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Genital ulcer disease

Last updated 22 Mar 2026 · STIs & Sexual Health

Genital Ulcer Disease

⚠️
Clinical Reminder: All genital ulcers should be considered infectious until proven otherwise. Co-infection with multiple STIs (including HSV + syphilis) is common. Always offer a full STI screen including HIV serology.

Introduction & Australian Epidemiology

Genital ulcer disease (GUD) encompasses a clinically and microbiologically diverse group of conditions characterised by disruption of the genital skin or mucosa. In Australia, the principal infectious causes are herpes simplex virus (HSV-1 and HSV-2), primary syphilis (Treponema pallidum), and — in returned travellers or Indigenous Australians from endemic regions — chancroid (Haemophilus ducreyi), lymphogranuloma venereum (LGV; Chlamydia trachomatis serovars L1–L3), and donovanosis (Klebsiella granulomatis).

Notifications data from the Australian Government Department of Health (NNDSS) demonstrate a sustained rise in infectious syphilis across Australia since 2011, with a particularly alarming multi-jurisdictional outbreak in remote Aboriginal and Torres Strait Islander (ATSI) communities across the Northern Territory, Queensland, South Australia, and Western Australia. Between 2011 and 2023, over 3,000 cases of infectious syphilis were notified in ATSI communities, including congenital syphilis cases previously considered eliminated. HSV-2 seroprevalence in Australian adults is approximately 12–15%, with HSV-1 now accounting for up to 50% of new anogenital herpes diagnoses due to orogenital transmission. LGV has re-emerged as a cause of proctitis and GUD in men who have sex with men (MSM) in urban centres. Donovanosis was declared eliminated as a public health problem in Australia in 2022 following a sustained eradication program, though sporadic cases in returned travellers still occur.

Pathophysiology & Microbiology

GUD arises through direct inoculation of pathogens at sites of microtrauma during sexual contact, triggering local inflammatory and immune responses:

  • HSV-1/HSV-2 (Herpesviridae): Primary infection involves replication in keratinocytes, retrograde axonal transport to sensory ganglia (sacral ganglia for genital HSV), and establishment of lifelong latency. Reactivation triggered by immunosuppression, UV exposure, menstruation, or stress. HSV-2 recurs more frequently genitally (~4–6/year) vs HSV-1 (~1/year).
  • Treponema pallidum (syphilis): Spirochaete penetrates intact or abraded mucosa, disseminates haematogenously within days. Primary chancre results from endarteritis obliterans and plasma cell infiltrate. Without treatment, progresses through secondary, latent, and potentially tertiary stages over years to decades.
  • Haemophilus ducreyi (chancroid): Gram-negative coccobacillus causing tender, purulent, undermined ulcers with painful inguinal lymphadenopathy (bubo). Endemic in sub-Saharan Africa and South-East Asia; rare but importable in Australia.
  • Chlamydia trachomatis L1–L3 (LGV): Obligate intracellular bacterium invading lymphatic tissue. In MSM, more commonly presents as severe proctitis than classic genital ulcer. Primary papule/ulcer at inoculation site, followed by inguinal lymphadenopathy (groove sign).
  • Klebsiella granulomatis (donovanosis): Progressive, painless, beefy-red granulomatous ulcers. Donovan bodies (intracytoplasmic inclusions) on biopsy. Chronic and destructive without treatment. Now rare in Australia.

Clinical Presentation & Diagnostic Criteria

Clinical features provide important diagnostic clues but cannot reliably differentiate causes without laboratory confirmation. Assess: number of ulcers, pain, induration, depth, edges, base, associated lymphadenopathy (tender vs non-tender), systemic symptoms, and full sexual history including travel and contact exposures.

HERPES SIMPLEX
HSV-1 or HSV-2
Multiple shallow, painful vesicles/ulcers on erythematous base; clustered; associated dysuria, tender inguinal LAD; systemic prodrome (fever, myalgia) in primary episode
Most common GUD in Australia; primary episode most severe
PRIMARY SYPHILIS
Treponema pallidum
Solitary, painless, indurated, clean-based chancre with rolled edges; non-tender rubbery inguinal lymphadenopathy; heals spontaneously in 3–6 weeks without treatment
Classic presentation; may be painful, multiple, or atypical in MSM / HIV
CHANCROID
Haemophilus ducreyi
Multiple painful, soft, ragged, purulent ulcers with undermined edges; tender unilateral bubo (fluctuant in 50%); may suppurate spontaneously
Travel exposure to endemic regions; rare in Australia
LGV / DONOVANOSIS
C. trachomatis L1–L3 / K. granulomatis
LGV: transient painless papule/ulcer then inguinal groove sign; in MSM: severe haemorrhagic proctitis. Donovanosis: progressive painless beefy-red granulomatous ulcer
MSM; returned travellers from endemic areas; ATSI communities (historically)

