STI-associated syndromes guide: Anogenital ulcers

On this page:

• Public health importance
• Common STI-associated etiology
• Clinical manifestations
• Diagnostic testing
  • HSV-1 and HSV-2
  • Syphilis
  • Other tests
• Empiric treatment and management
• Follow-up
• Reporting and partner notification
• References

Public health importance

A United States of America (US) study found that more than half of genital ulcers were due to Herpes simplex virus type 1 or 2 (HSV-1 or HSV-2)^{Footnote 1}. Genital herpes is a chronic infection characterized by recurrences and asymptomatic shedding. HSV-1 and HSV-2 can be transmitted vertically during pregnancy and delivery^{Footnote 2Footnote 3} and neonatal herpes can cause serious morbidity (including long-term neurological and developmental sequelae) and results in high mortality^{Footnote 4Footnote 5Footnote 6}.

Syphilis may also cause anogenital ulcers at the site of inoculation. Left untreated, syphilis has many severe complications. It can be transmitted vertically during pregnancy and congenital syphilis may have severe consequences for newborns and be fatal^{Footnote 7}. Even after treatment, a significantly higher risk of adverse pregnancy outcomes remains compared to pregnancies without syphilis infection^{Footnote 8}.

People with anogenital ulcers are at increased risk of acquiring or transmitting HIV ^{Footnote 9Footnote 10} .

Common STI-associated etiology

Sexually transmitted infections (STI) associated with anogenital ulcers include:

• Herpes simplex virus type 1 or type 2 (HSV-1 or HSV-2)
• Treponema pallidum causing syphilis
• Chlamydia trachomatis (CT) genotypes L1, L2 or L3 causing lymphocranuloma venereum (LGV)
• Haemophilus ducreyi causing chancroid
• Klebsiella granulomatis causing granuloma inguilale (dovonanosis)
• Mpox virus^{Footnote 11}

Anogenital ulcers in young, sexually active people are most often associated with a sexually transmitted infection (STI)^{Footnote 1}.

HSV-1 and HSV-2 have been found to account for more than half of STI-associated anogenital ulcers^{Footnote 1Footnote 12}.

Rates of infectious syphilis have increased in Canada in recent years and outbreaks have been declared in most provinces and territories since 2017. Syphilis should be considered in people presenting with anogenital ulcers.

Lymphogranuloma venereum (LGV) should also be considered as a cause of anogenital ulcers. Since 2004, there have been LGV outbreaks in Canada, mainly in gay, bisexual and other men who have sex with men (gbMSM).

Mpox should be considered as a possible cause of anogenital ulcers^{Footnote 13}. From April 28, 2022 until September 29, 2023, 1,515 cases of mpox were reported in Canada, disproportionately impacting gay, bisexual and other men who have sex with men (gbMSM)^{Footnote 14Footnote 15Footnote 16}.

Consider chancroid (Haemophilus ducreyi) and granuloma inguinale (Klebsiella granulomatis) in people who had sex while in an endemic area, in people with a sexual partner from an endemic area, and within outbreak situations^{Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21Footnote 22}. Chancroid is a major cause of anogenital ulcers in sub-Saharan Africa and in many parts of Southeast Asia and Latin America^{Footnote 23}. Granuloma inguinale is endemic in some tropical and developing areas, including India, Papua New Guinea, the Caribbean, Central Australia and southern Africa^{Footnote 24}.

Anogenital ulcers may also be due to non-sexually transmitted fungal, viral or bacterial infections, as well as non-infectious skin and mucosal conditions^{Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21Footnote 22}.

More than one etiology may be identified on evaluation^{Footnote 25}.

Even after a complete diagnostic evaluation, at least 25% of people with anogenital ulcers have no laboratory-confirmed diagnosis^{Footnote 26}.

