Genital ulcers and sexually transmitted infection mimics

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

Begin with the person's concern and language for their anatomy. Ask privately about onset, pain, prodrome, recurrence, oral or eye symptoms, bowel disease, systemic illness, trauma, menstruation, pregnancy possibility and every recent medicine. With permission, cover partners, anatomical sites and practices, barrier use, previous STI and whether any contact was unwanted. Explain that confidentiality is respected but cannot be absolute if someone is at serious risk. Assess an adolescent's competence and provide confidential care according to law and policy; safeguarding questions should be proportionate rather than triggered automatically by an ulcer.

Examination should use good light, explicit consent and an offered chaperone. Record number, size, edge, depth, base, induration, vesicles, discharge, surrounding dermatosis and groin nodes. Inspect oral mucosa, eyes and other skin when aphthosis, Behçet disease, Crohn disease, drug reaction or inflammatory dermatosis is plausible. Ulcers may appear red, violet, grey, brown or black against different skin tones; palpation of border and nodes and recognition of erosion, slough, necrosis and vesicles are more transferable than colour labels. Stop if consent is withdrawn and avoid repeated examinations merely to satisfy multiple teams.

Common infectious causes should be tested together because visual diagnosis is fallible and coinfection occurs. HSV PCR is lesion based; syphilis serology can be negative early and needs a documented repeat plan. HIV and exposure-site testing complete the risk assessment. If initial tests are negative, revisit medicine timing, recurrent aphthae, gastrointestinal symptoms and pathergy rather than declaring the lesion psychological. Acute non-sexually acquired ulcers often follow fever and are managed with analgesia, local care and exclusion of important infection; Behçet disease requires recurrent features, not a single ulcer. Any persistent indurated or bleeding focus warrants tissue diagnosis.

Key points

Genital-ulcer morphology is not sufficiently reliable to rule an STI in or out; HSV and syphilis can be painful, painless, multiple, atypical or coexist.
Take a private anatomy- and practice-based history, explain confidentiality and its limits, obtain consent for each examination and test and offer a chaperone.
Swab the base of a fresh vesicle or ulcer for HSV PCR; a dry late crust gives a poorer sample and a negative result does not exclude earlier herpes.
Request syphilis serology and repeat it when very early infection remains plausible; arrange direct lesion testing only through a service that can perform and interpret it.
Offer HIV and exposure-site gonorrhoea and chlamydia testing and assess hepatitis vaccination or testing from history rather than ordering a genital-only panel.
Non-sexually acquired acute genital ulcers can follow a febrile illness, especially in adolescents; the presentation does not itself establish sexual activity or abuse.
Aphthosis, Behçet disease, Crohn disease, fixed-drug eruption, lichen sclerosus, lichen planus, pyoderma gangrenosum, trauma and malignancy are important noninfectious causes.
First-episode genital herpes is treated promptly on clinical suspicion, commonly with oral aciclovir 400 mg three times daily for five days, extended if new lesions or healing continue.
A persistent indurated, keratotic, bleeding or unexplained test-negative ulcer needs urgent specialist examination and biopsy rather than repeated empirical antimicrobials.
Partner notification, abstinence until the advised point, condom limitations, vaccination, pregnancy implications and a named results route are part of treatment, not administrative extras.

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

Sexually transmissible infection

HSV and Treponema pallidum are the common priority infections, with coinfection and atypical morphology possible at any genital, anal or oral site.

Postinfectious aphthous inflammation

A systemic febrile illness can trigger an abrupt intense mucosal inflammatory response and non-sexually acquired acute genital ulceration.

Systemic inflammatory disease

Behçet disease, Crohn disease and neutrophilic disorders produce ulceration through recurrent vascular, granulomatous or dysregulated innate immune pathways.

Medicine, trauma or neoplasia

Fixed-drug reactions, severe adverse reactions, friction, pressure, accidental or inflicted injury and epithelial cancer all disrupt genital surface integrity.

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

1
HSV epithelial cytolysis
Viral replication destroys epithelial cells to form vesicles and ulcers before latency develops in sensory ganglia and permits later recurrence.
2
Syphilitic endarteritis
Local treponemal invasion and vascular inflammation produce a chancre and regional nodes before organisms disseminate systemically.
3
Aphthous immune injury
Dysregulated mucosal immunity recruits inflammatory cells that create deep painful necrotic ulcers despite absence of a sexually transmitted pathogen.
4
Barrier and tissue destruction
Drug cytotoxicity, neutrophilic inflammation, granulomatous disease, trauma or malignant invasion produces erosion that can converge on a similar visible endpoint.
5
Pain and urinary inhibition
Exposed inflamed nerve endings and urine contact cause severe burning, leading to reduced drinking, withholding and occasionally acute retention.

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

First-episode genital herpes

Grouped vesicles, shallow painful erosions, dysuria, tender nodes and systemic prodrome support HSV, but lesions may be sparse or atypical and require PCR.

Primary syphilis

A classically painless clean ulcer with rubbery nodes is suggestive, yet pain, multiplicity and coinfection occur, so serology and specialist testing remain necessary.