Investigations

  • Essential
    HSV PCR — Ulcer Swab
    Sensitivity 95–99%; types HSV-1 vs HSV-2. Swab base and edges of active ulcer. Medicare item 69375. Preferred over culture. If vesicles present, unroof and swab fluid.
  • Essential
    Syphilis Serology — Treponemal + Non-treponemal
    Combination EIA/CLIA treponemal + RPR/VDRL non-treponemal testing. In primary syphilis, serology may be negative in first 2–4 weeks — repeat at 6 and 12 weeks if negative and clinical suspicion high. T. pallidum PCR on ulcer swab increasingly available (highly sensitive in primary syphilis).
  • Essential
    HIV Serology — 4th Generation Ag/Ab
    All GUD patients. GUD increases HIV transmission risk 3–5 fold. Medicare item 71097.
  • Essential
    Chlamydia & Gonorrhoea NAAT
    Urethral/cervical/rectal as clinically indicated. Medicare item 69384. If LGV suspected in MSM with proctitis, specifically request LGV genotyping (C. trachomatis serovars L1–L3) — available at SA Pathology, VIDRL, QHSS reference labs.
  • Referral
    Chancroid PCR (H. ducreyi)
    Available at reference laboratories. Consider in returned travellers from endemic regions (sub-Saharan Africa, South-East Asia, Papua New Guinea). Culture has low sensitivity.
  • Referral
    Donovanosis — Tissue Biopsy / Crush Preparation
    Demonstrating Donovan bodies (intracytoplasmic inclusions in macrophages) or K. granulomatis PCR at reference lab. Consult specialist if suspected.
  • Available
    Hepatitis B & C Serology
    Offer as part of comprehensive BBV screening in all STI presentations. Medicare item 69381 (HBsAg).

Risk Stratification

  • High-risk / urgent: Suspected primary syphilis (notifiable — mandatory notification to state/territory health authority); GUD in pregnancy (risk of vertical transmission); GUD with systemic features (fever, rash, meningism); HIV-positive with new GUD; GUD in ATSI individual from outbreak-affected community; LGV proctitis with bleeding or systemic sepsis
  • Moderate-risk: Recurrent GUD not responding to standard HSV therapy (consider aciclovir resistance, especially immunosuppressed); GUD in returned traveller from sub-Saharan Africa, South-East Asia, India (consider chancroid, LGV, donovanosis); MSM with rectal symptoms and new GUD (LGV)
  • Standard priority: First or recurrent episode HSV in immunocompetent patient with typical features; known HSV-positive with prodromal recurrence
🔴
Notifiable Disease: Syphilis (all stages), LGV, donovanosis, and chancroid are notifiable conditions in all Australian states and territories. Notify the relevant state/territory health authority promptly. Contact tracing and partner notification are mandatory.

Empirical Antimicrobial Therapy

Herpes Simplex Virus — First Episode:

💊
Valaciclovir 500 mg
Valtrex® · Antiviral (nucleoside analogue) · First-line HSV, first episode
Adult Dose500 mg BD orally
Paediatric20 mg/kg (max 500 mg) TDS for 5 days (herpes genitalis >12 years)
RouteOral
Duration7–10 days (extend if incomplete healing at day 10)
Renal Adj.eGFR 30–49: 500 mg daily; eGFR <30: 500 mg daily or 250 mg BD; HD: 500 mg after each dialysis
Hepatic Adj.No dose adjustment required for mild-moderate hepatic impairment
PBS Status✓ PBS General Benefit

HSV — Recurrent Episodes & Suppression:

💊
Valaciclovir 500 mg — Episodic / Suppressive
Valtrex® · Antiviral · Recurrent HSV management
Episodic Dose500 mg BD × 3–5 days; or 1 g daily × 5 days; initiate at prodrome/first sign
Suppressive Dose500 mg daily (≥6 recurrences/year); 1 g daily if HIV co-infected
RouteOral
Renal Adj.Reduce suppressive dose to 250 mg daily if eGFR <30
Hepatic Adj.No adjustment required
PBS Status✓ PBS General Benefit

Primary Syphilis (high clinical suspicion — treat before serology confirmed):