Clinical manifestations

STI	Appearance of ulcer(s)	Site	Other features
Genital herpes (HSV-1 or HSV-2)	Grouped vesicles or pustules evolving to superficial circular or coalescing ulcers on an erythematous base that may take a couple of weeks to scab over Smooth margin and base	Anywhere in the "boxer short" area Glans, prepuce, pubis, inguinal, penile shaft, cervix, vulva, vagina, perineum, anus, rectum, legs and buttocks	Incubation: 1-26 days with a median of 6-8 days for primary genital herpesFootnote 27 Ulcers usually painful or pruritic Genital pain Enlarged, non-fluctuant and tender inguinal lymph nodes (most common in primary infection) Constitutional symptoms, such as fever, malaise and pharyngitis, are common with primary infection Atypical presentations, such as linear fissures in the vulva or rectum Recurrences, particularly with HSV-2
Primary syphilisFootnote 23	Papule evolving to a chancre Indurated with serous exudates Single ulcer in 70% of cases Smooth margin and base	At site of inoculation Internal genital tract, intra-anal and oral lesions may go unnoticed	Incubation: 3-90 days Painless ulcer Firm, enlarged, non-fluctuant, non-tender lymphadenopathy is common Lesions may heal without treatment
LGV	Self-limited single papule, which may ulcerate	At site of inoculation (penis, rectum, vulva, vagina, oral cavity, occasionally cervix)	Incubation: 3-30 days Painless ulcer Most frequently seen in gbMSM presenting with rectal symptoms (proctitis) Tender inguinal or femoral lymphadenopathy, mostly unilateral Signs and symptoms of urethritis maybe present If not treated, fibrosis can lead to fistulas, strictures and obstruction of the lymphatic drainage causing elephantiasis
Chancroid	Single or multiple necrotizing ulcer(s)	At site of inoculation External genitalia, rarely in vagina or on cervix	Incubation: 5-14 days Painful ulcers Often painful swelling and suppuration of regional lymph nodes, with erythema and edema of overlying skin
Granuloma inguinale	Single or multiple progressive ulcerative lesions Highly vascular (beefy red appearance) Bleeds easily on contact Hypertrophic, necrotic and sclerotic variants	At site of inoculation: usually in the genital, anal or groin regionsFootnote 29	Incubation: 1-180 days Painless Relapse can occur 6-18 months after apparently effective therapy
Mpox	Single or multiple macular, pustular, vesicular or crusted mucocutaneous lesionsFootnote 13Footnote 16Footnote 30 Lesions may progress from macules to papules to vesicles and then pustules, and then scab overFootnote 16Footnote 30 Lesions in the same area of the body tend to evolve synchronously Atypical lesions and/or lesions in multiple phases can be present in different areas of the body simultaneouslyFootnote 13Footnote 16	At site of inoculation, most commonly the anogenital area, but can occur anywhere on the body, including trunk, arms, legs, face, and palms and soles Footnote 13Footnote 16Footnote 30Footnote 31Footnote 32	Incubation: 3-21 daysFootnote 16Footnote 30Footnote 32Footnote 33 Infectious up to 4 days prior to symptom onset, and until scabs have fallen off and lesions have epithelialized (typically, 2-4 weeks)Footnote 16Footnote 33Footnote 34Footnote 35 Often painful, can present with pharyngitis or proctitisFootnote 13Footnote 16Footnote 32 Commonly associated with lymphadenopathyFootnote 13Footnote 16Footnote 30Footnote 32 Systemic symptoms, including fever, lethargy, myalgia, headache, can occur, frequently prior to the appearance of skin lesionsFootnote 13Footnote 16Footnote 30Footnote 32 Complications include soft-tissue superinfection, myocarditis, epiglottitis, encephalitis and, rarely, deathFootnote 13Footnote 16 Mpox infection during pregnancy may increase risk of maternal and fetal morbidity and mortalityFootnote 13Footnote 16 Individuals who are immunocompromised are more likely to experience severe diseaseFootnote 16

Diagnostic testing

Minimum testing for cases of anogenital ulcers should include HSV-1 and HSV-2 and syphilis^{Footnote 26}. Refer to etiology-specific Sexually transmitted and blood-borne infections (STBBI) Guide(s) for information on diagnostic testing and interpretation of results.

HSV-1 and HSV-2

• Obtain swabs from ulcerations or vesicles to test for HSV-1 and HSV-2 by nucleic acid amplification tests (NAAT) or viral culture (where available).

