Genital ulcer disease and less common STIs

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Genital ulcer disease is a syndrome rather than a visual diagnosis. HSV and syphilis dominate UK infection, while lymphogranuloma venereum, chancroid, donovanosis and mpox depend on anatomical exposure, travel and sexual network.

Ulcers can be hidden in the vagina, cervix, rectum or mouth. Pain, edge, base and lymph-node pattern are useful clues but have insufficient accuracy for organism-specific treatment without laboratory support.

LGV is caused by invasive C trachomatis L1–L3 serovars and may produce destructive proctitis. Chancroid is caused by Haemophilus ducreyi; donovanosis by Klebsiella granulomatis; mpox by monkeypox virus transmitted through close contact.

Non-infective disease is common and occasionally life threatening. Malignancy, inflammatory bowel disease, Behçet disease, aphthosis, drug reactions, trauma and necrotising infection remain active differentials when tests are negative or lesions fail to heal.

Key points

Most genital ulcers in UK practice are herpes or syphilis, and coinfection means both are tested regardless of appearance.
Swab fresh lesions for HSV NAAT and obtain syphilis serology with repeat testing after the early window when required.
Ask exact travel, country of partner, oral and anal exposure, sex-work contact, skin-to-skin networks, systemic symptoms and medicines.
LGV commonly presents as severe proctitis after rectal exposure or with transient ulcer followed by painful nodes; treat with doxycycline for 21 days.
Chancroid causes painful ragged ulcers with tender suppurative nodes and is mainly imported; confirm through specialist microbiology where possible.
Donovanosis causes slowly progressive painless beefy-red friable ulcers that bleed easily after exposure in endemic regions.
Mpox lesions are deep, firm and often umbilicated, with systemic symptoms and lymphadenopathy; follow current UKHSA testing and isolation advice.
Biopsy persistent or atypical ulcers to assess malignancy, inflammatory disease, fixed-drug eruption and other non-infective causes.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Common viral and treponemal infection

HSV and T pallidum cause most infectious genital ulcers encountered in UK sexual-health practice and may coexist.

Invasive chlamydial serovars

C trachomatis L1 to L3 strains invade lymphatic tissue and cause LGV ulcer, nodal disease or proctitis.

Imported bacterial infection

H ducreyi and K granulomatis follow sexual exposure in endemic regions and remain uncommon in the UK.

Close-contact viral exposure

Monkeypox virus spreads through direct lesion, body-fluid, respiratory or contaminated-material contact, with genital or perianal lesions common after intimate exposure.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Epithelial ulceration
Direct microbial replication or immune injury disrupts genital epithelium and exposes painful or painless inflamed tissue.
2
Lymphatic invasion
LGV organisms spread through draining lymphatics, producing buboes or proctitis; prolonged untreated inflammation can heal with fibrosis, stricture or fistulation.
3
Granulomatous expansion
K granulomatis survives within macrophages and drives progressive vascular granulation tissue that bleeds on contact and contains characteristic intracellular Donovan bodies.
4
Systemic inflammatory spread
Syphilis and mpox can disseminate beyond the inoculation site, producing constitutional illness, lesions at multiple sites and organ-specific complications.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Herpetic ulcer pattern

Grouped vesicles becoming multiple shallow painful ulcers with dysuria and tender bilateral nodes suggests HSV.

Syphilitic chancre

A solitary painless indurated clean-based lesion with regional nodes is classic, although multiple or painful chancres occur.

LGV proctitisRed flag

Severe anorectal pain, discharge, bleeding, tenesmus and systemic symptoms after rectal exposure resembles inflammatory bowel disease.

Chancroid syndrome

Deep painful ulcers with ragged undermined edges and unilateral tender fluctuant inguinal nodes follow endemic exposure.

Donovanosis lesion

Painless slowly enlarging beefy-red granulation tissue bleeds on contact and usually lacks regional lymphadenopathy.

Mpox eruptionRed flag

Deep firm lesions evolving synchronously through papule, vesicle and pustule stages with lymphadenopathy and systemic symptoms suggest mpox.

