Genital Ulcers: Differential Diagnosis and Management


Am Fam Physician. 2020 Mar 15;101(6):355-361.

  Patient information: See related handout on genital ulcers, written by the author of this article.

Author disclosure: No relevant financial affiliations.

Genital ulcers may be located on the vagina, penis, and anorectal or perineal areas and may be infectious or noninfectious. Herpes simplex virus is the most common cause of genital ulcers in the United States. A diagnosis of genital herpes simplex virus infection is made through physical examination and observation of genital lesions. The 2015 Centers for Disease Control and Prevention sexually transmitted disease guidelines provide strategies for the management of patients with genital ulcer disease. Specific testing includes a polymerase chain reaction test for herpes simplex virus; syphilis serology and darkfield microscopy or a direct fluorescent antibody test for Treponema pallidum; and/or culture for Haemophilus ducreyi in settings where chancroid is highly prevalent. Rarely, cases of Epstein-Barr virus may present with genital ulcers. Syphilis and chancroid cause genital ulcers and are mandatory reportable diseases to the local health department. In some cases, no pathogen is identified. It is important to consider noninfectious etiologies such as sexual trauma, psoriasis, Behçet syndrome, and fixed drug eruptions. Genital ulcers are symptomatic by definition, and the U.S. Preventive Services Task Force recommends screening for syphilis infection for those at risk, early screening for syphilis infection in all pregnant women, and against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including those who are pregnant.

Genital ulcers may be located on the vagina, penis, and anorectal or perineal areas and may be infectious (sexually transmitted infections [STIs], secondary bacterial, or fungal) or noninfectious (Table 1).13 The most common causes of STIs characterized by genital ulcers in the United States are genital herpes simplex virus types 1 and 2 (HSV-1, HSV-2).1 Less common infectious causes include syphilis (Treponema pallidum) and rarely chancroid (Haemophilus ducreyi), granuloma inguinale (donovanosis [Klebsiella granulomatis], formerly known as Calymmatobacterium granulomatis), and lymphogranuloma venereum (Chlamydia trachomatis serovars L1, L2, and L3).1 Genital ulcer disease commonly refers to ulcerations associated with STIs, but the ulcerations have also been reported as rare sequelae of mononucleosis (Epstein-Barr virus)4 and can be caused by noninfectious etiologies such as psoriasis, sexual trauma, Behçet syndrome, or fixed drug eruptions.1

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Clinical recommendationEvidence ratingComments

Oral acyclovir, valacyclovir (Valtrex), and famciclovir (Famvir) decrease symptom duration and viral shedding for herpes simplex virus initial or recurrent episodes.1,16,17


Centers for Disease Control and Prevention sexually transmitted disease guideline and supporting systematic reviews

Extensive genital ulcers may be treated with cool water or saline, topical antimicrobials, topical or oral analgesics, perineal baths, topical or oral anti-inflammatory agents, or cool compresses with Burow solution to decrease surrounding edema, inflammation, and pain.34


Systematic review of antimicrobial agents used for chronic wounds

Couples in which one partner has herpes simplex virus infection should be counseled that consistent condom and dental dam use during intercourse decreases, but does not eliminate, risk of transmission.21,41


Review article; randomized, double-blind, placebo-controlled trial

In patients with symptomatic herpes simplex virus outbreaks, suppressive therapy should be considered to reduce transmission to seronegative partners.17


Randomized, double-blind, placebo-controlled trial of valacyclovir suppressive therapy in 1,484 herpes simplex virus type 2 discordant heterosexual couples

HIV testing should be completed for all people with genital, anal, or perianal ulcers not known to have HIV infection.1


Expert consensus recommendation in Centers for Disease Control and Prevention guideline

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to

The Author

MICHELLE A. ROETT, MD, MPH, FAAFP, CPE, is a professor and chair in the Department of Family Medicine at the Georgetown University Medical Center and the MedStar Georgetown University Hospital, Washington, DC.

Address correspondence to Michelle A. Roett, MD, MPH, FAAFP, CPE, Department of Family Medicine, Georgetown University Medical Center, 4000 Reservoir Rd. NW, Bldg. D234, Washington, DC 20057 (email: Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.


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