STI-associated syndromes guide: Anogenital ulcers

This guide provides an overview of the management and empiric treatment of sexually transmitted infection (STI) - associated anogenital ulcers, which are characterised by vesicular, pustular, erosive, ulcerative, or crusted anogenital lesion(s) with or without regional lymphadenopathy.

Public health importance

A United States of America (US) study found that 70-80% of genital ulcers were due to Herpes simplex virus (HSV) type 1 or 2^{Footnote 1}. Genital herpes is a chronic infection characterized by recurrences and asymptomatic shedding. HSV can be transmitted vertically during pregnancy and delivery^{Footnote 2}^{Footnote 3} and neonatal herpes can cause serious morbidity (including long-term neurological and developmental sequelae) and results in high mortality^{Footnote 4}^{Footnote 5}^{Footnote 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 9}^{Footnote 10}.

Common STI-associated etiology

STIs 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)

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

HSV-1 and HSV-2 account for 95% of STI-associated anogenital ulcers^{Footnote 11}.

Since most provinces and territories are experiencing syphilis outbreaks, syphilis should be considered in people presenting with anogenital ulcers and rashes or proctitis.

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).

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 12}^{Footnote 13}^{Footnote 14}^{Footnote 15}^{Footnote 16}^{Footnote 17}. Chancroid is a major cause of anogenital ulcers in sub-Saharan Africa and in many parts of Southeast Asia and Latin America^{Footnote 18}. Granuloma inguinale is endemic in some tropical and developing areas, including India, Papua New Guinea, the Caribbean, Central Australia and southern Africa^{Footnote 19}.

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 12}^{Footnote 13}^{Footnote 14}^{Footnote 15}^{Footnote 16}^{Footnote 17}.

More than one etiology may be identified on evaluation^{Footnote 20}.

Even after a complete diagnostic evaluation, at least 25% of people with anogenital ulcers have no laboratory-confirmed diagnosis^{Footnote 21}.

Clinical manifestations

STI	Appearance of ulcer(s)	Site	Other features
Genital herpes (HSV)	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	Ulcers usually painful or pruritic Genital pain Enlarged, nonfluctuant 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 Incubation: 1-26 days with a median of 6-8 days for primary genital herpes^{Footnote 22} Recurrences, particularly with HSV-2
Primary syphilis^{Footnote 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	Painless ulcer Firm, enlarged, non-fluctuant, non-tender lymphadenopathy is common Lesions may heal without treatment Incubation: 3-90 days
LGV	Self-limited single papule, which may ulcerate	At site of inoculation (penis, rectum, vulva, vagina, oral cavity, occasionally cervix)	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 Incubation: 3-30 days
Chancroid	Single or multiple necrotizing ulcer(s)	At site of inoculation External genitalia, rarely in vagina or on cervix	Painful ulcers Often painful swelling and suppuration of regional lymph nodes, with erythema and edema of overlying skin Incubation: 5-14 days
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 regions^{Footnote 24}	Painless Incubation: 1-180 days Relapse can occur 6-18 months after apparently effective therapy

Diagnostic testing

Minimum testing for cases of anogenital ulcers should include HSV and syphilis^{Footnote 25}. Refer to etiology-specific guide(s) for information on diagnostic testing and interpretation of results.

HSV

Obtain swabs from ulcerations or vesicles to test for HSV by nucleic 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, dark field microscopy 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 laboratory or the National Microbiology Laboratory (NML) for LGV genotyping.
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 26}^{Footnote 27}^{Footnote 28}^{Footnote 29}^{Footnote 30}.

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 31}^{Footnote 32}^{Footnote 33}. The main treatment goals are to accelerate healing, prevent complications and reduce risk of transmission^{Footnote 34}. 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.

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

Follow-up

Arrange a follow-up visit 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 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.

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.

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

References

Footnotes

Footnote 1

Mertz KJ, Trees D, Levine WC, Lewis JS, Litchfield B, Pettus KS, et al. Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group. J Infect Dis 1998;178(6):1795-1798.

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Footnote 2

Prober CG, Corey L, Brown ZA, et al. The management of pregnancies complicated by genital infections with herpes simplex virus. Clin Infect Dis 1992;15(6):1031-1038.

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Footnote 3

Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S, et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991;324(18):1247-1252.

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Footnote 4

Lopez-Medina E, Cantey JB, Sánchez PJ. The mortality of neonatal herpes simplex virus infection. J Pediatr 2015;166(6):1529-1532. e1.