💉
Benzathine benzylpenicillin (BPG) 1.8 g IM
Bicillin L-A® · Beta-lactam antibiotic · Drug of choice for syphilis
Adult Dose1.8 g (2.4 million units) IM single dose
Paediatric50,000 units/kg IM (max 2.4 MU) single dose
RouteDeep intramuscular injection (divide between two sites if needed)
DurationSingle dose for primary/secondary/early latent syphilis (<2 years)
Renal Adj.No dose adjustment required
Hepatic Adj.No dose adjustment required
PBS Status⚠ PBS Authority Required (S100)

Chancroid (empirical — returned traveller with typical features):

💊
Azithromycin 1 g oral
Zithromax® · Macrolide antibiotic · Chancroid, first-line
Adult Dose1 g single oral dose
Paediatric20 mg/kg (max 1 g) single dose
RouteOral
DurationSingle dose; review at 3–7 days to confirm response
AlternativeCeftriaxone 250 mg IM single dose; or ciprofloxacin 500 mg BD × 3 days
Renal Adj.None required
Hepatic Adj.Use with caution in severe hepatic impairment
PBS Status✓ PBS General Benefit

Directed / Pathogen-Specific Therapy

Syphilis — Stage-Based Treatment:

💉
Benzathine benzylpenicillin (BPG) — Stage-Based
Bicillin L-A® · Beta-lactam antibiotic · All stages syphilis
Primary / Secondary / Early latent (<2 yrs)1.8 g (2.4 MU) IM × 1 dose
Late latent / Unknown duration1.8 g IM weekly × 3 doses (3 consecutive weeks)
NeurosyphilisBenzylpenicillin sodium 1.8–2.4 g (3–4 MU) IV 4-hourly × 10–14 days (specialist referral mandatory)
Penicillin AllergyDoxycycline 100 mg BD × 14 days (non-pregnant); desensitisation required in pregnancy
PBS Status⚠ PBS Authority Required (S100)

LGV (Lymphogranuloma Venereum):

💊
Doxycycline 100 mg
Doryx® · Tetracycline antibiotic · First-line LGV
Adult Dose100 mg BD orally
PaediatricContraindicated <8 years; 2.2 mg/kg BD (max 100 mg) for ≥8 years
RouteOral
Duration21 days (LGV proctitis or invasive disease); 14 days (uncomplicated genital LGV)
AlternativeAzithromycin 1 g weekly × 3 weeks (less robust evidence)
Renal Adj.None required
Hepatic Adj.Reduce dose in severe hepatic impairment
PBS Status✓ PBS General Benefit

Donovanosis:

💊
Azithromycin 1 g weekly / 500 mg daily
Zithromax® · Macrolide antibiotic · First-line donovanosis
Adult Dose1 g orally weekly; or 500 mg daily
RouteOral
DurationMinimum 3 weeks AND until all lesions have healed completely
AlternativeDoxycycline 100 mg BD; or co-trimoxazole 160/800 mg BD; or erythromycin 500 mg QID
PBS Status✓ PBS General Benefit

Aciclovir-Resistant HSV (immunosuppressed patients only):

💉
Foscarnet sodium
Foscavir® · Antiviral (pyrophosphate analogue) · Aciclovir-resistant HSV
Adult Dose40 mg/kg IV 8-hourly or 60 mg/kg 12-hourly
RouteIV infusion (minimum 1 hour)
DurationUntil clinical resolution (typically 14–21 days)
Renal Adj.Mandatory dose reduction per eGFR — see product information. Nephrotoxic; aggressive IV hydration required.
MonitoringRenal function, electrolytes, calcium, magnesium, phosphate daily during therapy
PBS Status⚠ PBS Restricted — ID specialist use

IV-to-Oral Switch Criteria

IV therapy is required for neurosyphilis and severe/disseminated HSV or aciclovir-resistant HSV (foscarnet). Switch to oral when all criteria met:

1
Clinical Improvement
Reduction in ulcer size, systemic symptoms resolved, afebrile for ≥24 hours, tolerating oral intake
2
No Dissemination
No evidence of CNS involvement, endophthalmitis, hepatitis, or endovascular dissemination
3
Susceptibility Confirmed
For HSV: confirmed aciclovir-susceptible isolate; switch to high-dose valaciclovir 1 g TDS to complete course. For neurosyphilis: complete full 10–14-day IV course; consolidation BPG IM weekly × 3 may be added per specialist advice.