Acute non-sexually acquired ulcer

A sudden deep painful necrotic-appearing ulcer follows a febrile or systemic illness in a person without relevant exposure after infectious and other causes are assessed.

Recurrent aphthosis or Behçet pattern

Repeated oral and genital aphthae with eye inflammation, skin lesions, pathergy, vascular or neurological features creates a systemic inflammatory pattern.

Crohn-related disease

Linear knife-cut fissures, oedematous tags, perianal disease, discharge or ulcers accompany bowel symptoms or can precede recognised intestinal disease.

Drug or inflammatory dermatosis

A sharply recurrent same-site dusky patch suggests fixed-drug eruption, while pallor, sclerosis, lacy erosions or widespread mucositis redirects to lichen or severe drug disease.

Malignant ulcerRed flag

A persistent indurated, rolled, keratotic, bleeding or enlarging ulcer and firm node requires urgent biopsy even when an initial infection test is positive.

Red flags requiring action

Pregnancy near delivery, neonatal or immune vulnerability, retention, inability to drink, severe pain out of proportion, necrosis, fever or neurological signs, ocular symptoms, widespread mucosal blistering, a persistent indurated or bleeding ulcer, groin nodes, or recurrent oral and genital ulcers with eye or neurological disease requires urgent escalation.

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 nucleic-acid amplification testFirst step
Why
Confirm HSV-1 or HSV-2 from an active genital lesion.
Interpretation and limitations
Vigorously swab the base of a fresh unroofed vesicle or ulcer with consent; sensitivity falls as lesions heal, so a negative late sample does not rule out clinical herpes.
02
Syphilis serology
Why
Detect treponemal infection and establish a baseline titre for disease activity and follow-up.
Interpretation and limitations
Request treponemal and quantitative non-treponemal testing through the local algorithm; repeat after the window period when early chancre remains plausible and investigate previous treatment history.
03
Comprehensive exposure-site STI screen
Why
Identify coinfection and protect partners and pregnancy.
Interpretation and limitations
Offer HIV testing and gonorrhoea and chlamydia NAAT from every exposed site, with hepatitis and pregnancy assessment when indicated; negative urine testing does not exclude pharyngeal or rectal infection.
04
Inflammatory and systemic assessment
Why
Investigate recurrent aphthosis, bowel disease, vasculitis or severe drug reaction.
Interpretation and limitations
Select FBC, inflammatory, renal, liver, nutritional and bowel tests from associated findings and refer eye or neurological symptoms urgently; HLA-B51 neither confirms nor excludes Behçet disease.
05
Skin or mucosal biopsy
Why
Diagnose malignancy, lichen planus, Crohn disease, immunobullous disease, pyoderma gangrenosum or an unexplained persistent ulcer.
Interpretation and limitations
Sample a viable active edge and include tissue for histology, immunofluorescence or culture only after agreeing handling; avoid debriding suspected pyoderma gangrenosum because pathergy may worsen it.

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

HSV and syphilis

Both can depart from textbook pain and number patterns and can coexist, making lesion PCR and serology complementary.

Acute genital aphthosis

Sudden deep painful ulceration after systemic illness with no relevant exposure emerges only after proportionate infectious and inflammatory assessment.

Behçet or Crohn disease

Recurrent oral ulcers with eye or vascular disease suggests Behçet, while knife-cut perianal lesions and bowel symptoms suggest Crohn disease.

Drug and inflammatory dermatosis

Same-site recurrence after a medicine, widespread mucositis, sclerosis or lacy erosions points to fixed drug, SJS, lichen sclerosus or lichen planus.

Trauma or malignancy

History and distribution may support injury, while persistence, induration, keratosis, bleeding or nodes requires biopsy for neoplasia.

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

01First-line ulcer screenTest common infections togetherFirst stepFirst lineA new genital vesicle, erosion or ulcer has no immediate surgical or skin-failure emergency.

1With consent, sample a fresh lesion base for HSV PCR and obtain syphilis serology, recording onset and whether an early repeat sample will be required.
2Offer HIV plus gonorrhoea and chlamydia testing from each exposed anatomical site and assess hepatitis, pregnancy and vaccination needs.
3Give analgesia, gentle saline or water cleansing, urination advice and a specific results, abstinence and return-symptom plan while tests are pending.

02First-episode herpes treatmentStart antiviral therapy promptlyPainful fresh vesicles or ulcers and clinical history make a first HSV episode likely.

1Start oral aciclovir 400 mg three times daily for five days without waiting for PCR when within the useful treatment window and no admission indication exists.
2Extend treatment when new lesions continue, healing is incomplete or complications persist, and use intravenous age- and renal-adjusted treatment for severe or disseminated disease.
3Provide analgesia, hydration and urination measures, discuss recurrence and transmission and arrange partner and pregnancy advice without blame.

03Noninfectious-ulcer routeUse pattern and time course after essential exclusionsCommon infection tests are negative or systemic, medicine, bowel or recurrent aphthous features predominate.