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Footnote 5

Whitley RJ, Roizman B. Herpes simplex virus infections. The Lancet 2001;357(9267):1513-1518.

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Footnote 6

Kropp RY, Wong T, Cormier L, et al. Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study. Pediatrics. 2006;117(6):1955-1962.

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Footnote 7

Finelli L, Berman SM, Koumans EH, Levine WC. Congenital syphilis. Bull World Health Organ 1998;76 Suppl 2:126-128.

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Footnote 8

Lumbiganon P, Piaggio G, Villar J, et al. The epidemiology of syphilis in pregnancy. Int J STD AIDS 2002;13(7):486-494.

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Footnote 9

Celum CL. The interaction between herpes simplex virus and human immunodeficiency virus. Herpes 2004;11 Suppl 1:36A-45A.

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Footnote 10

Wasserheit JN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis 1992;19(2):61-77.

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Footnote 11

Corey L, Holmes KK. Genital herpes simplex virus infections: current concepts in diagnosis, therapy, and prevention. Ann Intern Med. 1983;98(6):973-983.

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Footnote 12

Kropp RY, Wong T, Canadian LGV Working Group. Emergence of lymphogranuloma venereum in Canada. CMAJ 2005;172(13):1674-1676.

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Footnote 13

Public Health Agency of Canada. Reported cases and rates of notifiable STI from January 1 to June 30, 2004, and January 1 to June 30, 2003. 2004.

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Footnote 14

Centers for Disease Control and Prevention (CDC). Lymphogranuloma venereum among men who have sex with men--Netherlands, 2003-2004. MMWR Morb Mortal Wkly Rep 2004;53(42):985-988.

Return to footnote 14 referrer

Footnote 15

Nieuwenhuis RF, Ossewaarde JM, Gotz HM, et al. Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have sex with men. Clin Infect Dis 2004; 39(7):996-1003.

Return to footnote 15 referrer

Footnote 16

Infectious syphilis in MSM, Toronto, 2002: public health interventions. Annual Meeting of the International Society for STD Research; 2003.

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Footnote 17

Infectious syphilis in MSM, Toronto, 2002: outbreak investigation. International Society for Sexually Transmitted Diseases Research Congress; 2003.

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Footnote 18

Lewis DA. Epidemiology, clinical features, diagnosis and treatment of Haemophilus ducreyi-a disappearing pathogen? Expert Rev Anti Infect Ther, 2014;12(6):687-696.

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Footnote 19

O'Farrell N. Donovanosis. Sex Transm Infect. 2002;78(6):452-457.

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Footnote 20

DiCarlo RP, David H DH. The clinical diagnosis of genital ulcer disease in men. Clin Infect Dis. 1997;25(2):292-298.

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Footnote 21

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. 2002;51(No. RR-6):1-78

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Footnote 22

Aurelian L. Herpes simplex viruses. Clinical Virology Manual, Fourth Edition: American Society of Microbiology; 2009. p. 424-453.

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Footnote 23

Singh AE, Romanowski B. Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. Clin Microbiol Rev 1999 Apr;12(2):187-209.

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Footnote 24

Government of South Australia - SA Health. Donovanosis (granuloma inguinale) - including symptoms, treatment and prevention. SA Health 2019.

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Footnote 25

Kimberlin DW. Herpes simplex virus infections of the newborn. Semin Perinatol. 2007;31(1):19-25.

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Footnote 26

Van de Perre P, Segondy M, Foulongne V, et al. Herpes simplex virus and HIV-1: deciphering viral synergy. Lancet Infect Dis. 2008;8(8):490-497.

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Footnote 27

Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370(9605):2127-2137.

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Footnote 28

Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006;20(1):73-83.

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Footnote 29

Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185(1):45-52.

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Footnote 30

Smith C, Pogany L, Auguste U, Steben M, Lau T. Does suppressive antiviral therapy for herpes simplex virus prevent transmission in an HIV-positive population? A systematic review. Can.Commun.Dis.Rep. 2016;42(2):37-44.

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Footnote 31

Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015 Jun 5;64(RR-03):1-137.

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Footnote 32

Hollier LM, Eppes C. Genital herpes: oral antiviral treatments. BMJ Clin Evid 2015 Apr 8;2015:1603.

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Footnote 33

Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350(1):11-20.

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Footnote 34

Piret J, Boivin G. Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management. Antimicrob Agents Chemother 2011;55(2):459-472.

Return to footnote 34 referrer

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Date modified:: 2021-12-09

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