This disease is a sexually transmitted infection caused by Haemophilus ducreyi.

bubble_chart Epidemiology

This disease is more prevalent in tropical and subtropical regions and among lower socioeconomic groups of Black people, being a major cause of genital ulcer formation in developing countries. In recent years, outbreaks of soft chancre have been reported in some Western developed countries such as the United States and Canada, primarily occurring among impoverished, heterosexual populations who frequently have sexual contact with prostitutes. Over 50% of male soft chancre patients contracted the disease through contact with prostitutes.

In China, the incidence was relatively high before the 1940s. For instance, statistics from outpatient cases in Northeast China accounted for 10% to 13.6%. After the 1960s, intensive prevention and control efforts nearly eradicated the disease. However, since the 1980s, cases have re-emerged in some regions of China, though it remains a rare condition. Surveillance systems have reported an annual increase in soft chancre cases, with 7 cases in 1993 and 30 cases in 1994. Some cases may have been diagnosed solely based on smear test results without confirmatory pathogen diagnosis through culture methods.

The disease is more common in men and relatively rare in women, with a male-to-female ratio of approximately 9:1. This discrepancy may be due to asymptomatic lesions in the vagina and cervix, making them difficult to detect.

Recent studies have found that soft chancre is a significant cofactor in facilitating the heterosexual transmission of human immunodeficiency virus (HIV-1). Controlling and eliminating soft chancre is considered one of the effective measures to reduce the heterosexual spread of HIV-1.

Haemophilus ducreyi is a Gram-negative, non-spore-forming, aerobic bacillus with a strong affinity for carbon dioxide. It requires the supply of fresh blood for growth in artificial cultures, hence the name "haemophilus." It measures 0.5 × 1.5–2.0 μm, appearing as short bacilli with blunt, rounded ends. In pus from ulcers, the bacteria exhibit pleomorphism, forming chains, diplococci, large cocci, or rod-shaped structures. When sampled from lesions or cultured colonies, the bacteria often appear as two or more linked together in a chain, resembling a school of swimming fish, hence the term "fish school-like." In lymph node tissue sections, typical chained bacilli can be observed.

Haemophilus ducreyi is sensitive to temperature, losing viability at temperatures above 43–44°C within 20 minutes. It shows slightly greater resistance at 42°C but dies within 4 hours. At 37°C, it survives for 6–8 days, while at 10–20°C, it dies within 7–10 days. In this temperature range, it is less resistant than Escherichia coli and staphylococci but more resistant than gonococci. It has relatively strong resistance to cold, surviving for 1 week at 5°C and potentially up to 1 year when freeze-dried. However, it is weak against desiccation. In artificial cultures, temperature is a critical factor for growth.

Members of the Haemophilus genus require X factor and V factor for in vitro reproduction. The X factor is a heat-resistant substance, hemin, found in blood, while the V factor is heat-labile and acts as a coenzyme for dehydrogenases in blood. Haemophilus ducreyi has a high demand for the X factor but does not require the V factor. Injecting pure cultures into rabbits can induce facial ulcer sexually transmitted disease lesions. Humans do not develop lasting immunity after infection. When a suspension of Haemophilus ducreyi is used as an antigen, patients test positive in skin tests one week after injection. Once positive, the reaction may persist for years or even a lifetime.

After infection with Haemophilus ducreyi, the clearance of local bacteria in soft chancre primarily involves polymorphonuclear leukocytes. Whether other immune pathways participate in bacterial killing remains unclear, such as the alternative pathway of complement activation, and whether complement is involved in killing Haemophilus ducreyi in the serum. This process is likely primarily antibody-dependent, with complement enhancing the effect of antibodies. The sensitivity of bacteria to the response is determined by the composition of lipopolysaccharides.

