Genital ulcers

OVERVIEW: What every practitioner needs to know

Are you sure your patient has genital ulcers? What are the typical findings for this disease?

Genital herpes is the most common cause of genital ulcers in adolescents and young adults in the United States. With the first clinical episode, painful ulcers that may have begun as small papules or vesicles. Small lesions may coalesce into larger ulcers. Ulcers are superficial, nonindurated with erythematous edges and often exist as a cluster of multiple ulcers. Clinical diagnosis is imprecise; testing of specimens obtained from ulcers, either by polymerase chain reaction or viral culture, should be performed whenever possible. Antiviral medications can shorten the duration of outbreaks and, if taken daily, can reduce recurrences and decrease asymptomatic shedding.

Usually multiple, grouped vesicles that evolve into ulcers; typically painful. However, only one to two lesions may be present.

Tender inguinal adenopathy (not fluctuant) is present.

With the first clinical episode, constitutional symptoms are more likely to be present (fever, headache, myalgias, and malaise).

Urethritis (urethral discharge) may be seen in male patients and cervicitis (leading to vaginal discharge) may be present in female patients.

Urinary retention and anorectal symptoms (discharge, pain, tenesmus) may be present, depending on sites of infection (anal receptive intercourse).

Ulcers may also be found on buttocks and thighs; pharyngitis may be present as well.

In evaluating genital ulcers, always look for the presence of oral ulcers.

What other disease/condition shares some of these symptoms?

Epstein-Barr virus (EBV) infection with or without other signs and symptoms of infectious mononucleosis

Syphilis: sharply demarcated, firm and indurated; usually single ulcer; nontender lymphadenopathy

Chancroid (Haemophilus ducreyi): These are painful lesions with deep purulent base, ragged undermined margins, erythematous borders and foul-smelling yelllow-gray purulent necrotic exudate. Inguinal lymph nodes are typically unilateral, tender, and fluctuant. Lymph node may rupture and drain.

Lymphogranuloma venereum (LGV) (C. trachomatis, LGV serovar):
Primary lesion starts as a small, painless papule or pustule that erodes into an ulcer. The ulcer has elevated edges and is usually painless and nonindurated and heals rapidly. There is unilateral tender inguinal or femoral lymphadenopathy. LGV is unusual in the United States; ask about foreign travel.

HIV infection

Other viral infections: cytomegalovirus, influenza A; Mycoplasma pneumoniae

Extensive vulvovaginal candidiasis: can involve fissuring and ulceration of the vulva/lvaginal labia

Behçet syndrome (recurrent): oral and genital ulcers, uveitis, and to a lesser extent, arthritis, rash, thrombophlebitis

Allergic, chemical, irritant contact dermatitis: soaps, perfumes, depilatories, vaginal douches, spermicides, latex allergy, sanitary napkins

Lichen sclerosus: look for white, atrophic, parchment-like skin in addition to ulcers, pruritis

Lichen planus: pruritic purple papules and plaques, oral erosions, involvement of wrist and shins;

Pemphigus: vesicles and bullae

Other systemic diseases: Crohn disease, cyclic neutropenia, PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis), MAGIC syndrome (mouth and genital ulcers with inflamed cartilage). Look for fistulous tracts (Crohn disease) that may mimic ulcers (on vulva in female patients, involving scrotum in male patients).

Nutritional disorders: deficiencies of iron, folate or vitamin B12

Drug reaction: erythema multiforme can involve genital areas as well as hands and feet (look for target lesions); fixed drug eruption (take careful drug history)

Autoimmune progesterone dermatitis: cyclic pattern coinciding with end of menstrual cycle

Malignancies: (e.g., histiocytosis X, leukemia); treatment of malignancies may also induce ulcers

What caused this disease to develop at this time?

Exposure to an infectious agent; genital herpes can be spread through oral-genital as well genital-genital contact

Stress (e.g., in recurrence of genital herpes)

Exposure to offending agent or drug

Flare of underlying systemic illness

Occlusive undergarments, particularly in conjunction with hot weather or exercise

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Perform polymerase chain reaction and/or culture of genital lesions to identify herpes. Yield is highest from intact vesicles or pustules, less so from ulcerations, and least from healing lesions.

Perform darkfield examination or direct fluorescent antibody staining of smear from lesion to identify syphilis. Serologic test results (rapid plasma reagin, Venereal Disease Research Laboratory [VDRL], fluorescent treponemal antibody absorbed [FTA-ABS]) may be negative when primary lesion (chancre) is present.

If EBV infection is suspected, perform heterophile antibody testing (rapid test) or EBV IgM.

For chancroid, LGV, or HIV, perform appropriate culture or serologic testing.

Obtain a complete blood count, erythrocyte sedimentation rate, or C-reactive protein level if underlying systemic disorder is suspected.

Obtain iron, folate, and vitamin B12 levels if nutritional deficiency is suspected.

Wet prep (KOH or normal saline) obtained from lesions or from vagina may show hyphae or buds consistent with candidiasis.

Perform biopsy if lichen planus, sclerosus, or pemphigus is suspected or if infectious cause is unlikely.

All patients with a confirmed sexually transmitted infection should undergo testing for HIV.

Would imaging studies be helpful? If so, which ones?

Imaging studies not indicated.

If you are able to confirm that the patient has genital ulcers, what treatment should be initiated?

Management of any genital ulcer syndrome caused by a sexually transmitted organism must include screening for other sexually transmitted infections (HIV, chlamydia) and depending on the organisms identified, notification and treatment of recent sex partners. Table I presents the treatment of herpes.

