Chapter 258. Chancroid (Hemophilus Ducreyi)

Chancroid is a sexually transmitted disease caused by the organism Haemophilus ducreyi.1,2 It is characterized by painful genital ulcers and tender inguinal adenopathy that may suppurate. Also known as “soft chancre,” chancroid is one of the three major causes of genital ulcer disease among young sexually active patients in the United States; the other major causes are genital herpes and syphilis.

Epidemiology

Chancroid is a common cause of genital ulcer disease throughout the world but is not commonly reported in the United States. Although the prevalence of chancroid is low in the United States, the reason for this low prevalence may be due to underdiagnosis. Most clinicians do not have clinical experience with chancroid and thus do not consider it in the differential diagnosis. Most laboratories do not have the capability of isolating H ducreyi. Chancroid was more prevalent in the past (eFig. 258.1).3 Chancroid cases peaked to a high of 5001 in the United States in 1988; however, cases have steadily declined with the lowest number, 17, in 2005, and only 33 cases reported in 2006.3 In comparison, there were 9756 cases of primary or secondary syphilis reported in 2006.3 Of the cases in 2006, 12 were in males and 21 were in females. They were reported from just 8 states with most (82%) from southern states: 14 from South Carolina, 5 from North Carolina, 5 from Texas, and 1 case each from Louisiana, Virginia, and Florida. The remaining 6 cases were from New York and Michigan.

Other data suggest that the disappearance of chancroid in the United States may be due to lack of testing and underreporting.4-11 In a survey of 405 sexually transmitted disease (STD) clinics, only 32 (8%) tested patients for chancroid.4 Surveys in California from 1996 to 2003 found that less than 300 tests for chancroid were done, accounting for less than 0.1% of all tests done for STDs.5 However, in genital ulcer studies where testing for H ducreyi was done, chancroid has frequently been found. In a study in Brooklyn, New York, H ducreyi was identified in 27 of 65 (42%) cases in which a microbiologic diagnosis was established.6 Coinfection with syphilis was common. In New Orleans, Louisiana, similar findings were found in 299 men with nonsyphilitic genital ulcer disease; 39% had H ducreyi, 19% had herpes simplex virus (HSV), and the culture was negative in 41%.11 Using the sensitive polymerase chain reaction (PCR), it appears that chancroid may be even more common than previously thought. In a PCR study in Jackson, Mississippi, 59% of genital ulcer cases were due to H ducreyi.7,8 In another PCR study in STD clinics in 10 cities in the United States, H ducreyi accounted for a large proportion of genital ulcer cases.9 Cases of chancroid were identified in Memphis and Chicago and accounted for 12% to 20% of genital ulcer. In 10 patients with chancroid in Memphis, none were identified clinically. Thus, the burden of chancroid in the United States is unknown.

Chancroid is extremely common in certain developing countries. It is a major cause of genital ulcer disease in sub-Saharan Africa and in many parts of southeast Asia and Latin America.12-15 Definitive epidemiologic data are not generally available in these resource-poor countries because diagnosing chancroid is extremely problematic. Epidemiologic studies, primarily from Africa, demonstrate that the presence of genital ulcer disease, much of which may represent chancroid, is strongly associated with an increased risk of heterosexual transmission of human immunodeficiency virus (HIV).

Chancroid should be considered in high-risk groups such as prostitutes, drug users, and travel to a part of the world where chancroid is endemic. As many as 10% of patients with chancroid are coinfected with syphilis or herpes simplex virus (HSV).16

Clinical Features and Differential Diagnosis

The incubation period of chancroid is 3 to 10 days.16-19 The first lesion is generally a small papule that is surrounded by erythema. Within 2 to 3 days, a pustule forms that ruptures and leaves a circumscribed ulcer with ragged, undermined edges without induration (Fig. 258-1). The base of the ulcer is painful, has an erythematous base with a granular appearance, and usually is covered with a gray or yellow purulent exudate that bleeds when scraped. A typical chancroid ulcer is about 1 to 2 cm in diameter, but the size is variable, especially in HIV-infected patients.20 Often, infected persons have more than one ulcer. In men, the most common sites for the ulcers are on the distal prepuce, the mucosal surface of the prepuce on the frenulum, or in the coronal sulcus. In women, the majority of lesions are at the entrance to the vagina, the labia, or perianal areas. With vaginal or cervical lesions, there may be no symptoms. Unilateral painful tender inguinal adenopathy is present in as many as 50% of patients. Involved lymph nodes may become fluctuant to form painful buboes and if untreated may rupture, forming inguinal ulcers (eFig. 258.2). Adenopathy is less common in women. Most buboes arise 1 to 2 weeks after the appearance of the primary ulcer.