Syphilis

• Obtain swabs from ulcerations or vesicles to test for syphilis using direct tests (non-serological) such as NAAT or direct florescent antibody test (DFA). Consult local laboratory for direct test options.
• Conduct syphilis serology regardless of suspected stage of infection.

Other tests

• Chlamydia trachomatis (CT)-positive specimens from people with symptoms compatible with LGV and from sexual partners of people diagnosed with LGV should be forwarded to a provincial/territorial public health laboratory or the National Microbiology Laboratory (NML) for LGV genotyping.
• When mpox is suspected, lesion fluid and/or crust, scab, and skin swabs can be submitted for polymerase chain reaction (PCR) testing. Consult your provincial/ territorial public health laboratory or the NML for instructions regarding specimen handling and transport before submitting specimens^{Footnote 31}. If mpox is suspected, use of airborne, droplet and contact precautions are recommended^{Footnote 16}. 
• Consider testing for Haemophilus ducreyi (chancroid) and Klebsiella granulomatis (granuloma inguinale) in people at risk of exposure.
• For evaluation of vulvar ulcers, order biopsies, cultures, smears and serology, as appropriate.
• Offer HIV testing^{Footnote 36Footnote 37Footnote 38Footnote 39Footnote 40}.

Empiric treatment and management

The decision to treat empirically or to wait for test results should reflect the:

• Severity of the clinical condition
• Probability of infection
• Person's risk factors for sexually transmitted and blood-borne infections (STBBI)
• Person's willingness to abstain from sex and to return for test results or follow-up

Consider empiric treatment for genital herpes^{Footnote 26Footnote 41Footnote 42}. The main treatment goals are to accelerate healing, prevent complications and reduce risk of transmission^{Footnote 43}. Refer to the Genital herpes guide for treatment recommendations.

In people with risk factors for syphilis or LGV and compatible presentations, consider empiric treatment if follow-up is uncertain. Refer to the Syphilis or Chlamydia (including LGV) guides for treatment recommendations, as appropriate.

Supportive care is a central part of mpox management as there is limited data on the clinical effectiveness of specific treatments for mpox infections in humans^{Footnote 16}. Consult an infectious disease physician to discuss therapeutic options for suspected or confirmed cases^{Footnote 16}.

Some existing treatments for smallpox, such as TPOXX (tecovirimat monohydrate capsules) may have a role to play in select instances^{Footnote 16}. TPOXX is an oral antiviral agent that is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 13 kg. It does not currently have an approved Health Canada indication for mpox or other Orthopoxviruses^{Footnote 16}. However, recommendations for its off-label use can be found at the following webpage: CADTH Health Technology Review on Tecovirimat (Tpoxx): Update.

Consider consulting an experienced colleague if chancroid or granuloma inguinale is suspected.

Follow-up

Arrange follow-up to provide test results, re-evaluate the person and confirm diagnosis.

The need for test of cure (TOC) depends on which pathogen is confirmed by laboratory testing. In the case of suspected or confirmed genital herpes, LGV or syphilis infection, consult etiology specific STBBI Guides for follow-up and test of cure recommendations.

Consider consulting an experienced colleague for the management, treatment and follow-up of suspected chancroid or granuloma inguinale.

Suspected or confirmed cases of mpox and their contacts should follow isolation recommendations as per your provincial, territorial or local public health authority.

Repeat HIV testing if initial testing was done during the window period.

Reporting and partner notification

When treatment is indicated for an STI, notify, evaluate, test and treat (as appropriate) sexual partners. Refer to the etiology-specific guide(s) for guidance on reporting and partner notification.

For suspected or confirmed cases of mpox, refer to provincial, territorial or local public health authority's reporting requirements and recommendations for contacts. For up-to-date guidance on pre-exposure and post-exposure vaccination for mpox, refer to the Canadian Immunization Guide or provincial and territorial vaccination schedules and guidelines.

Refer to local public health authority for information on reporting requirements and partner notification for chancroid and granuloma inguinale.

References