Red flags requiring action

Rapidly spreading genital pain, swelling, crepitus or skin necrosis suggests Fournier gangrene and needs emergency debridement.
Severe rectal pain, bleeding, tenesmus, fever or constipation after anal exposure suggests LGV proctitis or another invasive rectal infection.
Firm umbilicated lesions with fever, lymphadenopathy and epidemiological exposure may represent mpox and require infection-control action.
A persistent indurated, fungating or bleeding ulcer requires cancer assessment and biopsy even when an STI test is positive.
Recurrent oral and genital ulcers with eye pain, neurological or vascular symptoms suggests Behçet disease.
Ulceration in pregnancy, profound immunosuppression or a neonate needs immediate specialist evaluation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
HSV-1 and HSV-2 lesion NAATFirst step
Why
Identify the most common infectious cause using a swab from a fresh vesicle or ulcer base.
Interpretation and limitations
Negative testing from a dry healing lesion is less reliable; repeat from a new lesion when probability remains high.
02
Syphilis serology and lesion PCR
Why
Detect treponemal infection and directly confirm an early chancre where available.
Interpretation and limitations
Repeat serology after an appropriate interval if initial tests are negative during very early disease.
03
Chlamydia NAAT with LGV typing
Why
Detect rectal or lesion C trachomatis and determine whether an invasive LGV serovar is present.
Interpretation and limitations
Do not delay 21-day treatment for severe compatible proctitis while specialist typing is pending.
04
Mpox lesion PCR
Why
Confirm monkeypox virus from appropriate lesion material under current UKHSA arrangements.
Interpretation and limitations
Use required personal protective equipment, packaging and notification; a negative test does not explain another ulcer cause.
05
H ducreyi or K granulomatis testing
Why
Confirm rare imported chancroid or donovanosis through reference culture, PCR, histology or microscopy.
Interpretation and limitations
Routine laboratories may not offer testing; discuss exposure and specimen collection with sexual-health microbiology before sampling.
06
HIV and wider STI screen
Why
Identify coinfection and immune factors that increase severity or alter healing.
Interpretation and limitations
Sample every exposed anatomical site and repeat blood tests after window periods when necessary.
07
Biopsy with histology and culture
Why
Investigate persistent, atypical, indurated, necrotic or repeatedly test-negative ulceration.
Interpretation and limitations
Biopsy the edge through dermatology, gynaecology, urology or colorectal services to assess cancer, inflammation and unusual infection.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Behçet disease

Recurrent oral and genital aphthae with uveitis, skin, neurological or vascular inflammation indicate Behçet disease rather than an isolated sexually transmitted infection.

Crohn disease

Perianal fissures, deep ulcers, fistulae and proctitis can mimic LGV; chronic diarrhoea, abdominal symptoms and endoscopic inflammation favour Crohn disease.

Fixed-drug eruption

A sharply demarcated recurrent erosion returns at the same site after exposure to a triggering medicine.

Trauma and dermatitis

Friction, irritant products and scratching cause superficial painful erosions; a clear exposure pattern and negative lesion testing support a non-infective diagnosis.

Genital malignancy

Persistent induration, ulceration, bleeding or altered architecture requires biopsy for vulval, penile, vaginal or anal cancer.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01FIRSTCover common dangerous diagnosesFirst stepA new anogenital ulcer is identified and no single cause has been confirmed.

1Take HSV NAAT, syphilis serology and direct treponemal testing where available before lesion treatment.
2Offer HIV and exposure-site chlamydia and gonorrhoea tests and take a pregnancy test where relevant.
3Start early herpes or syphilis treatment when clinical probability and follow-up risk justify it rather than waiting for every result.
4Provide pain, urinary and wound support and advise abstinence until diagnosis, treatment and partner plan are clear.

02PROCTITISTreat suspected LGVSevere proctitis or compatible ulcer and lymph-node disease follows relevant sexual exposure.

1Collect rectal chlamydia NAAT, request LGV typing and test for gonorrhoea, syphilis, HSV, HIV and enteric pathogens.
2Give doxycycline 100 mg orally twice daily for 21 days when LGV is confirmed or strongly suspected.
3Drain fluctuant buboes by needle aspiration through specialist care rather than incision that creates a chronic sinus.
4Arrange partner testing and treatment, abstinence, clinical review and test of cure when current guidance indicates.

03IMPORTEDManage chancroid or donovanosisUlcer morphology and exposure in an endemic area make a rare bacterial STI plausible.

1Contact specialist microbiology before swabbing or biopsy because diagnostic methods and specimen transport are organism specific.
2For chancroid, give azithromycin 1 g orally once when the specialist pathway supports the diagnosis.
3For donovanosis, give azithromycin 500 mg daily or 1 g weekly for at least three weeks and until lesions fully heal.
4Review at short intervals, screen for HIV and syphilis and biopsy any lesion failing to show expected healing.

04ATYPICALEscalate non-healing diseaseEscalationTests are negative, ulcers recur systemically or a lesion persists, indurates, bleeds or destroys tissue.