1Reconstruct fever, medicine and recurrence timing and examine mouth, eyes, skin and perianal region; request targeted tests rather than a broad autoimmune screen.
2For an acute non-sexually acquired ulcer, give adequate analgesia, barrier and urinary support and explain that the finding alone neither proves sexual transmission nor abuse.
3Refer recurrent multisystem disease to rheumatology, ophthalmology, gastroenterology or dermatology and obtain biopsy for persistent or diagnostically discordant disease.

04Persistent-ulcer routeExclude cancer and destructive inflammationAn ulcer is indurated, bleeding, progressive, associated with nodes or fails to heal after diagnosis-specific care.

1Arrange urgent vulval, penile, anal or dermatology specialist assessment and record the exact focus without repeated empirical antimicrobial courses.
2Obtain edge biopsy and nodal assessment, coordinating histology and microbiology when infection and neoplasia can coexist.
3Reconcile pathology with clinical evolution and repeat or deepen sampling when a benign superficial result does not explain the persistent lesion.

05Consent and safeguarding routeProtect autonomy while responding to riskThe person is under 18, lacks capacity, describes non-consensual contact or the history or other findings raise a safety concern.

1Offer private time, assess competence or capacity, explain confidentiality and its limits and record the person's words without leading or repeated questioning.
2Treat pain and infection and follow a specialist paediatric sexual-health or forensic pathway when indicated, preserving samples and avoiding repeated intimate examination.
3Seek safeguarding advice from the complete context; neither an STI nor a noninfectious ulcer alone determines what happened or replaces careful enquiry.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

First-line antiviral treatment shortens lesion formation and symptoms when begun promptly on clinical suspicion.

Aciclovir for first-episode genital herpes

Give 400 mg orally three times daily for 5 days in an adult with an uncomplicated first episode; extend if new lesions continue, healing remains incomplete or complications persist. Use specialist age-, weight-, pregnancy- and renal-adjusted dosing when these factors apply.

Ensure hydration and adjust for renal impairment; severe, disseminated, neurological, neonatal or immunocompromised disease needs urgent intravenous therapy. Pregnancy, especially near delivery, requires obstetric and sexual-health coordination.

Reduces severe surface pain and can enable hydration and urination while disease-specific treatment acts.

Topical lidocaine for short-term pain relief

Apply a small amount of an appropriate licensed topical local-anaesthetic preparation to external painful skin as directed, or use shortly before urination; combine with simple oral analgesia and cool saline or water care.

Avoid large areas, broken mucosal overapplication and duplicate local anaesthetics; stop if irritation occurs and seek urgent help for retention, toxicity symptoms or pain out of proportion.

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

Urinary retention and dehydration

Severe pain may prevent drinking or urination, particularly with extensive primary HSV or acute aphthous disease.

Disseminated or neurological infection

HSV can disseminate or affect meninges, brain, eye and neonate, especially in pregnancy and immune compromise.

Untreated syphilis

Infection can progress through systemic stages and cross the placenta, while partners remain exposed without notification and treatment.

Scarring and chronic pain

Deep or recurrent inflammation can distort anatomy and sustain pelvic-floor guarding, dyspareunia and fear after surface healing.

Delayed systemic or malignant diagnosis

Repeatedly attributing ulceration to an STI can postpone recognition of Crohn disease, Behçet disease, severe drug reaction or cancer.

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

Give every patient a named confidential route for results and document who will act on positive HSV, syphilis, HIV or other STI findings.
For syphilis record baseline quantitative titre, stage and treatment, arrange guideline-timed serological response checks and complete partner notification.
Reassess a test-negative ulcer that has not substantially healed within the agreed interval and biopsy persistent induration, bleeding, keratosis or nodal disease.
During pregnancy confirm obstetric, neonatal and sexual-health teams share the result and delivery or fetal-monitoring plan.
For adolescents and vulnerable adults document consent, confidentiality discussion, people present and safeguarding reasoning without stigmatising language.

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

Sample age matters

HSV yield is highest from a fresh vesicle or ulcer base and declines after crusting, making a negative late swab less reassuring.

Early syphilis can be seronegative

A compatible new chancre can precede detectable antibodies, so documenting a repeat serology date is part of the initial investigation.

A genital ulcer is not a disclosure

Non-sexually acquired acute ulcers and inflammatory dermatoses occur; safeguarding action rests on history, development and wider findings, not lesion location alone.

Sites follow practices

Urine NAAT cannot find every pharyngeal or rectal infection, so specimens must match anatomy exposed rather than identity labels.

11Common pitfallsFrequent interpretation and management errors.

01
Taking a superficial swab from an old dry crust and treating a negative HSV result as definitive.
02
Testing urine only despite oral or anal exposure and then declaring the STI screen complete.
03
Using an adolescent's caregiver as the default audience for a confidential sexual history without assessing competence and safety.
04
Equating an acute non-sexually acquired genital ulcer with abuse or using its label to dismiss a separate safeguarding disclosure.
05
Repeating antimicrobials for a persistent indurated or bleeding ulcer instead of obtaining biopsy.
06
Missing fixed-drug eruption because a recently stopped medicine is omitted from the exposure timeline.