As with other STDs, coinfection with HIV may result in atypical manifestations of chancroid. There may be numerous lesions, extragenital involvement, and delays in resolution after treatment.20,21

The differential diagnosis of genital ulcer disease in sexually active persons is broad and is greatly influenced by the geographic location in which the infection was acquired. Worldwide, the main infectious causes of genital ulcer disease are HSV (genital herpes), Treponema pallidum (syphilis), Hemophilus ducreyi (chancroid), Chlamydia trachomatis (lymphogranuloma venereum), and Klebsiella granulomatis, formerly known as Calymmatobacterium granulomatis (donovanosis or granuloma inguinale). In the United States, most cases are due to HSV, followed by syphilis and chancroid. Noninfectious causes include drug eruptions and Behçet disease. In the United States, the combination of a painful ulcer with tender inguinal adenopathy is suggestive of chancroid, and when accompanied by suppurative inguinal adenopathy is almost pathognomonic. However, patients with H ducreyi infection may have ulcers that can be confused with other causes of genital ulcer disease such as HSV or syphilis; as many as 10% with chancroid may be coinfected with T pallidum or HSV.

Diagnostic Evaluation

Diagnosis of chancroid on clinical grounds alone is difficult because the presentation is often not classic, and many clinicians have little experience with the disease. Definitive diagnosis requires isolation of the organism from a genital ulcer or involved lymph nodes.2 However, the organism is fastidious and is difficult to isolate. For culture, a swab should be used to obtain material from the purulent base of an ulcer (undermined edge after removing superficial pus) and should be plated directly onto culture medium.22,23 The material should be cultured on special media (GC agar base contained 1% to 2% hemoglobin, 5% fetal bovine serum, and 3 ug/mL vancomycin) that is not widely available. Sensitivity of culture is ~75% compared to PCR.13,24 Gram stain of purulent material may be misleading because most genital ulcers are polymicrobial; therefore, it is not recommended as a diagnostic test.

Given the low sensitivity of culture, alternative non-culture-based diagnostic tests have been evaluated. Serologic assays lack sensitivity during the acute infection and are not available commercially. Most promising are PCR-based techniques. These assays have high sensitivity and identify patients with chancroid, from whom bacterial cultures for H ducreyi are negative. Multiplex PCR assays that can simultaneously amplify and subsequently detect DNA from H ducreyi, T pallidum, and HSV from genital ulcer specimens are undergoing field trials and show promise. Multiplex PCR was found to have a sensitivity of 95% and 98% in studies conducted in Lesotho and New Orleans,13,24 with a specificity of 99.6% in the series from New Orleans. PCR offers similar advantages for the diagnosis of HSV and syphilis.23 Although there is no FDA-approved PCR test for H ducreyi in the United States, some commercial laboratories have PCRs for H ducreyi.2

Even if chancroid is diagnosed definitively, it is recommended that patients also be tested for HIV, and if the initial test is negative, retesting for both syphilis and HIV 3 months later.16

