative nodes.
- 2.4 million units IM once for primary, secondary or early latent infection.
- Persistent, indurated, bleeding, atypical or treatment-resistant lesions; severe pain/necrosis, systemic/ocular/neuro symptoms, pregnancy, retention or assault.
- Ulcers increase HIV transmission risk, coinfection is common, and untreated partners cause reinfection and ongoing community spread.
Further study and source material
- Slideshare: Genital ulcer (history, morphology, differentials, laboratory diagnosis and management).
- WHO symptomatic STI guidelines (genital-ulcer syndrome flow charts and practical recommendations).
- CDC diseases characterised by genital, anal or perianal ulcers.
- CDC syphilis treatment guidance.
- Uganda Clinical Guidelines 2023 — verify current national regimens.
Take-home: Treat genital ulcers as an urgent STI syndrome: examine carefully, test for syphilis/HSV/HIV, start evidence-based therapy promptly, protect partners, recognise ocular/neuro/pregnancy emergencies, and biopsy lesions that do not heal as expected.