When clinically diagnosed with soft chancre, an immunoblot adsorption test for Haemophilus ducreyi antigens can detect increased serum IgG and IgM antibodies. Serum antibody tests indicate the presence of specific antigenic determinants. Intradermal infection experiments with Haemophilus ducreyi in rabbits can elicit a strong antibody response, and the course of antibody synthesis is similar to that of other cellular infections, though humans produce a more complex antibody response than animals. Throughout the infection, there are identifiable significant common antigens. At certain stages of infection, both common antigens and individual-related antigens can be recognized. In summary, the role of the immune response to Haemophilus ducreyi in the host remains unclear, as humans can experience repeated infections. Clearly, there is no fully protective immunity.

bubble_chart Pathological Changes

The center is an ulcer, with epidermal hyperplasia at the ulcer margin. Below the ulcer, three vertically arranged inflammatory zones are visible: 1. **Ulcer base layer**: Predominantly polymorphonuclear leukocytes, mixed with red blood cells, fibrin, and necrotic tissue. 2. **Middle layer**: Numerous newly formed blood vessels, significant tissue edema, infiltration of neutrophils, lymphocytes, and histiocytes, with a notable presence of fibroblasts. 3. **Deep layer**: Diffuse infiltration of lymphocytes and plasma cells, particularly prominent around blood vessels. Using Giemsa and Gram staining, **Haemophilus ducreyi** may occasionally be detected in the superficial or deep layers.

The average incubation period after infection is 2 to 3 days. Most cases develop symptoms within about a week, while a few may manifest several weeks later. Symptoms in females are generally milder than in males, and the incubation period is longer.

The initial manifestation is an inflammatory small papule on the external genitalia. Within 24 to 48 hours, it rapidly forms a pustule, which ruptures after 3 to 5 days to form an ulcer with clearly defined borders. The ulcer is round or oval, with serrated edges and a turbid lower margin, surrounded by an inflammatory red halo. The base of the ulcer is covered with a yellow, lard-like purulent coating and a lot of purulent discharge, which, when removed, reveals bleeding. Pain is significant. On palpation, it feels soft and is termed a soft chancre.

Initially, there are only 1 to 2 soft chancres, but due to autoinoculation, new lesions may appear nearby. Most soft chancres occur in the genital area: in males, they are often found in the coronal sulcus, foreskin, glans, or frenulum; in females, they commonly appear on the labia, vulva, or posterior commissure. Extragenital sites such as fingers, lips, and tongue may also be affected.

The lymph nodes draining the affected area become swollen. About 50% of patients develop ulcers within days to two weeks. The injury is often unilateral (especially on the left side) and more common in males than females. This is called a bubo.

Soft chancre bubo presents as acute suppurative inguinal lymphadenitis, usually unilateral, with local redness, swelling, heat, and pain. When the bubo ruptures, it everts like a fish mouth, colloquially referred to as a "bubo." In recent years, due to early use of effective treatments, the infection's progression has been controlled, making typical soft chancre bubo less common.

Atypical soft chancres:

Transient chancroid: The soft chancre lesion is small and disappears within 4 to 6 days, but inguinal lymphadenopathy occurs around 2 weeks later, easily misdiagnosed as sexually transmitted lymphogranuloma or genital herpes.

Raised soft chancre: The ulcer base is a depressed chancre, with granulation tissue forming a raised appearance.

Follicular soft chancre: A small, pinhead-sized chancre forms a deep ulcer in the genital hair follicles.

Dwarf soft chancre: A very small lesion resembling the erosion caused by genital herpes but with an irregular base and sharply defined hemorrhagic edges.

Erosive soft chancre: The ulcer progresses rapidly and deeply, causing extensive necrosis and sloughing of the penis or labia within days, often leading to significant bleeding. This type of chancre is usually caused by mixed bacterial infections.

bubble_chart Auxiliary Examination

1. Bacteriological Examination:

Haemophilus is a Gram-negative bacillus, exhibiting pleomorphic characteristics under culture conditions, is easily stained, and lacks spores and motility.

1. Microscopic Examination: Smear specimens stained from open ulcers of soft chancre easily reveal Haemophilus ducreyi. For unruptured lesions, puncture abscesses or buboes to obtain puncture fluid for smear staining, which yields more typical results. Use methylene blue or Gram staining for microscopic observation under oil immersion at 10×100 magnification.

2. Culture Examination: Isolating soft chancre bacteria is challenging. When collecting pathological material, ensure to take pus from beneath the edge of the soft chancre ulcer or aspirated pus from punctured buboes as specimens. Alternatively, thoroughly rinse the ulcer base with saline, then use a saline-moistened cotton swab to collect the specimen for laboratory culture.