The Centers for Disease Control and Prevention (CDC) criteria make a definite diagnosis of chancroid only with isolation of H ducreyi from a lesion. A probable diagnosis is made if there are clinical findings compatible with the diagnosis (painful genital ulcer and tender, suppurative, inguinal adenopathy) with a negative dark-field microscopic examination for T pallidum, a negative serologic test for syphilis, and a negative culture for HSV or a clinical presentation not typical for herpes.2 Even with careful evaluation, the sensitivity and specificity of using clinical criteria for diagnosing chancroid are limited. In a study conducted in South Africa, the diagnostic accuracy of clinical criteria by experienced clinicians for laboratory-confirmed cases of chancroid was only 42% in men and 57% in women.12 Similarly, in a study in New Orleans, the diagnosis of chancroid by strict clinical criteria was very specific (94%) but lacked sensitivity (34%).11 In a study in Lesotho, chancroid was the clinical diagnosis in 80% of patients with genital ulcer disease, and in this study, the sensitivity was high (95%); however, the specificity was poor at 29% for culture and 41% for PCR.13 Because there is a lack of rapid and reliable diagnostic tests and typically treatment consists of single-dose therapy, treatment decisions for chancroid are generally based on a clinical diagnosis. Even if chancroid is diagnosed definitively, it is recommended that patients also be tested for HIV, and if the initial test is negative, retesting for both syphilis and HIV 3 months later.16

Treatment

Successful antimicrobial treatment of genital ulcers caused by H ducreyi cures infection, resolves clinical symptoms, and prevents transmission to others.2 However, in cases of extensive ulcerative disease, scarring may result despite successful antimicrobial therapy. A number of agents have been used and are recommended for the treatment of chancroid including erythromycin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. The CDC currently recommends 1 of 4 antibiotic regimens for treatment of chancroid: azithromycin: 1 g orally in a single dose; ceftriaxone: 250 mg intramuscularly in a single dose; ciprofloxacin: 500 mg orally twice a day for 3 days; or erythromycin base: 500 mg orally 3 times a day for 7 days.2

All 4 regimens are effective for treatment of chancroid in patients with HIV infection. Ciprofloxacin is contraindicated in pregnant and lactating women. A successful response to therapy is usually evident within 48 to 72 hours, as evidenced by decreased ulcer tenderness and pain. Complete healing of ulcers may take up to 28 days, but is often achieved in 7 to 14 days. Clinical improvement of ulcerative disease without lymphadenitis usually occurs shortly after treatment is initiated. Relief of pain is noted by most patients within 48 hours, and objective improvement in the ulcers is usually evident within 72 hours. Patients should be reexamined 3 to 7 days after beginning therapy. If no clinical improvement is evident after 7 days, the diagnosis may be incorrect or the patient could be coinfected with syphilis, HIV, or other agents.2 Other considerations include poor adherence with medications or that the organism may be resistant to the regimen prescribed.2

Prior to effective antimicrobial therapy, failure to aspirate fluctuant buboes was associated with the development of draining fistulas or secondary ulcers at the site of the ruptured buboe. Even since the availability of antimicrobials agents for chancroid, healing of fluctuant adenopathy has been shown to be slower than that of the ulcers and may require needle aspiration through adjacent intact skin. In a study of 35 patients with inguinal lymphadenitis, 8 of the patients developed fluctuance that required needle aspiration despite successful treatment of the genital ulcer with erythromycin.25 In a small study performed during a chancroid epidemic in New Orleans,27 patients with inguinal buboes were randomly assigned to either needle aspiration or incision and drainage.26 Both groups ultimately did well without any adverse events during the period of follow-up, but the patients managed with needle aspiration often required repeated aspirations. Thus, either modality can be used to treat fluctuant lymphadenitis associated with chancroid. In advanced cases, scarring may result despite eradication of infection.2

Response may be delayed in some patients. In uncircumsized men, healing is slower with ulcers under the foreskin. Patients with HIV infection must be closely monitored, as they may require longer courses of treatment than the standard regimens outlined above. Treatment failures have been observed with several of these regimens, and there is some suggestion that those individuals who are most immunosuppressed are at the greatest risk for failure of standard regimens. The erythromycin 7-day regimen appears to be most successful in HIV-infected persons.

To prevent further spread of H ducreyi disease, it is critical to identify all sexual contacts of infected individuals. The CDC recommends that all persons who have had sexual contact with a patient with proven H ducreyi infection within the 10 days before onset of the patient’s symptoms should be examined and treated.2,16 The examination and treatment of contacts should be administered even in the absence of symptoms.2 Standard precautions are recommended.16 Regular condom use may decrease transmission.16