Chancroid

Chancroid is an acute genital ulcer disease caused by Haemophilus ducreyi, a fastidious Gram-negative coccobacillus. Once common in Africa, Asia and the Caribbean, it has declined markedly worldwide but remains an issue in some resource-limited settings. It is rare in North America and Europe, and cases are usually imported. It is an important cofactor for HIV transmission, with a 10-fold increase in transmission risk.

Epidemiology and risk

• Spread by sexual contact with infected ulcers. Higher prevalence in men (male to female ratio from 3:1 to 25:1), among sex workers and their clients, uncircumcised men, and people with multiple partners.
• Strongly associated with HIV (ulcers act as portals of entry, HIV prolongs ulcers and complicates healing).
• Incubation 4 to 10 days (range 1 to 14), with no prodrome.
• Pathogenesis: H. ducreyi enters through micro-abrasions in skin and mucosa, producing a pustule that erodes into a ulcer through the effects of cytolethal distending toxin and other virulence factors. Organisms spread to regional lymph nodes via lymphatics, producing suppurative lymphadenitis (bubo).

Complications

• Suppurative inguinal buboes with rupture and sinus formation, phimosis or paraphimosis, urethral fistulas, extensive tissue destruction (phagedenic ulcer), secondary infection, genital scarring, and increased HIV acquisition.
• Rarely, extragenital lesions (autoinoculation of fingers, lips, breasts).
• Chancroid is one of the "genital ulcer disease" syndromes needing differentiation from syphilis, herpes, LGV and donovanosis, and mixed infections occur in 5 to 10% (with syphilis or herpes).

Genital ulcer

• Begins as a tender erythematous papule that becomes a pustule within 1 to 2 days, then erodes to a painful, shallow ulcer, 1 to 2 cm, with ragged, undermined, non-indurated (soft) edges, and a base covered with grey or yellow necrotic exudate. The base bleeds easily on scraping. Characteristically painful (distinct from syphilis).
• Often multiple (due to autoinoculation), with "kissing" lesions on opposing surfaces. Giant or serpiginous ulcers occur in HIV.
• Sites: men - prepuce, frenulum, coronal sulcus, glans, shaft. Women - labia, fourchette, vestibule, perianal region (often asymptomatic or with dysuria, dyspareunia, pain on defecation).

Inguinal lymphadenopathy (30 to 60%)

• Painful, unilateral (in two thirds) tender enlargement of inguinal nodes within 1 to 2 weeks, which becomes matted and fluctuant (bubo) with overlying erythema, and may rupture spontaneously, producing a draining sinus or an ulcer. Often associated with the ulcer.
• Systemic symptoms (fever, malaise) are uncommon.
• Variants: dwarf chancroid (small, shallow ulcers), follicular chancroid, transient chancroid (small ulcer with a bubo), papular chancroid, and phagedenic or gangrenous forms with extensive tissue destruction.

Differential diagnosis

• Genital herpes (multiple vesicles, painful, recurrent), primary syphilis (painless, indurated, non-tender nodes), LGV (small transient ulcer, bubo with groove sign), donovanosis (painless, beefy red, no adenopathy), fixed drug eruption, Behçet disease, traumatic ulcer, and carcinoma.
• Red flags: HIV co-infection, large buboes needing drainage, phimosis, lack of response to therapy, and mixed genital ulcer infection.

Definitive diagnosis requires isolating H. ducreyi, but this is difficult. A probable diagnosis can be made clinically and by exclusion:

• One or more painful genital ulcers.
• No evidence of T. pallidum infection by darkfield examination of the ulcer exudate or serological test performed at least 7 days after onset of ulcer.
• Typical ulcer appearance and regional adenopathy (suppurative adenopathy supports).
• Negative HSV test (PCR or culture) from the ulcer.

Laboratory tests

• Culture on selective media (gonococcal agar base supplemented with 1 to 2% IsoVitaleX, fetal bovine serum, vancomycin), incubated at 33 degrees Celsius in 5% CO2 with high humidity. Sensitivity under 80% (even lower in practice), and facilities are limited. Specimens from the ulcer base (after cleaning with saline) or bubo aspirate.
• Gram stain of ulcer exudate: "school of fish" or "railroad track" arrangement of Gram-negative coccobacilli. Low sensitivity and specificity.
• PCR (multiplex PCR for H. ducreyi, T. pallidum, HSV) is the preferred method where available. Not FDA approved in the US, but available at some laboratories.
• Bubo aspirate: Gram stain and culture (needle aspiration through intact adjacent skin).
• Biopsy for atypical cases.
• Mandatory concurrent testing: HIV, syphilis serology (repeat after 3 months), HSV PCR, hepatitis B, gonorrhoea and chlamydia (NAAT), and LGV testing if buboes. Offer repeat HIV testing at 3 months.

Antimicrobial therapy (any one of the following)

• Azithromycin 1 g orally as a single dose (preferred, observed single-dose therapy improves adherence).
• Ceftriaxone 250 mg IM as a single dose.
• Ciprofloxacin 500 mg orally twice daily for 3 days (contraindicated in pregnancy and children, and resistance is reported).
• Erythromycin base 500 mg orally three times daily for 7 days (alternative, more adverse effects, safe in pregnancy).
• In HIV-infected patients, the cure rate with single-dose regimens may be lower, so follow closely, and consider extended regimens (erythromycin 7 days, ciprofloxacin 7 days) if healing is slow.
• Pregnancy: erythromycin, azithromycin or ceftriaxone. Avoid fluoroquinolones.
• Syndromic treatment in resource-limited settings covers syphilis, chancroid, and herpes where appropriate: benzathine penicillin 2.4 million units IM, plus azithromycin 1 g orally single dose, plus aciclovir/valaciclovir for herpes where indicated.

Local management

• Aspiration of fluctuant buboes through intact adjacent healthy skin with a large-bore needle (16 to 18 gauge), repeated every 2 to 3 days as needed, to prevent spontaneous rupture and sinus formation. Incision and drainage is discouraged because of delayed healing, but is performed for large loculated buboes with packing in some settings.
• Ulcer care: saline cleansing, dry dressings, topical antiseptics, and analgesia (paracetamol 1 g, ibuprofen 400 mg).
• Phimosis: circumcision after resolution of the ulcers.

Follow-up

• Re-examine patients 3 to 7 days after therapy. Symptoms improve within 3 days, and ulcers heal in 1 to 2 weeks (large ulcers up to 2 to 3 weeks, slower in HIV). Buboes may take longer (2 to 4 weeks) and often need aspiration. If no improvement, consider incorrect diagnosis, co-infection (with HSV or syphilis), HIV infection, nonadherence, or antimicrobial resistance.
• Retest for syphilis and HIV at 3 months.

Partner management and prevention

• Examine and treat all sexual partners within the previous 10 days of symptom onset, irrespective of symptoms (azithromycin 1 g or ceftriaxone 250 mg). Partners should abstain until both are treated and ulcers are healed.
• Counselling on condom use, male circumcision (lowers risk), treatment of other STIs, and HIV prevention. Public health notification in endemic and non-endemic areas.
• Chancroid in children raises concern for sexual abuse.

Prognosis

Excellent with timely therapy. Untreated disease may persist for weeks to months. Complications include scarring, phimosis and fistulae. Treat HIV infection with antiretroviral therapy.