Etiology	Clinical presentation	Diagnosis	Treatment options
Infectious*
Herpes simplex virus infection	Usually multiple vesicular lesions that rupture and become painful, shallow ulcers (Figure 1) Constitutional symptoms, lymphadenopathy in first-time infections	Definitive: herpes simplex virus identified on culture or polymerase chain reaction testing of ulcer scraping or vesicle fluid aspirate Presumptive: typical lesions and any of the following factors Previously known outbreak Positive Tzanck smear of ulcer scraping Exclusion of other causes of ulcers Fourfold increase in acute and convalescent antibody titer results (in a first-time infection)	First episode Acyclovir (Zovirax), 400 mg orally three times daily for seven to 10 days, or 200 mg orally five times daily for seven to 10 days Famciclovir (Famvir), 250 mg orally three times daily for seven to 10 days Valacyclovir (Valtrex), 1,000 mg orally twice daily for seven to 10 days Recurrent episode Acyclovir, 400 mg orally three times daily for five days, 800 mg orally twice daily for five days, 800 mg orally three times daily for two days, or 200 mg orally five times daily for five days Famciclovir, 1,000 mg twice daily for one day, 500 mg orally once then 250 mg twice daily for two days, or 125 mg orally twice daily for five days Valacyclovir, 500 mg orally twice daily for three days or 1,000 mg orally once daily for five days Suppressive therapy Acyclovir, 400 mg orally twice daily or 200 mg orally three to five times daily Famciclovir, 250 mg orally twice daily Valacyclovir, 1,000 mg orally once daily Valacyclovir, 500 mg orally once daily, if fewer than 10 outbreaks per year
Syphilis (primary)	Single, painless, well-demarcated ulcer (chancre) with a clean base and indurated border (Figure 2) Mild or minimally tender inguinal lymphadenopathy	Treponema pallidum identified on darkfield microscopy or direct fluorescent antibody testing of a chancre or lymph node aspirate or Positive result on serologic nontreponemal testing (i.e., Venereal Disease Research Laboratories or rapid plasma reagin) that is confirmed with a positive result on serologic treponemal testing (i.e., fluorescent treponemal antibody absorption or T. pallidum passive agglutination)	Penicillin G benzathine, 2.4 million units intramuscularly in a single dose
Chancroid	Nonindurated, painful with serpiginous border and friable base; covered with a necrotic, often purulent exudate (Figure 3) Tender, suppurative, unilateral inguinal lymphadenopathy or adenitis	Gram stain suggestive of Haemophilus ducreyi (gram-negative, slender rod or coccobacillus in a “school of fish” pattern) Definitive: H. ducreyi identified on culture Presumptive: painful genital ulcer or ulcers with regional lymphadenopathy and no evidence of T. pallidum infection at least seven days after ulcer onset, and testing negative for herpes simplex virus	Needle aspiration of fluctuant buboes Azithromycin (Zithromax), 1 g orally in a single dose Ceftriaxone (Rocephin), 250 mg intramuscularly in a single dose Ciprofloxacin (Cipro), 500 mg orally twice daily for three days† Erythromycin, 500 mg orally four times daily for seven days
Lymphogranuloma venereum	Small, shallow, painless, genital or rectal papule or ulcer; no induration Unilateral, tender inguinal or femoral lymphadenopathy Rectal bleeding, pain, or discharge; ulcerative proctitis; constipation or tenesmus	Definitive: Chlamydia trachomatis serotype L1, L2, or L3 culture, identified from clinical specimen or Immunofluorescence demonstrating inclusion bodies in leukocytes of an inguinal lymph node (bubo) aspirate or Microimmunofluorescence positive for lymphogranuloma venereum strain of C. trachomatis Presumptive: Clinical suspicion Community prevalence Exclusion of other causes of proctocolitis, inguinal lymphadenopathy, or genital ulcers	Doxycycline, 100 mg orally twice daily for 21 days Erythromycin base, 500 mg orally four times daily for 21 days Pregnant or lactating women: erythromycin, 500 mg orally four times daily for 21 days
Granuloma inguinale (donovanosis)	Persistent, painless, beefy-red (highly vascular) papules or ulcers (Figure 4) May be hypertrophic, necrotic, or sclerotic No lymphadenopathy May have subcutaneous granulomas	Definitive Intracytoplasmic Donovan bodies on Wright stain or Positive result with Giemsa stain or biopsy of granulation tissue	Treatment should continue until lesions have healed Doxycycline, 100 mg orally twice daily for at least 21 days Azithromycin, 1 g orally once weekly for at least 21 days Ciprofloxacin, 750 mg orally twice daily for at least 21 days Erythromycin base, 500 mg orally four times daily for 21 days Trimethoprim/sulfamethoxazole (Bactrim, Septra) double strength, 160/800 mg orally twice daily for at least 21 days
Noninfectious
Behçet syndrome	Aphthous oral ulcers (100 percent of cases); genital ulcers (70 to 90 percent of cases)	Consider rheumatoid factor, antinuclear antibody testing May have positive antibodies to carboxyterminal subunit of SIP1 Biopsy may show diffuse arteritis with venulitis Diagnostic criteria: recurrent aphthous oral ulcers (more than three per year) and any two of the following Recurrent genital ulcers Eye lesions (e.g., uveitis) Cutaneous lesions (e.g., erythema nodosum) Positive pathergy test (2 mm erythema appears 24 to 48 hours after skin prick test) Biopsy may show diffuse arteritis with venulitis	Spontaneous regression is possible Pegylated interferon alfa-2a (Pegasys), 6 million units subcutaneously three times weekly for three months for mucocutaneous involvement
Fixed drug eruptions	Varied ulcerations that resolve with withdrawal of offending agent	Diagnosis of exclusion when ulcers resolve after drug withdrawal	Self-limited Topical analgesics or anti-inflammatory agents, as needed Consider treating exacerbation of underlying inflammatory disease if applicable