Table I.
First clinical episode genital herpes
  Acyclovir 400 mg TID for 7-10 days* or
  Acyclovir 200 mg five times per day for 7-10 days* or
  Famciclovir 250 mg TID for 7-10 days* or
  Valacyclovir 1 g BID for 7-10 days*
Daily suppressive therapy for recurrent genital herpes
  Acyclovir 400 mg BID or
  Famciclovir 250 mg BID or
  Valacyclovir 500 mg or 1 g daily (500 mg daily may be less effective than other regimens for individuals with very frequent recurrences (≥10/year)
Episodic therapy for recurrent genital herpes
  Acyclovir 400 mg TID for 5 days or
  Acyclovir 800 mg BID for 5 days or
  Acyclovir 800 mg TID for 2 days or
  Famciclovir 125 mg BID for 5 days or
  Famciclovir 1000 mg BID for 1 day or
  Famciclovir 500 mg once, followed by 250 mg BID for 2 days or
  Valacyclovir 500 mg BID for 3 days or
  Valacyclovir 1 g daily for 5 days

*Treatment can be extended if healing is incomplete after 10 days of therapy.

When multiple drug treatment options are listed, the decision about which option to use should be based on patient preference (e.g., ease of dosing, side effect profile) and cost (insurance coverage and out-of-pocket expenses)

BID = twice daily; TID = three times daily

Syphilis: 2.4 million units benzathine penicillin intramuscularly (IM)

Chancroid: Azithromycin 1 g in a single dose or ceftriaxone 250 mg IM in a single dose or ciprofloxacin 500 mg BID for 3 days or
erythromycin base 500 mg TID for 7 days

LGV: Doxycycline 100 mg BID for 21 days (alternative regimen: erythromycin base 500 mg four times daily [QID] for 21 days)

Candidiasis (see chapter on “vaginal discharge” for treatment options)

Discontinuation of sensitizing agent or drug; use of a low-potency steroid cream to treat contact/irritative/chemical dermatitis; severe cases may require use of mid- to high-potency steroid

Ulcers associated with an underlying systemic illness (HIV, Crohn disease) will improve with treatment of that illness and may recur with a flare of the underlying illness.

Ulcers of Crohn disease may respond to zinc oxide paste or an extended course or metronidazole.

What are the adverse effects associated with each treatment option?

Antiviral medications for treatment or suppression of genital herpes have an excellent long-term safety profile and are generally not associated with significant side effects.

Oral antibiotics can be associated with gastrointestinal side effects and vulvovaginal candidiasis.

What are the possible outcomes of genital ulcers?

Genital herpes: recurrences are likely with herpesvirus (HSV)-2 infection, less so with HSV-1. Daily suppressive therapy can greatly reduce symptomatic recurrences and also decrease the likelihood of asymptomatic shedding.

Syphilis, chancroid, and LGV can be cured with appropriate antibiotic treatment.

Ulcers caused by other viral infections are self-limited.

Ulcers that are indicative of allergic or chemical dermatitis or drug reaction will resolve with removal of the offending agent

What causes this disease and how frequent is it?

Genital ulcers caused by sexually transmitted infections are most often due to genital herpes, followed by syphilis and then chancroid.

LGV is unusual in the United States.

The prevalence of HSV-2 infection rises rapidly after puberty (1.6% of 14- to 19-year-olds and 10.6% of 20- to 29-year-olds). HSV-1 is increasingly common as the cause of genital herpes infections; in some recent studies, the majority of newly diagnosed genital HSV infections were due to HSV-1.

Cytotoxic effect of viral infection (e.g., in herpes or EBV infection)

Immune complex (EBV)

How do these pathogens/genes/exposures cause the disease?

Sexually transmitted organisms gain access presumably by way of microtrauma that occurs in the skin during sexual intercourse.

How can genital ulcers be prevented?

Correct and consistent condom use reduces the risk of acquiring sexually transmitted infections, although the degree of protection depends on the organism.

Daily suppressive therapy of genital herpes infection with antiviral medication will reduce symptomatic recurrences and asymptomatic viral shedding, making it less likely that an infected individual will transmit the infection to an uninfected partner.

Women should avoid douching and the use of scented feminine hygiene products.

Male and female individuals should avoid the use of sensitizing agents (e.g., depilatories, spermicides, latex).

Fixed drug eruption, offending drug should be avoided.

What is the evidence?

“Sexually transmitted diseases treatment guidelines, 2010”. MMWR. vol. 59. 2010. pp. 18-36.

Woods, ER, Emans, SJ, Emans, SJ, Laufer, MR, Goldstein, DP. “Vulvovaginal complaints in the adolescent”. 2005. pp. 525-64.

Sardy, M, Wollenberg, A, Niedermeier. “Genital ulcers associated with Epstein-Barr virus infection (uclus vulvae acutum)”. Acta Derm Venereol. vol. 91. 2011. pp. 55-9.

Huppert, J. “Lipschutz ulcers: evaluation and management of acute genital ulcers in women”. Dermatol Ther. vol. 23. 2010. pp. 533-40.

Hope-Rapp, E, Anyfantakis, V, Fouere, S. “Etiology of genital ulcer disease: a prospective study of 278 cases seen in an STD clinic in Paris”. Sex Transm Dis. vol. 37. 2010. pp. 153-8.

Bunker, CB. ” Disease”. 2004. pp. 135-19.

Ongoing controversies regarding etiology, diagnosis, treatment

Some experts recommend that all sexually active individuals be tested for HSV-2 antibody even if they have no symptoms of genital herpes.