Monitoring Parameters

Baseline
Full STI screen (HSV PCR, syphilis serology, HIV, chlamydia/gonorrhoea NAAT, hepatitis B/C serology). FBC, renal function if systemic symptoms or IV therapy planned.
1–3 months
Syphilis: RPR titre at 1 month post-treatment. Adequate response: 4-fold (2-dilution) decline in RPR by 3 months (primary/secondary) or 12 months (latent). Failure to decline → re-treatment or neurosyphilis exclusion.
3–4 weeks
LGV: Test of cure with NAAT 3–4 weeks after completing treatment. Monitor inguinal nodes. Sigmoidoscopy/proctoscopy for LGV proctitis to confirm mucosal healing.
6–12 months
Syphilis follow-up: RPR titres at 6 and 12 months (and 24 months for latent syphilis). HIV-positive patients: RPR at 1, 3, 6, 9, 12, 24 months. HSV suppression: reassess annually; consider stopping if recurrences remain infrequent.

Special Populations

🤰 Pregnancy
Syphilis BPG is mandatory — the ONLY validated treatment to prevent congenital syphilis. Doxycycline is inadequate and contraindicated in pregnancy. Desensitisation required for confirmed penicillin allergy. Serial RPR monthly after treatment. Universal first-trimester and third-trimester syphilis screening.
HSV Valaciclovir safe in pregnancy. Suppressive therapy from 36 weeks recommended if primary HSV acquired in pregnancy or frequent recurrences. Caesarean delivery if active lesions at labour onset.
LGV / Donovanosis Doxycycline CONTRAINDICATED. Use erythromycin 500 mg QID × 21 days or azithromycin (seek ID specialist input).
🛡️ HIV Co-infection
HSV More frequent, severe, prolonged recurrences. Higher rate of aciclovir resistance. Daily suppressive valaciclovir 500 mg reduces HSV-2 shedding and may reduce HIV transmission risk.
Syphilis Accelerated progression to neurosyphilis. Consider LP in all HIV-positive patients with syphilis of unknown duration or neurological symptoms. Some experts recommend 3-dose BPG even for early syphilis.
👶 MSM / High-Risk Groups
LGV screening High index of suspicion in MSM with proctitis or rectal ulcers. Request LGV genotyping specifically. Co-infection with HIV, syphilis, and gonorrhoea common.
Syphilis surveillance 3-monthly syphilis serology for sexually active MSM with multiple partners or PrEP users (ASHM Guidelines). PrEP does not protect against syphilis or HSV.
🫘 Renal Impairment
Valaciclovir Dose reduce per eGFR. eGFR 30–49: 500 mg daily. eGFR <30: 250 mg BD. HD patients: dose after each dialysis session.
Foscarnet Highly nephrotoxic — mandatory dose reduction per eGFR. Aggressive IV saline hydration required before each infusion. Avoid concurrent nephrotoxins.
Aboriginal and Torres Strait Islander Health

Infectious syphilis disproportionately affects Aboriginal and Torres Strait Islander (ATSI) communities across northern and central Australia. A multi-jurisdictional outbreak beginning in 2011 has resulted in thousands of notifications and multiple cases of congenital syphilis — a previously near-eliminated condition in Australia. The outbreak reflects the complex interplay of remote geography, limited healthcare access, population mobility, and broader social determinants of health.

Key responses include ASHM Syphilis Outbreak Response Guidelines for community health workers, rapid point-of-care (POC) syphilis testing programs (Determine Syphilis TP), and BPG stockpiling in outbreak-affected regions. POC testing allows immediate treatment without awaiting laboratory results — critical where follow-up is unreliable. Congenital syphilis screening is mandatory at the first antenatal visit and again in the third trimester for all pregnant women in outbreak-affected regions.

Healthcare Access
Implement point-of-care syphilis testing in remote clinics. Ensure BPG availability. Treat empirically when high clinical suspicion; do not wait for serology confirmation in outbreak regions.
Contact Tracing
Coordinate contact tracing with Aboriginal Health Workers and local ACCHO. Use online notification tools (letthemknow.org.au). Mandatory notification to state/territory health authority.
Cultural Safety
Ensure gender-concordant care where required. Use interpreters for patients whose first language is not English. Engage community health workers in health promotion and education.
Congenital Syphilis Prevention
Universal antenatal syphilis screening in first trimester and third trimester in outbreak regions. Immediate treatment with BPG if positive. Notify and treat all sexual partners.
⚠️
Syphilis Outbreak Alert: Any syphilis diagnosis in an ATSI individual must trigger immediate notification, contact tracing, and partner treatment. Refer to current CDNA/ASHM Syphilis Outbreak Response Guidelines. Do not wait for confirmatory serology to treat in high-risk clinical scenarios.