1Re-examine all skin and mucosa, medication exposure, gastrointestinal, ocular, vascular and systemic symptoms.
2Arrange biopsy and tissue microbiology through an appropriate vulval, penile, dermatology or colorectal service.
3Investigate Behçet disease, Crohn disease, fixed-drug eruption, aphthosis, pyoderma gangrenosum and malignancy.
4Treat necrotising infection or organ-threatening inflammation urgently without waiting for outpatient pathology.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Treats invasive C trachomatis serovars in rectal, nodal and ulcerative disease.

Doxycycline for LGV

Give 100 mg orally twice daily for 21 days for confirmed or strongly suspected lymphogranuloma venereum.

Avoid in pregnancy, separate from iron and antacids, counsel photosensitivity and oesophageal precautions, and confirm partner management.

Treats susceptible H ducreyi and allows a simple observed regimen.

Azithromycin for chancroid

Give 1 g orally as a single dose when chancroid is diagnosed or strongly supported through specialist sexual-health assessment.

Check QT and liver risk, vomiting and resistance; lack of improvement requires diagnostic review rather than blind repeat dosing.

Eradicates K granulomatis from chronic friable genital tissue.

Azithromycin for donovanosis

Give 500 mg orally once daily or 1 g orally once weekly for at least three weeks and until every lesion has completely healed.

Prolong treatment until healed, monitor liver and QT risks and interactions, and investigate relapse or non-response with biopsy.

Reduces pain, healing time and shedding while typed lesion confirmation is pending.

Aciclovir while HSV suspected

Give 400 mg orally three times daily for five days for a first compatible herpes episode started within five days or while new lesions appear.

Adjust for renal impairment, maintain hydration and continue investigation because herpes appearance does not exclude syphilis or another ulcer.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Rectal stricture and fistula

Untreated LGV inflammation heals with fibrosis, narrowing the rectum or creating chronic sinus and fistulous tracts.

Genital tissue destruction

Progressive donovanosis, necrotising infection or malignancy can cause scarring, bleeding, anatomical loss and secondary infection when recognition and definitive treatment are delayed.

Disseminated infection

Syphilis, mpox or severe herpes may spread systemically, producing neurological, ocular, hepatic or widespread cutaneous disease that requires urgent organism-specific care.

HIV acquisition and transmission

Ulcerated mucosa removes epithelial barriers and recruits susceptible inflammatory cells, increasing HIV acquisition and transmission probability during sexual exposure.

Diagnostic delay

Repeated empirical antimicrobial or steroid treatment can mask cancer, inflammatory disease or invasive infection, allowing the underlying lesion to progress.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review lesion size, pain, node changes, urinary and rectal function and systemic symptoms at a diagnosis-specific interval.
Confirm every pending HSV, syphilis, chlamydia, LGV and mpox result and revise treatment rather than allowing results to go unseen.
Document partner notification and site-specific testing and observe required infection-control or public-health restrictions.
For LGV ensure resolution of proctitis and assess persistent stricture, fistula or inflammatory bowel disease mimic.
For donovanosis continue therapy until complete healing and review for relapse after an apparently closed surface.
Biopsy any lesion that persists, indurates, bleeds or fails to improve as predicted.
Safety-net severe pain, spreading necrosis, retention, neurological symptoms, eye inflammation, pregnancy and sepsis.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Appearance is probabilistic

Painful herpes can be solitary and syphilitic chancres can hurt, so microbiology overrides a memorised visual stereotype.

LGV mimics IBD

Rectal LGV can produce ulceration, bleeding and imaging inflammation that resembles Crohn disease and worsens with delayed treatment.

Buboes are aspirated

Needle aspiration relieves fluctuant LGV or chancroid nodes while incision can create a persistent draining sinus.

Donovanosis bleeds easily

The beefy-red surface contains fragile granulation tissue and organisms within large mononuclear cells called Donovan bodies.

Mpox can be localized

Anogenital lesions may occur with limited generalized eruption, so exposure history and lesion PCR remain important.

One infection does not exclude another

HSV, syphilis and HIV can coexist, requiring parallel testing even after a convincing positive lesion result.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose a genital ulcer solely from whether it is painful.
02
Do not omit repeat syphilis serology after a high-risk early negative result.
03
Do not treat severe proctitis as inflammatory bowel disease before excluding LGV and infection.
04
Do not incise a fluctuant bubo routinely.
05
Do not stop donovanosis treatment before complete lesion healing.
06
Do not repeatedly prescribe STI treatment for a persistent lesion without biopsy.