Internationally, two standard culture media for soft chancre are used: GCHGS (Hammond gonococcal media), composed of gonococcal agar supplemented with bovine hemoglobin, fetal bovine serum, vancomycin, cellulose, and amino acids; and MHHb (Muller-Hinton agar), composed of Muller-Hinton agar, horse blood, vancomycin, and other culture components. Both media can be used simultaneously to improve the positivity rate.

Colonies typically form within 24–48 hours after inoculation, appearing gray-yellow and translucent, with a diameter of about 1–2 mm. Gram staining of material from the colonies reveals Gram-negative, paired short bacilli arranged in chains. Additionally, perform generation and transformation reactions for identification, including weakly positive oxidase test, negative peroxidase test, negative porphyrin test, positive nitrate reduction test, and positive alkaline phosphatase test.

Culturing Haemophilus ducreyi not only aids in diagnosis but also determines the antibiotic sensitivity of the isolated bacteria. Antibiotic-resistant strains of Haemophilus ducreyi have already been isolated.

2. Serological Diagnosis of Soft Chancre:

Infection with Haemophilus ducreyi produces antibodies. Serological tests, such as complement fixation, agglutination reactions, and indirect fluorescent antibody methods, can confirm this, though these methods are not yet widely adopted. Currently, IgM antibody sensitivity is 74%, and IgG antibody sensitivity is 94%, with specificities of 84% and 64%, respectively.

3. PCR Detection of Haemophilus ducreyi.

bubble_chart Diagnosis

Based on the history of sexual contact before the onset, especially unprotected intercourse, typical clinical manifestations and course, the occurrence of soft and flat papules, pustules, ulcers after a short incubation period, unilateral suppurative lymphadenitis, direct microscopic examination and culture detection of Haemophilus ducreyi, and PCR detection of Haemophilus ducreyi DNA, a diagnosis can be made.

Diagnostic basis: Barber proposed the following recommendations for the diagnosis of this disease as diagnostic criteria: ① Genital ulcer, single or multiple; ② Dark-field microscopy examination, negative for syphilis spirochetes; ③ Syphilis serological test negative; ④ Smear taken from the undermined edge of the lesion, no Donovan bodies (granuloma inguinale bacilli) found with Wright's staining, but short Gram-negative bacilli can be detected with Gram staining.

bubble_chart Treatment Measures

The natural course of untreated soft chancre can last for several months, with small lesions healing within 2 to 4 weeks. Due to the emergence of drug-resistant strains to sulfonamides, tetracyclines, and chloramphenicol, the treatment of soft chancre has become somewhat challenging.

I. Systemic treatment:

(1) Erythromycin, Lijunsha, Roxithromycin, Azithromycin;

(2) Ceftriaxone sodium, Zhibituo, Leshifuding, Temiejun;

II. Local treatment:

(1) For unruptured papules or nodules, apply ichthammol or erythromycin ointment externally.

(2) For ulcers, rinse with 1/5000 potassium permanganate or hydrogen peroxide, then apply erythromycin ointment externally. Because soft chancre

is prone to autoinoculation, thorough local cleaning and disinfection should be performed.

(3) For lymph abscesses; perform aspiration by puncturing the abscess cavity from distant normal skin to drain the pus.

III. Management of HIV co-infection

In such patients, ulcers heal more slowly, requiring a longer treatment course. Short-term treatment often fails, and a combination of two or more antibiotics should be used. If possible, Haemophilus ducreyi should be isolated from the lesion for antibiotic sensitivity testing.

Patients should be re-examined 3 to 7 days after treatment. If the treatment is effective, ulcer symptoms should improve within 3 days, and significant healing should be visible within 7 days. Otherwise, consider: whether the diagnosis is correct, whether there is co-infection with another STD pathogen, whether there is concurrent HIV infection, or whether Haemophilus ducreyi is resistant to antibiotics. Typically, the healing time of ulcers is related to their size, with larger ulcers possibly requiring two weeks to heal.

bubble_chart Differentiation

This disease is often misdiagnosed as genital herpes. Genital herpes presents with multiple, clustered vesicles during the herpes stage, and bacterial tests are negative. Additionally, when differentiating from hard chancre, it is important to note that the hard chancre of syphilis is firmer, has less purulent discharge, and is painless. Other acute vulvar ulcers should also be ruled out.

Comparison table of soft chancre and hard chancre