Ulkus Mole (Chancroid)

01Pathophysiology

Haemophilus ducreyi is a fastidious gram-negative coccobacillus that gains entry through microabrasions in the genital epithelium during sexual contact. Once the organism breaches the epidermis, it resists phagocytosis through production of cytolethal distending toxin (CDT) and lipooligosaccharide (LOS), both of which cause direct tissue necrosis and apoptosis of host immune cells. This cytotoxic activity is the reason the ulcer forms in the first place: the organism literally destroys the overlying tissue rather than provoking a granulomatous or indolent process.

The resulting ulcer is soft and non-indurated because, unlike syphilis, chancroid does not produce a significant fibrotic or organized immune response at the ulcer base. The base is filled with purulent, necrotic debris (reflecting the neutrophilic response to tissue destruction), and the edges are undermined because the organism spreads laterally beneath intact epithelium before the overlying tissue sloughs. This is why multiple "kissing lesions" can develop on apposing skin surfaces.

The painful nature of chancroid directly correlates with the intense acute inflammatory infiltrate. The neutrophil-rich response and tissue necrosis expose nerve endings, making the ulcer exquisitely tender, which is the single most important clinical distinction from the primary chancre of syphilis.

Regional spread occurs through lymphatic drainage to inguinal nodes, producing buboes. These lymph nodes undergo suppurative necrosis, meaning they fill with pus and can rupture through the skin if not drained. This unilateral, fluctuant, tender lymphadenopathy is a hallmark finding. The connection between pathophysiology and clinical presentation is direct: cytotoxin-mediated tissue destruction causes the painful, soft, dirty ulcer, and lymphatic spread of the same destructive process produces the suppurating bubo.

02Classification and Clinical Manifestation

Chancroid does not follow a formal staging system the way syphilis does, but the clinical course progresses through recognizable phases. The following table outlines the timeline and variants:

Key points for exam purposes: women may be asymptomatic carriers or present with internal ulcers (cervical or vaginal) that are not easily visible on external exam, which can delay diagnosis. Men almost always present with visible, painful ulcers.

03Diagnostic Workup

The diagnostic logic for chancroid on an exam follows a diagnosis of exclusion pathway in most clinical settings. When you encounter a vignette describing a painful genital ulcer, your mental algorithm should be:

First, rule out herpes, because herpes simplex is by far the most common cause of painful genital ulcers in developed countries. The key difference is that herpes produces grouped vesicles on an erythematous base that rupture into shallow, clean-based ulcers, whereas chancroid produces a deep ulcer with a dirty purulent base and undermined edges. HSV PCR or Tzanck smear will be negative in chancroid.

Second, rule out primary syphilis. Order RPR/VDRL and, if available, darkfield microscopy. The syphilitic chancre is painless and indurated, but co-infection is common enough that you must still test. Negative syphilis serology supports chancroid.

Third, if both herpes and syphilis are excluded and the clinical picture fits (painful soft ulcer, suppurative lymphadenopathy, appropriate epidemiologic risk), a probable diagnosis of chancroid is made. Culture or PCR can confirm it, but in practice, especially in resource-limited settings, treatment is often started empirically.

The "school of fish" gram stain pattern (parallel chains of small gram-negative rods) is frequently referenced in exam questions as a buzzword clue, but be aware that gram stain of the ulcer base has very poor sensitivity and should not be relied upon alone.

04Management and Treatment

Acute management centers on selecting one of the four recommended antibiotic regimens. The preferred choices for exam purposes are azithromycin 1 g PO single dose or ceftriaxone 250 mg IM single dose because both allow directly observed therapy, which maximizes compliance. Azithromycin is generally the most commonly tested "best answer."

Ciprofloxacin 500 mg PO twice daily for 3 days is an effective alternative, but remember it is contraindicated in pregnant or breastfeeding women and in children. If a vignette mentions pregnancy or lactation, the correct choice shifts to erythromycin base 500 mg PO three times daily for 7 days, which is the safest option in that population despite its longer course and gastrointestinal side effects.

Fluctuant buboes require intervention. Needle aspiration through intact, uninvolved skin is preferred over incision and drainage because it reduces the risk of chronic sinus tract formation, though I&D is acceptable if aspiration fails. Leaving a large fluctuant bubo undrained risks spontaneous rupture with chronic wound complications.

Follow-up is important: ulcers should show symptomatic improvement within 3 days and objective healing within 7 days. If there is no improvement by day 7, reconsider the diagnosis (is it actually herpes, syphilis, or LGV?), check for HIV co-infection (healing is significantly delayed in HIV-positive patients), consider antibiotic resistance, or evaluate for non-compliance.

Partner management is mandatory. All sexual contacts within 10 days before symptom onset should be treated empirically regardless of symptoms. HIV testing should be offered to all patients at the time of diagnosis and again at 3 months if initially negative.

Long-term management includes counseling on barrier protection and follow-up serologic testing for syphilis and HIV at 3 months, since the initial tests may have been performed during the window period.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common way students miss chancroid questions is by confusing it with primary syphilis. Both present as a genital ulcer with lymphadenopathy, and under time pressure, students default to the more familiar diagnosis. The discriminating feature that test-writers rely on is pain: chancroid is painful, syphilis is not. If the vignette describes a patient who complains that the ulcer hurts, syphilis drops significantly on the differential. Conversely, if the stem describes a patient who "noticed a sore but it doesn't bother him," that points away from chancroid.

A second common trap involves herpes vs. chancroid. Both are painful, but the morphology is different. Herpes classically begins as vesicles that rupture into small, shallow, clean ulcers, often in clusters. Chancroid produces a deeper ulcer with ragged edges, purulent exudate, and undermined borders. If the vignette says "grouped vesicles" or "burning/tingling prodrome," the answer is herpes. If it says "soft ulcer with purulent base and undermined edges," the answer is chancroid.

A third trap is the transient chancroid variant, where the ulcer heals on its own and the patient presents only with a painful inguinal bubo. Students who fixate on "genital ulcer disease" may not consider chancroid when no ulcer is visible at the time of presentation. The history of a recently healed genital sore followed by a fluctuant inguinal mass should trigger this diagnosis.

Finally, remember that chancroid is a co-factor for HIV transmission. Any question about chancroid that offers HIV testing as an answer choice is almost certainly testing whether you know to screen for HIV in the setting of genital ulcer disease. Always test for HIV, always treat partners, and always retest serologies at 3 months for both HIV and syphilis.

The core competency being tested is your ability to distinguish among the causes of genital ulcer disease using the pain/painless framework, ulcer morphology, and lymph node characteristics, and to recognize that chancroid is fundamentally a clinical and exclusionary diagnosis supported by the triad of painful soft ulcer + purulent undermined base + tender unilateral suppurative bubo.