Antibiotic Stewardship (ACSQHC NSQHS Standard 3)

  • Collect appropriate specimens (ulcer swab, serology) before antimicrobials where feasible. Empirical therapy is appropriate in high-risk scenarios but must be followed by laboratory confirmation and result review.
  • BPG is the only validated treatment for syphilis in pregnancy — do not substitute doxycycline. Arrange desensitisation if penicillin allergy.
  • Avoid empirical dual therapy (syphilis + HSV) unless specific epidemiological risk for both. Document rationale and review when results available.
  • Aciclovir/valaciclovir resistance is rare in immunocompetent patients. Do not escalate to foscarnet without virological confirmation (TK gene mutation testing at reference laboratories).
  • Confirm syphilis treatment response with serial RPR titres. Do not re-treat empirically for serofast state (persistent low-titre RPR after adequate treatment) without LP exclusion of neurosyphilis.
  • Contact tracing and partner treatment is an essential AMS obligation — notifiable disease requirements must be fulfilled and documented in the medical record.

Follow-Up & Prevention

  • Syphilis: RPR titres at 1, 3, 6, 12, and 24 months. All sexual contacts within relevant window periods (3 months for primary syphilis) must be notified, tested, and treated. Mandatory notification to state/territory health authority.
  • HSV: Counsel on transmission risk (asymptomatic shedding occurs in absence of lesions). Consistent condom use reduces but does not eliminate transmission. Discuss suppressive therapy for serodiscordant couples. HSV-2 type-specific serology identifies infected individuals even without symptoms.
  • LGV: Test of cure 3–4 weeks post-treatment. Notify and treat all sexual contacts. Follow up for anorectal stricture or fistula in prolonged/untreated LGV proctitis.
  • General prevention: PrEP does not protect against syphilis, HSV, or LGV. Ensure regular STI screening (3-monthly for high-risk MSM and PrEP users per ASHM guidelines). HPV vaccination (9-valent) recommended. Hepatitis B vaccination if non-immune.
  • Pregnancy: Universal first-trimester and third-trimester syphilis screening. Antenatal HIV and hepatitis B/C testing. HSV suppressive therapy from 36 weeks if primary HSV in pregnancy. Mode-of-delivery discussion in HSV-positive women approaching labour.

References

  • 01
    Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). Australian STI Management Guidelines for Use in Primary Care. Sydney: ASHM; 2021. Available from: https://www.sti.guidelines.org.au
  • 02
    Kirby Institute. Syphilis Outbreak Response Guidelines for Community Health Workers. Sydney: Kirby Institute, UNSW; 2020.
  • 03
    Communicable Diseases Network Australia (CDNA). Syphilis: CDNA National Guidelines for Public Health Units. Canberra: Australian Government Department of Health; 2022.
  • 04
    Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187. doi:10.15585/mmwr.rr7004a1
  • 05
    Read TR, Fairley CK, Vodstrcil LA, et al. Increasing LGV in men who have sex with men, Australia 2012–2018. Sex Transm Infect. 2019;95(7):490–494. doi:10.1136/sextrans-2018-053978
  • 06
    Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med. 2009;361(14):1376–1385. doi:10.1056/NEJMra0807633
  • 07
    Spelman DW. Syphilis: a re-emerging infection. Intern Med J. 2019;49(9):1081–1082. doi:10.1111/imj.14434
  • 08
    Marra CM, Maxwell CL, Smith SL, et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis. 2004;189(3):369–376. doi:10.1086/381227
  • 09
    Bowden FJ, Tabrizi SN, Garland SM, Fairley CK. Sexually transmitted infections: new diagnostic approaches and treatments. Med J Aust. 2002;176(11):551–557. doi:10.5694/j.1326-5377.2002.tb04548.x
  • 10
    National Notifiable Diseases Surveillance System (NNDSS). Communicable Diseases Intelligence. Canberra: Australian Government Department of Health; 2023. Available from: https://www.health.gov.au/topics/communicable-diseases/nndss
  • 11
    World Health Organization. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). Geneva: WHO; 2016. Available from: https://www.who.int
  • 12
    Australian Institute of Health and Welfare (AIHW). Australia's Health 2022. Canberra: AIHW; 2022. Available from: https://www.aihw.gov.au/australias-health